IRTA1 positivity helps identify a MALT‐lymphoma‐like subset of primary cutaneous marginal zone lymphomas, largely but not exclusively defined by IgM expression. (8th August 2021) - Carlsen, Eric D.
Abstract: Background: It has been proposed that primary cutaneous marginal zone lymphomas (PCMZLs) include a MALT‐lymphoma‐like IgM+ subset and a class‐switched subset, which is unlike most other MALT lymphomas. Whether expression of the MALT lymphoma‐associated biomarkers IRTA1 and MNDA would support this concept and whether they might help explain why some patients have both subtypes is uncertain. Methods: Twenty‐five PCMZLs from 21 patients were stained for IRTA1 by in situ hybridization and for MNDA by immunohistochemistry. In two patients, polymerase chain reaction (PCR)‐based B‐cell clonality studies were performed on biopsy specimens of metachronous lesions, which expressed different heavy chains. All results were correlated with the histopathologic and clinical findings. Results: Five of six IgM+ PCMZLs were IRTA1+ vs three of 18 evaluable class‐switched cases ( P = 0.0069). Two of the class‐switched IRTA1+ cases were in patients with clonally‐related IRTA1+ IgM+ PCMZLs. IRTA1 positivity showed a statistically significant correlation with several MALT‐lymphoma‐associated histopathologic findings. In contrast, all PCMZL cases showed at least some MNDA expression with no differences between IgM+ and class‐switched cases. Conclusions: IRTA1 identifies MALT‐lymphoma‐like PCMZLs that are largely but not exclusively IgM+. This supports the concept of two PCMZL subsets but suggests their distinction should not be based solely on their heavy chain expression.