Mesenchymal Chondrosarcoma

Staging is according to bone sarcoma protocols (see TNM staging of tumors of bone). See also the information on staging in section Bone tumors: Introduction.

A highly specific recurrent gene fusion between HEY1 and NCOA2 occurs in almost all mesenchymal chondrosarcomas. Mesenchymal chondrosarcomas are thought to arise from early, immature cartilage cells (chondroblasts), which differentiate into well-differentiated hyaline cartilage and then often undergo endochondral ossification to bone. The cartilage-to-bone production in this region involves the WNT/β-catenin pathway.

The tumors are variably grey/white/pink, firm to soft, and usually circumscribed masses, 0.9–30 cm in maximum diameter. Most lesions contain hard mineralized deposits that vary from dispersed foci to prominent areas; often either the cartilaginous component or the sheeted round cell component with necrosis and hemorrhage may predominate.

Mesenchymal chondrosarcoma is composed of small to medium-sized, poorly differentiated round cells with a high N:C ratio and a characteristic staghorn or pericytoid vascular pattern, admixed with various proportions of islands of well-differentiated hyaline cartilage. Spindle cell morphology can be present. In areas, the matrix may mimic osteoid deposition.

There is a biphasic appearance of medium-sized cells, oval to spindled in CNS tumors, that have a high N:C ratio and basophilic extracellular matrix.

Mesenchymal chondrosarcoma is an aggressive neoplasm, with estimated overall 5-year and 10-year survival rates (which range from study to study) as high as 60% and 40%, respectively. Distant metastases are occasionally observed even after a delay of > 20 years. The clinical course is frequently protracted and relentless, requiring long-term follow-up. There are no histological features correlative with prognosis. The presence of metastatic disease at initial presentation, tumor size, and (to a lesser degree) original site of the tumor, have been demonstrated to have an impact on survival in mesenchymal chondrosarcoma. Children, adolescents, and young adults tend to have a slightly better outcome. Craniofacial origin appears to be associated with a more indolent course and favorable prognosis, whereas axial origin has worse outcome. Complete resection combined with chemotherapy should be considered the standard of care.

Mesenchymal chondrosarcoma harbors a recurrent HEY1-NCOA2 rearrangement, representing an in-frame fusion of HEY1 exon 4 to NCOA2 exon 13 at the mRNA level. This fusion is detected in almost all well-characterized mesenchymal chondrosarcomas tested, and it is absent in other subtypes of chondrosarcomas. Given that HEY1 and NCOA2 are only approximately 10 Mb apart on chromosome 8, mapping to 8q21.13 and 8q13.3, respectively, and that both are in the same orientation, this fusion may arise via a small interstitial deletion, del(8)(q13.3q21.1), which is difficult to detect in most conventional cytogenetic preparations. The consistent molecular detection of the HEY1-NCOA2 fusion in this sarcoma establishes it as a defining molecular diagnostic marker.

Essential: undifferentiated tumor cells with a high N:C ratio; islands of cartilage.

Desirable: staghorn vascular pattern; HEY1-NCOA2 fusion.