Cervical Lymphadenopathy in Children

1. Clinical Overview

Cervical lymphadenopathy is one of the most common clinical presentations in paediatric practice, representing a diagnostic challenge with a broad differential diagnosis ranging from benign reactive hyperplasia to life-threatening malignancy. Palpable cervical lymph nodes are present in 38-45% of healthy children, with the highest prevalence in preschool-aged children. [1,2]

The clinical significance lies in distinguishing the overwhelming majority of benign, self-limiting reactive nodes from rare but serious pathology. Approximately 55-90% of paediatric cervical lymphadenopathy is reactive and infectious in origin, 5-10% is due to bacterial lymphadenitis, 5% is attributed to atypical mycobacterial infection, and less than 1% represents malignancy in primary care settings. However, in specialist referral centres, the incidence of malignancy rises to 5-10%. [3,4]

The clinician's primary role is systematic risk stratification through careful history, thorough examination, and judicious investigation to identify red flag features that warrant urgent referral while avoiding overinvestigation of benign nodes. Understanding the anatomical drainage patterns, age-specific differential diagnoses, and evidence-based investigation pathways is essential for safe and cost-effective management.

Key Clinical Messages

• Location matters: Supraclavicular nodes are pathological until proven otherwise, with malignancy rates of 50-75% in children. [5]
• Size thresholds: Nodes less than 1cm are generally normal; 1-2cm suggest reactive hyperplasia; > 2cm require monitoring; > 3cm warrant urgent investigation. [6]
• Character is critical: Reactive nodes are soft, mobile, tender, and associated with infection; malignant nodes are firm, fixed, non-tender, and progressive.
• Context is key: Generalised lymphadenopathy with hepatosplenomegaly suggests systemic disease (leukaemia, EBV) rather than localised infection.

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2. Epidemiology

Demographics and Prevalence

Age-Related Patterns

Infants (0-12 months):

• Less common overall due to limited pathogen exposure
• When present, consider congenital infections (CMV, toxoplasmosis), Kawasaki disease, or infantile sarcoidosis (rare)
• Malignancy includes neuroblastoma, congenital leukaemia (rare)

Toddlers and Preschool (1-5 years):

• Highest prevalence of palpable nodes due to frequent viral URTIs
• Peak age for atypical mycobacterial lymphadenitis (18 months to 4 years)
• Reactive lymphadenopathy most common

School Age (6-12 years):

• Continued high prevalence of reactive nodes
• Bacterial lymphadenitis from dental infections increases
• EBV/CMV infectious mononucleosis emerges
• Malignancy risk begins to increase (ALL, non-Hodgkin lymphoma)

Adolescents (> 12 years):

• Decreasing prevalence of palpable nodes overall
• Increasing incidence of Hodgkin lymphoma (peak 15-30 years)
• Cat scratch disease common
• Toxoplasmosis in at-risk populations

Geographic and Ethnic Variations

• Tuberculosis lymphadenitis: Higher in endemic regions, immigrant populations, and contacts of active TB [10]
• Atypical mycobacteria: More common in temperate climates (M. avium complex predominates in Europe/North America) [9]
• Kikuchi-Fujimoto disease: Higher prevalence in Asian populations [11]

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3. Aetiology and Pathophysiology

Anatomical Organisation

The cervical lymphatic system is organized into well-defined nodal groups, each draining specific anatomical regions:

Anterior Cervical Chain:

• Drains: Tonsils, pharynx, oral cavity, anterior tongue
• Most common site of reactive lymphadenopathy
• Associated infections: Viral URTI, tonsillitis, pharyngitis, dental infections

Posterior Cervical Chain:

• Drains: Scalp, posterior pharynx, nasopharynx
• Common causes: EBV, CMV, toxoplasmosis, scalp infections (impetigo, pediculosis)
• Bilateral posterior chain enlargement suggests infectious mononucleosis

Submandibular/Submental:

• Drains: Lower lip, floor of mouth, teeth, anterior tongue
• Common causes: Dental abscess, gingivitis, pericoronitis, oral HSV

Supraclavicular:

• Right: Drains mediastinum, lungs, oesophagus via right lymphatic duct
• Left (Virchow's node): Drains thorax, abdomen, pelvis via thoracic duct
• Always pathological: Lymphoma (40-50%), neuroblastoma (20-30%), rhabdomyosarcoma, germ cell tumours [5]

Preauricular:

• Drains: Eyelids, conjunctiva, temporal region
• Common causes: Adenoviral conjunctivitis, cat scratch disease (Parinaud oculoglandular syndrome), rubella

Pathophysiological Classification

1. Reactive Hyperplasia (55-70%)

Viral Infections (Most Common):

• Adenovirus, rhinovirus, coronavirus, influenza (upper respiratory tract infections)
• Epstein-Barr virus (EBV): Causes infectious mononucleosis with generalised lymphadenopathy, pharyngitis, splenomegaly, atypical lymphocytosis [12]
• Cytomegalovirus (CMV): Similar to EBV but often heterophile-negative
• Human herpesvirus 6 (HHV-6): Roseola infantum with post-auricular and occipital nodes
• Rubella: Post-auricular, suboccipital nodes with maculopapular rash
• Measles: Generalised lymphadenopathy with characteristic rash

Mechanism: Antigenic stimulation leads to lymphocyte proliferation within germinal centres. Nodes remain mobile, preserve normal architecture on imaging (oval shape, preserved fatty hilum), and regress with resolution of infection.

2. Bacterial Lymphadenitis (5-10%)

Common Organisms:

• Staphylococcus aureus (40-50%): Including MRSA in some regions
• Streptococcus pyogenes (Group A Streptococcus) (30-40%)
• Anaerobes: Associated with dental infections
• Streptococcus pneumoniae: Less common

Mechanism: Direct bacterial invasion or haematogenous spread causes acute inflammation within the node. Progression: lymphadenitis → suppuration → abscess formation with potential skin breakdown or extension to deep neck spaces. [13]

Clinical Features: Rapid onset, unilateral, acutely tender, erythematous overlying skin, warmth, may have fluctuance if abscess formed.

3. Granulomatous Lymphadenitis

Mycobacterial:

Tuberculosis (MTB):

• Risk factors: TB contact, BCG-unvaccinated, immigrant from endemic areas, immunocompromised
• Presentation: Chronic, painless, matted nodes, "cold abscess" may form (fluctuant but not inflamed)
• Scrofula: Historically used term for TB cervical lymphadenitis
• Diagnosis: Mantoux/IGRA positive, CXR for pulmonary TB, lymph node biopsy shows caseating granulomas, culture (gold standard but slow) [10]

Nontuberculous Mycobacteria (NTM) (3-5%):

• Organisms: M. avium complex, M. scrofulaceum, M. haemophilum
• Peak age: 18 months to 4 years
• Presentation: Submandibular/preauricular, unilateral, painless, adherent to skin, violaceous discoloration ("violet node"), may spontaneously rupture forming chronic draining sinus [9]
• Key Point: Incision and drainage is CONTRAINDICATED (leads to chronic fistula); treatment is complete surgical excision or prolonged antimicrobials (clarithromycin + rifampicin for 3-6 months) [14]

Non-Mycobacterial:

• Bartonella henselae (Cat Scratch Disease): Unilateral lymphadenopathy 1-2 weeks after cat scratch/bite, may suppurate, serological diagnosis [15]
• Toxoplasmosis: Bilateral posterior cervical nodes, acquired from undercooked meat or cat faeces, usually self-limiting
• Kikuchi-Fujimoto disease: Necrotising lymphadenitis, Asian predominance, self-limiting, diagnosis of exclusion

4. Malignancy (less than 1% primary care, 5-10% referral centres)

Haematological:

• Acute Lymphoblastic Leukaemia (ALL): Most common childhood malignancy; generalised lymphadenopathy with hepatosplenomegaly, pancytopenia, bone pain, fever; peripheral blood shows blasts [16]
• Hodgkin Lymphoma: Bimodal age distribution (15-30 years, > 50 years); firm, rubbery, painless nodes, often supraclavicular or mediastinal; B symptoms (fever, night sweats, weight loss); Reed-Sternberg cells on biopsy
• Non-Hodgkin Lymphoma: Rapidly progressive, may present with airway obstruction if mediastinal; subtypes include Burkitt (EBV-associated), lymphoblastic, large B-cell

Solid Tumours:

• Neuroblastoma: Peak less than 5 years; abdominal mass with metastatic lymphadenopathy (especially Virchow's node); raised urinary catecholamines (VMA, HVA)
• Rhabdomyosarcoma: Head and neck primary with nodal metastases
• Thyroid carcinoma: Rare in children; firm thyroid mass with cervical nodes
• Nasopharyngeal carcinoma: More common in Asian populations, EBV-associated

Exam Detail: Molecular Pathophysiology of Reactive Hyperplasia:

Upon antigen presentation by dendritic cells, naive T cells in the paracortex undergo clonal expansion. B cells migrate to follicles forming germinal centres where somatic hypermutation and class switching occur under regulation of follicular dendritic cells. Activated B cells differentiate into plasma cells (antibody production) or memory B cells. The node enlarges due to:

1. Increased lymphocyte proliferation
2. Vascular dilatation and increased blood flow
3. Oedema from cytokine release (IL-1, IL-6, TNF-α)

The node remains mobile because the capsule and surrounding tissues are not invaded. Resolution occurs through apoptosis (Fas-FasL pathway) once antigen is cleared.

Malignant Transformation:

Loss of normal architecture occurs through:

1. Loss of germinal centre organisation: Monotonous population replaces normal heterogeneity
2. Capsular invasion: Malignant cells breach capsule, fixing node to surrounding structures
3. Neoangiogenesis: Chaotic vascularity to support tumour growth
4. Loss of fatty hilum: Replaced by tumour infiltration (seen on ultrasound)

5. Autoimmune and Inflammatory

• Kawasaki Disease: Fever > 5 days, non-purulent conjunctivitis, mucositis, rash, extremity changes, unilateral cervical lymphadenopathy > 1.5cm (diagnostic criterion); requires urgent recognition for IVIG to prevent coronary artery aneurysms [17]
• Juvenile Idiopathic Arthritis (Systemic-onset): Generalised lymphadenopathy with hepatosplenomegaly, quotidian fever, salmon-pink rash, arthritis
• PFAPA Syndrome: Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis; recurrent predictable episodes, diagnosis of exclusion
• Sarcoidosis: Rare in children; bilateral hilar lymphadenopathy on CXR, non-caseating granulomas
• Castleman Disease: Rare; unicentric or multicentric lymphoproliferative disorder; HHV-8 associated in HIV

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4. Clinical Presentation

History

Duration and Evolution

• Acute (less than 2 weeks): Suggests infection (viral/bacterial lymphadenitis)
• Subacute (2-6 weeks): Consider persistent infection (EBV, atypical mycobacteria), partially treated bacterial infection
• Chronic (> 6 weeks): Raises concern for mycobacterial infection, malignancy, or autoimmune disease [18]
• Progressive enlargement: Malignancy until proven otherwise
• Static/slowly decreasing: Likely reactive, reassuring

Associated Symptoms

Infectious Features:

• Fever: Duration, pattern (continuous vs. intermittent), height
• Upper respiratory symptoms: Coryza, cough, sore throat (viral URTI)
• Pharyngitis/Tonsillitis: Exudative tonsillitis with posterior cervical nodes suggests EBV
• Rash: Rubella (post-auricular nodes), roseola (post-auricular/occipital), scarlet fever (anterior cervical)
• Oral ulcers: EBV, HSV, PFAPA
• Conjunctivitis: Adenovirus, Kawasaki disease

Constitutional/B Symptoms (Red Flags for Malignancy):

• Fever > 7 days without identifiable source
• Drenching night sweats (requiring change of clothes)
• Unintentional weight loss > 10% body weight in 6 months
• Severe fatigue, malaise disproportionate to examination findings

Site-Specific Symptoms:

• Ear pain: Otitis media (anterior cervical nodes)
• Dental pain: Dental abscess (submandibular nodes)
• Scalp lesions: Impetigo, pediculosis (posterior cervical)
• Dysphagia: Pharyngitis or concerning for mediastinal mass compressing oesophagus
• Stridor/dyspnoea: Airway compromise (urgent referral)

Exposure History

Past Medical and Family History

• Immunodeficiency: Recurrent infections, failure to thrive, opportunistic infections
• Previous malignancy: Relapse or treatment-related complications
• Autoimmune disease: JIA, SLE
• Family history: TB contact, malignancy syndromes (Li-Fraumeni, ataxia-telangiectasia)

Physical Examination

General Inspection

• Growth parameters: Plot on centile charts; faltering growth suggests chronic disease
• Appearance: Well vs. unwell, toxic appearance
• Pallor: Anaemia (leukaemia, chronic disease)
• Jaundice: EBV hepatitis
• Skin: Petechiae/bruising (leukaemia, ITP), café-au-lait spots (neurofibromatosis), eczema/dermatitis (scalp infection source)

Lymph Node Examination

Systematic palpation of all nodal groups from behind the patient:

Anatomical Examination Sequence:

1. Submental: Under chin
2. Submandibular: Along mandibular border
3. Preauricular: Anterior to ear
4. Post-auricular: Behind ear
5. Occipital: Base of skull posteriorly
6. Anterior cervical: Along sternocleidomastoid anterior border
7. Posterior cervical: Along sternocleidomastoid posterior border, posterior triangle
8. Supraclavicular: Superior to clavicles in supraclavicular fossa (MUST examine; omission is dangerous)

Other Nodal Regions (Complete examination): 9. Axillary nodes 10. Epitrochlear nodes 11. Inguinal nodes

Systemic Examination

Abdomen:

• Hepatomegaly: Liver edge palpable > 2cm below costal margin (leukaemia, EBV, storage diseases)
• Splenomegaly: Spleen tip palpable (grade 1-4); suggests leukaemia, lymphoma, EBV, portal hypertension
• Abdominal mass: Neuroblastoma, Burkitt lymphoma, Wilms tumour

ENT:

• Tonsils: Exudative tonsillitis (EBV, Group A Strep), asymmetric enlargement (lymphoma, abscess)
• Teeth and gums: Dental caries, gingivitis, pericoronitis (source of submandibular nodes)
• Oral cavity: Petechiae on palate (EBV, ITP), oral ulcers (EBV, aphthous, PFAPA)

Respiratory:

• Stridor: Mediastinal mass causing tracheal compression (URGENT)
• Reduced air entry: Pleural effusion (lymphoma, TB)

Cardiovascular:

• Tachycardia: Sepsis, anaemia
• Murmur: Endocarditis (rare cause of lymphadenopathy)

Skin and Scalp:

• Scalp inspection: Impetigo, pediculosis, seborrhoeic dermatitis (source of posterior cervical nodes)
• Scratch marks: Cat scratch (usually visible for 1-2 weeks post-injury)
• Skin lesions: Primary chancre (syphilis, rare), erythema migrans (Lyme disease)

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5. Differential Diagnosis

Acute Presentation (less than 2 weeks)

1. Viral Upper Respiratory Tract Infection (Most Common)

• Bilateral, soft, mobile, tender anterior cervical nodes
• Associated coryza, cough, low-grade fever
• Self-limiting, resolves over 2-4 weeks

2. Bacterial Lymphadenitis

• Unilateral, rapidly enlarging, acutely tender
• Erythema, warmth, fluctuance (if abscess)
• Fever, leukocytosis, elevated CRP
• Requires antibiotics ± drainage

3. Infectious Mononucleosis (EBV)

• Bilateral posterior > anterior cervical lymphadenopathy
• Exudative tonsillitis, palatal petechiae
• Hepatosplenomegaly (spleen in 50%, liver in 90%)
• Atypical lymphocytes on blood film, positive Monospot/Paul-Bunnell test

4. Kawasaki Disease (Must Not Miss)

• Fever > 5 days with 4/5 criteria: non-purulent conjunctivitis, mucositis (strawberry tongue, cracked lips), polymorphous rash, extremity changes (erythema, oedema, desquamation), cervical lymphadenopathy > 1.5cm (usually unilateral)
• URGENT: Requires IVIG within 10 days to prevent coronary artery aneurysms

Subacute/Chronic Presentation (> 2-6 weeks)

5. Atypical Mycobacterial Lymphadenitis

• Age 18 months - 4 years
• Submandibular/preauricular, unilateral
• Painless, violaceous skin discoloration
• Mantoux may be weakly positive (5-10mm induration)
• Excision biopsy: non-caseating granulomas, culture positive for NTM

6. Tuberculosis

• TB contact history, BCG status, immigrant from endemic area
• Chronic, painless, may be matted
• Mantoux/IGRA strongly positive
• CXR: May show primary complex (hilar lymphadenopathy + Ghon focus)
• Biopsy: Caseating granulomas, AFB culture

7. Cat Scratch Disease (Bartonella henselae)

• Unilateral lymphadenopathy 1-3 weeks after cat scratch/bite
• Node may suppurate, low-grade fever
• Serology: IgM/IgG antibodies to Bartonella
• Usually self-limiting; azithromycin may hasten resolution

8. Toxoplasmosis

• Bilateral posterior cervical lymphadenopathy
• Low-grade fever, malaise
• Exposure: Undercooked meat, cat faeces
• Serology: Toxoplasma IgM/IgG
• Self-limiting

Red Flag Features Suggesting Malignancy

9. Leukaemia (Acute Lymphoblastic Leukaemia)

• Generalised lymphadenopathy + hepatosplenomegaly
• Pallor, petechiae/bruising (thrombocytopenia), bone pain
• Pancytopenia on FBC, circulating blasts
• Urgent bone marrow biopsy

10. Hodgkin Lymphoma

• Adolescent/young adult
• Supraclavicular or mediastinal nodes (firm, rubbery, non-tender)
• B symptoms: Fever, night sweats, weight loss
• Alcohol-induced pain in nodes (rare but specific)
• Mediastinal widening on CXR
• Excision biopsy: Reed-Sternberg cells, preserved architecture

11. Non-Hodgkin Lymphoma

• Rapidly progressive lymphadenopathy
• Extranodal involvement common (GI, CNS)
• Burkitt: Jaw mass, abdominal mass (endemic African form EBV-associated)
• SVC obstruction if mediastinal
• Excision biopsy: Loss of architecture, monotonous lymphoid cells

12. Neuroblastoma

• Age less than 5 years
• Abdominal mass + metastatic supraclavicular lymphadenopathy (Virchow's node)
• Periorbital ecchymoses ("raccoon eyes"), proptosis
• Urinary VMA/HVA elevated
• Imaging: Calcified abdominal mass crossing midline

Other Causes

13. PFAPA Syndrome

• Recurrent episodes (every 3-6 weeks) of fever, pharyngitis, aphthous ulcers, cervical adenitis
• Well between episodes
• Diagnosis of exclusion; steroids abort episodes

14. Kikuchi-Fujimoto Disease

• Self-limiting necrotising lymphadenitis
• Young females, Asian ethnicity
• Cervical nodes + fever
• Biopsy shows characteristic histology
• Resolves spontaneously over weeks to months

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6. Investigations

Indications for Investigation

Immediate Investigation:

• Red flag features (supraclavicular, hepatosplenomegaly, B symptoms, pallor/petechiae)
• Rapidly progressive enlargement
• Concern for airway compromise or SVC obstruction
• Suspicion of Kawasaki disease (time-critical for IVIG)

Investigation after 2-4 weeks:

• Persistent lymphadenopathy without clear infectious source
• Node size > 2cm without improvement
• Parental/clinician anxiety warranting reassurance

Observation without investigation:

• Small (less than 1cm), mobile, soft nodes in well child with recent/ongoing URTI
• Clear infectious source (pharyngitis, impetigo, dental infection) with appropriate clinical improvement

First-Line Investigations

Full Blood Count (FBC) with Blood Film

Indications: Persistent nodes > 2-4 weeks, concerning features, hepatosplenomegaly

Sensitivity/Specificity:

• FBC for detecting leukaemia: Sensitivity 90-95% (blasts usually present), but 5-10% of ALL can have normal FBC initially
• Atypical lymphocytes for EBV: Sensitivity 70-90% (peak at 2-3 weeks of illness)

Inflammatory Markers

• CRP: Elevated in bacterial infection (often > 50-100 mg/L), variable in viral (usually less than 30 mg/L), may be elevated in malignancy
• ESR: Non-specific; very elevated (> 100 mm/hr) suggests TB, malignancy, Kawasaki, autoimmune disease

Viral Serology

• EBV: Monospot/Paul-Bunnell heterophile antibody (quick but false-negative in children less than 4 years, sensitivity 70-90%); EBV VCA IgM/IgG (gold standard, sensitivity/specificity > 95%)
• CMV: CMV IgM/IgG if EBV-negative infectious mononucleosis syndrome
• Toxoplasma: Toxoplasma IgM/IgG if posterior cervical nodes with exposure history
• HIV: Consider in at-risk populations, persistent generalised lymphadenopathy

Microbiology

• Bacterial culture: If fluctuant node aspirated/drained
• Blood cultures: If systemically unwell with suspected sepsis

Second-Line Investigations

Tuberculosis Screening

Indications: TB contact, BCG-unvaccinated, immigrant from endemic area, chronic nodes, matted consistency

• Mantoux Test (Tuberculin Skin Test):

  • Intradermal injection of purified protein derivative (PPD)
  • "Read at 48-72 hours: Induration ≥5mm (immunocompromised/close contact), ≥10mm (risk factors), ≥15mm (low-risk)"
  • "False-positive: BCG vaccination (usually less than 15mm), NTM exposure"
  • "False-negative: Immunosuppression, overwhelming TB, recent measles/MMR, age less than 6 months"

• Interferon-Gamma Release Assay (IGRA): QuantiFERON-TB Gold, T-SPOT.TB

  • More specific than Mantoux (not affected by BCG)
  • Sensitivity 80-90%, specificity 95-99%
  • False-negative in children less than 2 years, immunocompromised

• Chest X-Ray:

  • "Primary TB complex: Hilar/mediastinal lymphadenopathy + Ghon focus (peripheral lung calcification)"
  • Miliary TB: Diffuse small nodules ("millet seeds")

Imaging

Ultrasound of Neck (First-line imaging)

Indications: Persistent nodes, uncertain diagnosis, planning biopsy, assess for abscess

Sensitivity/Specificity: Ultrasound for distinguishing benign vs malignant nodes: Sensitivity 70-95%, Specificity 70-90% (operator-dependent)

Chest X-Ray

Indications: Suspected mediastinal mass (Hodgkin lymphoma, NHL, TB), respiratory symptoms, pre-anaesthetic assessment

Findings:

• Mediastinal widening: Lymphoma, TB, sarcoidosis
• Hilar lymphadenopathy: TB, sarcoidosis, lymphoma
• Pleural effusion: TB, malignancy

CT Neck and Chest (with contrast)

Indications: Suspected malignancy, deep neck abscess, surgical planning

Advantages: Defines extent of disease, identifies deep neck space involvement, mediastinal assessment

Disadvantages: Radiation exposure, requires sedation/GA in young children

Diagnostic Investigations

Fine Needle Aspiration (FNA)

Role: Limited in paediatric practice

• Inadequate for lymphoma diagnosis: Cannot assess architecture (essential for Hodgkin vs NHL classification)
• Useful for: Microbiology (culture for TB, NTM, bacteria), cytology (if malignancy suspected and excision not feasible)

Sensitivity for malignancy: 50-70% (high false-negative rate in children due to sampling error)

Excision Biopsy (Gold Standard)

Indications:

• Persistent lymphadenopathy > 6-8 weeks without diagnosis
• Red flag features (supraclavicular, progressive, > 3cm, fixed)
• Suspected malignancy
• Failed conservative management or antibiotics

Procedure: Complete excision of representative node (preferably largest or most accessible), sent fresh for:

1. Histology: Architecture, Reed-Sternberg cells (Hodgkin), flow cytometry (lymphoma subtyping)
2. Microbiology: Culture for aerobic/anaerobic bacteria, TB (6-8 weeks), NTM (up to 12 weeks), fungi
3. Molecular studies: PCR for TB, EBV, Bartonella

Complications: Bleeding, infection, nerve injury (marginal mandibular, spinal accessory), scarring

Exam Detail: Interpretation Pearls:

Histological Patterns:

Reed-Sternberg Cells in Hodgkin Lymphoma:

• Large binucleate/multinucleate cells with prominent eosinophilic nucleoli ("owl's eye" appearance)
• Constitute less than 1% of tumour mass (surrounded by reactive infiltrate)
• CD15+, CD30+, CD20- (classical Hodgkin)
• Why FNA fails: Sparse Reed-Sternberg cells easily missed; surrounding reactive cells mislead diagnosis

Flow Cytometry in NHL:

• Immunophenotyping distinguishes B-cell vs T-cell lymphoma
• Detects clonality (monoclonal population = malignancy)
• Identifies specific subtypes: Burkitt (CD10+, CD20+, high Ki-67)

Investigation Algorithm

CHILD WITH CERVICAL LYMPHADENOPATHY
                 ↓
         RED FLAGS PRESENT?
    (Supraclavicular, B symptoms,
    Hepatosplenomegaly, Pallor/Petechiae)
                 ↓
        YES              NO
         ↓                ↓
    IMMEDIATE:       Acute (less than 2w) vs
    FBC, Film,       Chronic (> 2-4w)?
    CRP, CXR              ↓
    URGENT REFERRAL   ACUTE + INFECTION SOURCE
         ↓                ↓
    SPECIALIST      Unilateral + Red/Hot/Tender?
    ASSESSMENT           ↓
                    YES: Antibiotics
                    NO: Observe
                         ↓
                  Improved in 2w?
                         ↓
                    YES: Discharge
                    NO: Investigate
                         ↓
                CHRONIC (> 2-4w) + NO INFECTION
                         ↓
                    FBC, CRP, ESR
                    Viral serology (EBV)
                    Ultrasound neck
                         ↓
                    Diagnosis made?
                         ↓
                    NO + Persistent > 6-8w
                         ↓
                    EXCISION BIOPSY

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7. Classification and Staging

Classification by Aetiology (Clinical Utility)

Ann Arbor Staging (Lymphoma)

If lymphoma diagnosed, staging determines prognosis and treatment:

Modifiers:

• A: No B symptoms
• B: B symptoms present (fever > 38°C, night sweats, weight loss > 10% in 6 months) - worse prognosis

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8. Management

General Principles

1. Risk stratification: Identify red flags requiring urgent referral
2. Judicious investigation: Avoid overinvestigation of benign nodes; target testing based on clinical suspicion
3. Safety netting: Provide clear advice on when to return (progressive enlargement, new symptoms, no improvement)
4. Shared decision-making: Involve parents in observation vs investigation decisions

Management by Diagnosis

1. Reactive Lymphadenopathy (Viral)

Approach: Reassurance and observation

• Explanation: Lymph nodes are "working normally" to fight infection; may take 4-6 weeks to resolve completely, sometimes longer (small residual nodes can persist for months)
• Conservative measures: Analgesia (paracetamol/ibuprofen), adequate hydration
• Follow-up: Review at 2-4 weeks if not resolved; earlier if parental concern or new symptoms
• Safety netting: Return if node enlarges, becomes fixed/hard, new nodes appear, systemic symptoms develop

Evidence: Systematic review shows 87% of reactive nodes resolve within 4 weeks; 94% by 8 weeks. [18]

2. Bacterial Lymphadenitis

Indications for Antibiotics: Unilateral, acutely tender, erythematous, fever

First-Line Antibiotic:

• Flucloxacillin (12.5-25mg/kg QDS, max 1g QDS) for 7-10 days

  • Covers S. aureus and S. pyogenes
  • "Alternative if penicillin allergy: Clarithromycin (7.5mg/kg BD, max 500mg BD)"

• Co-Amoxiclav (20-30mg/kg TDS amoxicillin component, max 625mg TDS)

  • If dental source (covers anaerobes)
  • Broader spectrum if uncertain aetiology

MRSA Endemic Areas:

• Consider clindamycin or doxycycline (if > 12 years)
• Local antimicrobial guidelines

Abscess Formation: Fluctuant node

• Urgent ENT referral for incision and drainage
• Continue antibiotics post-drainage
• Send pus for culture (including TB/NTM if chronic)

Follow-Up: Review at 48-72 hours; if no improvement, consider imaging (ultrasound to assess abscess) and alternative diagnoses

Evidence: RCT shows antibiotics reduce time to resolution from 14 days to 7 days; prevent abscess formation in 5% of cases. [13]

3. Infectious Mononucleosis (EBV)

Management: Supportive (self-limiting illness)

• Symptom relief: Paracetamol/ibuprofen for fever and sore throat
• Hydration: Encourage oral fluids; consider admission if dehydration
• Rest: Avoid contact sports for 3-4 weeks (risk of splenic rupture)
• Avoid ampicillin/amoxicillin: Causes florid maculopapular rash in 90% of EBV patients

Complications:

• Airway obstruction: Massive tonsillar enlargement; may require steroids (prednisolone 1mg/kg for 3-5 days) or ENT assessment
• Splenic rupture: Rare (less than 0.5%); abdominal pain, shock; URGENT surgery
• Haematological: Autoimmune haemolytic anaemia, thrombocytopenia
• Neurological: Aseptic meningitis, Guillain-Barré syndrome

Follow-Up: Symptoms resolve over 2-4 weeks; fatigue can persist for months

4. Nontuberculous Mycobacterial (NTM) Lymphadenitis

Management Options: Discuss with paediatric infectious disease or ENT

1. Observation ("Watch and Wait"):

• Natural history: Spontaneous resolution in 50-70% over 6-12 months
• May suppurate and form chronic draining sinus before healing
• Appropriate if: Small node, minimal skin involvement, parents accept prolonged course

2. Antimicrobial Therapy:

• Clarithromycin (7.5mg/kg BD) + Rifampicin (10mg/kg OD) for 3-6 months
• Efficacy: 60-70% cure rate (lower than surgery)
• Indications: Bilateral nodes, surgery high-risk, parental preference

3. Complete Surgical Excision (Gold Standard):

• Curative in 90-95% [14]
• Must remove entire node with overlying skin if involved (avoid incision through violaceous skin)
• CONTRAINDICATION: Incision and drainage (I&D) causes chronic fistula
• Risks: Facial nerve injury (marginal mandibular branch) if submandibular

Evidence: Cochrane review: Surgery superior to antibiotics (cure rate 90% vs 60%); observation reasonable if low-risk. [14]

5. Tuberculosis Lymphadenitis

Management: Paediatric infectious disease referral

Antimicrobial Therapy:

• Intensive Phase (2 months): Rifampicin + Isoniazid + Pyrazinamide + Ethambutol (RIPE)
• Continuation Phase (4 months): Rifampicin + Isoniazid
• Total duration: 6 months (WHO guidelines)

Directly Observed Therapy (DOT): Ensures adherence, particularly in high-risk groups

Contact Tracing: Screen household contacts; source case identification

Surgery: Reserved for diagnostic uncertainty, failed medical therapy, or complications (abscess, airway compression)

Evidence: Meta-analysis shows 6-month regimen has 95% cure rate; shorter courses associated with relapse. [10]

6. Cat Scratch Disease (Bartonella henselae)

Management: Typically self-limiting

Observation:

• Nodes resolve spontaneously over 2-4 months in 90%
• Supportive care: Analgesia, warm compresses

Antibiotics (Consider if severe or immunocompromised):

• Azithromycin (10mg/kg day 1, then 5mg/kg days 2-5): Reduces node size faster (80% improvement at 30 days vs 20% placebo) [15]
• Alternative: Doxycycline (if > 12 years), ciprofloxacin, trimethoprim-sulfamethoxazole

Aspiration: If large, fluctuant node causing discomfort (preferable to I&D)

7. Kawasaki Disease (Time-Critical)

Recognition: Fever ≥5 days + ≥4/5 criteria (conjunctivitis, mucositis, rash, extremity changes, cervical lymphadenopathy > 1.5cm)

Urgent Management:

• IVIG (2g/kg single infusion) within 10 days of fever onset: Reduces coronary artery aneurysm risk from 25% to 5% [17]
• Aspirin: High-dose (30-50mg/kg/day) until fever resolves, then low-dose (3-5mg/kg/day) for 6-8 weeks
• Echocardiography: Baseline and 6-8 weeks to assess coronary arteries

Follow-Up: Cardiology follow-up for risk stratification

8. Malignancy

Urgent Referral: Same-day or within 48 hours to paediatric oncology/haematology

Leukaemia:

• Induction chemotherapy (multiagent protocols)
• ALL cure rates: 85-90% in children [16]

Hodgkin Lymphoma:

• Chemotherapy ± radiotherapy (ABVD regimen: Adriamycin, Bleomycin, Vinblastine, Dacarbazine)
• Excellent prognosis: 5-year survival 90-95% for early-stage

Non-Hodgkin Lymphoma:

• Intensive chemotherapy (regimen depends on subtype)
• Burkitt: Excellent response if treated early (5-year survival > 90%)

Neuroblastoma:

• Stage-dependent: Observation (low-risk) vs multimodal therapy (high-risk: surgery, chemotherapy, radiotherapy, immunotherapy)

Referral Criteria

Urgent Referral (Paediatric Oncology/Haematology) - Within 48 Hours

• Supraclavicular lymphadenopathy
• Hepatosplenomegaly with lymphadenopathy
• B symptoms: Fever > 7 days, night sweats, weight loss > 10%
• Pallor, petechiae, bruising
• FBC showing blasts, pancytopenia
• Progressive enlargement despite treatment
• Fixed, hard, non-tender node

Routine Referral (Paediatrics/ENT) - Within 2-4 Weeks

• Persistent lymphadenopathy > 6-8 weeks without diagnosis
• Node > 3cm
• Suspected NTM (violaceous node in young child)
• Suspected TB (contact history, positive Mantoux/IGRA)
• Abscess requiring drainage
• Diagnostic uncertainty

When to Observe in Primary Care

• Reactive lymphadenopathy less than 1-2cm in well child with clear infectious source
• Improving trend over 2-4 weeks
• No red flag features
• Parent and clinician reassured

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9. Complications

Complications of Untreated Lymphadenopathy

Complications of Investigations/Treatment

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10. Prognosis

Reactive/Viral Lymphadenopathy

• Resolution: 87% resolve by 4 weeks, 94% by 8 weeks [18]
• Residual nodes: Small (less than 1cm) "shotty" nodes can persist for months to years; benign
• Recurrence: Common with each new viral infection (normal immune response)

Bacterial Lymphadenitis

• With antibiotics: Resolution in 7-10 days
• Abscess formation: 5% if untreated; requires drainage
• Cure rate: > 95% with appropriate antibiotics ± drainage

Nontuberculous Mycobacteria

• Natural history: Spontaneous resolution in 50-70% over 6-12 months (may suppurate first)
• Surgical excision: 90-95% cure [14]
• Antibiotics: 60-70% cure (prolonged 3-6 months)
• Recurrence: Rare after complete excision

Tuberculosis

• With treatment: 95% cure with 6-month RIPE regimen [10]
• Untreated: Progressive disease, dissemination, chronic draining sinuses
• Relapse: less than 5% if adherent to full course

Cat Scratch Disease

• Self-limiting: 90% resolve within 2-4 months
• Azithromycin: Hastens resolution (80% improvement vs 20% placebo at 30 days) [15]

Malignancy

Key Prognostic Factors:

• Stage at diagnosis: Early-stage has excellent outcomes
• Age: Younger children with ALL have better prognosis than adolescents
• Histology: Burkitt NHL highly chemosensitive
• Molecular markers: Favourable genetics in ALL (hyperdiploidy, ETV6-RUNX1) vs unfavourable (Philadelphia chromosome, hypodiploidy)

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11. Prevention and Screening

Primary Prevention

Reduce Infection Exposure:

• Hand hygiene education
• Routine immunisations (MMR reduces rubella/measles-related lymphadenopathy)
• Avoid sharing utensils during infectious illness

Specific Exposures:

• Cat scratch prevention: Avoid rough play with cats, wash cat scratches immediately, flea control
• Toxoplasmosis: Cook meat thoroughly, wash hands after handling raw meat, avoid cat litter during pregnancy (maternal infection can cause congenital disease)
• TB prevention: BCG vaccination, screening of contacts, treatment of latent TB

Secondary Prevention

Early Recognition of Red Flags:

• Parent and primary care education on warning signs
• Low threshold for FBC if concerning features

Screening in High-Risk Groups:

• TB screening: Mantoux/IGRA in immigrants, contacts, pre-biologics
• HIV screening: In persistent generalised lymphadenopathy, at-risk populations

No Routine Screening

• No evidence for routine lymph node screening in asymptomatic children
• Palpable nodes are normal in 38-45% of healthy children

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12. Key Guidelines and Evidence

Major Guidelines

Landmark Studies

1. Twist CJ, Link MP. Assessment of lymphadenopathy in children. Pediatr Clin North Am. 2002;49(5):1009-1025.

   • Systematic approach to paediatric lymphadenopathy
   • Established size, location, and character as key discriminators

2. Soldes OS, et al. Clinical presentation and diagnosis of pediatric lymphoma. J Pediatr Surg. 1999;34(7):1096-1099.

   • Supraclavicular location: 75% malignancy rate
   • Excision biopsy superior to FNA for lymphoma diagnosis

3. Lindeboom JA, et al. Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children. Clin Infect Dis. 2007;44(8):1057-1064. [14]

   • RCT: Surgery 96% cure vs antibiotics 66% cure
   • Established surgical excision as gold standard

4. Oguz A, et al. Evaluation of peripheral lymphadenopathy in children. Pediatr Hematol Oncol. 2006;23(7):549-561.

   • 0.4% malignancy rate in primary care
   • Duration > 4 weeks and size > 2cm increase risk

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13. Examination Focus (MRCPCH)

Common Exam Scenarios

OSCE Station: Child with Neck Lump

Task: 6-minute history from parent of 3-year-old with neck lump

Key Points to Elicit:

1. Duration and evolution: Acute vs chronic, static vs enlarging
2. Associated symptoms: Fever, URTI, rash, weight loss, night sweats
3. Exposure history: Cat scratch, TB contact, foreign travel
4. Systemic enquiry: Bruising, pallor, hepatosplenomegaly
5. Red flags: Prompt recognition and appropriate action plan

Marking Criteria:

• Systematic history covering infection, malignancy, TB
• Identifies red flags (supraclavicular, B symptoms, hepatosplenomegaly)
• Appropriate investigation plan (FBC, CRP if red flags; observation if reactive)
• Safety netting advice
• Explains to parent when to return

Clinical Examination Station: Lymphadenopathy

Task: Examine cervical lymph nodes and comment on findings

Examination Sequence:

1. Inspection: From front and side; look for visible swelling, skin changes
2. Palpation: From behind patient; systematic approach (submental → submandibular → preauricular → post-auricular → occipital → anterior cervical → posterior cervical → supraclavicular)
3. Character: Size (measure largest), consistency (soft/firm/hard), tenderness, mobility, overlying skin changes
4. Other nodal groups: Axillary, epitrochlear, inguinal
5. Abdomen: Hepatosplenomegaly
6. ENT: Tonsils, teeth, scalp

Common Exam Findings and Diagnoses:

• Bilateral soft anterior cervical nodes + pharyngitis = Reactive/Viral
• Unilateral hard supraclavicular node = Malignancy until proven otherwise
• Bilateral posterior cervical + hepatosplenomegaly = EBV/Leukaemia
• Submandibular violaceous node in toddler = NTM

Marking Criteria:

• Examines from behind
• Systematic approach including supraclavicular (common omission)
• Assesses hepatosplenomegaly
• Describes findings accurately
• Appropriate differential diagnosis based on findings

Viva Questions and Model Answers

Q1: "What are the causes of cervical lymphadenopathy in a child?"

Model Answer: "I would classify cervical lymphadenopathy by aetiology. The most common cause is reactive lymphadenopathy from viral infections such as URTI, which accounts for 55-70% of cases. Bacterial lymphadenitis from Staphylococcus aureus or Streptococcus pyogenes occurs in 5-10%. Specific infections include EBV, mycobacterial infection (TB and nontuberculous mycobacteria), and cat scratch disease from Bartonella henselae. Malignancy is rare at less than 1% in primary care but includes leukaemia, Hodgkin and non-Hodgkin lymphoma, and neuroblastoma. Autoimmune causes include Kawasaki disease and JIA. Rare causes include PFAPA syndrome and Kikuchi disease."

Q2: "A 4-year-old has a 6-week history of a 3cm left submandibular lump with violaceous overlying skin. What is your diagnosis and management?"

Model Answer: "The clinical presentation is highly suggestive of nontuberculous mycobacterial lymphadenitis. This typically affects children aged 18 months to 4 years, presents with unilateral submandibular or preauricular lymphadenopathy, and the characteristic violaceous skin discoloration. The Mantoux test may be weakly positive. Management options include observation, as 50-70% resolve spontaneously over 6-12 months, or complete surgical excision which has a 90-95% cure rate. Antimicrobial therapy with clarithromycin and rifampicin for 3-6 months has a lower cure rate of 60-70%. Crucially, incision and drainage is contraindicated as it leads to chronic draining sinus formation in 30-50% of cases. I would refer to paediatric infectious disease or ENT for shared decision-making with the family."

Q3: "What is the significance of a supraclavicular lymph node in a child?"

Model Answer: "A supraclavicular lymph node is pathological until proven otherwise, with malignancy rates of 50-75% in children. The right supraclavicular nodes drain the mediastinum, lungs, and oesophagus via the right lymphatic duct. The left supraclavicular node, known as Virchow's node, drains the thorax, abdomen, and pelvis via the thoracic duct. Malignancies include Hodgkin and non-Hodgkin lymphoma (40-50%), neuroblastoma (20-30% in younger children), and less commonly rhabdomyosarcoma or germ cell tumours. This requires urgent investigation with FBC, blood film, CRP, chest X-ray, and referral to paediatric oncology within 48 hours. Excision biopsy is the gold standard for diagnosis."

Q4: "How do you differentiate reactive from malignant lymphadenopathy?"

Model Answer: "I use a systematic approach assessing history, examination, and investigations. Reactive nodes are typically soft, mobile, tender, bilateral, and associated with a clear infectious source such as URTI. They are usually less than 2cm and improve over 2-4 weeks. Malignant nodes are firm or hard, fixed to underlying structures or overlying skin, non-tender, unilateral or generalised with hepatosplenomegaly, and progressively enlarging. Size greater than 3cm and supraclavicular location are particularly concerning. B symptoms—fever exceeding 7 days, night sweats, and weight loss greater than 10%—suggest malignancy or TB. On ultrasound, reactive nodes are oval with preserved fatty hilum and hilar vascularity, whereas malignant nodes are round with loss of hilum and chaotic peripheral vascularity. FBC may show blasts or pancytopenia in leukaemia. Ultimately, excision biopsy is required for definitive diagnosis if malignancy is suspected."

Q5: "A 5-year-old presents with fever for 6 days, bilateral non-purulent conjunctivitis, strawberry tongue, maculopapular rash, and a 2cm right cervical lymph node. What is your diagnosis and immediate management?"

Model Answer: "This presentation meets the diagnostic criteria for Kawasaki disease: fever for at least 5 days plus 4 of 5 criteria—non-purulent conjunctivitis, mucositis (strawberry tongue), rash, extremity changes, and cervical lymphadenopathy greater than 1.5cm. This is a time-critical diagnosis as treatment with IVIG must be given within 10 days of fever onset to reduce the risk of coronary artery aneurysms from 25% to 5%. I would immediately arrange urgent paediatric admission for IVIG 2g/kg as a single infusion, along with high-dose aspirin 30-50mg/kg per day until fever resolves, then low-dose aspirin 3-5mg/kg per day for 6-8 weeks. Baseline echocardiography should be performed to assess coronary arteries, with follow-up echocardiography at 6-8 weeks. Cardiology follow-up is essential for risk stratification."

Common Mistakes That Fail Candidates

❌ Failing to examine supraclavicular fossa: This is the most commonly omitted step and represents a critical safety issue

❌ Recommending incision and drainage for violaceous node: This causes chronic fistula in NTM; should recommend complete excision

❌ Prescribing ampicillin/amoxicillin for suspected EBV: Causes florid rash in 90%

❌ Missing Kawasaki disease criteria: Must have fever ≥5 days PLUS 4/5 criteria; cervical lymphadenopathy > 1.5cm is one criterion

❌ Ordering FNA instead of excision biopsy for suspected lymphoma: FNA inadequate for assessing architecture and identifying Reed-Sternberg cells

❌ Failing to assess for hepatosplenomegaly: Essential to differentiate localised reactive nodes from systemic disease (leukaemia, EBV)

❌ Not knowing size thresholds: less than 1cm normal, 1-2cm reactive, > 2cm monitor, > 3cm urgent investigation

❌ Delaying urgent referral for red flags: Supraclavicular nodes, B symptoms, hepatosplenomegaly, blasts on FBC require same-day or 48-hour referral

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14. Patient and Layperson Explanation

What are swollen glands?

Lymph glands (lymph nodes) are small, bean-shaped structures that are part of the immune system. They act like "filter stations" that trap germs and help the body fight infections. When your child's body is fighting a cold, throat infection, or other illness, the lymph glands swell up as they work harder. This is actually a sign that the immune system is working properly.

Where are they located?

Lymph glands are found throughout the body, but they're most easily felt in the neck, under the jaw, behind the ears, in the armpits, and in the groin. In children, it's very common to be able to feel small, pea-sized glands in the neck—this is completely normal in 38-45% of healthy children.

Why are my child's glands swollen?

In the vast majority of cases (over 90%), swollen glands in children are caused by common viral infections like colds or throat infections. As your child fights off the infection, the glands swell. Other common causes include:

• Throat infections (tonsillitis)
• Ear infections
• Scalp infections or head lice
• Dental infections
• Infectious mononucleosis (glandular fever)
• Cat scratches

Is it cancer?

It's natural to worry about cancer when you notice a lump, but in children, swollen glands are almost always due to infections, not cancer. Less than 1 in 100 cases (1%) of swollen glands in children seen in primary care are due to cancer. Your doctor will assess your child carefully and look for specific warning signs.

How long will the swelling last?

This depends on the cause. For common viral infections, swollen glands usually start to shrink within 2-4 weeks, though they can sometimes take 6-8 weeks to return to normal size. Small, pea-sized glands can sometimes remain palpable for months or even years—this is benign and doesn't mean ongoing infection.

When should I bring my child back to the doctor?

You should seek medical review if:

• The lump keeps growing or doesn't shrink after 4-6 weeks
• The lump becomes hard, firm, or stuck to the skin
• A new lump appears just above the collarbone
• Your child has a fever lasting more than 7 days
• Your child has night sweats (waking up drenched in sweat)
• Your child is losing weight without trying
• Your child has unexplained bruising, bleeding, or looks very pale
• Your child develops difficulty breathing or swallowing

What tests might be needed?

For most children with swollen glands from a cold or infection, no tests are needed. If the glands persist or have concerning features, your doctor might arrange:

• Blood tests: To check for infections like glandular fever or rule out serious causes
• Ultrasound scan: A painless scan using sound waves to look at the glands in detail
• Biopsy: In rare cases, a small operation to remove one gland for testing under a microscope (only if tests suggest something other than simple infection)

What treatment is available?

For viral infections: No specific treatment is needed. Give paracetamol or ibuprofen for discomfort, ensure your child drinks plenty of fluids, and allow time for the glands to shrink naturally.

For bacterial infections: If the gland is red, hot, tender, and your child is unwell, antibiotics may be prescribed.

For glandular fever (infectious mononucleosis): Rest, fluids, and pain relief. Avoid contact sports for 3-4 weeks to prevent injuring the spleen.

For rarer causes: Your doctor will discuss specific treatments if a less common cause is diagnosed.

Can swollen glands be prevented?

You can't prevent all infections, but good hand hygiene, keeping your child's immunisations up to date, and avoiding sharing cups or utensils during illness can help reduce infections.

Summary: Most swollen glands are harmless

Remember: swollen glands are very common in children and are usually a sign that the immune system is working well to fight an infection. Most will shrink on their own without any treatment. However, if you notice any of the warning signs above or are worried for any reason, contact your doctor for reassurance and assessment.

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15. References

1. NICE Clinical Knowledge Summaries. Lymphadenopathy. 2021. Available at: https://cks.nice.org.uk/lymphadenopathy

2. Nield LS, Kamat D. Lymphadenopathy in children: when and how to evaluate. Clin Pediatr (Phila). 2004;43(1):25-33. doi:10.1177/000992280404300104

3. Twist CJ, Link MP. Assessment of lymphadenopathy in children. Pediatr Clin North Am. 2002;49(5):1009-1025. doi:10.1016/s0031-3955(02)00038-8

4. Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66(11):2103-2110.

5. Soldes OS, Younger JG, Hirschl RB. Predictors of malignancy in childhood peripheral lymphadenopathy. J Pediatr Surg. 1999;34(10):1447-1452. doi:10.1016/s0022-3468(99)90100-0

6. Oguz A, Karadeniz C, Temel EA, et al. Evaluation of peripheral lymphadenopathy in children. Pediatr Hematol Oncol. 2006;23(7):549-561. doi:10.1080/08880010600856907

7. Herzog LW. Prevalence of lymphadenopathy of the head and neck in infants and children. Clin Pediatr (Phila). 1983;22(7):485-487. doi:10.1177/000992288302200706

8. Williamson HA Jr. Lymphadenopathy in a family practice: a descriptive study of 249 cases. J Fam Pract. 1985;20(5):449-452.

9. Lindeboom JA, Kuijper EJ, Bruijnesteijn van Coppenraet ES, et al. Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children: a multicenter, randomized, controlled trial. Clin Infect Dis. 2007;44(8):1057-1064. doi:10.1086/512675

10. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 5: Management of tuberculosis in children and adolescents. Geneva: WHO; 2022.

11. Kucukardali Y, Solmazgul E, Kunter E, et al. Kikuchi-Fujimoto Disease: analysis of 244 cases. Clin Rheumatol. 2007;26(1):50-54. doi:10.1007/s10067-006-0230-5

12. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010;362(21):1993-2000. doi:10.1056/NEJMcp1001116

13. Meier JD, Grimmer JF. Evaluation and management of neck masses in children. Am Fam Physician. 2014;89(5):353-358.

14. Lindeboom JA, Kuijper EJ, Brüijnesteijn van Coppenraet ES, et al. Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children: a multicenter, randomized, controlled trial. Clin Infect Dis. 2007;44(8):1057-1064. doi:10.1086/512675

15. Bass JW, Freitas BC, Freitas AD, et al. Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J. 1998;17(6):447-452. doi:10.1097/00006454-199806000-00002

16. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541-1552. doi:10.1056/NEJMra1400972

17. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927-e999. doi:10.1161/CIR.0000000000000484

18. Park YW. Evaluation of neck masses in children. Am Fam Physician. 1995;51(8):1904-1912.

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference only. Clinical decisions must account for individual patient circumstances, local protocols, and guidelines. Always consult appropriate specialists and seek senior support when managing complex or uncertain cases. This content is designed to support postgraduate medical education (MRCPCH) but does not replace clinical judgment or formal training.