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阴茎肉瘤样癌:15例临床病理研究

Sarcomatoid carcinoma of the penis: a clinicopathologic study of 15 cases.

作者信息

Velazquez Elsa F, Melamed Jonathan, Barreto Jose E, Aguero Fatima, Cubilla Antonio L

机构信息

Department of Dermatology, New York University Medical Center, New York, NY 10016, USA.

出版信息

Am J Surg Pathol. 2005 Sep;29(9):1152-8. doi: 10.1097/01.pas.0000160440.46394.a8.

DOI:10.1097/01.pas.0000160440.46394.a8
PMID:16096403
Abstract

Sarcomatoid carcinomas are uncommon, high-grade tumors, predominantly composed of spindle cells. Only a few cases arising in the penis have been reported. The aim of this study is to better define the clinicopathologic features of this neoplasm. A total of 400 cases of squamous cell carcinoma of the penis were reviewed from which 15 sarcomatoid carcinomas (4%) were identified. Clinical and pathologic features were evaluated in all cases. Immunohistochemical studies for expression of AE1/AE3, Cam 5.2, 34betaE12, EMA, vimentin, muscle specific actin, smooth muscle actin, desmin, S-100, p63, and p53 and in situ hybridization studies for HPV were performed in 5 cases. Information about lymph node status was available in 9 cases, and follow-up in 5 cases. The mean age was 59 years, and mean tumor size was 5 cm. Grossly, most tumors were large, polypoid, and ulcerated masses frequently affecting the glans (93%) and deeply invading corpora cavernosa (80%) and skin. Microscopically, the lesions were predominantly composed of atypical spindle cells disposed in interlacing fascicles, resembling fibrosarcoma or leiomyosarcoma, sometimes admixed with pleomorphic giant cells mimicking malignant fibrous histiocytoma. One case was predominantly composed of myxoid areas. Less frequent and focal patterns were pseudoangiomatous and epithelioid. Mitotic figures were numerous, and necrosis was prominent. Foci of heterologous differentiation toward bone (osteosarcomatous component) were present in 1 case. Four cases showed a minor mixed component of usual, papillary, verrucous, and basaloid carcinoma. Intrapenile metastasis ("satellitosis") was present in 4 tumors. One of the cases was multicentric with a separate independent focus of well-differentiated carcinoma with pseudohyperplastic features. Associated low- and high-grade squamous intraepithelial lesions were noted in 73% of the cases. Immunohistochemical studies and HPV in situ hybridization were done in 5 cases. The spindle cells were diffusely positive for vimentin and p53 and showed at least intermediate expression of 34betaE12 and p63 in all cases. EMA and AE1/AE3 were focally positive in 60% of the cases, and Cam 5.2 was focally positive in 1 case. Tumor cells failed to express muscle specific actin, smooth muscle actin, desmin, and S-100. HPV in situ hybridization was negative in all cases. Inguinal metastases were present in 89% of the cases. Two of five patients with adequate follow-up died of disease within 8 months of the diagnoses. In conclusion, penile sarcomatoid carcinomas are unusual, large, and aggressive tumors usually associated with lymph node metastasis and poor outcome. Differential diagnoses include sarcoma and melanoma. Cytokeratin 34betaE12 and p63 appear to be the more specific and sensitive markers to categorize these tumors as epithelial. Diffuse immunoreactivity for p53, compared with a more basal and focal reactivity in differentiated squamous cell carcinoma, may be indicative of a late mutation in the natural progression of the disease.

摘要

肉瘤样癌是一种罕见的高级别肿瘤,主要由梭形细胞组成。阴茎发生的此类病例仅有少数报道。本研究的目的是更好地明确该肿瘤的临床病理特征。我们回顾了400例阴茎鳞状细胞癌病例,从中识别出15例肉瘤样癌(4%)。对所有病例的临床和病理特征进行了评估。对5例病例进行了免疫组织化学研究,检测AE1/AE3、Cam 5.2、34βE12、EMA、波形蛋白、肌特异性肌动蛋白、平滑肌肌动蛋白、结蛋白、S-100、p63和p53的表达,并进行了HPV原位杂交研究。9例病例有淋巴结状态信息,5例有随访信息。平均年龄为59岁,平均肿瘤大小为5厘米。大体上,大多数肿瘤为大的、息肉样且溃疡的肿块,常累及龟头(93%),并深度侵犯海绵体(80%)和皮肤。显微镜下,病变主要由排列成交错束状的非典型梭形细胞组成,类似纤维肉瘤或平滑肌肉瘤,有时混有类似恶性纤维组织细胞瘤的多形性巨细胞。1例主要由黏液样区域组成。较少见且局灶性的模式为假血管瘤样和上皮样。有大量核分裂象,坏死明显。1例出现向骨的异源性分化(骨肉瘤成分)。4例显示有少量常见型、乳头状、疣状和基底样癌的混合成分。4个肿瘤存在阴茎内转移(“卫星灶”)。其中1例为多中心性,有一个具有假增生特征的高分化癌独立灶。73%的病例伴有低级别和高级别鳞状上皮内病变。对5例病例进行了免疫组织化学研究和HPV原位杂交。梭形细胞波形蛋白和p53弥漫性阳性,所有病例中34βE12和p63至少呈中等表达。60%的病例中EMA和AE1/AE3局灶性阳性,1例Cam 5.2局灶性阳性。肿瘤细胞不表达肌特异性肌动蛋白、平滑肌肌动蛋白、结蛋白和S-100。所有病例HPV原位杂交均为阴性。89%的病例有腹股沟转移。5例随访充分的患者中有2例在诊断后8个月内死于该病。总之,阴茎肉瘤样癌是不常见的、体积大且侵袭性强的肿瘤,通常伴有淋巴结转移且预后不良。鉴别诊断包括肉瘤和黑色素瘤。细胞角蛋白34βE12和p63似乎是将这些肿瘤归类为上皮性肿瘤更具特异性和敏感性的标志物。与分化型鳞状细胞癌中更位于基底且局灶性的反应性相比,p53的弥漫性免疫反应性可能表明疾病自然进展中的晚期突变。

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