Definition/General
Introduction:
Caseating lymphadenitis is characterized by granulomatous inflammation with central caseous necrosis resembling cheese in appearance and consistency
It is most commonly caused by Mycobacterium tuberculosis and represents a hallmark of chronic granulomatous infections
The caseous necrosis results from inability to completely eliminate the causative organism leading to tissue destruction.
Origin:
Primarily caused by Mycobacterium tuberculosis complex (M
tuberculosis, M
bovis, M
africanum)
Atypical mycobacteria (M
avium-intracellulare, M
scrofulaceum)
Fungal infections (Histoplasma capsulatum, Coccidioides immitis)
Other bacterial infections (Nocardia, Actinomyces)
Parasitic infections rarely
Hematogenous spread from pulmonary focus
Lymphatic spread from local infection.
Classification:
Classified by causative organism: Tuberculous caseating lymphadenitis (most common)
Atypical mycobacterial caseating lymphadenitis
Fungal caseating lymphadenitis
Other bacterial causes
By stage: Early granulomatous (minimal necrosis)
Established caseating (prominent caseous necrosis)
Advanced fibrocaseous (extensive fibrosis and calcification).
Epidemiology:
High prevalence in developing countries with endemic tuberculosis
India has highest burden globally
Bimodal age distribution: children (5-15) and young adults (20-40)
HIV co-infection dramatically increases risk
Immunocompromised patients susceptible to atypical mycobacteria
Geographic clustering in high TB prevalence areas.
Clinical Features
Presentation:
Chronic, painless lymphadenopathy with slow progression
Cervical lymph nodes most commonly affected (60-70%)
Matted lymph node masses in advanced cases
Cold abscess formation (fluctuant, non-tender)
Sinus tract formation with chronic discharge
Constitutional symptoms (fever, weight loss, night sweats)
Pulmonary symptoms if concurrent lung involvement.
Symptoms:
Low-grade fever (intermittent pattern)
Night sweats and weight loss
Chronic fatigue and malaise
Anorexia
Chronic cough (pulmonary TB)
Hemoptysis (advanced pulmonary disease)
Chest pain (pleural involvement)
Dysphagia (mediastinal lymphadenopathy).
Risk Factors:
HIV infection (20-fold increased risk)
Immunosuppressive therapy (corticosteroids, TNF-α inhibitors)
Malnutrition and protein-energy malnutrition
Diabetes mellitus
Chronic kidney disease
Household TB contact
Overcrowding and poor ventilation
Alcohol abuse and smoking.
Screening:
Tuberculin skin test (TST) or Interferon-gamma release assays (IGRA)
Chest X-ray and CT thorax
Sputum examination (AFB smear, culture, GeneXpert)
Fine needle aspiration cytology
Histopathological examination
Culture and drug susceptibility testing
HIV testing mandatory.
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Gross Description
Appearance:
Enlarged lymph nodes with thick, adherent capsule
Cut surface reveals yellow-white caseous material (cheese-like consistency)
Central caseous necrosis surrounded by gray-white tissue
Calcification in chronic cases (gritty consistency)
Matted lymph node complexes
Cold abscess formation with fluctuant areas.
Characteristics:
Firm to fluctuant consistency depending on stage
Caseous material has thick, paste-like consistency
No true suppuration (distinguishes from bacterial abscess)
Calcific deposits in healed lesions
Fibrotic capsule thickening
Adherence to surrounding structures
Sinus tract extension to skin.
Size Location:
Variable size from 1-10 cm
Cervical lymph nodes (posterior triangle most common)
Mediastinal and hilar lymph nodes (25% of cases)
Axillary lymph nodes (10-15%)
Abdominal lymph nodes (mesenteric, para-aortic)
Multiple anatomical sites in disseminated disease.
Multifocality:
Regional involvement following lymphatic drainage
Bilateral cervical involvement in advanced cases
Mediastinal spread from cervical disease
Generalized lymphadenopathy in miliary TB
Associated organ involvement (lungs, pleura, peritoneum)
Skip lesions possible.
Microscopic Description
Histological Features:
Epithelioid granulomas with central caseous necrosis
Caseous necrosis appears as homogeneous, eosinophilic, structureless material
Epithelioid cells surrounding necrotic center
Langhans giant cells with horseshoe-shaped nuclear arrangement
Chronic inflammatory cells at periphery
Fibrosis and calcification in chronic stages.
Cellular Characteristics:
Epithelioid cells (activated macrophages) with elongated nuclei
Langhans giant cells with peripheral nuclear arrangement
Caseous necrosis with complete loss of cellular architecture
Lymphocytes and plasma cells at granuloma periphery
Fibroblasts and collagen deposition
Rare acid-fast bacilli (AFB) in tissue sections.
Architectural Patterns:
Confluent granulomas with extensive caseous necrosis
Complete architectural effacement in advanced cases
Zonal pattern: central necrosis, epithelioid cells, lymphocytes, fibrosis
Capsular involvement with pericapsular extension
Calcification pattern in healed disease
Fibrotic scarring replacement.
Grading Criteria:
Extent of caseous necrosis (focal, extensive, complete)
Granuloma maturity (well-formed vs poorly formed)
Degree of fibrosis and calcification
Organism load (AFB density)
Activity assessment (epithelioid cell morphology)
Healing vs active disease patterns.
Immunohistochemistry
Positive Markers:
CD68 positive in epithelioid cells and giant cells
CD163 positive in M2 macrophages
Lysozyme positive in epithelioid cells
CD3 highlights peripheral T-lymphocytes
CD20 shows B-cells in preserved areas
Smooth muscle actin may be positive in epithelioid cells
Ki-67 low in granulomatous areas.
Negative Markers:
CD1a and Langerin negative (excludes Langerhans cell histiocytosis)
CD30 negative (excludes lymphoma)
Cytokeratin negative in epithelioid cells
S-100 negative in most cells
Melanoma markers negative
CD21 and CD23 highlight compressed FDC networks.
Diagnostic Utility:
Acid-fast bacilli (AFB) staining essential (Ziehl-Neelsen, Auramine-Rhodamine)
CD68 staining confirms histiocytic nature
Immunohistochemistry limited for TB diagnosis
PCR-based methods more sensitive
GeneXpert MTB/RIF for rapid diagnosis
Culture remains gold standard for definitive diagnosis.
Molecular Subtypes:
Drug-sensitive tuberculosis
Multidrug-resistant TB (MDR-TB) (isoniazid + rifampin resistant)
Extensively drug-resistant TB (XDR-TB)
Atypical mycobacterial species identification
Rapid molecular testing for resistance patterns
Whole genome sequencing for comprehensive profiling.
Molecular/Genetic
Genetic Mutations:
Mycobacterial resistance mutations (rpoB, katG, gyrA genes)
Host genetic susceptibility (HLA associations, NRAMP1)
Vitamin D receptor polymorphisms
TNF-α gene variants
IL-10 promoter polymorphisms
Complement component deficiencies
Primary immunodeficiency genes.
Molecular Markers:
Mycobacterial DNA by PCR (IS6110, 16S rRNA)
GeneXpert MTB/RIF for rapid diagnosis
Line probe assays for drug resistance
Interferon-γ release assays
TNF-α essential for granuloma maintenance
IL-12 and IL-23 in Th1 response
Complement activation products.
Prognostic Significance:
Excellent prognosis with appropriate anti-TB therapy (>95% cure rate)
Drug-resistant TB has prolonged treatment and worse outcomes
HIV co-infection increases mortality risk
Delayed diagnosis leads to complications
Immune reconstitution inflammatory syndrome (IRIS) in HIV patients
Complete healing with calcification typical.
Therapeutic Targets:
First-line anti-TB drugs: isoniazid, rifampin, ethambutol, pyrazinamide (HRZE)
Treatment duration: 6 months for drug-sensitive TB
Second-line drugs for resistant cases
Directly observed therapy (DOTS)
Drug susceptibility testing guided therapy
Surgical intervention for complications
Contact tracing and prevention.
Differential Diagnosis
Similar Entities:
Sarcoidosis (non-caseating granulomas)
Fungal lymphadenitis (histoplasmosis, coccidioidomycosis)
Atypical mycobacterial infection
Cat scratch disease (stellate abscesses)
Malignancy with sarcoid-like reaction
Foreign body reaction
Other granulomatous conditions.
Distinguishing Features:
Caseating lymphadenitis: caseous necrosis, Langhans giants, AFB positive, endemic areas
Sarcoidosis: non-caseating granulomas, bilateral hilar lymphadenopathy, elevated ACE
Histoplasmosis: organisms in macrophages, GMS positive, endemic regions
Cat scratch: stellate abscesses, neutrophils, Warthin-Starry positive
Sarcoid reaction: underlying malignancy, non-caseating pattern.
Diagnostic Challenges:
Paucibacillary disease with negative AFB stains
Atypical presentations in immunocompromised patients
Culture-negative cases requiring molecular methods
Mixed infections (TB + other organisms)
Drug-resistant organisms affecting treatment response
Immune reconstitution paradoxical reactions.
Rare Variants:
Miliary tuberculosis with disseminated lymphadenopathy
Scrofula (cervical TB in children)
Tuberculous lymphadenitis in HIV
Post-primary tuberculosis
Multidrug-resistant tuberculosis
Immune reconstitution syndrome
Calcified tuberculous lymph nodes
Atypical mycobacterial lymphadenitis.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Lymph node biopsy from [cervical/mediastinal/other] region, measuring [X.X] cm, with caseous consistency
Diagnosis
Caseating granulomatous lymphadenitis, consistent with mycobacterial infection
Stage Classification
Stage: [granulomatous/caseating/fibrocaseous], activity: [active/chronic/healing]
Histological Features
Shows [epithelioid granulomas] with [central caseous necrosis] and [Langhans giant cells]
Size and Necrosis
Size: [X.X] cm, caseous necrosis: [extensive/focal], granulomas: [well-formed/confluent]
Organism Detection
AFB stain: [positive/negative], PCR/GeneXpert: [positive/negative for MTB], resistance: [pattern if detected]
Special Studies
AFB stain: [positive/negative for acid-fast bacilli], morphology: [description]
GeneXpert MTB/RIF: [positive/negative], rifampin resistance: [detected/not detected]
Culture: [positive/negative/pending for M. tuberculosis], drug sensitivity: [pattern]
Final Diagnosis
Caseating granulomatous lymphadenitis, [drug-sensitive/drug-resistant] tuberculosis, requiring anti-TB therapy