Carcinoma arising in microglandular adenosis of the breast: clinicopathological and genetic analysis

Abstract

Aims: To study the clinicopathological, immunohistochemical and molecular features of carcinoma arising in microglandular adenosis (MGACA) of the breast.

Methods: Clinicopathological features of 13 cases of MGACA were analysed. All tumours were molecular subtype by immunohistochemistry (IHC) of AR, CD8, FOXC1 and DCLK1 expression. Next-generation sequencing including 511 genes was analysed.

Results: All tumours showed a histological spectrum ranging from microglandular adenosis (MGA) to atypical MGA (AMGA), ductal carcinoma in situ (DCIS) and MGACA. Invasive components in 10 of 13 tumours were invasive carcinoma of no special type (NST), 3 were metaplastic carcinoma with mesenchymal differentiation (including two cases of matrix-producing carcinoma) mixed with NST. All lesion-associated epithelial cells were triple negative (TNBC) and positive for S-100. Reticulin staining showed the presence of basement membrane in MGA, AMGA and DCIS, and its absence in invasive carcinoma. According to IHC-based TNBC molecular subtyping, 10 tumours were basal-like immune-suppressed (BLIS), 2 were luminal androgen receptor and 1 was immunomodulatory. 10 patients had gene mutations. Pathogenic germline mutations of the BRCA1 and BRCA2 genes were detected in four tumours (30.7%) and one tumour (7.7%). Somatic mutation rate of the TP53 gene was 69.2%. Amplification rates of MYC, FGFR2, JAK2 and MCL1 genes in our cohort were 46.2%, 15.4%, 15.4% and 7.7%, respectively.

Conclusion: MGACA is a rare breast carcinoma, with distinct morphological, immunohistochemical and molecular features. Most MGACA were BLIS molecular subtype of TNBC. TP53 and BRCA1 gene mutation and MYC gene amplification were the most common genetic changes in MGACA.

Keywords: Breast Neoplasms; Genes, Neoplasm; IMMUNOPHENOTYPING.