Poster Abstracts

View the ePosters here: https://cap-acp.multilearning.com/cap-acp/

 

POSTER PRESENTATIONS

 

All posters at the annual CAP-ACP meeting are presented in an ePoster format. The posters will be hosted on a website and the app, and will be viewed from both your own device as well as some larger screens in the exhibit area.

 

Poster judging will take place between 1700 and 1930 on Monday, June 12   posters that are under consideration for awards must ensure the first author is available to present the poster in person at this time.

 


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1700-1830

Screen 1.11 P40 Development of the national Expected Screening Rate for cardiovascular disease, type 2 diabetes, cervical cancer and colorectal cancer as a benchmark for Canadians.

Irene Maa,c, Maggie Guoc, and Christopher T. Nauglera-c.

aDepartment of Pathology and Laboratory Medicine,

bDepartment of Family Medicine, Cumming School of Medicine, University of Calgary;

cCalgary Laboratory Services; Calgary, AB.

Objective: To provide a benchmark for the percentage of patients that would be expected to be screened each year on a population basis if physicians were following current Canadian screening guidelines for cardiovascular disease (CVD), type 2 diabetes, cervical cancer, and colorectal cancer.

Methods: An Internet search was used to obtain the most recent Canadian screening guideline for each disease, which was then used as a reference. The estimated screening rate (ESR) was then calculated by determining the percentage of Canadian population that should be targeted or excluded from screening using Internet searches of the Canadian federal government or not-for-profit organization databases, or peer-reviewed literatures. For the two chronic diseases (CVD, type 2 diabetes), the ESR was calculated by: Sum (target populations from the risk groups/number of years between screenings). The ESR for the two cancers (cervical, colorectal) was calculated by: (100% of the target population – x% of the excluded population)/number of years between screenings.

Data and Results: The table below summarizes the results of the expected screening rates in Canada.

Conclusions: This benchmark can be used to guide any jurisdiction in Canada to assess the adequacy of disease screening on a population level.

Keywords: Expected Screening Rate, Screening Guidelines, Cardiovascular Disease, Type 2 Diabetes, Cancer.

Summary Table of Results::

Disease of Interest (Laboratory Test Used for Screening)

Canadian Guideline Source (Release Date)

% of Target Population to Screen

% of Population Should Not be Screened

Expected Screening Rate (ESR)

Cardiovascular Disease (Lipid Panel)

Canadian Cardiovascular Society (July 2016)

Low Risk (34.3%/5 years), Moderate Risk (9%/year), High Risk (19.3%/year)

N/A

35.3%/year

Type 2 Diabetes (Fasting Plasma Glucose and/or Hemoglobin A1c)

Canadian Diabetes Association, (April 2013)

Low Risk (39.2%/3 years), At Risk (12.9%/2 years), High to Very High Risk (at least 47.9%/2 years)

N/A

At least 43.5%/year

Cervical Cancer (Papanicolaou Test, Pap)

Canadian Task Force on Preventative Health Care (CTFPHC) (January 2013)

86.6%/3 years

15.3%

28.9%/year

Colorectal Cancer (Fecal Immunochemical Test, FIT)

CTFPHC (February 2016)

75.4%/2 years

24.6%

37.8%/year

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1700-1830

Screen 1.12 P25 User-Friendly QA: A Desktop Technical Feedback Form Increases Pathologist Participation in Quality Improvement

Corey Knickle1, Julianne Klein1,2, Paul Wawryko1,2, Shelley Ganske2, Gabor Fischer1,2.

1University of Manitoba, Winnipeg, MB, Canada;

2Diagnostic Services Manitoba

Objectives: Continuous quality improvement in the pathology laboratory requires consistent feedback on technical quality. Pathologists work under significant time pressure, limiting their ability to communicate defects if feedback processes are time consuming, such as paper forms or regular email. We have introduced an innovative user-friendly electronic technical Quality Assurance (“TQA”) form that has improved QA participation at Diagnostic Services Manitoba (DSM).

Methods: The TQA form was developed as a desktop icon. One click opens the e-mail form auto-addressed to the Charge Technologist and Quality Analyst, for feedback on specimen registration, grossing, fixation, embedding, microtomy, staining, cover-slipping, labelling or other problem related to the case. The Charge Technologist provides follow-up and feedback. The Quality Specialist monitors investigation completion and data in an electronic document system (Intelex). The process was rolled out at as a pilot at 3 DSM sites in 2014, and 3 other sites joined in 2015 to complete the implementation.

Results: In the 3 years before introduction (2011-13) there was an average of 22 feedback events from 5 people. Following implementation of the electronic TQA in 2014 the amount of feed-back started to increase. In the first year that all DSM sites used the process (2016) we had 156 completed forms (7x increase) from 25 people (5x increase). The new system provides more efficient follow-up, monitoring and trending of technical QA data.

Conclusions: A user-friendly electronic feedback mechanism can significantly improve the number of pathologists and cytotechnologists actively contributing to quality improvement in the laboratory.

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1700-1830

Screen 1.13 P19 Investigation of Immunohistochemistry Critical Assay Performance Controls (iCAPC) to Reduce Inter-Observer Interpretation Variability of BRAF V600E.

Nadia Galea, Ellen Caia,b, Steve Kallogera,b, Ariel Liua,b, Tyler Hickeya,b, Alisa Abozinaa,b, Fatemeh Derakhshana,b, Deidre Ongaroa,b, David S. Schaeffera,b.

aVancouver Coastal Health, University of British Columbia, Vancouver, BC;

bDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC.

Immunohistochemistry Critical Assay Performance Controls (iCAPC) are gold standard sets of tissue controls that robustly show strong, weak and negative expression for specified proteins, initially introduced to provide standardization and reduction of pre-analytical and analytical errors of the respective immunohistochemistry (IHC) stains. Within Vancouver Coastal Health, iCAPC are incorporated for all class II antibodies including BRAF V600E.

BRAF is a predictive and prognostic biomarker for cancers such as colorectal adenocarcinoma and metastatic melanoma. BRAF V600E protein detection by IHC is comparable to the gold standard polymerase chain reaction (PCR) assay.

An exhaustive review yielded no previous studies evaluating the efficacy of iCAPC in reducing inter-observer interpretation variability. In this study, 173 cases with reported BRAF mutational status were collected, providing two sets of slides: routine controls (115) and iCAPC (58). One pathology resident interpreted the two slide sets.

Kappa coefficients for the pathology resident’s results to the previous reports were calculated:

pre-iCAPC

iCAPC

Equivocal

0.2633

-0.0270

Mutated BRAFV600E protein is present

0.8109

0.8795

Mutated BRAFV600E protein is not identified

0.6961

0.8141

Based on this preliminary data, the use of BRAF V600E iCAPC decreases inter-observer interpretation variability. Five additional residents will review the two slide sets, with an additional 56 slides in the iCAPC set.

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1700-1830

Screen 1.14 P17 Survey of Physician Satisfaction with Anatomical Pathology Services in Alberta

Denise LaPerle MLTAngela Thompson MD, FRCPC, Allie Moskalyk MLT, Reanne Cunningham MLT and Máire A. Duggan MD, FRCP.

on behalf of the Provincial Anatomical Pathology Quality Steering Committee, Laboratory Services, Alberta Health Services (AHS)

Objective: To determine the satisfaction rate of physicians who utilize anatomical pathology (AP) services provided by AHS, the AP Quality team developed a satisfaction survey that was distributed to a select group of users.

Method: Published literature on methods to survey user satisfaction was reviewed. Canadian methodology was not found. Instead, a US based Q probe survey from the College of American Pathologists was used to inform the development of the Alberta survey. Survey questions were grouped as follows: 1) interaction/communication with pathologist, technologist, 2) administration; quality of the report; timeliness of reporting; responsiveness to problems; 3) overall satisfaction with services. A section for comments was also included. Physicians were mailed a paper copy of the survey and provided six weeks to complete and return it.

Results: 998 copies of the survey were distributed and 257 (26%) responded.

Measurement

Overall rate of satisfaction

Overall services

93% Very Good/Good

Quality of AP report/accuracy

94% Very Good/Good

Quality of professional interaction with pathologists

98% Very Good/Good

Courtesy of technical staff

94% Very Good/Good

Courtesy of secretarial staff

93% Very Good/Good

Some comments drew attention to problems with the timeliness of some reports.

Conclusions: Overall, there is a high level of satisfaction amongst this physician user group with AP services in Alberta. This survey serves as a baseline for future surveys that will determine if the action plan to address problems has been successful and the service continues to improve.

Keywords: Anatomical Pathology Physician Satisfaction Survey

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1700-1830

Screen 1.15 P30 Learner and teacher perceptions of pimping in a pathology residency program – a study using interviews and rich-picture drawings

Emily A. Goebel, MD1, Sayra M. Cristancho, PhD2, Christopher J. Watling, MD, FRCPC, MMedEd3, and David K. Driman, MBChB, FRCPC1.

1Departments of Pathology and Laboratory Medicine, Western University and London Health Sciences Centre, London, Ontario

2Centre for Education Research & Innovation, Schulich School of Medicine and Dentistry, Western University, London, Ontario

3Department of Clinical Neurological Sciences, Western University and London Health Sciences Centre, London, Ontario

Objective: Pimping is a distinct form of questioning in medical education that has proponents and detractors. It occurs in rounds and at one-on-one sign-out. Our study examines the use of and attitudes toward pimping in a pathology residency program to better understand its value and effectiveness.

Methods: Semi-structured interviews about pimping, based on grounded theory, were conducted, and participants were asked to draw a rich-picture of a pimping encounter. Data was analyzed using qualitative thematic analysis. There were 17 participants (8 pathology trainees and 9 pathologists).

Results: Negative emotions including anxiety and self-doubt occur during pimping (figure). For some, these resulted in motivation to study, while for others this was a futile, non-motivating experience. Most trainees felt they were being judged during pimping; however, they perceived that the intentions of pimping were not malicious, and in their best interests. This was supported by pathologists who stated that their motivation for pimping was to identify knowledge gaps, thus benefiting the trainee.

Conclusions: Recognizing and understanding how trainees and staff perceive pimping can help shape a teaching environment to be most conducive to a positive learning experience.

Figure: Two examples of rich-picture drawings illustrating perceptions of pimping encounters.

Keywords: medical education; pimping; teacher and learner perceptions; pathology; teaching

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1700-1830

Screen 1.16 P6 Photogrammetry Software for 3d Reconstruction of Gross Pathology Specimens – Building Canada’s First Virtual Surgical Specimen Library

Qi Yanga, Corey Knickleb, Daniel W. Rickeyc, Julianne Kleina,b, Gabor Fischera,b, Marc Duprea,b.

aDepartment of Pathology, University of Manitoba, Winnipeg, Manitoba;

bDiagnostic Services Manitoba, Winnipeg, Manitoba;

cCancerCare Manitoba, Winnipeg, Manitoba.

Background: Knowledge of gross pathology is essential for pathologists and pathology assistants however training in gross pathology presents unique challenges. Specimen handling for fixation, rarity of specific specimen types and scheduling of learners can be barriers to comprehensive training. Conventional specimen photography can help overcome some of these issues, but two-dimensional photographs are limited in their ability to provide details from three-diemensional specimens. To overcome some of these limitations, we sought to explore 3D reconstruction to enhace training in gross surgical pathology.

Objective: Assess the feasibility of 3D reconstruction technology for building a virtual surgical gross pathology specimen library.

Methods: Multiangle photographs of fresh and fixed surgical specimens were acquired using a Nikon D800 camera equipped with a 24-70mm f1.4G lens. Images were cropped and processed to achieve similar lighting and exposure levels. Photogrammetry software was used for 3D reconstruction.

Data and Results: Nineteen specimen reconstructions were attempted using 8 different surgical specimens. Adaptations to photography techniques and adjustments to the photogrammetry software settings allowed us to produce 16 successful reconstructions. The 6 best reconstructions have been included in our initial collection. The models can be 3D printed, and so far we have printed one model for demonstration purposes.

Conclusions: We have domonstrated that with photogrammetry software, 2D gross photos can be converted into high-resolution 3D models with preserved detailed gross features. This technique is a promising solution to enhance training and education in gross pathology.

Keywords: Photogrammetry, grossing, 3D, surgical specimen, education

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1830-1930

Screen 1.21 P42 Inflammatory myofibroblastic tumour of the central nervous system with an ALK mutation, report of a case

Alexandra SL Pettita, Kelly Dakin Hachea, Julia A. Bridgeb, Adrienne Weeksc, Sidney Croula.

aDepartment of Pathology and Laboratory Medicine, Dalhousie University, Halifax, NS,

bDepartment of Pathology/Microbiology, Pediatrics and Orthopedic Surgery, Nebraska Medical Centre, Omaha, NE,

cDivision of Neurosurgery, Dalhousie University, Halifax, NS.

Objective: Inflammatory myofibroblastic tumour (IMT) is a rare tumour that most commonly affects children and young adults. They generally arise in the lungs and deep intra-abdominal soft tissues, but can occur at many anatomical sites. We present the case of a 30 year old woman presenting with a long standing history of experiencing déjà vu, who had a CT scan demonstrating a large mass in the right middle cranial fossa. The lesion was removed with a gross total resection and the pathology demonstrated a hypocellular spindle cell lesion expressing vimentin, ALK, S100, MIC2 and Bcl2 on immunohistochemistry. An ALK rearrangement (2p23) was detected by FISH, confirming the morphological impression of IMT. ALK mutations occur in approximately 50% IMTs and may be associated with recurrence for central nervous system lesions.

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1830-1930

Screen 1.22 P4 Extracranial extension of a recurrent, transformed anaplastic pleomorphic xanthoastrocytoma: Case report

Kristopher D. Langdona, Daria Krivosheyab, Lee-Cyn Anga, Bret Wehrlia.

aDepartment of Pathology and Laboratory Medicine and

bDepartment of Clinical Neurosciences, Schulich School of Medicine and Dentistry, Western University, London, ON Canada

Pleomorphic xanthoastrocytoma (PXA) is a rare tumour comprising <1% of all primary central nervous system tumours and the majority (~98%) occur supratentorially. We report on a 40-year-old female with a past medical history of a rare posterior fossa/cerebellar PXA who presented with a right-sided neck mass, decreased shoulder power and longstanding right tongue deviation with right-sided hemiatrophy. The patient had tumour debulking 8 and 6 years prior and subsequent gamma-knife resection 4 years ago. Recent MRI demonstrated an enhancing posterior fossa mass extending to the skull base at the jugular foramen and another mass in the upper neck along the jugular bulb with displacement and encasement of the right common carotid artery down to C5. Resection of the neck mass reveals an anaplastic PXA with endothelial proliferation, necrosis and 6-7 mitoses/10 HPF. The tumour stains positive for GFAP, S100, synaptophysin, vimentin and weakly for CD99. 5-10% of the cells’ nuclei stain positively for p53. The tumour has close approximation with adjacent peripheral nerves and is positive in 2 lymph nodes. Comparison with the original tumour molecular and immunohistochemical profiles reveals a conserved BRAF V600E mutation but the transformed malignant glioma expresses dot-like EMA positivity which is negative in the original tumour.

Transformation of a PXA (WHO Grade II) into an anaplastic PXA (WHO Grade III) has been well documented, but extracranial extension is extraordinarily rare. We report herein the first documented case of a posterior fossa PXA that underwent malignant transformation and extracranial extension to the parapharyngeal space.

Keywords: Pleomorphic xanthoastrocytoma; central nervous system; extracranial extension; malignant transformation

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1830-1930

Screen 1.23 P10 Melanotic CNS Lesions in the Era of Genomics: A Case Report and Review of Literature

Maha Haddad1, PerryDhaliwal2, Stephen Yip3, Sherry Krawitz1.

1Department of Pathology, University of Manitoba

2Division of Neurosurgery, University of Manitoba

3Department of Pathology, University of British Columbia

Objectives: Describe the problematic diagnosis of melanotic tumours involving the central or peripheral nervous system (CNS, PNS).

Background: Pigmented tumours involving the CNS and PNS include melanotic schwannoma, leptomeningeal melanocytic tumours (meningeal melanocytoma, intermediate-grade melanocytic neoplasm, meningeal melanoma), metastatic melanoma and pigmented gliomas. Their biologic behaviour ranges from benign to malignant. Accurate diagnosis is therefore of paramount importance. Carney complex (melanotic schwannoma) may also be revealed. The common neuroectodermal origin of these tumours may explain the morphologic and immunohistochemical similarity leading to diagnostic challenges. Certain genetic markers such as GNAQ, GNA11, GNAS, BRAF, KIT, NRAS and PRKAR1A may facilitate diagnosis.

Case Report: A 67 year old male presented with neck pain and hemiparesis. MRI showed a large cervical spinal intradural mass extending through the C3-C4 foramen along the C4 nerve root. Microscopically, the tumour consists of sheets of predominantly epithelioid cells with abundant eosinophilic cytoplasm and round to oval nuclei with prominent nucleoli and occasional pseudoinclusions. The tumour is heavily pigmented and highly vascular with occasional psammomma bodies. Focal cellular atypia and small areas of necrosis are identified. Immunohistochemically, the tumour is positive for S-100, HMB45, MART1, Sox10 and E-Cadherin. Collagen IV envelops small groups of cells. The tumour is negative for pan-cytokeratin, EMA, CD31 and CD117. The tumour is also negative for hotspot mutations in BRAF, GNAQ, GNA11, GNAS, KIT and NRAS. No loss of expression of BAP1 or INI1 is seen.

Conclusions: Molecular analysis of this developmentally related group of tumours may facilitate diagnosis and prognosis.

Keywords: Melanotic schwannoma, melanocytic tumours

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1830-1930

Screen 1.24 P48 Understanding Alzheimer’s (AD) as a congenital clonal disease

S. A (Tony) Morris M.D., FRCPa

aLaboratory Services, Red Deer Regional Hospital, Red Deer, AB

Purpose: To present a model for the etiology and pathogenesis of AD, consistent with the disease epidemiology, genetics, pathology and intracranial transmission of neuropathic proteins.

Background: The origin of sporadic AD (sAD) is unclear. AD is characterized by i) rare familial (fAD) early-onset and common sAD late-onset disease variants; ii) a disease-specific proteinopathy; iii) a decades-long latency; and iv) a disease-specific neuroanatomic origin and intracranial spread.

fAD: Three autosomally inherited genes, involved with amyloid precursor protein (APP) production, cause fAD. Embryonic/fetal expression of the APP gene begins during neuronal differentiation and synaptogenesis. Mutant amyloid beta (AB) protein is overproduced and spreads transynaptically for decades prior to diagnosis. The AB proteinopathy of fAD and sAD forms are identical, thus sAD must be caused by somaticDNA mutations identical to the inherited germline mutations of fAD.

Somatic mutation: No two somatic cells are genetically identical. Somatic mutation is as common in embryonic cells as it is in the germline. Intrinsic somatic mutation (DNA replication error) is the ultimate cause of sporadic clonal neoplasia and of tumours requiring “second hit” mutations. Neuronal stem cell proliferation is almost exclusive to the embryonic/fetal period, producing over 10 x 1011neurons. The concordance of sAD in monozygotic twins and occurrence in somatic mosaicism necessitates very early embryonic mutation.

Model: sAD is a congenital clonal disease, originating from intrauterine homozygous somatic mutations of neuronal stem cells resulting in rare clone(s) overproducing AB neuropathic protein with decades-long transynaptic spread. The model is applicable to other neurodegenerative proteinopathies.

Keywords: Alzheimer’s, somatic mutation, congenital, mosaicism

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1700-1800

Screen 2.11 P58 Lipomatous tumours with atypia are not always liposarcoma: immunohistochemical evaluation of a series of lipomatous tumours with atypia, including a retroperitoneal pleomorphic lipoma

Ashley N. Flamana,b, Denis H. Gravela,b, Chi K. Laia,b, Susan J. Robertsona,b, Bibianna M. Purginaa,b.

aDepartment of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON;

bUniversity of Ottawa, Ottawa, ON

Objective: Pleomorphic lipoma/spindle cell lipoma (PL/SCL) is a benign lipomatous tumour that may mimic well-differentiated liposarcoma (WDLPS). Using fluorescence in situ hybridization (FISH) for MDM2 amplification as the gold standard for diagnosis of WDLPS, we studied the utility of CD34, S100, and the relatively new marker HMGA2 in the evaluation of lipomatous tumours with atypia. In addition, we describe 3 cases of PL that occurred in unusual locations including the arm, forehead and retroperitoneum (previously reported only once in an English-language journal without MDM2 analysis).

Method: Using MDM2 FISH and immunohistochemistry (IHC) for CD34, S100 and HMGA2, we analyzed 16 cases of PL/SCL and 11 cases of WDLPS.

Data and Results: PL/SCL was uniformly CD34 positive and negative for S100 and HMGA2, while WDLPS was HMGA2 positive (100%) and negative for S100 (91%) and CD34 (55%). In all tested cases, MDM2 was amplified in WDLPS (7/7) and not amplified in PL/SCL (5/5). The retroperitoneal PL shared the same morphology, IHC and MDM2 status as the other PL.

Conclusions: 5 cases of WDLPS showed aberrant staining with CD34, which was often difficult to interpret because of background staining. Due to its tidy nuclear staining and ease of interpretation, as well as its superior performance at differentiating PL/SCL and WDLPS, utilizing HMGA2 with CD34 is especially useful. In addition, the morphology and IHC should be used in concert with MDM2 analysis in the diagnosis of difficult lipomatous tumours. Finally, though rare, retroperitoneal PL/SCL do exist and must be considered in this location.

Keywords: Pleomorphic lipoma, spindle cell lipoma, liposarcoma, HMGA2, MDM2

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1700-1800

Screen 2.12 P22 Panfolliculoma, report of a rare cutaneous neoplasm and literature review

Nikoo Parvinnejad1, Christine Orr1, Ami Wang1, David Hurlbut1.

1Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON

Objectives: Panfolliculoma is a rare benign follicular neoplasm first described by Ackerman et al in 1993 and with less than 40 cases reported to date. It shows differentiation toward all elements of a hair follicle. The aim of our report is to discuss the classic clinicopathological features and potential diagnostic pitfalls associated with this rare entity.

Methods: We report a case of panfolliculoma that presented at an unusual site (abdomen), with review of the current literature on this topic.

Data and Results: Our patient is a 74 year old man who underwent right hemicolectomy for colonic adenocarcinoma. At the time of surgery, he was found to have an abdominal skin lesion, which was resected as a presumed basal cell carcinoma. Histopathology revealed a cystic, well circumscribed lesion in the dermis with connection to the overlying epidermis. There is evidence of differentiation toward all components of a normal hair follicle, including: basaloid follicular germinative cells, cells with clear cytoplasm resembling the outer root sheath, and trichilemmal-type compact keratinization. Focally, bright red trichohyalin granules, yellowish cornified cells and ghost cells are identified.

Conclusion: Differential diagnosis includes other benign and malignant adnexal tumour, such as trichoblastoma, trichoepithelioma, trichofolliculoma, and basal cell carcinoma. It is important to recognize the diagnostic features of panfolliculoma to avoid overcalling malignancy.

Keywords: Panfolliculoma, Cutaneous, Neoplasm

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1700-1800

Screen 2.13 P33 Reticulin staining in primary melanomas versus cutaneous metastatic melanomas

Niloufar Hosseinia, Shachar Sadea.

aDepartment of Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON

Objectives: To investigate the usefulness of reticulin staining in differentiating primary melanoma from cutaneous metastatic melanoma.

Design: Reticulin staining pattern was compared in 143 cases, comprising 48 primary melanomas, 47 cutaneous metastatic melanomas (20 in-transits, 15 satellitoses, 12 regular cutaneous metastatic melanoma), and 48 nevi (27 intradermal nevi (IDN) and 21 dysplastic nevi (DN)). Patterns of reticulin staining were defined as follows: around group-complete (AG-C): surrounding groups of melanocytes in >50% of lesion; around group-incomplete (AG-IC): engulfing groups of melanocytes in <50% of lesion; around cells (AC): surrounding single cells in >25% of lesion; around cells and around group-complete (AC+AG-C); and around cells and around group-incomplete (AC+AG-IC).

Results: Variable reticulin patterns were seen in all three groups. However, none of the primary or metastatic groups showed AC pattern. Two third of primary melanomas showed AG-C while majority of the metastatic melanoma demonstrated AG-IC pattern. In the metastatic group, AG-IC was observed in 11/12(91%) regular cutaneous metastatic melanomas, 14/20(70%) in-transits and 8/15(53%) satellitoses.

Primary melanomas

Cutaneous metastatic melanomas

Nevi

AG-C, n/total (%)

36/48(75.0)

14/47(29.7)

12/48(25)

AG-IC, n/total (%)

12/48(25.0)

33/47(70.2)

9/48(18.7)

AC, n/total (%)

0

0

1/48(2.0)

AC+AG-C, n/total (%)

0

0

22/48(45.8)

AC +AG-IC, n/total(%)

0

0

4/48(8.3)

Conclusion: Reticulin staining might be of some value in differentiating benign from malignant melanocytic lesions, however, its usefulness in differentiating primary from cutaneous metastatic melanomas is yet to be established. Studies with a larger sample size might result in more definite conclusions.

Keywords: Reticulin staining, primary melanoma, cutaneous metastatic melanoma, nevus

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1700-1800

Screen 2.14 P28 Utility of Ber-EP4 and MOC-31 confirmatory markers in basaloid skin tumour detection

Pavandeep Gilla, Christopher Nauglera, and Marie Abi Daouda.

aDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB

Objective: Ber-EP4 has been the traditional immunostain used in the diagnosis of basaloid skin tumours. Recently, MOC-31 has shown be superior to Ber-EP4 in the detection of basosquamous basal cell carcinoma (BCC) and centers, such as Calgary Lab Services, are now increasingly using both Ber-EP4 and MOC-31 antibodies together as confirmatory markers for these lesions. In our quality assurance study, we aim to assess the necessity of using both of these markers. We also aim to add to the limited literature on MOC-31 staining properties in cutaneous lesions.

Methods: 76 basaloid skin tumours stained with both Ber-EP4 and MOC-31 were obtained. Diagnoses included basosquamous BCC, Merkel cell carcinoma, adenoid cystic carcinoma, microcystic adnexal carcinoma, sebaceous carcinoma, trichoepithelioma, trichoblastoma, sebaceous adenoma, sebaceoma, and follicular induction overlying dermatofibroma. The distribution and intensity of Ber-EP4 and MOC-31 staining in these lesions was scored. These scores were analyzed using a truth table, Chi-squared test, and Pearson correlation co-efficient tests. The overall mean and standard deviation of the scores was also obtained.

Data and Results: Overall, MOC-31 did have slightly more robust staining properties and slightly higher sensitivity than Ber-EP4 in this study. However, we found Ber-EP4 and MOC-31 to be statistically equivalent immunostains.

Conclusions: We recommend the use of only one of these antibodies and favour MOC-31 as a confirmatory marker for the detection of basaloid skin tumours. MOC-31 staining properties in different cutaneous lesions are also described.

Keywords: Dermatopathology, basal cell carcinoma, immunohistochemistry

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1800-1930

Screen 2.21 P24 A fatal case of group A streptococcal infection following an endometrial biopsy: A case study

Kaitlin A. Vanderbecka, Patricia Farmera.

aDepartment of Pathology and Molecular Medicine, Queens University, Kingston, ON.

Objective: Group A streptococcal infection results in considerable mortality. The goal of this study is to review the details surrounding a case of a 40 year old healthy female with persistent menorrhagia in the setting of endometriosis and chronic abdominal pain who underwent an in-office endometrial biopsy and began exhibiting symptoms of systemic infection within forty-eight hours. She later died of invasive group A streptococcus infection thought to be associated with acute pelvic inflammatory disease. An autopsy was performed.

Method(s): An analysis of the patient’s case, medical records, biopsy and autopsy findings was completed. A review of the literature surrounding the incidence of initially unrecognized Group A Streptococcal infection resulting in invasive infection following an endometrial biopsy was performed.

Data and Results: Autopsy results, corresponding surgical pathology and blood cultures indicate cause of death from systemic invasive group A streptococcal infection.

Conclusions: Cases involving initially unrecognized group A streptococcal pelvic inflammatory disease leading to disseminated infection have been reported. Literature discussing the incidence of disseminated group A streptococcal infection following an out-patient endometrial biopsy is limited. This would appear to be one of the first reports detailing the demise of a patient with initially unidentified group A streptococcal infection following an endometrial biopsy. The details of this particular case may increase awareness of such a complication and improve patient safety.

Keywords: Group A streptococcus, sepsis, endometrial biopsy

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1800-1930

Screen 2.22 P26 Case report of Good pasture syndrome from the Autopsy table

Loganathan Kathiravelua, Gibson, I.W.a, Klein, J.b, Balachandra, T.a.

aDepartment of Pathology, Max Rady College of Medicine Rady Faculty of Health Sciences;

bPathology, Diagnostic Services Manitoba, Winnipeg, MB

Background: Goodpasture syndrome is rare serious autoimmune disease characterized by diffuse alveolar hemorrhage and glomerularnephritis cause by circulating antibodies against collagen type IV with bimodal distribution around 3rd to 4th and 6th to 7th decades with male preponderance. Patients usually present with constitutional symptoms such as malaise, fever and arthralgia, proceed to pulmonary and renal manifestations. We report an example of Goodpasture syndrome from autopsy on a female child who was hospitalized for 3 days.

Case Report: A 11 year old child admitted to the emergency room with a presentation of hemoptyis for 3 days. Antibiotic was started however she became septic and died. On autopsy examination grossly the trachea showed mild erythema. The right and left lung weight 1070 g, 1020 g, respectively, both showed extensive hemorrhagic consolidation. The right and left kidney weighed 160 g, 150 g. correspondingly, both had smooth cortical surface and unremarkable corticomedullary pattern.

Histologically lung parenchyma shows extensive hemorrhage with fibrin in air spaces, collection of hemosiderin and foci of capillaries. No large vessels vacuities is identified. Sections from both kidneys showed changes consistent with rapidly progressive crescentic glomerulonephritis (RPCG).

Conclusions: This case report presents autopsy findings of diffuse alveolar hemorrhage with fibrin in air space, in conjunction with rapidly progressive crescentic glomerular nephritis, which comprised of initial hemoptysis in a young girl followed by septic state and short fatal course.

Confirmatory test require ante mortem serum which was not available and post mortem samples are not suitable for immunopathology laboratory testing.

Keywords: Goodpasture syndrome, pulmonary haemorrhage and glomerularnephritis.

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1800-1930

Screen 2.23 P61 Infantile undifferentiated round cell sarcoma showing BCOR genetic abnormalities in a 28 day old infant

Miraliakbari, H. M.D.a, Stefanovici, C. MD, FRCPCa.

aDepartment of Pathology, University of Manitoba, Winnipeg, MB

We present a case of a retroperitoneal mass in a 28-day old infant boy. Initial interpretation showed that this mass represented a high grade undifferentiated round cell sarcoma, with high mitotic activity (>10 Mitotic Figures/ 10 High Power Fields) and large areas of necrosis. Immunostaining profile of this tumour revealed positivity for CD99, CD56, Bcl2, and weak reactivity for CD117. The tumour also showed strong and diffuse expression of BCOR and SATB2 nuclear reactivity. Reverse transcriptase DNA amplification for Ewing Sarcoma fusion transcript and Synovial Sarcoma fusion transcript were both negative. These findings fit with the newly described entity of an infantile undifferentiated round cell sarcoma showing BCOR genetic abnormalities. Herein, we review the histology, pertinent immuno-histochemical stains and cytogenetic abnormalities associated with these lesions.

Keywords: Infantile undifferentiated round cell sarcoma, BCOR, SATB2

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1800-1930

Screen 2.24 P7 On multifactorial causes of fetal death: a rare case of non-lethal in utero aortic dissection post-motor vehicle accident

Alysa A. Poulin1, Camelia Stefanovici1,2.

1University of Manitoba, Winnipeg, MB;

2Department of Pathology, Health Sciences Centre, Diagnostic Services of Manitoba, Winnipeg, MB

Introduction: The cause of fetal demise is attributed to three factors: fetal, maternal, or placental and requires thorough examination of both the fetus and the placenta.

Objective: We present the case of an in utero aortic dissection post-motor vehicle accident (MVA) that was not the immediate cause of fetal demise, as multiple other contributing factors were identified.

Methods: A 24 year old female, with a history of cocaine use, was involved in a major motor vehicle accident at 30-32 weeks gestation. She experienced premature rupture of membranes and delivered a stillborn male two days following the accident.

Data and Results: Perinatal autopsy revealed a Stanford type-B aortic dissection, a ventricular septal defect, evidence of chronic cerebral hypoxic change, and meconium aspiration. Toxic levels of cocaine metabolites were found in the fetal blood. Examination of the placenta revealed fresh parenchymal and retroplacental hemorrhage, along with myonecrosis of the umbilical vessels. Interestingly, cytogenetics revealed a trisomy 8 mosaicism of the fetus.

Conclusions: The cause of fetal demise following trauma is most often due to placental abruption. Aortic dissection, if left untreated, is lethal as it produces pericardial tamponade. Histological examination did not show tissue hemorrhage surrounding the aortic dissection, implying that fetal demise was likely initiated by a placental abruption at/near the time of the MVA. However, this is confounded by the presence of cocaine metabolites in the blood as cocaine (ab)use in pregnancy has been implicated in placental abruption/insufficiency. Our case demonstrates that multiple factors may contribute to intrauterine fetal demise.

Keywords: In utero aortic dissection, placental abruption, cocaine (ab)use, meconium aspiration

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1800-1930

Screen 2.25 P31 A case report of bile duct paucity in an infant with trisomy 18

Christine E. MacColl MDa, Jorge Arredondo MDa, Sarab Mohamed MDa, Radenka Bozanovic MDa.

aDepartment of Pathology and Molecular Medicine, McMaster University

Background: Cholestasis results in reduced bile excretion. When bile flow is obstructed due to destruction, reduction, or absence of interlobar bile ducts, this is known as bile duct paucity and is diagnosed with liver biopsy. The normal ratio of bile ducts to portal tracts in a term newborn is between 0.9 and 1.8. A ratio of less than 0.5 is diagnostic for paucity. Etiologies for bile duct paucity include Alagille syndrome, prematurity, congenital infections, metabolic and endocrine abnormalities. Bile duct paucity is also described as a rare feature of trisomy 18.

Case Presentation: A baby girl was born at term and a diagnosis of trisomy 18 was confirmed with postnatal cytogenetics. She did not exhibit features of Alagille syndrome. After developing pale stools and conjugated hyperbilirubinemia, she was investigated for an etiology of cholestasis. Non-invasive testing ruled out common causes. Liver core biopsy revealedtwo bile ducts present in eight portal tracts (duct to portal tract ratio of 2:8 = 0.25).

Discussion: The number of portal tracts on liver biopsy needed for a diagnosis of paucity in the newborn ranges in the literature from 5 to 20. The eight bile ducts identified on biopsy is adequate for diagnosis. The workup for a viral, metabolic, or endocrine etiology of paucity was negative. We therefore report a case of neonatal cholestasis due to paucity of bile ducts in association with trisomy 18. This report contributes an additional case to a rarely observed association.

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1800-1930

Screen 2.26 P5 Mammary Analogue Secretory Carcinoma of the Parotid Gland in a 6-year-old

Daniel Mandersa, Ryan Decostea, Chelsea Maedlera, Craig Midgenb, Liane Barbara Johnsonc, Robert Hartc, Martin Joseph Bullocka.

aDepartment of Pathology and Laboratory Medicine and Pathology, Dalhousie University, Halifax, NS;

bDepartment of Pathology and Laboratory Medicine and Pathology, IWK Health Center, Dalhousie University, Halifax, NS;

cDepartment of Surgery, IWK Health Center, Dalhousie University, Halifax, NS

Background: Mammary analogue secretory carcinoma (MASC) is a newly described salivary gland malignancy characterized by a t(12;15)(p13;q25) translocation that produces an ETV6-NTRK3 fusion protein. MASC has similar morphology to secretory carcinoma of the breast and shows immunoreactivity to S100, MUC4 and mammoglobin. MASC shares the same translocation as infantile fibrosarcoma and congenital mesoblastic nephroma. Very few cases of MASC have been described in the pediatric population. To our knowledge, the youngest patient to be diagnosed with MASC in the literature was 14 years old.

Clinical History: A 6-year-old male, with no previous medical history, presented to our institution with a 3month history of a right parotid mass that had been increasing in size. Initial fine-needle aspiration of the lesion was non-diagnostic. A CT scan revealed a predominantly cystic structure with a thin enhancing rim, no calcification, and no obvious solid soft tissue component within the superficial lobe of the right parotid gland. The differential diagnosis included sialocele and a first branchial cleft cyst. Additional imaging studies did not reveal any loco-regional or distant metastatic disease. Due to the increasing size, surgical excision of the lesion was undertaken. Histologic and immunohistochemical studies showed a neoplastic cystic lesion composed of mucin producing epithelial cells. The neoplastic cells were immunoreactive to antibodies directed against monokeratin, vimentin, CK8/18, S100, and mammoglobin. There was patchy positivity for p63, GCDFP15, EMA and DOG1. Mucicarmine highlighted mucin production within the neoplastic cells. Tissue was sent to the University of Nebraska Medical Center for molecularcytogenetic studies and confirmed the presence of a rearrangement of the ETV6 (12p13) locus in 100% of 200 interphase cells analyzed. These findings were consistent with a diagnosis of MASC. At the time of surgical excision, there was tumor spillage and positive margins. Due to the limited knowledge regarding management of these lesions in the pediatric population, external consultation on management and treatment strategies was sought. The patient underwent additional radiation therapy to the tumor bed following initial excision and was alive and well at an 8-month follow-up visit with no evidence of tumor recurrence.

Conclusion: To our knowledge, we report the youngest case of MASC in an otherwise healthy 6-year-old male.

Keywords: MASC, pediatric, salivary gland

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1700-1745

Screen 3.11 P32 GATA3 is a sensitive and specific marker for mesonephric carcinomas of the gynecologic tract

Angela S. Chenga, Jennifer Porsb, C. Blake Gilksa,b, Lien N. Hoangb.

aGenetic Pathologic Evaluation Center, Vancouver, BC

bDepartment of Anatomical Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, BC

Background: Mesonephric carcinomas are rare neoplasms of the gynecologic tract and are of mesonephric/Wolffian origin. They often exhibit a variety of morphologic patterns, which make them difficult to distinguish from other gynecologic neoplasms, particularly in the absence of adjacent mesonephric remnants.

GATA3 is a transcription factor involved in embryogenesis and cellular differentiation. It is a well-known immunohistochemical marker for breast and urothelial neoplasms, and has recently been described in mesonephric carcinomas. Here we investigate the sensitivity and specificity of GATA3 and TTF1 for mesonephric carcinomas, using an expanded series of gynecologic carcinomas.

Methods: The immunohistochemical expression of GATA3 and TTF1 were assessed in a series of 549 uterine carcinomas using tissue microarrays and/or whole sections.

Results: GATA3 distinguished mesonephric carcinoma from other uterine carcinomas (p < 0.001), while TTF1 did not (p = 0.0744) (Table 1).GATA3 had a sensitivity of 85.7% and specificity of 96.1%.In comparison, TTF1 had a sensitivity of only 14.3%.The proportion of GATA3 positive cells decreased as mesonephric carcinomas became poorly differentiated (solid/spindled). GATA3 was also positive in 13% of malignant mixed Mullerian tumors (MMMT).

Table 1. Immunohistochemical expression of GATA3 and TTF1 in 549 uterine carcinomas.

Diagnosis

Total # of cases

GATA3 (-) TTF1 (-)

GATA3 (-) TTF1 (+)

GATA3 (+) TTF1 (-)

GATA3 (+) TTF1 (+)

Endometrioid, grade 1-2

193

191 (99%)

1 (0.5%)

1 (0.5%)

0 (0%)

Endometrioid, grade 3

130

123 (95%)

2 (2%)

5 (4%)

0 (0%)

Serous

95

90 (95%)

1 (1%)

4 (4%)

0 (0%)

Clear Cell

30

28 (93%)

0 (0%)

1 (3%)

1 (3%)

Carcinosarcoma (MMMT)

70

61 (87%)

0 (0%)

9 (13%)

0 (0%)

Mesonephric

7

1 (14%)

0 (0%)

5 (71%)

1 (14%)

MIXED

12

12 (100%)

0 (0%)

0 (0%)

0 (0.0%)

Others:

Small Cell

4

4 (100%)

0 (0%)

0 (0%)

0 (0%)

Undifferentiated

4

4 (100%)

0 (0%)

0 (0%)

0 (0%)

Mucinous

3

0 (0%)

0 (0%)

0 (0%)

0 (0%)

Large Cell

1

1 (100%)

0 (0%)

0 (0%)

0 (0%)

Total cases

549

Conclusion: GATA3 is a sensitive and specific marker for mesonephric carcinomas, but is also positive in a proportion of MMMTs.

Keywords: GATA3; TTF1; Mesonephric Carcinoma; Immunohistochemistry

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1700-1745

Screen 3.12 P29 Clinicopathologic disparities in differentiated vulvar intraepithelial neoplasia (dVIN): A comparison of colposcopic and microscopic findings

Y. Ariel Liua, C. Blake Gilksa, Lien N. Hoanga.

aDepartment of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, BC.

Background: The putative precursor lesion to vulvar squamous cell carcinoma (SCC) is termed vulvar intraepithelial neoplasia (VIN). There are two distinct types of VIN: 1) usual VIN (uVIN), which is driven by human papillomavirus (HPV) infection and 2) differentiated VIN (dVIN), which occurs independently of HPV. Unlike uVIN, the histologic features of dVIN are subtle and often under-recognized. In this study, we contrast the histologic and physical examination findings in a series of patients with dVIN.

Methods: We identified 5 patients who had an eventual diagnosis of dVIN, multiple preceding biopsies which were reported as negative and colposcopic images available for review.

Results: The colposcopic findings and corresponding pathology results for each patient are summarized in Table 1.

TABLE 1: Colposcopic and pathology findings in 5 patients with dVIN with multiple preceding biopsies.

Patient

Timeframe

Colposcopy findings

Pathology findings

#1: 84 yo Hx of uVIN

Presentation

Raised white plaque with central ulcer and pushing borders on left labia minora, 1-2 cm, extending into vaginal canal.

Bx: Benign. (Acanthosis, scarring and chronic inflammation)

4 mo later

White plaque, 2-3 cm, with an enlarging ulcer.

Bx: Reactive. (Acute and chronic inflammation with plasma cells)

1 week later

Confluent white plaques, 1-2 cm central ulcer.

Bx: dVIN

#2: 57 yo

Presentation

Bx: Suggestive of verruca vulgaris. (Acanthosis, hyperkeratosis, papillomatosis)

6 years later

Bx: Benign. (Hyperkeratosis, acanthosis)

22 mo later

Bx: Possible condyloma. (Hyperkeratosis, parakeratosis, focal papillomatosis)

4 mo later

Raised white lesion with fine papillations on the left labia minora, 1-2 cm, extending into vaginal canal.

Bx: Reactive. (Acanthosis, hyperkeratosis, papillomatosis and reactive epithelial atypia)

2 mo later

1-2 cm white lesion.

Exc: dVIN

#3: 43 yo

Presentation

Bx: Benign.

11 mo later

A 6-8 cm papillomatous white lesion on right labia majora.

Bx: Squamous papilloma.

1 mo later

As above.

Bx: Squamous papilloma.

2 weeks later

As above.

Exc: Invasive well-differentiated SCC, 6.5 cm, and dVIN.

#4: 52 yo

Presentation

Superficial ulceration, 1-2 cm white plaques, background of edematous labia majora & minora.

Bx: Benign. (Hyperkeratosis)

4 mo later

Increase in ulceration, persistent white plaques on labia and anterior vestibule.

Bx: Suggestive of early LS. (Hyperkeratosis, parakeratosis and lichenoid inflammation)

20 mo later

Diffuse erythema around vulva to medial thigh, deep ulceration expanded to 3-4 cm, persistent white plaques, yellow exudate thought to be due to infection.

Exc: Invasive SCC, multifocal, with background of dVIN.

#5 80 yo Hx of LS

Presentation

1-2 cm white plaque on the left labia minora, extending into vaginal canal.

Bx: Not done.

6 mo later

Persistent 1-2 cm white plaque.

Bx: Reactive. (Irritative changes with hyperkeratosis, parakeratosis, acanthosis, edema and chronic inflammation)

35 mo later

2-3 cm fungating white lesion along anterior vestibule, labia minora and vaginal canal, extension onto right labia majora.

Exc: Verrucous carcinoma, 4 cm, dVIN and LS.

2 mo later

0.5 mm white papillary lesion.

Bx: Benign. (Acanthosis, parakeratosis)

1 mo later

White papillary lesion quickly growing back to previous size.

Bx: Squamous atypia with ulceration.

1 mo later

Solitary white lesion, 1 cm.

Exc: Verrucous carcinoma, 11 mm.

Abbreviations: yo: years old; LS: lichen sclerosus; dVIN: differentiated vulvar intraepithelial neoplasia; VIN: vulvar intraepithelial neoplasia; SCC: squamous cell carcinoma; Bx: biopsy; Exc: excision.

Conclusions: The histologic features of dVIN and HPV-independent SCC can be subtle on biopsies, and in striking contrast to the conspicuous lesions seen on clinical examination. In our series, 1-4 biopsies were done before dVIN was recognized. In 3 patients, a diagnosis of carcinoma was made before any preneoplastic lesion was diagnosed. This series highlights the importance of clinicopathologic correlation, repeat sampling or excision in clinically suspicious lesions and the need for better ancillary tools to help improve recognition of dVIN.

Keywords: Vulva; Squamous cell Carcinoma; Vulvar Intraepithelial Neoplasia; dVIN; simplex VIN

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1700-1745

Screen 3.13 P60 Concomitant bilateral serous borderline tumour with an ovarian teratoma composed of primary ovarian carcinoid and thyroid tissue, a case report

Kianoosh Keyhaniana, Mary Sentermana, Zohreh Eslamia.

aDepartment of Pathology and Laboratory Medicine, University of Ottawa/The Ottawa Hospital, Ottawa, ON

Primary neuroendocrine tumour (NET) is an infrequent ovarian germ cell tumour, and its coexistence with surface epithelial tumours is extremely rare. Rare cases of NET are reported to co-occur with a serous neoplasm. We report the co-existance of bilateral serous borderline tumou (SBT) with a teratoma composed of well-differentiated NET and thyroid tissue, which to the best of our knowledge has not been described yet.

A 63 year-old woman underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for an incidental imaging finding of bilateral complex ovarian masses. Her serum CA125 was 21 kU/L. Gross examination showed that the right ovary was completely replaced by a solid and cystic lesion and her left ovary contained an attached cystic lesion. Microscopic assessment revealed bilateral SBT and a right-sided teratoma with the major component of a well-differentiated NET and a small component of bland thyroid tissue. Immunohistochemistry confirmed that the SBT was positive for WT1, CK7, PR and ER. The NET showed positive reaction for chromogranin, synapthophysin and pancytokeratin and was negative for thyroglobulin and calcitonin.

Our observations indicate that although these two lesions were focally present close together, they were distinct entities within the ovary, in the manner of collision tumours. Thyroid tissue cells also did not intermingle with the insular arrangement of the NET.

Mature teratomas may be associated with mucinous surface epithelial neoplasms. However, the co-existence of a NET with a serous epithelial neoplasm is rarely reported. Our report is a rare example of collision between NET and bilateral SBT.

Keywords: Teratoma, Ovarian carcinoid, Serous borderline tumour

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1745-1930

Screen 3.21 P34 FGFR and B-Cells and Eos…Oh My!

A Rare Combination of B-Cell Acute Lymphoblastic Lymphoma with Eosinophilia and Abnormality of FGFR1 (8;13 Translocation).

Ian Brain1, Monalisa Sur.1,2, Franklin Ling3, Catherine Ross1,2.

1Department of Pathology and Molecular Medicine, McMaster University, Hamilton Ontario

2Department of Pathology and Molecular Medicine, Hamilton Health Sciences (Juravinski Hospital and Cancer Centre), Hamilton Ontario

3Department of Pathology, Grand River Hospital, Kitchener Ontario

Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 was an entity first included in the 2008 WHO blue book and subsequently updated in the 2016 revi-sion. As the verbose title suggests, this entity encompasses a heterogenous group of neoplasms all sharing the hall-mark of “prominent eosinophils” or “associated with peripheral blood or bone marrow eosinophilia” with one of the driver mutations mentioned above. There are multiple translocations and insertions that lead to rearrangements ofFGFR1.Most of the associated neoplasms are myeloid proliferations, commonly chronic eosinophilic leukaemia orAML. T cell acute lymphoblastic leukemias are also reported. B-cell acute lymphoblastic leukemias make up a small fraction of this already rare entity (most involving a rearrangement of the PDGFRB or PCM1-JAK2 gene). Inthe current literature there are only 8 previously reported cases of precursor B ALL with rearrangements of FGFR1 (t8;13).

In this case report we review a 35 year old gentleman who was found to have precursor B acute lymphoblastic leu-kaemia with eosinophilia and a rearrangement of FGFR1 representing the potential 9th case tobe presented in the literature.

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1745-1930

Screen 3.22 P41 Utility of PAX5/PD-1 double staining in the pathological diagnosis of angioimmunoblastic T-cell ymphoma

Shuo Xua, Yi Mi Rena, Jillann Jaynesa, David Pierre Le Bruna.

aDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, On.

Objective: Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common subtypes of peripheral T-cell lymphomas. It can resemble a number of conditions and lacks a unifying diagnostic hallmark. AITL cells have the immunophenotype of follicular T-helper (TFH) cells; however, immunostains are difficult to interpret due to the intimate association with B-cells. We developed a double stain for a cytoplasmic TFH marker, PD-1, and a nuclear B-cell marker, PAX5. We hypothesize that distinguishing AITL cells from B-cells using this stain will aid the distinction between AITL and its mimics.

Method: The PAX5/PD-1 double stain was established using the Leica PAX5(1EW) Bond Ready-To-Use mouse monoclonal antibody and Cell Marque PD-1(NAT105) mouse monoclonal antibody. PAX5 and PD-1 were detected as nuclear DAB and cytoplasmic Fast Red signals, respectively. Tonsils and appendices were used as control tissues. The double stain was applied to 16 retrospectively-identified AITL samples. Two follicular hyperplasia cases were also double stained.

Data and Results: In control tissues, PD-1-positive cells were largely restricted to the follicle centers; 10-20% of paracortical PAX5-negative lymphocytes expressed PD-1 weakly. In AITL, 10-95% of the paracortical PAX5-negative atypical cells were strongly positive for PD-1. No double-positive cells were identified. The staining pattern observed in follicular hyperplasia was identical to that in control tissues.

Conclusion: By permitting the confident determination of PD-1 expression status among non-B lymphocytes, the PAX5/PD-1 double stain has potential utility in the pathological diagnosis of AITL. Currently, we are preparing a TMA to compare the staining pattern between AITL and its mimics.

Keywords: Double stain, PAX5, PD-1, Angioimmunoblastic T-cell lymphoma, AITL

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1745-1930

Screen 3.23 P56 ALK-negative anaplastic large cell lymphoma arising in breast prostheses: Evolution of a new diagnostic entity

Carolyne E. Lemieuxa, Catherine Rossb, Monalisa Surb.

aDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON;

bDepartment of Pathology and Molecular Medicine, Juravinski Hospital, Hamilton, ON.

Objective: Primary breast lymphoma is rare and comprises up to 0.5% of primary breast malignancies. They are most commonly B cell non-Hodgkin’s lymphoma and present as a solid mass. In patients with prior cosmetic or reconstructive silicone or saline-filled breast prostheses, careful consideration of the prosthetic with a seroma or solid tumour warrants concern for anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), a rare T-cell non-Hodgkin’s lymphoma. The current literature supports an association between breast prostheses and ALK-negative ALCL.

Data and Results: We present 3 cases of primary extra-nodal ALK-negative ALCL arising in breast prosthesis:

Clinical Presentation

Medical History

Initial Diagnosis

Frozen Section Diagnosis/Prosthesis Fluid

Fluid Diagnosis

Follow-Up

66 yo F; Left breast implant erythema, pain (2006)

Infiltrating ductal carcinoma (1994); mastectomy and saline prosthesis reconstruction (1999)

Partially deflated implant with capsular contraction

Recurrence; anaplastic carcinoma

Primary ALK-negative ALCL

Prosthetic removal; CHOP chemotherapy and radiation

58 yo F; Right breast asymmetry, erythema and warmth (3/12 duration)

Bilateral silicone prostheses (2009)

Mastitis or implant rupture +/- abscess

Poorly differentiated tumour (query carcinoma, melanoma, lymphoma)

ALK-negative ALCL

Bilateral removal of prostheses with capsulectomies; radiation right breast

43 yo F; Left breast pain

Bilateral silicone prostheses

Unknown

Recurrent seroma with mixed inflammatory cells

ALK-negative ALCL

Bilateral removal of prostheses with capsulectomies

Conclusions: ALK-negative ALCL is a rare lymphoma and an association with breast implants has been identified. These three cases contribute to the evolving literature, now considered a new entity in the 2016 World Health Organization (WHO) classification of tumours of hematopoietic and lymphoid tissues. There is evidence suggesting these rare neoplasms behave in a relatively indolent fashion compared to nodal and extra-nodal ALK-negative ALCL, thereby rendering them to more conservative treatment options. An awareness of the radiologic and variable morphologic appearances mimicking other malignancies to avoid mislabelling these entities is important to avoid incorrect treatment and preserve optimal patient outcomes.

Keywords: breast implant, lymphoma, ALK-negative ALCL

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1745-1930

Screen 3.24 P20 Pseudohypercalcemia: a potential pitfall in calcium testing in multiple myeloma. A case report and audit.

Pouya Sadeghi Avala, Sudeep Shivakumarb, Manal Elnenaeia.

aDepartment of Pathology, Dalhousie University, Halifax, NS;

bDivision of Hematology, Dalhousie University, Halifax, NS.

Background: Hypercalcemia is present in 28% of patients diagnosed with Multiple Myeloma (MM), and is considered a myeloma defining event. Proper determination of serum calcium has both diagnostic and therapeutic implications. Rarely, the measured total calcium (tCa) is elevated with a discordant normal ionized calcium (iCa), a phenomenon known as pseudohypercalcemia. We report a recent case of pseudohypercalcemia and a retrospective audit at our institution.

Case: A 71 year old male underwent a partial nephrectomy for a left kidney mass. Postoperatively, his tCa increased to 2.8 mmol/L (reference: 2.2-2.6 mmol/L) and a subsequent bone marrow biopsy was consistent with MM. Serum protein electrophoresis revealed 69.2 g/L of a monoclonal IgG lambda. He continued to have an elevated tCa up to 3.8 mmol/L, but normal iCa. Given the pseudohypercalcemia, he did not require aggressive calcium lowering therapy.

Methods: We retrospectively searched our laboratory database for flow cytometry (FL) results containing the word “CD138”, between 2010 and 2016. Those patients were secondarily searched for an elevation in tCa > 2.8 mmol/L at any point during the search period. Charts were subsequently reviewed.

Results: A total of 1206 FL samples were identified, which yielded 64 patients with hypercalcemia; 52 (88%) had a confirmed diagnosis of MM, 22 (42%) of which had a corresponding iCa, 6 (27%) of whom had pseudohypercalcemia at some point during the search period.

Conclusions: Pseudohypercalcemia is under-recognized and likely more prevalent given the lack of concurrent tCa and iCa testing. This may lead to inappropriate therapy.

Keywords: Pseudohypercalcemia, Multiple Myeloma

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1745-1930

Screen 3.25 P38 Quality improvement in calcified specimen processing: A comparison of decalcification solutions and durations

Duc-Vinh Thaia, Lara Richera, Jason Karamchandania, Miriam Blumenkrantza.

aDepartment of Pathology, McGill University, Montreal, QC

Objective: Tissue decalcification is an essential step in the processing of calcified specimens. This study compares the effects of different decalcification methods on hematoxylin and eosin (H&E) staining and on immunohistochemistry and chromogenic in situ hybridization (CISH) studies routinely used in the assessment of decalcified specimens.

Methods: Eight pediatric tonsils were selected as proxies for bone marrow. They were routinely processed and decalcified with RDO (Apex), Surgipath Decalcifier I (Leica) or 10% formic acid (ACP Chemicals), for one to 24 hours. Tissue slides were assessed for H&E, with 22 immunohistochemical antibodies (including CD3, CD20, CD45, and Ki-67) and with kappa and lambda light chain CISH. Quality was semi-quantitatively scored on a three-point scale.

Data and Results: Optimal H&E staining quality was maintained in tonsils treated in SurgiPath Decalcifier I or formic acid, but there was progressive loss of basophilia in tissue treated for two hours or more in RDO. In the immunohistochemical and CISH studies, the cumulative scores of RDO-treated tonsils were significantly lower than the Surgipath Decalcifier I or formic acid groups. There was a significant decline in antigenicity by 24 hours of decalcification in both Surgipath Decalcifier I and RDO groups while it was maintained in the formic acid group.

Conclusion: In as little as two hours, decalcifying agents can harm the staining quality and antigenicity of well-fixedtissue. Our study highlights the importance of validating the effect of specific decalcification procedures on routine stains and on immunohistochemistry and CISH studies for accurate diagnostic interpretation.

Keywords: decalcification, staining, immunochemistry, hybridization, optimization

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1745-1930

Screen 3.26 P1 Hemoglobin and white cell count levels in patients clinicallysuspected to have essential thrombocythemia may help in predicting early primary myelofibrosis or unclassifiable myeloproliferative neoplasm: Results of a Canadian Personal Practice Assessment Program focused onhematologist / pathologist collaboration

Attilio Orazia, Catherine Rossa,b, Shireen Sirhanc.

aWeill Cornell Medical College, New York-Presbyterian Hospital, NY, USA;

bMcMaster University, Hamilton, ON;

cJewish General Hospital, McGill University, Montreal, QC

Objective: To examine applicability of the Carobbio algorithm in routine practice and its potential use in identifying among patients presenting with thrombocytosis and clinically suspected to have ET, those with early PMF or MPN-U.

Methods: A retrospective Personal Practice Assessment Program was conducted at 8 Canadian institutions. Eight hematology/pathology pairs reviewed charts of about 20 consecutive examined patients who presented with thrombocytosis and suspected to have ET. The first 5 out of 20 cases who met the Carobbio algorithm were selected for BM evaluation.

Results: A total of 122 patients with a clinical history indicative of ET were assessed. 48 met the criteria outlined in the Carobbio algorithm, Figure. The BM examination was performed on 33 patients. About one third of the 33 patients met the WHO classification for ET and one third for PMF.

Conclusions: Despite its methodological limitations, this initiative confirms that in real world clinical practice the Carobbio algorithm can be used to identify possible cases of early PMF and MPN unclassifiable among patients clinically suspected to have ET. It suggests a need for educational initiatives on using diagnostic algorithms to separate ET from PMF and the importance of hematologist-pathologist collaboration in reaching a final integrated diagnosis.

Keywords: hematologist-pathologist collaboration, essential thrombocythemia,primary myelofibrosis, myeloproliferative neoplasm, education

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1745-1930

Screen 3.27 P13 Analysis of CD123 and Retinoblastoma (Rb) protein immunohistochemistry in Blastic Plasmacytoid Dendritic Cell Neoplasm

Sundip Shah1, Chris Howlett1, Nikhil Sangle1.

1Department of Pathology and Laboratory Medicine, Western University

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as CD4+CD56+ haematodermic neoplasm, is a recent entity identified in the 2008 World Health Organization classification and is a very aggressive and rare subtype of acute myeloid leukemia. BPDCN is thought to originate from clonal proliferation of precursor plasmacytoid dendritic cells (PDC) and is believed to share a phenotypic commonality with PDC by having a strong expression to CD123 (IL-3 receptor α chain). Karyotypic analyses of these tumour usually reveals a complex karyotype, however a few recurrent chromosomal abnormalities have been identified, including loss of 13q in over half of cases. It has been postulated that the deregulation of the G1-S cell cycle checkpoint is a common abnormality in these tumours, and the loss of the retinoblastoma (RB1) gene (located at 13q) possibly playing a key role in this process. This quality assurance study will be used to analyze CD123 expression in multiple cases of bone marrow and skin BPDCN, including calculating its sensitivity and specificity, as well as validating the use of CD123 immunohistochemistry in the clinical laboratory for future diagnosis of BPDCN. In addition, immunochemistry for the RB protein (pRB) will be attempted, and correlated with karyotype results.

Keywords: Blastic plasmacytoid dendritic cell neoplasm, CD123, RB protein

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1700-1815

Screen 4.11 P45 Case report: GAPPS – syndromic progression from fundic gland polyps to metastatic gastric adenocarcinoma

Christine E. Orra, Andrea Hawryshb, Paul Manleya.

aDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario

bFamilial Oncology Program, Kingston General Hospital, Kingston, Ontario

Introduction: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a newly described autosomal dominant syndrome. It consists of hundreds to thousands of fundic gland polyps (FGP) localized to the body and fundus with potential progression to invasive adenocarcinoma. Only nine families have been described thus far with several cases advancing to adenocarcinoma. In 2016 the mutation was mapped to the APC promoter exon 1B.

Case: A 54-year-old woman presented in 2000 with thousands of FGP carpeting the gastric body and fundus with focal low grade dysplasia. Subsequent biopsies intermittently showed focal low grade dysplasia until June 2003 when she developed a villous adenoma. In 2014 the first focus of high grade dysplasia was identified. No colonic polyps were found on repeated colonoscopies. A recommendation of gastrectomy was refused. Extensive genetic testing for gastrointestinal polyp syndromes in August 2016 was negative; however GAPPS mutation analysis was not clinically available then. The dysplasia progressed to intramucosal carcinoma by November 2016. Genetic testing in January 2017 showed an APC promoter exon 1B mutation (c.-192A>G). Liver and omental metastases of poorly differentiated adenocarcinoma were diagnosed on February 2017. There is no family history of gastrointestinal cancer. Genetic assessment and counselling has been recommended for the patient’s first-degree relatives.

Discussion: GAPPS should be clinically considered in all patients with multiple FGP, especially those with focal dysplasia. Prophylactic gastrectomy is currently recommended for all mutation positive adults as metastatic adenocarcinoma has been found in asymptomatic family members in their thirties.

Keywords: GAPPS, Fundic Gland Polyps, APC Promoter Exon 1B

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1700-1815

Screen 4.12 P55 Idiopathic myointimal hyperplasia of mesenteric veins-a case report

Hui Wanga, Sheev Dattanib, Mary Kinlocha, Dilip Gillb, Chaturika Heratha.

aDepartment of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK;

bDepartment of Surgery, University of Saskatchewan, Saskatoon, SK.

Objective: To consider IMHMV in the differential diagnosis when endoscopic biopsy findings do not support the presumptive diagnosis of inflammatory bowel disease.

Introduction: Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare cause of ischemic colitis that can mimic inflammatory bowel disease clinically, leading to diagnostic pitfall. It generally occurs in young, previously healthy male patient with mainly rectosigmoid colon being involved. The definitive diagnosis is usually established by histopathological evaluation.

Case Presentation: A 61-year-old man with three-month history of significant diarrhea, urgency and abdominal pain was initially diagnosed with indeterminate colitis with suspicion of Crohn’s disease. It was refractory to steroid and infliximab treatment and the patient was hospitalized with toxic megacolon. An abdominal total colectomy was performed. Histopathological examination of colon showed features of ischemic colitis with marked myointimal hyperplasia of mural and extramural veins. Arteries were spared. The findings were consistent with IMHMV diagnosis.

Conclusion: For patients with IBD symptoms but without specific endoscopic features and refractory to steroid or immunosuppressant, IMHMV should be suspected.

Keywords: Idiopathic myointimal hyperplasia in mesenteric veins (IMHMV), inflammatory bowel disease (IBD), ischemic bowel disease, toxic megacolon

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1700-1815

Screen 4.13 P53 Sixty-two hepatocellular carcinomas arising in otherwise-healthy livers are shown to display larger size and more vascular invasion, but no difference in pT stage or WHO grade, as compared to their counterparts arising in diseased livers

Jeremy Danielsa, Oyedele Adeyia, Sandra Fischera.

aDepartment of Laboratory Medicine, University Health Network, University of Toronto

Objective: To determine whether hepatocellular carcinomas developing in healthy livers differ from those arising in abnormal ones.

Methods: Our institution’s pathology database was searched for years 2001-2015, for “Hepatocellular Carcinoma” (HCC) (only search term). Records were manually reviewed. Resections and explants were included in the study (n=1116). Recurrent and fibrolamellar cases of HCC were excluded. Data were abstracted for WHO tumor grade, T-stage, tumor size, presence of vascular invasion, and background fibrosis stage (Laennec). 62 cases without risk factors for HCC (the “otherwise-healthy group”) were identified (fibrosis stage <=2, with no liver infection, hemochromatosis, or cholangitis This cohort was compared to a HCC cases occurring in livers with cirrhosis (n=64) via tests of proportion and t-tests.

Results: 1. HCC’s occurring in otherwise-healthy livers were larger than those occurring in cirrhotic livers (mean size 10.2 vs 4.6 cm, p<0.001).

2. HCC’s occurring in otherwise-healthy livers were significantly more likely to have vascular invasion than those in cirrhotic livers (63% vs 44%, p=0.038).

3. There was no significant difference in T-stage between the two groups (pT1 32% vs 28% (p=0.634), pT2 54% vs 50% (p=0.663), pT3 14% vs 13% (p=0.873), and pT4 0% vs 3% (p=0.193).

4. There was no significant difference in WHO grade between the two groups (well-differentiated 6% vs 9% (p=0.525), moderately-differentiated 79% vs 77% (p=0.787), and poorly-differentiated 15% vs 9% (p=0.301).

Conclusion: Hepatocellular carcinomas which arise in otherwise-healthy livers display significantly more aggressive disease bymeasures of tumor size and rate of vascular invasion than those which arise in cirrhotic livers.

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1700-1815

Screen 4.14 P52 Heterotopic Pancreatic Tissue in Gallbladder

Konstantinos G. Sidiropoulosa,b, and Catherine J. Streutkera,b.

aDepartment of Laboratory Medicine, St. Michael’s Hospital, Toronto, Canada, M5B 1W8

bDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5S 1A8

Heterotopic pancreas (HP) involving the gallbladder is a rare finding. HP is usually missed on radiology and at the time of surgery, and is usually discovered incidentally at pathologic evaluation.

We present a case of heterotopic pancreatic tissue in the gallbladder of a 34-year-old female who presented to the emergency department with upper right abdominal pain and vomiting. Elevated serum amylase and serum lipase levels were detected, as well as elevated bilirubin (total 37; direct 20) was also detected; clinically she was considered to have common bile duct obstruction and gallstone pancreatitis.. However, abdominal ultrasound scan demonstrated a borderline enlarged gallbladder with no sonographic evidence of acute cholecystitis. Moreover, no stones were visualized in the common bile duct and a sonographically normal biliary tree was seen. No lesions were identified at cholecystectomy. Grossly, the gallbladder contained an intramural mass was detected measuring 1.5 cm. Several yellow/brown stones were present ranging in size from 0.1 cm – 0.3 cm. Histologically, sections of the gallbladder wall showed mucosa with mild chronic cholecystitis with focal intestinal metaplasia. A nodule of well-organized pancreatic tissue was present in the sub-serosal fat. This contained pancreatic acini and ducts as well as occasional islets. There was no evidence of acute or chronic pancreatitis.

The reports of HP have shown that it most often associated with chronic cholecystitis, though this may be coincidental as the incidence in patients without gallbladder symptoms and cholecystectomy is not known. It has also occasionally presentated as a gallbladder mass. HP in the gallbladder has also been reported to be associated with elevated serum amylase and lipase levels, mimicking true pancreatitis. While HP in the stomach and other sites such as small bowel is uncommon, HP tissue in the gallbladder is very rare, with less than 45 case reports identified upon literature review.

We provide evidence here of another rare case of HP within the gallbladder, and describe its interesting clinical presentation, gross and histological features.

Keywords: gallbladder, pancreas, heterotopic, cholecystitis

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1815-1915

Screen 4.21 P14 Impact of Routine Cell Block Generation on Diagnostic Yields for Fine Needle Aspirates from Various Sites

J. Alex B. MacNeila,b, Emily R. Filterb\a,b.

aDivision of Anatomical Pathology, Nova Scotia Health Authority, Halifax, NS;

bAnatomical Pathology, Dalhousie University, Halifax, NS.

Objective: At our institution, cell blocks (CBs) are routinely produced for all body fluid samples, lung fine needle aspirations (FNAs), non-salivary gland and non-thyroid head and neck FNAs, and endoscopic ultrasound-guided (EUS) FNAs that have undergone rapid on-site evaluation (ROSE). For all remaining FNA specimens, CBs are generated only if requested by the pathologist. A recentin-house trial evaluated the impact of routine CBs for all non-parotid and non-thyroid head and neck FNAs and revealed fewer false negative diagnoses with this approach. The aim of this studyis to further evaluate the utility of routine CB preparation for other FNA specimen types.

Method(s): This prospective study compared pre and post-CB diagnoses of FNAs obtained from lymph nodes, salivary glands, soft tissue lesions, EUS FNAs with and without ROSE, and other miscellaneous sites excluding thyroid and breast FNAs. Cell blocks were automatically generated for these FNA specimens over a period of four consecutive months. The pre and post cell-block diagnoses were compared and any potential impacts on diagnoses were recorded.

Data and Results: A total of 116 FNA specimens were included in the study. In 22 (18.9%) of these cases, the CB provided additional information that contributed to the final diagnosis. Parotid lesion FNAs were the most frequently associated with contributory CB material. In 9 of 38 parotid FNAs reviewed (23.7%), the CBs contained architectural features and/or confirmed lesional cell type allowing for a more definitive diagnosis.

Conclusions: The findings support routine generation of CBs for some specimen types, particularly parotid lesion FNAs.

Keywords: Cytology, cell block, fine needle aspiration, parotid, quality assurance

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1815-1915

Screen 4.22 P9 Practice Patterns in Gynecological and Non-Gynecological Cytopathology: Findings from 2009-2014 Surveys of Ontario Laboratories

Michele M. Weira, Shahidul Islamb, Zeina Ghorabc, Susan McRaea, Anne Ecobichon-Morrisd, Tammy Ashfield e.

aDepartment of Pathology, London Health Sciences Centre, London ON

bDepartment of Pathology, The Ottawa Hospital, Ottawa ON

cDepartment of Pathology, Sunnybrook Health Sciences Centre, Toronto ON

dDepartment of Pathology, Hamilton Health Sciences Centre, Hamilton ON

eInstitute for Quality Management in Healthcare, Toronto ON.

Objective: The Institute for Quality Management in Healthcare Centre for Proficiency Testing routinely surveys Cytopathology licensed Ontario laboratories to evaluate changes in practice. This study highlights sequential surveys of gynecological and non-gynecological practice from 2008 to 2013.

Method: Between 2009 and 2014, surveys were sent to all Cytopathology licensed Ontario laboratories requesting information from the previous calendar year about workload, workforce, specimen collection and preparation, screening and reporting practices.

Data and Results: Response rates were 94%-100%. Practice changes included: 1) reduction in the number of Ontario laboratories licensed for Cytopathology (community laboratories most affected with a 50% decrease in the number of gynecological and a 40% decrease in non-gynecological laboratories; 2) decrease in gynecological case numbers by 43% subsequent to 2011 Cancer Care Ontario Pap test screening guidelines; 3) increase in non-gynecological workload (32% for community and 11% for hospital laboratories); 4) reduction in cytotechnologist workforce (42% community and 12% hospital laboratories); 5) move to liquid-based preparations, most commonly ThinPrep®; 6) increase of non-medical laboratory technologists in specimen preparation; 7) stable and below maximum slide screening averages; 8) slight decrease in Negative for Intraepithelial Lesion or Malignancy diagnoses for gynecological cases with an increase in abnormal diagnoses.

Conclusions: Five sequential surveys collecting data on Cytopathology practices highlighted the decline in Pap test volumes, increase in non-gynecological volume and reduction of the cytotechnologist workforce in Ontario.

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1815-1915

Screen 4.23 P59 EBUS-TBNA in metastatic NSCLC: Do cytomorphological features correlate with standardized uptake value of PET scan?

Kianoosh Keyhanian MD MSca, Harman Sekhon MD MSc PhD FCAPa.

aDepartment of Pathology and Laboratory Medicine, University of Ottawa/The Ottawa Hospital, Ottawa, Ontario

Background/Objective: Positron emission tomography (PET) followed by endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) of the suspicious lymph nodes (LNs) is a standard procedure for staging of lung cancer. The objective of this study is to correlate cytomorphological features of metastatic non-small cell lung carcinoma (mNSCLC) with maximal standardized uptake value (mSUV) of PET scan in LNs.

Method(s): Fifty-seven lymph nodes with positive EBUS-TBNA cytology were reviewed from 49 NSCLC patients with prior PET scan. Student t-test was used for statistical comparisons.

Results: Mean patients’ age: 68.7, 67% male. LNs locations were: mediastinum: 48 (24 subcarinal, 24 para-tracheal), lung hilum: 8, axilla: 1. Cytological diagnoses were: Adenocarcinoma: 41 LNs, squamous cell carcinoma: 13 LNs, NSCLC: 3 LNs. We observed that histological patterns correlate with mSUV, with acinar and papillary (both mean values (Mv): 9.3) patterns associating with significantly lower mSUVs than solid pattern (Mv: 13.8) (both P values (Pv)<0.05). Similar difference exists between low and high grade adenocarcinoma (Mvs: 9.4 and 13.2, respectively. Pv<0.01). Other features that correlated with higher mSUV: LN size (correlation coefficient: 0.51, Pv: 0.006), presence of necrosis and moderate/severe nuclear atypia (both Pvs<0.01), LN site (mediastinal vs. hilar Mv: 11.6 vs. 7, respectively. Pv: 0.01) and lower lymphoid tissue yield (Mv: 7.7 vs. 11.4, Pv: 0.04).

Conclusions: In LNs with mNSCLC, certain cytomorphological features including histological pattern, grade, necrosis and moderate/severe nuclear atypia are associated with higher mSUV. Our results are consistent with previous reports of correlation between histologic subtype and SUV in primary lung tumours.

Keywords: EBUS-TBNA, Non-small cell lung carcinoma

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1815-1915

Screen 4.24 P51 Cytologic presentation of extracranial/-spinal metastases of non-hematolymphoid primary central nervous system tumors

1. Lorna Mirham MD1,2,4, 2. Scott L Boerner MD1,4, 3. Valerie Dube MD3,4, 4. William R Geddie MD1,4, 5. Hyang Mi Ko MD PhD1,4, 6. Gilda da Cunha Santos MD PhD1,4, 7. Joerg Schwock MD PhD1,4, and 8. Zeina Ghorab MD MSc2,4.

1University Health Network

2Sunnybrook Health Sciences Centre

3Credit Valley Hospital

4University of Toronto, Laboratory Medicine and Pathobiology, Toronto, Ontario, Canada

Authors Who Are Pathologists-In-Training: Lorna Mirham MD

Objectives: Extracranial/-spinal metastases (ECM) of primary central nevous system (CNS) tumors are rare and may be diagnostically challenging. We describe the cytomorphological and pertinent clinical features of ECM in a case series initially assessed by fine needle biopsy (FNB).

Design: An electronicsearch of the laboratory information systems of two tertiary care centers in Toronto (2000-2016) was performed using a list of diagnostic terms. Surgical specimens, FNB slides and clinicopathological data were reviewed and tabulated. Cases with direct extracranial extension of CNS neoplasms were excluded.

Results: Six cases with the original diagnoses of glioblastoma, glioblastoma with primitive neuroectodermal tumor component, anaplastic ependymoma, myxopapillary ependymoma, atypical meningioma, and hemangiopericytomawere identified. Median patient age was 48 years; range 25-66.. Interval between initial diagnosis and ECM was 4 months to 19 years. ECM was correctly diagnosed by FNB in all cases. FNB diagnosis was supported by immunohistochemistry in 4 cases. All cases had a prior surgical intervention at the primary site. Four cases had ipsilateral ECM in the parotid / retroantral area. Two primary midline tumors developed ECM in the scapular area.

Conclusion: ECM frequently involves the ipsilateral head and neck, and may be the initial manifestation of recurrence and systemic disease. Mechanisms of tumor cell seeding remain to be investigated. Our study underlines (i) the importance of long term clinical follow up and (ii) the value of FNB which rapidly discriminates aggressive ECM from other, potentially more indolent conditions, such as neoplasms of salivary gland origin.

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1700-1830

Screen 5.11 P47 miRNAs as diagnostic biomarkers for renal cell carcinoma subtypes by chromogenic in situ hybridization

Ashley Di Meoa,b, Mereet Hannaa, Rola Saleeba,b, Samantha Walaa,b, Adriana Krizovaa, Manal Gabrilc, Haiyan Zhaid, Maria D. Pasicb, Andrew Evansb, Fadi Brimoe, and George M. Yousefa,b.

aThe Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON;

bDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON;

cDepartment of Pathology, London Health Sciences Center and Western University, London, ON;

dBioGenex Laboratories, Fremont, CA;

ePathology, McGill University Health Centre, Montreal, QC.

Objective: To determine whether a limited number of miRNAs could accurately classify the most common RCC subtypes, oncocytoma and unclassified RCC. In addition, we aimed to determine the diagnostic utility of our miRNA classifier by in situ hybridization (ISH).

Methods: We extracted RNA from 93 formalin-fixed paraffin-embedded (FFPE) tissues including 30 ccRCC, 28 pRCC, 30 chRCC, 4 unclassified RCC tumors and 11 oncocytomas. We measured absolute expression of 6 miRNAs by qRT-PCR. Receiver operator characteristic curves were constructed and the areas under the curve were calculated to assess performance. We also tested miRNA expression ISH in an independent set of 98 FFPE renal tumors.

Data and Results: We developed a two-step miRNA classifier. In the first step, expressions of selected miRNAs were found to discriminate clear cell and papillary RCC from chromophobe RCC and oncocytoma. Two miRNAs were able to discriminate clear cell and papillary RCC from chromophobe RCC and oncocytoma (AUC: 0.91, p<0.0001). In the second step, the absolute expression of miR-126 was used to distinguish clear cell from papillary RCC (AUC: 0.98, p <0.0001) and two miRNAs were used to differentiate chromophobe from oncocytoma (AUC: 0.83, p =0.003).Select miRNAs were also useful in pointing to distinct histological types in unclassified RCC. ISHrevealed that miRNAs display a nuclear staining pattern capable of distinguishing ccRCC, pRCC, chRCC and oncocytoma.

Conclusions: miRNA expression can distinguish between RCC subtypes and oncocytoma. miRNA assessment by ISH is a clinically useful diagnostic tool that can complement current methods for renal tumor classification.

Keywords: Diagnosis; miRNA; tumor markers; RCC subtypes; precision medicine

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1700-1830

Screen 5.12 P54 Juxtaglomerular Cell Tumor. A Case Report.

David Garcia-Marqueza, Jose A. Gomeza.

aLondon Health Sciences Center, Department of Pathology and Laboratory Medicine, Western University, London, ON.

Background: Since its first description in the medical literature in 1967 as a renin-secreting renal tumor, approximately 100 cases of juxtaglomerular cell tumor (JCT) of the kidney have been reported.

Case Report: We present a case of this rare condition diagnosed on a 56-year-old female patient with long history of hypertension.

The tumor was found by MRI during work up for hypertension and a partial nephrectomy was performed. The neoplasm had the classical histological features of JCT including polygonal and spindled neoplastic cells arranged in sheets and nests. Individual cells had distinct cell borders and eosinophilic granular cytoplasm. Their nuclei were central, regular, with mild pleomorphism. Mitoses were inconspicuous.

Electron microscopy showed the characteristic rhomboid renin crystalloids confirming the diagnosis.

Conclusions: Our case represents the classical presentation of a JCT. Together with coarctation of the aorta, renal artery stenosis and pheochromocytoma, JCT is one of the few causes of hypertension that can be surgically corrected. The clinical records of this patient indicate that after surgery, blood pressure levels and electrolyte values have returned to normal.

Although classic in its presentation and morphological features, we considered relevant bring this case to the attention of the medical community. Hypertension is a widespread serious health problem. Awareness of this condition can facilitate diagnosis and treatment before long term complications ensue.

Keywords: juxtaglomerular cell tumor, renin, hypertension.

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1700-1830

Screen 5.13 P49 Sarcomatoid urothelial carcinoma of bladder: a retrospective single institution review

Elan Hahn1,2, Michelle R. Downes1,2.

1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;

2Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Objectives: To identify the frequency and pathologic features of sarcomatoid carcinoma in a large cohort of bladder specimens from a single academic institution.

Methods: A retrospective search of the laboratory information system (1999-2016) was performed to identify all urothelial carcinomas of bladder. Patient age and sex were noted (resections and cystectomy). The pathologic features of the cystectomy group were recorded and comparison was made (Fisher’s exact test) between sarcomatoid and non-sarcomatoid cases. All sarcomatoid cases were reviewed.

Data and Results: Sarcomatoid histology was noted in 15 cystectomies (n=405) and 13 biopsy/resections (n=1730). There was one case each with heterologous bone, chondrosarcoma, rhabdomyosarcoma and leiomyosarcoma components. The male:female ratio was 2.25:1 in the sarcomatoid vs 2.49:1 in non-sarcomatoid cases. The mean ages were 71.9 sarcomatoid vs 69.2 years non-sarcomatoid patients. In the cystectomy cohort, there was no significant difference between the groups in terms of margin status (positive margin: 5 sarcomatoid, 70 non-sarcomatoid, p=0.168), nodal status (positive nodes: 6 sarcomatoid, 124 non-sarcomatoid, p=0.590) or lymphovascular invasion status (positive: 7 sarcomatoid, 214 non-sarcomatoid, p=0.602). There was a significant difference (p<0.0001) in number of extravesical tumours (≥ pT3) between the groups, with a higher frequency in the sarcomatoid cohort.

Conclusions: Overall, the frequency of sarcomatoid differentiation was 1.31% in this single institution review (n=2135). A significant difference in high pT stage carcinomas was noted with urothelial carcinomas with a sarcomatoid component being more frequently extravesical than the non-sarcomatoid urothelial carcinomas.

Keywords: bladder, sarcomatoid, urothelial carcinoma

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1700-1830

Screen 5.14 P39 Pathologic Features of Bladder Neoplasia in Small Bladder Biopsies: A Single Centre Retrospective Review

Sameer Shivji1, Michelle R. Downes1.

1Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Objectives: We sought to review the characteristics of patients with bladder neoplasia at a single large academic centre as well as determine rates of recurrence and progression, and compare our findings with those previously published in the literature.

Methods: We performed a retrospective review through our electronic chart system at Sunnybrook Health Sciences Centre of small bladder biopsies with bladder neoplasia from 1999-2015. Epidemiologic and histologic data were collected for these cases, as was the presence of recurrence and/or progression. Furthermore, Chi square statistical analyses were conducted to assess for significant associations in patients who experienced recurrence or progression.

Results: We collected a total of 1626 cases, the overwhelming majority of which (95%) were of urothelial carcinoma. 27% of patients experienced recurrent disease and 6% experienced progression over the study timeline. Of the histological factors analyzed in the study, only the presence of concurrent carcinoma-in-situ (CIS) at initial biopsy was significantly associated with risk of progression (p<0.05).

Conclusions: The epidemiology of bladder neoplasia, including rates of recurrence and progression, at our institution are comparable with data previously published in the literature. The presence of concurrent CIS has been identified as a risk factor for future progression, and this finding was confirmed in our study. Overall, our findings show that our population of bladder neoplasia patients has a similar profile to that published in the literature and serves as an important first step to further study in the field.

Keywords: Urinary bladder, urothelial, papillary, recurrence, progression

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1700-1830

Screen 5.15 P2 Inflammatory Myofibroblastic Tumour of the Bladder, a diagnostic challenge

Soha Said Ramadan1, Nathan Wong2, Clara Campos1, Diana Munavish Joschko1, Elizabeth McCready1, Radenka Bozanovic1, Luis Braga2, Jorge Arredondo1.

1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON;

2Divison of Urology, McMaster University, Hamilton, ON

Introduction: In this case study, we report an Inflammatory Myofibroblastic Tumour (IMT) of the bladder in a 16-year-old female. IMT of the bladder is a rare spindle cell neoplasm with intermediate malignancy that is easily cured with surgical resection, with the possibility of local recurrence and -rarely- distant metastasis. Differentiating IMT from more aggressive bladder sarcomas or sarcomatoid carcinomas is, however, challenging due to its highly variable morphology and immunophenotype. Aberrant expression of the Anaplastic Lymphoma Kinase (ALK) gene supports the diagnosis of IMT over other entities. ALK over-expression in more than half of IMT cases led to its inclusion as a diagnostic criterion and the identification of multiple ALK fusion partners. In addition to reviewing the diagnostic challenges and pitfalls faced with this case and in the literature, we present the cytological and Electron Microscopy appearance, immunophenotypic profile, Fluorescence In-Situ Hybridisation (FISH) and Polymerase Chain Reaction (PCR) analysis, as well as report a rare ALK fusion partner.

Results: The IMT in this study demonstrates granular cytoplasmic ALK1 immunoreactivity, confirmed by FISH to be due to chromosomal rearrangement. PCR identified the ALK fusion partner as fibronectin-1 (FN1).

Discussion: This case is one of four IMT cases harbouring the FN1-ALK fusion gene, all of which identified in the bladder. Although the prognostic value of this gene arrangement and the significance of the bladder being its only identified site are yet to be determined, this finding expands the ALK fusion oncoprotein database for further exploration of alternate management strategies and therapeutic targets.

Keywords: inflammatory myofibroblastic tumour, ALK, NF1, bladder, chromosomal rearrangement

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1700-1830

Screen 5.16 P57 Hypertension caused by a renal juxtaglomerular cell tumour: A case report

Anjelica Hodgson1, and Michelle R. Downes1.

1Department of Anatomic Pathology, Sunnybrook Health Sciences Centre – University of Toronto, Toronto, ON, Canada

Juxtaglomerular cell tumours (JCT), also known as reninomas, are rare renal neoplasms thought to originate from the smooth muscle cells of the glomerular afferent arteriole. Here we present a case of a JCT in a 31 year old female with longstanding hypertension refractory to treatment with multiple antihypertensive agents. Biochemical work up revealed extremely elevated levels of serum renin (> 900 mg/L, normal range 5-60 mg/L) and aldosterone (1090 pmol/L, normal range 83-979 pmol/L) with associated hypokalemia (3.1 mmol/L). Abdominal ultrasound demonstrated a 3.8 cm centrally located solid echogenic mass near the sinus of the right kidney. No renal artery stenosis was identified. Further imaging with computed tomography showed a fairly well-circumscribed mass with no discernible fat, located in the interpolar region of the right kidney. The radiological differential included renal cell carcinoma, oncocytoma, and angiomyolipoma. The patient underwent an ultrasound guided renal biopsy. This consisted of two lesional cores of tissue showing a biphasic population of dilated tubules and intervening polygonal cells with uniform nuclei and inconspicuous nucleoli. Microcystic spaces were noted in addition to a lymphocytic infiltrate. The polygonal cells stained with CD34, synaptophysin and vimentin. Evaluation by electron microscopy demonstrated pathognomic rhomboid-shaped renin crystals. The patient is scheduled to undergo partial nephrectomy in the near future. This case highlights the classical presentation of a JCT and reminds us of the importance of keeping this very rare neoplasm in the differential diagnosis of a young patient with hypertension and a renal mass.

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1830-1930

Screen 5.21 P11 Renal Pathology in Immune Checkpoint Inhibitor-Associated Acute Kidney Injury

Kevin Yi Mi Rena, Alina Bocicariua, Amanda Shuo Xua, Sandip Senguptaa, Iain Younga.

aDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario

Background: Immune checkpoint inhibitors (CPI) are emerging as a novel class of therapy that targets inhibitory receptors expressed on T-lymphocytes, and have been increasingly used in the treatment of solid organ and hematolymphoid malignancies including melanoma, lung cancer and Hodgkin lymphoma. The immunomodulating properties of CPI have been associated with a unique spectrum of immune-related adverse events affecting multiple organs systems. Common adverse reactions include mucocutaneous irritation, colitis, hepatotoxicity, and endocrinopathies. Acute kidney injury (AKI) associated with CPI therapy has also been reported, with renal pathology described in only a few cases.

Methods: We describe the clinical and histologic features of 3 patients with CPI-associated AKI from our institution, including the first reported case of CPI-associated diffuse proliferative glomerulonephritis (GN). We also reviewed the clinicopathologic findings of 23 previously reported cases of CPI-associated AKI.

Results: The predominant pathology finding in 23 of 26 patients was acute tubulointerstitial nephritis (AIN). There was 1 case each of diffuse proliferative GN, membranous GN, and thrombotic microangiopathy. Glucocorticoid therapy was initiated in 24 patients, resulting in at least partial recovery of renal function in 18 patients. The 2 patients not treated with glucocorticoids had no improvements in renal function.

Conclusions: CPI associated AKI is an emerging entity that must be recognized by nephropathologists to enable early diagnosis and intervention. The predominant injury pattern is AIN with features similar to other causes of drug-induced AIN. The mechanism of injury is likely related to dysregulated autoimmune response due to the immunomodulating property of CPI.

Keywords: Renal pathology, Immune checkpoint inhibitor, Acute Kidney Injury

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1830-1930

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Screen 5.22 P35 Atypical anti-GBM disease with negative serology, a case report

Susanna A. McRae MD FRCPCa,b, Barbara Sporinova MDc, Hallgrimur Benediktsson MD FRCPCa,b.

aDepartment of Pathology, University of Calgary, Calgary, AB;

bCalgary Laboratory Services, Calgary, AB;

cDepartment of Medicine, University of Calgary, Calgary, AB.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis with linear IgG staining of glomerular basement membranes (GBM) by immunofluorescence (IF).1-3 Atypical cases with negative serology and unusual histology have been described; however, most show only focal crescents and have a benign clinical course.4-6 We present a case with negative serology but positive linear IgG staining by IF, with atypical histology and eventual renal failure.

Case: A 24-year-old man presented to hospital with combined nephrotic/nephritic syndrome, hemoptysis, and acute renal failure. Serology was negative for all antibodies including anti-GBM. Renal biopsy showed crescentic glomerulonephritis involving 70% of the glomeruli, diffuse endocapillary and mesangial hypercellularity and focal GBM duplication. IF showed strong linear GBM staining for IgG. Despite empiric treatment for anti-GBM disease his renal function did not recover and he is now dialysis dependent.

Discussion: A recently published series by Nasr et al. describes 20 atypical anti-GBM cases with similar histology; however, their cases showed only focal crescents and followed a benign course.4 A few reports have linked altered ratios of IgG subclasses to false negative immunoassay results, which best sense IgG1, the predominant subclass in typical anti-GBM disease.3,5,6 Our case showed linear staining for only IgG2 and IgG4. Reported cases limited to IgG2 and IgG4 antibodies have shown minimal renal dysfunction, contrary to our case.5,6 This represents a unique case with hybrid features between a more indolent “atypical anti-GBM disease” with a clinical course more in keeping with typical anti-GBM disease.

Keywords: anti-GBM disease; glomerulonephritis; immunoglobulin G (IgG) subclasses.

References:

1. Hellmark T and Segelmark M. Diagnosis and classification of Goodpasture’s disease (anti-GBM). Journal of Autoimmunity. 2014;48-49:108-112.

2. Greco A, Rizzo MI, Virgilio AD, et al. Goodpasture’s syndrome: A clinical update. Autoimmunity Reviews. 2015:14(3):246-253.

3. Segelmark M, Butkowski R, Wieslander J. Antigen restriction and IgG subclasses among anti-GBM autoantibodies. Nephrol Dial Transplant. 1990;5:991-996.

4. Nasr SH, Collins AB, Alexander MP, Schraith DF, Herrera Hernandez L, Fidler ME, Sethi S, Leung N, Fervenza FC, Cornell LD. The clinicopathologic characteristics and outcome of atypical antiglomerular basement membrane nephritis. Kidney International. 2016;89:897-908.

5. Ohlsson S, Herlitz H, Lundberg S, Selga D, Molne J, Wieslander J, Segelmark M. Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease. Am J Kidney Dis. 2014;63(2):289-293.

6. Zhao J, Yan Y, Cui Z, Yang R, Zhao M. The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHα3(IV)NC1 is associated with disease severity. Human Immunology. 2009;70:425-492.

 

1830-1930

Screen 5.23 P21 Severe Acute Interstitial Nephritis: Response to Therapy with Anti-thymocyte Globulin.

Tiffany Shaoa, Jordan Weinsteinc,d, Marc Goldsteinc,d, Serge Jothya,b.

aDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON;

bDepartment of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON;

cDepartment of Medicine, University of Toronto, Toronto, ON;

dDivision of Nephrology, Department of Medicine, St. Michael’s Hospital, Toronto, ON

Objective: To evaluate the potential effect of thymoglobulin therapy on the histopathology and clinical course of acute interstitial nephritis (AIN).

Method(s): Immunofluorescence and immunohistochemistry

Data and Results: A 43-year-old female presented with acute kidney injury and a serum creatinine of 1170 umol/L in July 2014. Her renal biopsy showed acute interstitial nephritis (AIN) with a predominately lymphocytic infiltrate and no apparent etiology. Despite corticosteroid therapy and subsequent addition of mycophenolate mofetil, she remained dialysis dependant. As a repeat biopsy in November 2014 showed similar findings of AIN she was admitted for thymoglobulin infusions and she came off hemodialysis 2 months later. A third renal biopsy 16 months after the infusions showed a lower density, patchy infiltrate of lymphocytes in the interstitium, and her creatinine has remained in the stable 140 umol/L range. Subsequent to thymoglobulin treatment, there was a marked and parallel decrease in the renal density of T lymphocytes, both T helper and T suppressor cells, and also monocytes/macrophages. Immunohistochemical characterization demonstrated that before and after treatment, the means of T-lymphocytes (identified by CD3 marker) in the renal cortex were 3853+/-436 and 663 +/-184 per unit area (P<0.0005), respectively.

Conclusions: Thymoglobulin is a potentially useful new treatment for interstitial nephritis. We report here a single case of partial response to thymoglobulin, however we need to also take into consideration the side effects of thymoglobulin including lymphopenia, which are occasionally observed in the treatment of acute cellular rejection of kidney allografts. To conclude, the present report is the first to show partial response of thymoglobulin therapy in a patient with acute interstitial nephritis.

Keywords: renal pathology, immunotherapy, interstitial nephritis

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1830-1930

Screen 5.24 P8 Chronic Allograft Hepatopathy: A Distinct Pattern of Chronic Graft Dysfunction from Ductopenic Rejection

Nawal Al-Mohammadia, Oyedele A. Adeyib.

aLaboratory Medicine and Pathobiology, University of Toronto, Toronto, ON and Laboratory

bMedicine Program, University Health Network, Toronto, ON

Objective: Chronic ductopenic rejection (DR) is a well-recognized pattern of liver allograft dysfunction characterized by ductopenia, cholestasis, and little fibrosis. We describe a different pattern of chronic graft injury characterized by graft fibrosis, portal hypertension (PH) andno ductopenia or other features of DR, which we call chronic allograft hepatopathy (CAH).

Method(s): Liver transplant electronic records of patients biopsied for cause from 2009-2016 at UHN are retrieved. Non-HCV patients with DR are identified. Also identified are patients without DR whose indication for biopsy had included PH. The H&E and trichrome stains of patients in both groups are reviewed as well as the clinical, biochemical, and radiologic parameters.

Data and Results: Seven patients with CAH are identified between 2009 and 2016. When compared with 22 DR patients over the same period, CAH exhibit no significant ductopenia, normal or near-normal bilirubin, and lower alkaline phosphatase. Unlike DR, CAH patients develop chronic microvascular and sinusoidal injury (figure 1) manifesting as subsinusoidal fibrosis, loss of portal microvasculature, and often elevated hepatic vein pressure gradient.

Conclusions: We describe a hitherto unrecognized pattern of chronic graft dysfunction termed CAH, characterized by non-cirrhotic sinusoidal PH in 7 patients whose clinical, biochemical, functional, and histopathological parameters are distinct from those of the better-known DR.

Keywords: Liver allograft, ductopenic rejection, chronic allograft hepatopathy

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1700-1830

Screen 6.11 P27 Pulmonary alveolar proteinosis in setting

Asghar Naqvi, MD, FRCPC1, Meirui Li3, Miranda Schell, MD, FRCP1, Clive Davis, MD, FRCPC2, Salem Alowami, MD FRCP1.

1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

2Divisions of Critical Care, Respirology, and General Internal Medicine, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

3Michael G. DeGroote School of Medicine, McMaster University

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of proteinaceous material in the alveoli due to decreased clearance of surfactant by alveolar macrophages. There are three types of PAP: hereditary, autoimmune, and secondary. Hereditary PAP mainly affects children, while the latter two occur in adults. PAP patients can be asymptomatic or present with vague complaints of dyspnea and cough. High-resolution computed tomography (HRCT) scan of the lungs show either bilateral diffuse ground-glass opacity or the characteristic “crazy-paving” pattern. Bronchoalveolar lavage is used in diagnosis in up to 83% of cases in recent years, replacing lung biopsy as the diagnostic tool of choice. Here, we report a case of a patient who developed PAP secondary to environmental exposure in the setting of chronic alcohol abuse, that was initially diagnosed as heart failure.

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1700-1830

Screen 6.12 P50 Pulmonary squamous carcinoma with lepidic pattern- a study of 9 cases

Hemlata Shirsata, Ashley Stuecka, Mathieu C. Castonguaya, Zhaolin Xua.

aDepartment of Pathology, Dalhousie University Halifax, Canada

Background: Pulmonary squamous carcinomas (PSC) are thought to arise from metaplastic bronchial epithelium(BE) through a metaplasia-dysplasia-carcinoma sequence. A lepidic growth pattern is frequently seen in adenocarciomas, but rarely reported in PSC. PSC entraps benign (frequently reactive) pneumocytes; entertaining adenosquamous carcinoma diagnosis.

Aim: To explore mechanism of peripheral PSC development and evaluate PSC cases showing lepidic-like areas.

Design: Nine cases of resected PSC with lepidic-like areas, diagnosed over 6 years, were retrospectively analyzed using H&E-stained sections and p40 and TTF1 (SPT24 clone) immunohistochemistry.

Results: All cases were peripheral invasive PSC with focal lepidic-like areas. Six cases showed superficial reactive alveolar pneumocytes undermined by malignant squamous cells, both TTF1 positive (more intense in pneumocytes); only squamous cells were p40 positive. One case had conventional metaplasia-dysplasia–carcinoma sequence of the ciliated BE with both BE and squamous cells staining for TTF1 in the metaplastic and in-situ component. Three cases had only superficial pneumocytes staining for TTF1 and basal cell staining for p40 which just represented lepidic pattern of spread. Three cases had entrapped hyperplastic reactive pneumocytes giving a pseudoglandular appearance.

Conclusion: Proliferating basal squamous cells were morphologically not similar to invasive component. This rules out cells extending from the invasive component towards alveolar wall. Other possibility is peripheral PSC arises from squamous metaplasia of type 2 pneumocytes with further dysplasia carcinoma sequelae. Lepidic like growth does exist in PSC. Entrapped pneumocyte hyperplasia can mimic adenosquamous carcinomas. Intense scrutiny of architecture and morphology of type 2 pneumocytes and TTF1 and p40 IHC can help distinguish them.

Keywords: pulmonary squamous cell carcinoma, lepidic

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1700-1830

Screen 6.13 P44 Differential expression of miRNAs in lung neuroendocrine tumors using barcoded small RNA sequencing.

Paula S. Ginter, Ivraym B. Barsoum, Xiaojing Yang, Kathrin Tyryshkin, Theresa Scognamiglio, Nicole C. Panarelli, Thomas Tuschl, Neil Renwick, Yao-Tseng Chen.

Lung neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that includes typical carcinoids (TC), atypical carcinoids (AC), small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinomas (LCNEC) (WHO 2004 Classification). The histopathlogical differentiation between these entities is sometimes challenging. To help provide a better molecular diagnostic and prognostic tool we identified in this study miRNA biomarkers that are differentially expressed in these four pathological types. RNA samples were extracted and validated from formalin-fixed paraffin-embedded (FFPE) tissue blocks. Using our newly developed approach; barcoded small RNA sequencing we generated miRNA expression profiles for a test set of three TCs, nine ACs, four LCNECs, and five SCLCs through. Our results were further confirmed by real-time PCR. Unsupervised hierarchical clustering indicated a clear separation of all NET groups from each other. Through feature selection, we identified candidate miRNA and cistronic miRNA clusters that separate TC vs. AC; LCNEC vs. SCLC, and carcinoid vs. neuroendocrine carcinomas. Our preliminary data revealed that a large miRNA cluster on chromosome 14q32 was downregulated in carcinomas (SCLC, LCNEC) vs. carcinoids (TC, AC). In this study we report different miRNA biomarkers with potential diagnostic and prognostic value for lung NETs.

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1700-1830

Screen 6.14 P18 Importance of gender, age, site and histological grade in neuro-endocrine tumors- Study from a tertiary cancer center

Haripreetha G Nair1, Sudha S Murthy1, Daphne Fonseca1, Vishal Rao1, Suseela Kodandapani1, Ravindranath Tagore1, Challa Sundaram1, Senthil Rajappa2, KVVN Raju3, KM Mallavarapu2, Subramanyeshwar Rao3.

1Department of Pathology, Basavatarakam Indo American Cancer Hospital and Research Institute,

2Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute,

3Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute.

Objective: Neuroendocrine tumors (NET) are rare but are being diagnosed more frequently in recent times. There is limited published data from India. Hence, this study from a tertiary care cancer hospital.

Methods: Retrospective analysis of data from the medical records of patients diagnosed on pathology between January 2012 and March 2016 were included in the study. The demographics, clinical presentation and site were noted. The pathology was reviewed with immunohistochemistry (IHC) with one or more neuroendocrine markers and/or Ki67 and tumors were graded per WHO criteria. The grade was correlated with site and age. Statistical analysis was performed using Chi square test.

Data and Results: There were 85 patients in the study with age ranging from 12-83(median 55) years with male preponderance (66%). Male gender and age >60years were significantly associated with NET (p= 0.001). The predominant site was lung (42%) followed by gastrointestinal and pancreatic (25%). The other sites included liver (9), head and neck (4), lymph nodes (4), mediastinum (3), spine (2), one each in cervix, urinary bladder, ovary, pelvis and distal extremities. Grade 3 tumors constituted 62% with majority (32%) occurring in lung. High grade tumors (46%) were predominantly seen in males (p=0.02). Regional or distant metastases were seen in 32 patients including 25(78.3%) high grade tumors.

Conclusions: Majority of NETs were high grade at the time of presentation with a male predominance, in the age group more than 60 years. Lung was the most common site.

Keywords: Neuroendocrine tumors, lung, gastro-intestinal-pancreatic, male gender, high grade

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1700-1830

Screen 6.15 P46 A case of congenital peribronchial myofibroblastic tumour presenting in a two-week-old girl.

Nick Baniaka, Fergall MaGeea, Mark Podberezina.

aLaboratory Medicine and Pathology, University of Saskatchewan, Saskatoon, SK

Objective: i) To add to the very limited literature on congenital peribronchial myofibroblastic tumour, a rare benign lung tumor. ii) To help ensure congenital peribronchial myofibroblastic tumour is included in the differential of a neonatal lung mass.

Results: We present a case of congenital peribronchial myofibroblastic tumour in a two-week-old girl. Imaging showed a vascular solid mass centered in the left mid and upper chest measuring 4.0 x 5.6 x 4.8cm. The mass had smooth well-defined margins with no associated rib destruction. The primary clinical differential was congenital cystic adenomatoid malformation. A left upper lobectomy was performed, revealing a mass with a solid pale tan cut surface with small pink tan interspersed foci. Histology showed a solid spindle cell tumor growing in fascicles with intermixed areas of cartilage. In the less cellular areas, a peribronchiolar distribution of tumor cells was seen. The nuclei were elongated with finely dispersed chromatin. Prominent mitotic activity was seen, but no atypical formswere present. Immunohistochemistry revealed positivity for SMA and vimentin.

Conclusions: Although less than 50 cases have been previously reported, congenital peribronchial myofibroblastic tumour needs to be included in the differential of a rapidly growing lung mass in the neonatal or antenatal period, in addition to other lesions, such as infantile fibrosarcoma, inflammatory myofibroblastic tumor, infantile myofibroma and monophasic fibrous type synovial sarcoma. The clinical behavior is diverse, but with early surgical resection, patients usually have a good outcome.

Keywords: Neonatal, Lung mass, Congenital peribronchial myofibroblastic tumour

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1830-1930

Screen 6.21 P3 Androgen receptor scoring in breast cancers: validation of ischemic and fixation times for immunohistochemical analysis

Justin Batemana and Susan J. Robertsona.

aDepartment of Pathology and Laboratory Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada

Objective: The role for androgen receptor (AR) scoring in triple negative breast cancer will become increasingly important as our understanding of the molecular basis of this disease broadens. With our study, we hope to validate the use of immunohistochemistry (IHC) to detect and score AR in breast cancer tissue specimens, with respect to common ischemic and formalin fixation times.

Methods: In this prospective study we assessed AR scores for different ischemic and formalin fixation times. Each fresh tissue specimen was cut into three sections for ischemic times of 1, 2, and 3 hours. Each of these sections were then subdivided into four sections and fixed in formalin for 24, 48, 72, and 96 hours. Blocks then underwent our own standardized AR IHC staining, and the researchers assigned H-scores.

Data and Results: Thirteen cases of invasive mammary carcinoma were acquired during the study period and processed as per our protocol. Analysis is currently underway.

Conclusions: The prognostic and predictive significance of AR has become increasingly recognized in the field of breast cancer. Validating AR IHC for routine laboratory use will hopefully contribute to patient care in the near future.

Keywords: Breast, Androgen Receptor, Immunohistochemistry

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1830-1930

Screen 6.22 P36 Upgrade Rate of Radial Scar/Complex Sclerosing Lesion diagnosed on Needle Core Biopsy

Florentina Matea1, Phillip Williams2.

1Department of Pathology and Molecular Medicine, McMaster University, Juravinski Hospital, 700 Concession St, Hamilton, ON, L8V 5C2

2Department of Pathology and Molecular Medicine, McMaster University, Juravinski Hospital, 700 Concession St, Hamilton, ON, L8V 5C2

Background: Radial scar (RS) and complex sclerosing lesion (CSL) are considered benign breast lesions with proliferative features. Guidelines for the selection of patients with RSL on core needle biopsy who require surgical excision are not well defined. At our institution, we routinely advise surgical excision of these lesions in order to exclude a more aggressive atypical or malignant component that was not sampled at the time of needle biopsy.

Purpose: The aim of this study is to determine the incidence of upgrade to high risk lesions and malignancy of those diagnosed on core biopsy and to identify histopathologic and radiological features on core biopsy that are associated with either benign, high risk or malignant features on excision. Accurate assessment of risk may spare patients unnecessary surgical procedures, which may entail risk of personal injury and death, as well as time and economic costs.

Methods: We retrospectively evaluated data on patients with mammographically detected RS and/or CSL sampled by core needle biopsy (CNB) between 2000 and 2016. Patients with concomitant atypia, DCIS/LCIS in situ on core biopsy and the ones with no subsequent excision were excluded. Demographic data, type of lesion, histological and radiological findings were correlated with subsequent surgical excision data. An upgrade from the needle biopsy of RS was defined as surgical excision pathology that revealed ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and/or invasive lobular carcinoma (ILC).

Results: A total of 25RS/CSL specimens associated with benign findings on core biopsy were reviewed. The 25 follow-up excisional biopsies revealed: 1 (4%) invasive ductal carcinoma and 0 (0%) in-situ carcinoma. Invasive component was an incidental finding and was situated away from the radial scar.

Conclusions: Results shows that isolated radial scar on needle biopsy may not warrant routine surgical excision given relatively low cancer upgrade rates. Advancement in breast imaging, pathology and multidisciplinary approaches to care may effectively guide non-surgical management of RS.

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1830-1930

Screen 6.23 P37 Anaplastic large cell lymphoma associated with breast implant capsule

Sejal S. Shaha, Vishal S. Chandana.

aDivision of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.

Objective: Primary breast lymphomas are uncommon and predominantly of B-cell phenotype. We present a rare case of primary anaplastic large cell lymphoma of the breast in association with a silicone breast implant capsule.

Method: A 66-year old woman underwent bilateral silicone breast implants 30 years ago with replacement in 2001. She recently presented with swelling and breast asymmetry. A seroma was noticed adjacent to the implant. Fluid was aspirated which showed atypical cells. She underwent removal of the right breast implant and capsule.

Data and Results: The sections of the capsule showed a fibrous wall containing large pleomorphic cells with prominent nucleoli and abundant pale cytoplasm. Immunostains demonstrated that the neoplastic cells were positive for CD30, CD43, and CD4, with aberrant loss of other T-cell markers, including CD2, and CD5. The CD3 stain was weakly positive in a small subset of neoplastic cells and clusterin was also very focally positive. No B-cell or plasma cell markers such as CD20, PAX-5 or CD138 were expressed. The tumor cells were negative for ALK-1, keratins, melanoma markers and CD34. In the absence of systemic disease per additional work-up, the findings support the diagnosis of seroma-associated primary anaplastic large-cell lymphoma.

Conclusions: Seroma-associated primary anaplastic large cell lymphoma is a distinct clinicopathological entity that arises in association with the effusion around a breast implant. The tumor is characterized by histologically malignant T-cells showing uniform CD30 expression, ALK negativity, and indolent clinical behavior. The treatment of choice is surgical removal of the capsule and implant.

Keywords: Lymphoma, breast, seroma, anaplastic.

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1830-1930

Screen 6.24 P43 A retrospective review of the diagnosis of papillary lesions of the breast – the Saskatoon experience

Yanping Gonga, Louise Quennevillea, and Henrike Reesa.

aDepartment of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK

Objective: To review the diagnostic accuracy of core biopsy for papillary lesions of the breast and provide feedback to physicians involved in the multidisciplinary management of these patients.

Methods: The pathology database of the Saskatoon Health Region was searched for all breast cases containing the terms papillary or papilloma accessioned in 2015. Core biopsy reports were matched with subsequent excisions, where available. Discordant cases were reviewed with additional studies to clarify the diagnosis.

Results: 44 papillary lesions were diagnosed on core biopsy in 2015. 15 (34.1%) were benign papillomas and 29 (65.9%)were atypical or malignant papillary lesions.

9 of the 15 patients diagnosed with a benign papilloma on core biopsy didn’t proceed to surgical excision. Only 1 of the 6 (16.7%) that were excised had an upgrade in diagnosis; this one case showed DCIS.

All 29 of the atypical or malignant lesions were excised; none gave benign results on excision. The results for this group were: DCIS in a papilloma (1 case; 2.3%), papillary DC1S (26 cases; 59.1%), and papillary lesion with atypical epithelial proliferation (2 cases; 4.5%).

Conclusions: The likelihood (16.7%) of atypia or malignancy on excision of a papillary lesion called benign on core biopsy is similar in our center to numbers reported from other centers. Close clinical follow-up of those patients is needed if non-surgical management is chosen.

Keywords: papilloma, breast, core biopsy