What are the diagnostic steps and treatment options for a patient suspected of having lymphoma?

Diagnostic Steps and Treatment Options for Suspected Lymphoma

The definitive diagnosis of lymphoma requires an excisional lymph node biopsy, followed by comprehensive imaging and laboratory studies to determine the extent of disease and guide treatment selection. 1, 2

Initial Diagnostic Approach

Clinical Assessment

• Comprehensive history focusing on constitutional symptoms (fevers, night sweats, unexplained weight loss >10% of body weight over 6 months, fatigue, pruritus) is essential for identifying B symptoms that impact staging and prognosis 1
• Thorough physical examination with measurement of all accessible lymph node groups and assessment of spleen and liver size is necessary 1

Laboratory Studies

• Complete blood count with differential to assess for cytopenias or leukocytosis 1, 2
• Comprehensive metabolic panel including LDH, uric acid, liver and kidney function tests 1, 3
• Mandatory screening for HIV, hepatitis B and C 2, 3
• Protein electrophoresis is recommended for B-cell lymphomas 4

Tissue Diagnosis

• Excisional lymph node biopsy is the gold standard and should be the first step in lymphoma workup 2, 3
• Core biopsies should only be performed when lymph nodes are not easily accessible 2, 3
• Fine needle aspirations are inappropriate for proper diagnosis and should only be used in rare emergency situations 2, 5
• Fresh frozen tissue should be stored when possible to allow for additional molecular analyses 2, 3
• The histological report should follow the World Health Organization classification 4, 3

Imaging Studies

• CT scan of neck, chest, abdomen, and pelvis with contrast is the minimum imaging requirement 1, 3
• PET-CT is preferred for staging and is particularly valuable for:
  • Confirming localized stage I/II disease
  • Identifying areas with high standardized uptake values suspected of disease transformation
  • Serving as a baseline for response assessment 4, 2

Bone Marrow Assessment

• Bone marrow aspirate and biopsy should be performed to determine disease extent 4, 3
• Given the high sensitivity of PET-CT for bone marrow involvement, bone marrow biopsy may not be necessary if PET-CT is available 2

Additional Evaluations

• For suspected CNS involvement: lumbar puncture for cerebrospinal fluid analysis and CT/MRI scan of the head with contrast 2, 3
• For suspected gastrointestinal involvement: gastrointestinal endoscopy 2, 3
• For male patients: evaluation for testicular involvement 2, 3

Staging and Risk Assessment

• Staging should be performed according to the Ann Arbor classification system 4
• For prognostic purposes, the International Prognostic Index (IPI) should be established for diffuse large B-cell lymphoma 4
• For follicular lymphoma, the Follicular Lymphoma-specific International Prognostic Index (FLIPI) should be determined 2, 3

Treatment Options

Diffuse Large B-Cell Lymphoma (DLBCL)

• For CD20+ DLBCL of all stages: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) given every 21 days for 6-8 cycles is the standard treatment 4, 6
• For young low-risk patients (aaIPI = 0) without bulky disease: six cycles of R-CHOP 4
• For young low-intermediate-risk patients (aaIPI = 1) or IPI low risk (aaIPI = 0) with bulky disease: either R-CHOP21 × 6 with radiotherapy to sites of previous bulky disease or intensified regimen R-ACVBP 4
• For young high- and high-intermediate-risk patients (aaIPI ≥ 2): six to eight cycles of R-CHOP 4
• For T-cell lymphoma: CHOP remains the standard treatment 4

Relapsed/Refractory DLBCL

• For suitable patients (no major organ dysfunction, age <65 years): conventionally-dosed salvage chemotherapy followed by high-dose treatment with stem cell support in responsive patients 4
• Salvage regimens include R-DHAP, R-ESHAP, R-EPOCH, R-ICE 4
• For patients not suitable for high-dose therapy: conventionally-dosed salvage regimens possibly combined with involved field radiotherapy 4

Follicular Lymphoma

• For limited stage I: extended field radiotherapy with curative potential 4
• For advanced stages: chemotherapy should be initiated only upon occurrence of symptoms, hematopoietic impairments, bulky disease, or lymphoma progression 4

Response Evaluation and Follow-up

Response Evaluation

• Adequate radiological tests should be done after 2-4 cycles and after completion of chemotherapy 4
• Initially pathologic bone marrow aspirate/biopsy or spinal tap should be repeated at the end of treatment 4
• Patients with incomplete or lacking response should be evaluated for early salvage regimens 4

Follow-up

• History and physical examination every 3 months for 2 years, every 6 months for 3 more years, then once a year 4
• Blood count and LDH at 3,6,12, and 24 months, then as needed 4
• Evaluation of thyroid function in patients with irradiation to the neck at 1,2, and 5 years 4
• CT scan at 6,12, and 24 months after end of treatment 4
• For patients who received chest irradiation at premenopausal age: screening for secondary breast cancers clinically and by mammography after age 40-50 4

Common Pitfalls and Caveats

• Core biopsies and fine needle aspirations often provide insufficient tissue for comprehensive diagnosis and should be avoided when excisional biopsy is feasible 2, 5
• Dose reductions due to hematological toxicity should be avoided to maintain treatment efficacy 4
• Febrile neutropenia justifies prophylactic use of hematopoietic growth factors in patients treated with curative intent 4
• Patients with high tumor burden require precautions to prevent tumor lysis syndrome 4
• Long-term follow-up is essential to monitor for late complications including secondary malignancies 4, 7