von Hippel-Lindau病的肾脏病理学特点

目的 探讨von Hippel—Lindau(VHL)病肾脏损害的病理特点及VHL多发性肾癌的治疗。方法 回顾性分析6例同一VHL病家族伴有肾脏损害患者的临床及病理资料；1例为双肾多发性囊肿，5例为双侧肾癌伴多发性囊肿。结果 5例双肾癌10侧肾脏中，行保留肾单位手术5侧，肾癌根治术3侧，带瘤随访2侧。1例多发肾囊肿者仅随诊观察。术后病理实质性肿块均为透明细胞癌。Fuhrman分级结果：Ⅰ级14枚，Ⅱ级6枚。TNM病理分期：T1N0M04例、T2N0M01例。切除14枚可疑的肾囊肿，术后病理恶性囊肿1枚，余为单纯囊肿。术后随访9～113个月，平均47个月，5例患者均存活且无肿瘤复发及远处转移；5例肾功能正常，1例肾功能较术前差，但无需血透治疗。结论 VHL病中肾脏损害包括肾癌及肾囊肿，常为双侧多发性，肿瘤为透明细胞癌且分级分期低。保留肾单位手术是治疗VHL病中肾癌的有效方法。     

上海仁济医院肾癌数据库资料分析

目的 探讨肾癌临床、病理、分期、分级与预后特征. 方法 分析2003年至2005年上海仁济医院泌尿科肾癌数据库435例患者临床和病理资料.采用WHO 1997年肾实质上皮性肿瘤组织学分类标准、2002年ATCC的TNM分期和临床分期、1982年Fuhrman病理分级.采用Kaplan-Meier法和Logrank检验对57例获随访的晚期患者行生存分析和预后因素判断. 结果 435例患者中,遗传性VHL病肾癌10例(2.4%)、散发性肾透明细胞癌372例(85.5%)、乳头状癌13例(3.0%)、嫌色细胞癌18例(4.1%)、集合管癌4例(0.9%)、嗜酸性细胞腺瘤4例(0.9 %)、未分类肾癌.14例(3.2%).行根治性肾切除术335例(77.0%),保留肾单位手术74例(17.0%),姑息性肾切除等手术26例(6.0%).遗传性VHL病肾癌均为双肾癌伴多发囊肿,临床分期Ⅰ期7例、Ⅱ期3例,病理分级Ⅰ级6例、Ⅱ级4例,基因测序均存在VHL基因突变,平均随访28.6个月,患者无肿瘤局部进展或转移,但4例患者出现同侧或双侧肿瘤再发.嫌色细胞癌临床分期均为Ⅰ期,病理分级Ⅰ级5例,Ⅱ级13例,平均随访19.8个月均存活,无肿瘤转移或复发.集合管癌临床分期均为Ⅰ期,病理分级均为Ⅲ级,平均生存时间11.3个月.肾透明细胞癌和乳头状癌临床分期Ⅰ期260例(67.6%)、Ⅱ期64例(16.6%)、Ⅲ期32例(8.3%)、Ⅳ期29例(7.5%),其中T1a 147例(38.2%)、T1b 113例(29.4 %);病理分级Ⅰ级124例(32.2%)、Ⅱ级219例(56.9%)、Ⅲ级40例(10.4%)、Ⅳ级2例(0.5%).57例晚期肾癌患者中位生存时间(16.0±1.3)个月,1年生存率55.0%,2年生存率31.0%.预后因素分析显示,临床分期、肿瘤大小、淋巴结转移、远处转移和病理分级是晚期肾癌解剖水平和组织学水平的预后影响因素. 结论 不同组织学亚型的肾癌生物学特征存在较大差异,遗传性VHL病肾癌存在基因突变,常为双侧、多中心、低Fuhrman分级透明细胞癌,易再发不易转移.肾嫌色细胞癌预后较好,而集合管癌预后差.在解剖水平和组织学水平,TNM分期、肿瘤大小、淋巴结转移、远处转移和肾癌病理分级是晚期肾癌的预后影响因素.     

von Hippel-Lindau病肾癌的诊治特点分析

目的 总结yon Hippel-Lindau(VHL)病肾癌的诊治经验. 方法 VHL肾癌患者28例.男16例,女12例.平均年龄45岁.双肾癌15例(同时11例、异时4例),单侧肾癌13例.行VHL基因检测25例.行保留肾单位手术或肾癌根治术24例,观察等待2例,保守治疗2例.结果 25例受检者均有VHL基因胚系突变,其中无症状患者14例.9例患者中有29个实性肿瘤曾被观察,平均44(12～86)个月,肿瘤平均生长速度0.531 cm/年;观察结束时,19个(65.5%)肿瘤生长>3 cm,仅1个肿瘤转移.24例手术切除实性肿瘤87个,其中肿瘤剜除术62个(71.3%)、肾下极切除1个、根治性肾切除术24个.术后病理报告24例均为肾透明细胞癌.TNM分期T1a8例、T1b7例、T2 8例、T3 1例.肿瘤86个,Fuhrman分级Ⅰ级73个、Ⅱ级12个、Ⅲ级1个,钙化结节1个.28例患者平均随访50(5～237)个月,存活26例,死亡2例,肿瘤局部复发4例. 结论 基因检测可早期发现无症状VHL患者;VHL病肾癌多生长缓慢,>3 cm的肿瘤多数不发生转移,可随访观察;保留肾单位手术是治疗VHL病肾癌安全有效的方法.     

肾细胞癌VHL基因改变与VEGF表达的关系及意义

目的：探讨肾细胞癌VHL基因异常与血管内皮生长因子（VEGF）表达的关系及意义。方法：应用聚合酶链反应（PCR）加单链构象多态性分析（SSCP）、多聚合酶链反应（Multiplex-PCR)及免疫组织化学方法检测42例肾细胞癌、18例远离肿瘤的正常肾脏及10例正常肾脏组织中VHL基因突变、异常甲基化及VEGF的表达。结果：肾癌组织中VHL基因改变（61．9％）与正常肾脏组织（3．6％）比较差别有显著性意义（P＜0．005）,VHL基因失活与肾癌组织类型及临床分期相关,与病理分级无关。VEGF在肾癌组织（64．3％）与正常肾组织（21．4％）中的表达差别有显著性意义（P＜0．005）,肾癌组织中VEGF表达与组织类型无关,与病理分级及临床分期相关,随病理分级及临床分期的升高而增高。VHL基因改变与VEGF表达间存在显著的相关性（P＜0．05）。结论：VHL基因在肾细胞癌中具有高频突变率,可负向调节VEGF的表达。     

von Hippel-Lindau病肾肿瘤与散发性肾细胞癌临床比较分析

目的 探讨von Hippel-Lindau(VHL)病肾肿瘤的临床特征. 方法回顾性分析9例VHL病肾肿瘤患者资料,其中男6例,女3例.平均年龄51岁.双侧肾肿瘤7例,单侧多中心表现5例,囊实性表现6例.同期散发性肾细胞癌患者46例,其中男30例,女16例.平均年龄55岁.肿瘤均为单发,单侧多中心表现2例,囊实性表现1例.分析2组患者在发病人群、肿瘤表现、疾病生存等方面的差异. 结果 2组患者性别、年龄比较差异无统计学意义(P>0.05).2组肾肿瘤双侧性、多中心性和囊实性表现比较差异均有统计学意义(P<0.01).VHL组甲均随访54个月,死亡4例,死于远处转移3例、死十恶液质1例.VHL病肾肿瘤与散发性肾细胞癌患者中位生存时间分别为136、42个月,2组比较差异无统计学意义(P=0.251),但生存曲线显示VHL病肾肿瘤患者生存率呈现较高趋势. 结论 VHL病肾肿瘤临床表现与散发性肾细胞癌不同,临床上应根据临床特征正确诊断,避免肾切除术,采取保留肾单位手术结合严密影像学观察治疗策略.     

von Hipple-Lindau基因突变与散发性肾透明细胞癌患者预后的关系

目的 探讨von Hippel-Lindau(VHL)抑癌基因突变与散发性肾透明细胞癌患者预后的关系. 方法应用聚合酶链反应(PCR)、PCR产物直接测序分析74例散发性肾透明细胞癌组织标本和相应远离肿瘤的正常组织标本中VHL基因突变情况.74例患者,病理分期为T1 51例(68.9%),T2 9例(12.2%),T3 14例(18.9%);病理分级为G1 15例(20.3%),G2 50例(67.6%),G39例(12.2%).随访其预后并进行统计学分析. 结果 VHL基因突变者40例(54.1%),不同病理分期和分级的肿瘤中VHL基因突变率差异无统计学意义(P值分别为0.915和0.237).随访34~107个月.平均71个月,因肿瘤死亡7例,出现远处肿瘤转移11例,5年无瘤生存率为78%.VHL基因突变组肿瘤死亡或转移等阳性事件发生率(15.0%,6/40)明显低于非突变组(35.3%,12/34,P=0.043).Logistic回归分析表明.患者预后与肿瘤病理分期、分级呈正相关,而与VHL基因是否突变呈负相关,三者的P值分别为0.016、0.024和0.033.对于T3和G3肿瘤患者,VHL基因突变者预后更好.P值分别为0.010和0.048. 结论 散发性肾透明细胞癌患者中VHL基因突变广泛,肾癌的病理分期和分级仍然是评估患者预后的有效指标.VHL基因突变失活可能提示肾透明细胞癌患者预后更好,尤其对于高分期和高分级肿瘤患者.     

家族性肾癌1家系报告

2006年10月至2015年9月安徽医科大学第一附属医院收治1家族性肾癌家系共4例肾癌患者。4例中术后病理诊断分别为单侧多发透明细胞癌1例,双侧多发透明细胞癌1例,双侧多发嫌色细胞癌2例。所有患者基因检测均未见VHL和FLCN基因突变。     

VHL病中泌尿系病变的基因及临床研究

VonHippel-Lindau病是一种常染色体显性遗传性肿瘤综合征，主要包括视网膜血管瘤，中枢神经系统成血管细胞瘤，肾癌，肾囊肿，胰腺肿瘤囊肿，嗜铬细胞瘤，附睾肿瘤等病变。其中泌尿系统病变的临床表现上常为双侧性多发性，在治疗上具有其特点，定位于3P25-26区域的VHL基因是抑癌基因，它与肿瘤发生有关，临床VHL基因的检测对于VHL病的早期诊断，VHL病家族成员的肿瘤监测具有重要价值。VHL病的基因治疗尚处于实验阶段。     

多灶性肾细胞癌24例临床分析

目的:总结多灶性肾细胞癌(MRCC)的围手术期诊治要点。方法:从复旦大学附属中山医院2011年12月~2017年6月收治的2 852例肾细胞癌患者中,筛选出符合入组要求的24例MRCC,男15例,女9例,中位年龄50(26~72)岁。单侧肾多发病灶21例(其中孤立肾1例),双侧肾多发病灶3例,术前发现的癌灶数2~8个/例。所有患者术前均行彩超、CTU或肾脏增强MRI检查。结果:3例双侧MRCC和1例孤立肾MRCC患者,术前行基因检测,结果提示1例患者高度疑似VHL综合征(Von Hippel-Lindau syndrome)。24例患者共行26次手术,其中肾部分切除术(PN)8例次,根治性肾切除术(RN)18例次。24例患者术后病理均为肾透明细胞癌;癌灶直径0.6~10.6cm。8例PN平均热缺血时间(26.0±4.5)min,切缘均为阴性。随访时间最长71个月,最短6个月,23例患者未见肿瘤复发转移,1例患者因肿瘤转移术后行分子靶向治疗,于术后32个月出现肿瘤进展而死亡。结论:对于MRCC患者,术前应行超声、CT/MRI等多种影像学检查,以提高诊断准确性,避免遗漏。双侧MRCC患者应行基因检测鉴别遗传性或散发性肾癌。手术治疗是目前主要的治疗方法大多数病例可通过RN完整切除病灶;对病灶数较少或者遗传性肾癌患者,可选择PN。     

Von Hippel-Lindau综合征并发肾癌二例诊治分析

目的分析Von Hippel-Lindau(VHL)综合征并发肾癌的临床特点,提高临床医生对VHL综合征的认识。方法回顾性分析我院泌尿外科收治的2例VHL综合征并发肾癌病人的临床资料,并结合文献复习。结果 2例中1例有家族史,行右肾肿物穿刺活检,病理未见癌细胞,病人后续就诊于其他医院,于当地医院外请专家行右肾癌根治术,术后病理检查提示肾透明细胞癌;1例无相关家族史,病人多发胰腺、肾脏囊肿,双肾多发肿物,肾肿物穿刺活检示肾透明细胞癌,无法行手术治疗,给予分子靶向药物舒尼替尼治疗2年,定期复查肾脏CT,发现肾肿物明显缩小。结论VHL综合征可发病于多个系统,其并发肾癌的特征不同于散发性肾癌。早期明确诊断和个体化治疗,能够提高VHL综合征病人生存率。     

Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience

OBJECTIVE: To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited. PATIENTS AND METHODS: We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC. RESULTS: In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis (P = 0.63); multifocality did not affect survival (P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival. CONCLUSIONS: Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality.     

Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome.

A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). In addition to the early development of renal epithelial tumors with morphologic similarity to human RCC, rats which bear the RCC gene are predisposed to the development of secondary primary cancers later in life. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At fourteen months of age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. Non-carrier siblings of affected animals did not have renal, reproductive, or splenic neoplasia. The finding of a specific constellation of familial neoplasms, including multicentric bilateral renal cell carcinoma, in this autosomal dominant disorder of rats suggests that this syndrome is analogous to human VHLD. In addition to its usefulness for studies of the biochemical and molecular mechanisms of renal carcinogenesis, this animal model will provide a unique tool to investigate how cancer susceptibility genes interact with environmental risk factors such as chemical carcinogens.     

PREVALENCE, MORPHOLOGY AND BIOLOGY OF RENAL CELL CARCINOMA IN VON HIPPEL-LINDAU DISEASE COMPARED TO SPORADIC RENAL CELL CARCINOMA

Purpose

Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology.

Materials and Methods

We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease.

Results

The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p <0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm.

Conclusions

Von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.     

P63蛋白在肾盂移行上皮细胞癌和肾细胞癌中的表达及临床意义

目的探讨P63基因在肾盂移行细胞癌（renal transitional cell carcinoma，RTCC）和肾细胞癌（renal cell carcinoma，RCC）组织中的表达及其意义。方法采用免疫组织化学SP法检测40例RTCC、50例RCC、10例正常肾组织中P63的表达，并分析P63表达与RTCC及RCC病理分级、临床分期、病理类型间的关系。结果正常。肾组织、RTCC、RCC中P63的阳性表达率分别为30％（3／10）、95％（38／40）、0％（0／50），组间差异有统计学意义（P〈0．01）；RTCC组中G1级与G2级P63的强阳性、中度阳性表达率显著高于G3级（P〈0．05）；Ta-T1期以P63强阳性为主（66．7％），随RTCC浸润程度的增加，P63染色强度逐渐减弱；T2期P63强阳性表达率为42．9％，T3-T4期降至0；RCC组中，所有肿瘤无论组织类型、级别、分期，P63表达均呈阴性。结论P63在RTCC中高表达，与RTCC病理分级、临床分期密切相关；P63可能参与RTCC的发生、发展，是评估RTCC预后的潜在因素之一；P63在RCC中不表达，可作为将RTCC从RCC中鉴别出来的有用指标之一。     

Von Hippel-Lindau disease and renal cell carcinoma in a 16-year-old boy.

Von Hippel-Lindau disease is a rare autosomal dominant disorder. Kidney lesions occur in the majority of cases, with renal cell carcinoma noted in 40% and renal cysts in 60%. Renal cell carcinoma in von Hippel-Lindau disease is usually bilateral and occurs at an earlier age than in patients with sporadic renal cell carcinoma. We report on a 16-year-old boy who, to our knowledge, is the youngest patient to present with von Hippel-Lindau disease and renal cell carcinoma. Controversy currently exists regarding the nature of renal cysts in von Hippel-Lindau disease and the optimal therapeutic approach (that is radical versus parenchymal sparing surgery). We review the histology of renal cysts and carcinoma, and discuss the rationale for selecting parenchymal sparing surgery.     

Twist、E-钙粘蛋白在肾癌转移进展中的意义

目的探讨Twist蛋白和E-钙粘蛋白在人肾细胞癌(renal cell carcinoma,RCC)组织中的表达及其相关性。方法应用免疫组织化学SABC染色方法检测40例RCC及癌旁正常组织中Twist蛋白、E-钙粘蛋白的表达情况,分析二者相关性。结果 RCC组织中Twist蛋白的阳性表达率(87.5%)明显高于癌旁肾组织中Twist蛋白的阳性表达率(32.5%);RCC组织中E-钙粘蛋白的阳性表达率(12.5%)明显低于其在癌旁肾组织中的阳性表达率(95.0%),Twist蛋白和E-钙粘蛋白表达在肾癌组织和癌旁组织中的差异均有统计学意义(P<0.01)。其中Twist的异常表达与RCC病理分级、临床分期、淋巴结转移呈正相关(P<0.05),E-钙粘蛋白的异常表达与RCC病理分级、临床分期、淋巴结转移呈负相关(P<0.05),而两者与患者的性别、肿瘤直径、年龄无相关性(P>0.05)。结论 Twist蛋白可能是RCC发生、发展及浸润转移的重要因素之一。     

Genetic identification of bilateral primary or metastatic nonpapillary renal cell carcinoma

OBJECTIVE: To clarify the clonality of bilateral tumours by genetic analysis of bilateral renal cell carcinomas (RCCs) using the VHL gene, which is inactivated in approximately 60% of RCCs and which plays a causal role in the development of most cases of nonpapillary RCC. PATIENTS AND METHODS: The study included 20 patients; seven had von Hippel-Lindau disease, three had papillary RCC and 10 had nonpapillary RCC. Paraffin-embedded blocks of tumour tissue were obtained from two of the three patients with papillary RCC and from nine of 10 with nonpapillary disease; all three exons of VHL were examined by direct sequencing. RESULTS: As reported previously, no VHL mutations were found in papillary tumours. However, in five of the nine nonpapillary cases, VHL mutations were identified in tumours on one or both sides. Three of the tumours had the same mutation on both sides, confirming a common origin. In the remaining two patients, the mutation status differed between the sides, confirming a bilateral primary origin. The former cases were characterized by a relatively large tumour on one side and multiple tumours on the other. CONCLUSIONS: In nonpapillary RCC multiplicity may suggest a metastatic origin. Such genetic information will be useful in treating and following patients with bilateral renal tumours.     

von Hippel-Lindau disease with bilateral multiple renal cell carcinoma managed by right radical nephrectomy and left repeat partial nephrectomy

von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by cysts and cystadenoma in the kidney, pancreas and epididymis and angiomas of the central nervous system and retina as well as renal cell carcinoma (RCC), phaeochromocytoma, islet tumors of the pancreas, and endolympatic sac tumors. VHL for its multicentric-characteristic and bilateralism often puts the surgeon in challenging situation. We present a case of VHL with bilateral RCC and retinal angiomas managed with right radical nephrectomy and left repeat partial nephrectomy.     

肾癌组织中HPIP表达与临床相关性分析

目的:检测肾细胞癌组织中人造血相关的PBX相互作用蛋白质(HPIP)的表达,研究其表达水平与肿瘤临床病理特征及临床转归的相关性。方法:收集62例肾细胞癌患者资料和手术标本,平均随访时间41.2个月,应用免疫组化方法检测HPIP在肾细胞癌组织中的表达情况,将肿瘤分期、分级、转移、生存率等临床病理资料与HPIP表达水平进行相关性分析。结果:在肾细胞癌中,HPIP的表达水平与非肿瘤组织相比显著增加,并且与肿瘤的转移(P0.001)、存活率(86.2%vs.72.7%,P0.005)存在相关性;HPIP表达水平在不同年龄、性别、手术方式组间差异无统计学意义(P0.05)。单变量分析显示HPIP的表达水平对肾细胞癌的发展和预后具有预测意义。结论:HPIP的高表达与肾细胞癌的进展呈正相关,检测HPIP的表达水平可用于肾癌的分期、分级及预后判断。     

Clear cell papillary cystadenoma of the epididymis and mesosalpinx: immunohistochemical differentiation from metastatic clear cell renal cell carcinoma

Clear cell papillary cystadenoma is a rare epithelial tumor of the epididymis, which may present as an isolated lesion or as a component of von Hippel-Lindau disease (VHLD). Recently, tumors have also been described in the female genital tract with similar histology. Recognition of clear cell papillary cystadenoma is critical because of its association with VHLD and its potential diagnostic confusion with metastatic renal cell carcinoma because of a shared architecture and clear cells. In this study, we report on the immunohistochemical differentiation of 5 clear cell papillary cystadenomas, 3 of the epididymis and 2 of the mesosalpinx, from metastatic renal cell carcinoma. In 2 cases, there was a history of renal cell carcinoma in the setting of VHLD; and in 1 of these cases, an epididymal papillary cystadenoma was initially considered to be metastatic renal cell carcinoma. Immunohistochemically, tumor cells were moderately intensely positive for cytokeratin AE1/AE3 and epithelial membrane antigen, strongly positive for CK7 and negative for CK20 and RCC. Four of 5 cases were negative for CD10. This staining profile contrasts with that reported for clear cell renal cell carcinomas, which are typically negative for CK7 and immunoreactive for renal cell carcinoma (RCC) and CD10. Our findings indicate that, in cases where there is uncertainty about the histologic diagnosis of clear cell papillary cystadenoma, the above immunohistochemical panel helps to rule out metastatic renal cell carcinoma.