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Tubulocystic renal cell carcinoma is an entity immunohistochemically and genetically distinct from papillary renal cell carcinoma

2015-08-27 13:27:51

HISTOPATHOLOGY; 27 August 2015: DOI:10.1111/his.12840


Thu Tran, Carol L Jones, Sean R Williamson, John N Eble, David J Grignon, Shaobo Zhang, Mingsheng Wang, Lee Ann Baldridge, Lisha Wang, Rodolfo Montironi, Marina Scarpelli, Puay-Hoon Tan, Novae B Simper, Eva Comperat, and Liang Cheng



Abstract



Aims


Some studies have suggested that tubulocystic carcinoma may be related to papillary renal cell carcinoma. We sought to compare and contrast the molecular and immunohistochemical profiles of tubulocystic carcinoma to those of papillary renal cell carcinoma.



Methods and Results


Twelve cases of pure tubulocystic renal cell carcinoma were subjected to fluorescence in situ hybridization assessment of chromosomal number for chromosomes 7 and 17, and for TFE3 translocation. Immunohistochemical labeling for AMACR, p63, cytokeratin 7, PAX 8, cytokeratin 20, and carbonic anhydrase IX was assessed in all tumors. No tumor exhibited gains of chromosomes 7 or 17, or TFE3 translocation by fluorescence in situ hybridization. Immunohistochemistry revealed all tumors to be nonreactive with antibodies to p63 and cytokeratin 20. Conversely, the antibody to AMACR gave a positive reaction in the neoplastic cells of all tumors. Four cases demonstrated focal labeling with antibody to carbonic anhydrase IX and 5 tumors showed focally positive reactions with antibody to cytokeratin 7. Recurrence and metastatic disease was not found for the patients with available follow up information.



Conclusions


Pure tubulocystic renal cell carcinoma is an indolent tumor with a good prognosis. Our data support the distinction of this neoplasm as a separate entity.



Introduction


Tubulocystic renal cell carcinoma was recognized as a distinct entity at the 2012 consensus conference of the International Society of Urological Pathology and included in the organization’s Vancouver Classification of Renal Neoplasia. The first series of cases illustrating this unique neoplasm was published in 1997 by MacLennan et al, who described tumors that microscopically consisted of well circumscribed cystic lesions lined by hobnail-shaped cells with minimal necrosis, hemorrhage, and mitotic activity, and a low propensity for recurrence and metastasis. Immunohistochemically, these tumors were found to react with antibodies to the
high molecular weight cytokeratin 34βE12 and UEA-1, which suggested a collecting duct origin, and consequently these rare tumors were given the name, “low grade collecting duct carcinoma.” Subsequently, more than 50 tubulocystic renal cell carcinomas have been reported, and the defining characteristics of this neoplasm have been well described.These malignancies are found more commonly in men and have a circumscribed, multicystic gross appearance that has been compared to “bubble-wrap.” Microscopically, these tumors are composed of variably sized tubules and cysts, lined by hobnail-shaped cells in a fibrotic stroma. The nuclei usually have prominent nucleoli, and mitotic figures are rare.



More recently, several studies have examined the immunohistochemical and molecular profiles of tubulocystic renal cell carcinoma, in attempts to further characterize this entity. Some of these studies have concluded that tubulocystic carcinoma may be related to papillary renal cell carcinoma. In our study, we sought to compare and contrast the molecular and immunohistochemical profiles of tubulocystic carcinoma to those of papillary renal cell carcinoma in an attempt to offer additional information regarding the relationship between these two entities.



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Key Words


Kidney | tubulocystic renal cell carcinoma | papillary renal cell carcinoma | fluorescence in situ hybridization (FISH) | immunohistochemistry