Confusable diagnoses · PANCE / PANRE

Hodgkin Lymphoma vs Non-Hodgkin Lymphoma

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

Hodgkin Lymphoma and Non-Hodgkin Lymphoma are easy to mix up on the boards. Here's a side-by-side comparison — presentation, workup, imaging, and first-line treatment — drawn from our full outlines.

Hodgkin Lymphoma vs Non-Hodgkin Lymphoma at a glance

  • Hodgkin Lymphoma: B-cell lymphoma defined by Reed-Sternberg cells in a reactive inflammatory background — highly curable with combined modality therapy.
  • Non-Hodgkin Lymphoma: Heterogeneous group of lymphoid malignancies (mostly B-cell) — DLBCL most common aggressive type, follicular lymphoma most common indolent.

Try two board-style questions on Hodgkin Lymphoma vs Non-Hodgkin Lymphoma

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Question 1HematologyMedium
A 28-year-old male has painless cervical lymphadenopathy, night sweats, and 10% weight loss over 2 months. Excisional lymph node biopsy shows large cells with bilobed nuclei and prominent eosinophilic nucleoli ('owl-eye' appearance) within a mixed inflammatory background. Which of the following is the most likely diagnosis?
  • AHodgkin lymphoma
  • BDiffuse large B-cell lymphoma
  • CChronic lymphocytic leukemia
  • DBurkitt lymphoma
Reveal answer & full explanation
Correct answer: A — Hodgkin lymphoma
  • AHodgkin lymphoma✓
  • BDiffuse large B-cell lymphoma
  • CChronic lymphocytic leukemia
  • DBurkitt lymphoma

Why Hodgkin lymphoma is correct

  • Reed-Sternberg cells — large binucleated cells with prominent eosinophilic nucleoli ('owl-eye' appearance) in a reactive inflammatory background — are the diagnostic finding.
  • Immunophenotype is CD15+ and CD30+.
  • Classic subtypes: nodular sclerosis (most common), mixed cellularity, lymphocyte-rich, lymphocyte-depleted.
  • Bimodal age distribution with peaks in the 20s and 60s fits this young patient.
  • 'B symptoms' (fever, night sweats, >10% weight loss) and painless cervical nodes are typical.
  • Spreads contiguously through adjacent lymph node groups.

Why the others are wrong

  • Diffuse large B-cell lymphoma — aggressive non-Hodgkin lymphoma with sheets of large B cells but no Reed-Sternberg cells; confused-with by shared 'large cell' morphology.
  • Chronic lymphocytic leukemia — small mature lymphocytes with lymphocytosis in older adults, not owl-eye cells or B symptoms in a young patient; right-concept-wrong-setting.
  • Burkitt lymphoma — 'starry sky' histology with MYC translocation (t(8;14)) and explosive growth; confused-with as another young-patient lymphoma but lacks Reed-Sternberg cells.

Additional high-yield points

  • Treatment is ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine); PET imaging guides therapy duration.
  • Prognosis is excellent, with cure rates exceeding 80%.
Question 2HematologyMedium
A 41-year-old man presents with 6 weeks of progressive painless cervical and axillary lymphadenopathy, drenching night sweats, and a 7-kg unintentional weight loss. On exam he has firm, rubbery, non-tender nodes and mild hepatosplenomegaly. Excisional node biopsy confirms diffuse large B-cell lymphoma. Which of the following is the strongest risk factor for developing this lymphoma?
  • ALong-term pesticide exposure
  • BUntreated HIV-1 infection
  • CLong-term hair-dye exposure
  • DHepatitis C virus infection
Reveal answer & full explanation
Correct answer: B — Untreated HIV-1 infection
  • ALong-term pesticide exposure
  • BUntreated HIV-1 infection✓
  • CLong-term hair-dye exposure
  • DHepatitis C virus infection

Why Untreated HIV-1 infection is correct

  • Immunosuppression is the strongest, best-established risk factor for non-Hodgkin lymphoma; untreated HIV carries a markedly increased risk (relative risk roughly 60-200 fold) of aggressive B-cell lymphomas including DLBCL, primary CNS lymphoma, and Burkitt lymphoma.
  • Loss of T-cell immune surveillance permits EBV-driven and other clonal B-cell proliferation, producing exactly the rapidly progressive DLBCL with B symptoms seen here.
  • Other major immunosuppressive states (post-transplant/PTLD, congenital immunodeficiency, iatrogenic immunosuppression) share this elevated risk, underscoring immune dysfunction as the dominant driver.

Why the others are wrong

  • Hepatitis C virus infection is a genuine infectious risk factor, but it only modestly (about 2-fold) raises the risk of marginal zone lymphoma and DLBCL, far less than the risk conferred by untreated HIV.
  • Long-term pesticide exposure is an environmental association with NHL, but the evidence is weak and the magnitude of risk is far smaller than immunosuppression.
  • Long-term hair-dye exposure is reported only as a limited-evidence environmental exposure; any association is minor and inconsistent, not a strong risk factor.
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Side-by-side comparison

FeatureHodgkin LymphomaNon-Hodgkin Lymphoma
At a glanceB-cell lymphoma defined by Reed-Sternberg cells in a reactive inflammatory background — highly curable with combined modality therapy.Heterogeneous group of lymphoid malignancies (mostly B-cell) — DLBCL most common aggressive type, follicular lymphoma most common indolent.
Classic presentationYoung adult (15-35) with painless cervical lymphadenopathy, mediastinal mass on CXR, and nodular sclerosing histology with Reed-Sternberg cells.; Painless cervical or supraclavicular lymphadenopathy (most common presentation); Mediastinal mass — dyspnea, cough, chest discomfort, SVC syndrome (typical of nodular sclerosing in young…Rapidly enlarging supradiaphragmatic node in an older adult with B symptoms — biopsy reveals diffuse large B-cell lymphoma. Burkitt: jaw/facial mass in an African child (endemic, EBV-associated); abdominal (ileocecal) mass in an otherwise healthy child or young adult elsewhere (sporadic); or in a patient with HIV or other…
Workup / key labsHistologic identification of Reed-Sternberg cells (or lymphocyte-predominant variants in NLPHL) with characteristic immunophenotype on excisional biopsy.; Excisional lymph node biopsy is essential for diagnosis (fine-needle aspiration is INSUFFICIENT — Reed-Sternberg cells need architectural context); Immunohistochemistry: classical HL…Tissue diagnosis with WHO-defined histologic and immunophenotypic criteria specific to subtype. Ann Arbor staging used; International Prognostic Index (IPI) prognosticates DLBCL and other aggressive lymphomas (age, stage, LDH, performance status, extranodal sites).; Excisional lymph node biopsy ESSENTIAL — needle biopsy may miss…
ImagingPET/CT — gold standard for staging and response assessment (Deauville 5-point score); CT chest/abdomen/pelvis if PET unavailable; Bone marrow biopsy NO LONGER routinely required if PET is performed (PET detects marrow involvement); Ann Arbor staging with Cotswolds modification: I (single nodal region), II (≥2 regions same side of…PET/CT — staging and response assessment (Deauville 5-point score); CT chest/abdomen/pelvis with contrast; MRI brain for primary CNS lymphoma or suspected CNS involvement; Echocardiogram (MUGA) before anthracycline; Endoscopy if GI involvement suspected
First-line treatmentEarly-stage (I-II) favorable: 2-4 cycles ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) + involved-site radiation (ISRT); response-adapted approach using interim PET to minimize toxicity; Early-stage unfavorable: 4 cycles ABVD + ISRT (or PET-adapted chemotherapy alone without ISRT); Advanced-stage (III-IV): nivolumab + AVD…DLBCL: R-CHOP × 6 cycles (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone); polatuzumab vedotin + R-CHP (POLARIX trial) improves PFS in higher-risk patients; cure rate ~60-70%; Follicular lymphoma (low grade, indolent): observation if asymptomatic and low burden; bendamustine + rituximab or R-CHOP if symptomatic;…

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Full outlines

Hodgkin Lymphoma Non-Hodgkin Lymphoma All 514 diagnoses

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.