EWSR1-family tumors and tumors of uncertain lineage

Question 1

Answer 1

Angiomatoid fibrous histiocytoma

Usually a subcutaneous tumor, but can occur essentially anywhere in the body. This is a tumor of intermediate malignant potential, with some cases showing local recurrence and regional metastasis, however distant metastases are very rare.

Characteristic architecture: Often a central, bloody, cystic space surrounded by sheets of histiocytoid tumor cells and then by a peripheral lymphoplasmacytic cuff.

Cytologically, cells are bland and histiocytoid. They may organize into short fascicles, whorls, form a sheet-like morphology, or be separated on a slightly myxoid/edematous background. The cystic space is actually lined by flattened tumor cells.

Characterized by fusions involving EWSR-family genes, most often EWSR1::CREB1, but may include EWSR1/FUS::CREB1/ATF1/CREM.

Most IHC is only positive in about 50% of cases: desmin, CD68, CD99, EMA.
The most sensitive IHC is SOX9, which is positive in 85% of cases.