Utility of ultrasensitive, US Food and Drug Administration-approved κ and λ dual in situ hybridization assay in the diagnosis of Hodgkin lymphomas.
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OBJECTIVES: Determination of B-cell clonality in formalin-fixed, paraffin-embedded tissues is challenging, especially in cases where tumor B cells are sparse. Flow cytometry is of limited utility in Hodgkin lymphomas, at least in part due to the rarity and fragility of the malignant cells. METHODS: We used a recently US Food and Drug Administration-approved, ultrasensitive κ and λ dual in situ hybridization assay (K/L dual ISH; Roche/Ventana Medical Systems) to evaluate B-cell clonality in 184 classic Hodgkin lymphomas (CHLs) and 113 nodular lymphocyte-predominant Hodgkin lymphomas (NLPHLs). RESULTS: Five CHLs and 11 NLPHLs were not scorable due to preanalytical variables. Of the 179 scorable CHL cases, none showed light chain messenger RNA expression in the Hodgkin/Reed-Sternberg cells, whereas 89% of NLPHLs (91/102) exhibited light chain expression in lymphocyte-predominant (LP) cells. Among NLPHLs, 66% (68/102) showed κ restriction, 20% (21/102) showed λ restriction, and 1.9% (2/102) showed dual κ and λ expression in the LP cells. There was no appreciable light chain expression in 10% (11/102) of cases. CONCLUSIONS: Although morphology and immunohistochemistry are usually sufficient to separate CHL from NLPHL, determining light chain restriction by K/L dual ISH could provide a valuable adjunct in challenging cases, potentially improving diagnostic accuracy and patient outcomes.