Abstract DFSP is a rare, low-grade soft tissue sarcoma characterized by locally aggressive growth and low metastatic potential. The fibrosarcomatous (FS) variant, which occurs in approximately 10-15% of cases, is associated with increased biological aggressiveness, higher rates of local recurrence, and a greater risk of distant metastasis, particularly to the lungs. DFSP involving the breast is exceptionally rare, especially in male patients, making diagnosis and treatment more challenging due to its clinical similarity to breast carcinomas. A 65-year-old male, ex-smoker, presented with a progressively enlarging left breast mass over a four-month period. On physical examination, the lesion appeared as an irregular, indurated, mobile mass, measuring 7x6 cm, with hyperemia and cutaneous infiltration. Breast ultrasonography demonstrated a solid, hypoechoic, heterogeneous, lobulated nodule (BI-RADS 4C). Chest CT revealed a 7.1x5.7x4.5 cm mass with no clear cleavage plane with the pectoralis major muscle. Core biopsy demonstrated a spindle cell neoplasm, CD34-positive and Factor XIIIa-negative, consistent with DFSP. Clinical staging was cT4b N0 M0. The patient underwent a wide local excision via simple mastectomy with partial resection of the pectoralis major muscle to achieve adequate deep margins, and immediate reconstruction was performed using an abdominal fasciocutaneous flap. Histopathological analysis confirmed DFSP with FS transformation (DFSP-FS), high mitotic rate, and all surgical margins were negative, with the closest deep margin exceeding 0.5 cm. Immunohistochemistry (IHC) showed diffuse CD34 positivity, negative S-100, p63 and CK, and Ki67 30% in fibrosarcomatous areas. DFSP involving the breast is extremely rare, particularly in males, with few reported cases. It contributes to diagnostic delays and frequent misclassification as more common breast malignancies. Clinical presentation can be insidious. Imaging exams, although useful for anatomical delimitation, are not specific for diagnosis. Ultrasonography and mammography may suggest solid lesions, but magnetic resonance imaging is superior in assessing the extent of local invasion and involvement of adjacent structures. Definitive diagnosis relies on histopathology and IHC, with CD34 positivity and absence of epithelial markers. The presence of fibrosarcomatous areas, with high mitotic activity and an elevated Ki67, indicates aggressive transformation and a worse prognosis. Wide surgical excision with negative margins remains the cornerstone of treatment to minimize recurrence. Simple mastectomy with wide margins, including resection of adjacent muscle tissue when necessary, is recommended in cases of extensive involvement or fibrosarcomatous transformation, as in the present report. Adjuvant radiotherapy is recommended in situations of positive margins, unresectable disease, or locoregional recurrence, contributing to the reduction of the local recurrence rate, as evidenced by retrospective studies and systematic reviews. Radiotherapy should also be considered in cases of DFSP-FS, due to its potential aggressiveness. The use of imatinib, a tyrosine kinase inhibitor that acts on the characteristic COL1A1-PDGFB gene fusion of DFSP, has proven effective in advanced, unresectable, or metastatic cases, offering an important therapeutic option for patients with refractory disease. This rare case of DFSP-FS infiltrating the male breast underscores the diagnostic challenges and therapeutic considerations associated with this entity. It highlights the critical importance of a multidisciplinary approach for timely diagnosis and optimal surgical management, ultimately improving patient outcomes. Citation Format: G. Neri Ferreira, L. Novis Leite Pinto, L. Martins de Brito Moraes, D. Franco Vieira de Oliveira, A. Coelho de Oliveira, A. Pereira Correia Carneiro, A. Dominique Nascimento Lima. Dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous transformation involving the male breast: A rare case report and comprehensive review of clinicopathologic features abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-15.
Ferreira et al. (Tue,) studied this question.