骨软骨瘤继发肉瘤变临床病理分析

Clinicopathologic features of osteochondroma with malignant transformation

目的分析骨软骨瘤继发肉瘤变的临床、影像学、组织病理学和免疫表型特征。方法回顾上海交通大学附属第六人民医院1991—2008年间诊断的骨软骨瘤463例，其中单发性408例，多发性55例；重点分析11例骨软骨瘤继发肉瘤变病例的临床、影像学和组织学形态特点；采用免疫组织化学EnVision二步法检测7例骨软骨瘤肉瘤变组织及10例未发生肉瘤变组织中CK、波形蛋白、S-100蛋白、p53及c—mye蛋白表达。结果11例骨软骨瘤恶变病例其中5例为单发性（单发性恶变率1．2％），6例为多发性（多发性恶变率10．9％）。男女比例为10：1。肉瘤变的部位分别是股骨4例，胫骨3例，肱骨1例，髂骨3例，耻骨1例，其中1例是髂骨和股骨联合病变。肉瘤变患者平均就诊年龄39．8岁，未肉瘤变骨软骨瘤平均就诊年龄20．4岁。肿瘤在骨表面结节状生长，体积巨大，边界不清，软骨帽厚度〉1．5cm，有广泛钙化。恶变成分为周围型软骨肉瘤Ⅰ～Ⅱ级，肿瘤细胞侵及周围软组织，偶可累及髓腔。免疫组织化学标记结果显示肿瘤细胞表达波形蛋白和S-100蛋白。p53阳性表达见于其中2例肉瘤变的病例（2／7），未发生肉瘤变的病例未检测到p53阳性表达。结论骨软骨瘤肉瘤变大多继发于多发性病例，发病年龄通常在30岁以后，有明显的男性发病优势，临床病史长，肿瘤体积巨大，软骨帽厚，钙化明显，结节状生长浸润周围软组织。恶变成分主要是周围型高分化软骨肉瘤，预后较好。p53基因突变可能是恶变的分子机制之一。

Objective To investigate the clinicopathologic, radiological and immunohistochemical characteristics of osteoehondroma with malignant transformation. Methods The clinical data, radiological imagings and hematoxylineosin stained histologie sections were reviewed in 463 cases of osteochondroma diagnosed in Shanghai 6th Hospital from 1991 to 2008, including 11 cases with malignant transformation. Immunohistochemical two-step staining was used to detect CK, vimentin, S-100 protein, p53 and c-myc expression in seven cases of osteochondroma with malignant transformation and 10 cases without malignant transformation. The relevant literature was reviewed. Results Among the 11 cases with malignant transformation, five were single osteochondroma （5/408,1.2%）, and six were multiple osteochondromas （6/55,10. 9% ）. The male to female ratio was 10： 1. These 11 cases were derived from femur （4 cases） , tibia （3 cases）, ilium （3 cases） , shoulder bone （1 case） and pubis （1 case）. There was one case that showed malignant transformation in both the femur and ilium. The mean ages for the malignant and nonmalignant cases were 39.8 years and 20.4 years respectively. All the malignant cases showed large sized lesions with prominent calcification in the thick cartilage caps. The malignant component was low grade, peripheral chondrosarcoma （ grade Ⅰ - Ⅱ ）. In some areas the tumor cells infiltrated the peripheral soft tissue and bone marrow. Of the seven cases with malignant transformation that had immunohistochemieal staining, all were positive for vimentin and S-100 protein; p53 protein was positive in 2 of 7 cases. Conclusions Malignant transformation of osteochondroma was usually encountered in multiple lesions. Most patients were more than 30 years old with a long clinical history and with a male predominance. These tumors showed thick cartilage caps with prominent calcification. The lobulated nature of the tumors was evident and they infiltrated the surrounding soft tissue. The sarcomatoid component was peripheral type, well differentiated chondrosarcoma, p53 mutation may explain part of the molecular mechanism in the malignant transformation.