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

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma characterized by NR4A3 gene rearrangements and a specific histological pattern.
• A recognized cellular variant of EMC exhibits increased cellularity and a solid growth pattern.

Purpose of the Study:

• To describe a distinct round cell subtype of extraskeletal myxoid chondrosarcoma.
• To differentiate this subtype from the traditional cellular variant and other round cell sarcomas.
• To highlight the diagnostic implications, including the role of molecular testing.

Main Methods:

• Retrospective review of institutional files over 22 years, focusing on cellular myxoid chondrosarcoma cases.
• Histological slide and clinical data review.
• Next-generation sequencing for gene rearrangement analysis (NR4A3, NR4A2).

Main Results:

• Identified three unique cases of a round cell subtype of EMC, distinct from 43 previously identified cellular EMC cases.
• These tumors showed a sheet-like proliferation of large, uniform round-to-epithelioid cells with high-grade nuclear atypia and brisk mitotic activity.
• Molecular testing revealed TCF12::NR4A3, EWSR1::NR4A3, and EWSR1::NR4A2 fusions; one patient developed metastases.

Conclusions:

• Described a novel round cell subtype of EMC characterized by uniform round-to-epithelioid cells and absence of chondromyxoid stroma.
• This subtype is distinct from the traditional cellular variant and requires molecular testing for accurate diagnosis.
• The identification of NR4A2 fusions broadens the genetic landscape of EMC, indicating that NR4A3 rearrangements are not always present.