Maxillary mesenchymal chondrosarcoma harboring HEY1::NCOA2 fusion in a 13-year-old girl: a rare case report and literature review

TL;DR

A rare case of maxillary mesenchymal chondrosarcoma in a 13-year-old girl is reported, diagnosed using HEY1::NCOA2 fusion and treated with a multimodal approach including sirolimus.

Contribution

This is one of the few reported pediatric cases of maxillary MCS with confirmed HEY1::NCOA2 fusion and sirolimus-based therapy.

Findings

HEY1::NCOA2 gene fusion confirmed diagnosis of mesenchymal chondrosarcoma in a pediatric patient.

Multimodal treatment including chemotherapy, radiotherapy, and sirolimus showed partial metabolic response.

Molecular diagnostics, particularly RNA sequencing, are crucial for accurate diagnosis and targeted therapy.

Abstract

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive subtype of chondrosarcoma, accounting for less than 1% of all chondrosarcomas. It predominantly affects adolescents and young adults and frequently arises in craniofacial bones and soft tissues. Diagnosis is challenging because of significant histological overlap with other high-grade spindle cell sarcomas, particularly when the cartilaginous component is minimal or absent. The identification of the HEY1::NCOA2 gene fusion has emerged as a highly specific molecular marker for MCS, substantially improving diagnostic accuracy and providing potential therapeutic implications.

We report the case of a 13-year-old girl who presented with a 3-month history of progressive right cheek swelling. Imaging revealed a destructive mass in the right maxillary sinus. Histopathological evaluation demonstrated a high-grade spindle cell tumor, initially interpreted as fibrosarcoma, showing diffuse vimentin positivity, a high Ki-67 proliferation index (35%–40%), and CD34 negativity. Comprehensive molecular analysis confirmed a pathogenic HEY1::NCOA2 gene fusion, while ETV6::NTRK3 fusion was excluded. The patient was treated with VAC chemotherapy (vincristine, actinomycin D, cyclophosphamide), local radiotherapy (60 Gy), cranial prophylactic radiotherapy (12 Gy), and subsequent debulking surgery. Follow-up 18F-FDG PET/CT demonstrated a partial metabolic response. Given persistent disease and molecular evidence suggesting activation of the PI3K/AKT/mTOR pathway in MCS, maintenance therapy with the mTOR inhibitor sirolimus was initiated.

This case highlights the pivotal role of molecular diagnostics—particularly RNA sequencing—in establishing the diagnosis of mesenchymal chondrosarcoma and differentiating it from other high-grade pediatric sarcomas with overlapping morphology. Identification of the HEY1::NCOA2 fusion not only confirms the diagnosis but may also support biologically targeted therapeutic strategies. Multimodal treatment incorporating chemotherapy, radiotherapy, surgery, and targeted maintenance therapy can achieve meaningful disease control in aggressive craniofacial MCS. To our knowledge, this represents one of the very few reported pediatric cases of maxillary MCS with confirmed HEY1::NCOA2 fusion managed with sirolimus-based maintenance therapy.

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