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clear cell papillary RCC

Wednesday 14 October 2009, by JA

Definition: Clear cell papillary renal cell carcinoma is newly-defined entity initially believed to be associated with end stage renal disease.

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, α-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.

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 co-expression of CA9, HIF-1α, 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.

Although clear cell papillary renal cell carcinoma is one of the forms of renal cell carcinoma associated with end-stage renal disease, this morphotype has also been described in otherwise normal kidneys.

There were three male patients and one female patient in this small reported series, with ages of patients ranging from 55 to 64 years. The tumors were 1.6–5 cm in maximum diameter with a thin pseudocapsule. Histologically clear cell papillary structures were associated with cysts lined by epithelial cells with clear cytoplasm. The papillae had prominent fibro-vascular cores and were covered with a single layer of clear cells with predominantly apical nuclei, exhibiting low-grade nuclear pleomorphism.

Tumor cells showed immunoexpression of CA-IX and cytokeratin 7. In one case focal expression of CD10 was seen, while AMACR and TFE3 were negative. FISH analysis showed gains of chromosome 17 in two tumors.

In all cases the tumors were confined to the kidney at diagnosis and no recurrence or metastases were reported in follow-up, which ranged from 1 to 48 months.

The principal differential diagnosis for these tumors in TFE3 translocation carcinomas with a prominent papillary pattern. Translocation carcinomas often require confirmation of TFE3 immunoexpression for diagnosis. Translocation carcinoma may also be differentiated by the absence of epithelial-lined cystic spaces surrounding papillary structures and the frequent presence of psammoma-like calcification.

In view of the constant occurrence of the papillary structures within cysts lined by clear cells in these tumors, the term clear cell papillary and cystic renal cell carcinoma is preferred to that of clear cell papillary renal cell carcinoma.

Immunochemistry

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, α-methylacyl-CoA racemase (AMACR), and TFE3.

All cases show strong co-expression of CK7, HIF-1α, GLUT-1, and CA9.

No expression of TFE3, CD10, or AMACR is seen.

Genetics

These tumors reportedly lack trisomies of chromosomes 7 and 17, deletions of 3p25, von Hippel-Lindau (VHL) gene mutations, and VHL promoter hypermethylation.

In seven tumours, array-CGH detected no chromosomal imbalances.

Subtypes

- clear-cell papillary RCC of the end-stage kidneys (#16434887#)

References

- Clear cell papillary renal cell carcinoma with characteristic morphology and immunohistochemical staining pattern. Gilani SM, Tashjian R, Qu H. Pathologica. 2012 Jun;104(3):101-4. PMID: #22931041#

- Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumour and a comparative genomic hybridization array study of seven cases. Adam J, Couturier J, Molinié V, Vieillefond A, Sibony M. Histopathology. 2011 Jun;58(7):1064-71. PMID: #21707708#

- 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. Rohan SM, Xiao Y, Liang Y, Dudas ME, Al-Ahmadie HA, Fine SW, Gopalan A, Reuter VE, Rosenblum MK, Russo P, Tickoo SK. Mod Pathol. 2011 May 20. PMID: #21602815#

- Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Tickoo SK, dePeralta-Venturina MN, Harik LR, Worcester HD, Salama ME, Young AN, Moch H, Amin MB. Am J Surg Pathol. 2006 Feb;30(2):141-53. PMID: #16434887#

- 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. Am J Surg Pathol. 2008 Dec;32(12):1780-6. PMID: #18779729#

- Clear cell papillary renal cell carcinoma: a distinct histopathologic and molecular genetic entity. Gobbo S, Eble JN, Grignon DJ, Martignoni G, MacLennan GT, Shah RB, Zhang S, Brunelli M, Cheng L. Am J Surg Pathol. 2008 Aug;32(8):1239-45. PMID: #18594469#

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