What are the major differential diagnoses for an enlarged tender posterior cervical lymph node?

Differential Diagnosis of Enlarged Tender Posterior Cervical Lymph Node

The major differential diagnoses for an enlarged tender posterior cervical lymph node include infectious causes (particularly toxoplasmosis, nontuberculous mycobacteria, Epstein-Barr virus, and bacterial lymphadenitis), lymphoma, and less commonly Kikuchi-Fujimoto disease, with the specific location in the posterior cervical chain being particularly characteristic of toxoplasmosis. 1

Infectious Etiologies (Most Common)

Toxoplasmosis

• Posterior cervical node enlargement is the characteristic presentation of clinical toxoplasmosis in adults, with a distinctive pattern of sinus histiocytosis seen in 17 of 18 posterior cervical nodes in confirmed cases 1
• This specific anatomical location is highly suggestive, as the characteristic histologic pattern was found in posterior cervical nodes but only 1 of 4 lymph nodes from other sites in toxoplasmosis patients 1
• Consider serologic testing and the clinical context of exposure to cats or undercooked meat 1

Nontuberculous Mycobacterial (NTM) Lymphadenitis

• Approximately 80% of culture-proven NTM lymphadenitis cases are due to Mycobacterium avium complex (MAC), with the disease typically presenting as unilateral (95% of cases) and generally not tender nodes 2, 3
• However, the posterior cervical location can occur, and a unilateral single or multiple painless lump, mostly located in posterior cervical or supraclavicular region, is characteristic 4
• The disease occurs insidiously and is rarely associated with systemic symptoms 2
• Tuberculin skin testing should be performed, though children with NTM lymphadenitis show variable reactions from negative to positive 2

Tuberculous Lymphadenitis

• Must be distinguished from NTM because it requires drug therapy and public health tracking 2
• In adults, more than 90% of culture-proven mycobacterial lymphadenitis is due to M. tuberculosis 2
• Look for history of TB exposure, positive tuberculin PPD skin tests in family members, and chest radiograph abnormalities 2

Viral Infections

• Epstein-Barr virus (infectious mononucleosis) commonly causes cervical lymphadenopathy 5
• Other viral causes include measles, adenovirus, and enterovirus 5

Bacterial Lymphadenitis

• Can mimic other causes of cervical lymphadenopathy and typically presents with rapid onset, fever, tenderness, and overlying erythema 3, 5

Kikuchi-Fujimoto Disease

• A self-limited disease of unknown etiology clinically defined by fevers accompanied by tender posterior cervical lymphadenopathy 6
• Often presents acutely or sub-acutely with non-specific features 6
• The differential diagnosis is broad and includes infectious, autoimmune, and malignant causes 6

Malignant Etiologies

Lymphoma (Hodgkin and Non-Hodgkin)

• Represents a primary concern, particularly with persistent lymphadenopathy 5
• B symptoms (fever, night sweats, weight loss) strongly suggest lymphoma and require PET/CT imaging 5, 7
• Post-transplant lymphoproliferative disorders should be considered in immunosuppressed patients and include reactive plasmacytic hyperplasia, infectious mononucleosis-like lesions, and various B-cell and T-cell lymphomas 2, 5

Metastatic Disease

• Thyroid cancer should be considered, as enlarged cervical lymph nodes >1 cm are found in 46.5% of patients with papillary thyroid cancer 8
• Other head and neck primary malignancies warrant consideration based on age, tobacco use, and alcohol abuse 7

Autoimmune/Inflammatory Causes

Rosai-Dorfman-Destombes Disease (RDD)

• Most patients present with bilateral, massive, and painless cervical lymphadenopathy with or without intermittent fevers, night sweats, and weight loss 2
• Mediastinal, axillary, and inguinal nodes may also be involved 2

Other Inflammatory Conditions

• Sarcoidosis, Kawasaki disease (particularly in children with nodes ≥1.5 cm), and drug hypersensitivity reactions 5

Critical Decision Points

Size Thresholds

• A lymph node ≥1.5 cm that has persisted for ≥2 weeks without significant fluctuation places a patient at increased risk for malignancy or chronic infection 3, 7
• Nodes >25 mm are always pathologic, while nodes ≤15 mm are typically reactive 5

Red Flags Requiring Urgent Workup

• Fixed, firm, or ulcerated nodes are suspicious and warrant immediate investigation 3
• Loss of fatty hilum, round shape (rather than oval), heterogeneous echogenicity on ultrasound, and central necrosis strongly suggest malignancy 5
• Age over 40 years, tobacco use, alcohol abuse, and B symptoms mandate aggressive workup 7

Common Pitfalls to Avoid

• Do not empirically treat with antibiotics in the absence of signs suggesting acute bacterial infection (rapid onset, fever, tenderness, overlying erythema) 3
• Do not rely on size alone, as normal-sized nodes can harbor microscopic metastases and enlarged nodes may be hyperplastic 5
• Mistaking NTM lymphadenitis for bacterial infection and treating with inappropriate antibiotics is a common error 3
• Partial resolution after antibiotics may represent infection in an underlying malignancy, so proceed to definitive workup if the node has not completely resolved 3

Recommended Diagnostic Approach

• Obtain tuberculin skin testing to help distinguish tuberculous from nontuberculous mycobacterial disease 2, 4
• Consider toxoplasmosis serologic testing given the posterior cervical location 1
• Fine-needle aspiration can provide initial cytopathology, though excisional biopsy remains the gold standard for definitive diagnosis 2, 7
• CT neck with IV contrast evaluates deep extension and assesses for matted nodes 7
• Schedule follow-up within 2 weeks to evaluate for resolution, progression, or persistence 3