What's new in the WHO 2022 classification of kidney tumours?

Abstract

The World Health Organization (WHO) 2022 classification of urinary and male genital tumours (5th edition) has significantly improved our understanding of the morphologic, immunohistochemical, and molecular characteristics of renal tumours. The aim of this review is to outline the most important changes and diagnostic updates in the WHO 2022 classification of kidney tumours. A major change in this edition is the grouping of renal tumours into broader categories that include "clear cell renal tumours", "papillary renal tumours", "oncocytic and chromophobe renal tumours", "collecting duct tumours" as well as adding two categories of "other renal tumours" and "molecularly defined renal carcinomas". Novel entities included in the WHO 2022 classification are eosinophilic solid and cystic renal cell carcinoma (ESC RCC), anaplastic lymphoma kinase (ALK)-rearranged RCC and ELOC (formerly TCEB1)-mutated RCC. The category of "other renal tumours" includes a group of diverse, unrelated renal tumours that do not fit into other categories. The group of "molecularly defined renal carcinomas" reflects recent discoveries in the renal tumour genomics. These molecularly-defined renal entities demonstrate a set of morphologic features reflecting genotype-phenotype relationships. Final diagnosis of such entities rests on phenotypic and immunohistochemical (IHC) correlation, usually associated with IHC surrogate makers that reflect specific genetic abnormalities.

Keywords: WHO; classification; kidney; pathology; renal cell carcinoma.

Figure 1.

Papillary renal cell carcinoma (PRCC) – novel patterns. (A) Biphasic (alveolo-squamoid) PRCC with larger eosinophilic cells showing frequent emperipolesis (cytophagocytosis), surrounded by smaller amphophilic to basophilic cells. (B) Cyclin-D1 immunoreactivity is present in the larger cells. (C) Papillary renal neoplasm with reverse nuclear polarity is consistently positive for GATA3 (D). (E) Warthin-like PRCC demonstrates brisk inflammation mimicking Warthin tumour of the salivary gland.

Figure 2.

FH-deficient RCCs usually presents with a variable morphologic patterns that frequently include papillary and intracystic (A) and tubulocystic growth (B). Prominent “cherry-red” nucleoli are at least focally present (C). FH immunostaining is absent in the tumour cells (D).

Figure 3.

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) shows solid and cystic areas (A). The cells have eosinophilic cytoplasm and indistinct borders (B). Cytoplasmic stippling (or coarse cytoplasmic granules) is a helpful and virtually ever-present finding (C). CK20 is diffusely or focally positive (D).

Figure 4.

ALK-rearranged RCC has typically heterogeneous morphology. (A) A circumscribed tumour with peripheral pseudocapsule seen at low power, with easily recognisable pools of mucin and aggregates of psammoma bodies/calcifications. (B) At higher power, papillary formations can be seen (top), adjacent to tubules with luminal mucin (bottom). (C) Papillary formations are set in a necrotic background. (D) Foci of mucin-containing signet-ring cells with an inflammatory background were also present. (E) ALK immunostaining is positive in the neoplastic cells. (F) Papillary formations also demonstrated unusual nuclear immunoreactivity for TTF1 (thyroglobulin was negative, not shown).

Figure 5.

ELOC (formerly TCEB1)-mutated renal cell carcinoma. (A) Thick fibromuscular bands are present at the tumoural periphery that separate areas with clear cell morphology. (B) Clear cell areas show compact growth and focal papillary formations (seen on the right). (C) Neoplastic cells often form branching tubules with clear cells and with often voluminous cytoplasm. (D) CK 7 immunostain is diffusely positive.

Figure 6.

Low-grade oncocytic tumour (LOT) demonstrates solid and compact nested growth pattern without a capsule (A). Tumour cells are eosinophilic with round to oval ‘low-grade’ nuclei and focal perinuclear halos (B). There are focal areas of loose stroma with pauci-cellular and irregular cell composition (C). CK7 is diffusely positive (D) and CD117 is typically negative (E). GATA3 is positive in LOT (F).

Figure 7.

Eosinophilic vacuolated tumour (EVT). (A) EVT is a circumscribed, but unenecapsulated eosinophilic tumour, with thick-walled vessels at the periphery. (B-C) Cells show large intracytoplasmic vacuoles and round to oval nuclei with prominent nucleoli. (D) Positive immunoreactivity to cathepsin K is present.