Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue

Abstract

Aims Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA. Methods and results Nephrectomy specimens of PRCC and PA from our 10‐year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow‐up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild‐type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non‐type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non‐type D PAs. Conclusions Type D PA was different from other types of PA and represented an analogue or a small‐sized PRNRP for their identical morphology, immunophenotype and molecular signature.

WHO 2022 landscape of papillary and chromophobe renal cell carcinoma

“…49,51,52 The number of this tumour reported in the literature is growing fast, with reports of >90 cases in the last 2-3 years, showing that it is often cystic, 52 may be found synchronously with other RCCs 50 and has an adenoma analogue. 47 Warthin-like pRCC is another pattern reported in a series of 11 patients, morphologically resembling Warthin tumour of the parotid gland. 53 Tumours show a predominant papillary architecture, with eosinophilic cells and focal pseudostratification, highgrade features, and surrounded by an intense lymphocytic infiltrate composed of B and T cells.…”

“…45 It is composed of papillae, with hyalinised or oedematous cores and lined by cells with abundant eosinophilic cytoplasm with small, low-grade nuclei lined against the apical pole of the cell (reverse polarity), sometimes with optical clearing. [45][46][47][48][49][50][51] The reported cases consisted of small tumours with good clinical outcome, with no recurrences, metastases, or deaths. 45,52 Characteristic GATA3 nuclear staining is found, as well as L1CAM staining.…”

The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth

“…Papillary renal neoplasm with reversed polarity (PRNRP) falls within the classical spectrum of pRCC, having been designated in literature as "oncocytic low-grade papillary RCC" or even "type 4 pRCC" [55][56][57][58][59]. Analysis of our cohorts revealed only four cases.…”

Papillary renal cell carcinoma: current and controversial issues

“…Tumours are usually small and can be partly cystic [57]. They have a quite characteristic morphology, recapitulated in several recent publications [56,[58][59][60][61][62][63], composed of thin papillae with hyalinised cores filled with a single row of eosinophilic cells with small uniform nuclei (sometimes with optical clearing) aligned and pushed against the apical pole (reversed polarity), frequently with peritumoral lymphoid aggregation. In the past, they have probably been fit into a 'low-grade oncocytic pRCC' designation, due to their low-grade cytology and absence of aggressive features, in line with their good clinical behaviour [61].…”