What are the paraneoplastic features of Hodgkin's lymphoma and how are they managed?

Paraneoplastic Features of Hodgkin's Lymphoma

The most common paraneoplastic features of Hodgkin's lymphoma include B symptoms (fever, night sweats, weight loss), neurological manifestations, cutaneous disorders, and hematological abnormalities, which should be managed with prompt treatment of the underlying lymphoma alongside targeted symptomatic therapy. 1

Common Paraneoplastic Manifestations

B Symptoms

• Fever: Unexplained fever >38°C 2
• Night sweats: Recurrent and drenching 2
• Weight loss: >10% of baseline body weight over 6 months 2

These symptoms are important prognostic factors and are designated as "B" in the Ann Arbor staging system 2. They typically resolve with successful treatment of the lymphoma.

Neurological Manifestations

• Cerebral vasculitis 3
• Optic neuritis 4
• Paraneoplastic encephalitis
• Peripheral neuropathy

Management approach:

• Corticosteroids (e.g., prednisone 100 mg daily) can rapidly improve neurological symptoms 3
• Anti-epileptic therapy for seizure manifestations
• Neurological symptoms typically resolve with treatment of the underlying lymphoma 3

Cutaneous Manifestations

• Generalized pruritus
• Eczematous eruptions 5
• Diffuse hyperpigmentation
• Acquired ichthyosis
• Erythema nodosum
• Prurigo nodularis 5

Management approach:

• Topical corticosteroids and antihistamines for symptomatic relief
• Definitive treatment requires addressing the underlying lymphoma 5

Hematological Abnormalities

• Leukocytosis
• Lymphopenia
• Anemia
• Hypoalbuminemia 1
• Hemophagocytic lymphohistiocytosis (HLH) 1

These abnormalities serve as prognostic biomarkers and typically improve with treatment of the lymphoma.

Diagnostic Approach for Paraneoplastic Features

1. Initial Assessment:

   • Complete blood count
   • Erythrocyte sedimentation rate (ESR)
   • Serum albumin and LDH levels
   • Liver and renal function tests 6

2. Imaging Studies:

   • CT scan of neck, thorax, abdomen, and pelvis
   • FDG-PET/CT scan (sensitivity 84%, specificity 90%) 6

3. Histopathological Confirmation:

   • Excisional lymph node biopsy is essential for diagnosis 2, 6
   • Bone marrow biopsy if B symptoms are present 6

4. Specialized Testing:

   • MRI for suspected neurological involvement
   • EEG for seizure manifestations 3
   • Skin biopsy for unusual dermatological presentations

Management Principles

1. Primary Treatment:

   • Treatment of the underlying Hodgkin's lymphoma is the definitive management for paraneoplastic manifestations
   • Early stages: Combined modality therapy with ABVD chemotherapy followed by involved-field radiotherapy 2
   • Advanced stages: Chemotherapy with ABVD or BEACOPP regimens 2

2. Symptomatic Management:

   • Neurological symptoms: Corticosteroids, anti-epileptics as needed
   • Cutaneous manifestations: Topical steroids, antihistamines
   • B symptoms: Antipyretics, supportive care until lymphoma treatment takes effect

3. Monitoring:

   • Regular assessment of paraneoplastic features to gauge treatment response
   • FDG-PET/CT is valuable for monitoring disease activity 6
   • Most paraneoplastic manifestations resolve with successful treatment of lymphoma

Clinical Pearls and Pitfalls

• Pearl: Persistent unexplained B symptoms should prompt investigation for Hodgkin's lymphoma, even in the absence of obvious lymphadenopathy
• Pitfall: Neurological paraneoplastic syndromes may be misdiagnosed as primary neurological disorders, delaying diagnosis of underlying lymphoma
• Pearl: Resolution of paraneoplastic features often precedes radiological evidence of disease response
• Pitfall: Recurrence of previously resolved paraneoplastic symptoms may indicate disease relapse and warrants prompt investigation

Special Considerations

• Paraneoplastic manifestations are driven by cytokines and inflammatory mediators produced by the tumor microenvironment 1
• The presence of B symptoms indicates a more aggressive disease course and affects staging and treatment decisions 2
• Paraneoplastic neurological syndromes in Hodgkin's lymphoma are rare but can be the presenting feature of the disease 3, 4