Hodgkin Disease (Lymphoma): Causes, Symptoms and Treatment

Hodgkin disease or Hodgkin's lymphoma is one of two common types of cancers of the lymphatic system. ( specifically the white blood cells) The other type, non-Hodgkin's lymphoma, is far more common.

Hodgkin lymphoma is a malignant neoplasm of B-cell origin , characterized by the presence of Reed-Sternberg (RS) cells in a background of mixed inflammatory cells. It arises primarily in lymph nodes and spreads in a contiguous, orderly fashion .

• Exact cause is unknown.
• Strong association with Epstein-Barr Virus (EBV) infection—especially in mixed-cellularity and lymphocyte-depleted subtypes.
• Increased risk in immunosuppressed patients , particularly those with HIV/AIDS .

Epidemiology

• Bimodal age distribution:
  • Early peak: 15–34 years
  • Late peak: >55 years
• More common in males , especially in childhood (up to 85% of pediatric cases).
• Less common than non-Hodgkin lymphoma.

Pathophysiology

• Malignant transformation of germinal center B-cells into Reed-Sternberg cells .
• RS cells:
  • Large, binucleated or multinucleated ("owl’s eye" appearance).
  • Immunophenotype: CD15+ and CD30+
  • Rarely express B-cell markers CD19/CD20 .
• EBV DNA is found in ~50% of cases, particularly MCHD (60–70%) and LDHD (up to 100% in HIV-positive).

Clinical Features

Typical Presentation:

• Painless lymphadenopathy (often cervical or supraclavicular; 80% above diaphragm)
• B symptoms (present in ~40% of patients):
  • Fever
  • Drenching night sweats
  • Unintentional weight loss (>10% in 6 months)
• Pruritus
• Alcohol-induced pain at lymph nodes (specific to HL)
• Mediastinal mass (causing chest pain, cough, SOB)
• Rare: Pel-Ebstein fever (cyclic fevers every 1–2 weeks)

Advanced Disease Signs:

• Splenomegaly, hepatomegaly
• Superior vena cava syndrome
• Paraneoplastic CNS syndromes (rare)

Histological Subtypes (WHO Classification)

Classical HL (95%) :

1. Nodular Sclerosis HL (NSHL) (60–80%)
   • Lacunar RS cells
   • Mediastinal involvement
   • Young adults; females
2. Mixed Cellularity HL (MCHL) (15–30%)
   • Classic RS cells
   • EBV common; associated with advanced disease
3. Lymphocyte-Depleted HL (LDHL) (<1%)
   • Elderly or HIV-positive
   • Poor prognosis; diffuse RS cells
4. Lymphocyte-Rich Classical HL (LRCHL) (5%)
   • Classic RS cells; good prognosis

Nodular Lymphocyte-Predominant HL (NLPHL) (5%)

• Popcorn cells (L&H variant RS cells)
• CD20+ , CD15- , CD30-
• Indolent course; may transform to aggressive non-Hodgkin lymphoma

Diagnostic Workup

Laboratory Studies

• CBC: Anemia, lymphopenia, eosinophilia, neutrophilia, thrombocytopenia
• ESR & CRP: Often elevated (indicator of tumor burden)
• LDH: May be elevated (associated with high tumor burden)
• LFTs: Elevated ALP may suggest liver or bone involvement
• Renal function & urinalysis: Evaluate for paraneoplastic nephrotic syndrome

Imaging

• Chest X-ray: Mediastinal widening
• CT neck, chest, abdomen, pelvis: Assess nodal spread, organ involvement
• PET-CT: Preferred for staging and monitoring treatment response

Histopathology

• Excisional lymph node biopsy is gold standard
  • Shows RS cells in classical HL
  • Immunohistochemistry confirms subtype
• Bone marrow biopsy: Required in advanced-stage or systemic symptoms

Staging – Ann Arbor System

• 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 involvement on both sides of diaphragm
• Stage IV : Disseminated disease with extranodal involvement (e.g., bone marrow, liver)

Add "A" or "B" to indicate absence or presence of B symptoms

Prognostic Factors

• Negative Predictors:
  • B symptoms
  • Elevated LDH
  • Bulky disease
  • Advanced stage (III/IV)
  • Male gender
  • Age >45
  • Low albumin
• Positive Predictors:
  • Nodular sclerosis subtype
  • Absence of B symptoms
  • Early-stage disease

Treatment

1. Early-Stage (I–IIA):

• ABVD chemotherapy (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) ± involved-field radiation therapy (IFRT)

2. Advanced-Stage (IIB–IV):

• ABVD or escalated BEACOPP (Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone)

3. Relapsed/Refractory Disease:

• High-dose chemotherapy + autologous stem cell transplant
• Brentuximab vedotin (anti-CD30 antibody-drug conjugate)
• PD-1 inhibitors (nivolumab, pembrolizumab) in selected patients

Complications

• Secondary malignancies (e.g., leukemia, solid tumors)
• Infertility (chemotherapy-induced)
• Cardiopulmonary toxicity (from Adriamycin, Bleomycin)
• Hypothyroidism (post-neck irradiation)

Key NCLEX/USMLE High-Yield Points

• Presence of Reed-Sternberg cells = diagnostic hallmark
• Alcohol-induced pain in lymph nodes = pathognomonic clue
• B symptoms indicate worse prognosis and guide staging
• PET-CT is crucial for staging and treatment monitoring
• CD15+ and CD30+ = classical HL; CD20+ = NLPHL
• Always confirm diagnosis with excisional biopsy , not FNA

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