Micropapillary variant of mucinous carcinoma of the breast shows genetic alterations intermediate between those of mucinous carcinoma and micropapillary carcinoma

Abstract

Aims Micropapillary variant of mucinous carcinoma of the breast (MPMC) is a rare histological form of oestrogen receptor (ER)‐positive invasive carcinoma that is characterised by micropapillary clusters of tumour cells in lakes of extracellular mucin. The aims of this study were to determine the genetic alterations underpinning MPMCs, and to determine whether they overlap with those of mucinous carcinomas and/or invasive micropapillary carcinomas. Methods and results DNA from five MPMCs was subjected to whole‐exome sequencing. Somatic mutations, copy number alterations and mutational signatures were determined with state‐of‐the‐art bioinformatics methods. No mutations in genes significantly mutated in breast cancer, including TP53, PIK3CA, GATA3, and MAP3K1, were detected. We identified copy number alterations that have been reported in invasive micropapillary carcinomas, such as recurrent gains in 1q, 6p, 8q, and 10q, and recurrent losses in 16q, 11q, and 13q, as well as a recurrent 8p12–8p11.2 amplification encompassing FGFR1. Like mucinous carcinomas, three of the five MPMCs analysed lacked PIK3CA mutations, 1q gains, and 16q losses, which are the hallmark genetic alterations of ER‐positive breast cancers, whereas two MPMCs harboured 16q losses and/or a complex pattern of copy number alterations similar to those found in breast‐invasive micropapillary carcinomas. Conclusions MPMCs are heterogeneous at the genetic level; some tumours show a pattern of somatic genetic alterations similar to those of mucinous carcinomas, whereas others resemble invasive micropapillary carcinomas at the genetic level. These findings suggest that MPMCs may not constitute one histological subtype, but rather a convergent phenotype that can stem from mucinous carcinomas or invasive micropapillary carcinomas.

Assessment of stromal tumor infiltrating lymphocytes and immunohistochemical features in invasive micropapillary breast carcinoma with long-term outcomes

“…In our analysis, the global average and the hot spot analysis of sTILs and their spatial distribution, TLS and the patterns of distribution of TAPC were similar between pure and non-pure IMPC. However, a recent study based on array comparative genomic hybridization technology revealed no significant differences in the structural genomic profile and immunophenotype of mixed cases as compared to those of pure IMPCs [31,32]. The implementation of more detailed molecular analysis at single cell level together with the integration of spatial information may be useful to better understand biologic differences between pure and non-pure IMPCs [33].…”

Sonographic Features of Pure Mucinous Breast Carcinoma With Micropapillary Pattern

“…MUMPC consists of micropapillary clusters of tumor cells with scalloped edges floating in stromal mucin (10). Compared with PMBC, MUMPC has a higher rate of lymph node metastasis and an outcome intermediate between that of mucinous carcinoma and micropapillary carcinoma (MPC) (11). MUMPC was described as a micropapillary variant of PMBC by Ng in 2002 (12).…”

Triple-Positive Breast Carcinoma: Histopathologic Features and Response to Neoadjuvant Chemotherapy

“…All cases were mixed tumors with a nonmucinous ductal component, except 1 tumor with features of ''micropapillary variant of mucinous carcinoma,'' a morphologic subtype with higher histologic grade and greater rates of lymphovascular invasion and lymph node positivity than pure mucinous carcinoma. [30][31][32][33] Published studies of this variant show the majority to be ER and PR positive, with up to 20% showing HER2 overexpression, although the rate of ''triplepositivity'' is not specifically indicated in these reports. Three tumors in our series displayed lobular differentiation, confirmed by lack of E-cadherin expression, including 2 pleomorphic invasive lobular carcinomas and 1 classic-type invasive lobular carcinoma.…”