Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research (JFCR) and Clinicopathology Center, The Cancer Institute Hospital of JFCR, Tokyo 135-8550, Japan; Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research (JFCR) and Clinicopathology Center, The Cancer Institute Hospital of JFCR, Tokyo 135-8550, Japan.
Pathol Res Pract. 2018 Feb;214(2):318-324. doi: 10.1016/j.prp.2017.10.018. Epub 2017 Nov 12.
Malignancy arising in fibrous dysplasia (FD) is rare. Approximately 100 cases have been reported so far, and osteosarcoma is the most common malignancy. We report a case of osteosarcoma in a 33-year-old Japanese man with monostotic FD of the right proximal femur from the age of 16 years. Histologically, relatively well-differentiated osteosarcoma was found in the FD lesion. Immunohistochemically, the FD was negative for p53 or MDM2, and the MIB-1 index was less than 1%, whereas the osteosarcoma was positive for both p53 and MDM2, and the MIB-1 index was up to 15%. The FD and osteosarcoma were negative for CDK4. Fluorescent in situ hybridization assay showed no amplification of the MDM2 gene, indicating that the osteosarcoma was a conventional osteosarcoma, not an intraosseous well-differentiated type. The original cell of malignancy in FD is unclear. Malignancy can be potentially derived from dysplastic cells in the area of the FD or cells in the adjacent normal tissues. GNAS gene mutation has recently been reported for fibrous dysplasia and the mutation is highly specific to fibrous dysplasia among fibro-osseous lesions including osteosarcoma. In this case, point mutations of GNAS were found in the FD and osteosarcoma but not in the adjacent normal tissues, suggesting that osteosarcoma was derived from the spindle cells of FD. This is the first report to clearly show that osteosarcoma is derived from the spindle cells in fibrous dysplasia (FD).
纤维结构不良（FD）中发生的恶性肿瘤很少见。迄今为止，已有约 100 例报告，其中骨肉瘤最为常见。我们报告了一例 33 岁日本男性的病例，他在 16 岁时患有右股骨近端单发性 FD，组织学上发现 FD 病变中存在分化相对较好的骨肉瘤。免疫组化染色显示，FD 中 p53 或 MDM2 阴性，MIB-1 指数小于 1%，而骨肉瘤中 p53 和 MDM2 均阳性，MIB-1 指数高达 15%。FD 和骨肉瘤均为 CDK4 阴性。荧光原位杂交检测显示 MDM2 基因无扩增，表明骨肉瘤为常规骨肉瘤，而非骨内高分化型。FD 中恶性肿瘤的原始细胞尚不清楚。恶性肿瘤可能来源于 FD 区域的发育不良细胞或邻近正常组织中的细胞。最近在纤维结构不良中报道了 GNAS 基因突变，该突变在包括骨肉瘤在内的纤维骨性病变中高度特异性地存在于纤维结构不良中。在该病例中，FD 和骨肉瘤中发现了 GNAS 的点突变，但在相邻的正常组织中未发现，提示骨肉瘤来源于 FD 的梭形细胞。这是第一个明确表明骨肉瘤来源于纤维结构不良（FD）中的梭形细胞的报告。
