肾脏特异性钙黏蛋白在肾上皮性肿瘤的表达及其临床病理意义

目的探讨肾脏特异性钙黏蛋白（Ksp—cadherin）的新抗体在肾细胞癌和肾嗜酸细胞腺瘤中的表达意义。方法收集166例肾脏肿瘤标本,其中肾原发性透明细胞癌120例、乳头状肾细胞癌20例（I型乳头状肾细胞癌15例,Ⅱ型乳头状肾细胞癌5例）、嫌色细胞癌18例、嗜酸细胞腺瘤8例。使用Ksp—cadherin、CD10、波形蛋白、上皮细胞膜抗原（EMA）、CK7进行免疫组织化学（EnVision法）染色。结果Ksp-cadherin的表达率分别是透明细胞癌23％（27／120）,乳头状肾细胞癌20％（4／20）,嫌色细胞癌18／18,嗜酸细胞腺瘤6／8。CD10、波形蛋白在透明细胞癌和乳头状肾细胞癌有高表达,CK7主要表达于嫌色细胞癌和乳头状肾细胞癌,EMA在这4种肿瘤均有高表达。此外,CDl0在肾嫌色细胞癌中也有表达,但其表达于胞质,而在其他肿瘤的表达在细胞膜。Ksp—cadherin在肾透明细胞癌的表达程度与其分期分级呈正相关。结论Ksp—cadherin局限表达于远端肾小管及其起源的肾脏肿瘤。在嫌色细胞癌和嗜酸细胞腺瘤中有高度的特异和敏感性,在透明细胞癌中的表达和分期分级有关,在肾脏常见的上皮性肿瘤中具有鉴别诊断和预后价值。     

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,     

肾细胞癌的临床病理与免疫表型研究

目的 研究肾细胞癌的临床病理特征、预后及免疫表型特点.方法 复习114例肾细胞癌的临床病理资料、HE切片,按2004年WHO肾肿瘤分类标准重新分类、随访并进行免疫组织化学染色.结果 114例.肾细胞癌包括5个类型,肾透明细胞癌77例(67.5%)、乳头状肾癌11例(9.6%)、肾嫌色细胞癌14例(12.3%)、Xp11.2易位_/TFE3基因融合相关性肾癌10例(8.8%)、未能分类肾肿瘤2例(1.8%).免疫组织化学结果,肾透明细胞癌主要表达CK(93.5%,72/77)、CD10(93.5%,72/77)、波形蛋白(75.3%,58/77),乳头状肾癌主要表达α-甲酰基辅酶A消旋酶(AMACR,11/11),肾嫌色细胞癌主要表达CD117(11/14),Xp11.2易位/TFE3基因融合相关性肾癌TFE3、AMACR、CD10和CK的阳性率分别为10/10、10/10、9/10和7/10.结论 肾癌是一组形态学上各有特征的异质性肿瘤,在形态学基础上,CD10、波形蛋白、CD117、AMACR、CK7、TFE3有助于亚型的诊断.     

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。     

肾集合管癌的临床病理分析

目的 观察肾集合管癌的临床病理特点,探讨其病理诊断与鉴别诊断.方法 对2例肾集合管癌的临床特点、病理学检查进行观察,采用免疫组化EnVision法检查CK7、CK19、CK20、34βE12、vimentin、CD10、P504S、E-cadherin的表达.并选择9例Ⅱ型、核分级为Ⅲ级的乳头状肾细胞癌、6例伴广泛肾实质侵犯的肾盂高级别尿路上皮癌与肾集合管癌进行形态学与免疫表型的比较.结果 肾集合管癌占同期上皮性肿瘤的0.66%,血尿为主要临床表现,1例患者术后3月死于肺转移.肿瘤均位于肾髓质,以管状结构为主,伴有肉瘤样分化,广泛侵犯肾实质,间质纤维化及中性粒细胞反应,周围集合管可见异型增生;免疫组化CK19及vimentin( ,2/2)、CK7及34βE12( ,1/2),CK20、CD10、P504S、E-cadherin均阴性.Ⅱ型乳头状肾细胞癌、尿路上皮癌未见集合管上皮异型增生;乳头状肾细胞癌表达vimentin( ,8/9)、CD10及P504S( ,7/9)、CK7( ,3/9)、CK19( ,1/9),34βE12、E-cadherin、CK20均阴性;尿路上皮癌CK7、CK19、34βE12均( ,6/6),E-cadherin( ,5/6),CK20( ,4/6),CD10、p504s、vimentin均阴性.结论 集合管癌是一种少见、高度恶性的肾上皮性肿瘤,形态和免疫表型多样化.灰白色肿块位于髓质、周围集合管上皮异型增生,无肾盂尿路上皮异型增生及原位癌存在可与乳头状肾细胞癌、尿路上皮癌鉴别.CD10、CK19、34βE12、P504S 、E-cadherin的染色有助于鉴别诊断.     

改良Hale胶状铁染色液的配制和应用

改良Hale胶状铁染色对于帮助临床病理医师诊断肾嫌色细胞癌是一个非常重要的技术方法,现将该法的试剂配制和染色步骤以及诊断特征介绍如下。[第一段]     

Collecting duct carcinoma of kidney: a clinicopathologic analysis of 4 cases

目的 探讨肾集合管癌(collecing duct carcinoma,CDC)的临床病理特点、诊断及鉴别诊断.方法 对4例CDC进行临床病理学观察及免疫组化标记,并复习相关文献.结果 肿瘤位于肾髓质内,镜下为管状、乳头状结构,肿瘤细胞呈靴钉样,伴间质纤维化及炎症细胞反应,肿瘤旁集合管上皮细胞可见异型增生;免疫表型示肿瘤细胞CKpan、CKL、CKH及CK7均(+),vimentin部分(+)(2/4),CK20、CD10、RCC均(-).结论 CDC是一种高度恶性的肾上皮性肿瘤,临床罕见,易误诊,免疫组化有助于诊断及鉴别诊断.     

肾集合管癌4例临床病理分析

目的探讨肾集合管癌(collecing duct carcinoma,CDC)的临床病理特点、诊断及鉴别诊断。方法对4例CDC进行临床病理学观察及免疫组化标记,并复习相关文献。结果肿瘤位于肾髓质内,镜下为管状、乳头状结构,肿瘤细胞呈靴钉样,伴间质纤维化及炎症细胞反应,肿瘤旁集合管上皮细胞可见异型增生;免疫表型示肿瘤细胞CKpan、CKL、CKH及CK7均(+),vimentin部分(+)(2/4),CK20、CD10、RCC均(-)。结论 CDC是一种高度恶性的肾上皮性肿瘤,临床罕见,易误诊,免疫组化有助于诊断及鉴别诊断。     

糖蛋白非转移性黑色素瘤蛋白B在肾嗜酸性肿瘤鉴别诊断中的意义

目的探讨糖蛋白非转移性黑色素瘤蛋白B(glycoprotein nonmetastatic melanoma protein B, GPNMB)在各种肾嗜酸性肿瘤中的表达情况, 并比较GPNMB与细胞角蛋白(CK)20、CK7、CD117在肾嗜酸性肿瘤鉴别诊断中的价值。方法收集南京大学医学院附属鼓楼医院病理科2017年1月至2022年3月传统类型肾肿瘤嗜酸细胞亚型, 包括22例肾透明细胞癌嗜酸细胞亚型(e-ccRCC)、19例肾乳头状细胞癌嗜酸细胞亚型(e-papRCC)、17例肾嫌色细胞癌嗜酸细胞亚型(e-chRCC)、12例肾嗜酸细胞瘤(RO)和新兴的具有嗜酸细胞特征的肾肿瘤类型, 包括3例嗜酸性实性囊性肾细胞癌(ESC RCC)、3例肾低级别嗜酸细胞肿瘤(LOT)、4例延胡索酸水合酶缺陷型肾细胞癌(FH-dRCC)以及5例肾脏上皮样血管平滑肌脂肪瘤(E-AML), 采用免疫组织化学EnVision法染色检测GPNMB与CK20、CK7、CD117在上述肿瘤中的表达情况, 并统计分析其在以上各种肾肿瘤鉴别诊断中的意义。结果 GPNMB在ESC RCC、LOT、FH-dRCC这3种新...     

具有乳头状结构的透明细胞肾细胞癌临床病理分析

目的探讨具有乳头状结构的透明细胞肾细胞癌的临床病理学特征及诊断与鉴别诊断。方法对12例具有乳头状结构的透明细胞肾癌进行光镜及免疫组织化学观察。结果12例中男性11例,女性1例,平均53岁。10例发生于右侧肾脏,2例发生于左侧肾脏,主要症状为血尿、腰腹痛或无明显症状仅体检发现。12例肿瘤组织形态学上都具有乳头状结构区域,占整体肿瘤的10%～30%,其他区域为经典型透明细胞癌排列区,乳头结构为原发性簇状微乳头、小管乳头或纤维血管轴心乳头及继发性囊性变形成、坏死形成或人工因素形成的乳头;免疫组化:CK(12/12)、CD10(9/12)、vimentin(11/12)、CK7(5/12)、AMACR(3/12)阳性,CD117和TFE3阴性。9例患者随访2至66个月,5例无瘤生存,3例复发,其中2例死亡。结论具有乳头状结构的透明细胞肾细胞癌属于透明细胞肾细胞癌范畴,以形态学上具有乳头状结构为特点,免疫表型与经典型透明细胞肾癌基本一致并具有一定的差异,这些特点对临床病理诊断具有很高的价值。     

Useful markers for differential diagnosis of oncocytoma, chromophobe renal cell carcinoma and conventional renal cell carcinoma

Renal oncocytoma, conventional RCC (granular cell type) and chromophobe RCC have different prognosis. Sometimes differentiation between them is difficult in HandE slides. In a 5-year study of 128 renal tumors, we selected 76 cases [30 conventional RCC (CRCC), 16 papillary RCC, 21 chromophobe RCC (ChRCC), 8 oncocytoma, 1 collecting duct carcinoma (cdc)] and staining with Hale's colloidal iron, CK7, CK8, CK18, CK19, CK20, Vimentin, EMA, CD10 and RCC marker were done. No significant difference was seen between renal tumor subtypes with CK8, CK18, CK19, CK20 and EMA. The most useful markers were Vimentin, CK7, CD10, RCC marker and Hale's colloidal iron. Hale's colloidal iron staining with diffuse reticular fine cytoplasmic pattern was present in ChRCCs, but was absent in other subtypes and oncocytomas. Vimentin, CK7, CD10, RCC marker and Hale's colloidal iron can be used for the differential diagnosis of problematic epithelial tumors of kidney (CRCC, ChRCC and oncocytoma) - i.e. ChRCC: Vimentin, CD10 and RCC marker - negative, CK7 - positive and positive diffuse fine reticular cytoplasmic pattern of Hale's colloidal iron; oncocytoma: Vimentin, CK7, RCC marker and CD10 - negative and Hale's colloidal iron - negative; CRCC: CK7 - negative, Vimentin, CD10 and RCC marker - positive and Hale's colloidal iron - negative.     

Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma

Distinguishing renal oncocytoma from chromophobe and other renal carcinomas is essential, considering their differing biological potentials. Although renal oncocytoma is considered a benign tumor, chromophobe renal cell carcinoma has potentially malignant biological behavior. The numerous reported studies on distinguishing these 2 entities have been based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. But none of these features has proven to be reliably specific, especially in tumors with overlapping phenotypes. We report a novel immunohistochemical approach based on the expression of a recently described kidney-specific cadherin (Ksp-cadherin) for the differential diagnosis of these 2 tumors. We compared Ksp-cadherin expression in 212 renal tumors, including 102 clear cell renal carcinomas, 46 papillary renal cell carcinomas, 30 chromophobe carcinomas, 3 collecting duct carcinomas, and 31 oncocytomas. In addition, we examined the expression of epithelial membrane antigen, vimentin, CK7, and Hale's colloidal iron staining. We found that chromophobe renal cell carcinomas consistently (96.7% of cases) demonstrated a distinctive membrane pattern of Ksp-cadherin expression, whereas renal oncocytomas (3.2%), clear cell renal cell carcinomas (0%), papillary renal cell carcinomas (2.2%), and collecting duct carcinomas (0%) usually did not express Ksp-cadherin. CK7 expression was found in 90.0%, 6.5%, 7.8%, 76.1%, and 33.3% of these tumor cases, respectively. Whereas CK7 was detected in different types of renal cell carcinomas, Ksp-cadherin was expressed almost exclusively in chromophobe renal cell carcinomas. Immunohistochemical analysis of Ksp-cadherin offers a fast, reliable approach for the distinguishing between renal oncocytoma and chromophobe renal cell carcinoma that is applicable for routine pathology laboratory studies without the need for time-consuming and costly ancillary studies.     

Role of carbonic anhydrase IX, α-methylacyl coenzyme a racemase,cytokeratin 7, and galectin-3 in the evaluation of renal neoplasms: a tissue microarray immunohistochemical study

Kidney tumors of various types may behave differently and have different prognosis. Because of some overlapping morphological features and immunohistochemical staining pattern, they may pose diagnostic challenge. Therefore, it is necessary to explore additional immunohistochemical stains to help classifying these epithelial neoplasms. Tissue microarrays of 20 cases each of renal cell carcinomas of clear cell, chromophobe, and papillary variants and oncocytoma were constructed and used to test a panel of immunohistochemical markers including carbonic anhydrase IX, galectin-3, cytokeratin 7 (CK7), and α-methylacyl coenzyme a racemase. Carbonic anhydrase IX was highly sensitive for clear cell renal cell carcinoma (90% positivity) and was negative in all other renal epithelial tumors except for 1 chromophobe renal cell carcinoma (chRCC). Expression of galectin-3 was found mostly in renal tumors with oncocytic features, including oncocytomas (100%) and chRCCs (89%). α-Methylacyl coenzyme a racemase was positive in papillary renal cell carcinoma (100%). CK7 was positive in papillary renal cell carcinoma (90%), chRCC (89%), and oncocytoma (90%). Although both chRCC and oncocytoma were positive for CK7, but with a different patterns, CK7 staining in chRCC was diffuse, whereas it was sporadic in oncocytoma. Panel of carbonic anhydrase IX, galectin-3, CK7, and α-methylacyl coenzyme a racemase is sensitive and specific for the differential diagnosis of the renal epithelial tumors.     

Expression of claudin-7 in benign kidney and kidney tumors

Claudins, a family of tight junction-related transmembrane proteins, have been implicated in the pathogenesis of various human neoplasms. Expression of claudin-7 was increased in chromophobe renal cell carcinoma in a recent oligonucleotide microarray study. We studied the expression of claudin-7 in benign and neoplastic kidneys by immunohistochemical staining. Distal nephron (distal convoluted tubule and thick ascending limb of Henle's loop) epithelium showed strong membranous staining in 100% (174/174) of the cases. Chromophobe renal cell carcinoma was positive for claudin-7 expression in 100% (36/36) of cases, while papillary renal cell carcinoma, oncocytoma and clear cell renal cell carcinoma were positive in 90% (71/80), 45% (21/47) and 7% (7/98) of the cases, respectively. Differential expression of Claudin-7 in different types of renal cell neoplasms can be useful in their differential diagnosis, particularly when used in a panel of markers. In addition, results from this study support previous reports of distal nephron origin for chromophobe renal cell carcinoma and oncocytoma. The data also suggest that, as far as claudin-7 expression is concerned, papillary renal cell carcinoma may be more closely related to the distal nephron, rather than the proximal nephron.     

The expanding role of renal mass biopsy

Usage of renal mass biopsy has increased in recent years, ranging from selected clinical scenarios to routine implementation in some institutions. Major tasks for the field of diagnostic histopathology include discriminating primary renal cell cancers from other tumors, especially metastases, hematolymphoid tumors, and urothelial carcinoma. Within primary renal cell neoplasms, relevant distinctions include recognizing clear cell papillary renal cell carcinoma, which despite its resemblance to clear cell cancer is nonaggressive, as well as discriminating oncocytoma from chromophobe carcinoma. Helpful immunohistochemical markers include PAX8 for verification of primary renal cell lineage and carbonic anhydrase IX for support of clear cell subtype. Cytokeratin 7 is generally considered the best marker for discriminating oncocytoma from chromophobe renal cell carcinoma, showing only rare positive cells in oncocytoma and greater staining in chromophobe carcinoma. For metastatic tumors, attempting to discriminate clear cell from non-clear cell types may be important for treatment selection.     

Onkozytom versus chromophobes Nierenkarzinom

The differentiation of oncocytic tumors of the kidneys is often difficult, particularly in renal biopsies. Differential diagnoses are chromophobe renal cell carcinoma (ChRCC), renal oncocytoma (RO), the oncocytic variant of papillary renal cell carcinoma (OPRCC), the eosinophilic variant of clear cell renal cell carcinoma (CCRCC) and hybrid oncocytic chromophobe tumors (HOCT). In difficult cases that cannot be resolved by morphology alone, immunohistochemistry is usually helpful. The RO and ChRCC show positive reactions for CD117, they are negative for vimentin and alpha-methylacyl-CoA racemase (AMACR), while CCRCC are positive for vimentin and OPRCC are positive for AMACR. To distinguish between RO and ChRCC, CK7, claudin-7 (both strongly positive in ChRCC and negative or patchy positive in RO) and epithelial cell adhesion molecule (EpCAM) can be used (positive in ChRCC, negative in RO); however, a diagnosis may remain difficult in some cases even with the use of immunohistochemistry. Thus, numerous new methods are being developed in the field of molecular pathology and computer-based morphometric tumor analysis; however, these new methods have not yet been applied in routine diagnostics.     

Hybrid chromophobe renal cell neoplasm

Hybrid renal cell neoplasms (HRCNs) containing areas of tumor cells displaying cytological features of chromophobe renal cell carcinoma (CHRCC) and renal oncocytoma (RO) have been recently described in patients with renal oncocytosis and Birt-Hogg-Dube (BHD) syndrome (autosomal dominant genodermatosis). In this study, we identified cases of sporadic HRCN. We reviewed 425 consecutive renal cell carcinomas (RCC), 18 CHRCC, six HRCN, and 25 RO. Five HRCN were identified, including four from the group of RCC and two from RO. Patient age ranged from 40 to 68 years (mean age: 54 years), and the male:female ratio was 4:1. Tumors measured from 1.8 to 5 cm (mean diameter: 3.0 cm). Tumoral necrosis was not seen. Vascular invasion into medium-sized veins was identified in one HRCN. Chromophobe cells accounted for 20-80% of the tumors. Hale's colloidal stain showed weak to moderate diffuse cytoplasmic staining in scattered cells corresponding to those displaying routine staining features of chromophobe cells. Areas of oncocytic cells in studied tumors and control oncocytomas showed negative or focal cytoplasmic staining usually bordering extra- or intra-cytoplasmic lumina. Immunostaining for cytokeratin 7 and vimentin showed focal immunoreactivity in three cases and negative reactivity in all six cases, respectively. None of the study cases had microscopic RO, as commonly seen in renal oncocytosis, or were associated with BHD syndrome Sporadic HRCN accounted for 1% of RCC. They were of smaller size than RCC and were associated with a favorable prognosis.     

Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma

AIMS: The histopathological diagnosis of chromophobe renal cell carcinoma can present a diagnostic challenge, as these tumours can resemble either conventional renal cell carcinoma or oncocytoma. The aim of this study was to determine whether cytokeratin 7 expression is of practical use in the distinction of these three entities. METHODS AND RESULTS: A total of 40 cases previously diagnosed as either chromophobe renal cell carcinoma, conventional renal cell carcinoma or oncocytoma were identified. A representative section of each was stained with H&E and cytokeratin 7. Following independent review of the cases by three pathologists, a consensus diagnosis for each case was reached and the pattern of cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal cell carcinoma in the study, all of which showed a characteristic peripheral membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of conventional renal cell carcinoma studied were negative for cytokeratin 7, while one case showed weak focal staining of <5% of the cells. The 10 cases of oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin 7, without the characteristic peripheral membrane accentuation seen in the chromophobe carcinomas. CONCLUSIONS: Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.