CNS and MSK Mesenchymal Chondrosarcoma: A Malignant Cartilage Tumor with Metaplastic Hyaline Cartilage that Recapitulates Growth Plate Endochondral Ossification
JC Fanburg-Smith, A Auerbach, JS Marwaha, Z Wang, EJ Rushing. Armed Forces Institute of Pathology, Washington, DC
Background: Mesenchymal chondrosarcoma (MCHSA), a rare malignant biphasic round cell and hyaline cartilage tumor, is most commonly musculoskeletal (MSK), but can occur in central nervous system (CNS). Sox9, a master regulator of chondrogenesis, was previously demonstrated by IHC in intraosseous MCHSA and conventional CHSA. Nuclear beta-catenin, involved in the Wnt/APC pathway, has been observed by IHC in CHSA, but not MCHSA. Osteocalcin (OC), a non-collagenous bone protein, was identified by IHC in osteosarcoma cells and matrix.
Design: Morphology and IHC and follow-up on MSK and CNS MCHSA and control cases from our files were obtained and studied.
Results: 22 MCHSA included 5 CNS (all female, mean age 30.2, mean size 7.8 cm, in frontal lobe (n=4) and spinal cord (n=1)) and 17 MSK (11F:6M, mean age 31.1, mean size 6.2 cm, 3 each of humerus and vertebrae, 2 each of pelvis, rib, tibia, neck soft tissue, one each of femur, unspecified bone, elbow soft tissue). CNS and MSK MCHSA had similar round cells, staghorn vasculature, increased mitotic activity, and centrally located metaplastic cartilage islands, in a zonal pattern from immature to proliferating to hypertrophic chondrocytes, then exhibiting cell death; 67% had central endochondral ossification (cells and matrix positive for OC). SOX9 reacted in 21/22 (95%) MCHSA in round cells and cartilage island chondrocytes. Beta-catenin highlighted cells adjacent to cartilage matrix in 35%. Round cells were 100% INI positive and 50% focal desmin and rare S100 and EMA positive, but negative for MyoD1, keratins, SMA, lymphoid markers, CD34, CD99, GFAP, ER, PR, and OC. Control small cell OSA were positive for OC, negative for SOX9. 80% patients with follow-up had pulmonary metastases and/or died within a mean of 5 years.
Conclusions: CNS and MSK MCHSA predominantly affect adult females with poor prognosis. Centrally, MCHSA forms hyaline cartilage that undergoes endochondral ossification, a metaplastic recapitulation of growth plate cartilage. Sox9 positivity supports cartilage phenotype. OC demonstrates bone cells and matrix resulting from endochondral ossification in central cartilage islands and is negative in round tumor cells, separating MCHSA from small cell osteosarcoma. Focal nuclear beta-catenin adjacent to cartilage supports the role of beta-catenin in chondrogenesis in MCHSA. SOX9 and OC and morphologic detail can separate MCHSA from other MSK and CNS round cell tumors.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 9, Monday Afternoon