MALT Lymphoma : Molecular Changes

MALT Lymphoma - Molecular Changes: Several mutually exclusive chromosomal translocations and numerical chromosomal anomalies have been described in extranodal marginal zone lymphomas (EMZL). The final common mechanism of these varied genetic changes appears to be deregulation and inappropriate activation of NF-κB signaling pathway. The genetic anomalies are as follows:

• Trisomies 3, 12, and 18 (20-30% of cases)
• t(11;18)(q21;q21)/BIRC3-MALT1
• t(14;18)(q32;q21)/IGH-MALT1
• t(1;14)(p22;q32)/IGH-BCL10
• t(3;14)(p14;q32)/IGH-FOXP1

The most common anomaly t(11;18)(q21;q21) is seen in EMZL of lung (40%), stomach (30%), and ocular adnexa (15%). It is rarely seen in salivary glands, thyroid, and skin. It fuses BIRC3 (previously known as API2) and MALT1, creating a functional BIRC3-MALT1 protein which constitutively activates both canonical and non-canonical NF-κB pathways. This translocation appears to be specific for EMZL and has not been observed in nodal or splenic MZL. t(11;18) positive EMZL rarely undergo high-grade transformation and are resistant to H. pylori treatment.

The t(1;14) and t(14;18) translocations juxtapose BCL10 and MALT1 genes, respectively, to the immunoglobulin heavy chain IGH locus at 14q32. The resultant overexpression of BCL10 or the MALT1 lead to constitutive activation of NF-κB pathway. Rare translocations in EMZL involving IGH include: t(X;14), t(5;14), and t(9;14).

t(3;14) translocation juxtaposes IGH and transcription factor FOXP1 whose overexpression stimulates WNT/β-catenin signaling and NF-κB pathway.

Image source: Schreuder MI et al. Novel developments in the pathogenesis and diagnosis of extranodal marginal zone lymphoma. J Hematop. 2017 Dec. 10(3-4): 91-107. Used under Creative Commons Attribution 4.0 International License.