Non-Hodgkin lymphomas

NHL Classification - The Lymphoma Lineup

• Primary Division: B-cell neoplasms (85%) vs. T-cell/NK-cell neoplasms (15%).
• Clinical Behavior:
  • Indolent (Slow): Waxing & waning course. E.g., Follicular, Marginal Zone, SLL.
  • Aggressive (Fast): Rapidly fatal without treatment. E.g., DLBCL, Burkitt, Mantle Cell.

⭐ SLL vs. CLL: Small Lymphocytic Lymphoma (SLL) and Chronic Lymphocytic Leukemia (CLL) are the same disease. The diagnosis is CLL if peripheral blood absolute lymphocyte count is >5,000/μL; otherwise, it's SLL.

Indolent B-Cell NHL - The Slowpokes

• Follicular Lymphoma: Most common indolent type.
  • Genetic hallmark: t(14;18) translocation → BCL2 overexpression (inhibits apoptosis).
  • Presents with waxing and waning, painless peripheral lymphadenopathy.
  • Histology: Nodule-like pattern of packed follicles.
  • Risk of transformation to aggressive DLBCL.
• Marginal Zone Lymphoma: Linked to chronic inflammation (e.g., H. pylori → MALT lymphoma).
• Small Lymphocytic Lymphoma (SLL): Tissue version of CLL; defined by <5,000 circulating monoclonal B-cells/µL.

⭐ The t(14;18) translocation juxtaposes the BCL2 gene with the immunoglobulin heavy chain (IgH) enhancer, driving overexpression and preventing apoptosis in follicular lymphoma cells.

Aggressive B-Cell NHL - The Fast & Furious

• Diffuse Large B-Cell Lymphoma (DLBCL): Most common NHL, often a rapidly enlarging mass. Can arise de novo or from indolent lymphoma transformation. Treat with R-CHOP.
• Burkitt Lymphoma: Extremely aggressive, linked to EBV.
  • Genetics: t(8;14) translocation of the c-myc gene.
  • Histology: Classic "starry sky" pattern.
• Mantle Cell Lymphoma: Aggressive course, poor prognosis.
  • Genetics: t(11;14) causes Cyclin D1 overexpression, driving the G1/S phase.

⭐ The "starry sky" in Burkitt's is formed by tingible body macrophages (stars) engulfing apoptotic tumor cells amidst a sheet of dark, uniform lymphoid cells (sky).

T-Cell Lymphomas - Cutaneous Creeps

• Mycosis Fungoides (MF): Most common cutaneous T-cell lymphoma (CTCL).
  • Indolent course; progresses from patch → plaque → tumor stage.
  • Histology: Pautrier's microabscesses-intraepidermal nests of neoplastic CD4+ T-cells with cerebriform nuclei.
• Sézary Syndrome: A leukemic, aggressive variant of CTCL.

  ⭐ Presents with a classic triad: generalized erythroderma (the "red man"), diffuse lymphadenopathy, and circulating malignant Sézary cells.

• Adult T-cell Leukemia/Lymphoma (ATLL):
  • Caused by HTLV-1; common in Japan, Caribbean.
  • Features: lytic bone lesions (→ hypercalcemia), skin lesions, hepatosplenomegaly.
  • Characteristic "flower cells" on blood smear.

Diagnosis & Staging - The NHL Workup

• Biopsy: Excisional biopsy is the gold standard for diagnosis, providing tissue architecture crucial for subtyping. Avoids sampling error of FNA.
• Labs: ↑LDH correlates with tumor burden and is a key prognostic factor in the IPI score.
• Staging: Ann Arbor system (I-IV) determines disease extent. Stage is the most important prognostic factor.

⭐ PET/CT is now standard for staging aggressive lymphomas like DLBCL, assessing treatment response, and detecting relapse.

• More common than Hodgkin, NHL presents with widespread, non-contiguous lymphadenopathy and extranodal disease.
• Burkitt Lymphoma: t(8;14) (c-myc), "starry-sky" histology, EBV association.
• Diffuse Large B-cell Lymphoma (DLBCL): Most common NHL in adults, very aggressive.
• Follicular Lymphoma: t(14;18) (BCL-2 overexpression), indolent course, can transform to DLBCL.
• Mantle Cell Lymphoma: t(11;14) (Cyclin D1), aggressive with a poor prognosis.
• Marginal Zone Lymphoma: Arises from chronic inflammation (e.g., H. pylori gastritis).