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Lymphoma (Hodgkin & Non-Hodgkin)

Malignancies of lymphocytes presenting with lymphadenopathy, B symptoms, extranodal disease, or mediastinal mass; classified broadly as Hodgkin or non-Hodgkin lymphoma

Review date
reviewed 2026-05-04
Reading time
10 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Hematology & Oncologycommonlong-term-condition
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Condition details
Hematology & Oncology
common
10 min read
reviewed 2026-05-04
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About This Page

This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.

Key points

  • Hodgkin lymphoma classically has painless lymphadenopathy, contiguous spread, and Reed-Sternberg cells
  • Non-Hodgkin lymphoma is more heterogeneous, often noncontiguous, and may present with extranodal disease
  • B symptoms are fever, drenching night sweats, and weight loss >10% in 6 months
  • Best diagnostic test for persistent suspicious lymphadenopathy is excisional lymph node biopsy
  • Treatment is subtype-specific: ABVD-based regimens for many Hodgkin cases; R-CHOP for many diffuse large B-cell lymphomas

Overview

Lymphomas are clonal malignancies of B cells, T cells, or NK cells. Hodgkin lymphoma is characterized by Reed-Sternberg cells in an inflammatory background and usually spreads predictably from one nodal region to adjacent regions. Non-Hodgkin lymphomas vary from indolent follicular lymphoma to aggressive diffuse large B-cell lymphoma and Burkitt lymphoma.

Epidemiology

Hodgkin lymphoma has a bimodal distribution with peaks in young adults and older adults. Non-Hodgkin lymphoma incidence increases with age and is associated with immunosuppression, HIV, EBV, H. pylori, hepatitis C, autoimmune disease, and certain exposures.

Clinical Features

Symptoms
Painless persistent lymphadenopathy
B symptoms: fever, drenching night sweats, weight loss >10% over 6 months
Pruritus or alcohol-induced lymph node pain in Hodgkin lymphoma
Cough, dyspnea, facial swelling from mediastinal mass
Extranodal symptoms: abdominal pain, GI bleeding, testicular mass, CNS symptoms depending on subtype
Signs
Rubbery, non-tender lymphadenopathy
Splenomegaly or hepatomegaly
Superior vena cava syndrome signs: facial swelling, venous distension, dyspnea
Waldeyer ring, abdominal mass, or extranodal lesion in NHL

Investigations

First-line
Excisional lymph node biopsyPreferred diagnostic test; preserves architecture for lymphoma classification
CBC, CMP, LDH, uric acidAssess cytopenias, organ function, tumor burden, and tumor lysis risk
HIV, hepatitis B/C testingImportant for etiology and before rituximab or chemotherapy
Second-line
PET/CT stagingStandard staging and response assessment in many FDG-avid lymphomas
Immunohistochemistry and flow cytometryDefines B/T-cell phenotype and subtype
Bone marrow biopsyUsed selectively depending on subtype and staging strategy
Specialist
Molecular/cytogenetic testingMYC, BCL2, BCL6 rearrangements; double-hit lymphomas require intensified approaches
Lumbar punctureFor high-risk CNS involvement such as Burkitt, testicular lymphoma, or neurologic symptoms

Management

NCCN Guidelines for Hodgkin Lymphoma, B-Cell Lymphomas, and T-Cell Lymphomas
1
Diagnostic pathway
  • Do not treat persistent unexplained lymphadenopathy with repeated antibiotics without evaluation
  • Excisional biopsy is preferred over FNA when lymphoma is suspected
  • Stage with PET/CT and risk stratify using disease-specific systems
2
Hodgkin lymphoma
  • Many classical Hodgkin regimens use ABVD-based therapy with PET-adapted approaches
  • Radiation may be used in selected early-stage disease
  • Monitor long-term for secondary malignancy, infertility, hypothyroidism, pulmonary toxicity, and cardiac toxicity
3
Non-Hodgkin lymphoma
  • DLBCL commonly treated with R-CHOP-like chemoimmunotherapy when CD20-positive
  • Indolent follicular lymphoma may be observed if asymptomatic and low tumor burden
  • Burkitt lymphoma is highly aggressive and requires intensive therapy plus CNS prophylaxis
  • H. pylori eradication can treat early gastric MALT lymphoma

Complications

  • Superior vena cava syndrome: Mediastinal lymphoma can obstruct venous return
  • Tumor lysis syndrome: Especially Burkitt and high-grade lymphomas
  • Infection: Disease and therapy cause immune dysfunction
  • Secondary malignancies: Therapy-related AML/MDS and solid tumors after radiation/chemotherapy
USMLE Step 2 CK Exam Tips
  • 1Reed-Sternberg cells = Hodgkin lymphoma
  • 2Hodgkin spreads contiguously; NHL often spreads noncontiguously and extranodally
  • 3Painless lymphadenopathy + B symptoms = lymphoma until proven otherwise
  • 4Best biopsy for suspected lymphoma is excisional lymph node biopsy, not FNA
  • 5EBV is associated with Hodgkin, Burkitt, and some immunodeficiency-related lymphomas
  • 6Starry-sky macrophages and MYC translocation = Burkitt lymphoma
  • 7H. pylori-associated gastric MALT lymphoma can regress with eradication therapy

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Verified Sources & References

NCCN Clinical Practice Guidelines in Oncology
ASCO Guidelines
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