What are the typical diagnosis and treatment options for lymphoma?

Diagnosis and Treatment of Lymphoma

The diagnosis of lymphoma requires a complete lymph node excisional or incisional biopsy with immunohistochemical analysis, followed by staging with CT scans and bone marrow evaluation, while treatment is based on lymphoma subtype with rituximab plus chemotherapy (R-CHOP, R-bendamustine) being the standard first-line therapy for most non-Hodgkin lymphomas and ABVD for Hodgkin lymphoma. 1, 2

Diagnosis

Initial Evaluation

• Complete lymph node excisional or incisional biopsy is essential for accurate diagnosis
  • Fine-needle aspirations are inadequate
  • Core needle biopsies should only be performed for difficult-to-access nodes (retroperitoneal) 1
• Preservation of fresh-frozen material for molecular analysis is recommended
• Immediate processing by an experienced pathology institute is necessary

Pathologic Assessment

• Minimum immunohistochemical panel should include:
  • For non-Hodgkin lymphomas: CD20, CD3, CD5, CD10, BCL2, BCL6, cyclin D1, CD21/CD23
  • For classical Hodgkin lymphoma: CD3, CD15, CD20, CD30, CD45, CD79a, PAX5 1
• Flow cytometry analysis including kappa/lambda, CD19, CD20, CD5, CD23, CD10
• Molecular studies in selected cases:
  • Genetic analysis for antigen receptor gene rearrangements
  • FISH to detect t(14;18), t(8;14), or variants 1

Staging Workup

• Laboratory tests:
  • Complete blood count with differential
  • Complete blood chemistry including LDH and uric acid
  • Screening for HIV, hepatitis B and C 3, 1
• Imaging:
  • CT scan of neck, chest, abdomen, and pelvis
  • PET-CT scan for accurate staging and later response assessment 1, 4
• Bone marrow aspirate and biopsy 3
• Diagnostic spinal tap with prophylactic cytarabine/methotrexate for high-risk patients (IPI >2, especially with bone marrow, testis, spine, or skull base involvement) 3

Staging Classification

• Ann Arbor staging system is used 3, 1:
  • Stage I: Single lymphatic region or localized involvement of single extralymphatic organ
  • Stage II: Two or more lymphatic regions on same side of diaphragm
  • Stage III: Lymphatic regions on both sides of diaphragm
  • Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs
• Mention of bulky disease is important 3

Treatment

Non-Hodgkin Lymphoma (NHL)

Early Stage (I-II) Follicular Lymphoma

• Radiotherapy is the treatment of choice with curative potential
  • Should be performed as extended field irradiation 3, 1

Advanced Stage (III-IV) Follicular Lymphoma

• Observation ("watch and wait") is appropriate for asymptomatic patients 1
• Treatment initiation criteria:
  • B-symptoms (fever, night sweats, weight loss)
  • Hematopoietic impairment
  • Bulky disease
  • Vital organ compression
  • Rapid lymphoma progression 3, 1
• First-line therapy options:
  • Rituximab plus chemotherapy (R-CHOP, R-CVP, R-bendamustine) 1, 2
  • Single agents like fludarabine or chlorambucil in selected cases 3
  • Maintenance rituximab for 2 years improves progression-free survival 1

Aggressive NHL (Diffuse Large B-Cell Lymphoma)

• First-line therapy: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) 1, 2
• For patients with curative intent (age <65, no major organ dysfunction):
  • Conventional salvage chemotherapy (R-DHAP, R-ESHAP, R-EPOCH, R-ICE) followed by high-dose therapy with stem cell support for relapsed/refractory disease 3
• For patients unsuitable for high-dose therapy:
  • Conventional salvage regimens with possible involved field radiotherapy
  • Individualized palliative care for elderly or comorbid patients 3

Hodgkin Lymphoma

• Early-stage: Combined modality therapy with abbreviated chemotherapy followed by involved-field radiation 5, 6
• Advanced-stage: More prolonged course of combination chemotherapy
  • ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is standard
  • Alternative regimens: Stanford V or BEACOPP 2
• Relapsed/refractory disease:
  • High-dose chemotherapy with autologous stem cell transplant
  • Brentuximab vedotin for transplant-ineligible patients or post-transplant failures
  • PD-1 inhibitors for subsequent lines 6

Response Assessment and Follow-up

Response Evaluation

• PET-CT after 2-3 cycles and at completion of treatment 1
• Adequate radiological tests after every 2 cycles of therapy and after last cycle 3
• Repeat initially pathologic bone marrow or spinal fluid evaluations at end of treatment 3

Follow-up Schedule

• History and physical examination:
  • Every 3 months for 2 years
  • Every 6 months for 3 more years
  • Then annually 3, 1
• Blood counts:
  • At 3,6,12, and 24 months
  • Then as needed for evaluation of suspicious symptoms 3
• Imaging:
  • Minimal adequate radiological examinations at 3,6,12, and 24 months
  • CT scan at least once during follow-up 3
• Thyroid function tests at 1,2, and 5 years for patients who received neck irradiation 3
• Breast cancer screening for women who received chest irradiation at premenopausal age 3

Special Considerations

Cardiotoxicity Monitoring

• Cumulative anthracycline dose must be tracked
• Echocardiography or MUGA scans for ejection fraction assessment before further anthracyclines 3, 7
• Doxorubicin carries risk of cardiomyopathy with incidences from 1-20% for cumulative doses from 300-500 mg/m² 7

Secondary Malignancies

• Increased risk of secondary acute myelogenous leukemia and myelodysplastic syndrome with anthracyclines 7
• Monitor for transformation of indolent to aggressive lymphoma, especially with rising LDH, disproportionate growth of single site, or new B symptoms 1

Treatment Complications

• Monitor for extravasation with doxorubicin (can cause severe tissue necrosis) 7
• Severe myelosuppression requiring transfusions, hospitalization, or leading to infection 7
• Extended anti-infectious prophylaxis should be considered with bendamustine-containing regimens 1

By following this comprehensive approach to diagnosis and treatment, patients with lymphoma can achieve optimal outcomes with careful monitoring for treatment-related complications and disease recurrence.