A stain that favours collecting duct carcinoma, and a quantitative clonality test

The edition in brief

Today's pathology edition is built around diagnostic and molecular tools a sign-out can use. NF2/Merlin immunohistochemistry helped separate collecting duct carcinoma from upper tract urothelial carcinoma: Merlin loss was seen in 63% of collecting duct carcinomas and none of 35 urothelial cases, making loss highly specific though not sensitive. A prospective two-centre study of a urinary DNA mutation-and-methylation assay (EpiMut-BC) detected bladder cancer with 85.9% sensitivity and 95.8% specificity, but only 70.3% sensitivity for early-stage tumours, so it supplements rather than replaces cystoscopy. A retrospective series subtyped 42 biliary tract neuroendocrine carcinomas into ASCL1, NEUROD1, POU2F3 and null types, with the null type independently predicting shorter survival (hazard ratio 3.48); notably, some POU2F3 tumours lacked chromogranin, synaptophysin and INSM1, a diagnostic trap. A clinic pearl restates universal mismatch-repair immunohistochemistry with reflex testing. The practice-changer is a clonal-relatedness index built from next-generation sequencing: across 120 paired gastrointestinal, hepatopancreaticobiliary and peritoneal tumours it discriminated clonal from independent lesions with an area under the curve of 0.99, far outperforming phenotype-based assessment, especially in hypermutable tumours.