Are all lymph nodes involved when a patient is diagnosed with lymphoma?

Lymphoma Does Not Involve All Lymph Nodes

No, lymphoma does not involve all lymph nodes at diagnosis—the disease can be localized to one or a few nodal regions (limited stage) or widespread (advanced stage), and staging determines the anatomic extent of nodal involvement. 1

Staging Determines Nodal Distribution

The modified Ann Arbor/Lugano classification system categorizes lymphoma based on the number and location of involved lymph nodes 1:

Limited Stage Disease

• Stage I: One lymph node or a group of adjacent nodes involved 1
• Stage II: Two or more nodal groups on the same side of the diaphragm 1
• Stage II bulky: Stage II disease with bulky features (largest tumor diameter should be recorded) 1

Advanced Stage Disease

• Stage III: Nodes on both sides of the diaphragm, or nodes above the diaphragm with spleen involvement 1
• Stage IV: Additional noncontiguous extralymphatic involvement beyond nodal disease 1

Clinical Presentation Varies by Stage

Lymphoma typically presents as painless adenopathy, which may be localized or generalized depending on stage 2:

• Approximately 40-50% of patients present with limited stage (I-II) disease, meaning only one or a few nodal regions are involved 1
• Systemic B symptoms (fever, unexplained weight loss, night sweats) occur more commonly in advanced stages but are not universal 1
• The designation of A (absence) or B (presence) of constitutional symptoms is only required for Hodgkin lymphoma, as these symptoms do not confer unfavorable outcomes in most non-Hodgkin lymphoma prognostic indices 1

Diagnostic Workup Identifies Extent of Disease

PET-CT is the standard imaging modality for FDG-avid lymphomas to determine which lymph nodes are involved 1:

• CT alone is indicated for non-avid histologies 1
• Tonsils, Waldeyer's ring, and spleen are considered nodal tissue in the staging system 1
• Bone marrow biopsy is no longer routinely indicated for Hodgkin lymphoma if PET-CT is performed; for diffuse large B-cell lymphoma, it's only needed if PET is negative and identifying discordant histology is clinically relevant 1

Treatment Allocation Based on Disease Extent

Patients are treated according to limited versus advanced disease, not strictly by Ann Arbor stage 1:

• Limited disease (stages I-II nonbulky) receives less intensive therapy
• Advanced disease (stages III-IV, or stage II bulky) receives more intensive systemic treatment
• Stage II bulky disease may be treated as either limited or advanced depending on histology and prognostic factors 1

Specific Lymphoma Subtypes Show Distinct Patterns

T-Cell Lymphoblastic Lymphoma

• Characteristically presents with a mediastinal mass and is far more frequent than B-cell lymphoblastic lymphoma 3
• Distinguished from acute lymphoblastic leukemia by predominantly nodal distribution with less than 25% bone marrow involvement 4

Hodgkin Lymphoma

• Often presents with contiguous nodal spread (one region to adjacent regions) 1
• Mediastinal involvement is common, with mediastinal mass ratio >0.33 considered an unfavorable risk factor 1

Critical Pitfall to Avoid

Do not assume all lymph nodes are involved simply because a patient has lymphoma—approximately 40-50% of patients have localized disease at presentation, and accurate staging with appropriate imaging (PET-CT for avid histologies) is essential to determine treatment intensity and prognosis 1, 2. The extent of nodal involvement fundamentally determines whether a patient receives limited-field radiation with abbreviated chemotherapy versus intensive systemic therapy 1.