Bode-Lesniewska B, Zhao J, Speel E J, Biraima A M, Turina M, Komminoth P, Heitz P U
Department of Pathology, University Hospital, Zurich, Switzerland.
Virchows Arch. 2001 Jan;438(1):57-65. doi: 10.1007/s004280000313.
The characterization of clinical, histopathological, immunohistochemical, and genetic features of intimal sarcomas arising in the pulmonary artery is presented in this study. Four resected lungs, one endarterectomy specimen and three biopsies from eight patients (four males and four females; median age 41 years) suffering from intimal sarcomas of the pulmonary artery using conventional stains, immunohistochemistry, and comparative genomic hybridization (CGH) were analyzed. The predominant clinical presentation was dyspnea (all eight patients) and febrile pulmonary disease (six of eight). Signs of embolic lung disease were present in all patients. One patient died postoperatively, six patients died of disease 8-35 months after presentation, and one patient was alive 6 months after surgery. Histopathological examination of the submitted material showed spindle cell, partially myxoid and pleomorphic sarcomas. Metastases were histologically confirmed in three patients (lung, pleura, and skull). Immunohistochemically, vimentin was strongly expressed in all tumors. Focal positivity was observed for alpha smooth muscle actin, CD117, CD68, p53, and bcl2. No reaction could be obtained for endothelial markers. The proliferation index Ki-67 was between 5% and 80%. Six examined tumors were positive for mdm2. In the CGH analysis, gains and amplifications in the 12q13-14 region were found in six of eight tumors (75%). Other, less consistent alterations, were losses on 3p, 3q, 4q, 9p, 11q, 13q, Xp, and Xq, gains on 7p, 17p, and 17q, and amplifications on 4q, 5p, 6p, and 11q. Intimal sarcomas of the pulmonary artery are tumors with an unfavorable prognosis and poorly differentiated morphology. A majority of tumors show a consistent genetic alteration (gains and amplifications in the 12q13-14 region) and overexpression of mdm2, implicating the mdm2/p53 pathway as a possible mechanism in the tumor pathogenesis.
本研究展示了肺动脉内膜肉瘤的临床、组织病理学、免疫组织化学及遗传学特征。对8例（4例男性，4例女性；中位年龄41岁）患有肺动脉内膜肉瘤患者的4个切除肺组织、1个动脉内膜切除术标本及3个活检样本，采用传统染色、免疫组织化学及比较基因组杂交（CGH）技术进行分析。主要临床表现为呼吸困难（8例患者均有）及发热性肺病（8例中的6例）。所有患者均有肺栓塞疾病体征。1例患者术后死亡，6例患者在出现症状后8 - 35个月死于疾病，1例患者术后6个月存活。送检材料的组织病理学检查显示为梭形细胞、部分黏液样及多形性肉瘤。3例患者（肺、胸膜及颅骨）经组织学证实有转移。免疫组织化学方面，波形蛋白在所有肿瘤中均强烈表达。α平滑肌肌动蛋白、CD117、CD68、p53及bcl2呈局灶阳性。内皮标记物无反应。增殖指数Ki - 67在5%至80%之间。6例检测肿瘤mdm2呈阳性。在CGH分析中，8个肿瘤中的6个（75%）在12q13 - 14区域发现有增益和扩增。其他不太一致的改变包括3p、3q、4q、9p、11q、13q、Xp和Xq缺失，7p、17p和17q增益，以及4q、5p、6p和11q扩增。肺动脉内膜肉瘤是预后不良且形态学分化差的肿瘤。大多数肿瘤显示一致的基因改变（12q13 - 14区域增益和扩增）及mdm2过表达，提示mdm2/p53通路可能是肿瘤发病机制中的一种机制。
