The edition · Pathology
A 2026 WHO reshuffle for mixed tumours, and why MMR staining alone is not enough
Plus a light-chain in situ test for the Hodgkin lymphoma grey zone, the immunostain pitfalls of clear cell renal carcinoma, and what a decade of points-based variant scoring did to uncertain results.
The edition in brief
Today's pathology edition opens on classification. A review sets out how the 2026 WHO scheme handles mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) — two components each at least 30%, with the non-neuroendocrine part not counting if it is only a precursor — and introduces amphicrine-like carcinoma for intimately intermixed differentiation, both requiring immunohistochemical confirmation. A dual kappa/lambda mRNA in situ hybridisation assay in 53 lymph node biopsies separated nodular lymphocyte-predominant from classic Hodgkin lymphoma in overlapping cases. A cohort of 108 molecularly verified clear cell renal cell carcinomas mapped how often immunostains such as cytokeratin 7 and CA9 stray from the textbook pattern, tying aberrant staining to architecture and to PBRM1 and BAP1 status. A molecular-diagnostics analysis showed a points-based variant-classification framework steadily cut rates of variants of uncertain significance over ten years. A clinic pearl reaffirms breast-biomarker pre-analytics. The practice-changer: a real-world series of upper gastrointestinal and pancreaticobiliary cancers shows mismatch-repair immunohistochemistry alone misses cases, and a multimodal workup with MSI, MLH1 methylation and sequencing is needed for accurate biomarker and Lynch screening.
The 2026 WHO scheme clarifies MiNEN and adds amphicrine-like carcinoma
Apply the 2026 WHO definitions when reporting mixed neuroendocrine tumours: reserve MiNEN for two components each at least 30%, and use amphicrine-like carcinoma for intimately intermixed differentiation.
Light-chain mRNA in situ hybridisation separates the Hodgkin grey zone
Consider kappa/lambda mRNA in situ hybridisation as an ancillary test to resolve cases that overlap between nodular lymphocyte-predominant and classic Hodgkin lymphoma.
Clear cell renal carcinoma strays from its textbook immunoprofile
Expect aberrant immunostaining in clear cell renal cell carcinoma, especially in metastatic or higher-grade tumours, and use molecular testing to resolve ambiguous cases.
A points-based framework steadily cut uncertain variant calls
Structured, points-based variant classification lowers rates of uncertain significance over time, and the score itself signals how likely a variant is to be reclassified.
Guard the pre-analytics for breast hormone-receptor and HER2 testing
Protect breast-biomarker accuracy at the pre-analytic step: short cold ischaemia, adequate neutral buffered formalin fixation, and documented times.
Mismatch-repair IHC alone is not enough in GI and pancreaticobiliary cancers
Work up mismatch-repair deficiency multimodally — immunohistochemistry plus MSI, MLH1 methylation and germline testing where indicated — rather than relying on immunohistochemistry alone.
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