A 72-year-old male presents with an ill-defined, deep-seated mass in his right calf. It has grown appreciably in the past few months and is now roughly the size of a golf ball. A core biopsy is performed, and a representative section is shown here. The tumor cells stain positively with antibodies to CD34 and CD31. What is the most likely diagnosis?

A. Angiosarcoma
B. Desmoid tumor
C. Leiomyosarcoma
D. Lymphoma
E. Rhabdomyosarcoma

The diagnosis in this case is angiosarcoma. Angiosarcoma is a rare tumor with a peak incidence in the 7^th decade of life (though it may occur at any age). Common sites affected are the head and neck, extremities, and soft tissues. Histologically, angiosarcoma can appear relatively well-differentiated with recognizable endothelial cells forming vascular channels, as in this case (here is the slide again, with a couple of the channels marked).

Here’s a higher power image showing a nice vascular channel in the center – it even has red cells in it!

Angiosarcoma may also present as a wildly undifferentiated tumor with solidly-packed, anaplastic spindle cells and no vascular channels. These cases are pretty hard to diagnose in real life (and even more so in a tray of “unknown” slides that the staff pathologists love to torture medical student and residents with).

One thing that is usually helpful in these undifferentiated angiosarcomas (and, by the way, in any undifferentiated tumor) is immunohistochemical staining. In the case of angiosarcoma, you’d use stains for CD31 (an endothelial cell marker) and CD34 (a hematopoietic progenitor cell antigen), both of which are positive in most cases of angiosarcoma. Most other tumors are not positive for both of these markers. Some cases of leiomyosarcoma, lymphoma, and rhabdomyosarcoma may show CD34 positivity – but none of these tumors shows positivity for CD31.