Most pancreatic acinar cell carcinomas carried homologous recombination defects

Design

Retrospective molecular profiling series (targeted NGS)

Population

8 acinar cell carcinomas, 7 amphicrine-like acinar carcinomas, 4 NETs from 2151 sequenced pancreatic cases, Korea

Primary outcome

Genomic alterations including homologous recombination deficiency

Effect

HRD-associated alterations in 7/8 (87.5%) acinar cell carcinomas and 29% of amphicrine-like tumours

Among 2151 pancreatic cases sequenced on a 323–343 gene hybrid-capture panel in a Korean centre, the authors identified eight acinar cell carcinomas, seven amphicrine-like acinar cell carcinomas (previously called MiNENs under the fifth WHO edition) and four neuroendocrine tumours.

Homologous-recombination-deficiency alterations — in BRCA1/2, ATM and FANCD2 — were present in seven of eight acinar cell carcinomas (87.5%) and 29% of the amphicrine-like tumours. The amphicrine-like group was heterogeneous: two showed a 'true hybrid' profile with both neuroendocrine (MEN1) and exocrine (APC, SMAD4, CTNNB1) drivers, while two looked molecularly like acinar carcinoma despite neuroendocrine differentiation.

The numbers are very small, but the direction matches earlier reports that acinar cell carcinoma is enriched for HR defects. That has two consequences for sign-out: an acinar diagnosis should prompt a recommendation for molecular testing and germline counselling, and the sixth-edition amphicrine-like category is not molecularly uniform.

• Confirm acinar differentiation with trypsin, chymotrypsin or BCL10 immunohistochemistry before signing out acinar cell carcinoma.
• Recommend tumour sequencing for homologous recombination genes in every pancreatic acinar cell carcinoma report.
• Suggest germline BRCA1/2 and ATM testing and genetic counselling, since some of these alterations are inherited.
• Use the WHO sixth-edition term amphicrine-like acinar cell carcinoma when a >30% intimately admixed neuroendocrine component is present.
• Note in the report that amphicrine-like tumours are molecularly heterogeneous.

Why it matters

A histological subtype that is often treated like ductal adenocarcinoma may often carry homologous-recombination alterations, a possible but untested therapeutic target.

Don't overread it

Eight acinar carcinomas from one centre; the 87.5% figure is imprecise and PARP-inhibitor benefit was not tested.

The statistics, in plain English

Seven of eight is a striking proportion, but with eight cases the true rate could plausibly lie anywhere from about half to nearly all. The finding supports testing, not a precise prevalence estimate.

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