Differential Diagnosis: Tender Multiple Swellings on the Lateral Side of the Neck

Key Examination Principle

1. Infectious / Inflammatory (Most Common - especially if TENDER)

A. Reactive Lymphadenopathy (Most Likely)

• The lymphatic channels of the neck drain the face, paranasal sinuses, oral cavity, and upper aerodigestive tract
• Any infection of these areas can cause reactive, palpable, mobile, tender cervical nodes with fever, rhinorrhea, otalgia, odynophagia, or dysphagia
• Nodes are typically soft, mobile, and bilateral

B. Suppurative Lymphadenitis

• Node becomes necrotic → abscess forms
• Fluctuant if liquefied, firm if not yet
• More common in bacterial than viral lymphadenopathy
• Seen on US as hypoechoic collection; CT shows rim enhancement
• Requires antibiotics ± incision and drainage

C. Infectious Causes by Organism

• Staphylococcus aureus, Group A Streptococcus (commonest)
• Bartonella henselae - Cat scratch disease (unilateral, very tender)
• Tularemia, Brucellosis, Typhoid, Bubonic plague (rare but important)
• Leptospirosis, Chancroid, LGV, Diphtheria

• Epstein-Barr virus (Infectious Mononucleosis) - classic posterior cervical and anterior cervical tender LAP, splenomegaly, exudative tonsillitis
• CMV - similar mononucleosis-like picture
• HIV - acute retroviral syndrome causes tender generalized LAP
• Herpes simplex, Hepatitis B, Measles, Mumps, Rubella, Dengue

• Tuberculosis (Scrofula) - TB cervical lymphadenitis is the most common extrapulmonary TB; may start tender, later matted/fixed; can develop collar-stud abscess with violaceous skin changes
• Nontuberculous Mycobacteria (M. avium, M. kansasii, M. intracellulare) - more common in children; skin shows violaceous discoloration

• Histoplasmosis, Cryptococcosis, Coccidioidomycosis (in endemic areas or immunocompromised)

• Toxoplasmosis - classically posterior cervical tender LAP
• Leishmaniasis

• Lyme disease (erythema migrans + LAP)
• Secondary syphilis (bilateral, rubbery, non-tender usually but can be tender)

2. Granulomatous Diseases

3. Congenital / Developmental (Lateral - can become tender if infected)

4. Salivary Gland Pathology

• Sialadenitis / Sialolithiasis (parotid or submandibular): Obstruction of Wharton's duct (submandibular) or Stensen's duct (parotid) → swelling tender at Level I/II; worse with eating; US shows calculus
• Parotitis (bacterial or viral/mumps): Pre-auricular and lateral facial/neck swelling, very tender, trismus
• Sialadenosis / Sjögren's: Usually bilateral, less tender

5. Neoplastic (Usually NON-tender, but large/rapidly growing nodes can be tender)

6. Autoimmune / Systemic

7. Other Lateral Neck Structures to Consider

Summary: Approach Based on Tenderness + Multiple Nodes

Tender + multiple nodes → MOST LIKELY:
  1. Reactive viral/bacterial lymphadenopathy (URTI, pharyngitis, dental)
  2. Suppurative lymphadenitis (Staph, Strep)
  3. Infectious mononucleosis (EBV)
  4. Acute HIV seroconversion
  5. TB lymphadenitis (early stage)
  6. Infected branchial cyst
  7. Cat scratch disease
  8. Kawasaki disease (children)
  9. Kikuchi-Fujimoto disease
 10. Drug-induced lymphadenopathy

Differential Diagnosis: Chronic Tender Lateral Neck Swellings (7 Months)

Top Priority Diagnoses

1. Tuberculous Lymphadenitis (Scrofula) - #1 Suspect

• Most common form of extrapulmonary TB (35% of cases worldwide, >40% in the US)
• Classically: painless nodes, but can be tender in early/active disease or with secondary infection
• Progression pattern over months:
  • Early: discrete, soft, mobile nodes
  • Later: matted, firm, nontender mass
  • Advanced: collar-stud abscess, fistulous tract draining caseous material
• Posterior cervical and supraclavicular nodes most commonly affected
• Associated pulmonary disease in <50% of cases - systemic symptoms (fever, night sweats, weight loss) may be absent
• NTM (Non-tuberculous Mycobacteria) - M. avium, M. intracellulare - causes a very similar picture, more common in children in Western countries; skin shows characteristic violaceous discoloration

2. Lymphoma - Must Rule Out

• Hodgkin lymphoma: Young adults (bimodal: 15-35 yr and >55 yr); rubbery, painless nodes classically; can feel tender with rapid growth; B-symptoms in ~25% - fever >38°C, drenching night sweats, >10% weight loss
• Non-Hodgkin lymphoma: Wider age range; can be bilateral lateral neck nodes; often more systemic
• Nodes typically firm, rubbery, non-tender - but tenderness after alcohol ingestion is a classic (though rare) feature of Hodgkin lymphoma

3. Chronic/Subacute Granulomatous Diseases

4. Kikuchi-Fujimoto Disease (Histiocytic Necrotizing Lymphadenitis)

• Disease of unknown origin, most common in young women
• Cervical lymphadenopathy (can be tender), fever, flu-like symptoms, rash
• Usually resolves within weeks to months - so 7 months is at the outer edge
• Diagnosis by excision biopsy: histiocytic necrotizing lymphadenitis without neutrophils
• Important to distinguish from lymphoma and lupus

5. Castleman Disease

• Rare lymphoproliferative disorder
• Unicentric form: single enlarged lymph node group (mediastinum or neck), can be tender
• Multicentric form: systemic, with fever, hepatosplenomegaly, generalized LAP
• Diagnosis by excision biopsy

6. IgG4-Related Disease

• Systemic immune-mediated fibrosing inflammatory condition
• Accompanied by asymptomatic or mildly tender lymphadenopathy
• May involve salivary glands (Mikulicz disease) - submandibular/parotid swelling alongside neck nodes
• Responds to corticosteroids
• Serum IgG4 elevated

7. Metastatic Malignancy (Lower probability if tender, but cannot exclude)

• Carcinoma of nasopharynx, oropharynx, thyroid, or larynx metastasizing to lateral cervical nodes
• Usually hard, fixed, non-tender - but painful if nerve involvement or rapid growth
• Nasopharyngeal carcinoma characteristically presents with posterior lateral cervical node metastasis as the first sign, sometimes bilateral
• Supraclavicular nodes: metastasis from lung, GI, or breast primaries

8. Kimura Disease

• Rare chronic inflammatory disorder; young Asian males
• Unilateral or bilateral cervical lymphadenopathy + soft tissue swelling + peripheral eosinophilia + elevated IgE
• Can persist for years; benign but recurrent

9. HIV-Related Lymphadenopathy

• Persistent Generalized Lymphadenopathy (PGL): bilateral symmetric involvement of >2 extra-inguinal sites for >3 months
• Tender or non-tender; part of chronic HIV infection
• Should always be on the differential in at-risk individuals

Ranked Differential for 7-Month Tender Lateral Neck Nodes

Mandatory Workup at This Stage

1. FNAC - first-line; AFB smear/culture, cytology, Xpert MTB/RIF
2. Mantoux test / IGRA (QuantiFERON-TB Gold)
3. CBC with differential - eosinophilia (Kimura), leukemia, lymphocytosis
4. CXR - hilar LAP (TB, sarcoidosis), pulmonary TB
5. CECT neck - nodal characteristics, matting, necrosis, vascular lesions
6. HIV serology
7. LFT, LDH, ESR, CRP, serum ACE
8. Serum IgG4 if other features suggest IgG4-RD
9. Excision biopsy if FNAC is non-diagnostic - mandatory to exclude lymphoma

The Harrison's Principles of Internal Medicine (22E) differential for chronic cervical lymphadenopathy explicitly lists: "lymphomas or metastatic carcinomas, and rare disorders like Kikuchi disease, Kimura disease, and Castleman disease" alongside TB as the key chronic conditions to consider.