多形性平滑肌肉瘤和去分化平滑肌肉瘤的临床病理学分析

Pleomorphic and dedifferentiated leiomyosarcoma： a clinicopathologic analysis

目的探讨多形性平滑肌肉瘤（PLMS）和去分化平滑肌肉瘤（DLMS）的临床病理学特征、鉴别诊断及生物学行为。方法回顾性分析2007年11月至2016年12月复旦大学附属肿瘤医院手术（8例）及会诊病例（41例）共49例PLMS和DLMS患者的临床资料、组织学形态和免疫学表型，其中33例有存档切片可供分析免疫表型，38例有随访资料。结果男性22例，女性27例；发病年龄24～83岁，平均52.5岁。肿瘤位于四肢15例，深部体腔14例，躯干11例，头颈部4例，膀胱2例，腹股沟、会阴部和股静脉各1例。肿瘤直径3～30 cm，平均9.1 cm。镜下观察：PLMS和DLMS具有大致相似的组织学形态，由经典平滑肌肉瘤（LMS）和多形性/未分化肉瘤成分组成，2种成分比例不等（至少局灶可见LMS成分），常相互混杂，亦可突然移行或逐渐过渡。其中，经典LMS成分呈典型平滑肌肿瘤特征，大多分化良好至中等，多形性/未分化肉瘤成分形态类似于未分化多形性肉瘤/恶性纤维组织细胞瘤。免疫组织化学表型方面，经典LMS成分至少表达1种肌源性标志物，多为强阳性，α－平滑肌肌动蛋白（α－SMA）、结蛋白、H－caldesmon、肌特异性肌动蛋白（MSA）和calponin的阳性比例分别为97.0%（32/33）、72.7%（24/33）、90.9%（20/22）、14/16和15/15。在29例（87.9%，29/33）中，多形性肉瘤成分至少表达1种肌源性标志物，多为局灶阳性或阳性强度较经典LMS成分弱：α－SMA、结蛋白、H－caldesmon、MSA和calponin的阳性比例分别为81.8%（27/33）、48.5%（16/33）、72.7%（16/22）、12/16和11/15。根据多形性肉瘤成分是否表达肌源性标志物，29例可归类为PLMS，4例为DLMS。Ki－67阳性指数为15%～70%，平均为40%。38例获得随访资料，11例（28.9%）死于该病，12例带瘤生存，14例无瘤生存，1例死于他因。中位无瘤生存和总生存时间分别为6个月和10个月。12例复发，11例转移，中位肿瘤进展时间为8个月。结论PLMS和DLMS由经典LMS和多形性/未分化肉瘤成分组成，仔细寻找典型LMS成分是其诊断关键。两者较经典LMS具有更强的侵袭性，预后不佳。

ObjectiveTo investigate the clinicopathologic features, differential diagnosis and biological behavior of pleomorphic leiomyosarcoma （PLMS） and dedifferentiated leiomyosarcoma （DLMS）.MethodsForty-nine cases were collected from November 2007 to December 2016, including eight that diagnosed at Fudan University Shanghai Cancer Center, and 41 consultation cases. The clinical findings and pathologic features were reviewed. Immunophenotype was obtained in 33 cases and follow-up information was available in 38 cases.ResultsThere were 22 males and 27 females with ages ranging from 24 to 83 years （mean 52.5 years）. Fifteen cases occurred in extremities, 14 in deep body cavity, 11 in the trunk, 4 in the head and neck, 2 in the bladder, and 1 each in the inguinal region, perineum and femoral vein, respectively. Tumor sizes ranged from 3 to 30 cm （mean 9.1 cm）. The tumors were composed of at least small foci of typical leiomyosarcoma （LMS） and areas of high-grade pleomorphic/undifferentiated sarcoma. The typical LMS component showed the characteristic morphology of smooth muscle differentiation and was low to intermediate grade in most cases. Pleomorphic areas were mainly composed of atypical spindle and polygonal cells admixed with variable large, bizarre atypical cells and multinuclear giant cells, mostly mimicking undifferentiated pleomorphic sarcoma. The pleomorphic and leiomyosarcomatous areas were usually intermixed, but the demarcation may be distinct or gradual in some cases. The classical LMS component was positive for at least one myogenic marker： α-SMA in 97.0%（32/33）, desmin in 72.7%（24/33）, H-caldesmon in 90.9% （20/22）, MSA in 14/16, and calponin in 15/15 of cases. The pleomorphic sarcoma component was reactive for at least one myogenic marker in 87.9% （29/33） of cases, usually showing focal and less intense immunoreactivity than classical LMS component： α-SMA was positive in 81.8%（27/33）, desmin in 48.5%（16/33）, H-caldesmon in 72.7% （16/22）, MSA in 12/16, and calponin in 11/15 of cases. Based on staining for muscle markers in the pleomorphic component, 29 cases were designated as PLMS, 4 as DLMS. Ki-67 index ranged from 15% to 70% （mean 40%）. Follow-up data was available in 38 cases （77.6%）, of which 11 patients （28.9%） died of disease, 12 patients were alive with unresectable or recurrent disease, 14 patients were alive with no evidence of disease and another one died of unrelated cause. The median disease-free and overall survival was 6 and 10 months respectively. Twelve patients exhibited local recurrence and 11 developed metastases. The median interval to progression was 8 months.ConclusionsThe identification of areas of typical LMS is crucial for accurate diagnosis of PLMS and DLMS. Both PLMS and DLMS show more aggressive behavior and poorer prognosis than ordinary LMS.