Nonconventional MYC-Positive Primary Cutaneous Angiosarcoma: Novel or Untested

Angiosarcoma is a rare and aggressive endothelial malignancy that typically affects the skin, soft tissues, and viscera. Although often found in the sun-exposed areas of the head and neck, subsets are associated with chronic lymphedema, radiation therapy, chemical exposures, and certain syndromes. The cases linked to prior radiation therapy or chronic lymphedema often have MYC (8q24) amplification. A 65-year-old woman developed a primary cutaneous angiosarcoma (pc-AS) on her upper back. She had no history of radiation exposure, lymphedema, or known predisposing genetic syndrome. Histopathology revealed a moderate to poorly differentiated angiosarcoma with high mitotic activity, blood-filled vascular channels, and deep extension near the fascia. Immunohistochemistry confirmed strong CD31 expression and MYC nuclear expression. Fluorescence in situ hybridization revealed a gain of MYC copy number without rearrangement, an atypical finding suggestive of whole or partial gain of chromosome 8. This case stands out as a rare example of MYC gain in a primary, nonchronic lymphedematous and nonradiation-associated angiosarcoma, and raises new questions about the role of MYC-driven pathogenesis even in cases that fall outside the typical secondary angiosarcoma pattern. Moreover, it also suggests that MYC gain might reasonably be included in the ancillary panel in the work-up of pc-AS. Furthermore, this case suggests that MYC oncogene dysregulation might represent a distinct clinicopathologic entity beyond those associated with chronic lymphedema or radiation.