Low-risk HPV in situ hybridisation flags digital papillary adenocarcinoma, if you look for dots

The edition in brief

Four studies for pathologists. In 12 digital papillary adenocarcinomas and 8 tubular adenomas, commercially available low-risk HPV chromogenic in situ hybridisation (which covers HPV42) was positive in every adenocarcinoma and no adenoma, while BRAF V600E showed the reverse; the signal was punctate and nuclear and sometimes visible only at high power. In 42 biliary tract neuroendocrine carcinomas subtyped by ASCL1, NEUROD1 and POU2F3 immunohistochemistry, the null type independently predicted shorter disease-specific survival (HR 3.48), and several POU2F3-type tumours were negative for chromogranin, synaptophysin and INSM1. GPNMB stained all 9 uterine PEComas diffusely but also 47% of leiomyosarcomas, so it cannot stand alone. A clonal-relatedness index from sequencing data separated clonal from non-clonal paired GI and hepatopancreaticobiliary tumours with AUROC 0.986, outperforming morphology, especially in hypermutated tumours. The pearl covers building a panel when a uterine spindle-cell tumour might be a PEComa.