IRTA1 positivity helps identify a MALT-lymphoma-like subset of primary cutaneous marginal zone lymphomas, largely but not exclusively defined by IgM expression

J Cutan Pathol. 2022 Jan;49(1):55-60. doi: 10.1111/cup.14111. Epub 2021 Aug 8.

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.

Keywords: IRTA1; MALT lymphoma; MNDA; cutaneous marginal zone lymphoma; skin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoglobulin M / biosynthesis*
  • Lymphoma, B-Cell, Marginal Zone* / diagnosis
  • Lymphoma, B-Cell, Marginal Zone* / metabolism
  • Lymphoma, B-Cell, Marginal Zone* / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Receptors, Fc / biosynthesis*
  • Skin Neoplasms* / diagnosis
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology

Substances

  • FCRL4 protein, human
  • Immunoglobulin M
  • Neoplasm Proteins
  • Receptors, Fc