Non-Hodgkin’s Lymphoma¶
Chapter 113 | Part 4: Oncology and Hematology
KEY CLINICAL POINTS¶
- NHL is a heterogeneous group of malignancies of mature B, T, and NK cells, distinct from Hodgkin’s lymphoma.
- 5-year survival rate is 74% for Caucasians, higher than for African Americans.
- WHO-HAEM5 classification includes B-cell and T-cell subtypes with specific genetic and morphologic features.
- Key risk factors include immunosuppression, HIV, EBV, HTLV-1, and chronic infections like H. pylori.
- Treatment varies by subtype: R-CHOP for DLBCL, BR for FL, and CAR-T for relapsed/refractory cases.
1. DEFINITION & OVERVIEW¶
Non-Hodgkin’s lymphoma (NHL) encompasses cancers of mature B, T, and NK cells. Distinguished from Hodgkin’s lymphoma (HL) by the absence of Reed-Sternberg cells and differing biologic/clinical features. NHL is classified into B-cell and T-cell subtypes based on cell origin. WHO-HAEM5 classification includes 12 categories (Table 113-1).
WHO-HAEM5 Classification of Lymphoid Malignancies¶
| B CELL | T CELL |
|---|---|
| Lymphoplasmacytic lymphoma (Waldenström’s macroglobulinemia) | T-cell granular lymphocytic leukemia |
| Hairy cell leukemia (HTLV-1+) | Adult T-cell leukemia/lymphoma (HTLV-1+) |
| Splenic marginal zone B-cell lymphoma | Extranodal NK/T-cell lymphoma, nasal type |
| Extranodal marginal zone B-cell lymphoma of MALT type | Enteropathy-associated T-cell lymphoma |
| Nodal marginal zone B-cell lymphoma | Hepatosplenic T-cell lymphoma |
| Follicular lymphoma | Subcutaneous panniculitis-like T-cell lymphoma |
| Mantle cell lymphoma | Mycosis fungoides |
| Diffuse large B-cell lymphoma (including subtypes) | Sezary syndrome |
| High-grade B-cell lymphoma with MYC and BCL2 rearrangements | Peripheral T-cell lymphoma NOS |
| High-grade B-cell lymphoma NOS | Angioimmunoblastic T-cell lymphoma |
| High-grade B-cell lymphoma with 11q aberrations | Anaplastic large-cell lymphoma, ALK+ |
| Burkitt’s lymphoma/Burkitt’s cell leukemia | Anaplastic large-cell lymphoma, ALK– |
| B CELL | T CELL |
|---|---|
| Primary mediastinal large B-cell lymphoma | Plasmablastic lymphoma |
| Mediastinal grey zone lymphoma | Primary effusion lymphoma |
| Primary large B-cell lymphoma of immune-privileged sites | HHV8+ DLBCL NOS |
| Intravascular large B-cell lymphoma | Intravascular large B-cell lymphoma |
1.1 WHO-HAEM5 Classification¶
B-cell and T-cell subtypes include diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and T-cell lymphomas like anaplastic large-cell lymphoma (ALCL).
2. EPIDEMIOLOGY¶
NHL is the 7th most common cancer in the US (80,550 new cases in 2023). Incidence is 10x higher in immunosuppressed patients (e.g., post-transplant). Male-to-female ratio ~1:1.5. Age >40, with peak incidence in 60–70 years. 20–40% increase in incidence over 20–40 years. Higher in Caucasians vs. African Americans.
Diseases/Exposures Associated with NHL Risk¶
| Inherited Immunodeficiency | Acquired Immunodeficiency | Chemical/Drug Exposures |
|---|---|---|
| Klinefelter’s syndrome | HIV | Phenytoin |
| Chédiak-Higashi syndrome | Autoimmune diseases | Dioxin, phenoxy herbicides |
| Ataxia-telangiectasia | Iatrogenic immunosuppression | Radiation |
| Wiskott-Aldrich syndrome | Acquired hypogammaglobulinemia | Prior chemotherapy/radiation |
| Common variable immunodeficiency | Anti-TNF drugs | N/A |
2.1 Risk Factors¶
Immunosuppression (HIV, organ transplant, autoimmune diseases), EBV, HTLV-1, H. pylori, hepatitis C, and genetic predispositions (e.g., ataxia-telangiectasia).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
NHL arises from genetic mutations in B/T/NK cells, often involving translocations (e.g., t(11;14) in MCL), mutations in MYC, BCL2, and other oncogenes. EBV and HTLV-1 are linked to specific subtypes (e.g., BL, ATL). Chronic antigenic stimulation (e.g., H. pylori) drives MALT lymphoma.
Genetic Features of B- and T-Cell Lymphomas¶
| GENETIC FEATURE | GENES | LYMPHOMA |
|---|---|---|
| t(8;14) | MYC/IgH | Burkitt’s lymphoma |
| t(2;8) | MYC/Igk | T-cell ALL |
| t(8;22) | MYC/Igl | T-cell ALL |
| t(11;14) | BCL1 (CCND1)/IgH | Mantle cell lymphoma |
| t(14;18) | BCL2/IgH | Follicular lymphoma, DLBCL |
| t(3;14) | BCL6/IgH | DLBCL |
| GENETIC FEATURE | GENES | LYMPHOMA |
|---|---|---|
| Trisomy 3 | Unknown | Splenic marginal zone lymphoma |
| 7q21 deletion | CDK6 | Splenic marginal zone lymphoma |
| inv(14) | TCL1 | Peripheral T-cell lymphoma, NOS |
| t(2;5) | NPM1/ALK | Anaplastic large-cell lymphoma |
| t(1;2) | TPM3/ALK | Anap, large-cell lymphoma |
| t(2;17) | CTLC/ALK | Anap, large-cell lymphoma |
| inv(2) | ATIC/ALK | Anap, large-cell lymphoma |
| Trisomy 5 | Unknown | Angioimmunoblastic T-cell lymphoma |
| Isochromosome 7q | Unknown | Hepatosplenic T-cell lymphoma |
3.1 Genetic Abnormalities¶
Common translocations include t(11;14) (MCL), t(14;18) (FL), and t(8;14) (BL). MYC, BCL2, and BCL6 mutations drive oncogenesis.
4. CLINICAL FEATURES¶
Symptoms include B symptoms (fever, night sweats, weight loss), lymphadenopathy, and extranodal involvement. Indolent NHLs (e.g., FL) present with painless lymphadenopathy, while aggressive subtypes (e.g., BL) present with rapid growth and systemic symptoms.
4.1 Subtype-Specific Features¶
Burkitt’s lymphoma: rapid growth, jaw/abdominal mass. FL: indolent, stage I/II. MCL: splenomegaly, lymphadenopathy. ALCL: CD30+ cells, ALK positivity.
5. DIFFERENTIAL DIAGNOSIS¶
Differentiate from reactive follicular hyperplasia, autoimmune conditions (e.g., Sjögren’s), and infections (e.g., EBV-related lymphomas). Consider other B-cell disorders like CLL and MZL.
6. INVESTIGATIONS & DIAGNOSIS¶
CBC, LDH, β -microglobulin, and imaging (CT/PET). Flow cytometry and immunohistochemistry for B/T-cell markers. Ann Arbor staging (Table 113-6) and IPI/FLIPI for prognosis.
Ann Arbor Staging for Lymphoma¶
| STAGE | DESCRIPTION |
|---|---|
| I | Single lymph node region (I) or single extranodal site (IE) |
| II | Two or more lymph node regions or limited extralymphatic involvement (IIE) |
| III | Lymph node regions on both sides of the diaphragm (III), including spleen (IIIS) or extralymphatic sites (IIIE) |
| IV | Diffuse or disseminated foci with lymphatic involvement |
6.1 Diagnostic Criteria¶
WHO classification, genetic testing (FISH for translocations), and staging with CT/PET.
7. MANAGEMENT & TREATMENT¶
R-CHOP for DLBCL, BR for FL, and CAR-T for relapsed/refractory cases. Targeted therapies (e.g., ibrutinib for MZL) and stem cell transplants for high-risk patients. PET/CT for response assessment.
7.1 Subtype-Specific Therapies¶
DLBCL: R-CHOP; FL: BR; MCL: R-CHOP + autologous transplant; ALCL: CHOP/CHOEP; PTCL NOS: CHOP/CHOEP.
8. PROGNOSIS & COMPLICATIONS¶
IPI and FLIPI predict outcomes. Complications include CNS involvement, treatment resistance, and secondary malignancies. Prognosis varies by subtype (e.g., 82% 8-year OS for ALK+ ALCL vs. 49% for ALK–).
8.1 Prognostic Indices¶
IPI: age, LDH, performance status, stage, extranodal involvement. FLIPI: age, stage, LDH, number of nodal sites, B symptoms.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: avoid chemotherapy in first trimester. Pediatric: aggressive treatment for high-risk subtypes. Elderly: consider less toxic regimens. HIV-positive patients require antiretroviral therapy alongside NHL treatment.
10. KEY POINTS & CLINICAL PEARLS¶
- NHL is heterogeneous, with distinct B/T-cell subtypes. 2. EBV, HTLV-1, and chronic infections are key etiologic factors. 3. R-CHOP is standard for DLBCL; BR for FL. 4. PET/CT guides treatment decisions. 5. CAR-T and targeted therapies improve outcomes in relapsed/refractory cases.