Angiosarcoma Revisited: Diagnostic Challenges and a 16-Year Retrospective Analysis from a Single Institution

Background & Objective: Angiosarcomas (AS) are rare, aggressive malignant tumors characterized by marked histopathologic heterogeneity, often mimicking other neoplasms and complicating diagnosis. This 16-year retrospective study aimed to evaluate the clinicopathological spectrum of AS, with particular emphasis on diagnostic challenges and strategies for accurate identification. Methods: We retrospectively reviewed 11 histologically confirmed cases of AS diagnosed at our institution between January 2008 and December 2023. The data collected included patient demographics, clinical presentation, tumor location, histopathologic features, immunohistochemical (IHC) profiles, treatment modalities, and clinical outcomes. Results: Patient ages ranged from 25 to 62 years, with a slight female predominance (male-to-female ratio, 0.8:1). Tumor locations were variable, and histologic patterns ranged from well-differentiated, low-grade vascular proliferations resembling hemangiomas to poorly differentiated neoplasms mimicking pleomorphic undifferentiated sarcomas. IHC findings demonstrated overlapping marker expression, including cytokeratin (CK) positivity, which may lead to misdiagnosis as carcinoma, and loss of H3K27me3 expression, which can raise suspicion for malignant peripheral nerve sheath tumors (MPNST). Several cases also exhibited morphologic features closely resembling epithelioid hemangioendothelioma. Conclusion: Angiosarcoma poses considerable diagnostic difficulty due to its morphologic variability and overlapping immunophenotypic profiles. Accurate diagnosis necessitates a multidisciplinary approach, integrating clinical, radiologic, and pathologic data. This study highlights the importance of diagnostic vigilance and comprehensive evaluation when assessing vascular neoplasms.