Hodgkin & Non-Hodgkin Lymphoma
A board-accurate lesson on Hodgkin and non-Hodgkin lymphoma: Reed-Sternberg biology and HL subtypes, the key NHL entities with their defining translocations/markers/smear findings, and first-line/next-best-step management.
Hodgkin vs Non-Hodgkin: the core split
Both are malignancies of lymphocytes classically presenting with painless, rubbery lymphadenopathy. Hodgkin lymphoma (HL) is defined by scattered Reed-Sternberg (RS) cells sitting in a reactive inflammatory background. It has a bimodal age distribution (peaks ~15–35 and >55), spreads contiguously node-to-node, stays localized longer, and is therefore more often curable. Non-Hodgkin lymphoma (NHL) is a heterogeneous group — ~85% B-cell, the rest T/NK-cell — that spreads non-contiguously (hematogenous), more often presents at extranodal sites and at disseminated stage, and ranges from indolent to highly aggressive. B symptoms — fever, drenching night sweats, and >10% weight loss over 6 months — carry staging and prognostic weight in both.
- Reed-Sternberg cell = binucleate/bilobed "owl-eye" nucleus; CD15+ and CD30+ (CD20−, CD45−) — diagnostic of classic Hodgkin.
- Nodular sclerosis = most common HL; young woman + anterior mediastinal mass; lacunar cells.
- Follicular lymphoma: t(14;18) → BCL2 overexpression (anti-apoptosis); indolent, waxing/waning nodes; can transform to DLBCL.
- Burkitt lymphoma: t(8;14) → c-MYC; "starry-sky" histology; Ki-67 ≈ 100%; high risk of tumor lysis syndrome.
- Mantle cell lymphoma: t(11;14) → cyclin D1; CD5+/CD23−; aggressive, poor prognosis.
- DLBCL = most common NHL overall; aggressive but potentially curable with R-CHOP.
- Gastric MALT lymphoma is driven by *H. pylori* — eradication alone can induce remission in early localized disease.
- Diagnose lymphoma with excisional lymph node biopsy (architecture + IHC needed) — FNA is inadequate.
Non-Hodgkin subtypes at a glance
| Subtype | Cytogenetics | Key markers | Board cue |
|---|---|---|---|
| Follicular | t(14;18) → BCL2 | CD10+, BCL2+, CD20+ | Indolent, waxing/waning nodes; transforms to DLBCL |
| Burkitt | t(8;14) → c-MYC | CD10+, BCL2−, Ki-67 ≈100% | Starry-sky; jaw (endemic/EBV) or abdomen (sporadic); TLS |
| Mantle cell | t(11;14) → cyclin D1 | CD5+, CD23−, CD20+ | Aggressive, poor prognosis |
| DLBCL | variable (BCL2/BCL6/MYC) | CD20+ | Most common NHL; rapidly enlarging mass; R-CHOP |
| Marginal zone / MALT | t(11;18) | CD20+ | Gastric → H. pylori; Sjögren, Hashimoto |
| Mycosis fungoides / Sézary | — | CD4+ T-cell | Cutaneous; Pautrier microabscesses; cerebriform nuclei |
- Painless rubbery lymphadenopathy, suspect lymphoma → excisional biopsy (not fine-needle) for architecture and immunohistochemistry.
- Young woman + anterior mediastinal mass + pruritus or alcohol-induced nodal pain → nodular sclerosis Hodgkin.
- Child/young adult with rapidly growing abdominal or jaw mass, very high LDH → Burkitt; start IV hydration + allopurinol or rasburicase for tumor lysis before/with chemo.
- Gastric MALT lymphoma with positive H. pylori → eradication (triple/quadruple therapy) first, not chemotherapy.
- Staging = PET-CT. First-line therapy: ABVD for classic HL, R-CHOP for DLBCL.
Hodgkin subtypes & prognosis
Classic HL subtypes: Nodular sclerosis (most common, ~70%; lacunar cells; broad fibrous bands; mediastinal). Mixed cellularity (abundant RS cells, EBV-associated, more B symptoms, older patients / HIV). Lymphocyte-rich (few RS cells, best prognosis among classic types). Lymphocyte-depleted (rare, worst prognosis, elderly/HIV). Prognosis tracks inversely with RS-cell burden — more lymphocytes and fewer RS cells means better outcome. Nodular lymphocyte-predominant HL is a distinct entity with "popcorn" (L&H) cells that are CD20+ and CD15−/CD30− (the mirror-image marker profile) — indolent with excellent prognosis.
The NHL landscape: indolent vs aggressive
Indolent (slow-growing, generally incurable): follicular [t(14;18)], marginal zone / MALT (H. pylori, Sjögren, Hashimoto; t(11;18)), and small lymphocytic lymphoma (tissue counterpart of CLL, CD5+/CD23+). Aggressive (but potentially curable): DLBCL, Burkitt, and mantle cell (biologically aggressive despite small cells). Key T-cell entities: mycosis fungoides (cutaneous CD4+ T-cell lymphoma; Pautrier microabscesses, cerebriform nuclei) with its leukemic phase Sézary syndrome; and adult T-cell leukemia/lymphoma from HTLV-1 (hypercalcemia, lytic bone lesions, skin lesions; Caribbean/Japan). Watch for follicular → DLBCL transformation (sudden nodal growth + rising LDH).
- Hodgkin first-line = ABVD: Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine.
- Its two organ toxicities: Bleomycin → lungs (pulmonary fibrosis); Adriamycin/doxorubicin → heart (cardiotoxicity).
- RS-cell markers: CD15 + CD30 = 45, but CD45 is NEGATIVE.
- Translocations by the numbers: Follicular 14;18 (BCL2) · Burkitt 8;14 (c-MYC) · Mantle 11;14 (cyclin D1).
Treatment & complications
Classic HL: ABVD ± involved-site radiation — highly curable, even at advanced stage. Monitor bleomycin pulmonary toxicity and doxorubicin cardiotoxicity; long-term survivors carry risk of secondary malignancy (notably breast cancer after chest radiation) and hypothyroidism. NHL: R-CHOP (Rituximab, Cyclophosphamide, Hydroxydaunorubicin/doxorubicin, Oncovin/vincristine, Prednisone) for DLBCL; rituximab (anti-CD20) is added to most B-cell NHL regimens. High-turnover lymphomas (Burkitt, bulky DLBCL) require tumor lysis prophylaxis: aggressive IV hydration plus allopurinol or rasburicase, with monitoring of K⁺, phosphate, uric acid, and Ca²⁺.
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