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IRTA1 Positivity in PCMZL: Implications Beyond IgM Expression

April, 04, 2024 | Lymphoma, MZL (Marginal Zone Lymphoma)

KEY TAKEAWAYS

  • The study aimed to investigate IRTA1 and MNDA expression in PCMZLs to understand their role in distinguishing IgM+ and class-switched subsets and potential implications for patients with both subtypes.
  • Researchers concluded that while IRTA1 identifies MALT-lymphoma-like PCMZLs predominantly IgM+, it suggests that distinguishing between PCMZL subsets should not rely solely on heavy chain expression.

It has been proposed that primary cutaneous marginal zone lymphomas (PCMZLs) comprise a MALT-lymphoma-like IgM+ subset and a class-switched subset, deviating from most other MALT lymphomas. Whether MALT lymphoma-associated biomarkers IRTA1 and MNDA support this distinction and elucidate the co-occurrence of both subsets remains uncertain.

Eric D. Carlsen and the team aimed to assess the expression of MALT lymphoma-associated biomarkers IRTA1 and MNDA in PCMZLs.

They performed an inclusive analysis involving 25 PCMZLs from 21 patients. They conducted staining for IRTA1 using in situ hybridization and for MNDA via immunohistochemistry. Additionally, polymerase chain reaction (PCR)-based B-cell clonality studies were conducted on biopsy specimens of metachronous lesions in 2 patients, showing different heavy chains. All findings were subsequently correlated with histopathologic and clinical data.

About 5 out of 6 IgM+ PCMZLs were found to be IRTA1+, compared to three out of 18 evaluable class-switched cases (P = 0.0069). Notably, two class-switched cases positive for IRTA1 were identified in patients with clonally-related IRTA1+ IgM+ PCMZLs.

Furthermore, IRTA1 positivity exhibited a statistically significant correlation with several MALT-lymphoma-associated histopathologic findings. Conversely, all PCMZL cases exhibited some degree of MNDA expression, with no discernible differences between IgM+ and class-switched cases.

The study concluded that IRTA1 is a marker for identifying MALT-lymphoma-like PCMZLs, primarily observed in IgM+ cases but not exclusively. This finding supports the existence of two distinct subsets within PCMZLs. However, it suggests that distinguishing between these subsets should not rely solely on heavy chain expression.

Source: https://pubmed.ncbi.nlm.nih.gov/34309899/

Carlsen ED, Bhavsar S, Cook JR, et al. (2024). “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. PMID: 34309899.

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