Apocrine Variant of Pleomorphic Lobular Carcinoma In Situ: Further Clinical, Histopathologic, Immunohistochemical, and Molecular Characterization of an Emerging Entity.

To date, the apocrine variant of lobular carcinoma in situ (AP-LCIS) has been cursorily described as a subtype of lobular carcinoma in situ (LCIS). We retrospectively reviewed 34 cases of AP-LCIS (including 23 associated with invasive lobular carcinoma) to fully characterize it. AP-LCIS typically presented with screen-detected calcifications in older women (mean age: 65 y) and was characterized by distended terminal duct lobular units with relatively large "pleomorphic" cells, central necrosis, and calcifications. AP-LCIS cells exhibited abundant eosinophilic occasionally granular cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Synchronous classic and/or florid LCIS was identified in 24/34 (70%) AP-LCIS, and in 9/11 (82%) pure AP-LCIS. Most (68%) cases of AP-LCIS were estrogen receptor-positive (50% strongly), 35% were progesterone receptor-positive, 26% were human epidermal growth factor 2-positive, 18% demonstrated high-proliferation rate (Ki67: >15%), and 90% were androgen receptor-positive. Aurora kinase A, immunoreactive in 38% of AP-LCIS cases, was not significantly associated with recurrence, development of invasion, or nodal positivity (P>0.05). Compared with conventional (nonapocrine) pleomorphic lobular carcinoma in situ (P-LCIS), aurora kinase A was expressed in a significantly greater proportion of P-LCIS (100%). AP-LCIS and P-LCIS did not otherwise differ in clinicopathologic features. Next-generation sequencing utilizing the Oncomine Comprehensive Panel v2, performed on 27 AP-LCIS cases, showed no specific molecular findings. In a mean follow-up of 57 months, 2 (of 11, 18%) pure AP-LCIS cases recurred (2 both in situ and invasive) and none metastasized or proved fatal. AP-LCIS should be regarded as another high-grade LCIS similar to P-LCIS in many respects, and pending additional studies should be managed similarly.

Lobular neoplasia and invasive lobular breast cancer: Inter-observer agreement for histological grading and subclassification.

Lobular neoplasia (LN), invasive lobular breast cancer (ILBC) and related pleomorphic variants represent a distinct group of neoplastic mammary gland lesions. This study assessed the inter-observer agreement of histological grading in a series of ILBC and LN. 54 cases (36x ILBC, 18x LN) were evaluated by 17 observers. 3978 classification calls on various histological features, including nuclear grade, proliferative activity (Ki67 immunohistochemistry, categorical scoring), histological grade and pleomorphism were obtained. Pairwise Cohen's kappa values were calculated and compared between various features and different observer subsets with variable histomorphological experience. In ILBC, pairwise inter-observer agreement for histological grade ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists compared with beginners (P < 0.001). Agreement for proliferation (Ki67) ranged from slight to almost perfect concordance and was also higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67) was superior to agreement for histological grade and nuclear grade, even among advanced and experienced histopathologists (P < 0.001). In LN, agreement for B-classification ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67 in LN) was superior to subclassification agreement based on conventional features, such as acinar distention and nuclear grade (P < 0.001). In summary, pairwise inter-observer concordance of histological grading of ILBC and LN is dependent on histomorphological experience. Assessment of proliferation by Ki67 immunohistochemistry is associated with favorable inter-observer agreement and can improve histological grading of ILBC as well as LN.

Breast carcinoma in situ: An observational study of tumor subtype, treatment and outcomes.

BACKGROUND & AIMS: To evaluate the clinical presentation, treatment and outcome of patients with breast carcinoma in situ (BCIS) with special emphasis on the role of the tumor subtype and local treatment in these patients. METHODS: Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM). RESULTS: In all, 6867 patients with BCIS were eligible during the 2010-2013 study period. Compared with the hormone receptor (HoR)+/HER- subgroup, patients with triple negative (TN) breast cancer were more likely to have tumors that were higher in grade and larger in size; they were also more likely to have tumors with ductal and comedo histology and were less likely to have tumors with cribriform and papillary histology (each P < 0.05). During the follow-up period, patients with TN breast cancer had an OS of 97.0% compared with 98.6 % in the HoR+/HER- subgroup (P < 0.05). Furthermore, the BCSM rate was 1.0% for the TN group compared with 0.1% for the HoR+/HER- subgroup (P < 0.05). Multivariate analysis revealed that patients with TN MBC had a poorer OS and BCSM (P <0.05). Multivariate analysis of OS with respect to the local treatment history showed that patients who received breast-conserving surgery (BCS) combined with radiotherapy (R) were more likely to have an improved OS (P < 0.05). Moreover, the results demonstrated that patients who underwent SLNB were more likely to have a lower BCSM (P < 0.05). CONCLUSIONS: The results demonstrate that BCIS appears to alter the prognosis associated with the TN subtype. Meanwhile, BCS plus R was a preferable option and resulted in survival rates that were better than those achieved with mastectomy; thus, SLNB should be considered as an appropriate assessment of axillary staging in patients with BCIS.