What is the diagnostic approach for lymphoma?

Diagnostic Approach for Lymphoma

Excisional lymph node biopsy evaluated by an expert hematopathologist is the gold standard for diagnosing lymphoma, followed by PET-CT staging for FDG-avid subtypes. 1, 2

Tissue Acquisition for Diagnosis

Primary Biopsy Method

• Excisional or incisional lymph node biopsy is mandatory and provides sufficient tissue for comprehensive analysis including formalin-fixed samples and fresh frozen material for molecular characterization. 1, 2
• Core needle biopsy should only be used when excisional biopsy is not feasible due to anatomic constraints or patient factors. 2, 3
• The tissue must be evaluated by an expert hematopathologist using immunohistochemistry, flow cytometry, and molecular studies as appropriate. 1

Required Pathologic Elements

• The histology report must include WHO classification diagnosis, minimum immunohistochemistry results, exclusion of Burkitt lymphoma and mantle cell lymphoma, and comprehensive evaluation through morphology, immunohistochemistry, flow cytometry, and molecular studies. 1

Initial Clinical Assessment

Symptom Documentation

• Document all constitutional B symptoms: fever, night sweats, unexplained weight loss >10% body weight over 6 months. 2, 3
• Record additional symptoms including alcohol intolerance, pruritus, and fatigue. 2
• Assess performance status as it directly impacts treatment decisions and prognosis. 2, 3

Physical Examination

• Examine all lymphoid regions systematically including cervical, supraclavicular, axillary, inguinal, and femoral nodes. 2
• Palpate for hepatosplenomegaly and abdominal masses. 2, 3
• Measure all accessible peripheral lymph nodes to identify optimal biopsy sites. 3

Laboratory Evaluation

Mandatory Blood Tests

• Complete blood count with differential to detect cytopenias or abnormal cell populations. 2, 3
• Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, albumin, and renal function. 2, 3
• Lactate dehydrogenase (LDH) as a tumor burden marker and prognostic indicator. 2, 3
• Uric acid level to assess tumor lysis risk, especially with high tumor burden. 2, 3

Infectious Disease Screening

• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing is mandatory before initiating rituximab or any chemotherapy due to reactivation risk. 2, 3
• Hepatitis C and HIV screening must be completed before treatment initiation. 2, 3

Staging Imaging

Primary Imaging Modality

• PET-CT from skull base to mid-thigh is the gold standard for staging FDG-avid lymphomas, providing superior accuracy for both nodal and extranodal disease compared to CT alone. 1, 2
• Contrast-enhanced CT of neck, chest, abdomen, and pelvis is appropriate for non-FDG-avid lymphoma subtypes. 1, 2
• Baseline chest X-ray should be obtained. 3

Bone Marrow Assessment

• Bone marrow aspirate and biopsy is required for complete staging in patients being considered for curative therapy. 1, 2
• Bone marrow biopsy may be omitted if PET-CT shows multifocal skeletal lesions or in certain circumstances with negative PET findings. 2

Staging System and Prognostic Assessment

• The Ann Arbor classification system with notation of bulky disease is the recommended staging framework. 1, 2
• Calculate the International Prognostic Index (IPI) for prognostic stratification and treatment planning. 1, 2
• Subtype-specific indices (FLIPI for follicular lymphoma, MIPI for mantle cell lymphoma) should be calculated based on histology. 2

Special Considerations for High-Risk Disease

• Lumbar puncture with prophylactic intrathecal chemotherapy is indicated for patients with more than two adverse IPI parameters or bone marrow involvement to prevent CNS relapse. 3

Critical Pitfalls to Avoid

• Never accept fine-needle aspiration or inadequate core biopsy as sufficient for initial lymphoma diagnosis—excisional biopsy provides the architectural detail necessary for accurate subtyping. 2, 3
• Never delay hepatitis B screening, as reactivation during anti-CD20 therapy or chemotherapy can be fatal. 3
• Never assume benignity based solely on imaging characteristics—tissue diagnosis is always required. 3