嫌色细胞型肾细胞癌

许多文献显示嫌色细胞型肾细胞癌(RCC)是一种具有低恶潜能生物学特性的肿瘤,其5年和10年生存率分别为78%～100%和80%一90%.决定肿瘤预后的常规参数包括肿瘤发展过程中的所有特征.145例的临床病理特征与预后相关.患者的平均年龄59岁(27-82岁),男女比例1.1:1.     

肾嫌色细胞癌的1例报道及文献复习

肾实质上皮性癌约占所有内脏恶性肿瘤的3％和成人肾癌的85％,肾嫌色细胞癌少见。目前,国外文献报道百余例,国内文献报道约21例,且有许多误诊病例。现报道1例肾嫌色细胞癌,并结合文献复习探讨其分型、诊断、鉴别诊断、预后及治疗。     

肾嫌色细胞癌4例临床病理分析及文献复习

肾嫌色细胞癌是由Thoenes等于1985年首次报道的肾肿瘤的一个新类型，约占所有肾癌的5％，在常规病理诊断中易与肾透明细胞癌和嗜酸细胞腺瘤混淆。笔者结合近期所遇4例嫌色细胞癌，从大体、光镜、电镜、免疫组化角度进行报道，并结合文献提出鉴别诊断要点。     

肾嗜酸细胞瘤和嫌色细胞癌的临床鉴别诊断及治疗

目的 探讨肾嗜酸细胞瘤和嫌色细胞癌的临床特点,诊断,鉴别诊断及治疗。方法 回顾性分析8例肾嗜酸细胞瘤,男5例,女3例,年龄23~74岁,平均58.8岁,肿瘤直径3~7cm,平均5.1cm;5例嫌色细胞癌,男3例,女2例,年龄35~72岁,平均54.5岁,肿瘤直径3~8cm,平均5.8cm。全部患者均行彩超、CT检查,并行手术切除肿瘤,术后经病理学检查证实。结果 肾嗜酸细胞瘤细胞呈圆形,胞质富含浓染嗜酸颗粒,彩超以等回声或低回声多见,CT平扫为密度较均匀,增强后大多均匀强化,术后随访时间 10~53个月,未发现复发和转移。嫌色细胞癌由两种细胞类型组成,即典型型及嗜酸型,胞质呈纤细网状结构,胞膜清晰。彩超以高回声多见,CT大多强化不均匀,随访时间 12~49个月,1例术后 1年出现转移灶后死亡。结论 根据临床,影像方面的差别,术前基本能鉴别诊断,确诊仍需病理。肾嗜酸细胞瘤为良性肿瘤,首选保留肾单位手术;对于嫌色细胞癌,肾癌根治术是首选方法。     

KIT和RCC在肾嫌色细胞癌和透明细胞癌颗粒细胞亚型中鉴别诊断中的价值

肾嫌色细胞癌、透明细胞癌颗粒细胞亚型（GRCC）和肾嗜酸细胞瘤三者的鉴别在病理诊断中一直比较困难。作者应用免疫组化方法分别检测了11例肾嫌色细胞癌、12例肾嗜酸细胞瘤和6例GRCC中KIT、CDl0、RCC和RON的表达,并探讨了上述指标在这3种肾上皮性肿瘤中的鉴别诊断价值。结果发现KIT在肾嫌色细胞癌和肾嗜酸细胞瘤中100％表达,表达模式为胞质／胞膜阳性和胞质阳性,相反,     

肾嫌色细胞癌和嗜酸细胞腺瘤的形态学、组织化学和免疫表型的比较研究

目的探讨肾嫌色细胞癌（ehromophobe renal cell carcinoma,CRCC）和嗜酸细胞腺瘤（oncocytoma）的临床病理学特征、诊断和鉴别诊断。方法对手术切除的13例肾嫌色细胞癌和6例肾嗜酸细胞腺瘤进行眼观、光镜和电镜观察,Hale胶体铁和免疫组化染色。结果嫌色细胞癌以实体结构为主,胞质半透明或嗜酸颗粒状,核皱缩,有核周空晕;其中6例（46％）为嫌色细胞癌嗜酸变型;电镜下见胞质内微泡和管泡状嵴线粒体;Hale胶体铁染色12／13阳性。嗜酸细胞腺瘤以巢状结构为主,胞质嗜酸颗粒状,核圆伴小核仁;1例（16．7％）出现核异型性;电镜下见胞质内层状嵴线粒体;Hale胶体铁染色阴性。免疫组化两者均表达E—cadhefin、EMA,不表达CD10、CK20、vimentin;CK7在10／13例嫌色细胞癌中呈强阳性表达,2／6例嗜酸细胞腺瘤呈灶性表达。结论肾嫌色细胞癌和嗜酸细胞腺瘤形态学各有特征,免疫表型相似,鉴别诊断基于生长方式和细胞学特征,Hale胶体铁染色和电镜检查是区分二者的有效手段。     

S100A1：一种区分嫌色细胞癌和嗜酸细胞瘤的强有力标记物

肾脏肿瘤比较常见的类型有普通型肾细胞癌、乳头状肾细胞癌、嫌色细胞癌和嗜酸细胞瘤，每种类型的肿瘤均有不同的临床特点，正确区分这些肿瘤具有重要的临床意义。在这些类型的肿瘤中，嫌色细胞癌和嗜酸细胞瘤是最容易混淆的两种病变。作者采用免疫组化和RT—PCR法分别检测了39例肾脏肿瘤（透明细胞癌9例、乳头状肾细胞癌6例、嫌色细胞癌9例和嗜酸细胞瘤15例）中S100A1蛋白和基因表达。免疫组化结果显示93％（14／15）嗜酸细胞瘤表达S100A1蛋白，其中强阳性9例、中等阳性4例、弱阳性1例，[第一段]     

CT多期增强扫描在肾细胞癌诊断中的应用

目的探讨CT多期增强扫描在肾细胞癌诊断中的应用价值。方法分析经手术病理证实的38例肾细胞癌患者,男27例,女11例,年龄25～72岁(平均48岁)。全部采用CT多期增强扫描。结果均为单肾单发病灶,形态上呈圆形或椭圆形35例,形态不规则3例;有明显假包膜26例(68%);密度呈较均匀稍低密度27例(71%);31例(82%)肿瘤呈重度强化,5例(13%)呈中度强化,2(5%)例呈轻度强化。35例(92%)强化不均匀。95%的病灶强化均呈"快进快出"型。CT分期准确率为95%。结论CT多期增强扫描是肾癌术前诊断与鉴别诊断的有效方法。     

嫌色性肾细胞癌和肾嗜酸细胞腺瘤中CK7、Claudin-7、Epcam、vimentin的表达及其临床意义

目的探讨CK7、Claudin-7、上皮细胞黏附分子(Epcam)和vimentin在嫌色性肾细胞癌(chromophobe renal cell carcinoma,Ch RCC)和肾嗜酸细胞腺瘤(renal oncocytoma,RO)中的表达,及其诊断与鉴别诊断的意义。方法采用免疫组化En Vision两步法检测24例Ch RCC和17例RO中CK7、Claudin-7、Epcam和vimentin的表达。结果 CK7、Claudin-7、Epcam和vimentin在Ch RCC中的阳性率分别为79.17%(19/24)、95.83%(23/24)、91.67%(22/24)、8.33%(2/24),在RO中的阳性率分别为23.53%(4/17)、41.18%(7/17)、29.41%(5/17)、0(0/17);CK7、Claudin-7和Epcam在这两种肿瘤中的表达差异有统计学意义(P0.05);虽然vimentin在两种肿瘤中的表达差异无统计学意义(P0.05),但与其它含有嗜酸性细胞的肾脏肿瘤表达差异有显著性。结论 CK7、Claudin-7和Epcam可作为鉴别Ch RCC与RO的免疫标志物,vimentin有助于Ch RCC、RO与其它含有嗜酸性细胞的肾脏肿瘤鉴别。     

Pigmented microcystic chromophobe renal cell carcinoma

We report a case of a 60-year-old female with a pigmented microcystic chromophobe renal cell carcinoma (PMCRCC). The tumor was 4.5cm in diameter, and was located in the right kidney. Grossly, on cross section, the tumor was light gray with multiple small brown to black pigmented foci up to 0.2cm in diameter. Histologically, the tumor showed a microcystic arrangement with cribriform areas and formation of adenomatous structures. The microcystic and cribriform areas were composed of larger pale cells and smaller eosinophilic cells, with cytological features of conventional chromophobe renal cell carcinoma (CRCC). The cytological features of the cells within the adenomatous structures were different. These cells were mostly columnar with nuclei at the base, and had a variable amount of pale to eosinophilic cytoplasm. There were foci of ample brown pigmentation located in the cytoplasm of the tumor cells and extracellularly. In addition, microscopic calcifications were present. Immunohistochemically, the tumor cells were positive for EMA, E-cadherin, cytokeratin CAM5.2, and cytokeratin AE1/AE3. Cytokeratin 7 was positive only focally. S-100 protein, melan A, HMB 45, vimentin, and CD117 were negative. PMCRCC is a rare tumor. To the best of our knowledge, only one series containing 20 cases of this variant of CRCC has been described to date. The important feature is that PMCRCC seems to have a relatively benign biological behavior, and distant metastases and sarcomatoid transformation are absent.     

A renal cell carcinoma with components of both chromophobe and papillary carcinoma

We report a case of a morphologically unusual renal cell carcinoma with features of both chromophobe and papillary carcinoma. Immunohistochemical analysis of high molecular weight cytokeratins (HMWCK), cytokeratin 7 (CK7), cytokeratin 19 (CK19), c-Kit, and α-methylacyl-CoA racemase (AMACR) demonstrated differential profiles for the two components of the tumor, consistent with the respective patterns commonly observed for pure chromophobe and papillary renal cell carcinomas. Specifically, the chromophobe tumor cells expressed CK7 and c-Kit weakly, while HMWCK, CK19, and AMACR were not detectable. In contrast, the papillary tumor cells expressed uniformly HMWCK, CK7, and c-Kit and focally CK19 and AMACR. Fluorescence in situ hybridization analysis of nuclei isolated from paraffin-embedded tumor tissue detected monosomy 1, disomy 7, and monosomy 17, a common and characteristic finding in chromophobe carcinomas, in a majority of, but not all tumor cells, whereas a population characterized by disomy 1, trisomy 7, and trisomy 17, a frequent finding in papillary carcinoma, was not identifiable. Electron microscopic analysis revealed numerous characteristic small cytoplasmic vesicles in the chromophobe areas, which were absent in the papillary component. This case illustrates the rare coexistence of two distinct and admixed histologic types of renal cell carcinoma.     

LMP2, a novel immunohistochemical marker to distinguish renal oncocytoma from the eosinophilic variant of chromophobe renal cell carcinoma

LMP2 is a subunit of the immunoproteasome that is overexpressed in oncocytic lesions of the thyroid gland. This study was designed to assess the expression profile and diagnostic utility of LMP2 in two renal oncocytic tumors that share similar morphologic features but have different clinical outcomes: renal oncocytoma (RO) and the eosinophilic variant of chromophobe renal cell carcinoma (CHRCC-EO). A total of 56 RO, 38 classic CHRCC, and 7 CHRCC-EO cases, as well 84 normal kidney controls, were selected from the Johns Hopkins surgical pathology archive and stained for LMP2 using a standard immunohistochemical protocol. Sections were scored for cellular location (nuclear versus cytosolic), intensity (from 0 to 3), and percent of area involved (from 0 to 100%), and an H score was calculated multiplying the intensity by the extent of the staining signal. The cytoplasmic expression of LMP2 was similar among the renal lesions, being present in 44 of 56 (79%) ROs, 27 of 38 (71%) CHRCCs, and 7 of 7 (100%) CHRCC-EO cases. The nuclear expression of LMP2, however, was more informative. All CHRCC-EO cases (7 of 7, 100%) strongly showed nuclear LMP2 staining, as opposed to only 2 of 56 (4%, P < 0.0001) ROs and 9 of 38 (24%, P = 0.0001) classic CHRCCs. These results suggest that the nuclear LMP2 expression can be used in clinical scenarios where histological distinction between RO and CHRCC-EO remains challenging.     

Fractal dimension of microvasculature in renal oncocytomas and chromophobe renal cell carcinomas

The aim of this study was to evaluate and compare the microvascular architectural complexity in oncocytomas and chromophobe renal cell carcinomas (ChRCCs) by fractal box-counting on CD34-labeled slides.     

Mitochondrial and chromosomal DNA alterations in human chromophobe renal cell carcinomas.

Renal cell tumours are characterized by the loss of chromosome 3p and trisomy of 5q segments (common, non-papillary renal cell carcinoma), or by trisomy of chromosomes 7 and 17 and loss of the Y chromosome (papillary renal cell carcinoma), or by random karyotype changes and mitochondrial DNA alterations (renal oncocytoma). We have studied by means of RFLP analysis the genomic and mitochondrial DNA in 11 chromophobe renal cell carcinomas, which have a unique morphology among kidney cancers. We found a loss of the constitutional heterozygosity at chromosomal regions 3p, 5q, 17p, and 17q, a combination of allelic losses that has not been found in other types of renal cell tumours. Three of the tumours showed a gross alteration in the restriction pattern of the mitochondrial DNA. A combined morphological and genetic analysis suggests that chromophobe renal cell carcinoma is a distinct entity.     

Claudin-7 is highly expressed in chromophobe renal cell carcinoma and renal oncocytoma

Claudin-7 has recently been suggested to be a distal nephron marker. We tested the possibility that expression of claudin-7 could be used as a marker of renal tumors originating from the distal nephron. We examined the immunohistochemical expression of claudin-7 and parvalbumin in 239 renal tumors, including 179 clear cell renal cell carcinoma (RCC)s, 29 papillary RCCs, 20 chromophobe RCCs, and 11 renal oncocytomas. In addition, the methylation specific-PCR (MSP) of claudin-7 was performed. Claudin-7 and parvalbumin immunostains were positive in 3.4%, 7.8% of clear cell RCCs, 34.5%, 31.0% of papillary RCCs, 95.0%, 80.0% of chromophobe RCCs, and 72.7%, 81.8% of renal oncocytomas, respectively. The sensitivity and specificity of claudin-7 in diagnosing chromophobe RCC among subtypes of RCC were 95.0% and 92.3%. Those of parvalbumin were 80.0% and 88.9%. The expression pattern of claudin-7 was mostly diffuse in chromophobe RCC and was either focal or diffuse in oncocytoma. All of the cases examined in the MSP revealed the presence of unmethylated promoter of claudin-7 without regard to claudin-7 immunoreactivity. Hypermethylation of the promoter might not be the underlying mechanism for loss of its expression in RCC. Claudin-7 can be used as a useful diagnostic marker in diagnosing chromophobe RCC and oncocytoma.     

C-kit overexpression is not associated with KIT gene mutations in chromophobe renal cell carcinoma or renal oncocytoma

Introduction

C-kit overexpression has previously been described in chromophobe renal cell carcinoma (cpRCC) and renal oncocytoma (RO). However, so far no KIT mutations have been found. The objective of our study was to analyse c-kit in a large cohort of renal tumors and to perform KIT mutation analysis in a subset cpRCC and RO cases with overexpression of c-kit.

Materials and methods

We studied the immunohistochemical expression of c-kit on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 948 patients with renal tumors. CpRCC and RO cases with c-kit overexpression (n = 23) were analyzed for KIT mutations in exons 9, 11, 13, 14, 15, and 17.

Results

Expression of c-kit was found in 6/642 (0.9%) clear cell RCC, 3/154 (1.9%) papillary RCC, 54/69 (78.3%) cpRCC, 37/45 (82.2%) RO and 2/30 (6.7%) of other unclassified tumor types. In none of the RO and cpRCC cases analyzed, a KIT gene mutation was found.

Conclusion

C-kit expression is found in the majority of cpRCC and RO, but these tumors do not harbor the usual c-kit activating mutations. This may have implications for the use of tyrosine kinase inhibitors in patients with advanced cpRCC and c-kit expression.