Germline BRCA2 Pathogenic Variant in Metaplastic Breast Carcinoma with Heterologous Mesenchymal Differentiation: A Case Report and Literature Review

Background and Clinical Significance: Metaplastic breast carcinoma (MBC) is a rare type of breast tumor with various subtypes. MBCs are typically high-grade and exhibit a particularly aggressive behavior, with a significant propensity for recurrence and specific chemoresistance, especially in neoadjuvant settings. One of its high-grade variants is the metaplastic carcinoma with heterologous mesenchymal differentiation (MCHMD). At present, the literature regarding the genetic predisposition of MBC and its connection with BRCA2 is limited. Hence, we present a rare case of a 51-year-old patient with a germline BRCA2 pathogenic variant affected by MCHMD. Case presentation: A 51-year-old Caucasian woman with a family history of breast cancer noticed a lump in her right breast. A needle biopsy of the mass resulted in a diagnosis of poorly differentiated (G3) invasive ductal carcinoma, associated with a dominant component of pleomorphic carcinoma with osteoclast-like cells. After surgery, the pathological report diagnosed a metaplastic carcinoma of the breast with heterologous mesenchymal differentiation (MCHMD) according to the WHO 2019 classification. Genetic testing revealed the presence of the pathogenic variant c.9676del of the BRCA2 gene. Conclusions: We report, to the best of our knowledge, the first case of a BRCA2 mutation in a woman with metaplastic carcinoma of the breast with heterologous mesenchymal differentiation.