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NA mismatch repair (MMR) is a highly conserved process involving the 4 key genes mutL homologue 1 (MLH1), mutS homologue 2 (MSH2), mutS homologue 6 (MSH6), and postmeiotic segregation increased [...], * Context.--The approval of pembrolizumab for treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) advanced cancers has led to increased requests for MSI and/or MMR immunoperoxidase (IPOX) testing. Diagnoses for patients with advanced-stage cancer are frequently made from cytology specimens. Objective.--To investigate the feasibility of using cell block (CB) preparations of effusions for MMR IPOX evaluation. Design.--Surgical pathology cases of colorectal and endometrial carcinomas with known MMR/MSI status and matched effusions with available CBs were identified. Cell block sections were evaluated for adequacy and stained with MMR IPOX (MSH2, MSH6, MLH1, and PMS2). The CBs were reviewed, the number of tumor cells quantified, and MMR IPOX was interpreted as retained, lost, suboptimal, or noncontributory. Results.--We identified 748 cases with MMR/MSI testing on surgical specimens having matched effusions. Of these, 131 cases (17.5%) had an available CB and 53 were deemed adequate for MMR IPOX staining. MMR IPOX results between effusion CBs and surgical pathology specimens were concordant in 45 of 53 (85%), inconclusive in 6 of 53 (11%), and discordant in 2 of 53 (4%) cases. Conclusions.--There was high concordance of MMR IPOX testing between cytologic and surgical specimens, with no false-positive and 2 false-negative CB results. Limited tumor cells, staining in cells indefinite as tumor, tumor staining heterogeneity, and lack of internal control staining were problematic in some cases. Our findings indicate that cytologic effusion specimens may be suitable substrates for MMR IPOX biomarker testing; however, inconclusive cases need to be interpreted with caution. (Arch Pathol Lab Med. 2021;145:46-54; doi: 10.5858/arpa.2019-0398-OA)

Background: The International System for Reporting Serous Fluid Cytopathology was recently proposed as a tiered structure to provide consistent reporting terminology for serous effusions. Because of the variation in reporting practices for indeterminate serous effusions, namely, the atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) groups, the authors retrospectively reviewed cases in these 2 categories at their institution and determined the associated risk of malignancy (ROM). Methods: Pleural, peritoneal, and pericardial effusions that were reported as AUS or SFM over a 1‐year period were reviewed, and their associated ROMs were calculated based on confirmation of malignancy by previous and/or subsequent fluid and/or tissue biopsy specimens from the same general location. Results: In total, 145 AUS and 98 SFM serous effusion cases were identified. The AUS category was used when the cells in question lacked the requisite quantitative (cell number) and/or qualitative (morphologic) features for a definitive diagnosis. Immunohistochemistry (IHC) or flow cytometry (FCM) was available in 15% of cases (n = 22) with inconclusive results. The ROM based on 69 cases with available follow‐up results was 39%. In contrast, the SFM category demonstrated cells that were morphologically suspicious for malignancy but sparse, precluding IHC or FCM (n = 63; 64%) or yielding inconclusive results (n = 35; 36%). The ROM in the SFM category, based on follow‐up results of 61 cases, was 64%. Conclusions: The ROM for SFM was significantly higher than that for AUS (P <.01), supporting separate diagnostic categories for these 2 groups. There is considerable variation in the reporting practices for indeterminate serous effusions, namely, the categories atypia of undetermined significance and suspicious for malignancy, with limited literature on their associated risk of malignancy. The reporting practice at a single institution is examined and demonstrates that the risk of malignancy in the suspicious for malignancy category is significantly higher than that for the atypia of undetermined significance category, thus providing support for retaining these as 2 separate diagnostic categories in the tiered reporting system for serous effusions. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed 25 fine-needle aspiration cases of sclerosing adenosis of the breast in conjunction with histologic features of the paired core-needle biopsy and radiologic findings. The original cytologic diagnoses were benign (n = 19), focally atypical (n = 3), and suspicious for carcinoma (n = 3). The frequent features, although not specific, were low-to-moderate cellularity, bland epithelial cells that focally formed cohesive groups/tubules or occasionally discohesive clusters or individual cells, and fragments of dense fibrous stroma. Some tubules had an angulated configuration. Myoepithelial cells were present in all cases but were scant or absent in small epithelial groups. These cytologic features closely reflected the histologic appearances (ie, compressed and attenuated tubules and sclerotic stroma), but may cause overinterpretation on cytologic smears, especially when angulated tubules, discohesive or individual epithelial cells, scanty myoepithelial cells, and nuclear atypia are noted concurrently. Familiarity with its cytologic features may prevent false-positive diagnosis. Histologic confirmation is recommended for difficult cases. [ABSTRACT FROM AUTHOR]