Microscopic description:

The tumor on low power shows papillary architecture with fibrovascular cores.

The papillae are lined by single layer of pink eosinophilic bland tumor cells with hobnail appearance on low power.

On high power tumor cells are low cuboidal with low N:C ratio, moderate to abundant amount of eosinophilic granular cytoplasm.

The nuclei are round, uniform, arranged apically away from the basement membrane (away from fibrovascular core) - reverse nuclear polarity.

No mitoses/ atypia.

On immunohistochemistry the tumor cells show strong nuclear staining for PAX8 suggesting primary renal neoplasm.

The tumor cells are positive CK7 and GATA3 and are negative for AMACR, Vimentin, CAIX, CD117.

Discussion:

M:F = 1:1

2/3 of tumors, right sided

Gross description:
  • Often circumscribed (mean ~2cm), soft, brown-tan mass, sometimes with cystic component and hemorrhage

Microscopy:
  • Loose papillary or tubular pattern
  • Focal or diffuse stromal hyalinization
  • Cuboidal cells with eosinophilic, finely granular cytoplasm
  • Apically located nuclei, low grade (WHO / ISUP grade 1 - 2)

Immunostains:
  • Always positive for CK7, PAX8, and GATA3
  • Always negative for CD117 and vimentin
  • L1CAM(CD171) stains basolateral membrane and EMA stains apical membrane
  • CD10 and AMACR can be positive, but often weakly and focally
  • CK20, CAIX and TFE3 are negative

Molecular:
  • %85 of PRNRP cases have KRAS mutations
  • 32% of cases have chromosomal abnormalities in chromosome 7, 17, and Y

At present PRNRP is considered as a variant of papillary renal cell carcinoma (its not a separate entity in current WHO), however many emerging studies have discussed relatively indolent behavior of these tumors.

Positivity of GATA3 and negativity of vimentin can be used to differentiate from type 1 and 2 papillary RCC.

Lack of CD117 can be used to exclude oncocytoma and chromophobe carcinoma.

KRAS mutation is another key point to differentiate from other renal cell carcinomas.

Type D renal papillary adenoma is the analogue of PRNRP. It has the identical morphology, immunophenotype and molecular signature, but the smaller size (<1.5 cm) and have been proposed to be precursors of PRNRP.

No recurrences, metastatic progression or tumor-related deaths after complete resection.

References:

Al-Obaidy KI, Eble JN, Cheng L, Williamson SR, Sakr WA, Gupta N, Idrees MT, Grignon DJ. Papillary Renal Neoplasm With Reverse Polarity: A Morphologic, Immunohistochemical, and Molecular Study. Am J Surg Pathol. 2019 Aug;43(8):1099-1111. doi: 10.1097/PAS.0000000000001288. PMID: 31135486.

Chang HY, Hang JF. Papillary renal neoplasm with reverse polarity. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumorPRNRP.html. Accessed February 28th, 2022.

Chang HY, Hang JF, Wu CY, Lin TP, Chung HJ, Chang YH, Pan CC. Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue. Histopathology. 2021 Jun;78(7):1019-1031. doi: 10.1111/his.14320. Epub 2021 Apr 10. PMID: 33351968.

CASE IMAGES