Undifferentiated Pleomorphic Sarcoma of the Breast: A Case Report and Literature Review.

Primary undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare and highly aggressive soft tissue neoplasm. Representing a diagnosis of exclusion, its rarity and the lack of multicentric studies have prevented the establishment of a clear consensus regarding optimal therapeutic strategies. We report the case of a 68-year-old woman presenting with a 15-cm bleeding right breast mass. Histopathological examination revealed a proliferation of pleomorphic, atypical cells admixed with numerous osteoclast-like giant cells and a high proliferative index (Ki-67 = 95%). Comprehensive molecular profiling identified pathogenic mutations in PIK3CA, TERT, TP53, and RB1, alongside multiple copy number alterations and an overall low tumor mutational burden (TMB: 4.5 mutations/Mb). Due to her unstable clinical condition, the patient did not receive adjuvant therapies and died three months after mastectomy. A systematic review of the English literature (2002-2026) identified a total of 57 other reported cases of primary breast UPS from 44 different studies. The data underscore the diagnostic challenge of differentiating UPS from more common entities with sarcomatoid features, such as metaplastic carcinoma. Surgery remains the definitive treatment, whereas systemic therapies generally show limited efficacy. Breast UPS is a highly heterogeneous tumor with a poor prognosis. This report highlights the necessity of integrating clinical, morphological, immunohistochemical, and molecular data to achieve an accurate diagnosis and emphasizes the need for larger case series to uncover tailored therapeutic options for this rare patient cohort.