What is lymphoma and how is it assessed?

What is Lymphoma and How to Assess It

Definition of Lymphoma

Lymphoma is a malignant neoplasm of lymphocytes comprising over 90 distinct subtypes, broadly classified into non-Hodgkin lymphoma (90% of cases) and Hodgkin lymphoma (10% of cases), with approximately 90% originating from B-cells and the remainder from T-cells or natural killer cells. 1, 2

• The disease can present in either aggressive or indolent forms, with fundamentally different treatment approaches—aggressive lymphomas are managed with curative intent due to their chemosensitivity, while indolent lymphomas are largely incurable and require balancing quality of life against treatment toxicity 1

Diagnostic Assessment

Tissue Acquisition for Diagnosis

An excisional or incisional biopsy is mandatory for initial lymphoma diagnosis—fine-needle aspiration alone is inadequate and should never be used as the sole diagnostic procedure. 3, 4

• Core-needle biopsy may be considered only when excisional biopsy is not feasible or to document relapse, but a nondiagnostic sample must be followed by excisional or incisional biopsy 3
• Fine-needle aspiration combined with core biopsy and ancillary techniques (immunohistochemistry, flow cytometry, PCR for gene rearrangements, FISH) may suffice only in highly selected circumstances when lymph nodes are inaccessible, particularly for chronic lymphocytic leukemia 3

Pathologic Evaluation

Diagnosis requires comprehensive evaluation by an experienced lymphoma pathologist incorporating morphology, immunohistochemistry, flow cytometry, and molecular studies to accurately categorize the lymphoma subtype. 3, 4

• Immunophenotypic analysis is essential for differentiating NHL subtypes and must include Pan-B and Pan-T-cell antigens, with additional B- and T-cell subset antigens based on morphologic features (cell size: small, medium, or large; presence of anaplastic morphology) and clinical features (patient age, nodal vs. extranodal location) 3
• Cytogenetic or molecular genetic analysis identifies characteristic chromosomal translocations and establishes clonality 3

Clinical Evaluation

History

Obtain a comprehensive history documenting constitutional "B symptoms": fevers exceeding 101°F (38.3°C), drenching night sweats, and unexplained weight loss greater than 10% of body mass over 6 months. 3, 4

• For Hodgkin lymphoma specifically, document fatigue, pruritus, and alcohol-induced pain, as their recurrence may herald disease relapse 3
• Record age, sex, performance status, and history of prior malignancy 3, 4

Physical Examination

Measure all accessible lymph node groups in centimeters and assess liver and spleen size in centimeters below their respective costal margins in the midclavicular line. 3, 4

• Physical examination alone has variable sensitivity among observers—organomegaly must be formally confirmed by CT imaging 3

Laboratory Studies

Essential laboratory workup includes: complete blood count, serum lactate dehydrogenase, comprehensive metabolic panel, hepatitis B surface antigen and hepatitis B core antibody testing. 3, 4

• Hepatitis B testing is mandatory before initiating anti-CD20 monoclonal antibody-based regimens due to reactivation risk, and reactivation can occur with chemotherapy alone 3
• MUGA scan or echocardiogram is required when anthracycline or anthracenedione-containing regimens are planned 3

Staging Assessment

Imaging

PET-CT is the gold standard for staging all FDG-avid nodal lymphomas (essentially all histologies except chronic lymphocytic leukemia) and must be performed as baseline before therapy to enable accurate subsequent response assessment. 3, 4

• PET-CT improves staging accuracy compared to CT alone for both nodal and extranodal sites, changing stage in 10-30% of patients (more often upstaging), which ensures fewer patients are undertreated or overtreated 3
• For non-FDG-avid lymphomas, CT chest/abdomen/pelvis with oral and intravenous contrast is the preferred imaging modality (unless coexistent renal insufficiency) 3, 4
• PET-CT is particularly critical before consideration of radiation therapy 3

Bone Marrow Assessment

Bone marrow biopsy with or without aspirate is essential whenever treatment is considered, though it may be deferred in certain circumstances. 3

• PET-CT is adequate for determination of bone marrow involvement in FDG-avid lymphomas and can be considered highly suggestive for involvement of other extralymphatic sites 3

Staging Classification

The Ann Arbor staging system remains the foundation for classification, with the Lugano classification incorporating modern PET-CT findings into staging criteria. 3, 4

• Staging defines disease as limited (stages I and II, nonbulky) or advanced (stage III or IV), with stage II bulky disease considered either limited or advanced based on histology and prognostic factors 3
• Document presence of bulky disease and B symptoms as part of staging 3, 4

Critical Pitfalls to Avoid

Never rely solely on physical examination for lymph node assessment or use fine-needle aspiration as the sole diagnostic procedure. 4

• Failing to obtain adequate tissue for comprehensive pathologic evaluation compromises accurate subtype classification 4
• Not performing baseline PET-CT before therapy in FDG-avid lymphomas prevents accurate response assessment 4
• Omitting hepatitis B testing before anti-CD20 therapy risks potentially fatal viral reactivation 3