What are the diagnostic and treatment approaches for a patient with suspected Non-Hodgkin Lymphoma (NHL)?

Diagnostic Approach to Non-Hodgkin Lymphoma

For suspected NHL, obtain an excisional lymph node biopsy immediately—fine needle aspiration or core biopsy alone is inadequate for proper diagnosis and should only be used in rare emergency situations when excisional biopsy is not feasible. 1, 2

Tissue Diagnosis Requirements

Biopsy technique is critical for accurate diagnosis:

• Excisional or incisional lymph node biopsy is mandatory to provide adequate tissue for comprehensive pathologic evaluation including morphology, immunohistochemistry, flow cytometry, and molecular studies 1, 2, 3

• Core needle biopsy is discouraged unless clinical circumstances make it the only safe option for obtaining diagnostic tissue 1

• FNA alone is never acceptable for initial NHL diagnosis, though it may be combined with core biopsy and ancillary techniques (PCR for gene rearrangements, FISH, immunophenotyping) when lymph nodes are not easily accessible 1

• The specimen must include fresh frozen and formalin-fixed samples for complete analysis 2

Immunophenotyping is essential and must include:

• Pan-B and Pan-T cell antigens as the initial panel 1
• CD20 staining for proper subtyping per WHO classification 2
• Additional B- and T-cell subset antigens based on morphologic and clinical features 1

Essential Staging Workup

Once tissue diagnosis is confirmed, complete the following mandatory studies:

Physical Examination

• Measure all accessible lymph node groups with attention to size, consistency, and mobility 1, 3
• Determine liver and spleen size 1
• Document performance status 1
• Document B symptoms (fever >38°C, drenching night sweats requiring clothing changes, unexplained weight loss >10% over 6 months) as these impact staging and prognosis 4, 3

Laboratory Studies (All Mandatory)

• Complete blood count with differential 1, 3
• Serum lactate dehydrogenase (LDH)—elevated levels indicate higher tumor burden and worse prognosis 1, 4, 3
• Comprehensive metabolic panel including liver and kidney function 1, 3
• Uric acid levels 2, 3
• Hepatitis B testing (HBsAg and HBcAb) is mandatory before any treatment due to reactivation risk with anti-CD20 therapy and chemotherapy 1
• Hepatitis C and HIV screening 1, 2, 3

Imaging Studies

• CT chest/abdomen/pelvis with oral and IV contrast (unless renal insufficiency present) is the minimum required imaging 1, 2, 3
• PET-CT is preferred for staging when available and should be obtained as baseline, though typically arranged outpatient rather than in ED 1, 2, 3
• PET is nearly universally positive in DLBCL and follicular lymphoma, approximately 90% positive in T-cell lymphoma and nodal marginal zone lymphoma, but less sensitive for extranodal marginal zone lymphoma 1

Bone Marrow Evaluation

Bone marrow biopsy with or without aspirate is part of essential workup for all lymphomas, with specific exceptions: 1

• Defer bone marrow biopsy in patients with low-bulk indolent disease and radiographic stage III disease if observation is planned, as it won't change management 1

• Bone marrow biopsy is essential for potentially early-stage indolent lymphoma (stage I or II); some experts recommend bilateral core biopsies in this situation 1

• Omit bone marrow biopsy in SLL/CLL when clonal lymphocytosis is identified by flow cytometry 1

• Bone marrow biopsy can be omitted in patients undergoing PET-CT evaluation, but must be performed if PET-CT is unavailable 1

• In early-stage DLBCL (stage I-II), bone marrow involvement occurs in only 3.6% of cases, and biopsy may be safely omitted in selected patients 1

• Bilateral cores are recommended if radioimmunotherapy is being considered 1

Cardiac Assessment

• MUGA scan or echocardiogram is required when anthracycline or anthracenedione-containing regimens are planned 1

Optional Studies (Depending on Lymphoma Subtype)

• β2-microglobulin for prognostic purposes 1
• Endoscopic ultrasound for gastric MALT lymphoma 1
• Head CT or brain MRI for mantle cell lymphoma and DLBCL 1
• Lumbar puncture for CSF analysis in mantle cell lymphoma and DLBCL 1

Prognostic Assessment

After staging is complete, calculate risk scores:

• International Prognostic Index (IPI) for diffuse large B-cell lymphomas 2
• Follicular Lymphoma International Prognostic Index (FLIPI) for follicular lymphomas 2
• Stage using Ann Arbor classification (I-IV) with notation of bulky disease and A/B symptoms 2, 4

Critical Pre-Treatment Considerations

Before initiating any therapy:

• Discuss fertility preservation and offer sperm banking or oocyte/ovarian tissue cryopreservation to patients of reproductive age 1
• Ensure hepatitis B screening is complete to prevent potentially fatal reactivation 1
• Verify cardiac function assessment if anthracyclines will be used 1

Common Diagnostic Pitfalls

Avoid these errors:

• Using FNA or core biopsy alone without excisional biopsy leads to misdiagnosis and inappropriate treatment 1, 2
• Failing to obtain adequate tissue for immunophenotyping prevents proper WHO subclassification 1, 2
• Omitting hepatitis B screening before anti-CD20 therapy (rituximab) or chemotherapy risks life-threatening viral reactivation 1
• Performing unnecessary bone marrow biopsies in stage III indolent disease when observation is planned wastes resources and causes patient discomfort 1