Department of Orthopedic and Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Hum Pathol. 2010 May;41(5):653-62. doi: 10.1016/j.humpath.2009.11.006.
Mesenchymal chondrosarcoma, a rare malignant round cell and hyaline cartilage tumor, is most commonly intraosseous but can occur in extraskeletal sites. We intensively observed the morphology and applied Sox9 (master regulator of chondrogenesis), beta-catenin (involved in bone formation, thought to inhibit chondrogenesis in a Sox9-dependent manner), and osteocalcin (a marker for osteoblastic phenotype) to 22 central nervous system and musculoskeletal mesenchymal chondrosarcoma. Cases of mesenchymal chondrosarcoma were retrieved and reviewed from our files. Immunohistochemistry and follow-up were obtained on mesenchymal chondrosarcoma and tumor controls. Twenty-two mesenchymal chondrosarcomas included 5 central nervous system (all female; mean age, 30.2; mean size, 7.8 cm; in frontal lobe [n = 4] and spinal cord [n = 1]) and 17 musculoskeletal (female-male ratio, 11:6; 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, and elbow soft tissue). The hyaline cartilage in most tumors revealed a consistent linear progression of chondrocyte morphology, from resting to proliferating to hypertrophic chondrocytes. Sixty-seven percent of cases demonstrated cell death and acquired osteoblastic phenotype, cells positive for osteocalcin at the site of endochondral ossification. Small round cells of mesenchymal chondrosarcoma were negative for osteocalcin. SOX9 was positive in both components of 21 of 22 cases of mesenchymal chondrosarcoma. beta-Catenin highlighted rare nuclei at the interface between round cells and hyaline cartilage in 35% cases. Control skull and central nervous system cases were compared, including chondrosarcomas and small cell osteosarcoma, the latter positive for osteocalcin in small cells. Mesenchymal chondrosarcoma demonstrates centrally located hyaline cartilage with a linear progression of chondrocytes from resting to proliferative to hypertrophic, which undergoes endochondral ossification, recapitulating growth plate cartilage and suggesting that this component of mesenchymal chondrosarcoma may be a differentiated (benign or metaplastic) component of a malignant metastasizing tumor. This hyaline cartilage component is morphologically different from cartilage of control chondrosarcoma. Mesenchymal chondrosarcoma can be separated from small cell osteosarcoma, using Sox 9 for cartilage and osteocalcin for osteoblastic phenotype. Rare nuclear beta-catenin expression at the interface between hyaline cartilage and small round cells potentially implicates the APC/Wnt pathway during endochondral ossification in morphologically benign hyaline cartilage component of mesenchymal chondrosarcoma.
间叶性软骨肉瘤，一种罕见的恶性圆形细胞和透明软骨肿瘤，最常见于骨内，但也可发生于骨骼外部位。我们对 22 例中枢神经系统和肌肉骨骼间叶性软骨肉瘤进行了形态学观察，并应用 Sox9（软骨发生的主要调节因子）、β-连环蛋白（参与骨形成，被认为以 Sox9 依赖的方式抑制软骨发生）和骨钙素（成骨细胞表型的标志物）进行检测。从我们的档案中检索并回顾了间叶性软骨肉瘤病例。对间叶性软骨肉瘤和肿瘤对照进行了免疫组织化学和随访。22 例间叶性软骨肉瘤包括 5 例中枢神经系统（均为女性；平均年龄 30.2 岁；平均大小 7.8cm；额叶 4 例，脊髓 1 例）和 17 例肌肉骨骼（女性与男性比例为 11:6；平均年龄 31.1 岁；平均大小 6.2cm；肱骨和椎体各 3 例，骨盆、肋骨、胫骨、颈部软组织各 2 例，股骨、未特指骨和肘部软组织各 1 例）。大多数肿瘤中的透明软骨显示出从静止期到增殖期到肥大期软骨细胞形态的一致线性进展。67%的病例表现出细胞死亡和获得成骨细胞表型，在软骨内成骨的部位，细胞对骨钙素呈阳性。间叶性软骨肉瘤的小圆细胞对骨钙素呈阴性。22 例间叶性软骨肉瘤中有 21 例 Sox9 在两种成分中均呈阳性。β-连环蛋白在 35%的病例中突出显示了小圆细胞和透明软骨之间罕见的核。对包括软骨肉瘤和小细胞骨肉瘤在内的颅骨和中枢神经系统对照病例进行了比较，后者的小细胞对骨钙素呈阳性。间叶性软骨肉瘤显示中心位于透明软骨，软骨细胞从静止期到增殖期到肥大期呈线性进展，经历软骨内成骨，再现生长板软骨，并提示间叶性软骨肉瘤的这种成分可能是一种具有恶性转移潜能的分化（良性或化生）成分。这种透明软骨成分在形态上与对照软骨肉瘤的软骨不同。间叶性软骨肉瘤可以通过 Sox9 用于软骨和骨钙素用于成骨细胞表型来与小细胞骨肉瘤区分开来。在形态学良性透明软骨成分中，β-连环蛋白在透明软骨和小圆细胞之间的界面上的罕见核表达，可能暗示 APC/Wnt 通路在软骨内成骨过程中的作用。
