Bovée J V, van Roggen J F, Cleton-Jansen A M, Taminiau A H, van der Woude H J, Hogendoorn P C
Department of Pathology, Leiden University Medical Center, The Netherlands.
Hum Pathol. 2000 Oct;31(10):1299-303. doi: 10.1053/hupa.2000.19308.
Multiple enchondromatosis (Ollier's disease) is a nonhereditary disease characterized by multiple central (medullary) cartilaginous bone tumors of unknown pathogenesis. It usually involves the extremities with a unilateral predominance, and sarcomatous transformation may occur. We report an autopsy-based genetic study of a 34-year-old man presenting in early adolescence with multiple enchondromas of the extremities, predominantly left-sided, compatible with Ollier's disease. Twelve years after presentation, malignant transformation to a high grade chondrosarcoma occurred in a tibial enchondroma. The patient died after widespread metastatic disease. Loss of heterozygosity (LOH), in the tibial chondrosarcoma and its metastases, was identified exclusively on chromosome bands 13q14 and 9p21, while being absent in the femoral enchondroma analyzed. Similarly, p53 overexpression was identified immunohistochemically in the tibial chondrosarcoma and its metastases, while being absent in the femoral enchondroma; LOH at 17p13 however, was not demonstrable. It is hypothesized that inactivation of putative tumor suppressor genes at 9p21 and 13q14, and overexpression of p53, identified in the chondrosarcoma and its metastases, but absent in enchondroma, may be related to sarcomatous transformation in Ollier's disease.
多发性内生软骨瘤病（Ollier病）是一种非遗传性疾病，其特征为多个中央（髓内）软骨性骨肿瘤，发病机制不明。它通常累及四肢，以单侧为主，可能发生肉瘤样变。我们报告了一项基于尸检的遗传学研究，对象为一名34岁男性，青春期早期出现四肢多发性内生软骨瘤，主要位于左侧，符合Ollier病。发病12年后，胫骨内生软骨瘤发生恶性转变为高级别软骨肉瘤。患者在发生广泛转移后死亡。在胫骨软骨肉瘤及其转移灶中，仅在染色体带13q14和9p21上发现杂合性缺失（LOH），而在分析的股骨内生软骨瘤中未发现。同样，在胫骨软骨肉瘤及其转移灶中通过免疫组化鉴定出p53过表达，而在股骨内生软骨瘤中未发现；然而，在17p13处未检测到LOH。据推测，在软骨肉瘤及其转移灶中鉴定出但在内生软骨瘤中未发现的9p21和13q14处假定肿瘤抑制基因的失活以及p53的过表达，可能与Ollier病中的肉瘤样变有关。
