Chromophobe renal cell carcinoma with prominent lymph node metastasis and polysomy of chromosome 21: poorly differentiated form or "presarcomatoid" form?

Lymph node metastasis of chromophobe renal cell carcinoma (RCC) is extremely rare. It has been recently reported that sarcomatoid chromophobe RCC frequently show polysomy of chromosomes 1, 2, 6, 10, and 17. In this article, we report an unusual case of chromophobe RCC. A 42-year-old Japanese woman presented with hematuria and complained of inguinal pain 2 months after the initial symptoms. Radical nephrectomy and renal hilar lymphadenectomy were performed. The tumor was 8 cm in greatest diameter; its cut surface was beige in color. Large metastasis to the renal hilar lymph node was identified. Histological examination of the right renal tumor met the criteria of chromophobe RCC. In addition to histological findings of typical chromophobe RCC, small cell foci, comedo-like necrosis, trabecular growth pattern, and sclerosing stroma were observed. However, no sarcomatoid foci were identified anywhere, despite extensive tumor sampling including lymph node lesions. Immunohistochemically, neoplastic cells were positive for E-cadherin and CD117 (c-kit). Ultrastructurally, tumorous cells contained abundant mitochondria and cytoplasmic microvesicles. Fluorescence in situ hybridization showed monosomy of chromosomes 2 and 10 and polysomy of chromosome 21. Finally, we suggest that this tumor may show the poorly differentiated or presarcomatoid form of chromophobe RCC.     

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.     

Immunohistochemical marker panel differentiates between the three most common subtypes of renal cell carcinoma independent from histomorphologic criteria

To develop a reliable immunohistochemical marker panel differentiating between the three most common renal cell carcinoma (RCC) subtypes without inclusion of histomorphologic criteria we investigated protein expression of vimentin, glutathione S-transferase alpha (GST-α), CD10, CD117 (C-KIT), carbonic anhydrase 2 (CAII), parvalbumin, alpha-methyl-CoA-racemase (AMACR), and cytokeratin-19 (CK 19) in 65 age and stage matched trios of clear cell carcinoma, papillary renal carcinoma and chromophobe renal carcinoma using tissue microarrays. All markers displayed significant differential expression among the subtypes (p < 0.001) except CAII (p = 0.192). According to positive (LR+) and negative (LR−) likelihood ratio, six markers (CD10, GST-α, AMACR, CK19, C-KIT and arvalbumin) demonstrated acceptable or good values to detect certain subtypes of RCC, but failed in terms of ruling out the respective subtypes. Based on the individual performance of these six markers, we combined them and reviewed each single case: LR+ for detection of clear cell RCC considerably increased by application of the six marker panel, but did not exceed 10. LR− was still >0.1; in case of papillary RCC LR+ rose beyond 10, but LR− remained >0.1. LR+ for recognition of chromophobe RCC rose far beyond 10, but LR− remained >0.1. Thus, the panel can reliably recognize two main RCC subtypes without inclusion of histomorphologic features. Further improvement is needed for consistent detection of clear cell RCC and for dependably ruling out all three main subtypes as well as identification of rare variants and benign lesions like oncocytoma.     

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。     

Chromophobe renal cell carcinoma: an immunohistochemical study of 21 Japanese cases.

Chromophobe renal cell carcinoma (RCC) is a newly established category of RCC composed histologically of characteristic "chromophobe" tumor cells. Although ultrastructural and immunohistochemical studies showed that these tumor cells present several features similar to those found in the intercalated cells of the collecting duct, immunohistochemical studies using antibody panels on a large number of cases are limited. We performed an immunohistochemical study of 21 Japanese cases of chromophobe RCC, along with cases of clear RCC and renal oncocytoma, to find hallmarks useful for precise differential diagnosis of these tumors. Chromophobe RCC was positive for epithelial membrane antigen but negative for vimentin. Cytokeratins did not show constant immunoreactivity in the three types of renal tumors. Furthermore, all of the chromophobe RCCs and renal oncocytomas were positive for E-cadherin but not for N-cadherin, whereas all of the clear RCCs were negative for E-cadherin, and 58% were positive for N-cadherin. The Ki-67 labeling indices were significantly lower in cases classified as (pT1) or Grade 2 chromophobe RCC than in cases of clear RCC. Immunoreaction for E-cadherin was demonstrated to be useful for distinguishing chromophobe RCC from clear RCC, and a low Ki-67 labeling index might indicate a favorable prognosis, as reported in several previous studies.     

Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers

The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes-vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.     

The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases

AIMS: To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. METHODS AND RESULTS: Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. CONCLUSIONS: MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.     

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.     

CD10 is expressed in a subset of chromophobe renal cell carcinomas.

CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas.     

Kidney-specific cadherin, a specific marker for the distal portion of the nephron and related renal neoplasms.

Renal cell neoplasms are presumably derived from different cell types of the nephron. Clear cell and papillary renal cell carcinoma (RCC) are thought to be of proximal tubular origin, whereas oncocytoma and chromophobe RCC are derived from intercalated cells of distal nephron. A few molecules, such as RCC marker and CD10, have been shown to be markers for clear cell RCC and papillary RCC. Such markers are not yet available for renal tumors presumably of the distal nephron. The expression of kidney-specific (Ksp) cadherin, a recently cloned gene thought to be transcribed exclusively in the kidney, was studied in normal human kidney, as well as in 105 primary renal neoplasms, including 42 clear cell RCC, 30 papillary RCC, 13 chromophobe RCC, and 20 oncocytomas. The expression patterns were compared with those of RCC marker. The Ksp-cadherin expression was noted preferentially in distal convoluted tubules with a basolateral membrane stain in normal kidney. All 13 chromophobe RCC and 19 of 20 oncocytomas showed diffuse and strong immunoreactivity for Ksp-cadherin, while only 14% clear cell RCC and 13% papillary RCC showed focal positivity. The RCC marker expression was detected in 85%, 98%, 15% and 0% of clear cell RCC, papillary RCC, chromophobe RCC, and oncocytoma, respectively. A few clear cell RCC and papillary RCC showed dual expression of both RCC marker and Ksp-cadherin, which appear to have distinct histologic features. These results demonstrated high sensitivity and specificity of Ksp-cadherin for distal convoluted tubules, which can be used as adjunct for diagnosis of chromophobe RCC.     

Utility of CK7 and CK20 immunohistochemistry in the detection of synchronous breast and colon carcinoma in a pleural effusion: a case report and supporting survey of archival material

We present a case of synchronous breast and colon carcinoma in a pleural effusion, to our knowledge the first such reported case in the English-language literature. The patient was a 55-yr-old white female with known metastatic breast and colon carcinoma who developed a malignant pleural effusion which demonstrated two strikingly different populations of malignant cells by immunohistochemical study of cell block material. One cell population demonstrated a cytokeratin (CK)7+/CK20-/ER+ phenotype, while the other demonstrated a CK7-/CK20+/ER- phenotype, consistent with breast and colon origin, respectively. An immunohistochemical survey of archival breast and colon primary and metastatic carcinomas confirmed the established CK7+/CK20- phenotype of breast and CK7-/CK20+ phenotype of colon primary carcinomas, and the maintenance of this phenotype in metastases thereof. A survey of benign and malignant mesothelial lesions confirmed the absence of staining for estrogen receptor, but showed 6/10 cases weakly positive for CK20, which has not been described in other published series. This unusual case graphically illustrates the utility of cytokeratin subset immunohistochemistry in effusion cytology.     

Chromophobe renal cell carcinoma with sarcomatoid change. A case report

Chromophobe renal cell carcinoma (RCC) is a newly established entity of renal neoplasm with histological and molecular biological features different from those of common RCCs. Chromophobe RCC shows characteristically cloudy and reticular cytoplasm and cellular features resembling distal nephron. Its prognosis has been reported to be more favorable than that of common RCCs. Recently, however, several cases have been reported which showed sarcomatoid change to present poor prognosis. Here we present a case of chromophobe RCC with sarcomatoid change which was once resected surgically. The surgically resected tumor was histologically composed of chromophobe epithelial cell sheets and sarcomatoid elements. The former showed positivity for colloid iron staining, and was immunohistochemically positive for E-cadherin and epithelial membrane antigen (EMA), whereas the latter was positive for vimentin instead of colloid iron and E-cadherin. EMA was focally positive in the sarcomatoid element. The patient died with systemic metastases 14 months after the operation. Histologically, the metastatic tumors were composed only of sarcomatoid element lacking epithelial element. Based on these findings and previous reports, this case supports the existence of a tumor progression pathway from chromophobe to sarcomatoid RCC. It is necessary to perform careful postoperative investigation of chromophobe RCC due to its possible histological progression to the sarcomatoid subtype.     

Distinct Cytoplasmic Expression of KL-6 Mucin in Chromophobe Renal Cell Carcinoma: A Comparative Immunohistochemical Study with Other Renal Epithelial Cell Tumors

The presence of cytoplasmic sialyl glycoproteins is a conspicuous feature in chromophobe renal cell carcinoma (RCC). We compared the immunohistochemical expression of sialyl glycoproteins in chromophobe RCC with that in other types of renal tumors. Formalin-fixed, paraffin-embedded tissues of surgically resected renal tumors (chromophobe RCC, 14 cases [10 cases of classic type and 4 cases of eosinophilic variant]; oncocytoma, 7 cases; and clear cell RCC, 9 cases) and kidneys from immature infants (4 cases) were immunostained with antibodies against sialyl glycoproteins (anti-KL-6 and anti-sialyl MUC1 antibodies). Cytoplasmic expression of KL-6 and sialyl MUC1 was distinctive in the chromophobe RCC and renal oncocytoma cells, and in the intercalated cells in collecting duct epithelia. Apical-surface staining of these sialyl glycoproteins was predominantly observed in clear RCC, in the epithelia of the distal tubule and collecting duct, and in the neonatal renal proximal tubule, but not in those of the adult renal proximal tubule. The above-mentioned observations provide additional evidence for similar phenotypic profiles of chromophobe RCC and renal oncocytoma, and the intercalated cells in collecting ducts and the oncofetal expression of sialyl glycoproteins in clear cell RCC. KL-6 is a potential tumor marker for renal tumors.     

Chromophobe renal cell carcinoma: useful diagnostic application of imprint cytology and fluorescence in situ hybridization of chromosomes 10 and 21 in two cases of typical and eosinophilic variants

Chromophobe renal cell carcinoma (RCC) is subdivided into typical and eosinophilic variants. We report such two cases with focus on imprint cytology and fluorescence in situ hybridization (FISH). The first case is a 53-year-old Japanese man and the second is a 76-year-old Japanese man. Histologically, the diagnosis of typical and eosinophilic variants of chromophobe RCC was suspected. In imprint cytology, irregularity of nuclear membrane, binucleation, perinuclear halo, and thick cell border were observed. Immunohistochemically, neoplastic cells of both tumors were positive for cytokeratin 7, E-cadherin, c-kit, and CD10. In FISH study, both tumors revealed the monosomy of chromosomes 10 and 21. Additionally, FISH study in eosinophilic variant of chromophobe RCC showed the disomy of chromosomes 7 and 17. In conclusion, we suggest that the combination study of imprint cytology and FISH of chromosomes 10 and 21 as well as routine histology may contribute to the accurate diagnosis of chromophobe RCC.     

Biphasic alveolosquamoid renal carcinoma: a histomorphological,immunohistochemical, molecular genetic,and ultrastructural study of a distinctive morphologic variant of renal cell carcinoma

Only a few cases of sarcomatoid renal cell carcinomas (RCCs) with squamous differentiation have been published. We present 2 RCCs exhibiting a hitherto not reported biphasic neoplastic cell population exhibiting a predominantly alveolar architecture where squamoid differentiation was identified in one of the neoplastic cell populations. None of the tumors showed chromophobe features or any evidence of sarcomatoid transformation. The tumors arose in 2 adult patients and were characterized by routine histology, immunohistochemistry, ultrastructure, array comparative genomic hybridization, confirmatory fluorescent in situ hybridization, and loss of heterozygosity analysis. Tumors measured 3 and 4 cm and were located within the renal parenchyma and had no pelvicalyceal connection. Both tumors were composed of a distinctly dual-cell population. The larger tumor cells displayed squamoid features and formed round well-demarcated solid alveolated islands that, in large parts, were surrounded by a smaller neoplastic cell component. The squamoid cells were immunoreactive for cytokeratins (CKs) (AE1-AE3, Cam 5.2, CK5/6, CK7, and CK20), epithelial membrane antigen, racemase/AMACR, and carboanhydrase IX (in 1 case focally). The small cell population was positive for CK7, epithelial membrane antigen, and racemase/AMACR, whereas CK20, AE1-3, and carboanhydrase IX were negative. CD10 was focally positive in the large squamoid cells in 1 case. Cathepsin K, E-cadherin, and CD117 displayed focal positivity in 1 case. Vimentin, RCC marker, parvalbumin, S100 protein, S100 A1, p63, p53, CDX2, uroplakin III, HMB45, TFE3, WT1, synaptophysin, chromogranin A, thyroglobulin, and TTF1 were negative. The proliferative activity (Ki-67) was low (1%) in the small cell component in both cases, whereas the large neoplastic tumor cells displayed a significantly higher proliferation (20%-35%). Ultrastructurally, desmosomes and tonofilaments were identified in the large tumor cells, confirming squamoid differentiation in a subset of tumor cells. Array comparative genomic hybridization of 1 analyzable case (confirmed with fluorescent in situ hybridization and loss of heterozygosity analysis) revealed partial or complete losses of chromosomes 2, 5, 6, 9, 12, 15, 16, 17, 18 and 22, (including biallelic loss of CDKN2A locus) and partial gains of chromosomes 1, 5, 11, 12 and 13. Follow-up at 6 years showed no recurrence or metastasis in 1 patient. The other (male) patients had a subcutaneous metastasis at presentation, but during a 1-year follow-up no evidence of recurrence or further metastatic events have been documented. Our data indicate that biphasic alveolosquamoid renal carcinoma is a unique and distinctive tumor. The large squamoid and small tumor cells have overlapping but still distinctive immunohistochemical patterns of protein expression. Multiple chromosomal aberrations were identified, some of them located in regions with known tumor suppressor genes and oncogenes.     

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.     

Typing of renal tumors by morphological and immunocytochemical evaluation of fine needle aspirates

Image-guided fine needle aspiration biopsy (FNAB) of renal masses can accurately evaluate malignancy. Adjunct methods are needed for accurate typing of renal cell carcinomas (RCC) and benign neoplasms. Cytopathological diagnoses of 79 routine ultrasound-guided FNAB of renal lesions were compared to consequent histological diagnosis and size of tumors. Cytology samples were sufficient for immunocytochemical subtyping in 43 cases (54.4%). The median tumor size was 2.8 cm, with 57 cases (76%) smaller than or equal to 4 cm. When a panel of immunocytochemical stainings (vimentin, CK7, CD117, P504S) was applied, accurate diagnoses were obtained in 11/12 (91.7%) of clear cell RCC (CRCC), 14/17 (82.3%) of papillary RCC (PRCC) and 5/7 (71.4%) of chromophobe RCC (ChRCC), respectively. Substantial cell pleomorphism with unusual immunostainings led to erroneous diagnosis of pheochromocytoma in CRCC with eosinophilic cytoplasm. Only 30% of CRCC were correctly diagnosed in the group without immunostaining, seven were suspicious for CRCC, and the remainder had unrepresentative material for CRCC. Cytopathological diagnoses were less accurate in oncocytomas (n = 11), regardless of immunocytochemical staining. Cystic nephromas (n = 2) and MEST (n = 1) were overdiagnosed as suspicious and positive for PRCC, respectively, with immunocytochemical staining not assisting in correct diagnosis. RCC can be accurately typed as CRCC, PRCC or ChRCC in fine needle aspirates in a routine clinical setting if the cellular material is sufficient and a panel of antibodies is used (vimentin, CK7, P504S, CD117). The classification of oncocytomas and cystic nephromas is not reliable since atypical morphology and immunocytochemical reactions overlap with RCC.     

Progesterone receptor reactivity in renal oncocytoma and chromophobe renal cell carcinoma

Aims:  To investigate the reactivity for oestrogen and progesterone receptors (ER and PR) in renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC).
Materials and methods:  Thirty-eight RO, 25 CHRCC, 20 papillary RCC with oncocytic cytoplasm and 10 clear cell RCC with dominant eosinophilic cytoplasm were submitted for immunohistochemistry for ER, PR, CD117 and RCC.
Results:  All cases of RO and CHRCC displayed moderately positive reactivity for PR. The nuclear reactivity ranged from 60% to 90% in RO and from occasional cells to 70% in CHRCC. In CHRCC, reactivity tended to be more prevalent in areas of tumour cells with eosinophilic cytoplasm. Progesterone reactivity was focal in areas. All RO and most CHRCC were reactive for CD117 and neither RO nor CHRCC was reactive for RCC. CD117 reactivity tended to be more intense in CHRCC than in RO. Negative reactivity for CD117 and positive reactivity for RCC were observed in almost all RCC, as reported in the literature.
Conclusions:  PR can be used in combination with CD117 and RCC in the differential diagnosis of RO and eosinophilic variant of CHRCC with other RCC with oncocytic or eosinophilic cytoplasm.     

Chromosomal abnormalities in renal cell carcinoma variants detected by Urovysion fluorescence in situ hybridization on paraffin-embedded tissue

Urovysion fluorescence in situ hybridization (UVFISH) identifies malignant cells in urine by detecting specific urothelial carcinoma-related chromosomal abnormalities. Some renal carcinomas (RCCs) share overlapping chromosomal aberrations with urothelial carcinoma. Malignant renal cells that are shed in urine can potentially cause a positive UVFISH result. We evaluated UVFISH in RCCs to determine its potential applicability to the diagnosis and grading of RCCs. Paraffin blocks from 39 RCCs (25 clear cell, 9 papillary, 2 chromophobe, and 3 sarcomatoid) and 15 controls (5 renal oncocytomas and 10 urothelial carcinomas) were tested. Of the RCCs, 15 (40%) were UVFISH-positive (9/25 [40%] clear cell, 3/9 [30%] papillary, 1/2 [50%] chromophobe, and 2/3 [67%] sarcomatoid carcinoma) and 24 (60%) were negative. Of the 15 controls, 8 (～50%) were UVFISH-positive (2/5 [40%] oncocytomas and 6/10 [60%] urothelial carcinomas) and 7 (～50%) were UVFISH-negative. Polysomy of chromosome 17 showed a statistically significant correlation with RCC subtype, being absent in most of the clear cell RCCs (P = .0096) compared with other RCCs. Polysomy of chromosome 7 was more frequent in high-grade than low-grade RCC (P = .0197) and more likely in high-grade clear cell than low-grade clear cell RCC (P = .0120). In conclusion, we showed that RCC has overlapping chromosomal abnormalities with urothelial carcinoma and can cause a positive UVFISH result. This has implications for the interpretation of Urovysion in patients whose urine contains malignant cells but who have negative cystoscopy and a concomitant renal mass. The chromosomal abnormalities observed in RCC are not distinct from those in urothelial carcinoma; therefore, UVFISH cannot distinguish these tumor types, nor can it type or grade RCC.