What is the recommended workup for a patient with a history of follicular lymphoma, suspected of having recurrent disease?

Workup for Suspected Recurrent Follicular Lymphoma

A repeat biopsy is mandatory to rule out histologic transformation to aggressive lymphoma before proceeding with any treatment decisions. 1

Tissue Diagnosis - The Critical First Step

• Obtain a new confirmatory biopsy at the site of suspected relapse to exclude transformation to diffuse large B-cell lymphoma, which occurs in a significant proportion of relapses and fundamentally changes management 1
• PET-guided biopsy of the site with highest tracer intensity uptake (maximum SUV) is recommended to target the most metabolically active area, which is most likely to show transformation 1
• Excisional or incisional lymph node biopsy remains the gold standard when accessible nodes are available 1, 2
• Core needle biopsy is acceptable only for inaccessible sites (e.g., retroperitoneal masses), but ensure adequate tissue for comprehensive pathologic evaluation including immunohistochemistry, flow cytometry, and molecular studies 1, 3
• Never rely on fine-needle aspiration alone - it is insufficient for reliable diagnosis and grading 1, 3

The rationale here is critical: transformation to aggressive lymphoma occurs in a substantial subset of patients and requires completely different treatment (DLBCL-type regimens rather than indolent lymphoma approaches). Missing this diagnosis leads to undertreatment and poor outcomes.

Imaging Studies

• PET-CT scan of neck, chest, abdomen, and pelvis is the preferred imaging modality for restaging recurrent follicular lymphoma, as it improves accuracy of staging for both nodal and extranodal sites 1
• CT scan with contrast (neck, thorax, abdomen, pelvis) is the minimum acceptable imaging if PET-CT is not immediately available 1
• Document presence of bulky disease (>6 cm) as this impacts treatment decisions 1

Laboratory Evaluation

• Complete blood count with differential to assess for cytopenias or leukocytosis 1, 2
• Comprehensive metabolic panel including LDH and β2-microglobulin as markers of tumor burden and for prognostic assessment 1, 2
• Uric acid level for tumor lysis syndrome risk assessment 1
• Immunoglobulin levels to assess immune function 1
• Hepatitis B, hepatitis C, and HIV screening as these infections impact treatment decisions, particularly with rituximab-based therapy 1, 2

Bone Marrow Assessment

• Bone marrow aspirate and biopsy of at least 20 mm in length should be performed as part of restaging 1
• Bone marrow involvement affects staging, prognosis, and may influence treatment selection 1, 3

Risk Stratification

• Calculate FLIPI score (>4 involved nodal sites, elevated LDH, age >60 years, stage III/IV, hemoglobin <12 g/dL) for prognostic purposes 1
• Document time to relapse from prior treatment - early relapse (<12-24 months from last treatment) indicates more aggressive disease requiring non-cross-resistant therapy 1
• Assess duration of response to prior rituximab-containing regimen - responses >6-12 months predict benefit from re-treatment with rituximab 1

Clinical Assessment Details

• Document presence of B symptoms (fever >38°C, night sweats, weight loss >10% over 6 months) as these impact staging and indicate need for treatment 1, 2
• Assess for symptomatic organ involvement, vital organ compression, ascites, pleural effusion, or rapid progression - these are indications for immediate treatment rather than observation 1
• Evaluate for hematopoietic impairment (cytopenias) which may indicate need for treatment 1

Common Pitfalls to Avoid

• Do not skip the repeat biopsy - assuming recurrent disease has the same histology as initial diagnosis is a critical error that can lead to inappropriate treatment 1
• Do not use ultrasound as primary imaging for retroperitoneal or deep-seated disease - it is less accurate than CT/PET-CT 3
• Do not delay tissue diagnosis in favor of additional imaging studies - histologic confirmation takes priority 3
• Do not start treatment without definitive histological diagnosis and lymphoma subtype classification 3

Decision Point: Observation vs. Treatment

After completing the workup, treatment is indicated only if the patient has:

• Symptomatic disease with B symptoms 1
• Hematopoietic impairment (cytopenias) 1
• Bulky disease (>6 cm) 1
• Rapid lymphoma progression 1
• Vital organ compression, significant ascites, or pleural effusion 1

Observation remains appropriate for asymptomatic patients with low tumor burden and confirmed follicular histology at relapse, as there is no survival advantage to early treatment 1, 4