What is the appropriate diagnosis and treatment approach for a patient suspected of having non-Hodgkin lymphoma, potentially with a history of immunosuppression?

Lymphoma: Diagnostic and Treatment Approach

For a patient with suspected non-Hodgkin lymphoma (NHL), obtain an excisional lymph node biopsy with immunohistochemistry including CD20 status, perform comprehensive staging with CT imaging and bone marrow biopsy, and initiate R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) for CD20-positive diffuse large B-cell lymphoma after screening for hepatitis B, C, and HIV. 1, 2

Initial Diagnostic Workup

Clinical Assessment

• Document constitutional "B symptoms" specifically: fever >38°C, drenching night sweats requiring clothing changes, and unexplained weight loss exceeding 10% of body weight over 6 months 3, 4
• Assess performance status as this directly impacts treatment eligibility and prognosis 3
• Examine all lymphoid regions systematically, palpating cervical, supraclavicular, axillary, and inguinal nodes, while checking for hepatosplenomegaly and abdominal masses 3, 4

Mandatory Laboratory Studies

• Complete blood count with differential to identify cytopenias or leukocytosis 1, 3
• Comprehensive metabolic panel including liver and renal function tests 1, 3
• Lactate dehydrogenase (LDH) and uric acid levels as tumor burden markers 1, 3
• Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis C, and HIV screening are mandatory before initiating rituximab therapy 1, 2
• Protein electrophoresis for B-cell lymphomas 1

Tissue Diagnosis: The Critical Step

Excisional lymph node biopsy is the gold standard and strongly preferred over core needle biopsy. 1, 3 Core needle biopsy should only be performed when excisional biopsy is anatomically impossible or in patients requiring emergency treatment who cannot tolerate surgery 1, 5

The tissue must be processed to provide:

• Formalin-fixed samples for routine histology 1, 3
• Fresh frozen material for molecular characterization (recommended but investigational) 1
• CD20 immunohistochemistry is mandatory as this determines rituximab eligibility 1
• Additional markers including CD45, CD3, and B-cell/T-cell markers to classify the lymphoma subtype 1
• Diagnosis according to WHO classification 1

Common Pitfall: Fine needle aspiration is inadequate for lymphoma diagnosis and should never be used as the sole diagnostic method. 3, 5

Staging Evaluation

Imaging Studies

• CT scan of chest, abdomen, and pelvis with contrast is the minimum requirement 1, 3
• PET-CT from skull base to mid-thigh is preferred for initial staging when available 3, 5
• Chest X-ray alone is insufficient but acceptable as part of comprehensive staging 1

Bone Marrow Assessment

Bone marrow aspirate and biopsy are mandatory for NHL staging unless PET-CT demonstrates bone marrow involvement 1, 5

Additional High-Risk Assessments

Consider diagnostic lumbar puncture with simultaneous prophylactic intrathecal chemotherapy (cytarabine or methotrexate) in high-risk patients with: 1

• More than two adverse International Prognostic Index (IPI) parameters
• Bone marrow involvement
• Testicular involvement
• Spinal or skull base involvement

Staging Classification

• Apply Ann Arbor staging system, documenting bulky disease (>10 cm) 1
• Calculate International Prognostic Index (IPI) for prognostic stratification 1

Treatment Approach for Newly Diagnosed DLBCL

Standard First-Line Therapy

For CD20-positive diffuse large B-cell lymphoma, R-CHOP (rituximab plus CHOP) given every 21 days for 6-8 cycles is the standard of care. 1, 6

This regimen consists of:

• Rituximab (anti-CD20 monoclonal antibody)
• Cyclophosphamide
• Doxorubicin (anthracycline)
• Vincristine
• Prednisone

Critical Pre-Treatment Considerations

Hepatitis B Reactivation Risk: All patients must be screened for HBV before rituximab initiation. HBV reactivation can cause fulminant hepatitis, hepatic failure, and death. 2 Patients with positive HBsAg or anti-HBc require antiviral prophylaxis and close monitoring during and after treatment. 2

Cardiac Assessment: Document cumulative anthracycline dose and obtain baseline echocardiography or MUGA scan to assess ejection fraction before initiating doxorubicin-containing regimens 1, 5

Tumor Lysis Syndrome Prevention: In patients with high tumor burden (elevated LDH, bulky disease), implement prophylaxis with hydration, allopurinol or rasburicase, and monitor electrolytes closely 1

Treatment Modifications

• Avoid dose reductions for hematological toxicity in patients treated with curative intent 1
• Use prophylactic granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia to maintain dose intensity 1

Role of Radiotherapy

Consolidation radiotherapy to sites of bulky disease has not proven benefit in the rituximab era and is not routinely recommended 1

Special Considerations for Immunosuppressed Patients

Patients with HIV-associated NHL require:

• Concurrent highly active antiretroviral therapy (HAART) to suppress HIV and improve immune function 7
• Multidisciplinary management addressing concurrent infections and complications 7
• Standard-dose chemotherapy can be administered successfully with appropriate supportive care 7

Response Assessment

Perform imaging evaluation:

• After 2-4 cycles of chemotherapy (mid-treatment assessment) 1
• After completion of all therapy 1
• PET-CT when positive at baseline is part of updated response criteria, but histological confirmation is strongly recommended before changing therapy based on PET positivity alone 1

Repeat bone marrow biopsy only if initially involved at diagnosis 1, 5

Relapsed/Refractory Disease

Biopsy Requirements for Relapse

• Early relapse (<12 months): Repeat biopsy not required unless clinical presentation suggests second malignancy 1
• Late relapse (≥12 months): Histological verification is mandatory to exclude transformation to follicular lymphoma 1

Salvage Therapy Approach

For patients under 65 years with adequate organ function, salvage chemotherapy (R-DHAP, R-ESHAP, or R-ICE) followed by high-dose chemotherapy with autologous stem cell transplantation in responding patients is the standard approach. 1

For patients ineligible for transplant, use alternative salvage regimens with or without involved-field radiotherapy 1

Surveillance After Complete Response

• History and physical examination every 3 months for 2 years, every 6 months for 3 additional years, then annually 1, 3
• Blood count and LDH at 3,6,12, and 24 months, then only for suspicious symptoms 1, 3
• CT imaging at 6,12, and 24 months after treatment completion 1, 3
• Routine surveillance PET scans are not recommended 1
• Monitor for secondary malignancies and late treatment effects 1, 3
• Thyroid function testing (TSH) at 1,2, and 5 years if neck irradiation was administered 1, 3

Critical Pitfall: Do not delay treatment while awaiting molecular studies or gene expression profiling, as these remain investigational and should not impact initial management decisions. 1