Hodgkin lymphoma (HL) is one of those Step 1 topics that looks straightforward—until a question stem starts sprinkling in painless lymphadenopathy, “B symptoms,” and some oddly specific cell markers. The good news: HL is high-yield because it’s pattern-based. If you can recognize the classic presentations, nail the pathology (especially Reed–Sternberg cells), and separate HL from non-Hodgkin lymphomas, you’ll pick up points fast.
Where Hodgkin Lymphoma Fits (Big-Picture Framework)
Hodgkin lymphoma = a B-cell malignancy characterized by a small number of malignant cells amid a large reactive inflammatory background.
Key Step 1 framing:
- The malignant cell is the Reed–Sternberg (RS) cell
- HL tends to spread contiguously (node-to-node)
- Often presents with painless lymphadenopathy and B symptoms
- Strong classic association with EBV (especially mixed cellularity subtype)
First Aid cross-reference (typical placement):
- Pathology → Hematopathology → Lymphomas (Hodgkin vs non-Hodgkin)
Definition (What You’re Actually Diagnosing)
Hodgkin lymphoma is a malignant lymphoma defined by the presence of:
- Reed–Sternberg cells (classic HL) in an appropriate reactive cellular background
Classic RS cells:
- Large, binucleate or bilobed nuclei
- Prominent nucleoli → “owl’s eyes”
- Typical immunophenotype: CD15+ and CD30+
Pathophysiology: What RS Cells Do (and Why Symptoms Happen)
The RS cell: “Small population, huge effect”
A high-yield concept: RS cells are relatively sparse, but they:
- Secrete cytokines/chemokines that recruit inflammatory cells (eosinophils, macrophages, lymphocytes)
- Create the tumor “bulk” via reactive infiltrate
- Drive systemic symptoms through cytokines (e.g., IL-1, TNF-α, IL-6-like effects)
Immunophenotype (classic HL)
- CD15+
- CD30+
- Often derived from germinal center B cells, but may have impaired Ig expression
EBV association
EBV contributes to oncogenesis in a subset, classically:
- Mixed cellularity HL (and also some cases of lymphocyte-depleted HL)
- EBV can promote B-cell survival/proliferation (Step-level: recognize the association more than the molecular details)
First Aid cross-reference:
- Microbiology/Immunology → EBV associations
- Pathology → Hematopathology → Hodgkin lymphoma markers (CD15/CD30)
Epidemiology & High-Yield Patterns
Age distribution (classic teaching)
- Bimodal: young adults and older adults (varies by subtype)
Nodal spread
- Contiguous spread is a classic differentiator from non-Hodgkin lymphoma (often noncontiguous)
Common presenting nodes
- Cervical or mediastinal nodes are common in classic HL (especially nodular sclerosis)
Clinical Presentation: How HL Shows Up on Test Day
Typical symptoms
- Painless lymphadenopathy (often cervical)
- B symptoms:
- Fever
- Night sweats
- Weight loss (>10% over 6 months)
High-yield “classic clues”
- Mediastinal mass (nodular sclerosis subtype)
- Pruritus (cytokine-mediated; can be prominent)
- Alcohol-induced pain at involved lymph nodes (classically associated, not super common but highly testable)
What the stem may emphasize
- Constitutional symptoms + painless LAD + imaging showing mediastinal widening
- Labs may show:
- Eosinophilia (from cytokine recruitment) in some cases
- Elevated inflammatory markers (nonspecific)
Subtypes of Hodgkin Lymphoma (Know the Classics)
Quick table: subtypes, associations, and buzzwords
| Subtype | Typical Patient/Setting | Key Histology/Buzzwords | EBV Association |
|---|---|---|---|
| Nodular sclerosis (most common) | Young adults; often female; mediastinal involvement | Lacunar cells, broad collagen bands → nodules | Variable |
| Mixed cellularity | Older adults; more systemic symptoms | Classic RS cells with mixed inflammatory background | Strong |
| Lymphocyte-rich | Often better prognosis | Many lymphocytes, few RS cells | Variable |
| Lymphocyte-depleted | Immunocompromised, older; more aggressive | Many RS cells, fewer lymphocytes | Often |
High-yield memory anchors:
- Nodular sclerosis = mediastinal mass + lacunar cells + collagen bands
- Mixed cellularity = EBV + classic RS + B symptoms
First Aid cross-reference:
- Pathology → Hematopathology → Hodgkin lymphoma subtypes (nodular sclerosis, mixed cellularity, etc.)
Diagnosis: What You Need to Confirm HL
1) Excisional lymph node biopsy (preferred)
High-yield principle: FNA is often insufficient for lymphoma architecture. HL diagnosis typically requires:
- Excisional biopsy to evaluate architecture and identify RS cells in the proper setting
2) Histology + immunostains
- RS “owl-eye” morphology
- CD15+ CD30+ (classic HL)
3) Staging workup (conceptual for Step 1; more Step 2-ish clinically)
- PET/CT for staging and response assessment
- Bone marrow biopsy in selected cases (depending on stage/symptoms)
Staging (The USMLE-Friendly Version)
HL uses Ann Arbor staging (you don’t need every nuance, but know the structure):
- Stage I: single lymph node region (or single extralymphatic site)
- Stage II: ≥2 lymph node regions on same side of diaphragm
- Stage III: lymph node regions on both sides of diaphragm
- Stage IV: disseminated involvement (e.g., liver, bone marrow)
Suffix:
- A: no B symptoms
- B: B symptoms present
High yield: Stage and B symptoms affect prognosis and treatment intensity.
Treatment (What Step 1/2 Want You to Recognize)
Core regimens
Most classic HL is treated with:
- Combination chemotherapy ± involved-field radiation (stage-dependent)
Common regimen tested:
- ABVD
- Adriamycin (doxorubicin)
- Bleomycin
- Vinblastine
- Dacarbazine
High-yield toxicity tie-ins (very testable)
- Doxorubicin → cardiotoxicity (dilated cardiomyopathy), “red man” urine, free radicals
- Prevention: dexrazoxane
- Bleomycin → pulmonary fibrosis
- Note: classically no significant myelosuppression
- Vinblastine → neuropathy + myelosuppression (microtubule inhibitor)
- Dacarbazine → myelosuppression, nausea/vomiting (alkylating-like)
First Aid cross-reference:
- Pharm → Antineoplastics (doxorubicin, bleomycin, vinca alkaloids, alkylating agents)
Modern additions (more Step 2/clinical, but increasingly testable)
- Brentuximab vedotin (anti-CD30 antibody-drug conjugate) in select settings (relapsed/refractory or combined regimens in some cases)
- PD-1 inhibitors (e.g., nivolumab, pembrolizumab) for refractory disease (tumor immune evasion concepts)
Prognosis: Why HL Is a “Good Lymphoma to Catch”
High-yield concept:
- HL is often highly curable, especially early-stage disease.
Prognosis depends on:
- Stage (I/II better than III/IV)
- Presence of B symptoms
- Bulk of disease (e.g., large mediastinal mass)
- Patient factors (age, comorbidities)
High-Yield Comparisons: Hodgkin vs Non-Hodgkin (Common Traps)
| Feature | Hodgkin Lymphoma | Non-Hodgkin Lymphoma |
|---|---|---|
| Key malignant cell | Reed–Sternberg cell | Malignant B/T/NK lymphocytes (varies) |
| Spread | Contiguous | Often noncontiguous |
| Extranodal disease | Less common | More common |
| Markers (classic) | CD15+, CD30+ | Varies (e.g., CD20 in many B-cell NHLs) |
| Classic clue | Mediastinal mass, “owl eyes,” B symptoms | Depends on subtype (e.g., Burkitt “starry sky”) |
HY Associations & “If You See X, Think HL”
Stem-to-diagnosis mappings
- Young adult + mediastinal mass + cervical LAD → nodular sclerosis HL
- EBV history + systemic symptoms + classic RS cells → mixed cellularity HL
- Painless LAD + “owl-eye” cells + CD15/CD30 positivity → classic HL
- Pruritus/eosinophilia in lymphoma context → cytokine-mediated, commonly seen with HL
- Pain in lymph node after alcohol → classic HL association
Rapid Review (Last-Minute Step 1 Checklist)
- HL is a B-cell lymphoma defined by Reed–Sternberg cells
- Classic RS immunophenotype: CD15+ CD30+
- Spread is typically contiguous
- Classic presentation: painless lymphadenopathy ± B symptoms
- Common subtype clues:
- Nodular sclerosis: mediastinal mass, lacunar cells, collagen bands
- Mixed cellularity: EBV association, systemic symptoms
- Diagnosis: excisional biopsy
- Treatment often includes ABVD
- Bleomycin → pulmonary fibrosis
- Doxorubicin → cardiotoxicity
- Often curable, especially early stages