The edition · Pathology
MTAP immunohistochemistry resolved borderline sequencing calls, often revealing homozygous loss
A 2,409-tumour exome study backs a cheap stain for an emerging therapeutic biomarker, the 2026 WHO classification tightens what counts as MiNEN and adds amphicrine-like carcinoma, and benign colorectal lymph nodes carry prognostic information.
The edition in brief
In 2,409 tumours profiled by whole-exome sequencing (Modern Pathology, 23 September 2026), MTAP immunohistochemistry agreed closely with sequencing for wild-type and homozygous deletion and reclassified a substantial share of 'probable heterozygous' calls as protein loss, confirmed as homozygous deletion by FISH; these ambiguous calls were not explained by low tumour cellularity. MTAP loss is emerging as a biomarker for PRMT5-MAT2A pathway inhibitors. A Histopathology review sets out the 2026 WHO gastrointestinal rules: MiNEN needs two recognisable components each of at least 30%, a precursor lesion does not qualify, and amphicrine-like carcinoma is introduced for intimately intermixed differentiation. A multicentre study of 10,410 non-metastatic colorectal lymph nodes classified them reproducibly as stimulated, unstimulated or depleted (κ 0.879), and a model built on these subtypes stratified survival in external cohorts. A sequencing-based clonal relatedness index separated clonal from independent GI carcinomas far better than morphology. Early-onset Merkel cell carcinoma was frequently node-positive at presentation. Pearl: report the lymph node count in colorectal resections.
WHO 2026: what is and is not MiNEN, and the new amphicrine-like carcinoma
Apply the 2026 WHO criteria: MiNEN needs two components of at least 30% each, precursors do not count, and intermixed tumours are amphicrine-like carcinoma.
Benign colorectal lymph nodes can be reproducibly subtyped on H&E, and the pattern tracks survival
H&E subtypes of non-metastatic colorectal nodes were reproducible and prognostic, but remain a research measure.
A simple sequencing index separated clonal from independent GI tumours far better than morphology
When both tumours have been sequenced, a clonal relatedness index is more reliable than morphology for metastasis versus second primary.
Merkel cell carcinoma under 50: often immunosuppressed and often node-positive at diagnosis
Do not let a younger age argue against Merkel cell carcinoma; check markers and ask about immunosuppression.
Count and report the lymph nodes in every colorectal resection
Aim for at least 12 nodes in colorectal resections and say so in the report when fewer are found.
MTAP immunohistochemistry settled ambiguous sequencing calls across 2,409 tumours
Use MTAP immunohistochemistry, with FISH where needed, to resolve indeterminate sequencing calls for MTAP deletion.
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