marginal zone lymphoma

**Definition/Types (3 subtypes):** 1. Extranodal MZL of MALT (~70%): stomach most common; also salivary gland (Sjögren), thyroid (Hashimoto), lung (BALT), ocular adnexa/conjunctiva (Chlamydia psittaci), skin (Borrelia). 2. Nodal MZL (~10%): lymphadenopathy without extranodal involvement; associated with HCV in some cases. 3. Splenic MZL: splenomegaly, often with villous lymphocytes in peripheral blood; associated with HCV; may have autoimmune cytopenias.

**Pathophysiology:** - Chronic antigenic stimulation/inflammation leads to reactive lymphoid proliferation, then clonal B-cell expansion, then lymphoma. Early on, growth is T-cell dependent (H. pylori-specific T cells), which explains why antibiotic therapy can work. - Cytogenetics: t(11;18)(q21;q21) creates the API2-MALT1 fusion, which causes constitutive NF-κB activation. It is associated with H. pylori-independent disease and nonresponse to antibiotics. Other translocations: t(1;14) (BCL10), t(14;18) (IGH-MALT1), t(3;14) (FOXP1). Trisomy 3 and 18 are also seen. - Splenic MZL: del(7q) is common. NOTCH2 and KLF2 mutations are also seen.

**Histology/Immunophenotype:** - Small to medium B cells with abundant pale cytoplasm ("monocytoid" cells) infiltrate the marginal zone around reactive follicles. - Lymphoepithelial lesions (neoplastic cells invading glandular epithelium) are characteristic of MALT lymphoma. - Markers: CD19, CD20, CD79a positive. CD5, CD10, CD23, and cyclin D1 negative. This helps distinguish MZL from CLL/SLL (CD5+, CD23+), mantle cell lymphoma (CD5+, cyclin D1+), and follicular lymphoma (CD10+, BCL6+, BCL2+).

**Clinical Features:** - Typically older adults, with a slight female predominance in MALT. - Gastric MALT: dyspepsia, epigastric pain, GI bleeding, or an incidental finding on endoscopy. - Usually indolent and localized at diagnosis, with a good prognosis (5-year survival >80-90%). - Risk of transformation to diffuse large B-cell lymphoma (DLBCL).

**Management:** - Gastric MALT, H. pylori positive: eradication therapy (e.g., PPI + clarithromycin + amoxicillin/metronidazole). This produces remission in the majority of localized cases. - Persistent or t(11;18)-positive disease: localized radiotherapy, or rituximab ± chemotherapy (e.g., bendamustine) for disseminated disease. - Splenic MZL: observe if asymptomatic. Treat HCV if present (antivirals can induce remission). Rituximab, with splenectomy as an option for symptomatic cases.

**High-Yield Pearls:** - "Only lymphoma treated with antibiotics": gastric MALT lymphoma, H. pylori. - Gastric MALT lymphoma and H. pylori are also linked to gastric adenocarcinoma risk. - Chlamydia psittaci is linked to ocular adnexal MZL. Borrelia is linked to cutaneous MZL. Campylobacter jejuni is linked to immunoproliferative small intestinal disease (IPSID), an alpha heavy chain variant of MZL. - Autoimmune disease (Sjögren, Hashimoto) increases risk. Sjögren patients have a ~Ɨ risk of parotid MALT lymphoma. - Stage with CT/PET, endoscopy with biopsy, and H. pylori testing (histology, stool antigen, or urea breath test).