Utility of Cytokeratin 7 for Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma

Leroy, Xavier; Moukassa, Donatien; Copin, Marie‐Christine; Saint, F.; Mazeman, E; Gosselin, Bernard

doi:10.1159/000020172

Cited by 88 publications

(65 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Oncocytomas also often have a distinctive pattern of labeling for CK7 wherein only scattered single cells and small clusters of cells show positive labeling. [21][22][23] Notably, this pattern was shared only by 1 of the 11 SDHdeficient RCCs in this study, whereas the remaining tumors were entirely negative for CK7. None of the other evaluated immunohistochemical stains were useful to distinguish SDH-deficient RCC and oncocytoma (Table 3), including positive nuclear staining for hepatocyte nuclear factor-1b (HNF1B), an emerging marker that exhibits an absence of reactivity in chromophobe RCC, 24 and diffuse labeling for kidney-specific cadherin, similar to both oncocytoma and chromophobe RCC.…”

Section: Discussionmentioning

confidence: 91%

Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma

et al. 2015

View full text Add to dashboard Cite

Patients with germline mutation of succinate dehydrogenase (SDH) subunit genes are prone to develop paraganglioma, gastrointestinal stromal tumor, and rarely renal cell carcinoma (RCC). However, SDH-deficient RCC is not yet widely recognized. We identified such tumors by distinctive morphology and confirmed absence of immunohistochemical staining for SDHB. Immunohistochemical features were evaluated using a panel of antibodies to renal tumor antigens. Targeted next-generation sequencing was performed on DNA extracted from paraffin-embedded tissue. Eleven tumors were identified from 10 patients, 22-72 years of age (median 40). Two patients had paragangliomas, 1 bilateral SDH-deficient RCC, and 1 contralateral oncocytoma. Grossly, tumors were tan or red-brown, 2-20 cm in diameter (median 4.25 cm). Fuhrman grade was 2 (n ¼ 10) or 3 (n ¼ 1). Stage was pT1a-pT2b. One patient developed widespread metastases 16 years after nephrectomy and died of disease 6 years later. All tumors were composed of uniform eosinophilic cells containing vacuoles or flocculent cytoplasmic inclusions. Architecture was primarily solid; entrapped renal tubules and intratumoral mast cells were common. By immunohistochemistry, tumor cells were negative for SDHB (11/11) and rarely SDHA (1/11). Labeling was uniformly positive for PAX8 and kidney-specific cadherin and absent for KIT, RCC, and carbonic anhydrase IX. Staining for broad-spectrum epithelial markers was often negative or focal (positive staining for AE1/AE3 in 4/10, CAM5.2 3/7, CK7 1/11, EMA 10/10). By sequencing, SDHB mutation and loss of the second allele were present in 5/6 tumors; the SDHA-deficient tumor showed no SDHB abnormality. SDH-deficient RCC is a unique neoplasm that is capable of progression, often harboring SDHB mutation. A monomorphic oncocytic renal tumor with solid architecture, cytoplasmic inclusions of flocculent material, and intratumoral mast cells should prompt evaluation of SDH status, as it may have implications for screening the patient and relatives. Negative immunohistochemistry for KIT and heterogeneous labeling for epithelial antigens are other supportive features.

show abstract

Section: Discussionmentioning

confidence: 91%

Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…CK 7 immunoreactivity in papillary renal cell carcinomas is positive in low-grade tumors but is generally negative in tumors with high-grade nuclei (24). In chromophobe renal cell carcinomas, however, two previous studies have reported disparate results (16,17). Taki et al (16) reported that 43% of chromophobe renal cell carcinomas (9/21 cases) were positive for CK 7, whereas Leroy et al (17) reported 100% positivity (6/6 cases).…”

Section: Discussionmentioning

confidence: 98%

“…In chromophobe renal cell carcinomas, however, two previous studies have reported disparate results (16,17). Taki et al (16) reported that 43% of chromophobe renal cell carcinomas (9/21 cases) were positive for CK 7, whereas Leroy et al (17) reported 100% positivity (6/6 cases). Both studies reported a characteristic cytoplasmic staining for CK 7 with frequent peripheral accentuation.…”

Section: Discussionmentioning

confidence: 98%

“…Both studies reported a characteristic cytoplasmic staining for CK 7 with frequent peripheral accentuation. The two studies also reported conflicting results for CK 7 expression in renal oncocytomas; Taki et al (16) reported focal CK 7 positivity in all three cases of oncocytomas, whereas Leroy et al (17) reported focal positivity in only 3/11 cases. Leroy et al (17) proceeded to conclude that immunohistochemical staining for CK 7 might be useful in the differential diagnosis of chromophobe renal cell carcinomas and renal oncocytomas.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cytokeratins 7 and 20 Immunoreactivity in Chromophobe Renal Cell Carcinomas and Renal Oncocytomas

Kothari

Wheeler

et al. 2002

Mod Pathol

View full text Add to dashboard Cite

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 paraffinembedded 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.

show abstract

“…[9][10][11][12][13][14] However, none of these modalities has thus far proven to be ideal. Therefore, more robust markers are still needed.…”

mentioning

confidence: 99%

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

et al. 2013

View full text Add to dashboard Cite

Chromophobe renal cell carcinoma (RCC) is a form of renal cancer that may be confused with other eosinophilic renal tumors, including oncocytoma, type 2 papillary RCC, and clear-cell RCC with eosinophilic features. There are currently no robust markers to distinguish these neoplasms. Chromophobe RCC and renal oncocytoma are presumably derived from the distal nephron. FXYD2 is a distal tubule regulator of the trimeric Na þ / K þ -transporting ATPase that is enriched in kidney tissue. In this study, we investigated the expression of FXYD2 in normal human kidney, 27 chromophobe RCCs, 30 oncocytomas, 15 clear-cell RCCs, and 11 papillary RCCs. Immunohistochemical staining for FXYD2 showed diffuse, strong immunoreactivity in the basolateral membrane of distal tubules of normal human kidney. Ninety-six percent (26/27) of chromophobe RCCs were immunoreactive for FXYD2 in a distinctly membranous pattern. Twenty-five of these tumors showed at least focal 2 þ staining. In contrast, only 17% (5/30) of renal oncocytomas, 11% (2/15) of clear-cell RCCs, and 0% (0/11) of papillary RCCs displayed FXYD2 immunoreactivity. None of these cases showed Z2 þ FXYD2 staining. A subset of cases was confirmed as oncocytoma or chromophobe RCC using cytokeratin 7, colloidal iron, and interphase fluorescence in situ hybridization analysis of chromosomes 1, 2, 6, 10, and 17. Among this subset, 100% (7/7) of chromophobe RCCs were FXYD2 positive, whereas 17% (2/12) of oncocytomas were stained with FXYD2. The oncocytomas that stained with FXYD2 did so in a weak (1 þ ), patchy manner. In contrast, chromophobe RCCs showed Z2 þ staining in 86% (6/7) of these tumors. For comparison, this subset was also stained for kidney-specific cadherin (Ksp-cadherin). Ksp-cadherin showed positive staining in 100% (7/7) of chromophobe RCCs and 33% (4/12) of oncocytomas. This is the first report demonstrating the potential utility of FXYD2 immunohistochemistry in the diagnosis of chromophobe RCC.

show abstract

Utility of Cytokeratin 7 for Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma

Cited by 88 publications

References 8 publications

Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma

Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma

Cytokeratins 7 and 20 Immunoreactivity in Chromophobe Renal Cell Carcinomas and Renal Oncocytomas

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

Contact Info

Product

Resources

About