The edition · Pathology
Mismatch repair status can differ between foci of the same prostate cancer
A 32-case series on mismatch repair deficiency in prostate cancer, poor observer agreement on grading appendiceal goblet cell adenocarcinoma, section thickness as a hidden variable in H&E images, and which cytology preparations hold up for sequencing.
The edition in brief
A single-institution series of 32 primary mismatch repair-deficient prostate adenocarcinomas found that 57% of cases (8 of 14) with immunohistochemistry on several blocks showed discordant status between foci, with deficiency confined to the highest-grade focus; Lynch syndrome was found in 5 of 15 who had germline testing. Seven pathologists grading 20 appendiceal goblet cell adenocarcinomas under WHO 5th edition criteria agreed fairly at best (Fleiss kappa 0.29, 95% CI 0.14 to 0.44); a two-tier system may be more reproducible. Confocal profiling showed that paraffin section thickness often differed from the microtome setting by more than 10%, and an AI model inferred thickness from H&E images (R² 0.86). In 455 cytology specimens, cell blocks performed like FFPE for hybrid-capture sequencing (median target coverage 98% or more), while Papanicolaou-stained smears covered 74.7% of targets with more GC bias.
Mismatch repair status in prostate cancer can differ by focus; test the highest-grade tumour
Test the highest-grade focus for mismatch repair in multifocal prostate cancer, and say which block was stained.
Grading appendiceal goblet cell adenocarcinoma: only fair agreement between expert pathologists
Treat three-tier grade for goblet cell adenocarcinoma as uncertain; report the features and consider a second review.
Section thickness is often not what the microtome says, and AI can read it from H&E
Section thickness varies more than expected; consider it when staining or AI results look unreliable.
Say which block you stained
Document which block and tumour area underlies each ancillary test result.
Cell blocks, not smears, are the safer cytology material for hybrid-capture sequencing
Prefer cell blocks for sequencing, and validate smears separately before relying on FFPE quality thresholds.
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