Aberrant expression of neuroendocrine markers in angiosarcoma: a potential diagnostic pitfall

Angiosarcomas (AS) are uncommon endothelial malignancies, usually arising from sun-damaged skin in older adults. Although most AS are readily diagnosed by light microscopy alone, immunohistochemistry (IHC) for endothelial markers such as CD31, CD34, FLI1, and ERG plays a valuable adjunctive role. However, IHC studies of AS must be interpreted with caution, as aberrant expression of markers such as cytokeratins, CD30, and CD117 may be seen. We report 3 cases of AS showing aberrant expression of the neuroendocrine markers synaptophysin and/or chromogranin A, previously unreported phenomena. Cases presented as metastatic lesions in the lung of a 48-year-old woman and as primary tumors of the kidney and neck in a 29-year-old and a 51-year-old woman, respectively. All cases expressed synaptophysin and/or chromogranin A, and various neuroendocrine/endocrine neoplasms were strongly considered as diagnoses by the initial evaluating pathologists. Additional morphological study and confirmatory IHC for CD31, FLI1, and ERG established the diagnosis of AS in all cases. Coexpression of synaptophysin and chromogranin A in 1 case suggests that at least some AS show true neuroendocrine differentiation. Awareness of this potential diagnostic pitfall is important for correct diagnosis and treatment of this rare subset of AS.