What are the common clinical presentations and treatment options for lymphoma?

Clinical Presentation of Lymphoma

Lymphoma most commonly presents as painless, progressive lymphadenopathy affecting multiple nodal regions, which is the hallmark finding that should prompt immediate diagnostic workup. 1, 2

Key Clinical Features by Presentation Pattern

Nodal Presentation (Most Common)

• Painless lymph node enlargement is the cardinal feature, typically involving multiple nodal regions simultaneously 1, 3
• Cervical, axillary, and inguinal nodes are most frequently affected, though any nodal group can be involved 4
• Nodes are typically firm, rubbery, and mobile in early disease but may become matted or fixed to surrounding structures in advanced cases 5
• Supraclavicular or epitrochlear lymphadenopathy is particularly concerning for malignancy and warrants urgent evaluation 5

Systemic B Symptoms (Indicate Advanced Disease)

• Fever >38°C without identifiable infection 1
• Drenching night sweats requiring clothing or bedding changes 1
• Unintentional weight loss >10% of body weight over 6 months 1, 2
• These symptoms occur more commonly in Hodgkin lymphoma than non-Hodgkin lymphoma and indicate worse prognosis 6

Hematologic Manifestations

• Cytopenias from bone marrow involvement: anemia, thrombocytopenia, or leukopenia 1
• Fatigue and weakness from anemia 2
• Increased infection risk from immune dysfunction 2

Bulky Disease Presentations

• Masses >7-10 cm indicate high tumor burden and necessitate treatment 1
• Mediastinal masses may cause cough, dyspnea, or superior vena cava syndrome 6
• Abdominal masses can present with early satiety, pain, or bowel obstruction 4

Critical Diagnostic Pitfalls to Avoid

The Fine Needle Aspiration Trap

Never rely on fine needle aspiration or core biopsy for initial lymphoma diagnosis—these are inadequate and should only be used in emergency situations. 1, 3 An excisional lymph node biopsy providing adequate tissue for both formalin-fixed and fresh frozen samples is mandatory for proper diagnosis and subtyping 7, 3. Core biopsies should only be considered when lymph nodes are not easily accessible (e.g., retroperitoneal masses) 1.

The Antibiotic Error

Do not empirically treat suspected lymphoma with antibiotics, as this delays diagnosis without benefit 5. If bacterial lymphadenitis is genuinely suspected based on acute onset, tenderness, and overlying erythema, a short trial may be appropriate, but lymphadenopathy persisting beyond 4 weeks mandates biopsy 5.

The Corticosteroid Catastrophe

Never give corticosteroids before obtaining tissue diagnosis—they can mask the histologic features of lymphoma and render the biopsy non-diagnostic. 5 This forces repeat biopsy after steroid washout, significantly delaying treatment.

Specific Presentations by Lymphoma Subtype

Diffuse Large B-Cell Lymphoma (30-58% of NHL)

• Rapidly progressive lymphadenopathy over weeks to months 7
• Extranodal involvement in 30-40% of cases, commonly affecting GI tract, bone, CNS, or testis 7
• More likely to present with B symptoms compared to indolent lymphomas 2
• Incidence increases dramatically with age: 0.3/100,000 at age 35-39 years to 26.6/100,000 at age 80-84 years 7

Follicular Lymphoma (Second Most Common NHL Subtype)

• Indolent course with waxing and waning lymphadenopathy over months to years 1
• 15-20% show spontaneous regression, making observation appropriate for asymptomatic patients 7, 1
• Bone marrow involvement is common (40-70% at diagnosis) 7
• Transformation to aggressive lymphoma (Richter transformation) occurs in 2-3% per year and presents as rapidly enlarging nodes, new B symptoms, or rising LDH 1

Hodgkin Lymphoma

• Orderly, contiguous spread through adjacent lymph node groups is characteristic 6
• Mediastinal involvement in 60-70% of cases 6
• B symptoms more common than in NHL (approximately 30-40% of cases) 6
• Pruritus without rash occurs in 10-15% and may precede other symptoms by months 6

When to Suspect Lymphoma

High-Risk Features Requiring Urgent Evaluation

• Lymph nodes >2 cm that persist beyond 4 weeks 5
• Hard, fixed, or matted nodes 5
• Supraclavicular or epitrochlear location 5
• Associated B symptoms 1, 2
• Progressive enlargement despite observation 1
• Elevated LDH without alternative explanation 7, 3

Moderate-Risk Features

• Multiple nodal regions involved 1
• Nodes 1-2 cm persisting beyond 6-8 weeks 5
• Age >40 years with new unexplained lymphadenopathy 5
• Absence of infectious symptoms (no pain, erythema, warmth) 5

Essential Workup Once Lymphoma is Suspected

Mandatory Initial Studies

• Excisional lymph node biopsy with adequate tissue for histology, immunohistochemistry (minimum CD45, CD20, CD3), and molecular studies 7, 3
• CT chest/abdomen/pelvis for staging 7, 3
• Bone marrow aspirate and biopsy 7, 3
• Complete blood count, comprehensive metabolic panel, LDH, uric acid 7, 3
• HIV, hepatitis B, and hepatitis C screening (mandatory before rituximab therapy) 7, 8

Additional Studies for High-Risk Features

• Diagnostic lumbar puncture with intrathecal chemoprophylaxis for patients with >2 adverse IPI factors, bone marrow involvement, testicular involvement, or paraspinal/skull base disease 7
• PET-CT for accurate staging, particularly in Hodgkin lymphoma and aggressive NHL 1
• Echocardiogram or MUGA scan before anthracycline-based chemotherapy 2

Prognostic Assessment

International Prognostic Index (IPI) for Aggressive Lymphomas

Calculate using 5 factors (1 point each): 7, 3

• Age >60 years
• Stage III or IV disease
• Elevated LDH
• ECOG performance status ≥2

• 1 extranodal site

Follicular Lymphoma International Prognostic Index (FLIPI)

Calculate using 5 factors (1 point each): 1

• Age >60 years
• Stage III-IV disease
• Hemoglobin <12 g/dL

• 4 nodal areas involved

• Elevated LDH