Who should a patient with multi-area lymph node enlargement be referred to?

Multi-Area Lymph Node Enlargement: Referral Pathway

Patients with multi-area lymph node enlargement should be referred to hematology-oncology for evaluation of potential lymphoma or systemic malignancy, with consideration for surgical consultation if excisional biopsy is needed for definitive diagnosis. 1, 2

Initial Assessment Before Referral

Before making the referral, document the following critical features:

• Lymph node characteristics: Size (nodes >1.5 cm in long axis or >1.0 cm in short axis warrant urgent evaluation), consistency (hard or matted nodes suggest malignancy), and distribution across multiple anatomical regions 3, 1, 2

• B symptoms: Presence of fever, night sweats, or unintentional weight loss strongly suggests lymphoma and necessitates expedited referral with PET-CT imaging 1, 4, 2

• Duration and pattern: Lymphadenopathy persisting beyond 4 weeks, especially without infectious symptoms, requires specialist evaluation 2

• Immunosuppression history: HIV status, organ transplantation, or immunosuppressive therapy significantly alters the differential diagnosis toward post-transplant lymphoproliferative disorders 1, 4

Referral Algorithm

Immediate Hematology-Oncology Referral (Within Days)

• Supraclavicular or epitrochlear lymphadenopathy (high malignancy risk) 2
• Nodes >2 cm with hard, fixed, or matted consistency 2
• Presence of B symptoms with multi-area involvement 1, 4
• Hepatosplenomegaly on examination 1

Urgent Referral (Within 1-2 Weeks)

• Multi-area lymphadenopathy persisting >4 weeks without clear infectious etiology 2
• Nodes 1.5-2 cm in multiple regions without improvement 1
• Abnormal complete blood count suggesting hematologic malignancy 1, 2

Surgical Consultation Consideration

Excisional biopsy remains the gold standard for definitive diagnosis of lymphoma, as it preserves nodal architecture necessary for accurate classification. 1 Direct surgical referral may significantly reduce diagnostic time compared to sequential needle biopsies—1.25 months versus 3 months in one study 5. This is particularly important when:

• Lymphoma is strongly suspected based on clinical presentation 5
• Fine needle aspiration has been non-diagnostic or equivocal 1
• The patient has a history of prior lymphoma and presents with new multi-area adenopathy 5

Pre-Referral Workup to Expedite Diagnosis

Obtain these studies before or concurrent with referral:

• Laboratory: Complete blood count with differential, comprehensive metabolic panel including LDH, and β2-microglobulin 1
• Imaging: CT chest/abdomen/pelvis for comprehensive nodal and extranodal assessment 1
• Infectious workup: Consider EBV serology, HIV testing, and tuberculosis screening based on clinical context 1, 2

Critical Pitfalls to Avoid

• Do not empirically treat with antibiotics when malignancy is suspected, as this delays diagnosis without benefit 2
• Avoid corticosteroids as they can mask histologic diagnosis of lymphoma 2
• Do not rely on needle biopsy alone for suspected lymphoma—sensitivity is only 67-68% and may require repeat procedures 5
• Do not delay referral for nodes in high-risk locations (supraclavicular, epitrochlear) even if size is borderline 2

Coordination with Specialists

The hematology-oncology team will coordinate multidisciplinary evaluation including pathology review, flow cytometry, immunohistochemistry, and molecular studies necessary for lymphoma classification 3, 1. If excisional biopsy is required, ensure fresh tissue is sent in saline (not formalin) for flow cytometry and additional studies 6.