Follicular lymphoma, mantle cell lymphoma, extranodal marginal zone lymphoma

A) Follicular Lymphoma

Overview

• Tumor of germinal center B-cells
• Affects middle-aged and elderly patients

Pathogenesis

• t(14;18) → fuses BCL2 to IgH → BCL2 overexpression → inhibits apoptosis
• Additional epigenetic/histone-modifying mutations
• Same mechanism as CLL/SLL (anti-apoptotic)

Morphology

• Lymph nodes have nodular appearance
• Tumor cells resemble normal germinal center B-cells:
  • Centrocytes: small cells with twisted/cleaved nuclei
  • Centroblasts: larger cells with vesicular nuclei and 1–3 nucleoli
• More large centroblasts → more aggressive behavior
• Markers: CD20, CD10, BCL2, BCL6

Clinical features

• Painless lymphadenopathy
• BM involvement in 80% of cases
• Indolent but incurable disease
• 40% transform to DLBCL
• Median survival: ~10 years
• Responds well to anti-CD20 (rituximab) or BTK inhibitors

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B) Mantle Cell Lymphoma

Overview

• Aggressive peripheral B-cell lymphoma composed of B-cells from the mantle zones of lymph follicles
• Occurs usually in men over 50 years

Pathogenesis

• t(11;14) → fuses cyclin D1 (chr. 11) to IgH (chr. 14) → ↑ cyclin D1 (cell cycle regulator) → uncontrolled tumor growth
• Tumor cells: surface IgM/IgD, CD19, CD20, CD5

Morphology

• Diffuse or nodular lymph node involvement
• Tumor cells larger than normal lymphocytes; irregular nucleus, no nucleoli, scant cytoplasm
• BM often involved; peripheral blood in 20%
• Extra-nodal: GI-tract → multifocal submucosal nodules resembling polyps

Clinical features

• Fatigue, lymphadenopathy
• Generalized disease: BM, spleen, liver, GI-tract
• Aggressive and incurable

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C) MALT Lymphoma (Extranodal Marginal Zone Lymphoma)

Overview

• Lymphoma involving mucosa-associated lymphoid tissue (MALT)
• Originates from B-cells in the marginal zone of MALT
• Common sites: salivary glands, stomach, conjunctiva
• Morphology: perifollicular proliferation of small centrocyte-like or monocytoid B-cells

Pathogenesis

• Develops in settings of chronic inflammatory disorders (infection or autoimmunity)
• Gastric MALT lymphoma: high association with H. pylori infection
  • H. pylori → chronic gastritis → gastric atrophy → B- and T-cell activation → lymphoid proliferation → mutations → MALT lymphoma
• Ocular/cutaneous MALT → Chlamydia psittaci
• Sjögren’s syndrome / Hashimoto thyroiditis → salivary gland / thyroid MALT lymphoma

Clinical features

• Indolent, slow progression
• Gastric type: H. pylori eradication (antibiotics) → regression of lymphoma
• Other sites: cured by excision or radiotherapy
• Transformation to DLBCL in <10% of cases

💡 High-yield: Follicular lymphoma = t(14;18)/BCL2; nodular pattern; CD10+/BCL2+; indolent but incurable; 40% → DLBCL. Mantle cell = t(11;14)/cyclin D1 + CD5+; aggressive, incurable; GI polyp-like lesions. MALT = gastric H. pylori association; eradication cures it; indolent.