Sporadic clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity

Kien, T.; Kohler, Derek M.; Belanger, Eric C.; Robertson, Susan J.; Don, Wang

doi:10.1080/00313020802197962

Cited by 29 publications

(25 citation statements)

References 13 publications

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“…The expression of CK7 in clear-cell RCCespecially small tumors-has been documented in the literature. 5 We have seen CK7 staining in clearcell RCC cases in which the morphological diagnosis of clear-cell papillary RCC was not even entertained owing to the absence of characteristic H&E features, and in those cases the CK7 labeling was patchy. Thus, we believe that this case represents an uncommon clear-cell RCC with patchy CK7 staining.…”

Section: Aberrationmentioning

confidence: 88%

“…We, and others, believe that a variety of other recently described entities, including renal angiomyoadenomatous tumor, 2 clear-cell tubulopapillary renal cell carcinoma, 3 renal cell carcinoma with prominent leiomyomatous proliferation 4 and clearcell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity 5 are either closely related, if not the same, tumors as clear-cell papillary renal cell carcinoma described in the literature with alternative nomenclature. 3,[5][6][7][8] Our contention is further supported by presentations at the most recent annual meeting of United States and Canadian Association of Pathologists (USCAP, 2011) regarding clear-cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor. 9,10 Despite the different nomenclature used, the tumors described share many morphological features and consistently express cytokeratin 7 (CK7) and carbonic anhydrase IX (CA9) while lacking labeling for a-methylacyl-CoA racemase (AMACR) and CD10.…”

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confidence: 91%

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Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

et al. 2011

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Over the past few years several investigators have independently described unique low-grade renal epithelial neoplasms with clear cytoplasm, focal to diffuse papillary architecture, and occasional leiomyomatous stromal metaplasia that are not currently recognized in the World Health Organization classification of renal tumors. These tumors have been referred to by a variety of names including clear-cell papillary renal cell carcinoma and recently ''clear-cell tubulopapillary renal cell carcinoma''. On the basis of the available data, such tumors are positive for cytokeratin 7 (CK7) and carbonic anhydrase IX (CA9), while being negative for CD10, a-methylacyl-CoA racemase (AMACR), and TFE3. These tumors reportedly lack trisomies of chromosomes 7 and 17, deletions of 3p25, von Hippel-Lindau (VHL) gene mutations, and VHL promoter hypermethylation. Herein, we report on nine cases of this tumor emphasizing detailed studies of the VHL gene and hypoxiainducible factor (HIF) pathway. Molecular studies performed included VHL mutational analysis, copy number changes assessed using single-nucleotide polymorphism arrays, and qRT-PCR for VHL mRNA expression. Immunohistochemical stains for markers of HIF pathway activation (HIF-1a, CA9, and glucose transporter-1 (GLUT-1)) as well as other relevant markers (CK7, CD10, AMACR, and TFE3) were performed. None of our tumors harbored VHL gene mutations, losses of chromosomal region 3p25, or trisomies of chromosomes 7 or 17. VHL mRNA was overexpressed in our tumors relative to normal renal tissue and clear-cell renal cell carcinoma. All cases showed strong co-expression of CK7, HIF-1a, GLUT-1, and CA9. No expression of TFE3, CD10, or AMACR was seen. The morphological, immunophenotypic, and molecular features of these unique low-grade tumors are sufficiently distinct to allow separation from other renal cell carcinoma subtypes. The coexpression of CA9, HIF-1a, and GLUT-1 in the absence of VHL gene alterations in clear-cell papillary renal cell carcinoma suggests activation of the HIF pathway by non-VHL-dependent mechanisms.

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Section: Aberrationmentioning

confidence: 88%

mentioning

confidence: 91%

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

et al. 2011

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“…The significance of these findings is not entirely clear. It has been suggested that previously reported examples of CK7-positive clear cell renal cell carcinomas 38 are in fact clear cell papillary renal cell carcinomas. 12 However, as clear cell papillary renal cell carcinomas lack chromosome 3p deletion and these tumors did not exhibit such morphology, the possibility that another subtype of CK7-positive 'clear cell' renal neoplasm exists remains open to further study.…”

Section: Tumors That Could Not Be Confidently Classifiedmentioning

confidence: 99%

Renal cell carcinoma with angioleiomyoma-like stroma: clinicopathological, immunohistochemical, and molecular features supporting classification as a distinct entity

et al. 2015

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Rare renal epithelial neoplasms have been recognized to have an angioleiomyoma or leiomyoma-like proliferation of stromal smooth muscle; however, the nature of these tumors and their relationships to other renal cell carcinomas are poorly understood. We analyzed 23 such tumors for their clinicopathological, immunohistochemical, and cytogenetic features using fluorescence in situ hybridization. Twelve showed a homogeneous combination of features and were reclassified as renal cell carcinoma with angioleiomyoma-like stroma. These were composed of neoplastic glandular structures lined by cells with mixed clear, pale, and eosinophilic cytoplasm forming occasional papillary tufts. The stroma resembled smooth muscle and often extended away from the epithelial component, entrapping perinephric fat or non-neoplastic renal elements. Immunohistochemistry showed the epithelium to have reactivity for: carbonic anhydrase IX, CD10, vimentin, cytokeratin 7, cytokeratin 34bE12, and PAX8 but not a-methylacyl-coA-racemase. The stroma labeled for smooth muscle (smooth muscle actin 3 þ , desmin 1 þ , caldesmon 3 þ ) but not epithelial antigens. Neither component showed substantial reactivity for HMB45, melan-A, cathepsin K, or TFE3 protein. An interrupted, conspicuous layer of CD34-positive endothelial cells rimmed the epithelium, imparting a two-cell layer pattern resembling myoepithelial or basal cells. Chromosome 3p deletion and trisomy 7 and 17 were uniformly absent. Follow-up was available for three patients, none of whom experienced malignant behavior. Eleven tumors were excluded from this category and considered to be clear cell renal cell carcinoma with a reactive proliferation of smooth muscle (n ¼ 4) or tangential sectioning of the pseudocapsule (n ¼ 2), renal cell carcinoma unclassified (n ¼ 4), or clear cell papillary renal cell carcinoma (n ¼ 1). In summary, renal cell carcinoma with angioleiomyoma-like stroma is a distinct neoplasm with characteristic morphological, immunohistochemical, and molecular features, unrelated to clear cell renal cell carcinoma. The immunoprofile overlaps partly with that of clear cell papillary renal cell carcinoma, though morphology and reactivity for CD10 are points of contrast.

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“…CD10 and 34BE12 show variable expression in these 2 tumor types, with the former more frequently positively expressed in CpRCC. Cytokeratin 7 appears to be the most reliable marker for differentiating these 2 entities, as it is nearly always diffusely, strongly positive in CpRCC while only infrequently positive in CCRCC 70,72 (Figure 4, D). In general, when CK7 labeling is present in a CCRCC, it is focal or, at most, patchy and centered around cystic spaces.…”

Section: Clear Cell Papillary Renal Cell Carcinomamentioning

confidence: 99%

“…While CK7 staining has been described in CCRCC, this is an uncommon finding; staining is usually patchy and centered around cystic areas within a tumor. [70][71][72] In contrast, most type 1 PRCCs will be diffusely positive for CK7. 72 The pattern of CA9 expression in PRCC, which is patchy and often perinecrotic when present, is usually easily distinguished from the diffuse membranous pattern seen in CCRCC 39,42,73,74 (Figure 2, D).…”

mentioning

confidence: 99%

Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine

Goyal

Gersbach

Yang

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.—The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and—with the exception of some rare tumors—the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. Objective.—To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. Data Sources.—Published literature and personal experience. Conclusions.—In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.

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Sporadic clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity

Cited by 29 publications

References 13 publications

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

Renal cell carcinoma with angioleiomyoma-like stroma: clinicopathological, immunohistochemical, and molecular features supporting classification as a distinct entity

Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine

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