Heterogeneous group of lymphoid malignancies (mostly B-cell) — DLBCL most common aggressive type, follicular lymphoma most common indolent.
Also known as: NHL, non-Hodgkin lymphoma, DLBCL, follicular lymphoma, Burkitt lymphoma, MALT, mantle cell lymphoma
Overview
Diverse group of lymphoid neoplasms arising from B cells (~85%), T cells, or NK cells, distinct from Hodgkin lymphoma by absence of Reed-Sternberg cells. Includes >60 WHO-defined entities ranging from indolent (follicular lymphoma, marginal zone, MALT, CLL/SLL) to aggressive (DLBCL, mantle cell, Burkitt, primary CNS lymphoma) and very aggressive (Burkitt, lymphoblastic lymphoma).
Epidemiology
Sixth most common cancer in US adults; annual incidence ~20 per 100,000. Median age at diagnosis ~67. DLBCL is the most common type (~30%), followed by follicular lymphoma (~20%). Slight male predominance. Incidence has risen over recent decades partly from improved diagnosis and aging population.
Try two board-style Non-Hodgkin Lymphoma questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1HematologyMedium
A 58-year-old man is evaluated for 3 months of epigastric burning, early satiety, and a 4-kg weight loss. Upper endoscopy shows thickened, erythematous gastric folds, and biopsies reveal a dense lymphoid infiltrate with lymphoepithelial lesions; immunohistochemistry confirms a CD20-positive extranodal marginal zone (MALT) lymphoma. Rapid urease testing and histology are positive for Helicobacter pylori. Staging PET/CT and bone marrow biopsy show disease confined to the stomach with no nodal or distant involvement. Which of the following is the most appropriate initial management?
ASingle-agent rituximab immunotherapy
BRituximab plus bendamustine chemotherapy
CInvolved-site gastric radiation therapy
DHelicobacter pylori eradication therapy
Reveal answer & full explanation
Correct answer: D — Helicobacter pylori eradication therapy
ASingle-agent rituximab immunotherapy
BRituximab plus bendamustine chemotherapy
CInvolved-site gastric radiation therapy
DHelicobacter pylori eradication therapy✓
Why Helicobacter pylori eradication therapy is correct
Localized (stage IE), H. pylori-positive gastric MALT lymphoma is driven by chronic antigenic stimulation from the infection; eradication alone induces lymphoma regression in roughly 75-80% of localized cases, making this one of the few malignancies curable with antibiotics.
Guideline-defined first line: triple/quadruple H. pylori therapy first, then endoscopic surveillance to confirm both bacterial clearance and histologic remission before escalating.
Why the others are wrong
Rituximab plus bendamustine chemotherapy is appropriate systemic therapy for symptomatic, advanced-stage, or H. pylori-independent marginal zone lymphoma, but overtreats localized H. pylori-positive disease that should respond to antibiotics first.
Involved-site gastric radiation therapy is the correct next step for localized gastric MALT that fails to regress after eradication or is H. pylori-negative, not the initial move when the organism is present.
Single-agent rituximab immunotherapy is reserved for localized disease that does not respond to eradication and cannot receive radiation, or for H. pylori-negative cases, and is premature before an antibiotic trial.
Question 2HematologyMedium
A 19-year-old man presents with a 2-week history of progressive abdominal distension and early satiety. Examination reveals a large, firm right lower-quadrant mass, and CT shows a bulky ileocecal tumor with retroperitoneal adenopathy. Laboratory studies show LDH 1,840 U/L and uric acid 9.2 mg/dL. Excisional biopsy demonstrates a diffuse infiltrate of medium-sized B cells with a "starry-sky" appearance and a Ki-67 proliferation index of nearly 100%; FISH confirms a t(8;14) MYC rearrangement. Dose-adjusted multi-agent chemotherapy is planned to begin. Which of the following complications is this patient most likely to develop?
AAnthracycline-induced cardiomyopathy
BTumor lysis syndrome with hyperkalemia
CTherapy-related acute myeloid leukemia
DTransformation to large B-cell lymphoma
Reveal answer & full explanation
Correct answer: B — Tumor lysis syndrome with hyperkalemia
AAnthracycline-induced cardiomyopathy
BTumor lysis syndrome with hyperkalemia✓
CTherapy-related acute myeloid leukemia
DTransformation to large B-cell lymphoma
Why Tumor lysis syndrome with hyperkalemia is correct
The biopsy (medium B cells, "starry-sky" pattern, Ki-67 ~100%, t(8;14) MYC) defines Burkitt lymphoma, the fastest-growing human tumor (doubling time ~24 hours).
High tumor burden and rapid turnover already produce a baseline elevated LDH and uric acid; cytotoxic therapy causes massive cell lysis that releases potassium, phosphate, and purines, precipitating hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, and acute kidney injury.
Standard of care is aggressive prophylaxis at diagnosis: vigorous IV hydration plus rasburicase (or allopurinol), exactly as recommended for Burkitt, double-hit, and bulky aggressive lymphomas.
Why the others are wrong
Anthracycline-induced cardiomyopathy is a dose-dependent late toxicity of doxorubicin monitored with a pre-treatment echo/MUGA; it is not the immediate, highest-likelihood complication when therapy is initiated in a high-turnover tumor.
Therapy-related acute myeloid leukemia is a delayed secondary malignancy seen years later, especially after alkylating agents, not the acute peri-induction risk here.
Transformation to large B-cell lymphoma is a complication of indolent lymphomas such as follicular lymphoma (~3%/year cumulative); Burkitt is already a very aggressive mature B-cell lymphoma and does not transform in this way.
🔒 Free preview limit reached
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Non-Hodgkin Lymphoma outline — plus all 514 diagnoses, 6,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Inherited: variants in HLA, TNFSF13B, RHOA, others
Pathophysiology
B-cell lymphomas arise from various stages of B-cell differentiation: pre-germinal center (mantle cell), germinal center (follicular, Burkitt, GCB-DLBCL), post-germinal center (ABC-DLBCL, plasmablastic, multiple myeloma), and marginal zone (MALT, splenic). Characteristic translocations involve juxtaposition of oncogenes (BCL2, BCL6, MYC, CCND1) to immunoglobulin enhancers, deregulating expression. T-cell lymphomas often involve mature peripheral T cells (PTCL, AITL, ALK+ ALCL) and tend to be more aggressive.
Clinical presentation
Symptoms
Lymphadenopathy — painless, peripheral or central; often progressive over weeks to months
B symptoms — fever, drenching night sweats, weight loss >10% (especially in aggressive lymphomas)
Extranodal disease (more common in NHL than Hodgkin): GI tract (MALT in stomach, intestinal involvement), CNS (primary CNS lymphoma, leptomeningeal), skin (cutaneous T-cell lymphomas mycosis fungoides/Sézary), bone marrow, testis, sinuses
Testicular mass (testicular lymphoma, often DLBCL)
Waldeyer's ring involvement (tonsillar enlargement, especially marginal zone, DLBCL)
Classic findings
Rapidly enlarging supradiaphragmatic node in an older adult with B symptoms — biopsy reveals diffuse large B-cell lymphoma. Burkitt: jaw mass in pediatric African patient (endemic) or abdominal mass in immunodeficient host (sporadic).
Differential diagnosis
Hodgkin lymphoma — Reed-Sternberg cells, CD30+ CD15+ CD20- CD45-, contiguous spread, bimodal age distribution
Reactive lymphadenopathy (viral, bacterial) — Tender, mobile nodes <1-2 cm, identifiable cause; resolves within weeks
Metastatic carcinoma — Hard, fixed nodes; primary site identifiable; characteristic histology and IHC
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).
Labs
Excisional lymph node biopsy ESSENTIAL — needle biopsy may miss architecture; flow cytometry, IHC, cytogenetics, FISH on fresh tissue
Follicular lymphoma (low grade, indolent): observation if asymptomatic and low burden; bendamustine + rituximab or R-CHOP if symptomatic; rituximab maintenance
Mantle cell lymphoma: bendamustine-rituximab; for younger fit patients, intensive induction (R-CHOP/R-DHAP or Nordic regimen) followed by autologous HSCT consolidation; BTK inhibitors (acalabrutinib, ibrutinib, zanubrutinib) for relapsed/refractory; chemo-free regimens (BTK inhibitor + rituximab + venetoclax) emerging
Burkitt lymphoma: intensive multi-agent regimen (R-EPOCH dose-adjusted, or CODOX-M/IVAC) with aggressive tumor lysis prophylaxis (rasburicase, hyperhydration) and CNS prophylaxis
MALT lymphoma (gastric, H. pylori-positive): H. pylori eradication ALONE achieves regression in ~75-80% of localized cases; rituximab ± involved-site radiation if no response
Marginal zone (splenic): rituximab; splenectomy if symptomatic and HCV-negative
Secondary malignancies: AML/MDS (especially with alkylators); other solid tumors
Infection from immunosuppression (PJP, fungal, viral reactivation)
Bowel perforation from rapidly responding GI lymphoma
CNS relapse — devastating in DLBCL with high-risk features
Transformation of indolent lymphoma (follicular → DLBCL ~3%/year cumulative)
PANCE pearls
Indolent vs aggressive distinction drives management: indolent = often observed initially, may not be curable; aggressive = treated immediately, often curable. (Paradox: aggressive lymphomas are more curable than indolent because they respond to chemotherapy.)
DLBCL = most common NHL; R-CHOP × 6 cures ~60-70%; subtype refinement (GCB vs ABC, double/triple-hit) guides intensification.
Gastric MALT lymphoma: treat H. PYLORI FIRST — eradication alone produces remission in most localized cases. This is one of the few cancers cured by antibiotics.
Burkitt lymphoma is the FASTEST-GROWING human tumor (doubling time ~24 hours) — initiate treatment urgently and prophylax against severe tumor lysis.
Mantle cell lymphoma is a CD5+ B-cell lymphoma that lacks CD23 (distinguishing it from CLL); CD23 is positive in CLL and negative in mantle cell.
International Prognostic Index (IPI): age >60, stage III/IV, LDH elevated, ECOG ≥2, ≥2 extranodal sites — each scores 1 point.
CAR-T cell therapy has revolutionized relapsed/refractory aggressive B-cell lymphomas — axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel induce durable remissions in ~40% of chemo-refractory disease.
Primary CNS lymphoma is almost always DLBCL; treat with high-dose methotrexate-based regimens. AVOID upfront whole-brain radiation in elderly due to severe neurocognitive toxicity.
References
NCCN 2024 — NCCN Clinical Practice Guidelines in Oncology: B-Cell and T-Cell Lymphomas (NCCN.org)
POLARIX — Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma (Tilly et al., NEJM 2022)
ZUMA-1 — Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma (Neelapu et al., NEJM 2017)
GALLIUM — Obinutuzumab for First-Line Treatment of Follicular Lymphoma (Marcus et al., NEJM 2017)
WHO 5th edition — WHO Classification of Haematolymphoid Tumours, 5th edition (2022)
Practice Hematology questions on FirstPassPA
Turn this outline into retention. 6,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
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.