Angiomatoid Fibrous Histiocytoma

Not clinically relevant

The most frequent genetic abnormality is the t(2;22)(q33;q12) translocation, resulting in an EWSR1-CREB1 fusion, in > 90% of cases. Less commonly, t(12;22)(q12;q12) translocation is detected, resulting in an EWSR1-ATF1 fusion. Few cases harboring a FUS-ATF1 fusion have been reported. EWSR1-ATF1 is more frequently associated with AFH of extrasomatic soft tissues. EWSR1–CREB family gene fusions have been recently reported in a subset of intracranial myxoid mesenchymal tumors that lack features typical of AFH, and thus it remains uncertain whether these represent a myxoid subtype of AFH or a novel entity.

These tumors appear as small, firm, nodular to cystic masses, with a wide size range (0.7–12 cm) and a median size of 2 cm. The cut surface often shows multilocular hemorrhagic areas, simulating a hematoma, to a yellowish-tan or white fleshy appearance.

Tumors are circumscribed, lobulated, and characterized by four key morphological components, found in varying proportions: (1) solid nodules of epithelioid to spindle cells arranged in a syncytial pattern with moderate amounts of eosinophilic cytoplasm and mildly atypical vesicular nuclei; (2) pseudoangiomatous spaces containing blood and surrounded by tumor cells; (3) a thick fibrous pseudocapsule with hemosiderin deposition; and (4) a pericapsular rim of lymphoplasmacytic cells with germinal centers, simulating lymph node metastasis. Nearly one-third of tumors lack cystic hemorrhagic spaces and show a completely solid appearance. Some cases lack any inflammatory component. Mitotic figures are generally few, although atypical mitotic figures may be present. A variable number of pleomorphic cells may be noted in some cases. A subtype of AFH is characterized by small blue round cells with hyperchromatic nuclei and scant eosinophilic cytoplasm, which can mimic an undifferentiated round cell sarcoma or epithelioid sarcoma. Myxoid forms have also been described, containing at least focal components of classic AFH.

Approximately 50% of cases are immunoreactive for desmin, which may be focal or diffuse. However, tumor cells are consistently negative for MYOD1 and myogenin. EMA, CD99, and CD68 are variably immunopositive in as many as 50% of cases.

The cytomorphological features of AFH are non-distinctive. Cellular smears show ovoid to spindled cells with moderate nuclear pleomorphism, arranged in loose clusters, containing moderate to abundant cytoplasm. Interspersed are blood products and a variable number of inflammatory cells.

Most tumors follow an indolent course, with local recurrence in nearly 15% of cases and metastasis in < 2–5% of cases, predominantly to locoregional lymph nodes and rarely to lungs, liver, and brain. Rare deaths have been reported from metastasis, although long-term survival after resection is reported in some metastatic cases. There are no clinicopathological factors that correlate reliably with clinical outcome. However, cases with incomplete surgical clearance and those occurring in deeper locations and extrasomatic sites have been observed to show higher rates of recurrence and metastasis.

The presence of EWSR1-CREB1 or alternative gene fusions can be diagnostically helpful.

Essential: clinical presentation as a small subcutaneous painless nodule; nodules of epithelioid to ovoid cells arranged in syncytial-like sheets; pseudoangiomatoid spaces; peripheral rims of lymphoplasmacytic cells, including germinal centers; immunohistochemistry: variable desmin, CD99, and EMA immunoreactivity.

Desirable (in selected cases): molecular studies confirming EWSR1 gene rearrangement.