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Research · 03 of 05

Light-chain mRNA ISH separates grey-zone NLPHL from classic Hodgkin

In grey-zone Hodgkin biopsies, strong cytoplasmic light-chain mRNA in tumour cells favours NLPHL; faint signal does not.

Design
Retrospective diagnostic study
Population
53 lymph node biopsies across NLPHL and classic Hodgkin lymphoma, including 15 borderline cases
Primary outcome
Kappa/lambda mRNA expression pattern in tumour cells
Effect
Canonical pattern in 13/13 NLPHL and 12/15 borderline; none in classic Hodgkin

A dual kappa/lambda mRNA in situ hybridisation assay was applied to 53 lymph node biopsies across the spectrum from nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) to classic Hodgkin lymphoma, including 15 borderline cases with overlapping features. Published in Modern Pathology on 23 September 2026.

Strong, diffuse cytoplasmic light-chain signal in tumour cells was seen in all 13 typical NLPHL and 12 of 15 (80%) borderline cases. Classic Hodgkin lymphoma was either negative or showed only faint perinuclear or granular signal, seen in 55% of lymphocyte-rich and 28% of other subtypes. A minority of borderline cases, including two EBV-positive ones, showed the faint pattern.

The series is small and the assay is not yet widely available. But it offers an objective tiebreaker in a distinction that changes treatment, and it makes the point that faint signal should not be read as a positive result.

  • Consider light-chain mRNA ISH for lymph nodes with overlapping NLPHL and lymphocyte-rich classic Hodgkin features
  • Read only strong, diffuse cytoplasmic signal in tumour cells as the NLPHL pattern
  • Do not treat faint perinuclear or granular signal as positive
  • Correlate with EBV status and the full immunophenotype

Why it matters

NLPHL and classic Hodgkin lymphoma are treated differently, and the borderline cases are where the call is hardest.

Don't overread it

A small series with a novel assay; it is not yet a validated diagnostic standard.

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