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.     

Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors

Keratin immunohistochemistry represents a widely applied differential diagnostic tool in surgical pathology. To investigate the value of keratin subtyping for the diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we performed a detailed immunohistochemical study, applying 22 different monoclonal keratin antibodies on a large series of 233 renal tumors [125 conventional, 22 chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66 oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7, 8, 18, and 19 was present in all tumor entities, albeit in varying quantities. With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct perinuclear and punctate dot-like pattern, which was not observed in renal cancer specimens. The only tumors showing immunoreactivity for keratin 20 were two type-2 papillary cancers. All other monospecific keratin antibodies yielded consistently negative results. Overall, in contrast to some recent publications, keratin subtyping generally appeared to be of additional value only for the differentiation of renal epithelial tumors. Hence, with respect to differential diagnostic value, Hales colloidal iron stain and vimentin immunostaining are still the most useful tools in renal tumor pathology.     

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.     

Cytokeratins 7 and 20 immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas.

Chromophobe renal cell carcinomas and renal oncocytomas share morphologic similarities and may present a diagnostic challenge on routine hematoxylin-eosin staining. Currently recommended additional studies of Hale's colloidal iron staining and electron microscopy are often difficult to interpret and technically challenging and may not be readily available. Previous studies have reported conflicting results with regard to the cytokeratin 7 staining pattern in chromophobe renal cell carcinomas and renal oncocytomas. Cytokeratin 20 expression in chromophobe renal cell carcinomas has not previously been studied. Formalin-fixed paraffin-embedded tissue of 11 chromophobe renal cell carcinomas and 21 renal oncocytomas were retrieved from the archived files (1984-2000) of four teaching hospitals. Of the 11 chromophobe renal cell carcinomas, eight stained positive (73%) for cytokeratin 7, one stained focally positive (9%), and two cases (18%) were completely negative. Cytokeratin 7 staining of the 21 oncocytomas revealed 4 positive (19%), 7 focally positive (33%), and 10 negative cases (48%). Cytokeratin 20 was uniformly negative on all 11 cases of chromophobe renal cell carcinomas and all 21 cases of oncocytomas. Cytokeratin 7 does not appear to show the consistent immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas, as has been previously suggested. Cytokeratin 20 immunostaining in chromophobe renal cell carcinomas and renal oncocytomas is uniformly negative. Despite the technical and interpretive challenges of Hale's colloidal iron, it is still the most useful stain in differentiating chromophobe renal cell carcinomas from renal oncocytomas.     

Complexity of expression of intermediate filament proteins, including glial filament protein, in endometrial and ovarian adenocarcinomas.

The expression patterns of intermediate filament proteins of primary and metastatic endometrial (n = 18) and ovarian (n = 24) adenocarcinomas were analyzed by immunocytochemistry using a panel of specific antibodies and by gel electrophoresis of cytoskeletal preparations, followed by immunoblotting. All cells of all endometrial adenocarcinomas studied contained the "simple epithelial"-type cytokeratins (CKs) 8, 18, and (mostly) 19, with variable numbers of cells also positive for CK 7 and vimentin. In addition, most of these tumors contained individual cells or groups of cells that were positive for the stratification-related CKs 4, 5, 6, 13, 14, and 17. The latter CKs were often associated with squamous cell foci, but were also found in some single (nonsquamous) tumor cells, indicative of early stages of squamous cell differentiation. Ovarian carcinomas of various histologic types and grades contained predominantly CKs 7, 8, 18, and 19. Serous, endometrioid, and anaplastic tumors, but not mucinous and clear cell tumors, also contained minor amounts of stratification-related CKs in variable combinations, mostly including CK 4. In all tumor types except mucinous tumors, vimentin was consistently detected in variable proportions of tumor cells which, however, were rather low in anaplastic carcinomas. Surprisingly, glial filament protein was detected in a minor proportion (< or = 20%) of tumor cells in seven of 14 serous and endometrioid ovarian carcinomas and in three of 18 endometrial carcinomas. These different intermediate filament expression patterns of müllerian duct-type carcinomas, only partly related to the morphologic appearance of the specific type of tumor, might reflect the multipotentiality of differentiation of müllerian duct-derived epithelia. Cytoskeletal features of potential diagnostic value, especially in metastatic carcinomas, are discussed.     

Claudin-7 and claudin-8: immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma

Claudin-7 and claudin-8 code for tight junction proteins expressed in distal nephron epithelium. In a recent oligonucleotide microarray study, we identified claudin-7 and claudin-8 as candidate markers to distinguish chromophobe renal cell carcinoma from other renal tumors, including oncocytoma. Distinction of these lesions can be difficult by light microscopy but is clinically important because chromophobe renal cell carcinoma has malignant biological potential, whereas renal oncocytoma is benign. Claudin-7 and claudin-8 expression was studied by immunohistochemistry in 11 chromophobe renal cell carcinomas and 17 oncocytomas using formalin-fixed paraffin-embedded tissue sections of tumor with adjacent nonneoplastic kidney. Steam antigen retrieval was performed before immunohistochemistry. Specificity was verified by negative control reactions without primary antibody and appropriate membranous staining patterns in positive control tissues (colon carcinoma and adjacent nonneoplastic kidney). Claudin-7 protein was expressed in a membranous pattern in 10 of 11 chromophobe renal cell carcinomas and 4 of 17 oncocytomas (P < .01). Claudin-8 was expressed in multiple patterns: In oncocytoma, 11 of 17 cases showed cytoplasmic, 4 of 17 membranous, and 2 of 17 negative reactions. In chromophobe renal cell carcinoma, 0 of 11 cases showed cytoplasmic, 3 of 11 membranous, and 8 of 11 negative reactions (P < .01). The immunohistochemical pattern of membranous claudin-7 and negative claudin-8 was seen in 7 of 11 chromophobe renal cell carcinomas and 1 of 17 oncocytomas (63% sensitivity, 84% specificity, 88% positive predictive value for chromophobe renal cell carcinoma). Negative claudin-7 and cytoplasmic claudin-8 were observed in 10 of 17 oncocytomas and 0 of 11 chromophobe renal cell carcinomas (59% sensitivity, 100% specificity and positive predictive value for oncocytoma). The distal nephron proteins claudin-7 and claudin-8 have potential use as immunohistochemical biomarkers in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma. Expression of claudin-7 and claudin-8 may reflect the relationship of chromophobe renal cell carcinoma and oncocytoma to intercalated cells of the cortical collecting duct. It may be necessary to identify additional biomarkers to include with claudin-7 and claudin-8 in a larger immunohistochemical panel to improve diagnostic sensitivity and specificity.     

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.     

Establishment and characterization of two divergent cell lines derived from a human chromophobe renal cell carcinoma.

The chromophobe renal cell carcinoma is a distinct type of renal cancer presumably derived from the intercalated cell of the collecting duct system and exhibiting a better prognosis than other types of renal cell carcinoma. Chromophobe carcinomas can be separated from other types of renal cell carcinoma by their characteristic cytomorphology, ultrastructural appearance, cytoskeletal architecture, and cytogenetic aberrations. As no permanent cell line of the chromophobe tumor type has previously been described, we are the first to report on the successful establishment and characterization of two divergent permanent cell lines, ie, chrompho-A and chrompho-B, derived from the same chromophobe renal cell carcinoma. With immunocytochemistry, two-dimensional gel electrophoresis, and Western blot, chrompho-A and chrompho-B exclusively exhibited cytokeratins (Nos. 7, 8, 18, and 19) but not vimentin. Ultrastructural studies revealed numerous cytoplasmic microvesicles as well as coated vesicles that are known to be characteristic features of the intercalated cell. Chrompho-B cells exhibited a shorter mean population doubling time (tD = 43 hours) than chrompho-A cells (tD = 51 hours). Both cell lines failed to produce tumors in nude mice with the subrenal capsule assay. Cytogenetic analyses revealed hyperdiploid chromosome numbers in both cell lines with telomeric associations as well as numeric aberrations known from chromophobe renal cell carcinomas in vivo.     

C-kit expression in renal oncocytomas and chromophobe renal cell carcinomas

C- kit encodes the membrane-bound tyrosine kinase KIT, whose expression has been identified in several types of human neoplasms. Recently, KIT has been reported to be a marker for chromophobe renal cell carcinoma (RCC) and renal angiomyolipoma. However, expression of this molecule has not been adequately studied in other renal tumors, particularly oncocytoma, which may morphologically resemble chromophobe RCC. In this study, we analyzed c- kit messenger RNA (mRNA) levels in 17 chromophobe RCCs and 20 renal oncocytomas obtained from complementary DNA (cDNA) microarrays. Furthermore, comprehensive immunohistochemical analysis of KIT protein using a monoclonal antibody was performed in 226 renal tumors including chromophobe RCC (n=40), oncocytoma (n=41), clear-cell RCC (n=40), renal angiomyolipoma (n=29), and papillary RCC (n=21) on tissue microarrays (TMAs) and was compared with immunostaining results from 25 chromophobe RCCs and 30 oncocytomas using standard sections. The staining intensity was semiquantitatively graded on a 3-tier scoring system. All chromophobe RCCs and oncocytomas showed significant overexpression of c- kit mRNA. The average increase of mRNA compared with normal kidney tissue was 7.4-fold for chromophobe RCCs and 7.4-fold for oncocytomas. Immunohistochemical expression of KIT was found in most chromophobe RCCs (95% in TMAs and 96% in conventional sections) and oncocytomas (88% in TMAs and 100% in conventional sections) but was infrequently observed in renal angiomyolipomas (17%), papillary RCCs (5%), and clear-cell RCCs (3%). Furthermore, the average KIT immunoreactivity in TMAs was stronger in chromophobe RCC (1.93) and oncocytoma (2.07) than in other subtypes of renal tumors tested, including angiomyolipomas (0.17), papillary RCCs (0.05), and clear-cell RCCs (0.03). In conclusion, we found a significant elevation of c- kit mRNA by cDNA expression microarrays and overexpression of KIT protein by immunohistochemistry not only in chromophobe RCCs but also in oncocytomas. In contrast, immunohistochemical expression of KIT was not detected in most other types of renal cell tumors evaluated. The differential expression of c- kit in these renal tumors may have diagnostic and therapeutic implications.     

Expression of kidney-specific cadherin in chromophobe renal cell carcinoma and renal oncocytoma

Kidney-specific cadherin (Ksp-cad) recently was proposed to differentiate chromophobe renal cell carcinoma (RCC) from oncocytoma based on a finding of Ksp-cad expression in 97% of chromophobe RCCs but only 3% of oncocytomas. However, another study showed no difference in Ksp-cad immunoreactivity between these 2 tumors. We attempted to evaluate Ksp-cad expression in renal tumors using expression microarrays and immunohistochemical analysis. Ksp-cad messenger RNA (mRNA) levels were examined in 158 renal tumors, including 15 chromophobe RCCs and 15 oncocytomas. Immunohistochemical analysis was performed on tissue microarrays containing 125 renal tumors, including 36 chromophobe RCCs and 41 oncocytomas. Ksp-cad mRNA compared with normal kidney tissue was 89% in chromophobe RCC and 64% in oncocytoma. Furthermore, 31 of 36 chromophobe RCCs and 31 of 41 oncocytomas showed Ksp-cad immunoreactivity. Ksp-cad was present in chromophobe RCCs and oncocytomas at mRNA and protein levels, providing strong evidence that Ksp-cad immunohistochemical analysis cannot be used in differentiating these tumors.     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

Different immunohistochemical patterns of Fhit protein expression in renal neoplasms.

BACKGROUND: The FHIT gene on human chromosome 3p14.2 is deleted in a variety of malignant tumors, including clear cell renal carcinomas (RCCs) resulting in a loss of expression of Fhit protein. The Fhit expression in specific subtypes of renal carcinomas has not been characterized. We have investigated the association of Fhit expression with particular subtypes of renal tumors to determine the role and specificity of this putative tumor suppressor gene in renal neoplasia. MATERIAL AND METHODS: The immunohistochemical expression of Fhit was tested in normal kidneys and in 109 renal neoplasms consisting of 51 clear cell RCCs, 26 papillary RCCs, two chromophobe carcinomas, six oncocytomas, four pelvic transitional cell carcinomas and 20 Wilms' tumors from formalin fixed and routinely processed tissue. RESULTS: Normal renal tubules expressed Fhit strongly and consistently. The majority (78%) of clear cell RCCs showed reduced or absent expression of Fhit, whereas the majority (74%) of papillary carcinomas, all chromophobe renal cell carcinomas, and oncocytomas were strongly positive. Sixty-eight percent of low-grade (G1 plus G2) but only 9% of high-grade (G3 plus G4) clear cell carcinomas were Fhit negative. Wilms' tumors demonstrated focal staining in the epithelial component in 8 of 20 cases (40%). CONCLUSIONS: The loss of Fhit expression in a high percentage of clear cell RCCs with conservation of Fhit in other types of tumors supports the proposed role of FHIT alterations in the genesis of clear cell carcinomas in contrast to other types of renal epithelial tumors. FHIT expression may play a role in epithelial differentiation of nephroblastomas (Wilms' tumors).     

Alpha-methyl CoA racemase expression in renal cell carcinomas

Alpha-methyl CoA racemase (AMACR), a new molecular marker for prostate cancer, has been recently reported to be one of the most highly expressed genes in papillary renal cell carcinomas (RCCs). We tested the diagnostic usefulness of AMACR antibody in a series of 110 renal tumors: 53 papillary RCCs (33 type 1, 20 type 2); 25 conventional RCCs; 6 chromophobe RCCs; 9 oncocytomas; 5 mucinous tubular and spindle tumors; 2 urothelial carcinomas; 7 angiomyolipomas; and 2 Bellini carcinomas. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections, with a primary prediluted rabbit monoclonal anti-AMACR antibody. Both type 1 and type 2 papillary RCCs exhibited cytoplasmic immunoreactivity for AMACR, with diffuse strong granular staining in 96.4% (53/55) of tumors, without correlation with type or nuclear grade. The 5 mucinous, tubular, and spindle cell carcinomas strongly expressed AMACR, and only 5 of 25 clear cell RCCs and 1 of 9 oncocytomas were focally reactive. The remaining 6 chromophobe RCCs, 5 urothelial carcinomas, and Bellini duct carcinomas showed no immunoreactivity for AMACR. Because high expression of AMACR is found in papillary RCCs (type 1 and 2) and in mucinous, tubular, and spindle cell carcinomas of the kidney, immunostaining for AMACR should be used in conjunction with other markers when histological typing of a renal tumor is difficult.     

Parvalbumin is constantly expressed in chromophobe renal carcinoma.

Chromophobe renal carcinoma is composed of neoplastic cell showing several features similar to those found in the intercalated cells of the collecting ducts. Because the distal nephron expresses calcium-binding proteins playing a role in calcium homeostasis, we reasoned that these proteins could be expressed by chromophobe carcinoma and therefore represent a diagnostic marker. We studied the immunohistochemical expression of different calcium-binding proteins (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75 conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in all primary chromophobe carcinomas and in one pancreatic metastasis; it was positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and calretinin were negative in all tumors, with the exception of two chromophobe carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be a suitable marker for distinguishing primary and metastatic chromophobe carcinoma from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they suggest a relationship between chromophobe renal carcinoma and renal oncocytoma and indicate that chromophobe carcinoma exhibits differentiation toward the collecting-duct phenotype.     

Expression of GLUT1 in primary renal tumors: morphologic and biologic implications

This study aimed to assess whether glucose transporter 1 (GLUT1) is useful in prognostication or differential diagnosis of renal tumors. GLUT1 immunostain for 228 renal tumors showed a membranous or cytoplasmic pattern. The membranous pattern was seen in 86.2% of 145 clear cell renal cell carcinomas (RCCs) and 100% of 11 transitional cell carcinomas (TCCs) but in no oncocytomas, other subtypes of RCC, or sarcomatoid areas of RCCs. The cytoplasmic pattern was seen in 55.2% of 145 clear cell RCCs, 38% of papillary RCCs (11/29), 13% of chromophobe RCCs (2/16), 22% of oncocytomas (5/23), and 82% of TCCs (9/11). Western blot showed a markedly increased GLUT1 protein content in clear cell RCCs compared with a low level in papillary RCCs and normal kidney specimens. GLUT1 expression in clear cell RCC was not significantly correlated with patient survival, tumor grade, or tumor stage. GLUT1 may be a novel target for immunotherapy and a useful marker in the differential diagnosis and classification of renal tumors.     

A case of liver metastasis from an oncocytoma with a focal area of chromophobe renal cell carcinoma: a wolf in sheep's clothing

In 2004, the World Health Organization classified the renal oncocytomas as benign neoplasms of the kidney. There are reports of subtypes of renal tumors, with similar histological morphology to oncocytoma, but with malignant potential, one of these tumors is the eosinophilic variant of chromophobe renal cell carcinoma. It is important to characterize the histological features and the subtype of tumor, as this predicts biological behavior and cancer-specific survival rate. A rare case of a liver metastasis from a focal area of eosinophilic variant of chromophobe renal cell carcinoma mixed in oncocytoma in a 69-year-old woman is reported. Although some renal tumors may contain oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma histology, caution should be exercised while diagnosing oncocytomas in needle biopsies as there may be unsampled area of chromophobe carcinoma which has a potential for metastatic spread representing a wolf in sheep's clothing.     

Carbohydrate metabolism in human renal clear cell carcinomas.

BACKGROUND: Renal cell carcinomas can be subclassified into clear cell carcinomas, chromophobe cell carcinomas, chromophilic cell carcinomas, and oncocytomas. Previous studies, in which no distinction among the different types of renal cell tumors and their grades of malignancy was performed, showed that these tumors had high glycolytic rates. EXPERIMENTAL DESIGN: The carbohydrate metabolism of control human kidney samples and renal clear cell carcinomas with different degrees of cytologic malignancy (G I, G II, and G III) was studied by determining the glycogen and glucose-6-phosphate levels and the activities of key enzymes involved in glycolysis (hexokinase, glucokinase, pyruvate kinase), gluconeogenesis (glucose-6-phosphatase, fructose-1,6-diphosphatase), and the pentose phosphate pathway (glucose-6-phosphate dehydrogenase) in these tissues and compared with those of a limited number of chromophilic cell carcinomas, chromophobe cell carcinomas, and oncocytomas. RESULTS: The glycogen and glucose-6-phosphate levels were significantly higher in G I, G II, and G III clear cut carcinomas than in control kidneys; glucokinase, hexokinase, and glucose-6-phosphate dehydrogenase activities remained unchanged, pyruvate kinase activity was enhanced, and glucose-6-phosphatase as well as fructose-1,6-diphosphatase activities were strongly reduced when compared with control kidney values. In chromophilic cell carcinomas glycogen content, glucose-6-phosphate dehydrogenase, and pyruvate kinase activities were elevated, while fructose-1,6-diphosphatase activity was reduced. In chromophobe cell carcinomas glycogen content was elevated and gluconeogenesis was reduced, whereas glycolysis was not activated. In oncocytomas glycogen was not detected and glucose-6-phosphate dehydrogenase, pyruvate kinase, and fructose-1,6-diphosphatase activities remained unchanged. CONCLUSIONS: It has been demonstrated that a series of characteristic changes occur in the carbohydrate metabolism of renal clear cell carcinomas: glycogen and glucose-6-phosphate levels increase, glycolysis is activated, and gluconeogenesis is reduced. Furthermore, the alterations of the carbohydrate metabolism within clear cell carcinomas are clearly distinct from those observed in chromophilic cell carcinomas, chromophobe cell carcinomas, and oncocytomas.     

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.