Non-myxoid solid variant of extraskeletal myxoid chondrosarcoma: An underrecognized subtype

Abstract

Introduction

Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma defined by NR4A3 gene rearrangements, typically featuring uniform cells with eosinophilic cytoplasm and mild atypia, arranged in cords or clusters within a chondromyxoid stroma. A cellular variant, characterized by increased cellular density and a solid growth pattern, has been recognized.

Methods

We encountered three cases of round cell sarcomas, diagnosed as EMC based on NR4A3 or NR4A2 rearrangements. To identify additional pure solid EMC cases, we performed a retrospective review of our institutional files spanning 22 years, focusing on cases labeled as "myxoid chondrosarcoma" with "cellular" features. Histologic slides and clinical data were reviewed.

Results

In addition to the three study cases, 43 cases of EMC with cellular features were identified, none of which exhibited the exclusive round-to-spindle cell morphology seen in the study cases. The three unique cases involved two females and one male (ages 42–62) with tumors in the proximal extremities and trunk. The tumors (3.5–10 cm) were well-circumscribed and densely cellular. One tumor exhibited a biphasic pattern with distinct round and spindle cell areas, whereas the other two were composed purely of round/epithelioid cells. High-grade nuclear atypia and brisk mitotic activity (9–13 per 10 HPFs) were observed, with necrosis identified in one case. Next-generation sequencing revealed TCF12::NR4A3, EWSR1::NR4A3, and EWSR1::NR4A2 fusions. Two patients developed metastases (lymph nodes and lungs), whereas one remained disease-free at last follow-up.

Conclusion

We describe a round cell subtype of EMC, distinct from the traditional cellular variant, characterized by a sheet-like proliferation of large, uniform round-to-epithelioid cells and the absence of chondromyxoid stroma. This potentially underrecognized subtype requires molecular testing for accurate diagnosis. Moreover, the presence of NR4A2 fusions, although rare, suggests that the absence of NR4A3 rearrangements does not entirely exclude EMC.