Histopathologic Features of Breast Tissue From Transgender Men and Their Associations With Androgen Therapy.

OBJECTIVES: To assess the histopathologic features of breast tissue of transgender men (TM) undergoing gender-affirming bilateral mastectomies in relation to androgen therapy (AT). METHODS: We reviewed 374 transgender bilateral mastectomy cases from 2017 to 2020. Of these, 314 (84.4%) patients received preoperative AT. We compared these with 127 cases of cisgender females undergoing elective breast reduction. RESULTS: Breast specimens from TM on AT, compared with cisgender women, showed a median higher gross percentage of fibrous tissue (P < .001), reduced lobular density (P = .004), higher amount of lobular atrophy (P < .001), and lower incidence of cysts (P < .001), apocrine metaplasia (P < .001), calcifications (P < .001), columnar cell change (P = .002), and atypia (P = .003). Each additional month of AT was associated with a 2% decrease in the odds of having nonapocrine cysts (P = .02), a 5% decrease in the odds of having usual ductal hyperplasia (P = .007), and a 0.14% decrease in median lobular density (95% confidence interval, -0.18 to -0.05). CONCLUSIONS: In this study, breast specimens from TM, particularly with a history of AT, had a higher proportion of fibrous tissue, fewer lobules, and a higher degree of lobular atrophy than cisgender females. Rare cases of atypia were not predicted by preoperative imaging or gross findings, supporting routine microscopic evaluation of these specimens.

Effects of COVID-19 pandemic on cytology: specimen adequacy in fine-needle aspiration of palpable head and neck masses.

INTRODUCTION: At our institution, palpation-guided fine-needle aspiration (FNA) is performed by the cytopathology service on an outpatient basis at the request of otolaryngologist surgeons. The aim of this study is to assess the effect of COVID lockdown measures on our FNA service with specific focus on adequacy rates. MATERIALS AND METHODS: All palpation-guided FNA performed in 2019 to 2020 were identified in our pathology database. Adequacy rates were compared for 3 time periods in 2020: pre-COVID, lockdown, and post-lockdown. RESULTS: In 2019, 121 FNAs were performed with 98% (119 of 121) obtained by pathology and only 2% (2 of 121) obtained by surgeons. In 2020, 89 FNAs were performed with 45% (40 of 89) collected by pathologists and 55% (49 of 89) by surgeons. During the pre-COVID period of 2020, 27 FNAs were collected, 85% (23 of 27) by pathologists, 8.7% of these (2 of 23) were nondiagnostic. Of the 4 FNAs performed by surgeons, all were positive for malignancy. During COVID lockdown all 24 FNAs were performed by surgeons with a 50% (12 of 24) nondiagnostic rate. Post-lockdown, with FNA referrals still below pre-COVID levels, surgeons performed 55.3% (21 of 38) of FNAs with 28.6% (6 of 21) non-diagnostic, while pathology performed 44.7% (17 of 38) with an 11.8% (2 of 17) nondiagnostic rate. CONCLUSIONS: Our FNA service noted significant changes in 2020 as a result of the COVID pandemic. Nondiagnostic rates were significantly increased in 2020 compared with 2019, primarily due to a shift to majority surgeon-performed palpation-guided FNA in the absence of cytopathology service during the lockdown period.

Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue.

IMPORTANCE: Trastuzumab deruxtecan (T-DXd) has shown efficacy in patients with breast cancer with ERBB2 immunohistochemistry (IHC) scores of 1+ or 2+ but not 0 as read in central pathology laboratories. The drug is currently being tested in large randomized clinical trials with registration intent for this patient population. OBJECTIVE: To determine the suitability of the current standard ERBB2 IHC assays to select patients with low ERBB2 positivity for treatment with T-DXd. DESIGN AND SETTING: Assessment of data from College of American Pathologists surveys and assessment of analytic data from a Yale University-based study of concordance of 18 pathologists reading 170 breast cancer biopsies. RESULTS: The total survey data set included scores over 2 years from 1391 to 1452 laboratories of 40 ERBB2 cores from each laboratory (20 cores twice a year for a total of 80). College of American Pathologists surveys show that 19% of cases read by the laboratories generate results with less than or equal to 70% concordance for IHC ERBB2 score 0 vs 1+. When 18 pathologists read the scanned slides from a selected set of breast cancer biopsies using a 4-point scale, there was only 26% concordance between 0 and 1+ compared with 58% concordance between 2+ and 3+. CONCLUSIONS AND RELEVANCE: In this study using a current standard ERBB2 IHC assay, the scoring accuracy for ERBB2 IHC in the low range (0 and 1+) was poor. This inaccuracy in the real world could lead to misassignment of many patients for treatment with T-DXd.

Sentinel Nodal Metastasis Detection in Endometrial Carcinoma With Microcystic, Elongated, and Fragmented (MELF) Pattern by Cytokeratin Immunostaining.

OBJECTIVES: The microcystic, elongated, and fragmented (MELF) pattern of myoinvasion in endometrial carcinoma (EC) is associated with an increased risk of lymph node metastasis. Our aim is to assess the role of cytokeratin immunohistochemical (IHC) stains in detecting sentinel nodal metastasis in MELF pattern tumors. METHODS: We recovered 19 MELF pattern EC hysterectomies with lymphadenectomy from our files. Negative nodes were subjected to cytokeratin AE1/AE3 IHC. Ten additional cases with sentinel lymph node (SLN) biopsies primarily assessed by IHC were also analyzed. RESULTS: Of the 19 cases of EC, 6 had positive lymph nodes based on H&E-stained sections at the time of their initial diagnosis. With the addition of IHC stains, 8 previously negative cases were found to have node metastases, and 3 of these were SLNs. Among the 10 cases primarily assessed by IHC, 5 had malignant cells in their SLNs. CONCLUSIONS: Cytokeratin IHC staining detected malignant cells in 9 of 16 cases with SLNs in our sample of women with MELF pattern of myoinvasion. Immunohistochemical stains should be routinely performed on SLNs from all MELF-positive cases to detect occult lymph node metastases and isolated tumor cells.

Interobserver variability in breast carcinoma grading results in prognostic stage differences.

The AJCC Cancer Staging Manual 8th edition included tumor grade in the pathologic prognostic stage for breast carcinomas. Due to the known subjectivity of tumor grading, we aimed to assess the degree of interobserver agreement for invasive carcinoma grade among pathologists and determine its effect on pathologic prognostic stage. One hundred consecutive cases of invasive stage II carcinomas were independently graded twice, with an 4-week intervening wash-out period, by 6 breast pathologists utilizing established Nottingham grading criteria. Inter- and intra-observer variability was determined for overall grade and for each of the 3 scoring components. Interobserver variability was good to very good (κ range = 0.582-0.850) with even better intra-observer variability (mean κ = 0.766). Tubule score was the most reproducible element (κ = 0.588). Complete concordance was reached in 54 cases and 58 cases in rounds 1 and 2 respectively. In round 1 this resulted in different pathologic prognostic stage in only 25 of discordant cases, 18 of which were stage IA versus IB. In conclusion, grading agreement between pathologists was good to very good and discordant grades resulted in small changes to pathologic prognostic stage.