The edition · Pathology
MTAP immunohistochemistry resolves ambiguous sequencing calls, and the MiNEN definition is tightened
A pan-cancer concordance study supports MTAP immunohistochemistry for borderline deletion calls, a review spells out the 30% rule and new amphicrine-like category for mixed neuroendocrine tumours, and two histopathology series add immunophenotype data in renal and bladder carcinoma.
The edition in brief
In 2,409 tumours profiled by whole-exome sequencing, MTAP immunohistochemistry agreed closely with genomic status in wild-type and homozygously deleted tumours and reclassified a substantial proportion of tumours called heterozygous by sequencing; protein loss in those cases matched FISH-confirmed homozygous deletion, and the ambiguous calls were not explained by low tumour cellularity. A review of mixed neuroendocrine-non-neuroendocrine neoplasms restates that each component must make up at least 30%, that a precursor or intramucosal non-neuroendocrine component does not qualify, and introduces amphicrine-like carcinoma for intimately intermixed differentiation; both require immunohistochemistry. In 108 molecularly verified clear cell renal cell carcinomas, KER7 staining was commoner in primary than metastatic tumours (45% versus 13%) and in PBRM1 wild-type tumours, and CA9 negativity occurred only in metastases. In 79 bladder small cell carcinomas, immunohistochemistry separated high and low neuroendocrine phenotypes with different Nectin-4, DLL3 and SLFN11 profiles.
Mixed neuroendocrine tumours: the 30% rule, what is excluded, and amphicrine-like carcinoma
Check the proportion of each component and the nature of the non-neuroendocrine element before using the term MiNEN, and confirm neuroendocrine differentiation with immunohistochemistry.
Clear cell renal cell carcinoma: aberrant immunostaining is common and tracks with metastasis and PBRM1 status
When a renal tumour has an unexpected stain such as KER7 positivity or CA9 negativity, weigh it against morphology and consider molecular confirmation before changing the diagnosis.
Bladder small cell carcinoma splits into two immunophenotypes with different therapeutic targets
In a bladder small cell carcinoma, consider noting the neuroendocrine phenotype in the report so that targeted-therapy discussions can draw on it, without implying a treatment recommendation.
Match the control to the antibody before reading a surprising negative
Before reporting a surprising negative stain, confirm the external and internal controls worked.
MTAP immunohistochemistry can settle borderline sequencing calls
Consider MTAP immunohistochemistry, with FISH confirmation when results are discordant, to resolve borderline copy number calls, after validating your own antibody and cut-offs.
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