The edition · Pathology
In multifocal prostate cancer, mismatch repair loss sat in the highest-grade focus, so that is the block to stain
A series of 32 mismatch repair-deficient prostate cancers found discordant staining between foci in more than half of those tested on several blocks. Plus p53 immunohistochemistry in Barrett's across a national panel, FOG1 as a marker of gastro-oesophageal origin, Rb in cervical neuroendocrine carcinoma, and same-day nanopore methylation for brain tumours.
The edition in brief
A single-institution series of 32 treatment-naive mismatch repair-deficient (MMRd) prostate adenocarcinomas found 38% were grade group 5, but 28% were grade group 2, and 78% had cribriform or intraductal carcinoma. Loss mostly involved MSH2/MSH6. Five of 15 patients tested had Lynch syndrome. Where several blocks were stained, MMR status differed between foci in 8 of 14, with deficiency always in the highest-grade focus. A Dutch national expert panel reviewing 1,146 Barrett's oesophagus consultations found p53 immunohistochemistry reproducible (kappa 0.65 among 13 pathologists) and decision-changing: it moved 37% of indefinite-for-dysplasia biopsies to low-grade dysplasia and 17% to non-dysplastic. FOG1 stained 91% of gastro-oesophageal adenocarcinomas but under 8% of colonic ones, while about half of gastro-oesophageal tumours were CDX2 negative or low. In 29 cervical neuroendocrine carcinomas, 27 of 28 tested were HPV positive, and all of those showed partial Rb loss, unlike the complete loss typical of lung small cell carcinoma. Nanopore sequencing gave same-day methylation classes for paediatric CNS tumours that matched histology at family level in every case. The pearl covers documenting which block went for biomarker testing.
p53 immunohistochemistry in Barrett's was reproducible across a national panel and changed diagnoses
Use p53 immunohistochemistry as an adjunct in Barrett's biopsies that are indefinite or borderline, and report the pattern by name.
FOG1 stained nine in ten gastro-oesophageal adenocarcinomas and few colonic ones
FOG1 may identify gastro-oesophageal origin where CDX2 fails; it needs independent validation before routine use.
Cervical neuroendocrine carcinomas were HPV-driven and showed partial, not complete, Rb loss
To separate cervical from lung small cell carcinoma, consider Rb pattern and HPV in situ hybridisation; p16 alone will not do it.
Same-day nanopore methylation matched arrays for paediatric brain tumour families
Nanopore methylation can give a same-day family-level CNS tumour class that agrees with arrays, if fresh tissue is available.
Name the block that went for biomarker testing, and why it was chosen
Test the highest-grade block and say which block it was in the report.
Mismatch repair loss in prostate cancer was confined to the highest-grade focus in more than half of multiblock cases
In multifocal prostate cancer, test mismatch repair status on the highest-grade focus, and consider a second block if the first is intact.
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