Subspecialized breast pathologists have suboptimal interobserver agreement in Ki-67 evaluation using 20% as the cutoff.

PURPOSE: Ki-67 expression levels in breast cancer have prognostic and predictive significance. Therefore, accurate Ki-67 evaluation is important for optimal patient care. Although an algorithm developed by the International Ki-67 in Breast Cancer Working Group (IKWG) improves interobserver variability, it is tedious and time-consuming. In this study, we simplify IKWG algorithm and evaluate its interobserver agreement among breast pathologists in Ki-67 evaluation. METHODS: Six subspecialized breast pathologists (4 juniors, 2 seniors) assessed the percentage of positive cells in 5% increments in 57 immunostained Ki-67 slides. The time spent on each slide was recorded. Two rounds of ring study (R1, R2) were performed before and after training with the modified IKWG algorithm (eyeballing method at 400× instead of counting 100 tumor nuclei per area). Concordance was assessed using Kendall's and Kappa coefficients. RESULTS: Analysis of ordinal scale ratings for all categories with 5% increments showed almost perfect agreement in R1 (0.821) and substantial in R2 (0.793); Seniors and juniors had substantial agreement in R1 (0.718 vs. 0.649) and R2 (0.756 vs. 0.658). In dichotomous scale analysis using 20% as the cutoff, the overall agreement was moderate in R1 (0.437) and R2 (0.479), among seniors (R1: 0.436; R2: 0.437) and juniors (R1: 0.445; R2: 0.505). Average scoring time per case was higher in R2 (71 vs. 37 s). CONCLUSION: The modified IKWG algorithm does not significantly improve interobserver agreement. A better algorithm or assistance from digital image analysis is needed to improve interobserver variability in Ki-67 evaluation.

Low interobserver agreement among subspecialised breast pathologists in evaluating HER2-low breast cancer.

AIMS: Metastatic HER2-low breast cancer (HLBC) can be treated by trastuzumab deruxtecan. Assessment of low levels of HER2 protein expression suffers from poor interobserver reproducibility. The aim of the study was to evaluate the interobserver agreement among subspecialised breast pathologists and develop a practical algorithm for assessing HLBC. METHODS: Six breast pathologists (4 juniors, 2 seniors) evaluated 106 HER2 immunostained slides with 0/1+expression. Two rounds (R1, R2) of ring study were performed before and after training with a modified Ki-67 algorithm, and concordance was assessed. RESULTS: Agreement with 5% increments increased from substantial to almost perfect (R1: 0.796, R2: 0.804), and remained substantial for three categories (<1% vs 1%-10% vs >10%) (R1: 0.768, R2: 0.764). Seniors and juniors had almost perfect agreement with 5% increments (R1: 0.859 and 0.821, R2: 0.872 and 0.813). For the three categories, agreement remained almost perfect among seniors (R1: 0.837, R2: 0.860) and substantial among juniors (R1: 0.792, R2: 0.768). Binary analysis showed suboptimal agreement, decreasing for both juniors and seniors from substantial (R1: 0.650 and 0.620) to moderate (R2: 0.560 and 0.554) using the 1% cut-off, and increasing from moderate to substantial (R1: 0.478, R2: 0.712) among seniors but remaining moderate (R1: 0.576, R2: 0.465) among juniors using the 10% cut-off. The average scoring time per case was higher (72 vs 92 s). CONCLUSIONS: Subspecialised breast pathologists have suboptimal agreement for immunohistochemical evaluation of HLBC using the modified Ki-67 methodology. An urgent need remains for a new assay/algorithm to reliably evaluate HLBC.

Intraoperative assessment of axillary sentinel lymph nodes by telepathology.

PURPOSE: Although axillary dissection is no longer indicated for many breast cancer patients with 1-2 positive axillary sentinel lymph nodes (ASLN), intraoperative ASLN assessment is still performed in many institutions for patients undergoing mastectomy or neoadjuvant therapy. With recent advancements in digital pathology, pathologists increasingly evaluate ASLN via remote telepathology. We aimed to compare the performance characteristics of remote telepathology and conventional on-site intraoperative ASLN assessment. METHODS: Data from ASLN evaluation for breast cancer patients performed at two sites between April 2021 and October 2022 was collated. Remote telepathology consultation was conducted via the Aperio eSlideManager system. RESULTS: A total of 385 patients were identified during the study period (83 telepathology, 302 on-site evaluations). Although not statistically significant (P = 0.20), the overall discrepancy rate between intraoperative and final diagnoses was slightly higher at 9.6% (8/83) for telepathology compared with 5.3% (16/302) for on-site assessment. Further comparison of performance characteristics of ASLN assessment between telepathology and conventional on-site evaluation revealed no statistically significant differences between deferral rates, discrepancy rates, interpretive or sampling errors, major or minor disagreements, false negative or false positive results as well as clinical impact and turn-around time (P ≥ 0.12). CONCLUSION: ASLN assessment via telepathology is not significantly different from conventional on-site evaluation, although it shows a slightly higher overall discrepancy rate between intraoperative and final diagnoses (9.6% vs. 5.3%). Further studies are warranted to ensure accuracy of ASLN assessment via telepathology.

Low-grade adenosquamous carcinoma of the breast: a clinical, morphological and immunohistochemical analysis of 25 patients.

AIMS: Due 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 RESULTS: Twenty-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. CONCLUSIONS: LGASC 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.

Primary sinonasal myxofibrosarcoma: a clinicopathological study of five cases and review of the literature.

Myxofibrosarcoma is a malignant pleomorphic fibroblastic sarcoma with variably myxoid stroma, and is characterised by a distinctive curvilinear vascular pattern. In the head and neck area, myxofibrosarcoma is extremely rare, with only a handful of case reports in the literature to date. We report the first case series of primary sinonasal myxofibrosarcoma across two institutions. Among the five cases (2 female, 3 males, aged 52-82 years old), four arose from the maxillary sinus and one from the sphenoid sinus. Four patients received surgical resection and three with adjuvant radiotherapy. The tumours ranged from 2.9 to 5.6 cm in greatest dimensions. All tumours demonstrated extensive myxoid stroma (>50% myxoid component) with a characteristic curvilinear, elongated, thin-walled vasculature with perivascular condensation of tumour cells. All but one were classified as intermediate to high grade myxofibrosarcoma. Among the four patients with follow-up information, three reported no local recurrence or distal metastasis, and one had local recurrence. Myxofibrosarcoma should be included in the differential diagnosis of sinonasal tumours with a pleomorphic spindle cell morphology and a 'null' immunophenotype.