PATHOLOGY

Renal cell carcinomas with papillary architecture and clear cell components: the utility of immunohistochemical and cytogenetical analyses in differential diagnosis
Gobbo S, Eble JN, Maclennan GT, Grignon DJ, Shah RB, Zhang S, Martignoni G, Brunelli M, Cheng L
Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN double daggerDepartments of Pathology and Laboratory Medicine, Case Western Reserve University, Cleveland, OH section signDepartments of Pathology and Laboratory Medicine, University of Michigan, Ann Arbor, MI daggerDipartimento di Patologia, Universitá di Verona, Verona, Italy
Am J Surg Pathol. 2008; [Epub ahead of print]

• Although histologic features enable an accurate diagnosis in most renal carcinomas, overlapping morphologic findings between some renal neoplasms make subclassification difficult. Some renal carcinomas show papillary architecture but are composed extensively of cells with clear cytoplasm, and it is unclear whether they should be classified as clear cell renal cell carcinomas or papillary renal cell carcinomas. We analyzed the immunohistochemical profiles and the cytogenetic patterns of 14 renal carcinomas showing papillary architecture in which there were variable amounts of cells with clear cytoplasm. The patients were 8 women and 6 men (mean age: 54 y). Immunohistochemistry and fluorescence in situ hybridization analysis distinguished 2 different groups. The first consisted of 10 renal cell carcinomas with strong immunoreactivity for alpha-methyl coenzyme A racemase, of which 9 also expressed cytokeratin 7. All of these neoplasms showed gains of chromosome 7 or 17 and chromosome Y was lost in all the male patients whereas 3p deletion was detected only in one case. In the other 4 renal cell carcinomas, cytokeratin 7 was not detected and alpha-methylacyl-CoA racemase was positive in only 1. In these neoplasms, no gain of chromosome 7 or 17 and no loss of chromosome Y were observed, whereas 3p deletion was detected in 3 of them. None of the 14 neoplasms showed immunoreactivity for TFE3. The combined use of immunohistochemistry and cytogenetics enabled us to provide a definitive diagnosis for 12 of 14 renal cell carcinomas with papillary architecture and clear cell components: 9 cases were confirmed to be papillary renal cell carcinomas and 3 cases were confirmed to be clear cell renal cell carcinomas. Despite these ancillary techniques, 2 cases remained unclassified. Our study establishes the utility of these procedures in accurately classifying the great majority of renal cell carcinomas with these findings.
  
  
• Editorial Comment
  In some tumors, the pathologist finds clear cell component in an otherwise papillary tumor. The usual papillary renal cell carcinoma may be either type I or II. In the former, the cells have scant cytoplasm and due to this cytological feature, the tumor has a blue tinge in the microscopic examination. Type II tumors have abundant eosinophilic cytoplasm. In case there is a clear cell component, the differential diagnosis is papillary renal cell carcinoma with clear cell component vs. clear cell (conventional) renal cell carcinoma with papillary features. The study by Gobbo et al. shows that immunohistochemical and cytogenetical analyses are important for the differential diagnosis.
  Two other tumors that may have papillary architecture with clear cell component must be recognized: the renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions (1) and the renal cell carcinoma associated with acquired cystic kidney disease (2). The latter is easily diagnosed due to the association with patients submitted to hemodialysis. To exclude the former it is necessary that TFE3 is negative in immunohistochemistry.
  It is controversial the significance of a clear cell component when the diagnosis is the usual papillary renal cell carcinoma. Some consider these tumors to have a good prognosis, which goes along with their low nuclear grade. Others, however, have shown that a clear cell component is associated with a higher stage (3-5).
  In spite of this controversy, it is important that the practicing pathologist adds to his pathology report the finding of a clear cell component in cases of usual papillary renal cell carcinoma.

References
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5. Teixeira DA, Billis A, Stelini RF, Vital-Brasil AA, Denardi F: Papillary renal carcinomas with clear cells: clinicopathological features. Mod Pathol 2007; 20(suppl 2):180A.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
E-mail: athanase@fcm.unicamp.br