The edition · Pathology
Not every single-hit TP53 mutation in MDS carries the same risk
Variant function and allele fraction split monoallelic TP53 MDS into groups that behave like wild-type or like multi-hit disease, three Hodgkin tissue markers fail validation, and a pan-TRK stain earns a place in the naevus of Reed workup.
The edition in brief
In 4,505 patients with myelodysplastic neoplasms from two cohorts, monoallelic TP53 mutations were heterogeneous: variants with a high functional phenotype score and an allele fraction of 22% or more had leukaemia-free survival close to multi-hit disease (9.2 vs 7.8 months), while low-score, low-fraction variants behaved like wild-type (44.7 vs 37.2 months). Within the EORTC-GELA H9 trial, immunohistochemistry for c-MET, HLA class II and CD68 showed no association with progression-free survival in early-stage classic Hodgkin lymphoma, so none is ready for routine prognostic use. An optimised pan-TRK stain in 79 pigmented spindle cell naevi of Reed was highly specific for NTRK3 rearrangement (PPV up to 100%) but missed about two thirds, making it a rule-in rather than a rule-out test. A meta-analysis of 15 studies found AI models classified membranous, IgA and minimal change nephropathy accurately on retrospective data, without enough head-to-head evidence to claim superiority over pathologists. The pearl covers tumour cellularity on molecular requests.
Three tissue biomarkers failed validation in early-stage Hodgkin lymphoma
c-MET, HLA class II and CD68 staining carried no prognostic value in early-stage Hodgkin lymphoma and should not be reported for that purpose.
Pan-TRK staining in naevus of Reed: specific, but misses most fusions
Pan-TRK can rule in an NTRK3-rearranged Reed naevus but cannot rule one out; keep molecular testing for difficult cases.
AI classified common glomerular diseases accurately on retrospective data
AI shows high accuracy for common glomerular diseases on retrospective data but is not ready to replace integrated renal biopsy reporting.
State tumour cellularity on every molecular request
Send tumour cellularity with every molecular request so that allele fractions and negative results can be interpreted.
TP53 variant function and allele fraction split monoallelic MDS into distinct risk groups
Report TP53 variant identity, allele fraction and allelic state in MDS - monoallelic cases range from wild-type-like to multi-hit-like risk.
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