Microscopic Description:

Tumor is arranged in papillary architecture with central fibrovascular cores which at places are expanded by cystic macrophages.

The tumor cells lining the cores are tall columnar to polygonal filled with bright eosinophilic to clear foamy cytoplasm.

The nuclei are located away from the core and show anisonucleosis and pleomorphism with focal bi-multi-nucleation and uniformly displaced chromatin. Rare mitosis seen. Few cells show eosinophilic nucleoli and pseudoinclusions.

Occasional bizarre cells are also seen.

There is presence of intracellular hemosiderin pigment in some cells.

Immuno-histochemistry:

Positive: PAX-8, AMACR, CD-10, SDHB (Retained), FH (Retained)

Negative: CK-7, CD-117, CK-20, GATA-3

Ki-67- low, CA-IX- Non specific

Careful assessment of morphology and immunohistochemistry clearly rules out other differential diagnoses.

Clear cell renal cell tumor are low grade tumors which can show papillary configuration, but nuclei are oriented towards luminal aspect. Positivity for CK7 and cup like staining for CA-IX and patchy or negative staining for AMACR and CD-10 favors this tumor.

Oncocytomas composed of polygonal cells filled with eosinophilic granular cytoplasm, round nucleus, dispersed chromatin and central small nucleolus. These are also negative for CK7 but exhibit positivity for CD117.

Papillary renal cell carcinomas show variable morphology including papillary, tubular, squamoid and solid. The cells show positivity to CK7, PAX-8 and AMACR while are negative for CA-IX, CD-117 and GATA3.

Discussion:

Oncocytic variant of papillary renal cell carcinoma has recently been described in literature as a subset of papillary renal cell carcinoma. The tumor has been studied to show overlapping features of papillary renal cell carcinoma.

The clinical presentation is same as in most of the renal tumors which include hematuria, abdominal discomfort. But significant number of cases were detected as an incidental finding. Most cases presented at WHO stage I/II.

Radiologically it presents as a well demarcated enhancing mass lesion.

Diagnosis is confirmed by histo-morphological features and supportive immunohistochemistry (Positive: PAX-8, AMACR, CD-10, Negative: CK7, CD117 ,CK20, GATA3, CA-IX,). Proliferation index is generally low.

The genetic analysis done in few studies show the overlap with classic papillary renal cell carcinoma. Trisomies of chromosome 7, 17 and loss of chromosome Y has been described most common findings. Less frequent changes were gain of chromosome 3p, 11q,17q and loss of chromosome 4q.

It has been shown to have a favorable prognosis and rare chance of metastasis after complete resection.

In conclusion, Renal cell tumor with distinct oncocytic and papillary architecture with secondary features like nuclear inclusion, nucleoli and intracellular pigment should be tested with panels of IHC markers and genomic sequencing for better classification of the tumor.

References:

Williamson SR, Hartmann A, Martignoni G, Hes O, Rioux-Leclercq NC, Saleeb RM. Papillary renal cell carcinoma. In: Moch H, Amin MB, Tickoo SK, Turajlic S eds. Urinary and male genital tumors. Lyon, France: IARC; 2022. (WHO classification of tumor series, 5th edition.; Vol. 8) https://tumourclassification.iarc.who.int/chapters/36.

Xia Q, Li L, Shen Q, Rao Q, Yu B, Zhang R, et al. Clinicopathologic features of oncocytic papillary renal cell carcinoma. J Diag Pathol. (2014) 21:4–7. doi: 10.3969/ j.issn.1007-8096.2014.01.002 22.

Nian Y, Wang Y, Yi L, Hus, G. Oncocytic papillary renal cell carcinoma: a case report and literature review. J Clin Urology(China). (2013) 28:764–5. doi: 10.13201/ j.issn.1001-1420.2013.10.01

Lefèvre M, Couturier J, Sibony M, Bazille C, Boyer K, Callard P, et al. Adult papillary renal tumor with oncocytic cells: clinicopathologic, immunohistochemical, and cytogenetic features of 10 cases. Am J Surg pathology. (2005) 29:1576–81. doi: 10.1097/01.pas.0000184821.09871.ec 2.

Mai KT, Kohler DM, Robertson SJ, Belanger EC, Marginean EC. Oncocytic papillary renal cell carcinoma with solid architecture: mimic of renal oncocytoma. Pathol Int. (2008) 58:164–8. doi: 10.1111/j.1440-1827.2007.02205.x 3.

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