2
eosinophilic cells with brisk inammation
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 tubulo-
papillary 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 morphol-
ogy with trabecular, alveolar, papillary, micro-
cystic 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 (MCN-
LMP), CCPRCT and oncocytoma should not
be made on needle biopsy alone because of
limited sampling and overlapping features with
malignant counterparts.
NEW CATEGORY OF
MOLECULARLY DEFINED
RENAL TUMORS
This heterogeneous group of tumors often shows
signicant morphologic overlap with other renal
tumors. Denitive diagnosis requires molecular
studies like NGS, RNAseq, FISH or RT-PCR
(Mod Pathol 2021; 34: 1167-1184, Mod Pathol
2021; 34: 1392-1424).
Issue 19 || September 2022
WHAT’S NEW IN KIDNEY
TUMOR PATHOLOGY
2022: WHO 5TH EDITION
UPDATES
Maria Tretiakova
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
ORCID
Maria Tretiakova
https://orcid.org/0000-0002-0819-9638
Abstract
The 5th edition WHO Classication of Urinary
and Male Genital Tumours (2022) introduces
signicant 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 dened
entities and emerging/provisional entities.
UPDATES IN ESTABLISHED
RENAL TUMORS
Papillary renal cell carcinoma (PRCC)
• Subclassication into type 1 and type 2 is no
longer recommended.
• PRCC has classic morphology (papillae with
vascular cores, foamy histiocytes and psam-
moma bodies) but can exhibit other appear-
ances, including predominant solid phenotype,
biphasic pattern with squamoid alveolar cells,
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, immunoprole and clinical
behavior.
TFEB-rearranged RCC
• Tumor has either translocation or amplication
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-amplied RCC is an often high-grade
and high-stage tumor with frequent oncocytic
and papillary morphology affecting older
patients (Fig. 1).
• 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 bromuscular
bands and septa.
• Morphologically mimic conventional clear cell
and tuberous sclerosis-associated RCCs.
PathologyOutlines.com
WHAT’S NEW
IN PATHOLOGY?
Sponsored by an unrestricted grant from Roche
Fig. 1. TFEB-amplified RCC.