Clear Cell Tubulopapillary Renal Cell Carcinoma: A Study of 36 Distinctive Low-grade Epithelial Tumors of the Kidney

Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 09/2010; 34(11):1608-21. DOI: 10.1097/PAS.0b013e3181f2ee0b
Source: PubMed


Recently several low-grade renal cell tumors, distinct from those recognized by the 2004 World Health Organization classification of renal tumors, have been described. These tumors had similar clinicopathologic features, being low-stage tumors with cystic, tubuloacinar, and/or papillary architecture. The tumor cells were low grade with variable amounts of clear cytoplasm that was positive for cytokeratin 7 (CK7), but negative for CD10. Genetic changes characteristic of clear cell or papillary renal cell carcinoma were not seen in these tumors. We investigated the morphologic, immunohistochemical, and genetic features of 36 additional tumors. Immunohistochemistry was carried out for CK7, carbonic anhydrase 9, α-methylacyl-CoA racemase, CD10, TFE-3, and desmin. Interphase fluorescence in situ hybridization was carried out with centromeric probes for chromosomes 3, 7, 17, and a subtelomeric probe for 3p25. Sequencing of von Hippel-Lindau gene and analysis of the methylation status of the promoter region was also carried out in 2 tumors. Thirty-six tumors from 33 patients (mean age: 60.4 , range: 26 to 88; 17 men and 16 women) were studied. Three patients had bilateral tumors and 1 patient had von Hippel-Lindau disease. Follow-up was available in 60% (20/33) of the patients for a mean of 27.4 (range 1 to 85) months. No patient had evidence of the disease after surgery except for the patient with von Hippel-Lindau disease, who was alive with stable disease in the contralateral kidney. All 36 tumors were small (mean size 2.4 cm; range 0.9 to 4.5 cm) and low stage (pT1). The majority was cystic and had prominent fibrous capsule and stroma. The tumors were composed of variable amount of cysts, papillae, tubules, acini, and solid nests. The most characteristic histologic features were branching tubules and acini and anastomosing clear cell ribbons with low-grade nuclei. All tumors were strongly positive for CK7 and variably positive for CA9, but largely negative for CD10, and negative for α-methylacyl-CoA racemase and TFE-3. All but 1 tumor had no gains of chromosomes 7 and 17 and deletion of 3p. Only 1 tumor had low copy number gains of chromosomes 7 and 17. VHL gene mutation and promoter methylation were negative in 2 tumors analyzed. We show that these tumors, which we term as "clear cell tubulopapillary renal cell carcinoma," constitute a unique subtype in the spectrum of renal epithelial neoplasia based on their characteristic morphologic and immunohistochemical features.

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Available from: Huiying He, Sep 22, 2015
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    • "Renal angiomyoadenomatous tumor (RAT) and clear cell papillary renal cell carcinoma (CCPRCC) are 2 relatively recently described low-grade neoplastic entities with overlapping histologic features and with indolent clinical behavior so far [1] [2] [3] [4] [5] [6]. Recently, RAT and CCPRCC have been thought of as 2 ends of a spectrum of 1 nosologic entity. "
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    ABSTRACT: We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.
    Full-text · Article · Feb 2013 · Human pathology
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    • "No recurrent DNA copy number aberrations have been identified. In particular, the copy number changes characteristic of clear-cell RCC and papillary RCC have not been seen[23]–[25]. A significant attribute of this tumor is its indolent clinical course, with no tumor recurrences or metastases reported to date[22]–[24]. "
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    ABSTRACT: Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide. Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has traditionally been divided into clear-cell and non-clear-cell categories, with papillary RCC forming the most common subtype of non-clear-cell RCC. Renal neoplasms with overlapping histologies, such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors, are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications. In this review, we discuss the histologic, immunohistochemical, cytogenetic, and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor's microscopic appearance and its molecular fingerprint.
    Full-text · Article · Dec 2012 · Chinese journal of cancer
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    • "Additionally, immunohistochemical staining demonstrates strong expression of cytokerain 7 (CK7), no or low expression of CD10 and racemase and negative expression of transcription factor E3 (TFE3).9,10,14,15 Molecular genetic studies have revealed that CCPRCCs harbor different pathogenic mechanisms from clear cell RCCs (CCRCCs) and papillary RCCs (PRCCs).12-14,16 CCPRCCs show no loss of chromosome 3p where the von Hippel-Lindau (VHL) gene is located, which is associated with CCRCC. "
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    ABSTRACT: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently established subtype of renal epithelial tumor. The aim of this study was to identify the diagnostic criteria of CCPRCC with an emphasis on immunohistochemical studies, and to report three cases with concurrent other-type renal cell carcinoma (RCC). A total of 515 RCC patients that consecutively underwent surgical resection at Seoul National University Hospital from 1 January 2010 to 31 December 2011 were screened. Each case was reviewed based on the histologic features and was evaluated immunohistochemically. A total of 15 CCPRCCs were identified, which composed 2.9% of the total RCCs. The mean age was 52 years, and the average tumor size was 1.65 cm. All 15 cases showed low nuclear grade, no lymph node metastasis and no distant metastasis. The CCPRCCs showed variable architectural patterns including cystic, trabecular, papillary, and acinar. All of the cases showed moderate to intense immunoreactivity for cytokeratin 7 (CK7). CD10 was negative or showed focal weak positivity. Three cases had concurrent other-type RCC, including a clear cell RCC and an acquired cystic disease-associated RCC. The strong CK7 and negative or focal weak CD10 expression will be useful for the diagnosis of CCPRCC.
    Full-text · Article · Dec 2012 · The Korean Journal of Pathology
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