Poster Presentations



The poster board size is 8 feet wide x 4 feet high.


Posters are to be mounted during the afternoon of Sunday, July 13 between 1300 and 1700, and taken down at 2000 on Monday, July 14 after the Monday evening poster presentation session.


Poster judging will take place on Monday evening, starting at 1730 – posters that are up for awards must have the first author present at this time.




Case Report of a Rare Complication of Open Heart Surgery Masquerading as a Gun Shot Wound: An Autopsy Diagnosis

I.Kak1, V. Nair2. 1Department of Pathology and Molecular Medicine, McMaster University, Room HSC 2N20A, 1280 Main Street West, Hamilton ON L8S 4L8,; 2Department of Pathology and Molecular Medicine, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2,

Background: Deep sternal wound infection or Poststernotomy mediastinitis is an uncommon but dreaded complication of open-heart surgery with an incidence of 1-3% but high mortality, ranging from 10-35%. Sternocutaneous fistulas are known to be infrequent sequelae of deep sternal wound infection with rates varying from as low as 0.25% to 10%. Reports have documented prosthetic valve endocarditis as a serious consequence of surgical valve replacement but scarce articles have described deep sternal wire infections causing the same.

Case report: 52 year old male smoker with aortic valve replacement in 2011, on Coumadin and Monocor, was found dead on September 2013 with a hole along a surgical scar over the sternum, mimicking a gun-shot wound. Chest radiograph revealed no foreign body and no evidence of homicidal, suicidal or accidental cause was found. Examination of the deceased revealed a chronic fistulous tract from a deep sternal wire infection to the skin, in addition to a chronic sinus tract eroding into the root of the aorta with recent prosthetic valve endocarditis.

Discussion: Till date, no reports of concomitant sternocutaneous fistula and prosthetic valve endocarditis arising from deep sternal wound infection have been described. This case is unique, not only due to its initial misleading presentation, but additionally, it is the sole descriptor of a combined occurrence of two rare but feared complications of deep sternal wound infection, either of which can be fatal alone.



Fatal Streptococcal Infections in Infants and Children: A Clinico-Pathological Study

K.P.Whelan1, J.Reyes1, D.A. Chiasson1. 1Division of Pathology, DPLM, Hospital for Sick Children, 555 University Ave, Toronto, Ont. M5G 1X8.

Background: Streptococcal infections may manifest as bacteremia, pneumonia, or meningitis resulting in significant morbidity and rarely death. There is a paucity of literature delineating the clinical-pathological features of fatal Streptococcal infection in post-neonatal infants and children. We, therefore, undertook a clinic-pathological review of autopsies where Streptococcal infection was the primary cause of death.

Methods: Our autopsy data base was searched from January 1997-Febuary 2014 for deaths over 1 month of age in which the primary cause of death was Streptococcal infection. Pre-mortem clinical data was extracted and post-mortem data was analyzed for sites of infection and microbiology. The clinical-pathological features of the Streptococcal species, S. pneumonia[SPn], S.pyogenes[SPy], and S. other (S. viridians, agalactiae, and bovis) were compared.

Results: The cause of death was attributed to Streptococcal infections in 44 patients: SPn n=20; SPy n=17; and S.other n=7. The ages ranged from 1 month to 15 years with a mean age of 4.3 years. There was a female predominance in the SPy group, F:M ratio of 3:1, compared to 1:1 in the other groups. The majority of children were previously healthy, n=25/44, and many had not had medical attention prior to the terminal presentation. SPy cases had a more rapid course from symptom onset to terminal presentation (SPy – average of 5.5 hours, SPn-18.5 hours, and for S. other -9.5 hours) Primary sites of infection included lungs and meninges. Blood culture positivity within each group was: SPy-17/17; SPn-15/20; and S. other-7/7.

Conclusion: Streptococcal infection, especially S. pyogenes and S. pneumonia remains an important, often sudden, cause of death in otherwise healthy infants and children.



Inflammatory Myofibroblastic Tumor of the Aortic Valves Causing Sudden Cardiac Death: A Case Report and Review of the Literature

Sameh Youssef, Bin Xu, Richard S. Fraser, Chantal Bernard, Department of Pathology, Montreal Children’s Hospital, McGill University Health Centre, Montreal, Quebec, Canada, H3H 1P3.

Background: Cardiac inflammatory myofibroblastic tumor (IMT) is a rare entity affecting predominantly infants, children, and young adults. Although most tumors have a benign clinical course after complete surgical resection, some have significant clinical effects.

Methods and Results: We described a case of a 9-year-old girl who had sudden cardiac death as a result of occlusion of the left circumflex coronary artery (LCX) by IMT. At autopsy, a structurally normal heart showed a polypoid papillary tumor attached on the aortic valve with extension of one tumor frond into LCX. Histologically, the tumor was composed of bland spindle cells, admixed with lymphocytes and plasma cells. The spindle cells were positive for vimentin and smooth muscle actin. ALK-1 was negative by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). The IgG4 count was low. A diagnosis of cardiac IMT was rendered. A review of 57 cases of cardiac IMTs reported in the literature is presented.

Discussion: Cardiac IMTs account for less than 5% of primary cardiac tumors, with a total of 57 cases reported to date. The majority are endocardium-based polypoid lesions protruding into the cardiac cavity, with 12% showing aortic valve involvement. Compared to extra-cardiac IMTs, cardiac IMT is associated with lower incidence of ALK-1 overexpression, less frequent recurrence, and higher risk of disease-related mortality, including sudden cardiac death due to occlusion of a coronary artery. Although IMT is in general considered to be a neoplasm with intermediate biologic potential, this case emphasizes that cardiac IMTs may have a fatal consequence. This tumor should be considered in the differential diagnosis of unexplained chest pain and syncope in pediatric patients.



Improving Autopsy Turnaround Times Using Lean Management Principles

Susan Cromwell1, David A. Chiasson1,2, Gino R. Somers1,2. 1Division of Pathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children; 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON.

Background & Objectives: Our hospital performs approximately 60 hospital (consented) pediatric autopsies per year. Our aim is to have 90% of autopsies signed out by 90 days from the date of autopsy (turnaround time [TAT]); considered a key performance indicator. Only 26-48% of autopsy reports have been completed by 90 days since 2010. Delays in TAT are frustrating for clinicians and families. The objective of this study was to find methods to improve TAT using LEAN management principles.

Methods: A working group was formed of administrative, technical and professional staff. Value stream mapping highlighted potential areas of improvement. Metrics from the 2010-2013 pathology LIS CoPath provided TAT data.

Results: Value stream mapping showed 25 steps from autopsy to sign out, identifying two main areas for improvement: Time to complete microscopy; and time to sign out after Quality Assurance (QA) rounds. Three tools were implemented to address the delays: A visible autopsy whiteboard; weekly meetings around the whiteboard; and a time-tracker form highlighting key deadlines. After implementation, 83% met the desired TAT. Variability was also decreased.

Conclusions: The current climate demands increased efficiency while maintaining fiscal responsibility. LEAN management principles applied to our autopsy sign-out workflow has helped identify areas of waste and sources of potential improvement, thus improving our sign out times and associated variability, without changing our staffing levels or scheduling structure.



Prognostic Significance of Human Tissue Kallikrein-Related Peptidases 6 and 10 in Gastric Cancer

D.L. Kolin1, K. Sy2, F. Rotondo1, M.N. Bassily3, K. Kovacs1, C. Brezden-Masley4, C.J. Streutker1, G.M. Yousef1. 1Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON M5B 1W8; 2Department of Pathology, Credit Valley Hospital, Mississauga, ON L5M 2N1; 3Department of Community Medicine and Public Health, Menoufiya University, Egypt; 4Department of Medicine, St. Michael’s Hospital, Toronto, ON M5B 1W8.

Objectives: Kallikreins are a group of serine proteases which are differentially expressed in many human tumours and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer.

Methods: We constructed a gastric tumour tissue microarray from 113 gastrectomy specimens, and quantified KLK6 and KLK10 expression using immunohistochemistry. A whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining.

Results: KLK6 expression was positively correlated with nodal involvement (p=0.002), and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed tumours expressing high levels of KLK6 were associated with significantly lower overall survival (p=0.04). KLK10 overexpression was a predictor of advanced-stage disease (p<0.01).

Discussion: This study confirms previous findings of an association between increased KLK6 expression, advanced stage, and worse clinical outcomes in gastric cancer. Automated image analysis can help overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation. Conclusion: Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer.



MCM2: A Potential Biomarker to Distinguish Luminal A from Luminal B Breast Cancer

Einas M. Yousef1, David Laperrière1, Sylvie Mader1, Louis Gaboury1. 1Institute for Research in Immunology and Cancer (IRIC), Montreal, Quebec, Canada. QC, H3T 1J4.

Microarray-based gene expression profiling studies have underscored the heterogeneity of breast cancer. Estrogen receptor positive breast cancers comprise two clinically distinct subtypes: Luminal A and Luminal B. Because Ki-67 assessment has raised a number of issues, there is a need for a robust and validated immunohistochemical assay to distinguish between these two subtypes. Objective: To find out a new biomarker that could facilitate our ability to distinguish these two subsets.

Methods: In silico analysis was carried out to identify genes whose expression pattern varied differentially between Luminal A and B tumors. In this study we selected out MCM2. Tissue microarrays from 300 breast cancer patients were studied immunohistochemically to measure levels of MCM2 expression and a wide array of biomarkers.

Results: MCM2 is overexpressed in luminal B when compared to luminal A subtype (p<0.0001). In addition, MCM2 could distinguish Luminal A from Luminal B based on a 40% index cut-point.

Conclusion: MCM2 is a promising biomarker to make the distinction between Luminal A and Luminal B tumors. An independent validation cohort is needed to confirm the clinical utility of MCM2.



miRNAs are Potential Predictive Markers for Sunitinib Treatment Response in Metastatic Renal Cell Carcinoma

H. Khella1, H. Butz1, A. Seivwright1, F Rotando1, A Evans1, P. Kupchak1, M. Dharsee1, L. Sugar3, C. Sherman3, M. Jewett2, G. Bjarnason3, G. M.Yousef1,4. 1Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, ON, M5B 1W8; 2Princess Margaret Hospital, Toronto, ON, M5G 2M9; 3 Sunnybrook Odette Cancer Center, Toronto, ON, M4N 3M5; 4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8.

Objectives: To examine the clinical utility of miRNAs as predictive markers in renal cell carcinoma

Methods: We compared miRNA expression between patients with short term (<12 months) vs. prolonged (≥12 months) survival under sunitinib treatment. 30 primary pretreatment RCC specimens were collected and miRNA expression was profiled by TaqMan Low Density Array Cards. For validation, miRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction. Target prediction and pathway analyses were performed. We validated one of these miRNAs targets on the same set of patients using immunohistochemistry. Also, we tested the effect of these miRNAs on cellular proliferation and angiogenesis.

Results: We identified miRNAs that are differentially expressed between patients with short term (<12 months) vs. prolonged (≥12 months) survival under treatment. We developed statistical models that can accurately distinguish between the two groups based on the expression of 2-3 miRNAs. We validated our models in the discovery set and an independent set of 60 patients. Target prediction analysis showed that these miRNAs are involved in VEGF, Wnt, TGFb and mTOR mediated signaling and cell-cell communication. These miRNAs can affect cellular proliferation and angiogenesis.

Conclusion: Our analysis suggests that miRNAs represent potential predictive markers for sunitinib response of in RCC.



Integrative Analysis of Clear Cell Renal Cell Carcinoma: Disease Network Reveals the Role of KIAA0101 in Cancer Cell Migration and Invasion

Henriett Butz1, Peter M. Szabo2, Roy Nofech-Mozes1, Fabio Rotondo1, Kalman Kovacs1, Lorna Mirham1, Hala Girgis1, Dina Boles1, Attila Patocs3, George M. Yousef1. 1Department of Laboratory Medicine, and the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, Canada; 2Biometric Research Branch, Division of Cancer Treatment and Diagnosis, NCI-NIH, Bethesda, Maryland, USA; 3HAS-SE “Lendulet” Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences, Hungary.

Objectives: Our aim was to assemble transcriptomic, proteomic and miRNA data using an integrative approach for investigating clear cell renal cell carcinoma (ccRCC) pathogenesis, and for finding new, potential biomarkers.

Methods: We obtained high-throughput mRNA, miRNA and protein data from publicly available databases and literature. We integrated data of totally 593 ccRCC and 389 normal kidney specimens. We performed pathway analysis and built a network of ccRCC disease. The TCGA database and tissue microarray (TMA) were used for validation. Functional analyses were done by proliferation, migration and invasion assays followed by siRNA experiment.

Results: Metabolic proccesses were the most significant signalling pathways in ccRCC. Among them, we identified and validated Aryl-Hydrocarbon Receptor (AHR) signaling to be involved in tumorogensis, and AHR as a good prognostic marker. Using network analysis, we identified GRHL2 to be a promising diagnostic biomarker and drug target. Based on our ccRCC network, KIAA0101 was found to be important pathogenetic factor enhancing tumor cell migration and invasion. We also demonstrated that KIAA0101 over-expression was correlated with poor prognosis and also as a diagnostic marker.

Conclusions: Using integrative bioinformatical analyses we identified the most characteristic pathways and molecules among which some of them are applicable for biomarkers or new, potential drug targets.



miR-194 Is A Marker For Good Prognosis In Clear Cell Renal Cell Carcinoma

R. Nofech-Mozes1,2, H. Khella1, M. Gabril3, A. Evans4, G.M. Yousef1,2. 1Department of Laboratory Medicine, and the Keenan Research Centre in the Li Ka Shing Knowledge Institute St. Michael’s Hospital, Toronto, Canada. 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. 3Department of Pathology, Western University, London, Canada. 4Pathology, UHN, Toronto, Canada.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in adults. There is an unmet need to identify prognostic markers for improving patient care. miR-194 is involved in the regulation of epithelial to mesenchymal transition (EMT) and has been reported to be down regulated in several cancers. In ccRCC, miR-194 has been shown to act as a tumor suppressor. Our study evaluated the potential significance of mir-194 as a prognostic marker in ccRCC. In a cohort of 276 patients with primary or metastatic ccRCC, we correlated the expression of miR-194 with multiple clinicopathological features including disease free and overall survival, tumor size, clinical stage, and histological grade. RNA was extracted from FFPE tissue and expression was evaluated by reverse transcription and qPCR using miR-194-spicific probes. Our result show miR-194-positive patients had a significantly higher chance of disease-free survival (HR = 0.56 , 95% CI = 0.31-0.99, p = 0.046) and a significantly better overall survival (HR = 0.44, 95% CI = 0.19-1.00, p = 0.05) compared to miR-194-negative patients. After controlling for clinicopathological variables in a multivariate analysis, miR-194-positive tumors retained significant decreases in the odds ratio of disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in ccRCC. Moreover, miR-194 is a marker for good prognosis for patients with tumors less than or equal to 4 cm (small renal masses), which have several treatment options. These findings were validated on an independent data set from The Cancer Genome Atlas. miR-194 positive tumors were associated with a better prognosis and thus, it represents a potential prognostic biomarker that can boost the accuracy of other prognostic models in patients with RCC.



miR-210 Is A Prognostic Marker In Clear Cell Renal Cell Carcinoma

S. Samaan1, H. Khella1, A. Girgis1, A Evans2, E. Lianidou1, M. Gabril3, S. N. Krylov4, G. Alo3, M. Jewett2, G. Bjarnason5, H. El-said; G. M. Yousef1. 1Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto; 2Urologic Oncology, Princess Margaret Hospital; 3Dept of Pathology, London Health Sciences Center and Western University, London; 4York University, Toronto; 5 Medical Oncology and Hematology, Sunnybrook Odette Cancer Center, Toronto.

Objective: miRNAs are short non-coding RNA molecules that control the expression of their target genes, and are implicated in cancer. We explored the role of miR-210 as a prognostic marker in clear cell renal cell carcinoma (ccRCC).

Methods: We analyzed the expression of miR-210 by qRT-PCR in 276 cases of primary ccRCC. We also compared its expression in 40 pairs of adjacent normal and cancerous tissues, as well as in primary and metastatic tumors, common RCC subtypes and the benign oncocytoma. Finally, we validated our results with an independent dataset of 481 cases from The Cancer Genome Atlas.

Results: miR-210 was significantly overexpressed in ccRCC compared to normal kidney, and its expression was higher in metastatic than in primary tumors. miR-210-positive patients had a statistically higher chance of disease-recurrence and shorter overall survival relative to miR-210-negative patients. Kaplan-Meier survival curves indicate that miR-210-positive patients had significantly lower disease-free survival (p = 0.015) and overall survival (p = 0.011). Papillary RCC showed comparable miR-210 overexpression, while much less upregulation was seen in chromophobe RCC and oncocytoma. Our in-silico analysis showed a negative correlation between miR-210 expression and a number of its predicted gene targets which are downregulated in ccRCC tissues relative to normal kidney.

Conclusion: Our results demonstrate the role of miR-210 as a potential independent marker of poor prognosis in ccRCC and a potential therapeutic target.



Amplification and Overexpression of MYC in a Leiomyosarcoma: Cytogenetic, FISH, Array-CGH and Immunohistochemistry Analyses

Adewale Adeyinka1 Nandita Barnabas2, Jessica Sanchez2, Dhananjay Chitale3. 1Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada Departments of 2Medical Genetics and 3Pathology, Henry Ford Health System, Detroit, MI, U.S.A.

Leiomyosarcomas (LMS) are uncommon in the female genital tract and the literature on leiomysarcomas of the vagina consists mostly of case reports. We report the cytogenetic, FISH, array-CGH and immunohistochemical findings in a leiomyosarcoma from a 49-year-old woman who presented with a painful vaginal mass. Tumor microscopy showed a cellular spindle cell tumor composed of oval to spindly cells arranged in sheets or fascicles and stained positive for smooth muscle markers (SMA, HHF35). About 90% of metaphase cells from short-term cultures of tumor cells had 49 chromosomes including three copies of a derivative chromosome 8. The remaining 10% cells had four copies of the derivative chromosome. FISH studies showed that each derivative chromosome consisted in its entirety of chromosome 8 material, had two copies of MYC and 8qter signals, lacked 8pter signal, and was devoid of centromeric alpha satellite or satellite III signal of any of the 24 chromosomes. Microarray-CGH study on DNA extracted from the tumor confirmed amplification of 8q12.1-q22.2 and 8q24.13-qter as the sole genetic abnormality in the tumor. IHC using MYC antibody showed strong positive staining in tumour nuclei. Our findings indicate that amplification of 8q including MYC is a primary genetic abnormality as well as a pathway of evolution in the leiomyosarcoma.



Dedifferentiated Chondrosarcoma In An Adolescent

A. Pettit1, JP. King3, M. Gross2, S. Afzal4, G. Boyd3, K. Dakin Haché1. 1Department of Pathology and Laboratory Medicine, 2Department of Orthopedic Surgery, 3Department of Diagnostic Imaging, QE II Health Sciences, Halifax, 4Department of Pediatric Oncology, IWK Health Centre, Halifax.

Dedifferentiated chondrosarcoma is exceedingly rare in the pediatric population with only three reported cases in the literature. We report a 17 year old male who presented with left hip pain. Initial radiographs suggested a benign degenerative process. Subsequent investigations prompted biopsy showing a primitive spindle cell neoplasm with a fibrosarcomatous growth pattern, myxoid matrix, and weak S100 expression. The main differential diagnosis included synovial sarcoma and malignant peripheral nerve sheath tumor. The molecular evaluation was negative for SS18/SSX1 and SS18/SSX2 fusion transcripts by RT-DNA amplification. No SS18 gene rearrangement was detected by fluorescence in situ hybridization. There was no history of neurofibromatosis and origin from a peripheral nerve was not demonstrated on the excision specimen. Additional studies were negative for rearrangement of the DDIT3 and EWSR1 gene loci, arguing against unusual patterns of myxoid liposarcoma and Ewing /PNET family of tumors, respectively. Cytogenetics evaluation demonstrated an abnormal karyotype with numerous structural and numerical abnormalities. Difficulties in classification prompted extensive sampling of the excision specimen which revealed a ~ 5 mm focus of low grade chondrosarcoma with abrupt transition to the non-cartilaginous primitive neoplasm, supporting a diagnosis of dedifferentiated chondrosarcoma. In some cases, extensive sampling is the only means for classifying primitive sarcomas. The incidence of pediatric dedifferentiated chondrosarcoma may be underestimated in the literature as a result of overgrowth of the precursor lesion or undersampling of the specimen.



Primary Angiosarcoma of the Bone: A Case Report and Review of the Literature

A Nistor1, S Holmes2, D. Gomez1, K Perry1. 1Department of Pathology, 2Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada.

Background: Primary angiosarcoma of the bone is an uncommon malignant tumor accounting for less than 1% of primary bone tumors. Variable 5-year survival rates of 10-30% have been reported and complete surgical resection is considered essential for outcome.

Case report: We report a case of a 22-year old male who presented with ankle pain and was diagnosed with a lytic bone lesion in the distal tibia. MRI showed an intramedullary bone tumor with cortical disruption and a biopsy showed this to be a high-grade angiosarcoma. The patient underwent radical surgery consisting of below knee amputation. On the resection specimen, a diagnosis of angiosarcoma was confirmed by histological and immunohistochemical analysis and a second metachronous focus was found within the second metatarsal bone. Consequently, a diagnosis of multicentric angiosarcoma of the bone was made. Following resection, clinical and radiologic follow up showed the patient to be alive and well 6 months after surgery with no evidence of metastatic disease.

Conclusion: Angiosarcoma is an extremely rare primary bone malignancy with poor survival in patients with unresectable or metastatic disease. Accurate histological diagnosis and pathological staging is important to ensure appropriate risk stratification and clinical management.



Sinonasal Myopericytoma: A Case Report and Literature Review

C. Hamilton, K.A. Dakin Haché and M.J. Bullock. Department of Pathology and Laboratory Medicine, QE II Health Sciences, Halifax B3H 2Y9.

Myopericytoma is a benign, typically subcutaneous, tumor which exhibits differentiation characteristic of myopericytes (perivascular myoid cells). These lesions have a distinct appearance and immunophenotype; however, they are often under-recognized and misdiagnosed. Most cases of myopericytoma do not recur and only very rare malignant examples have been described. The entity forms a continuum with other soft tissue tumors including myofibroma, angioleiomyoma, and infantile hemangiopericytoma. We report a case of myopericytoma in an 86 year old female who presented with an intranasal mass. A single case of sinonasal myopericytoma has been previously reported. A more common tumor which enters the differential diagnosis is glomangiopericytoma (sinonasal-type hemangiopericytoma). We discuss the distinction between these two lesions. Myopericytoma, although well described within the soft tissue literature, may be more common than was previously recognized in the head and neck mucosa, and it should be included in the differential diagnosis of vascular lesions arising in the sinonasal cavity.



Lingual Osseous Choristoma – A Rare Case Report

F. Matea, S. Alowami1, D. Lukic. Department of Pathology, McMaster University, 1200 Main Street, Hamilton, ON, L8N 3Z5.

Introduction: The osseous choristoma by definition is a mass of histologically normal bone tissue but in abnormal location. This can be in the skin (previously known as osteoma cutis), or in the oral cavity mucosa (previously known as osteoma mucosae). The later, if affects the tongue is called lingual osseous choristoma. Originally described in 1913 by Montserrat, and renamed in 1971 by Krolls, lingual osseous choristoma is a rare condition, with fewer than 100 cases reported. The pathogenesis of this rare tumor is a controversial problem and its nomenclature also remains an issue of debate. It normally presents as a hard mass, either pedunculated or sessile, mostly located on the dorsum of the tongue, near the foramen cecum and circumvillate papillae. Here, we report a case of lingual osseous choristoma in a 44-year-old patient, successfully treated with surgical excision.

Case presentation: A 44-year-old woman presented with a mass over the dorsum of posterior tongue. An excisional biopsy was performed under general anesthesia to remove one white, hard nodule measuring (0.5 × 0.5 × 0.3 cm). Microscopic examination after decalcification revealed a well-demarcated mass of dense lamellar bone with haversian canals, surrounded by a layer of thin fibrous connective tissue and covered by normal squamous mucosa.

Conclusion: To conclude, osseous lingual choristoma is a rare condition of academic interest. Awareness of this entity is essential to avoid misdiagnosis with different osseous bone tumor.



Case Report of a Cytokeratin Negative Intra-Abdominal Desmoplastic Small Round Cell Tumour in a Young Female Patient

Jennifer M. Dmetrichuk MBChB, PhD, Xueping Fang, MD, MSc. McMaster University, Hamilton, Ontario, L8S 4L8.

Objective: Desmoplastic Small Round Cell Tumours (DSRCT) are rare, highly aggressive, mesenchymal tumours which occur primarily in the peritoneal cavity of young males. In most cases, the neoplastic cells show immunohistochemical evidence of epithelial, mesenchymal and neuronal differentiation. We report here a case of a molecularly confirmed intra-abdominal DSRCT in 26-year old female patient that does not display the characteristic immunohistochemical profile.

Method: The patient was investigated for a 2-year history of pelvic pain and intermenstrual bleeding. MRI revealed a solid 3.6 cm lesion in the right adenxa which was felt to be likely ovarian in origin. Surgery revealed a right pelvic sidewall mass and was sent for histopathological evaluation. The case was sent to Mount Sinai Hospital in Toronto for further molecular studies.

Results: Histological sections revealed nests of small blue round cells embedded within hyalinized and edematous stroma with minimal desmoplastic reaction. Mitoses were rare and no necrosis was identified. Immunohistochemical studies showed the neoplastic cells were positive for desmin, vimentin, CD 56, CD99, and focally positive for calretinin, NB84A and synaptophysin. They were negative for AE1/AE3, CK7, CK20, CK 18, EMA, Cam 5.2, 34BE12, MOC 31, CDX-2, WT-1, TTF-1, inhibin, chromogranin, NSE, GFAP and S100. Congo red was also negative. The EWSR1/WT-1 fusion product was identified and EWSR1/ERG was negative in keeping with a diagnosis of a DSRCT.

Conclusion: We report here a rare case of a CK negative intra-abdominal DSRCT in a young female. The use of molecular genetic techniques is particularly helpful to confirm the diagnosis of this rare tumour.



Diagnostic Value of Caldesmon, Cyclin D1 and Beta Catenin in Pediatric Fibroblastic/Myofibroblastic Tumors

M Hassan1, J de Nanassy1, A Nasr2, D El Demellawy1. 1Pathology & 2Surgery Departments. Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada

Introduction: Unlike many other soft tissue tumors, immunohistochemistry (IHC) plays a relatively minimal role in the diagnosis of pediatric fibroblastic/myofibroblastic tumors (PFMT).

Design: We studied 38 cases of common PFMT presented to us. Clinical data and pathology were reviewed and a panel of IHC is performed (table 1).



CAF (n5)

IDF (n4)

PF (n6)

NF (n1)

IMF (n5)

DF (n6)

IMF (n5)

IFS (n5)

GF (n1)































Cyclin D1










Beta Catenin






























Pax 2










*focal. CAF: calcifying aponeurotic fibroma, IDF: infantile digital fibromatosis, PF: plantar fibromatosis, NF: nodular fasciitis, IMF: infantile myofibromatosis ,IFS: infantile fibrosarcoma, GF: Gardner fibroma, DF: desmoid fibromatosis.

Conclusions: PFMT are heterogenous group of tumors showing a spectrum of differentiation. The presence of colponin staining is a characteristic feature of DF, IDF and IMF. Caldesmon, cyclin D1 and beta-catenin are diagnostically helpful markers in PMFT.



Intimal Sarcoma Presenting As Massive Pulmonary Thromboembolism: A Rare Case And Review Of Literature

P. Borowy-Borowski1, N. Parasu2, S. Anand3, S. Popovic1. 1 Department of Pathology and Molecular Medicine, 2Department of Radiology, 3Department of Oncology, McMaster University, Hamilton Health Sciences, Hamilton, Ontario.

Intimal sarcomas are very rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation. Pulmonary intimal sarcomas are most common, followed by aortic origin. We describe the case of a 24-year old man who presented with a two and a half month history of shortness of breath and cough that progressed to hemoptysis and marked decrease in tolerance of physical activity. He was referred by his general practitioner for pulmonary function testing and results were consistent with asthma. Further work up included a CT scan with findings of extensive central bilateral pulmonary thromboemboli, well-circumscibed bilateral pulmonary nodules, and mediastinal/ hilar lymphadenopathy. CT guided biopsy of the pulmonary nodule was obtained. Morphologic and immunohistochemical features were in keeping with undifferentiated sarcoma with spindle cell and pleomorphic morphology. Molecular confirmation was accomplished by FISH analysis using probes sets for MDM2 (MDM2/CEP12) and PDGFRA (FIPIL1, CHIC2, and PDGFRA) revealing marked amplification of both MDM2 and PDGFRA gene regions. Based on the medical literature, proper diagnosis of intimal sarcoma is often delayed due to nonspecific clinical presentation that is related to tumor emboli. Molecular findings of (co) amplification of PDGFRA and MDM2 confirmed in the current case could be a useful diagnostic test, and also potential therapeutic target in this very rare type of sarcoma with poor prognosis.



Clinical-Pathologic Significance Of Androgen Receptor (AR) Expression In Hormone Receptor (HR) Negative Breast Cancer

D. Farnell1, G. Pond2, S. Mukherjee2, M. Levine2, A. Bane1,2. 1Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario; 2Department of Oncology, McMaster University, Hamilton, Ontario.

Hormone receptor (HR) negative breast cancers have a poor prognosis and are difficult to treat.

A subset of HR negative breast cancers has been demonstrated to express androgen receptor (AR), however the clinical significance of AR expression is poorly characterized. In this study we examined the expression of AR in a historical cohort of 130 HR negative breast cancers and correlated AR expression with clinical-pathologic tumor characteristics and patient outcome. Immunohistochemistry and Allred scoring was used to quantify AR expression. Kaplan-Meier methods were used to estimate overall survival at 5 years. Fisher’s exact, Wilcoxon rank sum and log-rank tests were used to compare tumor characteristics and overall survival between subtypes. 107 (82.3%) of the 130 HR negative tumors were classified as triple negative (TN) while 23 (17.7%) were HER2 over-expressing, and 26 (20.0%) expressed AR. AR expression was observed in 15% of TN and 43% of HER2 overexpressing tumors (p=0.004). When compared to AR negative tumors, patients with AR positive tumors were more likely to be older age at diagnosis; mean age 69.85 years vs 61.2 years, p=0.023. There was no significant difference between the AR positive and negative tumors with regards to tumor grade (p=0.13), stage (p=0.85), overall survival (83.3% vs 73.9% at 5 years, p=0.56) or event-free survival (65.6% vs 68.4% at 5 years, p=0.85), nor was an interaction with HER2 expression observed. AR expression is observed in approximately 20% of HR negative breast cancers and correlated with older age at diagnosis and HER2 overexpression. No significant differences in pathological tumor characteristics or patient outcome are observed for AR+ HR- tumors as compared to AR- HR- tumors irrespective of whether the tumors are TN or HER2 over-expressing.



Comparison Of HER2 Testing On Breast Core Biopsies By IHC/DISH

H. Faragalla1,2, D. Moto3, J. Karamchandani1,2. 1 St. Michael’s Hospital, Toronto, ON, Canada 2Department of LMP, U of T, Toronto, ON, Canada 3Department of Biology, University of Western Ontario.

Objectives: HER2 status is critical in the management of patients with invasive breast cancer. Surgical excision specimens are the gold standard for assessing HER2 status. Dual in situ hybridization (DISH) is a new bright field technique recently introduced for assessing HER2 amplification. The aim of this study is to compare IHC and DISH HER2 on invasive mammary carcinoma on needle core biopsies.

Methods: 73 cases of invasive breast cancers on core biopsy were stained for HER2 IHC followed by DISH on scores 0, 1, 2 and 3 for determination of HER2 amplification. The results of HER2 IHC and DISH were compared. The results of HER2 on needle core biopsy and excision specimens were also compared. Currently the guidelines for HER2 IHC 2 + changed, 13 of the score 1+ core biopsies were rescored using the new guidelines

Results: 34 patients were scored 0, 16 patients were scored +1, 11 patients were scored 2+ and 12 patients were scored 3+. There was 100% concordance between IHC and DISH in all needle core biopsies with scores 0, 1 and 3. Only one out of 11 IHC equivocal 2+ cases was amplified on DISH. There was no change in HER2 status between the needle core biopsy and excision specimen. Two biopsies score 1 were upgraded to 2 using the new guidelines.

Conclusion: Our results show strong concordance between IHC and DISH of HER2 expression on invasive mammary carcinoma on needle core biopsies.



Pure Intralymphatic Breast Carcinoma After Neoadjuvant Chemotherapy: A Case Report

J. Maxwell and S. Tang. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer. Pure intralymphatic breast carcinoma, defined as residual carcinoma present exclusively in lymphovascular spaces after neoadjuvant chemotherapy, is a rare but important pattern of breast carcinoma.

Objectives: To highlight the histological features and clinical significance of post-neoadjuvant pure intralymphatic breast carcinoma. Methods: A case report with literature review.

Case Report: A 56 year old patient with locally advanced right breast carcinoma underwent neoadjuvant chemotherapy and modified radical mastectomy. A 5 cm fibrous area was identified grossly. Microscopy showed sheets and nests of malignant cells in lymphatic spaces, with foci of necrosis, over a 3.7 cm area. D2-40 staining confirmed exclusive lymphatic involvement. Margins were negative but 2/17 lymph nodes were involved. Despite post-operative radiotherapy, the patient experienced local recurrence at 15 months, bony metastases at 23 months and a malignant plural effusion at 27 months post-surgery. The patient is currently receiving chemotherapy at 42 months after her initial diagnosis.

Conclusion: There are several diagnostic problems associated with identifying pure intralymphatic breast carcinoma, including the definition and staging of invasive carcinoma and the clinical significance of residual disease. The clinical course of this patient suggests that this pattern of residual breast carcinoma is very aggressive, as previously suggested by Rabban et al. Regardless of staging, the presence of pure or predominantly pure intralymphatic carcinoma is associated with a 3-fold increase in death.



Oncogenic Signaling Dysregulation Mediated by miRNA Networks in Breast Cancer

K.G. Sidiropoulos1,2, N.M.A. White1,2 , Q. Ding1, P.Boulos1, A.Bui1, G. Pampalakis3, G.Sotiropoulou3, and G.M. Yousef1,2. 1The Keenan Research Center in the Li Ka Shing Knowledge Institute and Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, Canada, M5B 1W8 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5S 1A8 3Department of Pharmacy, University of Patras, 26500, Rion-Patras, Greece

A large scale investigation of miRNA network dysregulation was conducted in breast cancer cell lines using miRNA arrays with reconstitution of kallikrein expression including KLK6. Enrichment models and target prediction identified putative convergent and divergent pathways with altered expression including MAPK, cell cycle, EMT transition, and extracellular matrix pathways. Putative miRNA gene targets were validated with a mRNA arrays, and confirmation was further made by miRNA inhibitors and mimcs. Large clinical datasets were assayed to clinically validate our results including IlluminaHiSeq and Agilent expression array data from the The Cancer Genome Atlas (TCGA). Differential expression of miRNA networks and mRNA target genes was found in the molecular subtypes of breast cancer (basal-like, Her-2, luminal A, luminal B). Confirmation of reduced long-term patient survival (OS and RFS) was demonstrated with. Our data suggests the biological differences between breast cancer molecular subtypes (including basal-like, Her2, Luminal A, and Luminal B), patient survival, and their propensity for invasion and metastasis can be explained in part by miRNA networks induced by KLK5.



The Prognostic/Predictive Ability Of PhH3 In Breast Cancer

Lee LH1, Bigras G2, Tang P3, Yang H1. 1Department of Pathology, University of Calgary, Calgary Alberta; 2Department of Pathology, University of Alberta, Edmonton, Alberta; 3Department of Oncology, University of Calgary, Calgary, Alberta.

Objective: Phosphohistone H3 (PhH3) can be visualized in dividing cells from late G2 phase to early telophase by immunohistochemistry. This study aims to investigate the prognostic/predictive ability of PhH3 count by correlating with Oncotype DX recurrence score (RS), MBR grade, and mitosis.

Methods: All cases of invasive breast carcinoma with RS results from our institution between 2007 and 2010 were selected. Whole tumor sections were stained for PhH3. PhH3 counts were reported as the average of two pathologists’ independent count of 10 consecutive high power fields in the region of highest staining concentration. All cases were reviewed and regraded, and chart review was performed to determine patient outcomes.

Results: 47 cases were assessed (25 low RS, 15 intermediate RS, 7 high RS). PhH3 correlated well with RS (r=0.688, p<0.001). Other correlations were: PhH3 vs mitotic count (r=0.868, p<0.001), PhH3 vs mitotic score (r=0.713, p<0.001), PhH3 vs MBR grade (r=0.650, p<0.001), RS vs mitotic count (r=0.617, p<0.001), RS vs mitotic score (r=0.439, p=0.002), and RS vs MBR grade (r=0.487, p=0.001). Significant correlation between PhH3 and RS remained after controlling for mitotic count (r=0.390, p=0.007), mitotic score (r=0.595, p<0.001), MBR grade (r=0.560, p<0.001) and all three (r=0.367, p=0.014) by partial correlation. Two patients died of metastasis, one 12 months, and one 38 months after diagnosis. One had intermediate RS, and one had high RS; both were in the top third of PhH3 count. All other patients are alive and recurrence-free.

Conclusions: Correlation between PhH3 and RS is strong, and a significant correlation remains after controlling for mitotic score, mitotic count, and MBR grade. Given that RS has an established strong relationship with prognosis and therapy responsiveness, PhH3 thus may also be an important marker in breast cancer, providing prognostic/predictive information independent of mitosis and MBR grade.



To Which Extent Can Physical Activity Exert Its Anti-Inflammatory Effect in Breast Tissue?

M. Hanna1,4, I. Dumas1,4 , M. Orain1,4, B. Têtu1,2,3,4, S. Jacob1,2,3,4 and C. Diorio1,3,4. 1Axe Oncologie du CRCHU de Québec, 2Service de pathologie et 3Centre des maladies du sein Deschênes-Fabia de l’Hôpital du Saint-Sacrement, 4Centre de recherche sur le cancer, Faculté de médecine de l’Université Laval, Québec, Québec. G1S 4L8.

Physical activity may decrease breast cancer risk through affecting the expression of inflammatory markers in breast tissue, markers that play a role in breast carcinogenesis. We examined the association of physical activity with the protein expression levels of pro-inflammatory markers [tumor necrosis factor-a (TNF-a) and interleukin 6 (IL-6)] and anti-inflammatory marker [lactoferrin] in normal breast tissue. Information on different types (occupational, recreational and household) and total physical activity performed by 164 women having breast cancer was collected using a validated questionnaire. For each participant, six cores of normal breast tissue were extracted from mastectomy blocks and used to build up tissue microarray (TMA) blocks. TMA cut sections were stained by immunohistochemistry and digitized. The expression of inflammatory markers (intensity and proportion of positive cells) was visually estimated in normal epithelium and stroma present on digitized TMA images. Quick score was obtained by multiplying the intensity by the proportion of positive cells. Associations were assessed by multivariate generalized linear models. Higher total physical activity was significantly inversely associated with lower expression levels of TNF-a in normal breast tissue after adjustment for confounders (ptrend=0.013). Conversely, household physical activity was associated with higher expression levels of lactoferrin in normal breast tissue after adjustment for confounders (ptrend=0.023). In our study, there was some evidence of physical activity anti-inflammatory effect in breast tissue.



Can Physical Activity Affect Breast Tissue Composition?

M. Hanna1,4, I. Dumas1,4, B. Têtu1,2,3,4, S. Jacob1,2,3,4 and C. Diorio1,3,4. 1Axe Oncologie du CRCHU de Québec, 2Service de pathologie et 3Centre des maladies du sein Deschênes-Fabia de l’Hôpital du Saint-Sacrement, 4Centre de recherche sur le cancer, Faculté de médecine de l’Université Laval, Québec, Québec. G1S 4L8.

The mechanisms mediating the association of physical activity with decreased breast cancer risk remain poorly determined. One potential mechanism by which physical activity may protect against breast cancer is by modulating breast tissue composition. We examined the association of physical activity with age-related lobular involution, a histologic assessment of breast tissue composition. Age-related lobular involution is inversely associated with breast cancer risk. We conducted a cross-sectional study among 164 pre- and postmenopausal women having breast cancer. Information on different types (occupational, household and recreational) and total physical activity, performed in the year preceding the diagnosis, was gathered using a validated questionnaire. The age-related lobular involution in terms of degree and the predominant lobule type was assessed on normal background breast tissue contained on hematoxylin and eosin stained slides. Associations were assessed using multivariate generalized linear models. There was a positive association between both occupational or total physical activity and the predominant lobule type among premenopausal women after adjustment for age and waist circumference (p=0.018 and p=0.026 for occupational and total physical activity, respectively). Paradoxically, occupational and total physical activity were inversely associated with the predominant lobule type among postmenopausal women after adjustment for age and waist circumference (p=0.019 and p=0.013 for occupational and total physical activity, respectively). Physical activity may protect against breast cancer by modulating breast tissue composition in premenopausal women. Further studies are needed to elucidate the effect of physical activity on breast tissue composition.



Tumour-Infiltrating Lymphocytes As A Predictor Of Response In Neo-Adjuvant Endocrine Therapy In Breast Cancer

N Chang1, SW Hakim1, Z Kos1, DH Gravel1, A Arnaout2, SJ Robertson1. 1Department of Laboratory Medicine, 2Department of General Surgery, University of Ottawa, Ottawa ON, Canada (Data presented in part at USCAP).

The potential predictive value of tumour-infiltrating lymphocytes (TILs) in breast cancer is recognized. Though still controversial, TILs have been associated with complete pathologic response and survival in neoadjuvant chemotherapy. However, few studies exist on TILs in neoadjuvant endocrine therapy (NET). We explored the response of ER+ tumours to short course aromatase inhibitor, and whether a raw TIL count could predict treatment response (TR) to NET. Patients with strongly ER+ invasive breast cancer on core biopsy were treated with anastrozole for 14-35 days prior to definitive resection. We evaluated TILs in biopsies and resection specimens from 19 NET patients (NETPs) and 23 retrospective controls. TILs were scored as: 0 (absent), 1 (weak), 2 (moderate), 3 (dense). Ki67 and ER/PR status were reviewed for TR. TILs correlated with Ki67 in biopsies from all cases (Pearson R=0.488, p<0.001), indicating higher raw TIL count is associated with more proliferative tumours. Ki67 significantly decreased between biopsy and resection in NETPs (m=-14.6, sd=17.8, p=0.002), but not in controls. PR Allred scores also significantly decreased post-NET (Wilcoxon signed-rank test Z=-3.41, p<0.001). TILs correlated with Ki67 in resections from controls (R=0.439, p<0.02), as expected with no intervention, but not in NETPs. No correlation was found between post-NET change in Ki67 and change in TIL or TIL score. No significant difference was found in TILs pre- and post-NET. When NETPs were divided into responders and non-responders based on ≥40% Ki67 drop from baseline, no significant difference was found in TILs pre- and post-NET in responders, or in TIL change in responders versus non-responders. Although short course NET led to a rapid suppression of ER+ tumour proliferation, raw TIL count does not predict TR. The lack of change in TILs pre- and post-NET does not preclude alteration of lymphocyte subtypes, for which further study may be warranted.



Anaplastic Lymphoma Kinase (ALK) Rearrangements in Inflammatory Breast Carcinoma

Micheal G. Keeney, Vishal S. Chandan, Eunhee Yi, William R. Sukov, Judy C. Boughey, Sejal S. Shah. Mayo Clinic, Rochester, MN-55902, USA.

Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer characterized by rapid tumor progression, early metastasis and poor survival. Anaplastic lymphoma kinase (ALK) gene rearrangements have been described in several tumors including non-small cell lung carcinomas. A recent report indicated that ALK gene amplification was a common feature in IBC tumor cell lines and that small-molecule ALK inhibitors were effective in mouse xenograft models.

Method: 50 cases with IBC were identified from the cancer registry during the period of 11 years, of which 17 cases had material available for this study. Immunohistochemical stain with ALK antibody (Clone ALK1; 1:100; Dako) was performed and the immunoreactivity was scored for each case as 0, 1+, 2+ and 3+ using our previously published criteria. Fluorescent in-situ hybridization assay (FISH) using a break apart assay with probes for ALK (ALK probe; Abbot, IL) was performed to detect ALK rearrangements in cases with ALK staining.

Results: Of the 17 cases (16 cases of invasive ductal carcinoma and 1 case of metaplastic carcinoma), ALK immunoreactivity was negative in 15 cases (0 in 11 cases and 1+ in 4 cases), equivocal (2+) in 2 cases and positive (3+) in 0 cases. FISH for ALK gene rearrangement was negative in all 6 cases with immunoreactivity (1+ and 2+ cases).

Conclusions: ALK immunoreactivity was negative in 88% of cases and equivocal in 12% of cases of IBC. FISH was negative in all the cases that showed immunoreactivity. These results suggest that ALK rearrangement may not be a principal event in IBC tumorigenesis and hence IBC may not be responsive to ALK targeted therapy.



How to Avoid Misinterpretation of Mammary Unilocular, Cystic Squamous Carcinoma (UCSC) as a Benign Keratinous Cyst

Z. Eslami1, N. Buza2, N. Beck3, R.Butler3, F.A. Tavassoli2. 1Department of Pathology, McGill University, Montreal, QC. 2Department of Pathology and 3Department of Radiology, Yale School of Medicine, New Haven, CT.

Primary squamous carcinoma (SC) of the breast is rare accounting for less than 0.1% of breast cancers. Origin from the overlying skin, metastases from other sites, and epidermal inclusion / keratinous cyst should be excluded. Often displaying solid and cystic components, the UCSC can be a particular diagnostic challenge. Accumulation of keratinous debris and/or reactive inflammatory cells may result in its misinterpretation as either an abscess or a keratinous cyst. Two recent cases are contrasted to illustrate problems that may prevent a timely, accurate diagnosis. The 67 years old presented with a palpable mass associated with erythema, the 73 years old had a mass discovered by routine imaging. Mammographically, both lesions were deep-seated, complex cystic lesions. The older patient had a core biopsy interpreted as SC; mastectomy showed a 4.3 cm UCSC, pT2 pN0(sn;i-). The 67 year old had two aspirations and a core biopsy of the lesion; all were interpreted as benign. The cyst was removed simply because it failed to resolve after several months. The excision showed a 7.8 cm UCSC. Lined by a well differentiated squamous epithelial lining, unequivocal invasive carcinoma emanated from the cyst lining at multiple foci. Both tumors were EGFR positive. To prevent misinterpretation of the rare UCSC, correlation of clinical, radiographic and pathologic findings is crucial. Location is a most helpful clue. While the differential diagnosis of a superficially located, squamous lined cyst in the breast should include an epithelial inclusion/keratinous cyst, the possibility of a cystic SC should not be ignored. If deeply located, however, a well differentiated SC must be considered even if a core biopsy fails to capture the clearly invasive component. Complete excision without delay maybe the only way to accurately diagnose such a lesion. Deep location in the breast is an important clue. The potential value of using EGFR as a target for therapy should be explored further



Pathology Role in Predictive Significance of Thymidine Phosphorylase Expression in Patients with Breast Cancer Treated with Capecitabine

Z.Eslami1, A.Tedeschi2, G. Omeroglu1, C. Mihalcioiu2, A. Omeroglu1. 1Department of Pathology and 2Department of Oncology, McGill University, Montreal, QC.

Capecitabine (Xeloda) is a cheomotherapeutic agent used in the treatment of breast cancer. The last step of this enzymatic process employs the enzyme thymidine phosphorylase (TP) that is found predominantly in tumor cells. The objective of this clinico-pathology study was to determine the correlation between TP expression in the tumor tissue and the clinical outcome to capecitabine based therapy in patients with locally advanced or metastatic breast cancer. We obtained formalin fixed, paraffin embedded breast cancer tissue from 18 patients who received at least one cycle of capecitabine. The following variables were analyzed as potential determinants of benefit from a capecitabine based therapy: TP expression, ER, PR, HER-2 and Ki67 status. Clinical outcome was measured as time to progression (TTP). Overall, median TTP was 10.5 months ranging from 0-36. Moderate to weak tumor TP expression in the invasive component was found in patients with ER(-) tumors conversely, patients with an ER(+) tumors were found to have no staining of TP. Moreover, no correlation was detected between TP staining in the DCIS component and the patients ER tumor status. The TP staining intensities reported in both the invasive and DCIS component did not correlate to TTP on capecitabine therapy. Overall, the general trend observed was that the ER(+) group expressing lower levels of TP (invasive) had a median TTP 17.1 months compared to the ER(-) group expressing higher levels of TP (invasive) which had a median TTP of 7.7 months. Our study indicates that patients having an ER(+) tumor status express lower levels of TP (invasive) have longer TTP when compared to patients having an ER(-) tumor status express higher levels of TP (invasive) with shorter TTP. Consequently, tumor TP expression does not seem to predict outcome to capecitabine chemotherapy.



Redo Aortic Valve Replacement in a Patient With Undiagnosed Anomalous Origin of Right Coronary Artery Leading to Eventual Cardiac Arrest – A Rare Case Report and Review of Literature

D.M. Ravi1, V. Nair2. 1Department of Pathology, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5. 2Department of Pathology, Hamilton General Hospital, Barton street east, Hamilton, ON.

Congenital anomalies of the coronary artery although rare can have serious health implications in terms of morbidity and mortality. We discuss a case of a 62 year old male with a history of severe aortic insufficiency induced heart failure diagnosed in 2011. He had an aortic valve replacement (AVR) with a size 25 porcine surgical aortic valve (SAV) with no complications as a consequence of the procedure. The preoperative echocardiogram revealed severe chronic aortic insufficiency and globally hypokinetic left ventricle and the pre-operative angiogram showed right coronary artery to be large, dominant, widely patent and the left main coronary artery to be widely patent. He came back a year later, with worsening heart failure and was diagnosed with severe mitral regurgitation and mild para-valvular aortic insufficiency. The surgeons performed a mitral valve replacement and redo AVR with a size 25 porcine SAV. Post-operative day 1, he had an acute episode of seizure followed by cardiogenic shock and acute heart failure. He was unresponsive to intensive inotropic therapy and he passed away. Autopsy revealed that he had an anomalous origin of the right coronary artery from left coronary sinus in a right dominant circulation. Also, the stent post of the bioprosthetic aortic valve was found to be obstructing the ostia of the right coronary artery which most likely lead to the cardiogenic shock in the patient. This case is an excellent learning experience for cardiologists, cardiovascular surgeons and pathologists. Although rare, anomalous origin of coronary arteries is an important entity and early diagnosis can reduce post-operative morbidity and mortality in these patients. Moreover pre-operative angiogram is an important tool in recognizing the abnormal origin and course of the coronary arteries.



An Intramyocardial Mesothelial Inclusion Cyst Obstructing the Right Ventricular Outflow Tract: A Case Report

R. Peerani1,2, V. Kotha3, D. Deva3, A. Yan4, A. Pinter4, D. Latter5, S. Hill5, C. Streutker1,2. Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario 2Department of Laboratory Medicine, 3Department of Medical Imaging, 4Division of Cardiology, 5Division of Cardiovascular Surgery, St. Michael’s Hospital, Toronto, Ontario.

Intramyocardial cysts are relatively uncommon in occurrence; hydatid, bronchogenic and epithelial inclusion cysts are most frequently reported in the literature. We report a benign intramyocardial mesothelial cyst found to obstruct the right ventricular outflow tract of a 51 year old man. The patient presented with chest pain two weeks after a cavotricuspid-isthmus ablation for persistent atrial fibrillation/flutter; he had also had an earlier ablation performed 20 years previously. Upon pathological examination, the cyst was unilocular and contained clear serous fluid. Microscopically, the cyst was present within myocardium and was lined by flattened cells. The lining cells, on immunohistochemistry, were strongly positive for cytokeratin 7 (CK7), low molecular weight keratin (LMWK), and calretinin, consistent with mesothelial origin. The cells did not stain for thyroid transcription factor-1 (TTF-1) and podoplanin (D2-40). This mesothelial inclusion cyst may have been a congenital lesion but an alternate possibility is iatrogenic displacement of native pericardial mesothelial cells during ablations. We believe that this case is the first reported of a benign intramyocardial mesothelial inclusion cyst causing obstruction in the heart.



Assessment of Error Reduction by Implementation of 10% Random Rescreen of Negative Pap Smears – A Quality Assurance Exercise

A.Gaucher, B.Sc. MLT (Cyto), J.L. Benoit MD., FRCP(C). Department of Cytopathology, Laboratory Medicine, Saskatoon Health Region, Saskatoon, Saskatchewan, S7K 0M7.

Although pap smears have proven to be effective, some laboratories report a 20% to 30% false negative rate. Errors are known to occur. In addition to the targeted rescreening already performed in our cytology laboratory, we undertook a quality assurance exercise to assess the effectiveness of 10% random rescreen of negative pap smears on reducing screening errors. During a 12 month period (January 1, 2013 to December 31, 2013), our lab received 51,052 pap smears. A total of 4618 (9.1%) normal pap smears were selected for random rescreening. Specific revised report criteria were identified and applied consistently. Data was compiled monthly and analyzed at the end of the evaluation period. A total of 219 (4.7%) reports were revised by a senior cytotechnologist and cytopathologist. 132 cases (60.3%) were revised with changes to the T-zone status. Organisms (Fungus or TVO) were missed in 38 (17.4%) of the rescreened cases, followed by data entry errors occurring in 19 cases (8.7%). 14 cases (6.4%) represented changes to unsatisfactory diagnosis and 6 cases (2.7%) failed to identify the presence of endometrial cells in women over the age of 40. 10 cases (4.6%) represented false negatives ranging from ASCUS to ASC-H to LSIL. Trends were noted in primary screener results. False negative cases were reviewed by the primary screening cytotechnologist as part of quality assurance and continuing education. At the end of the study period, although 10% random rescreen did detect a few significant screening errors, we concluded it was not an effective means of reducing errors and evaluating cytotechnologists. In general, the process was considered inefficient use of technologist resources to detect only a small number of errors.



Cytohistological Correlation in Adenosquamous Carcinoma of the Cervix

Williams AS, Offman SL, MacIntosh, RF. Division of Anatomical Pathology, QEII Health Sciences Centre & Dalhousie University, Halifax, Nova Scotia.

Background: Adenosquamous carcinoma (ASC) of the cervix is defined by the presence of malignant squamous and glandular components and is cited to account for between 5-25% of all cervical carcinomas. Cervical cytology traditionally focuses on the detection of squamous lesions. Glandular or combined squamous-glandular lesions may be overlooked. Previous studies have not examined cases of ASC using the Bethesda system for reporting to evaluate the presence of combined lesions in cervical cytology. Aim: To determine the most common Bethesda system cytological diagnoses in cases of ASC and to evaluate cases for combined squamous and glandular lesions on cytology.

Methods: An electronic search of the pathology record system at the QEII Health Sciences Center in Halifax identified 30 cases of ASC diagnosed by histology between January 1, 1995-June 30, 2013. Of the 30 cases, 15 had both histology and cytology specimens available and were included in this review. The cytology and histology slides were systematically reviewed without reference to the previous pathology reports.

Results: The overall Bethesda system cytological diagnosis was a squamous lesion in 10 (66.7%) cases, a glandular lesion in 3 (20%) cases, and malignancy-NOS in the remaining 2 (13.3%) cases. In 4 of the 10 overall squamous lesions there was a coexistent AGC-EC and in another 1 case a coexistent AIS. In 1 of the 3 overall glandular lesions there was coexistent ASC-H. In both cases where the overall diagnosis was malignancy-NOS, no definite background squamous or glandular lesion was identified. Combining these results, coexistent squamous and glandular abnormalities were seen in a total of 6 of 15 cases (40%).

Conclusions: Using the Bethesda system, squamous lesions and malignancy-NOS account for 80% of the cytological diagnoses in cases of ASC. In the setting of ASC, careful evaluation may allow for cytological identification of combined squamous and glandular abnormalities in up to 40% of cases.



Primary Extra Nodal T Cell Lymphoma Presenting as a Parotid Mass: Potential Diagnostic Pitfalls of Fine Needle Aspiration Cytology

Babita Kajal1 Monalisa Sur2, Catharine Ross2, Tariq Aziz2 and Shangguo Tang1. 1Department of Pathology and Molecular Medicine, McMaster University. 2Department of Pathology, Juravinski cancer center, Hamilton, Ontario, Canada.

Background: Parotid lymphomas are uncommon and often under diagnosed. This misdiagnosis may lead to unnecessary diagnostic procedures; subsequently delay in the initiation of treatment and mismanagement.

Objectives: To highlight the cytology diagnostic pitfalls of hematolymphoid neoplasms in the parotid gland presenting as a primary mass. Methods: Retrospectively review of a case of T cell lymphoma in parotid with subsequent involvement of bone marrow and abdominal lymph nodes.

Case presentation: A 63 year old male with history of lip squamous cell carcinoma, presented with a left parotid mass. Cytology smears demonstrated a cellular aspirate consisting of clusters of atypical spindled to oval cells with moderate cytological pleomorphism and increased mitosis with possible occasional mucus cells with absence of keratinization in the cells. A high grade mucoepidermoid carcinoma was favored over a poorly-differentiated squamous cell carcinoma and further investigation with additional tissue was suggested. A second FNA showed similar cytomorphology and broader differentials including benign and malignant epithelial lesions were given. The patient was then treated with radical radiotherapy. Later the patient developed back pain and pancytopenia. Bone marrow biopsy revealed an ALK negative T cell lymphoma, favoring peripheral T-cell lymphoma with co-expression of CD30 and CD15. Subsequently, abdominal lymph node biopsy showed an ALK negative anaplastic large cell lymphoma. The patient was then treated with hyper CVAD. Results: Retrospective review of parotid lesion cytology along with additional immunocytochemical studies revealed similar profile noted on the bone marrow biopsy and lymph node supporting a diagnosis of ALK negative anaplastic large cell lymphoma.

Conclusions: Due to rarity, most of hematolymphoid malignancies in unusual extra nodal sites are overlooked and awareness of such lesions with appropriate ancillary tests is necessary to avoid diagnostic pitfalls.



Metastatic Renal Cell Carcinoma to Thyroid: Potential Diagnostic Pitfalls of Fine Needle Aspiration Cytology

D.M. Ravi, S. Alowami, L. Vincic, S. Tang. Department of Pathology & Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5.

Background: Metastatic renal cell carcinoma (RCC) to the thyroid can pose diagnostic challenges on fine needle aspiration (FNA) cytology since it can mimic primary thyroid neoplasm.

Objectives: The authors report a case of metastatic renal cell carcinoma to the thyroid that was initially diagnosed as suspicious for hurtle cell neoplasm on FNA cytology and discuss the diagnostic approaches and potential cytology pitfalls of metastatic RCC to thyroid.

Case presentation: A 73 year old female with a history of clear cell RCC was found to have a single heterogeneous thyroid nodule (2 cm) on post-surgical staging CT scan. A diagnosis of suspicious for Hurthle cell neoplasm was rendered on FNA. No immunocytochemical testing was performed due to lack of enough tissue in the cell block. The thyroid nodule was monitored quarterly and fifteen months later, the nodule increased in size to 2.5 cm. A repeat FNA consisted of cellular aspirate showing large fragments of cells with papillary architectures, as single and groups of loosely cohesive abnormal cells with mild to moderate cytologic atypia, small but conspicuous nucleoli with abundant foamy and granular cytoplasm. Some cells had clear cytoplasm. The cytological features were more suggestive of hurthle cell neoplasm but given the clinical history of RCC, immunocytochemistry was performed and it revealed that the neoplastic cells were positive for RCC, vimentin, CD10 and EMA and negative for TTF-1 and thyroglobulin. A diagnosis of metastatic RCC was rendered. Retrospective review of the first FNA material showed similar cytological features.

Results & Conclusion: This case has proven to be an excellent learning experience. Clinical history with a high index of suspicion on thyroid FNA cytology with appropriate ancillary tests is necessary to avoid diagnostic pitfalls.



A Retrospective Quality Assurance Review of Thyroid Follicular-Type Lesions with Cyto-Histologic Correlation

Pouneh Dokouhaki, MD; Hoda Elshoni, MD; Janine Benoit, MD, FRCP. Department of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8.

The Bethesda System (TBS) has significantly improved the consistency and accuracy of thyroid cytology reporting. However, there are controversies about the predictive value of the follicular lesion-type category. We aimed to study the cyto-histological correlation in 3 abnormal follicular-type categories of TBS i.e. Atypical/Follicular lesion of undetermined significance (A/FLUS), Follicular neoplasm (FN) and Follicular neoplasm/Hurthle cell type(HCT).For this purpose, all thyroid FNA biopsy specimens performed in Saskatoon Health Region during a 30-month period (Jan2010-Jun2013)were included and the cases in any of 3 follicular-lesion categories were reviewed by 2 independent observers.

There were 75 cases of follicular-type lesions during this period (5.6% of total thyroid FNAs).In A/FLUS category(38),17(44%) were clinically observed,12(29%) had a benign lesion either by repeat FNA or histology,5(13%) had follicular neoplasm and 4(10%) had Papillary Thyroid Carcinoma(PTC).There were 27 cases in FN category, out of which 7(26%) were clinically observed,5(19%) had benign lesions,11(41%) had follicular neoplasm and 4(15%) had PTC.A total of 10 cases fitted into HCT category with1(10%) being followed clinically,8(80%) had follicular neoplasm and1(10%) had PTC in the resection specimen. On retrospective case review, the potential pitfalls and limitations of cytological diagnosis of follicular lesions of thyroid were identified and will be discussed. Our findings show that the cytological diagnosis of follicular-type lesions has its limitation for detection of thyroid neoplasms and therefore, attention must be paid to the salient cytomorphological features of each TBS categories to avoid over/underdiagnosis of neoplasms in thyroid nodules. In this regard, rigorous quality control and continuous education in thyroid cytopathology is crucial.



Pancreas EUS-FNAB – An Analysis of Equivocal Results, the London Experience

S.McRae, M.G.Joseph, B.M.Yan, N.Hussain, M.Al Beshir, E.Filter, M.M.Weir. Department of Pathology, London Health Sciences Centre & Western University, London, ON, N6A 5A5.

Purpose: (1) To examine the frequency and reasons for equivocal diagnoses in pancreas endoscopic ultrasound fine needle aspiration biopsy (EUS-FNAB); (2) To assess outcomes and classify neoplasia risk; (3) To develop strategies to reduce equivocal diagnoses.

Materials and Methods: Cytology reports from pancreas EUS-FNAB (2008-13) with a diagnosis of atypical (AT), indeterminate (IN) or suspicious (SU) were assessed. Reasons for equivocal diagnoses, surgical follow-up results, number of passes performed at rapid on-site evaluation (ROSE) and number of cases referred for internal consultation were recorded.

Results: From a total of 489 cases, 147 cystic lesions were excluded. Of the remaining 342 solid lesions, 162 (47%) were diagnosed as AT (53%), IN (12%) or SU (35%). The main reasons for equivocal diagnoses were low overall cellularity (38%) and gastrointestinal (GI) contaminant with rare atypia (53%). Follow-up surgical biopsy was available in 76 (47%) cases. Neoplasia risk was 77% in the AT category, 78% in IN category and 92% in the SU category with adenocarcinoma as the most common outcome (48/76, 63%). ROSE was performed in 149 (92%) equivocal cases with an average number of passes similar in each category (AT 5.7, IN 6.1, SU 5.9) compared to a lower number (4.7) for neoplastic category. In 74 (46%) equivocal cases internal consultation was sought from one or more cytopathologists.

Conclusions: (1) The main reasons for equivocal diagnosis were low overall cellularity or abundant GI contamination with rare atypia; (2) Neoplasia risk was similar for AT and IN and significantly higher for SU category;(3) Future strategies includes redefining and possibly merging AT and IN categories, communication of neoplasia risk for equivocal categories, continued peer review of equivocal cases and further evaluation of impact of sampling technique and ROSE.



A Competency Based Assessment Tool for Pathology Resident Grossing

Allison Osmond, William Stecho, David Garcia Marquez, Aaron Haig, Teresa Van Deven, Michele Weir. Western University, London, Canada.

Background: The Royal College of Physicians and Surgeons of Canada will be phasing in competency based learning objectives for resident training. The aims of the study are: 1) to examine the attitudes of pathology residents towards grossing specimens as a baseline and 2) to examine utility of a competency based assessment tool and log book for grossing specimens.

Design: A survey of residents’ attitudes on grossing and competency based training was obtained for our program and nationally. A competency based checklist for grossing gynecological specimens & logbook with milestones were designed and tested on one senior resident and subsequently implemented on one junior resident during a 1 month gynecologic pathology rotation. Impact was assessed by examining comments from participants & supervisors; and variety of specimens grossed.

Results: The majority of Western residents (86%) reports receiving minimal feedback on specimens grossed and not having clear grossing objectives on number & type of specimens, compared to 68% nationally for the latter. They (67%) report that grossing skills are not emphasized in our program. Advantages identified by Western residents for the assessment tool were: immediate feedback on grossing deficiencies with supervisors, greater emphasis on grossing objectives (skills, type of specimens) and increased awareness of grossing procedures. One realization was that the assessment process was less intense and more user friendly than anticipated by the residents. Supervisors identified opportunity to give feedback on and teach around grossing deficiencies as advantages. Supervisors’ realizations were: checklists were not as time consuming or complicated as expected. A variety of specimens were grossed by the resident.

Conclusions: From the survey, Western residents report some challenges regarding specimen grossing, some of which are comparable nationally. The competency based assessment tool & logbook instituted at Western for grossing serves to increase emphasis and feedback on resident grossing and allowed supervisors opportunity for timely feedback.

Keywords: Competency based medical education, Royal College of Physicians and Surgeons, Surgical pathology, resident grossing



Canada’s First Accredited Pathologists’ Assistant Graduate Program: A Self Study And Review

J. Strong, E. Tugaleva, S. Chakrabarti, N.G. Chan. Department of Pathology, London Health Sciences Centre, Western University, London, Ontario N6A 5A5.

Background: Western University’s Pathologists’ Assistant (PA) graduate program is the first in Canada to earn accreditation by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS). This is an emerging profession with bountiful employment opportunities. Aim: To evaluate the effectiveness of our program in graduating highly qualified PAs and to elicit feedback for the continued improvement of our program.

Methods: We solicited feedback from former graduates through a confidential, voluntary, electronic survey that investigated their current employment, experience during training and suggestions for improvement.

Results: The survey response rate is 15 out of 19 graduates (79%), with representation from all 5 years of graduating students. After graduation, 3 respondents (16%) entered medical school. All of the remaining respondents (84%) found employment as a PA; most found employment before the end of the program. Graduates are employed throughout Canada where their duties have included examination of surgical specimens (100%), assisting in postmortem examinations (58%), administrative duties (58%), and research (25%). Only 1 respondent (5%) has completed the American Society for Clinical Pathology (ASCP) certification examination. Some respondents specified suggestions for improvement during their clinical rotations. All of the respondents noted that our program met their expectations.

Discussion: Our program has been effective in training PAs and employment opportunities are plentiful for our graduates. We have gained valuable insight on how to improve our program. For example, graduates should be further encouraged to write the ASCP certification examination and hospital staff who teach our students need further support in their mentorship roles.



Pediatric Pathology Cases: Retrospective Review at London Health Sciences Centre for Training Purposes

Julie A. Montgomery1, Nancy G. Chan1, Aaron R. Haig1. 1 London Health Sciences Centre, Department of Pathology, University of Western Ontario.

Pediatric pathology is a specialized area in pathology that often does not receive sufficient focus in training of residents and pathologists’ assistant (PA) graduate students. This is due to the relative rarity of many of the specimens.

It is critical, however, that trainees in surgical pathology receive adequate training and exposure to achieve a level of competence in this area. For example, the Royal College of Physicians and Surgeons of Canada requires two blocks in pediatric pathology or equivalent longitudinal experience during residency.

Our goals are to ensure adequate exposure during training and the capture of less common cases for future trainees.

At our institution, rather than have a dedicated pediatric pathologist, the majority of the pediatric material is distributed according to subspecialty. The challenge has been to ensure adequate exposure, as well as appropriate documentation, for anatomical pathology residents.

As part of a quality assurance initiative, we examined the number, distribution and type of pediatric surgical cases in 2013. London Health Sciences Centre received 1873 surgical cases from the pediatric population in 2013. The distribution was as follows: breast (1.4%), eye (1.6%), GI (59%), GU (5%), gynecology (2%), head and neck (9%), hematology (4%), lung (1%), muscle/bone (4%), skin (10%) and other (3%).

There are no specific quotas designated for residents by the Royal College or for PA students by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS).

We found that our institution has a significant number of pediatric surgical cases covering a wide spectrum of disease, allowing for adequate exposure for our trainees. In addition, our trainees are required to complete a log of their pediatric case experiences in order to ensure adequate longitudinal experience. Select cases were chosen to make a teaching set in order to assist in future training.

Keywords: pediatric pathology, residency training, residency education, pathologists’ assistant (PA) graduate students



The Value of Medicolegal Autopsies in a Pathology Residency Training Program

K. Duan, R. Fraser. Department of Pathology, McGill University Health Center, Montreal, Quebec. H3G 1A4

Objective: To review our institution’s experience with medicolegal (coroner) autopsies with respect to the number and type of cases performed and their educational value in our residency training program.

Methods: We performed a retrospective review of all medicolegal autopsies undertaken at the Montreal General Hospital between May 2012 and Sept 2013. Data was retrieved from coroner cause of death statements and final autopsy reports.

Results: Fifty-four medicolegal autopsies requested by the Montreal Coroner’s Office were performed during the study period. They comprised 20.5% (54/263) of all adult autopsies. Ages ranged from 23 to 92 years (median 52). Pre-autopsy cause of death was considered to be natural (87.0%), accidental (7.4%), or suicide (5.6%); suspected homicide cases were not performed. After autopsy, 21 (38.9%) cases were considered to have a definite and 24 (44.4%) a probable anatomical cause of death; in 9 cases (16.7%), no anatomical cause of death was identified. Common definite causes of death included cerebral hemorrhage (6), pulmonary thromboembolism (4) and coronary thrombosis (4). Uncommon (rare) causes included rhabdomyolysis, aortic dissection, coronary arteritis, and gastric ulcer perforation. Thirteen (24%) cases had additional pathological findings of significant educational value unrelated to the cause of death.

Conclusion: Medicolegal autopsies performed in a hospital setting can serve a useful function in pathology residency training programs. In addition to elucidating the cause of death, they illustrate pathological processes unaltered by medical/surgical intervention, increase the number of cases with which residents have contact and frequently have “incidental” findings of significant educational value.



Education In Standardized Gross Examination And Tissue Submission Practice In Non-Tumor Colorectal Resections

P. Erivwo1, L. Gai1, H.S. Currens1, A. Taher1, F.X.Torres1, S.S. Raab1. 1Discipline of Laboratory Medicine, Memorial University of Newfoundland, St John’s NL.

Background: The lack of education in standardized gross examination practice may result in failures in patient safety, timeliness, and effectiveness of care delivery. Although standardized protocols and checklists exist for many gross examination procedures, the application of these protocols often is inconsistently applied to non-tumor specimens such as colonic resections.

Design: In our practice of residents and pathologist assistants performing gross examination, we performed a retrospective review of 90 consecutive cases of non-tumor colonic resections. Based on a literature review, we identified 19 important gross descriptors for inflammatory bowel disease (IBD), 9 for diverticular disease (DD) and 13 for ischemic colitis (IC). A descriptor defined a specific gross feature of the serosa, wall, or mucosa. We used a standardized checklist to determine the use of each descriptor and the number of blocks submitted in each case.

Results: We found a lack of descriptor use standardization and block submission number based on disease. For IBD, the highest, lowest, and mean number of descriptors used were 10 of 19 (6.7% of cases), 1 of 19 (3.3% of cases), and 5.5±2.4. For DD, these numbers were 5 of 9 (3.3% of cases), 1 of 9 (6.7% of cases), and 3.0±1.0. For IC, these numbers were 7of 13 (3.3% of cases), 2 of 13 (33% of cases), and 3.0±1.5. For the disease categories, individual descriptors were used at variable frequency, although the absence of descriptor use was high. For IBD, DD, and IC, the mean and highest number of blocks submitted were 12.7 and 24, 10.2 and 20, and 10.2 and 21, respectively.

Conclusion: The lack of education in and use of standardized gross room descriptor checklists and block submission protocols resulted in high levels of practice variability in block submission and insufficient gross descriptions for many cases. We propose the use of and implemented standardized checklists for non-tumor colonic resection specimens to improve diagnostic quality.



The Prognostic Significance Of EGFR, HER2 And c-MET Overexpression In Resectable Gastric Carcinoma (GC)

A.Paliga1, H.Marginean1, B.Purgina1,B.Tessier2, D.Jonker1, E.C.Marginean1. 1The Ottawa Hospital, ON; 2McGill Univ., Montreal, QC, Canada

Background: This study investigates the prognostic value of overexpression of EGFR, HER2 and c-Met by immunohistochemistry (IHC) in Canadian patients with GC and correlates expression with clinicopathologic characteristics.

Design: Tissue microarrays (TMA) containing 4 cores/tumor were constructed from 120 consecutive GC resected from 2002-2008, stained for EGFR, HER2 and c-Met by IHC, and scored from 0-3+. Receptor expression was compared with clinicopathological characteristics and survival.

Results: Of 113 evaluable cases – median age 64 (range 29-94), 72% were male, histologic type: intestinal 76%, diffuse 14%, mixed 10%. We observed no correlation between T, N stage and EGFR, HER2 or c-Met overexpression. Differences were observed according to histologic type: intestinal type expressed more frequently HER 2 (10/12; p=0.26) and c-Met (51/65; p=0.02).
IHC Expression n/% Median OS in months HR [95% CI],

IHC Expression


Median OS in months

HR [95% CI],




EGFR overexpression




1.60, [0.89-2.87], p=0.11

HER2 overexpression




0.51, [0.22-1.18], p=0.11

c-Met overexpression




1.17, [ 0.74-1.87], p=0.49



13 months

0.18, [0.02-1.43], p=0.04



not reached

Conclusions: HER2 overexpression in GC trended to superior OS, while EGFR and/or c-Met overexpression trended to poor OS. However, only the group of EGFR+/ c-Met+/HER2- reached statistical significance. Larger studies to confirm our findings are warranted, as targeted therapy may provide a major therapeutic advance.



Sensitivity And Specificity Of Community Fecal Immunotesting (FIT) Screening For Colorectal Carcinoma In Calgary, Alberta

Amber L. Crouse1, Lawrence De Koning1, S.M. Hossein Sadrzadeh1, Christopher Naugler1,2. 1Calgary Laboratory Services and the Department of Pathology and Laboratory Medicine University of Calgary, Calgary, Alberta, T2L 2K8. 2Department of Family Medicine, University of Calgary, Calgary, Alberta. Correspondence: Christopher Naugler (

Objective of Study: Community based programs are an ideal way of promoting colorectal cancer screening by primary care physicians. Fecal Immunochemical testing (FIT) is a screening method used in these types of programs. FIT has advantages to the patient as well as to clinical laboratories. In this study we assessed the operational test characteristics of a FIT pilot program in Calgary, Alberta.

Methods: 457 patients underwent FIT testing and had corresponding biopsy results that were classified as carcinoma, advanced polyp, and low-grade polyp. From these results, Receiver Operator Characteristic (ROC) curves were constructed. Subgroup analysis was also performed on males and females and for ages greater than and less than the mean age of 62. Areas under the curve (AUC) were derived from the maximum FIT and biopsy results.

Data: For carcinoma, advanced polyp, and low-grade polyp the AUCs were 0.79 (95% Cl 0.71-0.87), 0.57 (95% Cl 0.50-0.64) and 0.49 (95% Cl 0.41-0.54) respectively.

Conclusion: These results indicate that FIT was a good predictor of colorectal carcinoma, but a poor predictor of advanced and tubular adenomas. Additionally, FIT was more predictive in women and in younger individuals. The poor performance of FIT for adenomas suggests that FIT may miss early stage lesions and therefore should not be considered equivalent to screening colonoscopy.



Human Tissue Kallikrein-Related Peptidase 6 and 10 are Highly Expressed in Early Gastroesophageal Junction Adenocarcinoma

A. Grin1,2, M. Tripathi1,2, F. Rotundo1,2, M.N. Bassily3, G. Yousef1,2. 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada; 2Department of Laboratory Medicine, and the Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital Toronto, Canada.; 3Department of Community Medicien and Public Health, Menoufiya University, Egypt.

Gastroesophageal junction (GEJ) adenocarcinoma and its precursor, Barrett’s esophagus (BE), are increasing in incidence. The diagnosis of dysplasia and early GEJ cancer can be challenging and while early tumors are generally associated with a good prognosis, some behave aggressively. Members of the kallikrein gene family represent potential diagnostic and prognostic biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 6 (KLK6) and human tissue kallikrein-related peptidase 10 (KLK10) by immunohistochemistry in early GEJ adenocarcinoma and in BE with and without dysplasia. KLK6 and KLK10 immunohistochemistry was performed on a series of 30 early GEJ adenocarcinomas and an expression score was given for the tumor and surrounding dysplastic and normal Barrett’s mucosa, if present. KLK6 and KLK10 showed significantly increased expression in tumor compared to both dysplastic (p=0.009; p=0.05) and non-dysplastic BE (p=0.0002; p=0.0001). Increased KLK6 staining intensity was seen in tumor at the invasive front (p=0.006). There was no significant relationship between KLK 6 or KLK10 and histopathologic markers of poor prognosis. KLK6 and KLK10 are highly co-expressed in early GEJ adenocarcinomas with increased intensity of KLK6 at the invasive front. KLK6 and KLK10 expression may be useful diagnostic markers in GEJ tumors and KLK6 may be a marker of increased invasiveness.



Primary Squamous Cell Carcinoma Of The Transverse Colon In A Patient With Crohn’s Disease

C. Maedler1, L. Richer1, C. Lussier2, V. Marcus1. Department of Pathology, 1Montreal General Hospital, McGill University, Montreal, Quebec, H3G 1A4, 2Hôpital du Haut-Richelieu, Saint-Jean-sur-Richelieu, Quebec, J3A 1B7.

Inflammatory bowel disease is associated with approximately 1% of new colorectal cancers each year. The relative risk of developing colorectal cancer in Crohn’s disease is at least 2.5 times greater than the general population, with adenocarcinoma representing the majority of cases. We report a rare case of primary squamous cell carcinoma (SCC) arising in the transverse colon of a patient with Crohn’s.

This 33 year-old female with Crohn’s disease presented with an abscess in the transverse colon. Despite CT-guided drainage, a residual abscess remained. The patient then underwent a subtotal colectomy with an en-bloc resection of a segment of adherent jejunum. Microscopic examination showed high-grade glandular dysplasia of both the colon and ileum with two synchronous colonic adenocarcinomas (pT1 and pT2; pN0). Moreover, a primary SCC of the transverse colon with invasion into the jejunum (pT4b; pN1a) was identified in the abscess cavity. Immunohistochemistry for human papilloma virus was negative. No other primary SCC was identified. Two months later, the patient was found to have new and extensive liver lesions which were cytologically confirmed SCC metastases (pM1a). Seven months after initial presentation, she succumbed to her disease.

Although SCC of the anorectal region has been described in Crohn’s disease, primary SCC of the transverse colon is exceedingly rare. This case is notable because of the unusual presentation of primary SCC, as well as its aggressive course in a young patient. We review here the literature pertaining to gastrointestinal tract SCC in Crohn’s disease.

Although SCC of the anorectal region has been described in Crohn’s disease, primary SCC of the transverse colon is exceedingly rare. This case is notable because of the unusual presentation of primary SCC, as well as its aggressive course in a young patient. We review here the literature pertaining to gastrointestinal tract SCC in Crohn’s disease.



Evaluation Of Efficiency Of Histological Criteria In Detecting Lynch Syndrome (HNPCC) In Colorectal Carcinoma

PA Williams, E Tomiak, LE Bourns, F Halwani. Department of Pathology and Laboratory Medicine, and Medical Genetics; EORLA, The Ottawa Hospital and University of Ottawa, Ontario, Canada.

Introduction: Lynch syndrome (LS), or hereditary non-polyposis colorectal cancer, is the most common inherited colorectal carcinoma (CRC) syndrome accounting for 2-5% of all cases. Pathologists initiate IHC testing based on patient age and defined histological criteria. This study aimed to evaluate the efficiency of these criteria.

Design: All CRC cases diagnosed at The Ottawa Hospital (TOH) from January 2012-July 2013 were reviewed. Cases with MMR deficiency were reviewed with Medical Genetics for referral rates and outcomes.

Results: Of 480 cases of CRC reviewed, 90 (19%) cases had IHC performed for MMR status with 45 (9%) cases having intact MMR gene expression and 45 (9%) deficient (39 MLH1, 4 MSH2, 1 MSH6 and 1 PMS2). 15 patients were referred for genetic counseling with 5 patients declining, 9 patients tested and 1 pending. 3 germline pathogenic mutations were identified (1 each in MLH1, MSH2 and PMS2) with 4 cases pending. Histological criteria that were informative are: right colon cancer (82% vs 44%, p=0.0004), intraepithelial lymphocytes (IEL) (67% vs 31%, p=0.007), high histologic grade (60% vs 22%, p=0.0003) and any amount of mucinous differentiation (60% vs 27%, (p=0.0014). Other criteria without statistical significance were mucinous carcinoma (>70%), Crohn’s-like lymphoid aggregate (CLLA), stage and tumor size.

Conclusions: At TOH the incidence of LS with current detection is 0.6% of total CRC cases. Standardization of histological criteria will increase detection rate. We recommend testing be performed on any CRC that fulfils any of the following single criterion: 1) age <70 years, 2) right colon, 3) IEL, 4) high grade and 5) any mucinous differentiation. Using this strategy, 62% of total CRC cases will be tested with a positive predictive value of 57% and negative predictive value of 92%. We also recommend better physician and patient awareness of the value of genetic testing to other family members.

The basic assumption of any of the statistical test is that the sample is chosen at random from the population of patients, which is not the case if testing for MSI is based on somewhat subjective decisions by the clinicians/pathologists.

Based on the SAS output age in the average is older in the MSI group than the MSS group, and statistically significant. This can be explained by the fact that there will be many more hypermethylation patients who are older in the MSI group than LS, and therefore bring up the average age. Also, clinicians are more inclined to request MSI status for purposes of mono-therapy chemo vs multi drug in older patients who are less likely to tolerate multi drug. Reflex is to test the younger patients for MSI/LS.

S&S – in calculating the S&S, 5 characteristics were grouped together in order to determine what constituted a ‘Positive test’ or indicator, meaning that any ONE of the five may be present. It does not take into account patients who may have more than one or which factor may contribute more than the others to the test sensitivity or specificity.

PPV: 57%

NPV: 92%

Ideally we would have MSS/MSI test for ALL cases, but we do not, therefore these statistics are not entirely valid, a discussion around this is needed.

Future directions: Funding for BRAF and testing~100 cases for MMR that were not previously tested based on our “new” criteria.


a + b

= 97.78 %

95% CI: 88.19 % to 99.63 %


c + d

= 26.67 %

95% CI: 14.62 % to 41.95 %

Positive Likelihood Ratio

100 – Specificity

= 1.33

95% CI: 1.11 to 1.60

Negative Likelihood Ratio

  100 – Sensitivity  

= 0.08

95% CI: 0.01 to 0.61

Disease prevalence

  a + b  
a + b + c + d

= 50.00 % (*)

95% CI: 39.27 % to 60.73 %

Positive Predictive Value

a + c

= 57.14 % (*)

95% CI: 45.35 % to 68.37 %

Negative Predictive Value

b + d

= 92.31 % (*)

95% CI: 63.90 % to 98.72 %



Clear Cell Adenocarcinoma of the Colon

Jasim Radhi, Laboratory Medicine, Peterborough Regional Health Centre, Peterborough, ON Canada.

Background: Primary clear cell colonic adenocarcinoma is extremely rare. These tumors should be differentiated from metastatic renal cell carcinoma and other metastatic clear cell cancers. This report described two cases arising in the sigmoid colon.

Cases report: Two elderly male patients underwent sigmoidectomy which revealed rather large polypoid tumor masses. Histological examination showed adenocarcinoma well to moderately differentiate with florid clear cell changes and consist of rather uniform cells with clear to faintly pinkish cytoplasm. Both tumors seem to arise from pre-existing adenomas with clear cell morphology. The tumor cells contain intracytoplasmic glycogen. They expressed CK20 and were negative for CK 7 by immunohistochemical staining.

Conclusion: Clear cell colonic adenocarcinoma is rare type of colon cancer. They closely mimic metastatic clear cell carcinoma in morphology. The literature includes only few cases, mostly involving the left side of the colon.



Analysis Of Liver Core Biopsy Data From A Community Hospital

K Wu1, J Liu1. 1Department of Pathology and Molecular Medicine, McMaster University

Objective: To survey the epidemiology of liver tumors and medical liver diseases using two year consecutive liver biopsy data at a single community hospital site.

Methods: Results of 196 Liver biopsies from 2012-2013 were collected at a single community hospital. Demographics from all patients were obtained. Distribution and gender statistics of liver tumors and medical liver diseases were calculated.

Results: The mean age of all the patients was 60.4(SD 12.8, range 27-86). Men accounted for 59.7% and women accounted for 40.3% of the patients. A total of 64 out of 196 cases were liver tumors, with male to female ratio of 1.9:1. Metastatic adenocarcinoma was the most common type of liver tumors overall (50%, N=32). Cholangiocarcinoma was the most common type of primary liver tumor (16%, N=10). Hepatocellular carcinoma(HCC) was the second most common primary liver tumor (11%, N=7). Among medical liver diseases (N=132), Steatohepatitis was the most common at 39% (N= 52, male to female ratio 1.14:1). Billiary tract disease was next most common at 12 %( N = 16). Autoimmune hepatitis was found in 7% of medical liver cases (N=9, male to female ratio 1:8)

Conclusions: Gender distribution of liver tumors is in keeping with North American demographic data. Cholangiocarcinoma is more common than HCC in our data, possibly due to lower prevalence of hepatitis B & C at this geographical location. Steatohepatitis is the most common medical liver disease, which agrees with literature data. Autoimmune hepatitis is significantly over-represented in our data amongst medical liver disease (9/132) compared to the U.S epidemiology data.



A Novel Pdgfra Gene Mutation In A Gastrointestinal Stromal Tumor (GIST)

K.G. Sidiropoulos1, A. Pollet2, C. Brezden-Mazley3, A. Grin4. 1Department of Laboratory Medicine and Pathobiology, University of Toronto; 2Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto; 3Department of Medical Oncology, St. Michael’s Hospital, Toronto; 4Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON, Canada.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract, representing 1-3% of gastrointestinal malignancies. Activating mutations are most commonly found in the KIT gene in 75-80% of GISTs.

Platelet-derived growth factor receptor alpha (PDGFRA) gene is mutated in ~5% of GIST, most frequently in gastric GIST. Mutation mapping with correlation to sensitivity to tyrosine kinase inhibitor therapy is important for optimal patient outcomes. Here we describe a high-grade GIST arising within the small bowel mesentery of a 37 year old man. Mutation analysis demonstrated a novel GIST mutation in exon 18 of the PDFGRA gene, located within the tyrosine kinase domain. Clinical follow-up at 1 year showed no evidence of recurrence or metastasis, suggesting that this mutation is sensitive to imatinib.



Heterogeneity of Mucinous Tumors of the Vermiform Appendix, Correlation Of Histology And Immunohistochemical Analysis of BRAF Expression

Liena Zhao1, Wei Xiong1, David Capper2, Stefan J Urbanski1. 1Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Foothills Medical Center, Calgary, Alberta, Canada; 2Department of Neuropathology, Heidelberg University and Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ),69120 Heidelberg Germany.

Introduction: The mucinous neoplasia of vermiform appendix has been discussed on numerous occasions, however, the reliable identification of the precursor lesions remains elusive. Although it seems intuitively reasonable to suggest that appendiceal sessile serrated adenomas (SSAs) are the precursor lesions for the mucinous tumors of the appendix, such an association is difficult to prove. Two separate approaches are possible. One is to show morphologic continuity between SSAs and mucinous tumors, and the other to demonstrate the common molecular mechanisms operating in SSA and mucinous tumors. It has been shown that BRAF V600E mutation is the common molecular mechanism of SSA. We have attempted both approaches using archival material which has been collected over a period of 20 years.

Materials and methods: Twenty-five cases of sessile serrated adenomas, mucinous tumors, and mucinous adenocarcinoms of the appendix in the past 20 years were obtained for morphological examination, immunohistochemistry and molecular studies. Immunohistochemistry with antibody to BRAF V600E (clone VE1) on 1 case of SSA alone, 3 cases of mucinous neoplasms with pre-existing SSAs, 1 case of SSA with high grade dysplasia merging with mucinous adenocarcinoma, as well as 2 cases of the normal vermiform appendix was performed in collaboration with the group at the Heidelberg University in Germany.

Results: Morphological assessment of the twenty-five cases identified four appendices where SSA was continuous with mucinous tumor. In one case, SSA with high grade dysplasia was merging with mucinous adenocarcinoma. Cytoplasmic immunoreactivity for BRAF was present in the epithelial cells in the case of SSA. Two out of three cases of mucinous tumors arising from pre-existing SSA showed cytoplasmic positivity for BRAF both in the mucinous tumor as well as in the SSA. The case of mucinous adenocarcinoma exhibited cytoplasmic immunoreactivity both in the mucinous adenocarcinoma and in the SSA. Normal appendiceal mucosa was negative for BRAF.

Conclusions and future work: Our date suggest that the serrated pathway (BRAF V600E mutation) is operating within the tumorigenesis of the mucinous neoplasia of the vermiform appendix. This small sample analysis also indicates the presence of molecular heterogeneity both within the SSA as well as in the mucinous tumors of the appendix. Future work to be undertaken includes BRAF mutation analysis and/or molecular test on microsatellite instability.



Large Inflammatory Myoglandular Polyp of the Colon Treated by Endoscopic Mucosal Resection, A Case Report

S. Al-Bazzaz1, P. Kortan2, S. Al-Haddad1. 1Department of Laboratory Medicine, St Michael’s Hospital, Toronto, ON M5B 1W8; 2Department of Medicine, St Michael’s Hospital, Toronto, ON M5B 1W8.

Inflammatory myoglandular polyps (IMGP) are uncommon benign polyps of the large bowel, with only 70 cases reported to date. Here we report the largest IMGP removed completely endoscopically without the need for surgery. An 82 year old man presented with constipation and rectal bleeding. Colonoscopy revealed a pedunculated sigmoid polyp, 7cm in diameter with a red, smooth, spherical, hyperemic surface with patchy mucous exudates and erosions. After a biopsy was reported as a hyperplastic polyp, it was decided to remove the polyp endoscopically due to its large size. Histological examination showed surface erosions, hyperplastic glands with occasional cystic dilatations and inflammatory granulation tissue and radiating smooth muscle fibers in the lamina propria. The case was reported as IMGP. Because IMGP has a distinct endoscopic and histological appearance, several groups have suggested considering it a distinct entity. It is important for pathologists to differentiate this polyp from Peutz-Jehgers polyp, polypoid lesions associated with mucosal prolapse and juvenile polyps.



Lymph Node Dissection in Total Gastrectomy Specimens. A Retrospective and Prospective Institutional Review

Satwinder Multani1,2, Joanna C Walsh1,2. 1Department of Pathology, University of Western Ontario; 2Department of Pathology and Laboratory Medicine, London Health Science Centre

Introduction: Gastric cancer (GC) is the third leading cause of cancer death worldwide. Recent recommendations suggest that at least 16 lymph nodes (LNs) be pathologically assessed to ensure adequate staging in gastric cancer resections. This study aims to address the issue of pathological assessment of LNs resected in total gastrectomy specimens at a specialist center; firstly to quantify the mean number of LNs per specimen, and secondly to determine if this could be improved by providing an education session to pathologist’s assistants (PAs), and pathology residents.

Methods: A retrospective review of GC resections was performed by searching the LHSC archive for total gastrectomies performed between January 2010 and August 2013. Total number of LNs and number of positive LNs per case were recorded. An education session was then provided to emphasize to gross room staff the importance of retrieving a minimum of 16 LNs per case. The grossing protocol was amended to include the use of GEWF (glacial acetic acid, ethanol, distilled water, and formaldehyde) to attempt to identify additional LNs in cases where 16 nodes were not identified. LN counts in total gastrectomies performed subsequent to the education session were then assessed.

Results: Between January 2010 and August 2013, 20 total gastrectomies were performed at LHSC. The mean number of LNs per case was 20.6 (range 3-64). Following the education session 2 total gastrectomies were performed with a mean node count of 16.5 (range 14-19).

Conclusion: To date, the number of post-education session total gastrectomies is too small to draw definite conclusions; however, the routine LHSC grossing protocol yields a mean of 20.6 LNs per case. The lack of a significant increase in LN count immediately following the education session suggests that the routine protocol of thorough gross examination at our institution is optimal and meets recommended adequacy criteria.

Keywords: Gastric cancer, lymph node dissection, total gastrectomy.



Sporadic Desmoid Tumor of Probable Pancreatic Origin: A Rare Case Report

S. Xu1, D. Hurlbut1, S. Nanji2 and CH. Chen1. 1Department of Pathology and Molecular Medicine, and 2Department of Surgery, Queen’s University, Kingston General Hospital, Kingston, Ontario.

Desmoid tumors are locally aggressive neoplasms of (myo)fibroblastic origin characterized by their infiltrative growth with a high tendency for local recurrence, but lack metastatic ability. Intra-abdominal desmoids are frequently associated with familial adenomatous polyposis (FAP) or prior trauma. Desmoids arising in the pancreas are rare; only 11 cases have been reported with the majority being sporadic. We report a case of desmoid of probable pancreatic origin in a 33 year-old healthy female with no family history of FAP or malignancy. She presented with abdominal discomfort. CT scan revealed a well-circumscribed, solid, hypovascular mass measuring 14.4 x 13.4 x 10.3 cm that appeared to arise from the pancreatic tail. Surgical en-bloc excision of the tumor was performed. Grossly the tumor appeared epicentered in the retroperitoneum with contiguous pancreatic tail involvement. Microscopy showed an unencapsulated hypocellular mass composed of cytologically uniform and bland spindled cells arranged in broad sweeping fascicles within a collagenous stroma. The tumor cells exhibited strong nuclear immunoreactivity for β-catenin, and were negative for DOG1, CD117, S100, desmin, SMA and MSA, compatible with a desmoid. The resected transverse colon showed no evidence of polyposis. It is unclear whether this tumor arose primarily from the pancreas or the retroperitoneum although the sporadic nature is supportive of pancreatic origin. Syndromic desmoids tend to arise through somatic second-hit mutations superimposed on a germline mutation of the APC gene, whereas sporadic desmoids are more commonly associated with uniallelic mutations of the β-catenin gene. Syndromic desmoids have a significantly higher recurrence risk. The patient underwent no further treatment and is currently disease free 7 months after surgery.



Clear Cell Papillary Renal Cell Carcinoma: Histological Spectrum and Immunohistochemical Features of Two Cases

B.Kajal1, D.Lukic1, S.Alowami1. 1Department of Pathology and Molecular Medicine, McMaster University; 1Department of Pathology, St Joseph Hospital, Hamilton, Ontario, Canada.

Background: Clear cell papillary renal cell carcinoma “CCPRCC” is a low grade tumor of distinct entity, yet has not been added to WHO classification; this tumor has overlapping morphological features of both conventional renal clear cell carcinoma and papillary renal cell carcinoma and have positive immunoprofile for both entities. This is a less aggressive tumor compared to conventional clear cell renal carcinomas. CCPRCC poses a diagnostic dilemma for most of the pathologists. We aimed to study the histological spectrum and immunohistochemical profile of these rare tumors. True outcome of these lesions is still unknown due to limited literature available.

Design: These two cases were presented at our institution from 2011-2013 and were studied with respect to morphological details and immunohistochemical profile.

Results: Histological examination showed areas of papillary, cystic and conventional morphology. Nuclei were of low grade and showed luminal arrangement. Immunohistochemical stains showed diffuse positivity with CK7, AEI/AE3, CAM 5.2, EMA, Vimentin, and E-cadherin and negative expression with CD10 and CKIT; hence expressing the classical positive markers for both conventional and papillary renal cell carcinoma.

Conclusions: As CCPRCC is a challenging entity, a definite and accurate diagnosis is critical to manage these patients. In conclusion meticulous sampling, detailed careful histological examination and judicial use of immunostains are the key features solving this rare histological quandary.

Abbreviation used: CCPRCC, Clear Cell Papillary Renal Cell Carcinoma.



Ectopic Splenic Tissue in the Testicle: A Case Study

J. Boone, J. Cheesman, R. Ellis, V. Ring, N. Juneja, and V. Maksymov. Department of Laboratory Medicine, Grand River Hospital, Kitchener, Ontario.

Objective: To demonstrate how ectopic splenic tissue in the testicle (splenogonadal fusion) can clinically simulate a malignancy.

Method: Review of a case of a 56 year old male who presented with a left testicular mass clinically suspicious for malignancy.

Results: On gross examination, a left testicle (6.0 x 2.8 x 2.5 cm, 73 g) with attached epididymis, spermatic cord, and tunica vaginalis was received. On sectioning, a brown, homogeneous, solid, firm, encapsulated tumour-like mass (2.6 x 2.0 x 2.0 cm) was identified in the upper pole of the testis. A similar appearing vermiform paratesticular mass (3.5 x 1.2 x 1.0 cm) was identified adjacent to but separate from the main tumour mass. On microscopic examination, benign splenic parenchyma with no significant pathologic abnormality was identified in both lesions. There was no evidence of malignancy.

Conclusion: Ectopic splenic tissue (splenogonadal fusion) is a rare benign anomaly resulting from fusion of the splenic and gonadal primitive tissue during embryogenesis. This entity is usually left sided, although occurrence on the right side has been reported. This case study demonstrates an example of splenogonadal fusion which mimicked a malignancy. Splenogonadal fusion should be considered in the differential diagnosis of testicular masses.



Are Additional Deeper Levels in Bladder Biopsies Crucial?

Gena Ibrahim1, Manal Y. Gabril1, Jose A. Gomez1, Madeleine Moussa1. 1 Department of Pathology, Western University, London, Ontario, Canada.

Introduction: Microscopic examination of the routine three levels from bladder biopsies obtained from flat or papillary lesions identified in cystoscopy occasionally fails to identify a pathological lesion. However abnormalities may be found on additional deeper levels. The objective of this study is to assess the significance of deeper levels in bladder biopsies performed to diagnose papillary or flat lesions after routine levels are non-diagnostic as well as to revise the ideal number of levels which should be routinely examined in bladder biopsies in order to diagnose flat or papillary lesions encountered at cystoscopy.

Methods: 82 bladder biopsies performed at our institution (2012-2013) were included in this study. The total number of levels in each case was recorded. The pathological diagnoses from all cases were correlated with the cystoscopic findings and with the additional deeper levels in order to reach a diagnosis.

Results: 31/82 (37.8%) cases required additional tissue levels (the number of additional levels ranged from 3 to 9). 21/31 (67.7%) of these cases were positive for malignancy (low or high grade papillary urothelial carcinoma). All of the 21 malignant cases had positive or suspicious cystoscopic findings. 10/31 (32%) cases were negative for malignancy and had negative or suspicious cystoscopic findings.

Discussion: In approximately 37.8% (31/82) of the cases, the initial three levels were non-diagnostic. 67.7% (21/31) of these cases had urothelial carcinoma which correlated with positive or suspicious cystoscopic findings. Based on these preliminary data, we realize that additional deeper levels are often essential in establishing an accurate diagnosis and therefore we suggest that the recommendation for the appropriate number of levels in bladder biopsies should be revised.



Non-Papillary and Basal-Like Variant of Urothelial Carcinoma are Associated with Unfavourable Clinical Outcome

Mai KT1, Truong LD2, Gulavita P1, Ball CG1, Hakim SW1, Busca A1, Levac J1, Kos Z1, Flood TA1, Belanger EC1. 1The Ottawa Hospital and University of Ottawa, Pathology and Laboratory Medicine, Ottawa, ON, Canada; 2Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, Weill Cornell Medical College of Cornell University.

Objective: Urothelial carcinoma (UC) exhibiting large areas positive for urothelial basal cell immunohistochemical markers, basal-like UC (BUC) has not been identified. Herein, we characterize this aggressive variant of urothelial carcinoma.

Design: Consecutive invasive UC were grouped into non-muscle invasive (Group 1) and muscle invasive UC (Group 2). Representative sections were immunostained with CK20 and urothelial basal cell markers, CK5 and CD44. Staining for CK5 and CD44 was scored as high for staining of > 50% thickness of the epithelial nest or epithelium (BUC) and low for < 50% (non-BUC).

Results: There were a total of 248 patients with invasive UC, including 143 patients in Group 1 (papillary: 129, non papillary: 14) and 105 in Group 2 (papillary: 9, non-papillary: 96). Invasive component with high CK5/CD44 score (BUC) was noted in 15% and 36% for papillary and non-papillary UC in Group 1 and 36% and 79% for Group 2. Neoplastic cells in both groups with high CK5 score (BUC) were often uniform with mild to moderate atypia. BUC were associated with higher stage, rates of lymphovascular invasion and lymph node/distant metastases. UC in most cystectomy specimens with pT0/1 disease displayed low CK5 score or was frequently papillary. CK20 reactivity was low to negative in BUC and non-BUC with cellular dedifferentiation.

Conclusions: Muscle invasive UC was predominantly non–papillary BUC. Most UC in cystectomy specimens with superficial invasion (pT0 /1) were of papillary non-BUC type. CK5 immunostaining can identify invasive BUC, a category of UC with aggressive behavior, often requiring radical cystectomy.



Superficial Invasive Urothelial Carcinoma of Large Nested Variant with Regional or Distant Metastases: A Variant of Urothelial Carcinoma with Hidden Evidence of Stromal Invasion

Shaheed W. Hakim, Christopher G. Ball, Joelle Levac, Fawaz Halwani, Trevor A. Flood, Eric C. Belanger, Kien T. Mai. The Ottawa Hospital and University of Ottawa, Pathology and Laboratory Medicine, Ottawa, ON, Canada

Background: Superficial (non-muscle) invasive urothelial carcinoma (SINUC) is a well-known entity and is characterized by its features of disease recurrence and progression. Its potential of regional and distant metastases, however, has not been well investigated.

Method: We reviewed all cases of SINUC in our institution for a period of 4 years to identify SINUC with metastasis.

Results: Of 165 SINUC, there were 5 (3 ureter, 2 bladder) with regional lymph node metastasis (2/5) and distant metastasis (3/5 cases, in lung and/or bone). Male:female ratio was 3:2, and patient age ranged from 55-90. The SINUC were multifocal in 4 cases and measured up to 3 cm in diameter. Microscopically the SINUC predominantly formed solid and compact tumor masses with an endophytic pattern associated with subtle papillary growth. The neoplastic cells showed mild to moderate cytologic atypia, reaching high grade urothelial carcinoma (UC) in 3 cases. The invasive component consisted of medium to large nests of often slightly irregular contours extending beyond the basal contour of the neoplasm. Peri-tumoral edema, as evidenced by retraction artefact, was present in 4 cases. These 4 cases were originally diagnosed as non-invasive UC. The remaining case was a high grade SINUC associated predominantly with small invasive cell nests. Immunostaining revealed strong and diffuse CK5 and CD44 reactivity in 4 cases and variable reactivity for CK20.

Conclusion: SINUC with regional and distant metastases are often under-diagnosed as noninvasive UC due to the failure to recognize large invasive cell nests.



High Grade Urothelial Carcinoma with Multiple Coexistent Histological Components, Including an Area with Rhabdoid Differentiation

Shiquan Liu1, MD, PhD; Samuel Chen2, Frank Chen1, MD, PhD. 1Department of Pathology, Buffalo General Medical Center, State University of New York, Buffalo, NY, USA; 2City Honors School, Buffalo, NY, USA.

It is not uncommon for high-grade urothelial carcinoma (UA) to show divergent differentiation with the most common being squamous followed by glandular. However, rhabdoid differentiation in UA, which portends poor prognosis, is very rare. Here we present a bladder UA with rhabdoid as well as other histologic features. The patient was a 91-year-old female with history of gross hematuria who was found to have a large tumor protruding into the bladder lumen from the right lateral/posterior wall. The tumor fragments via transurethral resection measured 9.1 x 6.5 x 1 cm in aggregate and weighed 23.7 grams. Morphologically, the tumor demonstrated high grade UA with an area showing abundant eosinophilic cytoplasm, eccentric, large hyperchromatic nuclei, and prominent eosinophilic nucleoli, consistent with rhabdoid differentiation. Immunohistochemically, this area was positive for desmin and muscle specific actin, supporting above interpretation. There were also areas showing neuroendocrine, sarcomatoid, glandular and squamous features. Scattered giant cells were also noted. Immunohistochemical stains for vimentin and synaptophysin/chromogranin were positive in areas with sarcomatoid feature and neuroendocrine differentiation, respectively. Based on the overall morphological features and immunohistochemical patterns, this tumor was diagnosed as high grade urothelial carcinoma with rhabdoid, neuroendocrine, sarcomatoid, glandular and squamous differentiations. Similar cases in the literature were reviewed and compared with this case.



The Profile Of Mgmt Promoter Methylation Status In Brain Tumors

C.F. Li1,5, D.G. Munoz1,5, S.J. Bauer1, O. Pangan1, C.I. Coire2,5, J. Karamchandani1,5, J. Keith3,5, J.P. Provias4,6, S. Jothy1,5. 1Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, Ontario; 2Department of Laboratory Medicine, Trillium Health Partners, Mississauga, Ontario; 3Department of Laboratory Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario; 4Department of Laboratory Medicine, Hamilton General Hospital, Hamilton, Ontario; 5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario; 6Department of Pathology and Molecular Medicine, McMaster University Hamilton, Ontario.

O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation is a marker predicting benefit from chemoradiotherapy with temozolomide, and is used clinically to guide therapeutic decision-making for patients with malignant gliomas. We implemented a nested, gel-based methylation specific PCR to determine MGMT promoter methylation status, and received 134 FFPE-brain tumor specimens for testing. There were 110 cases of glioblastoma, WHO grade IV, in patients aged from 19 to 86-years-old, 68 males and 42 females. There were 24 cases of other gliomas that included anaplastic astrocytoma, anaplastic oligoastrocytoma, oligodendroglioma, anaplastic oligodendroglioma, anaplastic pilocytic astrocytoma and central nervous system primitive neuroectodermal tumor, WHO grade II-IV, in patients aged from 6 months to 91-years-old, 12 males and 12 females. Although the percentage of cases with MGMT promoter methylation was lower in glioblastoma (58%) compared to that in other gliomas (75%), this did not reach statistical significance (p > 0.05). The percentage of cases with MGMT promoter methylation was 83%, 69% and 59% in tumors with WHO grade II, III and IV, respectively. Thus, in our study, there was a trend that gliomas with a lower WHO grade were likely to display MGMT promoter methylation, although this did not reach statistical significance (p > 0.05). In glioblastoma patients at age of 64 years and younger, the percentage of cases with MGMT promoter methylation was 54%, while it was 64% in patients at age of 65 years and older, but this was not a statistically significant difference (p > 0.05). In patients diagnosed with glioblastoma, the percentage of cases with MGMT promoter methylation was 60% in males and 55% in females. This was not a statistically significant difference (p > 0.05). However, when a glioblastoma was located in the temporal lobe, the percentage of cases with MGMT promoter methylation was 61% in males and only 18% in females, and this was statistically significant (p < 0.05). Therefore, MGMT promoter methylation status is related to gender in temporal glioblastoma. As more cases are accrued, the significance of the trends observed will be re-examined.



Population Study Of Uterine Leiomyosarcoma Incidence, Mortality And Survival

O’Meara, A.1, Lytwyn, A.1, Elit, L.1, Akhtar-Danesh, N.1. 1McMaster University, Hamilton, ON, Canada.

Objective: Uterine leiomyosarcoma (U-LMS) is the most common uterine sarcoma. Five year survival is 15-30%. Current histologic criteria, correlated with patient outcomes, were proposed in 1994 and incorporated into WHO classification in 2003. Stage is the only consistent prognosticator for survival. We estimated trends in incidence and mortality indices from 1992 to 2008.

Methods: We searched Canadian Cancer Registry with ICD-10 codes C54 (uterine corpus) and C55 (uterus), and included only cases with ICD-O-3 codes 8890/3 (U-LMS), 8891/3 (epithelioid LMS) and 8896/3 (myxoid LMS). A flexible parametric model estimated relative survival (RS) by age group in women diagnosed with U-LMS between 1992 and 2008. We estimated crude probability of death (CPD) to compare deaths due to U-LMS versus other causes.

Results: There were 838 women; median age at diagnosis 53.0 years; 461 deaths. Incidence of U-LMS decreased from 1992 to 2008. Excess mortality rate peaked in the first year after diagnosis for all ages. RS decreased with increasing age. RS correlated inversely with year of diagnosis. CPD showed most deaths were due to U-LMS, with a greater proportion due to other causes in older age groups.

Conclusion: Peak in excess mortality in the first year after diagnosis may represent deaths of patients presenting in advanced stage. Decreased RS with age warrants further investigation to determine possible factors. Refinement in histologic criteria likely account for the apparent decreasing incidence of U-LMS over time, leaving tumors with worse prognosis in the U-LMS category and explains the apparent worsening RS in recent years.



Gynandroblastoma Including a Juvenile Granulosa Cell Tumor Component: A Rare Entity

Williams AS, Offman SL. Division of Anatomical Pathology, QEII Health Sciences Centre & Dalhousie University, Halifax, Nova Scotia.

Background: Gynandroblastoma is an uncommon to rare ovarian tumor characterized by the admixture of granulosa-theca cell and Sertoli or Sertoli-Leydig cell components, with the minor component comprising at least 10% of the tumor. In most cases the granulosa cell tumor component is of adult type and there have been only 8 reports of gynandroblastoma with a juvenile granulosa cell tumor component.

Case description: A 33 year old female underwent unilateral oophorectomy for an ovarian mass. The specimen received was a single enlarged, multicystic ovary measuring 7.5 x 6.5 x 4.5 cm. The serosal surface was intact and lacked nodularity. Serial sectioning revealed that the ovary was largely replaced by variably sized cysts, up to 3.4 cm diameter, filled with thin serous fluid. Bright yellow nodules, up to 0.4 cm, were present in the cyst walls. A minor component of the tumor was light tan and solid. Microscopic examination revealed distinct areas of granulosa cell tumor (GCT; 80%) mixed with both Sertoli cell tumor and well-differentiated Sertoli-Leydig cell tumor (20%). The GCT component was composed of various patterns of adult GCT (aGCT) in addition to juvenile GCT (jGCT); the latter showed nests of mitotically active cells with eosinophilic cytoplasm and rounded nuclei that lacked prominent nuclear grooves. The nests were interrupted by cyst-like spaces (macrofollicles) with variably eosinophilic to basophilic fluid. Of the GCT component, jGCT composed approximately 50%. Immunohistochemical evaluation demonstrated strong, diffuse vimentin expression in the jGCT with less avid staining in aGCT and a lack of expression in Sertoli components. Conversely, CD10 expression was strongest in the Sertoli components, weaker in the aGCT, and absent in the jGCT.

Discussion: Gynandroblastoma with a jGCT component is a rare entity. To the best of our knowledge, only 8 cases of gynandroblastoma with a possible jGCT component have been reported to date. The impact of a jGCT component on the otherwise good prognosis of gynandroblastoma is not known.



Divergent Presentations of Intravascular Leiomyomas: A Case Series

Sim J, Islam S, Sekhon H, Lamba M

Purpose: To illustrate the varied presentations of intravenous leiomyomatosis (IVL) and challenges that this entity presents.

Background: IVL is a rare tumor which, despite having been originally described in 1896, continues to be a challenging entity both conceptually with its pseudo-malignant behaviour and clinically due to a gamut of possible presentations. Tumor presentations in the literature range from syncopy to mortality from Budd-Chiari syndrome to the more common presentation of an incidental finding in a uterus removed for leiomyomata.

Methods: The pathology database at our institution was searched for all internal cases of intravascular leiomyoma. 4 cases were retrieved for clinicopathological review.

Results: The first of the 4 patients had a unique and complicated presentation. She had been followed and anticoagulated for a presumed thrombus in the IVC which eventually extended into both the pulmonary artery and through a patent foramen ovale. This turned out to be an intravascular leiomyoma with cardiac extension. The other 3 patients had incidentally detected IVL following surgery for known leiomyoma.

Conclusions: Both of these types of presentations present pitfalls. First of all, an incidental finding of IVL with uterine leiomyoma ideally requires hysterectomy with bilateral salpingo-oophrectomies to minimize likelihood of recurrence of the tumor. However, a second surgery to remove the ovaries does not always occur. The second pitfall is intracardiac extension of leiomyoma which may be mistaken for thrombus or even atrial myxoma with extension into the IVC.



Neurogenic Ovarian Cyst – A Rare Monodermal Teratoma

K Williams, P Williams, J Michaud, D El Demellawy. Department of Pathology, Children’s Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada

Introduction: Monodermal teratomas (MDT) are rare neoplasms that contain tissue derived from a single germ line. Most commonly, they are composed of thyroid tissue (Struma ovarii). MDT composed of other mature tissues are exceedingly rare. We report a case of a mature cystic teratoma composed entirely of mature neurogenic tissue.

Design: This case report reviews the histology and immunohistochemistry (IHC) of a mature neurogenic cystic teratoma composed entirely of neural tissue. A review of the electronic surgical pathology archives from 1975-2013 at our institution was conducted for all monodermal teratomas, as well as a thorough electronic review of the medical literature.

Results: Review of archives reveals this is the only case of ovarian pure neurogenic MDT. Review of the medical literature revealed only three cases of pure neurogenic cystic MDT.13 Detailed clinical, histological and immunophenotypic features of the current tumor is compared to the 3 cases reported in the literature. In the current case a wide IHC panel has been used including GFAP, EMA, Neurofilament, MAP 2 and NeuN and PGP9.5.

Conclusions: We report a case of pure neurogenic MDT of the ovary. This exceedingly rare tumour has been described only three times in current medical literature. To our knowledge, this is the first case with mature neurons and cerebellar elements. References:1. Spaun E, Rix P.Benign cystic monodermal teratoma of neurogenic type. Int J Gynecol Pathol. 1990;9(3):283 .2. Sah SP, Verma K, Rani S. Neurogenic Cyst of Ovary: An Unusual Massive Monodermal Teratoma. J Obstet Gynaecol Res. 2001;27(1):21. 3. Fogt F, Vortmeyer AO, Ahn G, et al.Neural cyst of the ovary with central nervous system microvasculature. Histopathology. 1994;24(5):477.



Repeated Length Polymorisms To Distinguish Somatic β-HCG Secreting Carcinoma From Trophoblastic Tumor: A Case Report

Mary Anne Brett, Monalisa Sur, Jeffrey Terry, Alice Lytwyn. McMaster University, Department of Pathology, Hamilton, Ontario, Canada.

Objective: Morphologically, β-HCG secreting somatic carcinoma can be difficult to distinguish from epithelioid trophoblastic tumors (TT). However, their distinction is critical due to their potentially differing prognoses and choice of chemotherapy. Presence of biparental alleles in TT can be identified with molecular testing. We describe a patient who presented with metastatic carcinoma and elevated serum β-HCG, and contrast this to an epithelioid TT in another patient.

Data and Results: A 32 year old female with recent possible spontaneous abortion presented with bilateral DVTs, and was found to have an increased serum β-HCG, a retroduodenal mass and multiple nodules in her lungs, liver, and para-aortic lymph nodes. Biopsy showed an epithelioid EMA and HCG positive neoplasm with otherwise non-contributory immunohistochemistry IHC. Molecular testing for biparental alleles in repeated length polymorphisms was negative, consistent with somatic origin. The second patient was a 35 year old pregnant female with aberrant serum β-HCG and a uterine epithelioid tumor positive for HCG. Clinical and pathologic findings were characteristic of epithelioid TT and molecular testing was not required. These 2 cases illustrate that HCG secreting tumors of different etiologies may have similar appearances, and when clinical and/or IHC findings are inconclusive, molecular testing may be useful.



Decidualized Endometrioma In Pregnancy: A Case Study

J. Boone, J. Cheesman, R. Ellis, V. Ring, and V. Maksymov. Department of Laboratory Medicine, Grand River Hospital, Kitchener, Ontario.

Objective: To contrast the imaging, gross, and microscopic characteristics of decidualized endometriomas and malignant ovarian tumors, and to propose a sampling guideline for suspected decidualized endometriomas.

Methods: Review of a case of decidualized endometrioma presenting in a 29 year old primigravid female with elevated serum CA-125 and sonographic features concerning for malignancy.

Results: The patient presented at 9 weeks gestation with a complex, multiloculated, solid and cystic right ovarian mass, radiographically concerning for malignancy. Her serum CA-125 was elevated at 86 U/mL. At 13 weeks she underwent a right salpingooophorectomy. On gross examination, the specimen consisted of solid ovarian mass, 12 cm in diameter, with multiple mucoid cyst-like areas. On histological examination, there was abundant decidualized endometrial stroma with inactive endometrial glands. The final pathological diagnosis was benign ovarian endometriosis with no evidence of malignancy.

Conclusion: Decidualized endometriomas present with clinical and radiological features concerning for ovarian malignancy and should be included in the differential diagnosis of pelvic masses presenting in pregnancy, even when malignancy is strongly suspected. Generous sampling, including areas of thickened cyst wall, solid areas, mural nodules, and papillary projections, should be performed to rule out malignant transformation.



Paravaginal Female Adnexal Tumor Of Probable Wolffian Origin

R. Yu1, S. Alowami1,2, A. Lytwyn1, M. Sur1. 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, L8S4L8; 2St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, L8N4A6.

Objective of the study: Female adnexal tumor of probable wolffian origin (FATWO) is a lesion of uncertain malignant potential that arises predominantly in the broad ligament, mesosalpinx, and ovarian hilus. Its occurrence in the paravaginal area is rare. The rarity of FATWO renders it susceptible to diagnostic pitfalls with other malignancies, particularly when it occurs at an unusual site. We describe a case of a 29-year-old female with a 6.6 cm left paravaginal FATWO that invaded into the vaginal lumen.

Method: An initial biopsy was performed and worked up with immunohistochemistry. Subsequently, the patient underwent a wide local excision.

Data and Results: The initial biopsy demonstrated features suggestive of spindle cell epithelioma, but with increased Ki67 proliferation index, for which a wide excision was recommended. The excision specimen showed epithelioid and spindle cells with areas of sieve-like pattern, prompting reconsideration as FATWO and a differential diagnosis of endometrial carcinoma and synovial sarcoma. Immunostains were diffusely positive for cytokeratins and focally positive for CD10, EMA, and calretinin. p16, CD99, CD56, and CD57 were positive, but of unknown significance. Myogenin, desmin, vimentin, AFP, Bcl-2, inhibin, WT-1, CEA, and S-100 protein were negative. CD117/c-kit, for which recent studies have suggested a possible role for Gleevac therapy in FATWO, was negative. FISH analysis for t(X;18), to exclude synovial sarcoma, was negative.

Conclusions: FATWO displays various architectural patterns, most commonly sieve-like. But this architecture may not be well appreciated on small biopsies, which may show mainly areas of spindle cells. Awareness of FATWO in unusual sites will help to avoid these diagnostic pitfalls.



Pathological Phenotyping Of Uterine Leiomyomas From Patients With Hereditary Leiomyomatosis And Renal Cell Cancer (HLRCC) Syndrome

S. Strickland1, G.Graham2, C. Gilpin2, I. Teo1, E.Belanger1, B. Djordjevic1.
1Department of Pathology University of Ottawa, and 2Department of Medical Genetics, Children’s Hospital of Eastern Ontario, Ottawa Ontario K1H 8M5.

Background: HLRCC syndrome is an autosomal dominant disorder resulting from mutations in the fumarate hydratase gene which predisposes patients to cutaneous and uterine smooth muscle tumors as well as renal cell carcinoma. The latter is often aggressive and can present in young patients. Uterine leiomyomas (ULs) are more common, and their recognition may offer an opportunity to identify patients with HLRCC. Recently, the histological features of HLRCC ULs have been described, however, the specificity and sensitivity of these features is not known. The aim of this project was to compare the frequency of previously described HLRCC features in ULs of patients with known HLRCC syndrome to those in patients with sporadic ULs.

Design: 4 patients with known HLRCC and ULs, and 100 patients under the age of 41 with no personal or family history of HLRCC syndrome and ULs (multiple with at least one >3 cm or solitary >10 cm) were identified. The following tumor pathological features were assessed: tumor number and size, cellularity, mitotic activity, nuclear enlargement, and presence of prominent nucleoli and perinucleolar clearing.

Results: Increased cellularity (8%) and focal cells with prominent nucleoli and perinucleolar clearing (67%) were commonly found in sporadic ULs The most distinguishing characteristic of HRLCC ULs compared to sporadic ULs was the presence of diffusely distributed cells (5-10%) with a combination of both enlarged (3x) nuclei with irregular contours and eosinophilic nucleoli with perinucleolar clearing. These features were identified in 100% of HRLCC and 3% of presumed sporadic ULs.

Conclusion: Recognition of specific morphologic features in ULs may identify patients who can benefit from genetic testing for HLRCC syndrome. If subsequently diagnosed, these patients and their family members can be followed by renal cancer surveillance programs.



Differential Expression of PAX8 in Invasive and in situ Endocervical Adenocarcinoma

S. Card MD1, G. Han MD, MSc2, S. Nofech-Mozes MD2, V. Dube MD2, N. Ismiil MBChB2, Z. Ghorab MD2, E. Slodkowska MD2, F.I. Lu MD2, M. Khalifa MD, PhD2 and M. Cesari MD, CM2. 1University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Ontario and 2Sunnybrook Health Sciences Centre, Department of Anatomical Pathology, Toronto, Ontario.

Objective: To characterize PAX8 staining patterns in in situ (AIS) and invasive (ADC) adenocarcinoma of the endocervix.

Design: 85 surgical specimens diagnosed as adenocarcinoma at our institution from 2009-2012 were reviewed and classified as usual, intestinal, or mixed types. The review yielded 65 and 49 cases of AIS and ADC, respectively, with 29 samples harboring both lesions. PAX8 staining was scored semiquantitatively with overall staining scores (SS) obtained for AIS and ADC by multiplying the nuclear score (0 = <1%; 1 = 1-25%; 2 = 26-50%; 3 = 51-75%; 4 = >75%) by the intensity score (1 = weak; 2 = moderate; 3 = strong) for each case.

Results: In general, ADC showed lower staining scores than AIS, with significant differences in mean staining score for all cases (p=0.0154). This trend was also seen between cohorts with usual type morphology only (p=0.0060). As compared to usual type morphology, intestinal type morphology showed decreased PAX8 expression, with significantly lower mean staining scores for combined AIS and ADC (p=0.00021). Using arbitrary binary (positive/negative) groupings over a range of staining scores from 4 to 8, the tendency for lower levels of expression in ADC (all types) was maintained as compared to AIS (p=0.0055 to p=0.0132).

Conclusion: PAX8 staining is significantly decreased in ADC as compared to AIS, and may be a useful adjunct in difficult cases. AIS or ADC of intestinal type shows low PAX8 staining.



Congenital Toxoplasmosis Diagnosed on Placental Histology in Triplets

Z. Khan, P. Farmer. Department of Pathology and Molecular Medicine, Kingston General Hospital, Canada.

Background: Neonates with congenital toxoplasmosis are at risk of infection-associated complications, including ophthalmologic and neurologic disabilities. Congenital toxoplasmosis, even asymptomatic at birth, should be treated early to reduce long-term disease sequelae.

Case: A 38-year-old, gravida four woman with unremarkable prenatal screening, delivered triplets at 32 weeks 4 days gestational age. The histologic examination of the placenta revealed a trichorionic-triamnionic placentation, with fetal membranes of all three triplets demonstrating intracellular organisms morphologically and immunohistochemically consistent with Toxoplasma gondii. Her post-delivery blood serology was positive for toxoplasmosis. The ophthalmologic assessment of triplet A revealed bilateral chorioretinal scars. The cranial ultrasound revealed intracranial calcifications and grade 1 intraventricular hemorrhage. Cerebrospinal fluid analysis revealed abundant red blood cells with decreased glucose and elevated protein concentrations. Triplets B and C appeared clinically normal. The cranial radiographic imaging and ophthalmologic examination were unremarkable. CSF cultures and serologic studies including, PCR analysis on urine and CSF were negative for the parasite. The triplets received antibiotic treatment for 1 year. At the age of 4 years, the triplets showed appropriate growth and neuropsychomotor development. Triplet A showed complete resolution of intracranial calcifications on imaging and bilateral stable chorioretinal scars on ophthalmological examination.

Conclusion and Discussion: Our findings show that placental examination is an effective tool for the early diagnosis of toxoplasmosis acquired in utero. The diagnosis of congenital toxoplasmosis based on placental examination in the present case prompted early antimicrobial treatment and prevented long term disease sequelae.



Low Grade Follicular Lymphoma with High Proliferative Rate: An Adverse Prognostic Marker?

Aisling O’Meara1, Zahra Merali1, Catherine Ross1 and Monalisa Sur1. 1McMaster University, Department of Pathology, Hamilton, ON, Canada.

Background: Follicular lymphoma is a monoclonal neoplastic proliferation of follicle centre B cells which accounts for one-third of all adult cases of non-Hodgkin lymphoma. It usually follows an indolent, incurable course with a median survival of 7-10 years. A subset of low grade FL is known to transform into high grade treatment-resistant lymphoma with a poor prognosis, usually diffuse large B cell lymphoma (DLBCL). In cases of low grade FL with high proliferative index (LG-HPI) it is unclear if histologic grade or PI is linked to its clinical aggressiveness.

Design: We identified new diagnoses of LGFL in our institution, defined as grade I or II/III (WHO criteria), between 2006 to 2012. PI was performed on all cases using Ki-67 immunohistochemistry and each case was interpreted independently by two hematopathologists. Cases of LGFL with PI >20% were interpreted as LG-HPI.

Results: We identified 103 new diagnoses of LGFL. 48 cases were LG-HPI, a frequency of 46.6%. In the LG-HPI group: the majority (52.0 %) were grade 2; 66.7% relapsed (average 37.3 months); 6.3% transformed into DLBCL; overall survival: 12.5% died (average 32.3 months).

Conclusion: LG-HPI had a higher relapse rate and shorter disease-free survival than LG-LPI group suggesting higher PI confers an increased risk of recurrence. More patients died of disease in the LG-HPI group indicating PI may be an important prognostic factor in LGFL. 6.3% of cases transformed into DLBCL in the LG-HPI group suggesting LG-HPI may have suboptimal response to traditional chemotherapy regimens and consequently this distinct entity may behave more aggressively.



Tissue Location Of Clonal Plasma Cells In Patients With Monoclonal Gammopathy Of Uncertain Significance (MGUS)

A. Wang, L. Shepherd, D. Lebrun, D. Good, P. Farmer. Department of Pathology and Molecular Medicine, Queen’s University, Kingston General Hospital, Kingston, Ontario.

Background: In small tissue biopsies of lymphoid rich lesions, observing the restriction of kappa and lambda light chain (K/L) expression by immunohistochemistry (ihc) is helpful evidence of a clonal neoplasm and influences whether a definitive diagnosis of lymphoma is rendered. A recent case of a core needle biopsy of a lymph node involved by follicular lymphoma illustrates a potential diagnostic pitfall of the demonstration of plasma cell clonality by K/L ihc. In this case, the plasma cells are K restricted by ihc, but are L restricted by flow cytometry (both results validated with adequate controls). Given the patient’s history of K restricted monoclonal gammopathy of uncertain significance (MGUS), it is speculated that the patient’s K restricted monoclonal plasma cells had infiltrated the L restricted follicular lymphoma. In the literature, clonal MGUS plasma cells located outside of the bone marrow cavity has never been reported. In this study, we examined the K/L expression in various tissue types from MGUS patients to elucidate the presence or absence of extramedullary clonal plasma cells.

Design: 11 MGUS patients with tissue containing plasma cells resected in our institution from 2010 to 2012 were identified. 12 tissue samples (2 lymph nodes; 8 colon; 1 appendix; and 1 small bowel) were stained for K/L and CD138 by immunohistochemistry.

Results: No striking difference between the K/L staining is observed. CD138 staining is negative in all cases.

Conclusion: In the small number of tissue samples tested, a clonal plasma cell proliferation has not been identified. In the future, we will validate these findings in a larger MGUS cohort and expand our cohort to include patients with multiple myeloma.



CD10-Positive Mantle Cell Lymphoma: Not A Distinct Entity By RNA Profiling

E. Mahe, A. Akhter, A. Mansoor; Department of Pathology & Laboratory Medicine, University of Calgary, Alberta, Canada, T2N2N9.

Mantle cell lymphoma (MCL) is very rarely CD10-positive; a review of the published literature notes only 42 CD10-positive MCL cases in the past 13 years, some described as having blastoid morphology or accompanied by other immunophenotypic or genetic abnormalities. As part of a larger study of the gene expression profile of 115 cases of classical MCL, we identified a subset of 9 CD10-positive cases. Of these, we were able to extract sufficient RNA from formalin-fixed and paraffin-embedded tissue to analyze 8, in concert with 8 other randomly selected CD10-negative MCL cases from our larger cohort. These 16 cases were subjected to a broad Nanostring RNA codeset analysis, which included probes for genes associated with Germinal-centre and Activated B-cell phenotypes, as well as the B-cell receptor, Toll-like receptor, NF-kB, AKT/Mtor, JAK/STAT, MAP-kinase, and MyD88 pathways. Bioinformatics analysis was performed using the BRB software platform. We were unable to demonstrate a gene expression difference between CD10-positive and CD10-negative MCL. We conclude that there is insufficient evidence to suggest that CD10-positive MCL cases have a cell of origin distinctive from cases of MCL that are CD10-negative, nor is there any evidence to suggest that any of the other molecular pathways in our analysis might account for this form of aberrant expression.



Follicular Lymphoma in situ A Case Report with Flow Cytometry Correlation

Hemlata Shirsat1, Heidi Paulin1, Wenda Hasegawa2, Dietrich Werner1. Dept of Pathology1, Dept of Clinical Hematology2, Dalhousie University, Halifax, Nova Scotia. B3H1V8

Introduction: Follicular Lymphoma in Situ is defined as a lymph node with presence of focal reactive germinal centers containing centrocytes staining strongly for BCL2 protein in an otherwise normal lymph node, associated with t(14;18) IGH/BCL2 translocation. These “in situ” lesions are incidental findings that may be transient, precede the development of Follicular Lymphoma, or are associated with overt Follicular Lymphoma elsewhere.

Case: Forty nine year old male patient had mesenteric lymphadenopathy and a biopsy showed predominant reactive changes with a follicular hyperplasia pattern. Immunohistochemisty studies identified irregular small B-lymphocytes CD10, BCL6, and strong BCL2 positive in the germinal centers. On flow cytometry a neoplastic B-cell population with a very bright CD10, dim CD20, dim CD19, and dim CD38 expression separate from the normal germinal center B-cell population was also identified. A bone marrow biopsy was negative for involvement by lymphoma.

Discussion: The diagnosis of Follicular Lymphoma in Situ is based on immunohistochemistry studies. Our case report shows the additional utility of flow cytometry in identifying these lesions.



Lymphoma of Female Genital Tract

K Jafari1, R Musani1, G Rasty1. 1Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Canada.

Objective: Extra nodal lymphoma of female genital tract is a rare presentation and accounts for less than 1% of NHL. It often poses a challenged and delayed diagnosis as the clinical presentation overlaps with common gynecological problems and imaging results are non-specific. Our objective is to add to the current literature for further characterisation of this rare presentation.

Method: We retrospectively identified and reviewed all the patients who were diagnosed primarily with lymphoma of cervix, uterus, vagina and fallopian tube between 2001 and 2013. This assessment consists of the clinical presentation, histological sub-type, clinical staging, treatment modality and response to treatment.

Results: In 12 years period we identified 10 patients. The average age at the time of diagnosis was 58.6 Y (43-68) and our average follow up time was 4.1 Y (1.3-10). The presenting symptoms were variable, and nonspecific. Concurrent unrelated gynecological problems were present in 5 cases (50%) and in 4 of them caused patients’ primary presenting symptoms, including 1 case with stage 4 lymphoma. B symptoms were present only in 1 case of DLBCL. Histological subtypes in this series are as follows: DLBCL in 5 cases, Follicular lymphoma in 3 cases, 2 out of 3 were in transformation to DLBCL, and MALT lymphoma in 2 cases. We included 3 cases at stage 4 disease with both nodal and extra nodal involvement. The bulk of the disease in these cases was female genital tract with pelvic lymphadenopathy.

Conclusion: Due to rarity of Non Hodgkin lymphoma in female genital tract, the literature in this regard is still evolving. Assessment of available data is of value to better characterise it and evaluate role of multimodal treatment in this matter.



The Molecular Profiling of Non-Small-Cell (NSC) Lung Cancer Samples

M. Forsythe, W. Greer, D. Bethune, W. Mozaychi, S. Douglas, M. McNeil, S. Snow, H. Henteleff, M. Castongay, Z. Xu. Dalhousie University, Halifax, NS.

Lung cancer is one of the most frequent causes of cancer-related deaths among men and women. Each type of lung tumour can be classified into four main types of cancer cells: adenocarninoma, squamous cell carcinoma, small cell carcinoma, and large cell carcinoma. Adenocarcinoma is the most common type of lung cancer in non-smokers and has been associated with a number of recurring mutations in ALK, EGFR, KRAS, PIK3CA, BRAF, and HER2 among other genes. Traditional chemotherapy has been largely ineffective. Recently, more effective drugs that target specific mutations have been developed. One of these drugs, Crizotinib, is a kinase inhibitor that is effective against ALK gene mutations. The object of this study is to determine if any correlations exists between genotypes and clinical phenotypes of the patients. The analyzed samples were primarily adenocarcinoma. Such correlations may allow for early diagnosis and treatment. Over 480 samples from our tumour bank were analyzed for the previously mentioned mutations using various procedures, including SNaPShot, FISH and fragment analysis for insertion/deletion mutations. At this point in the analysis, 7.5% of the samples have exhibited the EGFR mutation, 20.3% KRAS, 0% BRAF, 1.1% PIK3CA, 0% HER2 and 0.4% ALK. Correlations were made with specific patient data, including tumour stage, survival time and vascular/lympathic invasion. Of 50 patients who had a short survival time 26% expressed KRAS and 4% expressed EGFR. Molecular profiling may provide useful information in NSC lung cancer and may prove useful in guiding future targeted therapy, especially in cases where there are metastases or where the tumour relapses.



Nodal and Extranodal Amyloid Deposition in Marginal Zone Lymphoma: A Clinicopathologic Study of 5 Cases

Qi Zhang1, Cady Pocrnich1, Christopher Howlett1, Jessica Shepherd1, Angelika Hahn2, Annie Kurian3, *Kamilia Rizkalla1. 1Department of Pathology, 2Department of Neurology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada; 3Department of Pathology, Bluewater Health, Sarnia, ON, Canada.

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is the most common subtype of marginal zone lymphoma (MZL), with stomach being the most common primary site, followed by salivary gland, lung and ocular adnexa. Although clinically indolent, MALT lymphoma has the potential of local recurrence and systemic spread. Amyloid deposition is an unusual complication of MALT lymphoma and it has been reported to be limited to the lymphoid neoplasm. However, in this study, we report the clinicopathological features of 5 cases of MALT lymphomas with amyloidosis within the lesional tissue as well as amyloid deposits in other organs, having no significant lymphoma infiltrates. Of the two patients presented as primary ocular adnexal MALT lymphoma, one had amyloidosis at the mesentery and bowel wall, and one had deposits in the soft tissue of the jaw. Another patient formed an abdominal wall tumour-like amyloid lesion. Amyloid deposits are noted at recurrence sites in 4 cases. Clinical follow-up revealed amyloid neuropathy and possible renal amyloidosis in 2 patients. There are no association between plasmacytoid differentiation and development of amyloidosis. In conclusion, pathologists should be aware of the association between MALT lymphoma and amyloid deposition, which can be seen at primary site, or in a different organ, and Congo-red stain is to be performed on any MALT lymphoma biopsies with suspicious findings. Amyloid deposits can carry dismal prognosis.



PTPN11 Mutations in AML/MDS by Next-Generation Sequencing: A Single Institute Experience Using a Large Patient Cohort

Rashmi S. Goswami, Mark J. Routbort, Rajesh R. Singh, John Galbincea, Farhad Ravandi, Tapan Kadia, Naveen Pemmaraju, Guillermo Garcia-Manero, Hagop M. Kantarjian, L. Jeffrey Medeiros, Rajyalakshmi Luthra, Keyur P. Patel. Departments of Hematopathology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054.

Background and objective of the study: PTPN11 encodes for the tyrosine phosphatase Shp2, which is known to regulate several cellular processes. Mouse models with PTPN11 mutations show expansion of the stem cell compartment with development of myeloproliferative disorders. Somatic PTPN11 mutations are known to play a role in the development of juvenile myelomonocytic leukemia (JMML), but are rarely found in acute myeloid leukemias (AML) or myelodysplastic syndromes (MDS). Our objective was to examine myeloid neoplasms at MD Anderson for PTPN11 mutations by next-generation sequencing and characterize our findings.

Methods: 720 consecutive AML/MDS samples were tested for mutations using custom panels on a MiSeq (Illumina) platform. A retrospective analysis was performed to determine which cases had PTPN11 mutations and these were correlated to clinical findings.

Data and results obtained: Of the 720 cases, 19 demonstrated PTPN11 mutations including 14 AML and 5 MDS cases. The incidence of myelodysplasia was significantly higher in cases with PTPN11 mutation compared to wild type PTPN11. Out of the 19 mutated cases, 10 were associated with myelodysplasia (3 cases of MDS, 4 cases of therapy-related myeloid neoplasm, and 3 cases of acute myeloid leukemia with MDS-related changes).

Conclusions: PTPN11 mutations are present in a small subset of AML/MDS cases and are associated with myelodysplasia. Identification of PTPN11 mutations may provide a basis for targeted therapy in this subset of AML/MDS patients.



Hodgkin’s Lymphoma with Unusual Intrasinusoidal Involement

Weiwei Chen, MD, PhD, Maurice Barcos, MD, PhD. Department of Pathology, Buffalo General Medical Center, Buffalo, NY 14209.

Hodgkin’s lymphoma (HL) and anaplastic large cell lymphoma (ALCL) can usually be distinguished from each other by their distinct histological and immunophenotypic features. However, occasionally HL may show morphological appearances strikingly similar to ALCL. Rarely have such cases been documented in the literature. Here we report a case of classical nodular sclerosis Hodgkin’s lymphoma showing unusual instrasinusoidal pattern of infiltration. Examination of the cervical lymph node excised from a 62 year-old female reveals a prominent proliferation of large atypical mononuclear cells not only in the cortical and medullary areas but also within the subcapsular sinuses. These neoplastic large cells are positive for CD30, CD15, MUM-1 and PAX-5, with a MIB1 proliferation index of >50%, and are otherwise negative for CD45, TIA-1, granzyme B, CD56, CD57, EMA, CD3, CD20 and pancytokeratin by immunohistochemistry. Furthermore, the tumor cells are negative for ALK-1 on immunostain. These features are suggestive of HL instead of ALCL. The treatment and prognosis of HL is different from ALCL and hence it is very important for pathologists to recognize HL presenting with unusual intrasinusoidal involvement.



A Flow Cytometry Method for Assessment of Functional Cell Mediated Immunity

Suzanne Vercauteren1,2,3, Nicholas E Sunderland1, Peter van den Elzen1,2,3, and Angela Tsang2. 1UBC, VGH, Pathology and Laboratory Medicine, 2BC Children’s and Women’s Hospital, and 3Child and Family Research Institute (Vancouver).

Traditional methods (3H-TdT stimulation assay) for determining functional lymphocyte activity are cumbersome, and involve radioisotopes, as well as providing limited information. An alternative more informative flow cytometric based assay was developed. The first phase was to design a quantitative flow cytometric assay to assess T and B-cell proliferation in response to non-specific mitogens (PWM, PHA, SAC), using peripheral blood mononuclear cells from patients with suspected immunodeficiencies (n=43), and controls (n=30). The 3H-TdR method is as previously described. PBMCs in the flow cytometry arm were harvested and run by flow to calculate the number of events over a fixed time period. Comparison is made between unstimulated and stimulated populations for each stimulant, as well as with the 3H-TdR assay. We then expanded our panel to known human disease causing microbials and tested 15 otherwise healthy individuals. Flow cytometry method shows good correlation with 3H-TDR assay with R2 values of 0.50 for PHA, 0.70 for PWM and 0.67 for SAC. Correlation to 3H-TdR assay using non specific antigens is good. Correlation between assays using microbial stimulation with Rubella, Mumps, CMV and Candida is excellent especially when CD3+ cells are used (R2 0.54, 0.71, 0.97). Using CD3+ gated cells, the presumed effector cells to the stimulants, reduces background noise and may give more reliable results. The correlations with Measles, VZV, and HSV is low (R2 0.14, 0.37, 0.24). This may be due to a few controls with unusual results or the antigens used. Further statistical analysis is underway as is testing of more individuals. This flow cytometry assay lacks radioactive substances, and allows lymphocyte subpopulation analysis. Reporting units with the new assay to the current clinical standard (3H-TdR assay) facilitates clinical implementation.



Disseminated Aspergillosis with Multiple Organ Involvment in an Immunocompromised Patient

Y. Li, J. C-H Chen, J.P. Rossiter. Department of Pathology and Molecular Medicine, Queen’s University and Kingston General Hospital, Kingston, Ontario, K7L 2V7.

Aspergillus is an opportunistic organism preferentially found in an oxygen-rich environment that typically infects human hosts via inhalation. Aspergillus infection is notoriously hazardous in immunocompromised individuals due to the ability of the pathogen to disseminate beyond lungs hematogenously and the associated high mortality rate (30-95%). It is not uncommon for such an infection to remain undiagnosed until late in clinical evolution because of its often nondescript clinical presentation. Although aspergillosis can be suspected based on serological tests, a definitive diagnosis of invasive aspergillosis requires the demonstration of the organisms in tissue. Here we report a case of disseminated aspergillosis in a previously healthy 74 year-old female who was put on dexamethasone (4 mg po qid) for management of brain edema related to a large frontal meningioma while awaiting surgery. She presented in rapidly progressive respiratory failure with multiple cavitary lung lesions on imaging studies. A transbronchial lung biopsy showed microorganisms with characteristic morphologies for aspergillus. Unfortunately, she passed away shortly after the diagnosis despite antifungal regimen. Postmortem examination revealed extensive disease burden in the lungs and widespread dissemination to other organs, including the brain, thyroid gland, heart and kidneys. Histology displayed organisms with characteristic hyphal morphology with 45 degree branching, tissue invasion and necrosis. Movat stain further demonstrated extensive angioinvasion. Post-mortem lung culture confirmed the organism as Aspergillus fumigatus. This case illustrates the most aggressive manifestations of aspergillus infection in an immunosuppressed host and underlines the importance of maintaining a high clinical suspicion in an immunocompromised individual with infectious symptomatology and the value of early biopsy in such cases.



The International Collaboration on Cancer Reporting (ICCR): Development of Evidence-Based Core Datasets for Cancer Pathology

JR Srigley1,2; F Bosman3; B Chmara4; J Dvorak4; L Hirschowitz5; M Judge6; A Kwiatkowski1; MK Washington4; M Wells3, 5; DW Ellis6. 1Canadian Partnership Against Cancer, Toronto, Ontario, Canada; 2Canadian Association of Pathology, Toronto, Ontario, Canada;3European Society of Pathology; 4College of American Pathologists, Northfield, United States; 5Royal College of Pathologists, London, United Kingdom;6 Royal College of Pathologists of Australasia, Sydney, Australia.

Objectives of Study: Cancer pathology datasets are foundational elements for clinical cancer care, surveillance, public health management and epidemiological research. Global collaboration in standardization of cancer pathology datasets development is essential for international benchmarking in cancer control and to reduce the burden of data set development to the pathology community, but has not been previously attempted. The objective of the project is to develop a process for the production, dissemination and implementation of international evidence-based pathology cancer datasets using the best international expertise available.

Methods: The International Collaboration on Cancer Reporting (ICCR) was established in 2011 among the Pathology Colleges and Associations of the USA, UK, Canada and Australia. Cancer datasets from various organisations are harmonised and updated by internationally recognised pathologists and subjected to evidentiary and worldwide review, followed by publication in peer-reviewed journals. Key international cancer organisations endorse and participate in the process.

Data, Results and Discussion: Four datasets have been published and posted to the ICCR website to date and another six are currently in production. The International Agency for Research in Cancer (IARC) has partnered with ICCR to synchronise the publication of subsequent ICCR datasets with future WHO Tumour Classification volumes (Blue books). The ICCR is engaging with organisations involved in tumour staging including the Union for International Cancer Control (UICC) and the American Joint Commission on Cancer (AJCC). The European Society of Pathology (ESP) joined ICCR as a founding member in 2013, bringing over 68 countries and more than one billion people under a common process.

Conclusions: The ICCR has developed an efficient process for the production of internationally standardized and evidence-based datasets that can be used in both developed and developing countries. Engagement with key international cancer and pathology organisations will foster their adoption worldwide for international benchmarking in cancer management and control.



Secretory Activity in Colorectal Villous Adenomas: Is Mckittrick-Wheelock Syndrome a Discrete Entity?

Peter Nicholson1, Christopher Naugler2. 1Department of Pathology and Laboratory Medicine, Dalhousie University, Halifax, Nova Scotia; 2Department of Pathology and Laboratory Medicine and Department of Family Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.

Colorectal villous adenomas are infrequently associated with a syndrome of fluid and electrolyte depletion known as McKittrick-Wheelock Syndrome (MWS). The purpose of our study was to determine whether villous adenomas that cause MWS represent a distinct secretory phenotype or simply the extreme of a secretory continuum, a question that is debated in the literature. We performed a retrospective case-control analysis comparing the closest prior serum electrolyte values for 317 patients diagnosed with villous adenoma at polypectomy to those of 881 age and gender-matched controls diagnosed with hyperplastic polyp at polypectomy. Conditional logistic regression was performed to calculate the odds ratio for each electrolyte. Differences in serum electrolyte values between cases and the mean values of matched controls were then tested for normality. Significantly (p=0.002) lower potassium values were observed in villous adenoma cases, with an odds ratio of 0.648 (95% CI 0.494-0.851). Shapiro-Wilk tests of normality for all three electrolytes were non-significant, consistent with differences for each electrolyte comprising a normal distribution. We conclude that colorectal villous adenomas are associated with significantly lower serum potassium values that are attributable to a normally distributed continuum of secretory activity, the extreme end of which may manifest as clinically apparent electrolyte depletion as seen in MWS.



miR-199a-3p Iis Downregulated in Papillary Renal Cell Carcinoma Type 1 and Targets MET and MTOR

S.J. Wala1,2, J. Karamchandani1, Y. Youssef1, S. Al-Haddad1, R. Saleeb1, A. Evans3, G. Yousef1,2. 1Department of Laboratory Medicine and Pathobiology, St. Michael’s Hospital, Toronto, Ontario, M5B 1W8; 2Department of Laboratory Medicine and Pathobiology, Toronto, Ontario, M5S 1A8; 3Department of Pathology, Toronto General Hospital, Toronto, Ontario, M5G 2C4.

Papillary renal cell carcinoma (pRCC) is the second most common subtype of renal cell carcinoma (RCC), and can be further classified as type 1 or 2. To our knowledge, the role of dysregulated microRNA (miRNA) expression in pRCC type 1 has not yet been thoroughly investigated. Total RNA, including miRNAs, was extracted from fresh frozen pRCC type 1 tissues and matched normal kidney. The expression level of miR-199a-3p was measured to be significantly downregulated in pRCC type 1 by quantitative reverse transcription PCR (qRT-PCR) (P < 0.0001). Using target prediction analysis, MET and MTOR were identified as potential targets of miR-199a-3p. By qRT-PCR, we measured a higher expression for MET in pRCC type 1 compared to normal kidney (P = 0.003). A mimic for miR-199a-3p was transfected into 786-O cells, and a decrease in the mRNA expression level of MET and MTOR was observed compared to untransfected cells and negative control. The interaction between miR-199a-3p with MET and MTOR was further validated by performing a 3′ UTR luciferase reporter assay. We noted a decrease in luminescence signal between cells co-transfected with miR-199a-3p mimic and plasmid encoding for the 3′ UTR of MET or MTOR compared to cells transfected with plasmid only. MET regulates the focal adhesion pathway, and we noted that many members of the focal adhesion and extracellular matrix pathway are dysregulated in pRCC type 1 compared to normal kidney tissue by qRT-PCR. In conclusion, miR-199a-3p may have a tumor suppressive function in pRCC type 1 by downregulating the expression of MET and MTOR, and members of the focal adhesion pathway may serve as therapeutic targets for this RCC subtype.



Posttransplant Malignancy in Heart and Lung Transplant Recipients: A Clinicopathological Study

K. Caicedo, D. Yu, C. Sergi, S. Girgis, B. Chiu. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta.

Solid organ transplantation (SOT) is an extremely viable treatment for patients with end stage organ diseases, however, posttransplant malignancy (PTM) remains one of the long-term complications in organ transplantation. Objective: We performed a clinico-pathological review of PTM in heart transplantation (HT) and/or lung transplantation (LT) in our institution.

Method: Recipients of HT and/or LT at the University of Alberta Hospital were retrieved from Netcare and Copath data systems. PTM from the HT and LT recipients were reviewed and classified as: 1. Cutaneous, 2. Posttransplant lymphoproliferative disorder (PTLD), and 3. Non-cutaneous Non-hematolymphoid (NCNH) types.

Results: 921 transplant procedures were conducted between 1996 and 2011 which included 510 heart and 424 heart- and/or lungs. There were 230 PTM developed in 113 patients: 156 cases of cutaneous type (66%), 24 cases of PTLD (10%), and 55 cases of NCNH (24%). The cumulative incidence rate of PTM in HT and LT was 14.5% and 9.2% respectively, representing more than 2-fold increase compared with the general population. The latency period of PTM onset ranged from 4 months to 10 years, with skin of the head and neck, ano-genital tract and lung being the most common organs involved. Squamous cell carcinoma was the most common cancer type, often multifocal, recurrent and associated with HPV infection. PTLD commonly (50%) involved extranodal sites and associated with EBV infection.

Conclusion: PTM are common in HT and LT recipients, and commonly involving head and neck, PTLD of nodal-extranodal, ano-genital and lung. Oncogenic viruses play an etiologic role in the development of PTM in HT and LT recipients.



Metastatic Hepatic Meningioma: 2 Cases with Review

Christine Orr, Jenna-Lynn Senger, Rajni Chibbar, Mark Hiken, Rani Kanthan. Dept. of Pathology & Lab Medicine, University of Saskatchewan, Saskatoon, SK, S7N 0W8.

Objective: Although meningiomas are usually benign indolent tumors, distant metastases can occur infrequently; metastasis outside the central nervous system is extremely rare. Two cases of urgent liver biopsies received by the triage anatomical pathologist are discussed.

Method: A liver biopsy in a 31-year-old female and a 70-year-old female were worked-up for primary vs. secondary lesion in the anatomical surgical laboratory. A Medline literature review was undertaken to determine the prevalence of such unusual hepatic lesions.

Results: Examination of the liver biopsy in both cases confirmed the presence of neoplastic cells consistent with a malignant neoplasm likely non-hepatic in origin. Additional clinical history revealed repeated surgeries for meningioma. Immunohistochemical studies working in consultation with the neuropathologist confirmed the presence of metastatic hepatic meningioma.

A literature review identified twelve cases of metastatic hepatic meningioma.

Conclusion: Though extracranial metastases from meningiomas are of rare occurrence, a high degree of clinical suspicion is warranted in examination of such extracranial presentations. Detailed clinical history with communication between ‘subspecialized’ pathologists (ie neuropathologists and GI pathologists) is of paramount importance for accurate identification of these unusual hepatic metastases.



Calcifying Pseudoneoplasm of the Neural Axis: 2 Case Reports

L. Kocovski1, N. Parasu2, J. Provias1, S. Popovic1. 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario; 2Department of Radiology, McMaster University, Hamilton, Ontario.

Calcifying pseudoneoplasm of the neural axis is an uncommon condition with excellent prognosis but is often misdiagnosed due to its nonspecific clinical presentation and varied findings on radiology. The authors report two cases of calcifying pseudoneoplasm with corresponding pathologic and radiologic findings.

The first case was documented in a 64-year-old woman, who presented with lower back pain with radiation to her left leg. Imaging of her lumbar spine revealed a 3.8 x 2.2 cm calcified lesion at the level of vertebrae L5 and S1. A subsequent excision exposed an extradural lesion at L5. Histopathologic examination showed amorphous and granular calcifying material with occasional fibrohistiocytic and giant cell reaction, consistent with calcifying pseudoneoplasm of the neural axis.

The second case was documented in a 70-year-old man, who presented with headaches, decreased memory, disordered speech, and falls. Imaging of his head revealed a 2.4 x 2.6 cm well circumscribed, lobulated, calcified lesion within the basal frontal lobe. Subsequent resection exposed an intradural mass with nodular arrangement of amorphous and granular calcifying material associated with fibrohistiocytic and giant cell reaction.

Both patients had a favourable post-operative course and failed to show any clinical or radiologic sign of recurrence.



Orbital IgG4-related Disease with Superposed Grave’s Ophtalmopathy Mimicking an Orbital Tumor

Soufiane El Hallani, Susane Robertson, Paula Blanco, James Farmer, Manisha Lamba. Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa ON, Canada.

Background: Immunoglobulin (IgG) 4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. While IgG4-RD in association with Hashimoto’s thyroiditis has been reported, the relationship between IgG4-RD and Graves’ disease is not well known.

Case Report: We describe the case of a 56-year-old woman with chronic Grave’s ophtalmopathy who presented with acute onset of eyelid swelling and conjunctival injection. CT scan demonstrated the presence of an infiltrative right orbital mass and lachrymal gland enlargement, mimicking a lymphoma. Biopsy samples from the orbital mass tissue showed non-neoplastic lymphoplasmacytic infiltration, increased number of IgG4-positive plasmacyte per high-power field and IgG4-positive/IgG-positive plasmacyte ratio of > 40%. The histopathological findings of orbital tissue matched the characteristic features of IgG4-RD. The patient responded well to corticosteroid therapy.

Discussion: We discuss here the simulation of orbital tumour by IgG4-RD and the association with Graves’s disease with questionable pathogenesis overlapping. Further data and reports are needed to gain more knowledge about a rare presentation.



Cavernous Hemangioma of the Uvula: Report A Rare Case with Literature Review

Minhua Wang1, MD, PhD; Samuel Chen2, Frank Chen1, MD, PhD. 1Department of Pathology, Buffalo General Medical Center, State University of New York, Buffalo, NY, USA; 2City Honors School, Buffalo, NY, USA.

Hemangiomas of the oral cavity are relatively rare with a prevalence rate of less than 1%, mostly involving lips, tongue, buccal mucosa, and palate. Cavernous hemangioma is a subtype of hemangioma. The involvement of uvula by a cavernous hemangioma is extremely rare. To date, only less than 10 cases have been reported in the English literature. Here we report such a case with analysis of its histologic and immunohistochemical features. The patient was a 58-year-old white male with a mass on the left side of his uvula. Because a simple excision of this lesion would have rendered the inferior portion of the uvula pedunculated, possibly causing a globus sensation, a partial uvulectomy was done to maintain the integrity of the remaining uvular structure. Grossly, the lesion was a tan-pink polypoid mass partially covered by squamous mucosa, measuring 0.8 x 0.5 x 0.3 cm. Microscopic examination revealed poorly circumscribed large cavernous spaces lined by flattened endothelium, separated by scant connective tissue, morphologically consistent with cavernous hemangioma. Immunohistological study showed that CD34 stain highlighted the endothelial cells, supporting this diagnosis. By reporting this case with rare erratic location of cavernous hemangioma, we like to raise the awareness that cavernous hemangioma is also in the differential diagnosis when a patient presents with an elongated uvula or uvular mass.



Application of the Histologic Risk Model to Low Stage Oral Squamous Cell Carcinoma: Impact on Recurrence and Death

Namita Sinha1, Matt Rigby2, S. Mark. Taylor2, Michael L. McNeil2, Robert.D. Hart2, Jonathan R.B. Trites2, Martin J. Bullock1. 1Department of Pathology; 2Department of Surgery & Division of Otolaryngology, QEII Health Sciences Center, Dalhousie University, Halifax, Nova Scotia.

Background: Surgery is the mainstay of treatment for stage I/II OSCC and adjuvant therapy is needed in patients with high-risk prognostic factors. We used the existing Risk Model to assess 3 histological features (perineural invasion (PNI), lymphocytic host response (LHR), worst pattern of invasion (WPOI)) and classified the patients in three risk categories (RC- low (L), intermediate (I) and high (H)). We correlated RC and other variables with recurrence and death.

Design: We studied all patients with stage I/II OSCC who received surgical treatment between January 2001 and July 2012 for WPOI, LHR and PNI on H&E stained sections. Histological Risk Assessment score was applied. Recurrence and mortality were determined. Univariate association between these outcomes and multiple factors were tested using a 2-tailed Fisher exact test.

Results: We reviewed 59 cases with stage I/II OSCC. We found recurrence was significantly associated with RC (H- 37.5% vs. I/L-8.7%; P =0.024), PNI (present-77.8% vs. absent-13.0%; P=0.037) and LHR (absent/little-52.6 vs. moderate/complete-11.1%; P=0.003). Although in the complete cohort there was no statistically significant association between RC and death, the evaluation of cases with longer follow up (>3 years) does show a statistically significant association.

Conclusion: Our preliminary results indicate that the RC is useful tool to assess risk of recurrence and possibly death. RC may be useful to determine which patient should receive adjuvant treatment in low stage OSCC.



Looking Beyond Morphology: Percerving the Molecular Ascribes to the Gleason Grades and their Biological Significance

Qiang Ding QD1, Zsuzsanna Lichner1, Carol Saleh1,, Sara Samaan1, Peter Kupchak1, Moyez Dharsee1, Annika Fendler2, Kenneth R Evans1, Klaus Jung2, George M Yousef1*. 1Department of Laboratory Medicine St. Michael’s Hospital, Toronto, Canada, M5B 1W82. 2Department of Biology, Chemistry and Pharmacy, Free University, Berlin, Germany.

The Gleason grading (GG) system is based on the architectural features of prostate cancer. There is significant interobserver bias among pathologists in the assigning of GG, and biopsy can under represent the tumor grade. It is important to reveal the biological attributes of the GG and reclassify them according to biology rather than the morphology. miRNAs are short, single stranded RNA molecules. We analyzed global miRNA expression from formalin-fixed paraffin embedded tissues extracted from pure areas of GG 3-5. A total of 40 miRNAs were found to be significantly differentially expressed between the different Gleason grades. 11 miRNAs were found to be significantly dysregulated between Gleason grades 3 and 4. miR-29c was found to be significantly downregulated between both Gleason grades 3 and 4 as well as Gleason grades 4 and 5. Target prediction of miR-29c and miR-34a showed that these miRNAs are involved in focal adhesion kinase and MAP-kinase pathways. We validated gene expressions of Col1A1, Src, Prkca, MAPK13 and ITGB before and after miR29c or miR34a transfection. Over expression of miR-29c in prostate cancer cell line resulted in significant reduction in cell proliferation.

Conclusion: Our results suggest that miR might be a biomarker for distinguish the prostate cancer progression and promising biomarkers for prognosis.



Utilization of Image Analysis for Estimating Surface Area of a Region Selected for Microdissection

Sherine Salama MD, Nagham Abdalahad MD, PhD, Elzbieta Slodkowska MD, Sharon Nofech-Mozes MD. Sunnybrook Health Sciences Centre and University of Toronto

Automated high-speed, high-resolution whole slide image technology is being rapidly adopted in pathology as a research and clinical tool. Advanced techniques enables use of formalin fixed paraffin embedded tissue (FFPE) for a growing number of molecular assays. These methodologies often require macro or microdissection to enrich the content of the cells targeted for analysis. Since there is a relationship between the surface area represented by the lesion, the region of interest (ROI) and the yield of nucleic acids, pathologists are often requested to estimate the surface area involved by the lesion and algorithms are developed to determine the number of sections required to secure successful assays. This study aims to demonstrate the utility of slide imaging technology over conventional estimation of surface areas marked for macro/microdissection.

Material and Method: 200 breast archival specimens with ductal carcinoma in situ (DCIS) accessioned in our institution over 5 years were retrieved. Optimal slide representing the tumor was selected. ROI was manually marked and surface area estimated by multiplying the largest contiguous linear span of DCIS by the extent of perpendicular linear dimension giving an estimated surface area. The same set of slides was scanned by Aperio XT at 20x resolution. Using the annotation tools of e-Slide Manager, the outlines of area affected by DCIS were marked and surface area calculated. Statistical analysis performed by obtaining the median and range of the readings and compared by Paired Student t-Test.

Results: Scanning was successful in all slides. The median manually measured pathologist estimated surface area was 12 mm2 with the range of (1-476 mm2). The median surface area of ROI based on image analysis was 8.27 mm2 with the range of (0.19- 444.6 mm2) .This was significantly different with a p value of less than 0.0001. Surface area of the lesion targeted area was overestimated in 86.6% of the cases. 123 out of 200 cases were over estimated by 25%, 33 of them were more than 50%.

Conclusions: Image analysis is a useful tool, with growing availability that can enhance the accuracy of measurement of ROI selected for macrodissection for molecular testing in research and clinical settings. Irregular and complex geometric shapes contribute to the inaccuracy of manual measurement.



Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case Presentation

Allison Osmond1, Emily Filter1, Mariamma Joseph1, Keith Kwan1. 1Western University, London, Canada.

Carcinoid tumor is a well-known primary endobronchial lung neoplasm. Although calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near complete ossification of these tumours is an unusual finding that is rarely reported in the literature. A 45 year old man presented with two episodes of hemoptysis and progressive exertional wheezing over a 9 month period. He had an unremarkable medical history and was an ex-smoker. A CT scan revealed a calcified 4.2 cm hilar mass with associated right middle lobe collapse. Bronchoscopy confirmed the presence of a highly vascular and obstructive endobronchial mass. Initial endobronchial fine needle aspiration of the mass was indeterminate. A right middle lobe resection was undertaken with intraoperative consultation for preliminary diagnosis and to determine bronchial resection margin status. Intraoperative gross examination revealed a hard calcified mass not amenable to sectioning, precluding conventional frozen section assessment. Cytology scrape smears were obtained from a focus of grossly viable endobronchial tumour (Diff Quik and H&E). Intraoperative smears revealed a cellular neoplasm with features highly suggestive of a well-differentiated neuroendocrine (carcinoid) neoplasm. Microscopic examination of the formalin-fixed decalcified mass confirmed the preliminary cytologic diagnosis of carcinoid (typical) tumor, with extensive ossification. We present a very unusual case of an endobronchial carcinoid tumor with extensive ossification in a 45 year old male.

Keywords: carcinoid tumor, ossification, lung, intraoperative cytology



Pleuroparenchymal Fibroelastosis: An Autopsy Case Report and Review of the Literature

M.D. Carter, MD, PhD & M.C. Castonguay, MD, FRCP(C). Department of Pathology and Laboratory Medicine, QE II Health Sciences Centre, Halifax B3H 2Y9.

Pleuroparenchymal fibroelastosis (PPFE) is a rare form of fibrosing interstitial pneumonia, first described in the English literature in 2004, and usually idiopathic. Its hallmark features include marked bilateral pleural thickening and intense subpleural fibroelastosis, predominantly affecting the upper lobes. We report an autopsy case of PPFE in a 78-year-old male non-smoker with a history of ischemic heart disease and Gilbert syndrome, who presented with progressive dyspnea, dry cough, and weight loss six years prior to death; a diagnosis was not established clinically, and surgical lung biopsy had not been performed. Gross autopsy findings included bilateral well-circumscribed dense upper lobe and superior lower lobe pulmonary fibrosis and bilateral severe plaque-like pleural thickening. Microscopic examination of the lungs revealed dense interstitial pulmonary fibrosis in the upper lobes and superior segments of the lower lobes, consisting of an admixture of fibrosis (variably dense collagenous and loose fibromyxoid) and elastosis. Elastic connective tissue stains revealed relative preservation of elastotic alveolar septa, with apparent airspace fibrosis. There was also diffuse pleural fibrosis (focally calcified and plaque-like), with dense adhesion to the chest wall (“fibrothorax”). No ferruginous bodies or significant mineral dust deposition were seen. This case adds to the few reports of PPFE and is intended to review the clinical, radiographic and pathological features of this rare condition.



Combined Pulmonary Fibrosis and Emphysema in Lung Explant Recipients: A Single Institution Experience

Y.R. Hsu1, C. Chung2, C. Sergi1, B, Chiu1. 1Department of Laboratory Medicine and Pathology; and 2Department of Medicine, University of Alberta, Edmonton, Alberta.

Combined pulmonary fibrosis and emphysema (CPFE) is a recently described clinical entity with poor prognostic outcome. CPFE is characterized by upper-lobe emphysema and lower-lobe fibrosis on high-resolution CT of the lungs, with impaired gas exchange on pulmonary function test.

Objective: We aimed to characterize the histologic spectrum of fibrosis in explanted lungs with coexisting pulmonary fibrosis and emphysema (PF+E).

Methods: All explanted lungs at the University of Alberta Hospital were retrieved from Netcare and CoPath data systems. The degree of interstitial fibrosis in explanted lungs was graded as mild, moderate and severe.

Results: Between 1996 and January 2014, in a total of 292 cases, including 181 with emphysema and 111 with idiopathic pulmonary fibrosis (IPF) of usual interstitial pneumonia (UIP) pattern, we identified PF+E in 37 patients (13%). In 34 lungs explanted for emphysema, the degrees of interstitial fibrosis were: mild 10 (29%), moderate 22 (65%) and severe 2 (6%). Three lungs explanted for IPF (severe fibrosis) also had moderate emphysema. In addition, mild and moderate secondary pulmonary hypertensive arteriopathy was present in 14% and 19% of those with PF+E, respectively.

Conclusion: Coexisting PF+E is an uncommon histologic finding in lung explant specimens for end-stage emphysema or IPF. However, the association of moderate to severe interstitial fibrosis and secondary pulmonary vasculopathy in patients with pulmonary emphysema may be important risk factors for poor prognostic outcome.



Discordance Between Intraoperative Frozen Section Consultations with Final Histologic Diagnosis

1Aaron Adesina, 2Fergall Magee. 1Department of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan, 2Laboratory Medicine, Saskatoon City Hospital, Saskatoon, Saskatchewan.

Correlation of intraoperative frozen section consultation with the final histological diagnosis is an important component of an institution’s quality assurance program.

A retrospective review of pathology reports of 134 intraoperative frozen section consultations from 100 consecutive cases in Saskatoon Health region hospitals, Saskatchewan Canada was carried out[Jan-April, 2013]. The frozen sections and permanent slides of all potentially discordant cases were reviewed to identify reason for error. The clinical records were also reviewed for potential adverse impact on immediate clinical management.

Intraoperative diagnosis correlated with final diagnosis in 116 [86.5%] of cases, 9[6.7%] diagnoses were deferred till permanent section evaluation, 5 [55%] of the deferred cases were CNS [this represented five [86%] out of six of CNS cases].

Discordance was identified in 9 [6.7%] cases, 5[55%] were classified as major [clinical impact], 4[44%] as minor.

One of the cases with major discordance resulted from an interpretation error while the other five resulted from tissue sampling or sectioning technique. The cases with minor discordance resulted from tissue sampling or sectioning technique.

Neither the number of Pathologists nor the number of sections showed any impact on the outcome in the study.

These results of this study demonstrate high diagnostic accuracy of intraoperative consultation. Deferral rates varied by specimen site but showed CNS [55%] predominance. Discordance resulting in major clinical impact was more likely due to tissue sampling or sectioning technique highlighting the need for the development of a robust sampling and sectioning criteria.



Satisfaction with Breast Cancer Reporting, A Survey of Users at Eastern Health, NL

A Tate1,2, L Gai1,2, V Curran1, B Carter1,2. 1Memorial University of Newfoundland, 2Eastern Health, St. John’s NL, A1B 3V6.

Introduction: Methods and styles of pathology reporting of invasive breast cancer and ductal carcinoma in situ (DCIS) are important in effective diagnosis and treatment. The purpose of this study was to explore the perceptions of high yield consumers of breast pathology reports in order to identify key ways to improve reporting. Semi-structured interviews were conducted with a purposive sample of high yield consumers of breast pathology reports.

Methods: Ten physicians (medical, radiation, and surgical oncologists, clinical associates, and pathologists) were interviewed. Respondents were invited to comment on key features of quality and effective reporting, including features and elements of detail, protocol reporting, format, and changes to improve diagnostic decision-making. Interviews were recorded, transcribed and analyzed using thematic analysis technique. Reliability was confirmed through concurrent analyses by two investigators.

Results: Four main themes arose from the analyses. 1) Formatting and style of report, including spacing and alignment of text elements was important for ease of readability and should be consistent between pathologists and between labs across the province. 2) Organization of data should be consistent between all labs / pathologists so that all elements of the College of American Pathologists (CAP) checklists are present and in the same order. 3) Many clinicians requested a summary line of the diagnosis and key staging features at the beginning of the report. 4) All clinicians preferred the synoptic format over narrative, for ease of understanding and completeness of data.

Discussion: Current users of breast cancer pathology reports are satisfied with the CAP checklists, and consistent use by all pathologists would address completeness concerns. Consistent system wide formatting is limited by current CAP license restrictions. Pathologist’s response to these results will be sought and presented back to the clinicians.



Quality Assessment: Discordance Between Clinical and Post-Mortem Diagnosis

A. Stahl, J. Kalra. Department of Pathology and Lab Medicine, University of Saskatchewan and Royal University Hospital, Saskatoon, Saskatchewan, S7N 0W8, Canada.

The prevalence of medical errors in health care systems has compromised the quality of health care delivery. Autopsy, as an established quality assurance tool helps discover diagnostic discrepancies and plays a major role in contributing to clinical knowledge, medical education and quality assurance programs. The purpose of this study was to use autopsy to determine the rate of concordance and discordance between clinical diagnoses and post-mortem findings in patients admitted to the hospitals of the Saskatoon Health Region (SHR). We also evaluated the impact of diagnostic modalities such as Computerized Tomographic Scanning (CT) and Magnetic Resonance Imaging (MRI) on clinical diagnoses. A retrospective record review of the medical and autopsy charts was carried out for all the deceased adult in-patients admitted during 2006 to 2011. A total of 7417 in-patient deaths were registered for the study period. Autopsies were performed on 442 of the deceased resulting in an autopsy rate of 6%. In accordance with selection criteria, 167 (96 males; 71 females) cases were included for this study. The mean age of subjects was 64.6 ± 15.1 years. The concordance rate between clinical and autopsy diagnosis was found to be 72.5%. The discordance rate was 21% and in 6.6% of the study population a conclusive clinical or autopsy diagnosis was not finalized. CT scans and MRI were found to be confirmatory or diagnostic in 61.5% and 35.3% of the autopsy patients respectively. This study shows that the concordance and discordance rates between clinical diagnosis and post–mortem findings in SHR are consistent with those reported in the literature.These results suggest that despite the technical advances in diagnostic modalities, diagnostic discrepancies remain prevalent in the present day health care system. The study also emphasizes the value of autopsies as an effective quality improvement and educational tool with a strong impact on quality assessment programme.



A Single Institution Comparison Of Pathology And Surgical Intraoperative Consultation Records

Tarren Vyas, Corwyn Rowsell. Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, University of Toronto. Toronto, ON M4N 3M5.

Introduction/Objective: During intraoperative consultation (IOC), accurate communication between pathologist and surgeon is essential to avoid errors in intraoperative management. Our study examines discordance between written IOC pathology reports and corresponding operative reports at our institution.

Methods/Design: All IOC performed at Sunnybrook Health Sciences Centre within a one year period were reviewed and the written diagnosis in the IOC report was compared with the corresponding operative report, where available. All discrepancies between the two reports were noted. These included discrepancies in the information provided in the two reports, whether more information was found in the operative report than in the IOC report, and if the pathology stated a favored or equivocal diagnosis while the operative report referred to it as a firm diagnosis.

Results: 1016 cases were reviewed. 123 IOC reports had no corresponding operative report in the electronic patient record while 180 operative reports had no mention of the IOC that took place. 18 operative reports mentioned only a portion of the IOC that took place, while four described an IOC procedure different from that actually performed. Of the 691 cases where a direct comparison could be made, 22 (2.2%) of diagnoses were discordant between the 2 reports. In 42 (4.1%) cases additional diagnostic information was stated in the operative report than the IOC report, and in 16 (1.6%) cases had operative reports stated a firm diagnosis while the pathology report indicated a favoured/equivocal diagnosis.

Discussion/Conclusion: Our study demonstrates that pathology and surgical records of IOC show inconsistencies and a minority are frankly discordant. This may reflect ineffective communication of results from pathologists to surgeons, inaccurate/incomplete recording of results by either party, or additional “offline” discussions in the intraoperative setting. Institutional policies should aim to ensure clear, direct communication between pathologists and surgeons with concise, accurate documentation by both parties to enhance patient safety and avoid potential negative medicolegal consequences.



Quality Assurance Programs for External and Interpretive Pathology in Canada – Is There Room for Improvement?

G. Mitera, D. Banerjee, B. Carter, L. Geldenhuys, R. Henderson, F. Magee, M. McLachlin, T. Rahmeh, E. Ravinsky, B. Têtu, M. Trotter, R. Wolber, N. Camuso, J. Srigley. On Behalf of the Quality Initiative for Interpretive Pathology (QIIP) Thought Leaders Group, Canadian Partnership Against Cancer, Toronto, Ontario.

Robust quality assurance (QA) programs incorporating both technical and interpretive aspects of QA are integral to accurate pathology diagnosis and quality of care. However, the extent of interpretive pathology QA implementation across Canada remains unknown. The objective of this study was to document the current landscape for pathology QA in Canada. An environmental scan was conducted to determine the types and extent of current pathology QA programs in place. An electronic survey was administered to key stakeholders and senior decision makers in cancer pathology. Targeted interviews were conducted with pathology leaders in each province to verify survey results and resolve ambiguous responses. Nine of ten provinces currently have a professional group representing pathologists. All ten provinces currently have a technical QA program in place. Of these, 2/10 provinces are governed through Accreditation Canada, 3/10 provinces through the Ontario Laboratory Accreditation Program and 5/10 provinces by separate provincially-led programs. For interpretive pathology QA, 2/10 provinces have a coordinated interpretive QA program, while 8/10 provinces do not, but 3 of those provinces plan to implement one. This is the first study to document the current provincial landscape for technical and interpretive pathology QA in Canada. Large pan-Canadian variations remain for the level of integration and future plans to develop and integrate interpretive pathology QA programs within provinces. To ensure uniform quality of diagnostic care for patients, next steps should include the development of a pan-Canadian recommendations framework for interpretive pathology quality to help guide senior decision-makers in implementing such quality programs within their provinces.



Benford’s Law for Forensic Pathology Quality Assurance

Jeremy Daniels1, Alice Lytwyn1,2, John Fernandes1, Jemila Hamid1,2. 1Department of Pathology and Molecular Medicine, and 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.

Introduction/Objective: Benford’s Law is a statistical principle that specifies the expected frequency of a given number for each digit(s) of count data, and has been used to identify deviations in data in accounting, physical and medical sciences and public health. Our objective was to determine whether Benford’s Law can be used for Quality Assurance of Manner of Death classifications for a Regional Forensic Pathology Unit.

Methods: Monthly counts for Manner of Death were collected from Hamilton General Hospital Forensic Pathology database for 35 months from January 2011 to November 2013. We used the chi-squared test to examine deviation from expected Benford’s Law frequency distribution for the first and second digit of the monthly counts, as well as for the first 2 digits together. We also conducted second order testing for differences between monthly count frequency.

Results: There were N=2352 decedents. The first and second digits of the monthly counts did not deviate significantly from the Benford’s Law distribution (p=0.83 and 0.99, respectively). The first 2 digits together, and the second order testing deviated significantly from Benford’s Law (p=0.001 and 0.007, respectively).

Conclusion: Manner of Death reporting in this Regional Forensic Pathology Unit appeared robust. First and second digit applications of Benford’s Law may be useful for Quality Assurance efforts, while first 2 digit and second-order tests are less likely to apply



Using Real Time Audits to Improve the Quality of Surgical Pathology Services

L. Litsas, M. Giuliano. Department of Pathology and Laboratory Medicine. London Health Sciences Centre and St. Joseph’s Health Care. London, Ontario. N6A 5A5.

Objective: The Surgical Pathology department of a multisite acute care teaching hospital processed over 54,000 surgical specimens in 2013. To support continuous quality improvement, the department initiated the creation and implementation of real time error audits to identify specific quality issues at each point of surgical specimen processing and inform quality improvement initiatives.

Design: Two types of error audits were developed: an error ticket sheet for use by staff in each step of the surgical pathology specimen process and a quality assurance form for Pathologists to record errors in surgical pathology final reports. Error sheets were placed in all areas for staff to complete and collected daily from December 2, 2013 to January 22, 2014. Pathologists completed quality assurance forms for surgical pathology final reports in 2013. The data from both audits were entered into a database for analysis.

Results: From the error ticket sheets, a total of 315 errors were reported. The most common errors were: not complete or incomplete process task order entry, 94(30%); labeling errors, 59(19%); technical errors, 39(12%) and staples in tissue, 38(12%). From the quality assurance forms, 82 errors were reported. The top two errors were problems with the gross description, 31(38%) and combined problems with gross description and tissue section taken, 10(12%).

Conclusions: Real time audits are useful in identifying specific and common errors for each step of the surgical pathology specimen process. The data collected helps to inform quality improvement initiatives while also providing real time data to compare baseline performance against future performance.



Random Weekly Retrospective Review Of Non-Gyn Cytology: An Effective Internal Quality Assurance Tool

A. Raminhos, S.G..Ferguson, M.M.Weir, K. Marshall, E.Filter and M. G. Joseph. Department of Pathology, London Health Sciences Centre (LHSC) & Western University, London, ON, N6A 5A5.

Purpose: 1) To analyze results of a non -gyn quality assurance (QA) method in our cytopathology laboratory at LHSC. 2) To develop ongoing in-house strategies to resolve issues which are related to three phases of test cycle.

Materials and Methods: Every week, five recent non-gyn samples, one per day, excluding urine, were randomly selected. Pre-analytic, analytic and post analytic parameters (2011-13) were reviewed by 1of 3 cytotechnologists using a cytology guidance form and results documented in an excel spread sheet. Cases with issues were reviewed by the resident on cytology and one or more senior cytopathologists. Appropriate actions were undertaken to resolve issues and to prevent future occurrences. Issues were discussed at the monthly cytology team meetings.

Results: A total of 753 non –gyn cases were reviewed. There were 99 (13%) minor issues; 65 (66%) pre-analytic, 33 (33%) analytic and 1 (1%) post analytic. Common pre-analytic issues were related to accessioning particularly e-ordering which included minor typographical errors, use of wrong fixative, transportation delays for external hospital samples and minor technical sample processing issues. Analytical and post analytical issues included absence of observational templates (e.g. Thyroid) in reports and minor delays in turn around time. There were no major or minor issues affecting diagnosis or patient management. Our strategies included re-education of house staff on sample submission and correction of technical issues related to cytopreparation and reporting terminology.

Conclusions: We present a simple and effective internal non gyn quality assurance tool that can be implemented in both high and low volume cytopathology laboratories. Residents can be easily trained to participate in this QA program. Results of this QA program would permit division head and cytology staff to undertake more focused root cause analysis of in-house issues allowing appropriate and timely action plans.



Factors Affecting Renal Biopsy Adequacy: Is the Number of Passes Related to Renal Biopsy Adequacy?

N. Sinha1, A. Dini, L. Geldenhuys2. 1Division of Anatomical Pathology, Department of Pathology; 2Division of Nephrology, Dalhousie University, Halifax, Nova Scotia.

Introduction: While a renal biopsy may be critical to making the diagnosis, it is an invasive procedure with rare, but potentially fatal complications. Since the number of cores submitted would approximate the number of passes, we conducted a pilot study comparing the number of cores with adequacy for three one month periods 1. prior to implementing the interventions, 2. between implementing the first (decreasing the number of radiologist) and second (on-site adequacy assessment in the biopsy suite) interventions, 3. after the second intervention.

Methods: We recorded the state of adequacy and the number of passes for all native renal biopsies reported at our institution for September- 2006, 2011 and 2012, and calculated the adequacy rate and the average number of cores for each period for adequate/ unsatisfactory/suboptimal biopsies.

Results: The adequacy rates for these periods were 25%, 67% and 83% respectively showing the gradual increase in adequacy after each of the interventions. The average numbers of cores collected for all biopsies for each of these periods were 3.9, 4 and 3.2 showing that overall the number of cores did not increase as adequacy increased, however 3 cores were found to be adequate in 80% of all satisfactory cases. The results were as follows: 2006: adequate group = 3 cores; unsatisfactory /suboptimal group = 4.2 cores; 2011: adequate group = 3.7 cores; unsatisfactory/suboptimal group = 6 cores; 2012: adequate group = 3.2 cores; unsatisfactory/suboptimal group = 3 cores.

Conclusion: These findings suggest that renal biopsy adequacy is not related to the number of passes/cores but 3 passes are mostly adequate. Our findings suggest the 2 interventions are responsible for the adequacy of the specimen without increasing the number of passes. The sample size of the pilot study is, however, small, and expansion of the time periods examined would be required in order to obtain results of greater statistical significance.



Modelling Canadian Quality Control Test Programme for Steroid Hormone Receptors in Breast Cancer using Hierarchical Modelling: Diagnostic Accuracy Study

Pérez Ta,e, Makrestsov, N.b,c,e, Garatt J.c, Torlakovic E.c,d, Gilks CBb,c, and Mallett, Se. aDepartment of Statistics and OR III. Complutense University of Madrid, Spain.; bDepartment of Pathology and Laboratory Medicine, University of British Columbia, cCanadian Immunohistochemistry Quality Control (CIQC) and Canadian Association of Pathologists, dDepartment of Pathology, University of Toronto, Canada; eCenter for Evidence-Based medicine, Department of Primary Care Health Sciences, University of Oxford, UK.

Background: The Canadian Immunohistochemistry Quality Control programme (cIQc) monitors laboratory performance for estrogen receptor (ER) and progesterone receptor (PR) tests used in breast cancer treatment management. Current methods assess sensitivity and specificity at each time point, compared to a reference standard. We investigate alternative performance analysis methods to enhance the quality assessment.

Methods: We used three methods of analysis: meta-analysis (MA) of sensitivity and specificity of each laboratory across all time points; sensitivity and specificity at each time point for each laboratory; and fitting generalized estimating equation (GEE) models to examine differences between laboratories adjusted by test and time point.

Results: 88 laboratories participated in quality control at up to 13 time points using typically 37 to 54 histology samples. In MA across all time points no laboratories have sensitivity or specificity below 80%. Current methods, presenting sensitivity and specificity separately for each run, result in wide 95% confidence intervals, typically spanning 15% to 30%. GEE modelling of a single diagnostic outcome demonstrated that 82% to 100% of laboratories had no difference to reference standard for ER and 75% to 100% PR, with the exception of one run for PR. Laboratories with significant differences to reference standard identified with GEE also have reduced performance by MA across all time points.

Interpretation: cIQc programme has a good design, and with GEE modelling has sufficient precision to measure performance at each time point and allow laboratories with a significantly lower performance to be targeted for advice.



The Application Of A Multi-Tissue Spring-Roll Control Block In Immunohistochemistry

R. Mantha1, B. Wehrli1, 2. 1Department of Pathology, University of Western Ontario; 2Immunopathology, LLSG Clinical Laboratories, London Health Sciences Centre.

The modern practice of pathology involves the use of immunohistochemistry (IHC) for the detection of tumour cell markers with prognostic and therapeutic significance. The presence of control tissue mounted onto the same slide as a patient’s sample, and thus subjected to the same treatment, is important to demonstrate the validity of a test. The current methodology used to prepare these external control tissues at LHSC is somewhat of a cumbersome process with preparation of these control tissues needing to be done on a fairly continuous basis. The preparation and application of a multi-tissue spring-roll control block and its purported benefits have been documented previously. In the present study, we have prepared a multi-tissue spring-roll control block designed to act as a general control in our lab. Twelve tissue types were selected: the majority non-tumoural (colon, kidney, liver, lung, placenta, pancreas, tonsil, salivary gland, adrenal gland, spleen) and readily obtained in our routine workload. Metastatic melanoma was less commonly available. Amniotic membrane was chosen as a wrapping material for its convenience as well as to provide a positive control itself. After initial paraffinization, the spring-roll was sectioned transversely and these 3 mm cross-sections were again embedded to act as external IHC controls. This multi-tissue control block was approximately 2 – 3X more efficient than our current methodology, while providing the same degree of quality assurance. While the prospective collection of tissues was time-consuming, it is still feasible at a large, tertiary centre such as LHSC and, with regular use, this method could potentially save time and resources.



A Case of Multifocal Mature Ganglioneuroma Presenting as a Primary Pediatric Renal Mass and Extra Renal Nodules

Allison Osmond, Fahd Al Sufiani, Aaron R. Haig, Nancy G. Chan. Western University, London, Canada.

Mature ganglioneuromas are benign peripheral neural tumors that develop along the sympathoadrenal axis. Primary ganglioneuromas with lymph node metastases have been previously reported in adults. We report a ganglioneuroma presenting as a primary renal mass with extra-renal tumor nodules and lymph node metastases. The patient, a 4 year old girl, was found by ultrasound to have a renal mass while she was being investigated for recurrent UTIs. A subsequent CT scan revealed a soft tissue mass along the central portion of the right kidney with surrounding hydronephrosis. Smaller nodules with punctate calcifications were noted adjacent to the right adrenal gland and posterior to the inferior vena cava. The preoperative diagnosis was Wilms’ tumor. Intraoperatively, the tumor lay in the retroperitoneum and extended into the hilum of the right kidney; there were also multiple, large periaortic, paracaval, and portal calcified nodules. One of these presumed lymph nodes was submitted for an intraoperative frozen section, which revealed mature neuronal tissue with minimal lymphocytic infiltrates. Examination of the formalin-fixed nephrectomy specimen demonstrated a fleshy renal pelvic mass (maximum diameter 7.0 cm). The lymph node-like nodules were uniformly pale tan and firm. The final histological classification of the renal tumour was ganglioneuroma, local stage 3; lymph node involvement was indeterminable due to a lack of defining nodal architectural evidence. In summary, this is an example of mature ganglioneuroma presenting as a primary pediatric renal mass with extra renal nodules. Regarding its origin, the neoplasm is either an ‘automaturing’ neuroblastoma metastatic to the regional lymph nodes or a multifocal ganglioneuroma arising from intra-renal and extra-renal adrenal rests. (We are grateful for the opinions of Dr, D. A. Ramsay (Neuropathologist, LHSC, London, Canada) and Dr. Elizabeth J. Perlman (Children’s Oncology Group, Chicago, Illinois).



Inflammatory Myofibroblastic Tumor of the Aortic Valves Causing Sudden Cardiac Death: A Case Report and Review of the Literature

Sameh Youssef, Bin Xu, Richard S. Fraser, Chantal Bernard, Department of Pathology, Montreal Children’s Hospital, McGill University Health Centre, Montreal, Quebec, Canada, H3H 1P3.

Background: Cardiac inflammatory myofibroblastic tumor (IMT) is a rare entity affecting predominantly infants, children, and young adults. Although most tumors have a benign clinical course after complete surgical resection, some have significant clinical effects.

Methods and Results: We described a case of a 9-year-old girl who had sudden cardiac death as a result of occlusion of the left circumflex coronary artery (LCX) by IMT. At autopsy, a structurally normal heart showed a polypoid papillary tumor attached on the aortic valve with extension of one tumor frond into LCX. Histologically, the tumor was composed of bland spindle cells, admixed with lymphocytes and plasma cells. The spindle cells were positive for vimentin and smooth muscle actin. ALK-1 was negative by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). The IgG4 count was low. A diagnosis of cardiac IMT was rendered. A review of 57 cases of cardiac IMTs reported in the literature is presented.

Discussion: Cardiac IMTs account for less than 5% of primary cardiac tumors, with a total of 57 cases reported to date. The majority are endocardium-based polypoid lesions protruding into the cardiac cavity, with 12% showing aortic valve involvement. Compared to extra-cardiac IMTs, cardiac IMT is associated with lower incidence of ALK-1 overexpression, less frequent recurrence, and higher risk of disease-related mortality, including sudden cardiac death due to occlusion of a coronary artery. Although IMT is in general considered to be a neoplasm with intermediate biologic potential, this case emphasizes that cardiac IMTs may have a fatal consequence. This tumor should be considered in the differential diagnosis of unexplained chest pain and syncope in pediatric patients.



Ultrastructural Features Of Cryofibrinogenemia In Renal Biopsy

S. Al-Bazzaz1, M. Schreiber2, S. Cohen1, S. Jothy1. Divisions of Pathology1, and Nephrology2, St. Michael’s Hospital, Toronto, ON, M5B 1W8, and Departments of Laboratory Medicine and Pathobiology1, and Medicine2, University of Toronto.

Objective: Document the ultrastructure of renal changes in cryofibrinogenemia, which so far has not been reported in details.

Methods: Case report, histopathology, immunofluorescence and electron microscopy; comparison with other glomerulopathies associated with deposition of fibers. A 49 year-old female presented with fatigue and severe fibromyalgia, proteinuria (3 g/day), serum creatinine of 128 and hematuria. Serum C3, IgG1 and IgG2 were reduced and there was no evidence of monoclonal gammopathy. The work up for underlying malignancy was negative. Cryoglobulin was repeatedly negative but cryofibrinogen was positive (measured as 3%). Kidney biopsy showed endocapillary hypercellularity. Immunofluorescence showed deposits of C3 in the peripheral capillary loops of the glomeruli. Electron microscopy revealed randomly arranged microtubular structures in the subendothelial area of glomerular capillary loops. These microtubules have a mean diameter of 38 +/- 7 nm and contain a single dense fibrillar structure in their center. There was no evidence of amyloid by Congo red staining or electron microscopy.

Conclusions: As compared with other glomerulopathies, we concluded that the ultrastructural features of the cryofibrinogen deposits are distinct from those observed in: cryoglobulinemia, fibrillary glomerulonephritis and amyloid, but overlap with those of immunotactoid nephropathy. Cryofibrinogen deposition may be a renal biomarker of some cases of fibromyalgia.



Crescentic Glomerulonephritis With Double Positive ANCA Serology

T. Shao1, J. Perl2, Z. Harel2, S. Jothy1, Divisions of Pathology1 and Nephrology2, St. Michael’s Hospital, Toronto, ON, M5B 1W8, and Departments of Laboratory Medicine and Pathobiology1, and Medicine2, University of Toronto, Toronto, ON, M5S 1A8.

Objective: Double-positive serology for anti-myeloperoxidase (MPO) and anti- proteinase 3 (PR3) is rare, and its presentation with venous thrombosis and leucopenia has not been described. The objective is to report an unusual case of ANCA-associated glomerulonephritis with double anti-MPO and anti-PR3 serology, associated with venous thrombosis and leucopenia.

Methods: Histopathology, immunofluorescence, electron microscopy, ANCA serology.

Data and results: The index case is a 74-year–old woman with a history of recurrent unprovoked deep venous thrombosis, and was treated with warfarin and inferior vena cava filter. The patient subsequently developed bilateral recurrent subdural hematoma. Over the next two months, she developed nausea and vomiting and a 30 lbs weight loss, associated with serum creatinine 482 without uremic symptoms. Work-up was negative for solid and hematological malignancies and infections. Urine tests showed 3+ protein, 4+ blood, proteinuria 2.05 g/day, urine microscopy showed no RBC casts, and hematology revealed persistent leucopenia. The ELISA ANCA test on the serum was positive for both anti-MPO: 15, anti-PR3: 8. Ultrasound revealed right renal vein thrombosis. Renal biopsy showed active crescentic glomerulonephritis with crescents in 42% of the glomeruli, including 25% cellular crescents. Immunofluorescence and electron microscopy showed no immune deposits. The patient’s condition did not respond to rituximab treatment.

Conclusions: Double-positive serology for anti-MPO and anti-PR3 may explain this rare presentation associating severe crescentic glomerulonephritis with thrombosis and leucopenia.



Phospholipase A2 Receptor and α-Enolase In The Immunodignosis Of Membranous Nephropathy

Ying Zhang1, Marvin J. Fritzler2, Dan Muruve3, Pietro Rivani3, Hallgrimur Benediktsson1

1Department of Pathology and Laboratory Medicine, University of Calgary; 2Faculty of Medicine, University of Calgary; 3Division of Nephrology, University of Calgary.

Background: Membranous nephropathy (MN), a leading cause of nephrotic syndrome in adults, is most often idiopathic, but may be secondary to other conditions. M-type phospholipase A2 receptor (PLA2R) has been identified as a key B cell target in adult idiopathic MN (IMN). Other podocyte autoantigens include SOD2, aldose reductase, α-enolase and SC65.

Objective: To investigate the diagnostic value of PLA2R and α-enolase and their potential role in the pathogenesis of MN.

Methods: 22 patients with biopsy-proven MN including 18 IMN and 3 secondary MN, were selected based on availability of serum samples. Expression of PLA2R, α-enolase, and the localization of IgG subclasses and complement were detected by direct or indirect immunofluorescence. Autoantibody titers in sera were assessed by a cell-based biochip assay and an addressable laser bead immunoassay (ALBIA).

Results: PLA2R expression was detected in glomerular capillaries in 11/22 MN patients. Anti-PLA2R antibodies were detected in 6 and α-enolase antibodies in 4 of the 22 sera. Patients were divided into 2 groups according to their PLA2R staining status in renal sections (PLA2R positive and PLA2R negative). No significant differences in proteinuria, serum creatinine, age, gender or pathological stages (p>0.05) were found between patients with positive or negative PLA2R in biopsies. IgG4 is dominant in PLA2R positive IMNs, but not in PLA2R negative IMNs; PLA2R positive patients have stronger C3 staining than PLA2R negative patients (p=0.03).

Conclusions: Assessment of PLA2R antigen expression in renal biopsies is a more sensitive indicator of MN than anti-PLA2R antibodies. ALBIA is a reliable, quantitative immunoassay for detecting PLA2R and α-enolase antibodies in circulation. PLA2R likely participates in the activation of complement protein C3.



Basal Cell Carcinoma Arising in a Trichilemmal Cyst: A Case Report and Review of the Literature

Schell, Miranda1; Kajal, Babita1; Deb, Pratima2; Alowami, Salem3. 1Department of Pathology and Molecular Medicine, McMaster University, 2 Department of Pathology and Molecular Medicine, McMaster University Medical Centre; 3Department of Pathology, St-Joseph’s Hospital.

Benign trichilemmal (pilar) cysts are common skin lesions, typically occurring on the scalp. Trichilemmal cysts are thought to arise from the isthmus of anagen hairs. These are typically surgically excised with limited clinical follow-up. While very rare, carcinomas may arise within these cysts. We present a case of a basal cell carcinoma arising in a trichilemmal cyst and a review of the current literature.

Case report: A 76 year-old male with a history of colonic carcinoma, but no previous history of cutaneous malignancies presented with a slowly enlarging cyst on the skin in left hip area. Surgical consultation was sought. The lesion was excised and received in the pathology laboratory at McMaster University Medical Centre. The specimen consisted of an unoriented ellipse of light tan skin (5.0 x 3.5cm) with a glistening light-tan cystic structure (5.0 x 2.5 x 3.0cm) on the deep surface. The cut surface revealed a smooth, glistening cyst wall lining filled with serous fluid. Present within the cyst wall was a tan, firm nodule (3.5 x 2.5 x 1.1cm) exuding thick creamy material. Representative sections were submitted. Microscopic examination revealed a deep dermal cyst lined by several layers of squamous epithelium with abrupt keratinization. Within the wall of the cyst was an infiltrating lesion composed of nests and cords of basaloid cells. The stroma was fibrotic with retraction around the tumor nests. Mitoses and necrosis were readily identified. The features were in keeping with a basal cell carcinoma arising within the wall of a trichilemmal cyst.

While basal cell carcinomas typically do not metastasize, they tend to recur and may be locally aggressive. Hence, clinical follow-up is recommended. To date, very few similar cases have been reported in the literature. We emphasize the importance of careful gross and microscopic examination of all cysts, especially in the setting of an unexpected gross appearance.



Follicular Mucinosis with a Clonal T-Cell Pattern – A Case Report

David Garcia-Marquez1, Bret Wehrli1, Christopher Howlett1, Mariamma G. Joseph1. Department of Pathology, London Health Sciences Centre and Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.

Follicular Mucinosis (FM) is an uncommon cutaneous condition presenting clinically as follicular papules or plaques. The face, neck and scalp are most commonly affected. Histologically it is characterized by mucin deposition within the folliculosebaceous units and a lymphocytic infiltrate centered around the hair follicles. It can be primary (idiopathic) or secondary, frequently associated with mycosis fungoides.

We present a 48 year-old male with a solitary plaque on the posterior neck; histologically consistent with FM. Immunohistochemical studies confirmed a T-cell proliferation positive for CD4, CD5 and CD3, with partial loss of CD7. T-cell receptor Beta (TCRβ) and T-cell receptor Gamma (TCRγ) gene rearrangement assays showed a reproducible clonal pattern in a single reaction (TCRβ). Although this result was considered inconclusive, the possibility of a T cell neoplasm was suggested. Monoclonal rearrangement of T cell receptors has been demonstrated in approximately 50% of tested cases in primary and secondary FM. Long term clinical follow up is recommended.

Key words: Follicular Mucinosis, Mycoses Fungoides



Primary Cutaneous Adenoid Cystic Carcinoma of the Scrotum: A Rare Case Report

DM Ravi1, S.Salama1, S. Alowami1. 1Department of Pathology, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5.

Background: Adenoid cystic carcinoma of the salivary glands is not uncommon (approximately 15% of the head and neck tumors). Primary cutaneous adenoid cystic carcinoma (PCACC) is rather uncommon and its involvement of the scrotal region in particular is extremely rare.

Case presentation: Here we discuss a case of a 56 year old male, with a history of a pea-sized cystic lesion in the right peno-scrotal region of 5 year duration. He denied any systemic symptoms. It remained unchanged until recently when he noticed it to have flattened out. Excision of the 2 cm lesion revealed microscopically, presence of areas showing monotonous appearing basaloid tumor cells with cribriform pattern. The cells had prominent nucleoli, occasional mitosis with focal clear cell and minor mucinous differentiation and no sebaceous features. The surgical margins were clear. Periodic acid Schiff (with and without diastase), Mucicarmine and Hale’s stain showed small amount of acidic and neutral mucin. Immunohistochemistry showed tumor cells to stain positive for p63, S100, CK18, c-kit and BerEP4 which helped conclude it to be primary adenoid cystic carcinoma of scrotal skin. Our patient did not have any evidence of metastases or a head and neck tumor, clinically or by imaging, and a wider local excision of the area was performed due to the risk of local recurrence. He is being monitored quarterly by his oncologist.

Conclusion: This case is an excellent learning experience and highlights the importance of accurate diagnosis of this rare condition. To the best of our knowledge this is the second report of a PCACC in the scrotum.



Plasmacytoid Malignant Melanoma: A Rare Variant

L. Kocovski1, A. Bane1, S. Tang1, S. Salama1, S. Alowami1. 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario.

Plasmacytoid melanoma is an unusual variant of malignant melanoma. The plasmacytoid morphology can be found in a variety of other malignancies including carcinomas, plasma cell neoplasms, lymphoproliferative disorders, and sarcomas. The authors report a rare case of plasmacytoid malignant melanoma.

A 78-year-old man, with remote history of skin lesions previously treated with liquid nitrogen, presented with an enlarging erythematous mass on his left posterior shoulder. A fine needle aspirate showed atypical findings with single cells with high nuclear to cytoplasmic ratio, mono- and multi-nucleation with prominent nucleoli and intranuclear inclusions. Differential diagnosis at this stage favoured sarcoma. A subsequent excision showed a large nodule within the dermis, composed mainly of sheets and nests of cells with plasmacytoid morphology, and less than 5% of the nodule comprised of pseudoglandular morphology. Review of the excision and immunohistochemical analysis revealed the malignant plasmacytoid cells stained with vimentin, S-100, HMB45, and melanoma cocktail, in keeping with melanoma. Subsequent thorough clinical examination, imaging, and investigations failed to reveal any site for a primary melanoma. A subsequent wide local excision and sentinel lymph node excision revealed a focal positive deep margin and negative lymph node. Four months following the initial excision, however, radiological imaging noted metastatic disease to the lungs and residual disease at the excision site.

The plasmacytoid morphology can be found in a variety of malignancies. In order to prevent potential misdiagnoses of this aggressive malignancy, thorough histological examination should be aided by an appropriate immunohistochemical panel to confirm melanoma and exclude erroneous differentials.



Adult Solitary Cutaneous Myofibroma: A Diagnostic Pitfall

R. Yu1, S. Salama1,2, S. Alowami1,2. 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, L8S4L8; 2St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, L8N4A6.

Objective of the study: Cutaneous myofibroma is a tumor of perivascular myoid differentiation that is most commonly diagnosed in infancy, either as a solitary or multicentric lesion. In contrast, cutaneous myofibroma of adult-onset is a relatively rare tumor. Like its infantile counterpart, adult cutaneous myofibroma exhibits benign biologic behavior. The adult tumor is clinically significant, however, because it is highly susceptible to misdiagnosis both clinically and histopathologically. We report a case of a 58-year-old female with a 1.3 cm right forearm lesion, removed by excisional biopsy.

Data and Results: Microscopic examination showed a well-circumscribed, non-encapsulated dermal proliferation consisting of small rounded nodules with whorls of bland spindle cells associated with a fibrotic stroma. There was a prominent vascular background, but without thickened blood vessel walls. On immunohistochemistry, there was strong, diffuse positive staining for vimentin and weaker positive staining for actin. EMA, desmin, h-caldesmon, S-100 protein, MART-1/Melan-A, factor XIII, and CD31 were negative. Ki67 proliferation index was low.

Conclusions: Cases sent for expert consultation have been misdiagnosed as fibrohistiocytic tumors, fibroblastic/myofibroblastic tumors, vascular tumors, smooth muscle tumors, and neural tumors. Awareness that solitary cutaneous myofibroma can occur in adults may help to avoid these diagnostic pitfalls and prevent unnecessary re-excision for suspected malignancy.



Cutaneous Lymphadenoma: A Diagnostic Pitfall

R. Yu1, S. Salama1,2, S. Alowami1,2. 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, L8S4L8; 2St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, L8N4A6.

Objective of the study: Cutaneous lymphadenoma is a rare epithelial neoplasm that is currently considered a variant of nodular trichoblastoma with adamantinoid features. Although it exhibits benign biologic behavior, recognition of cutaneous lymphadenoma is important because its rarity creates a diagnostic pitfall to the unsuspecting surgical pathologist who may readily misdiagnose the lesion as the much more common, locally destructive basal cell carcinoma or one of its histologic mimics. We describe a case of a 67-year-old-female with a left posterior ear nodule, removed by excisional biopsy.

Data and Results: Microscopic examination showed a well-circumscribed, unencapsulated, intradermal nodule of variably-sized, round-to-irregularly shaped epithelial lobules. The deep margin was rimmed by a prominent lymphocytic infiltrate. The lobules were rimmed by small, bland, flat-to-cuboidal basaloid cells without peripheral palisading. Centrally the lobules consisted of larger cells admixed with lymphocytes. The stroma surrounding the lobules showed dense collagen with numerous scattered lymphocytes, which in some areas appeared to penetrate the tumor lobules and obscure stroma-lobule boundaries.

Conclusions: Close attention to morphologic features on routine H&E stain alone allows accurate diagnosis of cutaneous lymphadenoma from basal cell carcinoma and other histologic mimics without use of ancillary studies.



Pseudoglandular Squamous Cell Carcinoma: A Diagnostic Pitfall

R. Yu1, G. Gohla1,2, X. Fang1, S. Alowami1,2. 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, L8S4L8; 2St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, L8N4A6.

Objective of the study: Pseudoglandular squamous cell carcinoma (SCC) is a variant of SCC that is found almost exclusively in sun-damaged skin of elderly patients. The pseudoglandular variant is important to recognize because it is susceptible to misdiagnosis, not only by morphology as an adenocarcinoma, but also by sampling error if biopsies do not capture areas disclosing features of usual type SCC. We describe the case of an 83-year-old male with a 1.3 cm skin nodule on the left neck, removed by excisional biopsy.

Data and Results: Routine H&E stain showed near complete glandular architecture, suggestive of adenocarcinoma. The overlying squamous epithelium showed no epidermal squamous dysplasia. Identification of few scattered foci of keratinization prompted reconsideration as SCC with pseudoglandular formation. Immunostains showed the neoplastic cells were reactive for Z622, 34βE12, CK5/6, and p63. Further diagnostic support was lent on procuring the patient’s medical record, with documentation of radiotherapy for a 3 cm SCC of the left pinna, 1 year prior.

Conclusions: Awareness of the pseudoglandular variant of SCC is important to avoid misdiagnosis of adenocarcinoma in biopsies with extensive glandular architecture throughout. Excisional biopsies are preferable to maximize the probability of finding features of usual type SCC, which may be focal and missed on other types of skin biopsy.



Syringoid Carcinoma vs. Other Adnexal Tumors: A Case Report

Abedi SM1, Salama S2, Alowami S3. Department of Pathology and Molecular Medicine, St. Joseph’s Healthcare, McMaster University, Hamilton, Ontario, L8S-4L8.

Background: Syringoid carcinoma (eccrine carcinoma) is a rare malignant adnexal tumor with eccrine differentiation that often histologically resembles a syringoma. They most commonly occur in middle aged women on the head and neck region, however different ages and sites have been reported. Histologically they present as basaloid ductal structures with an infiltrating pattern and perineural invasion often involving the underlying sub cutis and or skeletal muscle. They are frequently misdiagnosed histologically as either microcystic adnexal carcinoma (MAC) or adenoid cystic carcinoma. Syringoid carcinomas are treated surgically with wide excision however, other malignant adnexal tumors have shown good response to adjuvant radiotherapy. Syringoid carcinomas are locally aggressive tumors with rare nodal metastasis.

Case: A 68 year old male with no previous significant medical history presented with a rapidly growing 2.7 cm lesion on his right temple that was surgically excised and sent for histological examination. On low power, a “syringoma-like” lesion was seen with small ducts (tadpole-like) and a fibrotic stroma. Contrary to a benign syringoma this lesion had an infiltrating pattern that extended the full thickness of the tissue including the underlying fat and resection margins. On high power, there were relatively uniform hyperchromatic nuclei, lack of cellular atypia and no mitosis with significant perineural involvement. No keratocysts and or squamous differentiation were present. Immunohistochemistry highlighted both the lumina of the small ducts (EMA) and perineural involvement (S100). These features yielded a diagnosis of syringoid carcinoma.

Conclusions: This case highlights the histological characteristics needed to diagnosis a rare malignant adnexal lesion. Particular emphasis should be given to low power evaluation of architecture (circumscribed vs. infiltrative) and supporting immunohistochemistry studies (EMA and S100). With reported adjuvant therapy success for certain adnexal tumors, correct pathological diagnosis is crucial to good patient care.



Rapidly Evolving Compartment Syndrome in a Case of Congenital Kaposiform Hemangioendothelioma – Diagnosis by Pathology, a Key Feature for Correct Treatment – A Learning Experience

Memon S, Arrendondo JL. Department of Pathology & Molecular Medicine, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.

Objective & Introduction: To report and present a case of congenital Kaposiform hemangioendothelioma (KHE). Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor of intermediate malignant potential, with about 100 cases reported in the literature. It usually occurs in the extremities, retroperitoneum, deep soft tissue and bones of children. It is mostly complicated by its association with Kasabach-Merritt Syndrome (KMS).

Case Presentation: We present a classic case of congenital Kaposiform hemangioendothelioma associated with KMS at birth. The infant was born to 36 year old primigravida by caesarian section in view of a poor biophysical profile (2/8). The routine antenatal screening tests were all normal. Within 22 hours of birth, this male neonate was admitted in the NICU with a clinical presentation of rapidly progressive swelling and erythema of left leg with areas of violaceous discoloration around the knee, onset of which was noted at birth. General surgery and orthopedic sugery were consulted; urgent MRI was requested with query septic joint. The imaging showed no evidence of joint effusion, vascular malformation, necrosis, dislocation, fracture or deep venous thrombosis.

For this atypical presentation cellulitis and necrotizing fascitis was at the front of everyone’s (clinicans, surgeons, radiologists) mind and the baby was started on empiric antibiotics. Due to increasing swelling and development of compartment syndrome the baby was taken to OR on day 2 of life for fasciotomy and biopsy. At that time, the blood count showed low platelets of 64 x 109/L (150-400 x 109/L), hemoglobin of 102 g/L (145-225 g/L), absent leukocytosis and cultures were negative.

Pathology Results: The histopathology diagnosis changed the entire picture by displaying proliferation of spindle to ovoid cells with irregular distribution, forming faint glomeruloid nodules and fasicular-like pattern intermixed with numerous red blood cells in slit-like spaces. The lesion lacked definite vascular lumen or endothelial lining, reminiscent of kaposiform appearance. On immunohistochemistry this lesion was positive for CD31, CD34, D2-40 and negative for human herpes virus type 8 (HHV8) and GLUT-1, thus confirming the diagnosis of Kaposiform hemangioendothelioma.

Conclusion: This case stresses the importance of histopathology for the accurate diagnosis and proper treatment of Kaposiform hemangioendothelioma. This is a rare condition, that can mislead the clinicians and radiologists towards diagnosis like infectious process as seen in this case. In addition the baby had a classic association with Kasabach-Merritt Syndrome. Early diagnosis is critical for treatment of this potential fatal deep-seated lesion due to consumption coagulopathy.