The capillary lobule variant of radiation‐associated angiosarcoma in the setting of breast cancer: A diagnostic pitfall

AIM: Post‐radiation angiosarcoma is an iatrogenic event seen in the setting of breast cancer treatment. Histopathologically, there are morphologic variants of angiosarcoma that mimic benign entities, including the capillary lobule variant of post‐radiation angiosarcoma. We present the largest case series to date of this histopathologic variant of post‐radiation angiosarcoma. METHODS AND RESULTS: Cases of the capillary lobule variant of post‐radiation angiosarcoma from institutional/consultation archives from 2008 to June 2022 were reviewed. For inclusion, tumors had to occur in irradiated skin and exhibit a multi‐lobular proliferation of tightly packed capillary‐like vessels, as previously described in this variant. Prior ancillary studies were also reviewed. Eight cases met the criteria. All occurred in women treated with radiation for breast cancer (median age 75 years). All cases had similar findings, including a multi‐lobular proliferation of tightly packed vessels, infiltrative cords, and atypical single endothelial cells. A conventional angiosarcoma pattern was also seen in five cases. All cases tested were positive for vascular markers (CD31, CD34, and/or ERG) and MYC. MYC amplification was shown by FISH in all cases tested. Smooth muscle actin (SMA) was positive in pericytes in the capillary lobules in all five cases tested and areas of conventional angiosarcoma in two of three cases. CONCLUSIONS: The capillary lobule variant of angiosarcoma is a rare and therefore potentially under‐recognized variant of post‐radiation angiosarcoma. The lobular architecture and SMA positivity may mimic benign vascular proliferations. Careful attention to histopathologic features and ancillary tests may facilitate accurate diagnosis.