Maria Tretiakova

doi:10.4132/jptm.2022.08.16

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Newsletter What’s new in kidney tumor pathology 2022: WHO 5th edition updates: Maria Tretiakova^,; Journal of Pathology and Translational Medicine 2022;56(6):383-384.
DOI: https://doi.org/10.4132/jptm.2022.08.16
Published online: September 8, 2022

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

Corresponding Author: Maria Tretiakova, MD, PhD Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA E-mail: mariast@uw.edu

This article has been published jointly, with consent, in both Journal of Pathology and Translational Medicine and PathologyOutlines.com

• Received: August 13, 2022 • Accepted: August 16, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
UPDATES IN ESTABLISHED RENAL TUMORS
NEW CATEGORY OF MOLECULARLY DEFINED RENAL TUMORS
EMERGING/PROVISIONAL ENTITIES
Meet the Authors
REFERENCES

Abstract

The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduces significant changes relevant to daily practice, especially in the completely restructured renal cell tumor chapters. Herein we highlight the most important diagnostic updates of known kidney tumor types, new and molecularly defined entities and emerging/provisional entities.

Papillary renal cell carcinoma (PRCC): • Subclassification into type 1 and type 2 is no longer recommended.; • PRCC has classic morphology (papillae with vascular cores, foamy histiocytes and psammoma bodies) but can exhibit other appearances, including predominant solid phenotype, biphasic pattern with squamoid alveolar cells, eosinophilic cells with brisk inflammation mimicking Warthin tumor or predominant vacuolated cells mimicking clear cell RCC.; • Many tumors previously diagnosed as type 2 PRCC now constitute independent entities.
Clear cell papillary renal cell tumor (CCPRCT): • Renamed from carcinoma to tumor due to uniformly indolent behavior.; • Low-stage, low-grade tumor with tubulopapillary and cystic architecture composed of clear cells with linearly aligned luminally oriented nuclei.; • Co-express CK7 and CAIX (cup-like), often positive for HMWCK, but negative for CD10, and lack recurrent cytogenetic abnormalities or VHL gene alterations.
Chromophobe RCC (ChRCC): • ChRCC can have non-conventional morphology with trabecular, alveolar, papillary, microcystic or cystic architecture, but all these phenotypes typically maintain CK7/CKIT co-expression, characteristic chromosomal monosomies and favorable prognosis.
Diagnostic recommendations: • An unequivocal diagnosis of multilocular cystic neoplasm of low malignant potential (MCNLMP), CCPRCT and oncocytoma should not be made on needle biopsy alone because of limited sampling and overlapping features with malignant counterparts.

This heterogeneous group of tumors often shows significant morphologic overlap with other renal tumors. Definitive diagnosis requires molecular studies like NGS, RNAseq, FISH or RT-PCR [1].
TFE3-rearranged RCC (formerly named MiTF family Xp11 translocation RCC): • Heterogeneous tumors in younger patients with mixed papillary and solid architecture, psammoma bodies and clear to eosinophilic cytoplasm.; • Express nuclear TFE3 and variably melanocytic markers and cathepsin K.; • TFE3 rearrangement with > 20 different gene partners creates fusion subtypes with variable tumor morphology, immunoprofile and clinical behavior.
TFEB-rearranged RCC: • Tumor has either translocation or amplification of TFEB on t(6;11).; • TFEB-translocation RCC is a low-stage indolent biphasic neoplasm with nests of large clear cells and smaller cells clustered around basement membrane material.; • TFEB-amplified RCC is an often high-grade and high-stage tumor with frequent oncocytic and papillary morphology affecting older patients (Fig. 1).
Fig. 1.; TFEB-amplified RCC.

• Both subtypes consistently express nuclear TFEB, cathepsin K and melanocytic markers.

ELOC (formerly TCEB1)-mutated RCC (novel entity)

• Uncommon indolent clear cell tumor with solid and papillary growth patterns and nodular appearance due to traversing fibromuscular bands and septa.

• Morphologically mimic conventional clear cell and tuberous sclerosis-associated RCCs.

• Consistently immunoreactive for CK7 and can be focally positive for HMWCK.

• Develops due to bi-allelic inactivation of TCEB1 (ELOC) on chromosome 8 encoding for elongin C of the VHL complex with intact VHL and mTOR pathway genes.

Fumarate hydratase (FH)-deficient RCC

• Renamed from hereditary leiomyomatosis-associated RCC.

• Aggressive tumor with mixed papillary, solid, tubulocystic and cribriform architecture, composed of high-grade cells with cherry-red macronucleoli.

• Germline (majority of cases) or somatic FH gene mutations should be suspected with immunostaining demonstrating FH protein loss and/or 2-succinocysteine (2SC) gain.

Succinate dehydrogenase (SDH)-deficient RCC

• Rare tumor with distinct solid morphology of bland eosinophilic cells with bubbly inclusions.

• Loss of SDHB protein expression and germline mutation in SDH gene complex.

ALK-rearranged RCC (novel entity)

• Very rare group of extremely heterogeneous eosinophilic tumors which develop due to fusions of anaplastic lymphoma kinase gene (ALK) at 2p23 resulting in ALK protein overexpression.

• May show cytoplasmic vacuolization; solid, papillary or cribriform architecture with mucin production; psammoma bodies; metanephric-like, rhabdoid or spindle cell morphology (Fig. 2).

Fig. 2.

ALK-rearranged RCC.

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SMARCB1-deficient renal medullary carcinoma

• Renamed from renal medullary carcinoma.

• Highly aggressive medulla-centered adenocarcinoma predominantly affecting patients with sickle cell trait (hemoglobinopathy) and of African ancestry.

• Presents as locally advanced or metastatic disease with fast-growing infiltrating tumor composed of cords, nests, tubules and cribriform structures in desmoplastic background with brisk mitoses.

• Loss of SMARCB1 (INI1, SNF5, BAF47) protein expression on immunostaining reflects inactivation of SMARCB1 at 22q11.23 by chromosome translocations or deletions.

Eosinophilic solid and cystic RCC

• Novel distinct entity in “OTHER RENAL TUMORS” category

• Originally described in patients with tuberous sclerosis complex, but can occur sporadically due to TSC1 or TSC2 mutations.

• Indolent tumor disproportionately affecting women, with only rare reported metastases.

• Solid and cystic architecture, voluminous eosinophilic cytoplasm and coarse basophilic granularity.

• CK20 and cathepsin K are positive and there is a lack of CK7/CKIT expression (Fig. 3).