多房囊性肾细胞癌的临床分析及其与von Hippel—Lindau基因突变的相关性研究

A clinical analysis of multilocular cystic renal cell carcinoma and its correlation with mutation of the von Hippel-Lindau gene

目的提高对多房囊性肾细胞癌（MCRCC）的认识及诊治水平，分析MCRCC中von Hippel—Lindau（VHL）基因的作用。方法回顾性分析2000—2010年17例MCRCC患者资料，占同期收治512例肾癌的3．32％。男11例，女6例。年龄37～61岁，平均46岁。术前常规行B超、CT等检查，误诊为肾盂旁囊肿1例。应用PCR、PCR产物直接测序等方法分析11例MCRCC组织和相应远离病灶的正常组织中VHL基因突变的情况。结果17例患者行根治性肾切除术14例，其中1例先行囊肿去顶术，术中囊壁组织冰冻病理检查提示透明细胞癌，改行根治性肾切除术；行肾部分切除术3例。肿瘤直径2．2～6．0cm，平均（3．6±1．2）cm。术后病理均为MCRCC，镜下主要表现为纤维囊壁组织内衬单层或数层肿瘤细胞，核小致密，胞质透亮。TNM分期均为T1N0M0，病理分级G1 14例，G2 3例。术后随访9～36个月，平均12个月，均未见复发及转移。11例MCRCC组织中7例（64％）存在VHL基因突变，而正常组织标本均未发现VHL基因突变。结论MCRCC作为肾细胞癌的一种少见的独立亚型，病理及临床上易漏诊或误诊。CT等影像学检查有助于术前诊断，因其预后良好，手术方式推荐保留肾单位手术。VHL基因突变与MCRCC的发生存在一定关系。

Objective To discuss the diagnosis and surgical management of multilocular cystic renal cell carcinoma （MCRCC） and to evaluate the gene function of the mutation of von Hippel-Lindau （VHL） gene in MCRCC. Methods Seventeen MCRCC cases （ 11 men and 6 women） out of 512 cases of renal cell carcinoma from 2000 to 2010 were retrospectively analyzed. The mean age of the 17 patients was 46 years （37 -61 years）. Ultrasonography and CT were available in all 17 cases, and 1 case was misdiagnosed as parapelvic renal cyst. The mutation of VHL gene was detected by PCR in the specimens of cancerous tissue and adjacent normal tissue from 11 cases of MCRCC. Results Three of 17 cases underwent nephron sparing surgery, the others underwent radical nephrectomy. One case underwent unroofing of parapelvic renal cyst, but the rapid frozen pathology of the cyst wall showed renal cell carcinoma of clear type. As a result, radical nephrectomy was eventually performed. All 17- cases were confirmed as MCRCC by evaluating pathological characteristics, such as the cyst wall lined by single or several layers of clear tumor cells and the nuclei which were small and anachromasis. Clinical stages of all cases were Tl NoM0, in which there were 14 cases with pathological T1 G1 and 3 cases with pathological T1 G2. All patients underwent a follow-up of 9 to 36 months （mean, 12 months） without recurrence or metastasis. Mutation of VHL gene was detected in 7 of 11 cases （64%） , but all adjacent normal tissues were negative. Conclusions As a rare subtype of renal cell carcinoma, MCRCC is difficult to diagnose, CT is an essential measure in diagnosis of MCRCC preoperatively. Because of the good prognosis of reported cases, nephron sparing surgery for the treatment of MCRCC is recommended. VHL gene mutations may play an important role in the carcinogenesis of MCRCC.