Select Updates in Pathology of Kidney, Testis, and Penile Cancer for 2026
A 2026 pathologist-facing review codifies how HPV status and TP53 mutations should shape penile cancer prognosis
Journal: Human Pathology | Published: 2026-01-05 | Type: Review | PMID:41500272Authors: Tekin Burak, Whaley Rumeal D, Collins Katrina, Erickson Lori A, Cheng Liang, Gupta Sounak — Mayo Clinic, Indiana University, Brown University
Funding/COI: Funding not disclosed. Three of six authors (Erickson, Cheng, Gupta) are Editor, Senior Associate Editor, and Associate Editor at Human Pathology, the journal that published this paper. They recused from peer review; editorial responsibility was delegated elsewhere. The remaining authors declare no competing interests.
Summary
This is a narrative review written by practicing pathologists, for practicing pathologists — it synthesizes recent literature rather than generating new data. It covers three organ systems: FLCN-mutated kidney tumors (linked to Birt-Hogg-Dubé syndrome), mesothelium-derived paratesticular lesions, and penile squamous cell carcinoma. The penile cancer section is the most clinically consequential, establishing TP53 mutational status and high-risk HPV (hrHPV) status as key prognostic biomarkers that pathology reports should routinely address.
Claims
Penile SCC / HPV: High-risk HPV-positive penile squamous cell carcinomas represent a molecularly distinct subtype with different prognosis compared to HPV-negative tumors; the review recommends standardizing hrHPV testing in pathology workups
Penile SCC / TP53: TP53 alterations are highlighted as prognostically significant in HPV-negative penile SCC, paralleling what is established in head-and-neck squamous cell carcinoma
Penile SCC / staging: The review notes nuances in pathologic staging that affect prognostic accuracy — specific staging parameters are discussed but no new staging criteria are proposed
Kidney / FLCN: Summarizes diagnostic criteria for both conventional and non-conventional FLCN-mutated renal tumors; endorses GPNMB immunohistochemistry as a useful diagnostic marker
Kidney / ESC RCC: Flags diagnostic pitfalls for eosinophilic solid and cystic renal cell carcinoma
Testis: Recommends replacing "PNET" with "embryonic-type neuroectodermal tumor" when describing somatic transformation of testicular germ cell tumors; provides recommended IHC panels for sex cord-stromal tumors
Note: As a review, this paper does not report effect sizes, sample sizes, or p-values. All claims are synthesized from prior literature; readers should trace individual citations within the paper for primary data.
Study Quality
This is a narrative review with no systematic search methodology described, no PRISMA flow diagram, and no explicit quality appraisal of included studies. That is not inherently disqualifying for a practice-update piece aimed at pathologists — the genre has a different purpose than a meta-analysis. It aims to distill evolving diagnostic criteria and nomenclature, which it appears to do competently given the authors' institutional affiliations. However, without a systematic search, there is no way to assess whether the literature is fully represented or selectively cited.
The penile cancer section's emphasis on TP53 and hrHPV aligns with emerging consensus in the field, supported by the molecular subtyping work published in recent years. The kidney and testis sections appear to reflect current WHO and CAP guidance updates, though the review does not make this explicit.
Red Flags
Journal COI: Three of six authors hold editorial positions at Human Pathology. Recusal is documented, but publishing a review in a journal where half the author list sits on the editorial board is a structural conflict — the delegated review process is less transparent than arm's-length peer review
No funding disclosed: For a review from high-profile academic centers, "not listed" warrants a raised eyebrow, though no commercial interest is evident from content
Narrative, not systematic: No methodology section, no search strategy, no inclusion/exclusion criteria — the reader cannot verify completeness
No primary data: Every claim in this paper traces back to other papers; the review adds synthesis, not evidence
Scope breadth: Covering kidney, testis, and penile cancer in a single review risks superficiality; the penile SCC section in particular would benefit from more granular discussion of HPV genotype-specific outcomes
Strengths
Written by subspecialty urological pathologists at major academic centers — the synthesis reflects genuine domain expertise
The nomenclature update for testicular neuroectodermal tumors (away from "PNET") is a practical, actionable clarification that reduces diagnostic ambiguity
GPNMB IHC as a kidney tumor marker is a genuinely emerging area; flagging it for practicing pathologists has diagnostic utility
The TP53/hrHPV framing for penile SCC mirrors the precision oncology approach that has proven valuable in analogous cancers, and pushing pathologists to standardize reporting is worthwhile
Honest about diagnostic pitfalls — the ESC RCC section addresses where misclassification happens, which has practical value
Verdict
Read this if you are a urological pathologist who needs a concise orientation to what changed in 2026 diagnostic criteria. As evidence, treat it as a pointer, not a source — every claim here requires following the citations to primary literature before drawing clinical conclusions. The editorial COI is real and should have been better managed, but there is no obvious sign that it distorted the content. The penile cancer section's push to standardize TP53 and hrHPV reporting in pathology reports is the most broadly relevant takeaway.