What are the diagnostic steps and treatment options for a patient presenting with symptoms suggestive of Hodgkin's (Hodgkin lymphoma) lymphoma?

Diagnostic Approach for Hodgkin Lymphoma

The definitive diagnosis of Hodgkin lymphoma requires an excisional lymph node biopsy, followed by comprehensive staging with PET-CT imaging, laboratory tests, and risk assessment to determine appropriate treatment strategy. 1

Initial Presentation and Clinical Features

• Hodgkin lymphoma typically presents with painless lymphadenopathy, most commonly affecting cervical lymph nodes (>60% of cases) 1
• B symptoms should be carefully documented as they impact staging and prognosis:
  • Fever >38°C
  • Drenching night sweats requiring changing clothes/bedding
  • Unexplained weight loss >10% of body weight within 6 months 2
• Other disease-related symptoms to assess include fatigue, pruritus, and alcohol-induced pain 1

Diagnostic Workup

Required Biopsy

• Excisional lymph node biopsy (or biopsy from another affected organ) is mandatory for diagnosis 1
• Histological classification according to WHO criteria:
  • Classical Hodgkin Lymphoma (cHL) - 95% of cases
    • Characterized by Hodgkin and Reed-Sternberg (HRS) cells positive for CD30 and CD15, occasionally CD20+, CD45- 1
  • Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) - 5% of cases
    • Characterized by lymphocyte predominant (LP) cells positive for CD20 and CD45, negative for CD15 and CD30 1

Imaging Studies

• Chest X-ray - mandatory 1
• Contrast-enhanced CT scan of neck, chest, and abdomen - mandatory 1
• Whole-body PET scan - strongly recommended for accurate staging and response assessment 1
• Bone marrow biopsy - no longer indicated if PET-CT is performed due to high sensitivity of PET-CT for bone marrow involvement 1

Laboratory Tests

• Full blood cell count 1
• Erythrocyte sedimentation rate (ESR) 1
• Blood chemistry including:
  • C-reactive protein (CRP)
  • Alkaline phosphatase (AP)
  • Lactate dehydrogenase (LDH)
  • Liver enzymes
  • Albumin 1
• Screening for hepatitis B, hepatitis C, and HIV is compulsory 1

Staging and Risk Assessment

• Staging according to Ann Arbor classification with consideration of clinical risk factors 1
• Risk stratification into three categories:
  • Limited stage (early favorable)
  • Intermediate stage (early unfavorable)
  • Advanced stage 1
• Risk factors to assess:
  • Large mediastinal mass (>1/3 of horizontal chest diameter)
  • Extranodal disease
  • Elevated ESR (>50 with B symptoms; >30 without B symptoms)
  • Three or more involved lymph node areas 1

Pre-Treatment Evaluations

• Cardiac function assessment:
  • ECG
  • Echocardiography 1
• Pulmonary function tests 1
• Reproductive counseling for patients of reproductive age 1
• Serum pregnancy test for women of reproductive age 1
• ENT specialist consultation with fiberoptic nasolaryngoscopy if PET-CT unavailable 1

Treatment Approaches Based on Stage

Limited-Stage Disease

• Standard treatment: Combined modality therapy
  • 2-3 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) 3, 4
  • Followed by 20-30 Gy involved-field radiotherapy (IFRT) 1
• This approach has shown superior tumor control compared to radiotherapy alone 1

Intermediate-Stage Disease

• Standard treatment: 4 cycles of ABVD followed by 30 Gy IFRT 1
• This approach achieves tumor control and overall survival rates exceeding 85-90% at 5 years 1

Advanced-Stage Disease

• Longer course of combination chemotherapy, often without radiotherapy 5
• Newer agents including brentuximab vedotin and anti-PD-1 antibodies are now being incorporated into frontline therapy 5

Response Evaluation and Follow-up

• Interim response evaluation should be performed:
  • After completion of chemotherapy/prior to radiotherapy in early and intermediate stages
  • After four cycles in advanced stages 1
• Final staging should be performed after completion of treatment with:
  • Physical examination
  • Laboratory analyses
  • CT scans 1
• PET scans may identify persistent disease activity, but false positives must be excluded 1

Treatment of Relapsed Disease

• High-dose chemotherapy followed by autologous stem cell transplant is standard of care for most relapsed patients 5
• For patients who fail autologous transplant, options include:
  • Brentuximab vedotin
  • PD-1 blockade
  • Non-myeloablative allogeneic transplant
  • Clinical trials 5

Common Pitfalls to Avoid

• Failure to obtain an adequate excisional biopsy specimen - core needle biopsies may not provide sufficient material for accurate diagnosis 1
• Omitting PET-CT when available - this is now considered standard for accurate staging 1
• Neglecting reproductive counseling before treatment - chemotherapy and abdominal radiotherapy can cause permanent infertility 1
• Overlooking screening for hepatitis and HIV - these are mandatory before treatment initiation 1
• Missing the distinction between classical HL and NLPHL - these entities have different treatment approaches 1