Androgen Receptor Expression in Endometrial Carcinoma.

Endometrial carcinoma (ECA) is frequently hormonally driven and can be treated with endocrine-based therapy, yet hormone receptor status is not routinely assessed. In particular, little is known about the significance of androgen receptor (AR) in ECA. Androgen has antiproliferative effects in the healthy endometrium and could serve a similar role to progesterone in curbing the progression of estrogen-dependent neoplasia. There may also be a subset of ECA that benefits from androgen antagonistic therapy. We herein investigate AR expression across ECA subtypes and compare its expression to estrogen receptor (ER) and progesterone receptor (PR). Immunohistochemical staining for AR, ER, and PR was performed on an endometrial tissue microarray containing 50 ECA with a variety of morphologic subtypes as well as 20 benign and 9 atypical hyperplastic endometria. AR was expressed by 54% (27/50) of ECA including 60% of low grade endometrioid carcinomas, 70% high grade endometrioid carcinomas, 70% serous carcinomas, 50% carcinosarcomas, and 20% clear cell carcinomas. High AR expression was chiefly restricted to a subset of serous carcinomas (50%). AR expression occurred most often in concert with ER staining, although 5 high grade cancers (1 serous carcinoma, 4 carcinosarcomas) showed AR expression in the absence of ER. In summary, AR positivity is seen in over half of ECA in our study, including the majority of low grade endometrioid carcinomas, high grade endometrioid carcinomas, and serous carcinomas. High level expression is seen in half of serous carcinomas and a subset of serous carcinomas and carcinosarcomas show some degree of AR staining in the absence of ER, suggesting a possible role for androgen inhibition in treatment of these cases.

ALK-positive large B-cell lymphoma (ALK + LBCL) with aberrant CD3 expression.

ALK-positive ( +) large B cell lymphoma (ALK + LBCL) is a rare distinct subtype of diffuse large B cell lymphoma presenting with high stage and aggressive behavior. Although B cell markers such as CD20, CD19, and CD22 are generally negative, plasmacytic markers including CD138, CD38, and MUM1 are positive. T cell markers are negative with rare exceptions. We report an unusual case of ALK1 + LBCL in a 58-year-old man with partial expression of CD3 without other T cell antigen expression. The tissue was evaluated with flow cytometry, immunohistochemistry, fluorescent in situ hybridization, and gene rearrangement studies. Gene rearrangement studies for IGH and TCR gamma were performed. Flow cytometry did not demonstrate any abnormal lymphoid populations. Tissue sectioning shows a malignant plasmacytic large cell neoplasm which expresses CD45 but is negative for CD20, CD79a, and PAX5. Plasmacytic markers CD138 and MUM1 are positive with kappa light chain restriction. Strong granular cytoplasmic expression of ALK is present. FISH showing disrupted ALK supports the diagnosis while MYC, BCL6, and BCL2 are intact. Gene rearrangement studies show coexisting IGH and TCR gamma clones; however, the TCR peak was present within a polyclonal background suggesting the disputed cells are likely only a subset of the T cell population. ALK + LBCL can present with an ambiguous immunophenotype, which warrants the use of multiple B cell, T cell, and plasmacytic antibodies. CD3 expression in this entity is rare and of uncertain clinical significance, but warrants further study.

Performance of MYC, BCL2, and BCL6 break-apart FISH in small biopsies with large B-cell lymphoma: a retrospective Cytopathology Hematopathology Interinstitutional Consortium study.

Introduction: Fluorescence in situ hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have MYC, BCL2, or BCL6 rearrangements. Small-volume biopsies such as fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are increasingly used to diagnose lymphoma and obtain material for ancillary studies such as FISH. However, the performance of FISH in small biopsies has not been thoroughly evaluated or compared to surgical biopsies. Methods: We describe the results of MYC, BCL2, and BCL6 FISH in a series of 222 biopsy specimens, including FNAB with cell blocks, CNBs, and surgical excisional or incisional biopsies from 208 unique patients aggregated from 6 academic medical centers. A subset of patients had FNAB followed by a surgical biopsy (either CNB or excisional biopsy) obtained from the same or contiguous anatomic site as part of the same clinical workup; FISH results were compared for these paired specimens. Results: FISH had a low hybridization failure rate of around 1% across all specimen types. FISH identified concurrent MYC and BCL2 rearrangements in 20 of 197 (10%) specimens and concurrent MYC and BCL6 rearrangements in 3 of 182 (1.6%) specimens. The paired FNAB and surgical biopsy specimens did not show any discrepancies for MYC or BCL2 FISH; of the 17 patients with 34 paired cytology and surgical specimens, only 2 of the 49 FISH probes compared (4% of all comparisons) showed any discrepancy and both were at the BCL6 locus. One discrepancy was due to necrosis of the CNB specimen causing a false negative BCL6 FISH result when compared to the FNAB cell block that demonstrated a BCL6 rearrangement. Discussion: FISH showed a similar hybridization failure rate in all biopsy types. Ultimately, MYC, BCL2, or BCL6 FISH showed 96% concordance when compared across paired cytology and surgical specimens, suggesting FNAB with cell block is equivalent to other biopsy alternatives for evaluation of DLBCL or HGBCL FISH testing.

Small volume biopsy diagnostic yield at initial diagnosis versus recurrence/transformation of follicular lymphoma: A retrospective Cyto-Heme Interinstitutional Collaborative study.

BACKGROUND: Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL). METHODS: The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial FL diagnosis and suspected recurrence or transformation of FL. A total of 676 workups beginning with SVB were assessed for the mean number of biopsies per workup, the proportion of workups requiring multiple biopsies, and the proportion with a complete diagnosis including grade, on initial biopsy. RESULTS: Compared to workups performed for question transformation/recurrence, those done for initial FL diagnosis were significantly more likely to require multiple biopsies (p < .01), had a higher mean number of biopsies per workup (1.7 vs. 1.1, absolute standardized difference = 1.1), and a lower complete diagnosis rate at initial biopsy (39% vs. 56%). At initial FL diagnosis, NCB +/- FNA was associated with fewer biopsies per workup compared to FNA +/- CB (1.2 vs. 1.9), fewer workups requiring multiple biopsies (23% vs. 83%), and a higher complete diagnosis rate (71% vs. 18%). In contrast, during assessment for transformation/recurrence, NCB and FNA showed a similar mean number of biopsies per workup (1.2 vs. 1.2) and few workups required multiple biopsies (6% vs. 19%). CONCLUSIONS: SVB at initial FL diagnosis often required additional biopsies to establish a complete diagnosis. In contrast, when assessing for transformed/recurrent FL, additional biopsies were generally not obtained regardless of SVB type, suggesting that in these clinical settings SVB may be sufficient for clinical decision-making.

Diagnostic Discrepancies in Small-volume Biopsy for the Initial Diagnosis, Recurrence, and Transformation of Follicular Lymphoma: A Multi-Institutional Collaborative Study.

Small-volume biopsies (SVBs) including fine-needle aspiration (FNA), cell block, and needle core biopsies (NCB) are increasingly utilized to diagnose and guide the clinical management of lymphoma. We established a multi-institutional interdisciplinary collaboration of cytopathologists, hematopathologists, and oncologists focused on the role of SVB in the management of patients with follicular lymphoma (FL). To assess the performance characteristics of SVB in this setting, we evaluated all consecutive SVBs performed for clinical indications of initial diagnosis, recurrence, or transformation of FL over a 5-year period and focused on the 182 that had at least one subsequent biopsy within 3 months as part of the same clinical work-up. The most common outcome of a subsequent biopsy as part of the same clinical work-up was a more specific diagnosis usually assigning the pathologic grade (111/182, 61%), followed by a complete agreement with the SVB (24/182, 13%), and change from nondiagnostic on initial biopsy to diagnostic on subsequent biopsy (21/182, 12%). A minority resulted in a diagnostic change from benign to lymphoma (17/182, 9%), a change in FL grade (5/182, 3%), or change in the lymphoma diagnostic category (4/182, 2%). There were no cases where an initial diagnosis of lymphoma was overturned. The distribution of discrepancies was similar across initial SVB types (FNA, FNA + cell block, NCB with or without FNA). Tissue limitations were noted in a minority of cases (53/182, 29%) and were enriched among initially nondiagnostic biopsies (16/21, 76%). Flow cytometry immunophenotyping was performed in the majority of cases both at the first and last biopsy (147/182, 81%). SVB can be a powerful method to detect FL in various clinical indications, with discrepant cases mostly resulting from a refinement in the initial diagnosis.

Global Cytopathology-Hematopathology Practice Trends.

OBJECTIVES: Small-volume biopsy-fine-needle aspiration biopsy (FNAB) with or without core biopsy-is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out. METHODS: This study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated. RESULTS: Most respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma. CONCLUSIONS: This survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services.

Global Health Education in Pathology Residency.

OBJECTIVES: Pathology and laboratory medicine (PALM) services in low- and middle-income countries are essential to combat the increasing prevalence of cancer in addition to providing documentation of cancer types and trends for future allocation of public health resources. There are many ways PALM as a whole can engage on the global health front. This study summarizes the efforts and results of a global health educational and clinical elective for pathology residents in Quetzaltenango, Guatemala. METHODS: Pathology residents led and implemented the project, working alongside an in-country pathologist and project collaborator to instill project sustainability and allow for future capacity building. RESULTS: An educational elective was established between the pathology departments of the University of Virginia and Hospital Regional de Occidente in Quetzaltenango, Guatemala. Two residents at a time engaged in a month-long educational elective assisting and learning from the in-country pathologist in anatomic pathology clinical work. CONCLUSIONS: The project is an example of a global health initiative centering on the enhancement of PALM services in a low-resource environment via a bidirectional, sustainable educational exchange.

Impact of initial biopsy type on the time to final diagnostic biopsy in patients with follicular lymphoma and suspected histologic transformation.

Diagnosis of histologic transformation (HT) of follicular lymphoma (FL) requires tissue biopsy. While surgical biopsy represents the gold standard, less invasive procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are frequently performed. In this retrospective multi-institutional study including 269 patients with FL and suspected HT, the median time from initial clinical suspicion to final diagnostic biopsy was similar whether the workup began with FNAB, CNB, or surgical biopsy (4, 9, and 6 days, respectively; p=.27), despite more subsequent biopsies performed following initial FNAB. Periprocedural complications were uniformly minimal. Biopsy-proven HT was more common in the initial surgery group and in workups including positron emission tomography/computed tomography (PET/CT). Our findings, derived from US academic centers with specialized procedural and pathology expertise, suggest that FNAB, CNB, and surgical biopsy are all viable initial diagnostic procedures that can inform clinical decision-making in select FL patients with suspected HT.