Hoda, Raza S.

Aims . To identify the most common reasons for consultation to a large specialty breast pathology service at a major institution. To provide insight into the overall challenges in practicing breast pathology. Methods . The anatomic pathology database at one institution was searched for all breast consultations received in 2021, excluding in-house patients and patients who were transferring care. Results . A total of 553 patients met the criteria ( n = 553) from a variety of academic and private practices. For each patient, the paperwork from the submitting institution was reviewed to identify the specific question, and subsequently classified into 14 categories. The reason for the consultation request was not provided for 78 (14%) patients, and a review of the outside diagnoses, where applicable, was performed. In summary, the top 5 reasons for consultation were: (1) assistance with classification of atypical intraductal epithelial proliferations (32%); (2) evaluation for the presence of (micro-)invasive carcinoma (14%); (3) evaluation of fibroepithelial (12%), (4) papillary (11%), and (5) spindle cell lesions (7%). Conclusion . We show an ongoing educational and practice gap for pathologists who most commonly struggle with classifying atypical precursor lesions, specifically when these are small and focal, or bordering on intraductal carcinoma (32%, 177/553). The second most common reason for consultation was classifying invasive carcinomas as microinvasive and subtypes (total of 20.4%, 113/553). As such, our data supports the continued need for rigid and clear criteria for diagnosing threshold lesions (namely atypical hyperplasias) and intraductal carcinoma of the breast.

Introduction: Solitary fibrous tumor (SFT) is a fibroblastic tumor with malignant potential that is underpinned by a recurrent inv12(q13q13)-derived NAB2::STAT6 fusion. Breast and axilla are uncommon locations for this entity. Methods: Records of two academic institutions were electronically searched for breast and axillary SFTs. Clinical and pathologic data were reviewed. Literature review for breast or axillary SFTs was performed. Present study and previously reported tumors were stratified using five SFT risk models: original and modified Demicco metastatic risk, Salas local recurrence risk, Salas metastatic risk, and Thompson local recurrence risk. Results: Five patients with breast or axillary SFT were identified. Median age was 49 years, and median follow-up (available for four patients) was 82 months. Three patients showed no evidence of disease, and one developed recurrence. Literature review identified 58 patients with breast or axillary SFT. Median age was 54 years, and median follow-up (available for 35 patients) was 24 months. Thirty-one patients showed no evidence of disease, three developed recurrence, and one developed metastasis. Original and modified Demicco models and Thompson model showed the highest sensitivity; original and modified Demicco models and Salas metastatic risk model demonstrated the highest specificity. Kaplan–Meier models were used to assess recurrence-free probability (RFP). Original and modified Demicco models predicted RFP when stratified by “low risk” and “moderate/intermediate and high risk” tumor, though sample size was small. Conclusions: While many SFTs of breast and axilla remain indolent, a subset may develop recurrence and rarely metastasize. The modified Demicco risk model demonstrated optimal performance characteristics.

AimsDue to its rarity and non‐specific clinical and pathological features, low‐grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple‐negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management.Methods and resultsTwenty‐five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow‐up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple‐negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow‐ups up to 108 months.ConclusionsLGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.

Among gynecologic cancers, uterine serous carcinoma (USC) has been shown to be human epidermal growth factor receptor 2 (HER2) amplified and trastuzumab has been included in the recent National Comprehensive Cancer Network (NCCN) guidelines for treatment of advanced stage or recurrent USC with HER2 overexpression/amplification. There is limited literature suggesting that a subset of high-grade endometrioid carcinomas with aberrant p53 expression may also be HER2 amplified and these patients could benefit from the addition of targeted therapy. We identified 59 p53-aberrant (mismatch repair proficient) FIGO 3 endometrioid carcinomas of the uterus. HER2 immunohistochemistry was performed in all 59 tumors and HER2 fluorescence in situ hybridization (FISH) was performed in 52 of the 59 cases. Four of the 59 cases were HER2 3+ by immunohistochemistry (6.7%), using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2007, 2013, and 2018 criteria. HER2 FISH was performed in 3 of the 4 cases and was amplified in all 3. Nine, 8, and 7 tumors showed 2+ HER2 staining when applying 2018, 2013, and 2007 criteria, respectively, FISH was performed in 7 tumors and none were amplified. An additional 4 cases did not perfectly meet the 2018 ASCO/CAP criteria but were assigned a score of 2+, none were amplified by HER2 FISH. The remaining 42 cases showed 1+ or no staining for HER2, FISH was successfully performed in 38 tumors and none showed amplification. Approximately half of the tumors fulfilled criteria for HER2-low or HER2-very low (10 HER2-low and 20 HER2-very low). Our data shows that a subset of p53-aberrant high-grade endometrial endometrioid carcinoma express HER2 and these patients may benefit from the addition of targeted therapy. The role of targeted therapy in HER2-low gynecologic carcinoma is currently unexplored.