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Mahul B Amin - One of the best experts on this subject based on the ideXlab platform.
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claudin 7 and claudin 8 immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal Oncocytoma
Human Pathology, 2009Co-Authors: Adeboye O Osunkoya, Mahul B Amin, Cynthia Cohen, Diane Lawson, Maria M Picken, Andrew N YoungAbstract:Summary 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 P
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ultrastructural observations on mitochondria and microvesicles in renal Oncocytoma chromophobe renal cell carcinoma and eosinophilic variant of conventional clear cell renal cell carcinoma
The American Journal of Surgical Pathology, 2000Co-Authors: Satish K Tickoo, John N Eble, Mitual Amin, Thomas Christopherson, Richard J Zarbo, Mahul B AminAbstract:On light microscopic examination, the morphologically overlapping features of granular eosinophilic cytoplasm in renal Oncocytoma and the eosinophilic variants of chromophobe renal cell carcinoma and conventional (clear cell) renal cell carcinoma may pose difficulties in diagnosis. We investigated the ultrastructure of 5 renal Oncocytomas, 7 eosinophilic variants of chromophobe renal cell carcinoma, and 5 eosinophilic variants of conventional (clear cell) renal cell carcinoma. Special attention was paid to mitochondria and microvesicles and interrelations thereof. The electron microscopic features were correlated with the light microscopic findings. All of the tumors had abundant mitochondria. Although abundant microvesicles were present in all of the chromophobe renal cell carcinomas, scant numbers of microvesicles were also sometimes present in renal Oncocytomas (2 of 5) and in the eosinophilic variant of conventional (clear cell) renal cell carcinoma (1 of 5). The mitochondria in all three types of renal neoplasms studied differed in morphology, being predominantly uniform and round with predominantly lamellar cristae in renal Oncocytoma, variable in shape and size with predominantly tubulocystic cristae in chromophobe renal cell carcinoma, and swollen and pleomorphic with rarefied matrix and attenuated cristae in the eosinophilic variant of conventional (clear cell) renal cell carcinoma. Variable numbers of mitochondria in all of the chromophobe renal cell carcinomas had outpouchings of the outer membranes, some of which carried parts of inner membrane within them. These outpouchings closely resembled the nearby cytoplasmic microvesicles, as did the tubulocystic cristae of the mitochondria. Some microvesicles contained homogeneous, electron-dense, finely granular matrix, similar to that seen in mitochondria. In one of seven chromophobe renal cell carcinomas, microvesicles were present in rough endoplasmic reticulum, and in two others, mitochondria were present within some vesicles. These features strongly suggest a close relationship between the microvesicles and mitochondria. Based on the role of vesicle formation in normal mitochondriogenesis, and some of our observations, we propose that defective mitochondriogenesis may be the source of microvesicles in chromophobe renal cell carcinomas.
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discriminant nuclear features of renal Oncocytoma and chromophobe renal cell carcinoma analysis of their potential utility in the differential diagnosis
American Journal of Clinical Pathology, 1998Co-Authors: Satish K Tickoo, Mahul B AminAbstract:Chromophobe renal cell carcinoma and renal Oncocytoma have overlapping morphologic, histochemical, immunohistochemical, and ultrastructural features; however, their distinction is critical inasmuch as the former neoplasm has a malignant potential and the latter is widely believed to be a benign tumor. In this study, we investigated the potential utility of nuclear features in differential diagnosis. Nuclear contours, nuclear chromatin pattern, binucleation or multinucleation, pleomorphism, and mitotic activity were assessed semiquantitatively in routine H&E-stained sections from 16 cases of chromophobe renal cell carcinoma and 21 cases of renal Oncocytoma. All cases of chromophobe renal cell carcinoma were found to have wrinkled, “raisinoid” nuclei in varying proportions, whereas all renal Oncocytomas had predominantly round, relatively uniform nuclei. Binucleation or multinucleation was significantly more common in chromophobe renal cell carcinoma. Nuclear chromatin tended to be coarser in chromophobe renal cell carcinoma and nucleoli were seen more commonly in renal Oncocytoma. Of the renal Oncocytomas, 19% had distinct foci of “degenerative” nuclear atypia with pleomorphism. This type of atypia was absent in chromophobe renal cell carcinoma. Our study shows that in association with the well-described cytoplasmic and architectural features, nuclear parameters are valuable discriminants between chromophobe renal cell carcinoma and renal Oncocytoma. Frequent binucleation and “raisinoid” nuclei with perinuclear halos, resulting in “koilocytoid atypia,” is highly characteristic of chromophobe renal cell carcinoma.
Ximing J Yang - One of the best experts on this subject based on the ideXlab platform.
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renal small cell Oncocytoma with pseudorosettes a histomorphologic immunohistochemical and molecular genetic study of 10 cases
Human Pathology, 2011Co-Authors: Ximing J Yang, Naoto Kuroda, Fredrik Petersson, Radek Sima, Petr Grossmann, Michal Michal, Milan Hora, Z Kinkor, Sandra TrivunicAbstract:Summary A cohort of a heretofore not described rare subtype of renal Oncocytoma, small cell Oncocytoma with pseudorosettes is presented. Patients were 6 women and 4 men with ages ranging from 51 to 76 years. The tumors displayed areas composed of small cells ("oncoblasts") featuring scant cytoplasm and small, round monomorphic nuclei. The small cell areas constituted 15% to 60% of the total tumor volume (mean, 28.5%; median, 22.5%). No necrosis or mitotic activity was discerned. All tumors also contained areas composed of characteristic oncocytes comprising 40% to 85% of the total tumor volume. In all cases, a varying number of pseudorosettes were identified. The pseudorosettes were composed of small globules of (periodic acid–Schiff–positive) hyaline basal membrane–like material surrounded by small "oncoblastic" cells. The immunohistochemical profile was variable, including at least focal positivity for AE1-3 (10/10), cytokeratin 7 (7/10), epithelial membrane antigen (10/10), c-kit (6/10), antimitochondrial antigen (MIA;10/10), PAX-2 (9/10), AMACR (racemase;6/10), CD10 (5/10), parvalbumin (8/10), vimentin (6/10), claudin 7 (10/10), and claudin 8 (3/10). No immunoreactivity for carbonic anhydrase 9, HMB-45, S-100A1, and TFE3 was documented. We found no differences in the immunophenotype in the small cell oncocytes/oncoblasts that formed pseudorosettes and those that did not. However, there were differences in the immunohistochemical profile of classic oncocytes and small cell oncocytes/oncoblasts. Using array comparative genomic hybridization, no chromosomal changes were identified in any of the cases examined (n = 3). No numerical changes of chromosomes 7 and 17 were revealed on fluorescence in situ hybridization analysis (n = 3). In conclusion, we herein present the first study on small cell renal Oncocytomas with formation of pseudorosettes. This is a rare subtype of Oncocytoma, which may, especially on a core biopsy, present differential diagnostic difficulties. The immunohistochemical profile of these tumors is variable and differs in significant respects from that of conventional renal Oncocytoma. Awareness of this entity and its immunohistochemical variability should help in distinguishing this rare tumor from malignant tumors with similar (small cell) histomorphologic features. All tumors behaved in a benign fashion during follow-up (mean, 3.1 years; median, 1 year).
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expression of kidney specific cadherin in chromophobe renal cell carcinoma and renal Oncocytoma
American Journal of Clinical Pathology, 2006Co-Authors: Brian P Adley, Anita Gupta, Chunyan Luan, Ximing J YangAbstract: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.
David G Bostwick - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical analysis of chromophobe renal cell carcinoma renal Oncocytoma and clear cell carcinoma an optimal and practical panel for differential diagnosis
Archives of Pathology & Laboratory Medicine, 2009Co-Authors: Junqi Qian, Harpreet Singh, Isabelle Meiers, Xiaoge Zhou, David G BostwickAbstract:● Context.—The separation of chromophobe renal cell carcinoma, Oncocytoma, and clear cell renal cell carcinoma using light microscopy remains problematic in some cases. Objective.—To determine a practical immunohistochemical panel for the differential diagnosis of chromophobe carcinoma. Design.—Vimentin, glutathione S-transferase (GST-), CD10, CD117, cytokeratin (CK) 7, and epithelial cell adhesion molecule (EpCAM) were investigated in 22 cases of chromophobe carcinoma, 17 cases of Oncocytoma, and 45 cases of clear cell carcinoma. Results.—Vimentin and GST- expression were exclusively observed in clear cell carcinoma. CD10 staining was more frequently detected in clear cell carcinoma (91%) than in chromophobe carcinoma (45%) and Oncocytoma (29%). CD117 was strongly expressed in chromophobe carcinoma (82%) and Oncocytoma (100%), whereas none of the cases of clear cell carcinomas were immunoreactive. Cytokeratin 7 was positive in 18 (86%) of 22 cases of chromophobe carcinoma, whereas all Oncocytomas were negative for CK7. EpCAM protein was expressed in all 22 cases of chromophobe carcinoma in more than 90% of cells, whereas all EpCAM-positive Oncocytomas (5/17; 29%) displayed positivity in single cells or small cell clusters. Conclusions.—Using the combination of 3 markers (vimentin, GST-, and EpCAM), we achieved 100% sensitivity and 100% specificity for the differential diagnosis of chromophobe carcinoma, Oncocytoma, and clear cell carcinoma. The pattern of ‘‘vimentin/GST-’’ effectively excluded clear cell carcinoma, and homogeneous EpCAM expression confirmed the diagnosis of chromophobe carcinoma rather than Oncocytoma. CD117 and CK7 were also useful markers and could be used as second-line markers for the differential diagnosis, with high specificity (100%) and high sensitivity (90% and 86%, respectively). (Arch Pathol Lab Med. 2007;131:1290–1297)
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renal Oncocytoma multifocality bilateralism metachronous tumor development and coexistent renal cell carcinoma
The Journal of Urology, 1999Co-Authors: Christopher Dechet, David G Bostwick, Michael L Blute, Sandra C Bryant, Horst ZinckeAbstract:AbstractPurpose: We analyzed a large series of cases of renal Oncocytoma to define the incidence of coexistent renal cell carcinoma, multifocality, bilateralism and metachronous tumor development.Materials and Methods: Between 1980 and 1997, 100 men and 38 women with a mean age of 68 years with Oncocytoma, were treated surgically at our institution. We analyzed tumor characteristics and reviewed specimens for coexistent renal cell carcinoma.Results: Tumors were discovered incidentally in 58% of the cases. Specimens were obtained from 84 radical and 70 partial nephrectomies. Tumor size ranged from 0.3 to 14.5 cm. (median 3.2). Oncocytoma was unilateral in 131 cases (95%) and bilateral in 7 (5%), while there were multiple Oncocytomas in 8 (6%). Mean followup was 41 months (range 0 to 200). The disease specific survival rate was 100% and no patient had metastasis. In 6 patients (4%) metachronous Oncocytoma developed during followup. No patient had locally recurrent Oncocytoma after partial nephrectomy for a ...
Martin Susani - One of the best experts on this subject based on the ideXlab platform.
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expression of kidney specific cadherin distinguishes chromophobe renal cell carcinoma from renal Oncocytoma
Human Pathology, 2005Co-Authors: Peter R Mazal, Markus Exner, Andrea Haitel, Sigurd Krieger, Brent R Thomson, Peter S Aronson, Martin SusaniAbstract: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.
Satish K Tickoo - One of the best experts on this subject based on the ideXlab platform.
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ultrastructural observations on mitochondria and microvesicles in renal Oncocytoma chromophobe renal cell carcinoma and eosinophilic variant of conventional clear cell renal cell carcinoma
The American Journal of Surgical Pathology, 2000Co-Authors: Satish K Tickoo, John N Eble, Mitual Amin, Thomas Christopherson, Richard J Zarbo, Mahul B AminAbstract:On light microscopic examination, the morphologically overlapping features of granular eosinophilic cytoplasm in renal Oncocytoma and the eosinophilic variants of chromophobe renal cell carcinoma and conventional (clear cell) renal cell carcinoma may pose difficulties in diagnosis. We investigated the ultrastructure of 5 renal Oncocytomas, 7 eosinophilic variants of chromophobe renal cell carcinoma, and 5 eosinophilic variants of conventional (clear cell) renal cell carcinoma. Special attention was paid to mitochondria and microvesicles and interrelations thereof. The electron microscopic features were correlated with the light microscopic findings. All of the tumors had abundant mitochondria. Although abundant microvesicles were present in all of the chromophobe renal cell carcinomas, scant numbers of microvesicles were also sometimes present in renal Oncocytomas (2 of 5) and in the eosinophilic variant of conventional (clear cell) renal cell carcinoma (1 of 5). The mitochondria in all three types of renal neoplasms studied differed in morphology, being predominantly uniform and round with predominantly lamellar cristae in renal Oncocytoma, variable in shape and size with predominantly tubulocystic cristae in chromophobe renal cell carcinoma, and swollen and pleomorphic with rarefied matrix and attenuated cristae in the eosinophilic variant of conventional (clear cell) renal cell carcinoma. Variable numbers of mitochondria in all of the chromophobe renal cell carcinomas had outpouchings of the outer membranes, some of which carried parts of inner membrane within them. These outpouchings closely resembled the nearby cytoplasmic microvesicles, as did the tubulocystic cristae of the mitochondria. Some microvesicles contained homogeneous, electron-dense, finely granular matrix, similar to that seen in mitochondria. In one of seven chromophobe renal cell carcinomas, microvesicles were present in rough endoplasmic reticulum, and in two others, mitochondria were present within some vesicles. These features strongly suggest a close relationship between the microvesicles and mitochondria. Based on the role of vesicle formation in normal mitochondriogenesis, and some of our observations, we propose that defective mitochondriogenesis may be the source of microvesicles in chromophobe renal cell carcinomas.
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discriminant nuclear features of renal Oncocytoma and chromophobe renal cell carcinoma analysis of their potential utility in the differential diagnosis
American Journal of Clinical Pathology, 1998Co-Authors: Satish K Tickoo, Mahul B AminAbstract:Chromophobe renal cell carcinoma and renal Oncocytoma have overlapping morphologic, histochemical, immunohistochemical, and ultrastructural features; however, their distinction is critical inasmuch as the former neoplasm has a malignant potential and the latter is widely believed to be a benign tumor. In this study, we investigated the potential utility of nuclear features in differential diagnosis. Nuclear contours, nuclear chromatin pattern, binucleation or multinucleation, pleomorphism, and mitotic activity were assessed semiquantitatively in routine H&E-stained sections from 16 cases of chromophobe renal cell carcinoma and 21 cases of renal Oncocytoma. All cases of chromophobe renal cell carcinoma were found to have wrinkled, “raisinoid” nuclei in varying proportions, whereas all renal Oncocytomas had predominantly round, relatively uniform nuclei. Binucleation or multinucleation was significantly more common in chromophobe renal cell carcinoma. Nuclear chromatin tended to be coarser in chromophobe renal cell carcinoma and nucleoli were seen more commonly in renal Oncocytoma. Of the renal Oncocytomas, 19% had distinct foci of “degenerative” nuclear atypia with pleomorphism. This type of atypia was absent in chromophobe renal cell carcinoma. Our study shows that in association with the well-described cytoplasmic and architectural features, nuclear parameters are valuable discriminants between chromophobe renal cell carcinoma and renal Oncocytoma. Frequent binucleation and “raisinoid” nuclei with perinuclear halos, resulting in “koilocytoid atypia,” is highly characteristic of chromophobe renal cell carcinoma.
