Definition/General
Introduction:
Splenic tuberculosis is infection of the spleen by Mycobacterium tuberculosis, occurring as part of miliary tuberculosis or rarely as isolated splenic involvement
It represents hematogenous dissemination from pulmonary or extrapulmonary sites
Splenic TB is characterized by granulomatous inflammation with caseous necrosis
In India, it represents a significant diagnostic challenge due to high TB burden and varied presentations.
Origin:
Results from hematogenous spread of mycobacteria from primary infection sites (usually lungs)
Miliary tuberculosis: Most common pattern with multiple organ involvement
Primary splenic TB: Rare, may occur without obvious primary site
Reactivation disease: In immunocompromised patients
Atypical mycobacteria: May also cause similar lesions.
Classification:
By pattern: Miliary tuberculosis (multiple small granulomas)
Macronodular tuberculosis (large granulomatous masses)
By stage: Acute disseminated TB
Chronic tuberculosis
By organism: M
tuberculosis
Atypical mycobacteria
By response: Drug-sensitive
Drug-resistant (MDR/XDR).
Epidemiology:
High prevalence in India: Part of 2.7 million active TB cases
Age distribution: Any age, but peak in young adults (20-40 years)
Risk factors: HIV co-infection (50-60% of cases)
Immunosuppression, malnutrition
Gender: Male predominance (1.5:1)
Associated mortality: 15-25% if untreated.
Clinical Features
Presentation:
Fever (90-95% of patients): Often prolonged, low-grade
Weight loss (80-85%): Significant, >10% body weight
Splenomegaly (60-70%): Moderate to massive enlargement
Hepatomegaly (50-60%): Often accompanies splenomegaly
Lymphadenopathy (40-50%): Multiple sites involved.
Symptoms:
Constitutional symptoms: Night sweats, malaise, anorexia
Chronic fatigue and weakness
Abdominal symptoms: Left upper quadrant discomfort
Early satiety due to splenomegaly
Respiratory symptoms: Cough, dyspnea (pulmonary involvement)
Hematologic symptoms: Easy bruising (hypersplenism).
Risk Factors:
HIV co-infection: Strongest risk factor, increases risk 20-fold
Immunosuppression: Corticosteroids, chemotherapy, organ transplant
Malnutrition: Protein-energy malnutrition, vitamin deficiencies
Diabetes mellitus: 3-fold increased risk
Chronic diseases: Chronic kidney disease, liver disease
Age extremes: Children <5 years, elderly >65 years.
Screening:
High-risk populations: HIV patients, immunocompromised individuals
Diagnostic tests: Tuberculin skin test, Interferon-gamma release assays
Imaging studies: Chest X-ray, CT chest and abdomen
Laboratory studies: AFB smear, cultures, Gene Xpert
Tissue diagnosis: Splenic biopsy in suspected cases.
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Gross Description
Appearance:
Multiple small nodules (miliary pattern): 1-3 mm gray-white nodules scattered throughout spleen
Large nodular masses (macronodular): 2-5 cm masses with central caseous necrosis
Confluent granulomas: Multiple granulomas coalescing into larger masses
Caseous material: Yellow-white, cheese-like necrotic centers.
Characteristics:
Enlarged spleen: Weight 400-1500g (normal 150g)
Firm consistency: Due to granulomatous inflammation and fibrosis
Cut surface: Multiple gray-white nodules with yellow centers
Calcification: In chronic cases, visible as gritty areas
Cavitation: Rare, but may occur in large lesions.
Size Location:
Miliary pattern: Numerous 1-3 mm nodules throughout spleen
Macronodular pattern: Few large nodules 2-5 cm in diameter
Random distribution: No specific anatomic predilection
Bilateral involvement: Both splenic lobes affected
Hilar involvement: May extend to splenic hilum and vessels.
Multifocality:
Multiple granulomas: Present in >95% of cases
Systematic involvement: Usually part of disseminated disease
Associated organ involvement: Liver (90%), lungs (80%), lymph nodes (70%)
Bone marrow involvement: Common in miliary TB
CNS involvement: Serious complication in 10-15% cases.
Microscopic Description
Histological Features:
Epithelioid granulomas: Well-formed granulomas with central caseous necrosis
Langhans giant cells: Multinucleated cells with peripheral nuclei arrangement
Caseous necrosis: Central zone of structureless, eosinophilic necrotic material
Lymphocytic infiltrate: Surrounding granulomas
Acid-fast bacilli: May be demonstrable in necrotic areas.
Cellular Characteristics:
Epithelioid cells: Activated macrophages with elongated nuclei and abundant eosinophilic cytoplasm
Langhans giant cells: Multiple nuclei arranged at cell periphery
Lymphocytes: Predominantly T-cells surrounding granulomas
Plasma cells: Present in chronic inflammation
Neutrophils: May be present in acute phases or secondary bacterial infection.
Architectural Patterns:
Well-formed granulomas: Classic tuberculous granuloma with epithelioid cells, giant cells, and caseous necrosis
Confluent granulomas: Multiple granulomas merging together
Zonal arrangement: Central caseous necrosis surrounded by epithelioid cells, then lymphocytes
Peripheral fibrosis: Chronic cases show fibrous tissue around granulomas.
Grading Criteria:
Active tuberculosis: Prominent epithelioid cells, giant cells, fresh caseous necrosis
Chronic tuberculosis: Extensive fibrosis, calcification, organized granulomas
Healing tuberculosis: Fibroblastic proliferation, reduced inflammatory activity
Complicated tuberculosis: Secondary bacterial infection, extensive necrosis.
Immunohistochemistry
Positive Markers:
CD68: Positive in epithelioid cells and giant cells
Lysozyme: Positive in epithelioid cells
CD3: Positive in surrounding T-lymphocytes
Interferon-γ: May be positive in activated T-cells.
Negative Markers:
Cytokeratins: Negative in epithelioid cells
S-100: Usually negative (helps distinguish from other conditions)
CD20: Negative in epithelioid cells (positive in scattered B-cells)
CD1a: Negative (helps exclude Langerhans cell histiocytosis).
Diagnostic Utility:
Confirmation of granulomatous inflammation: CD68+ epithelioid cells
T-cell response demonstration: CD3+ lymphocytes
Exclusion of other conditions: Negative markers help rule out malignancy
Assessment of immune response: Pattern of inflammatory cells.
Molecular Subtypes:
Classical TB granulomas: Well-formed epithelioid granulomas with caseous necrosis
Atypical presentations: In immunocompromised patients, may lack classic features
Drug-resistant TB: May show more extensive necrosis and inflammation
HIV-associated TB: May have atypical granuloma formation.
Molecular/Genetic
Genetic Mutations:
Host susceptibility genes: IL-12, IFN-γ receptor deficiency
HLA associations with TB susceptibility
Mycobacterial resistance genes: rpoB (rifampicin resistance), katG (isoniazid resistance)
MDR-TB genes: Multiple drug resistance mutations
XDR-TB genes: Extensively drug-resistant mutations.
Molecular Markers:
Mycobacterial DNA: PCR detection of M
tuberculosis complex
Gene Xpert: Rapid detection and rifampicin resistance
Cytokine expression: IFN-γ, TNF-α, IL-12 in immune response
Bacterial load markers: Quantification of mycobacterial burden.
Prognostic Significance:
Drug susceptibility: Sensitive TB has excellent prognosis with treatment
Drug resistance: MDR/XDR-TB has poor prognosis
HIV co-infection: Significantly worsens prognosis
Extent of disease: Disseminated disease has higher mortality
Host immune status: Immunocompromise affects outcomes.
Therapeutic Targets:
First-line anti-TB drugs: Isoniazid, rifampicin, ethambutol, pyrazinamide
Second-line drugs: For drug-resistant cases
Newer drugs: Bedaquiline, delamanid for XDR-TB
Host-directed therapy: Immune modulators
Duration: 6-24 months depending on resistance pattern.
Differential Diagnosis
Similar Entities:
Other granulomatous diseases: Sarcoidosis (non-necrotizing granulomas)
Histoplasmosis (fungal organisms)
Malignancies: Hodgkin lymphoma (Reed-Sternberg cells)
Carcinomas with granulomatous reaction
Other infections: Atypical mycobacteria, brucellosis
Autoimmune conditions: Chronic granulomatous disease.
Distinguishing Features:
TB vs sarcoidosis: Caseous necrosis present vs absent
AFB positive vs negative
TB vs fungi: AFB stain vs fungal stains (GMS, PAS)
TB vs lymphoma: Granulomatous inflammation vs neoplastic cells
Molecular testing: PCR for specific organism identification.
Diagnostic Challenges:
Paucibacillary disease: Few organisms may be difficult to detect
Atypical presentations: In immunocompromised patients
Mixed infections: TB with other opportunistic infections
Sampling issues: Adequate tissue sampling crucial
False negatives: AFB stain may be negative in up to 50% cases.
Rare Variants:
Primary splenic TB: Isolated splenic involvement without obvious primary site
Tuberculous abscess: Large caseous masses mimicking abscesses
Calcified TB: Chronic cases with extensive calcification
Atypical mycobacteria: M
avium-intracellulare complex in immunocompromised
Spinal TB with splenic involvement: Part of disseminated skeletal TB.
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
[Biopsy/splenectomy] specimen with clinical history of [fever, weight loss] and [risk factors]
Gross Description
[Miliary/macronodular] pattern with [number] granulomas and [caseous necrosis characteristics]
Microscopic Findings
Well-formed epithelioid granulomas with [caseous necrosis], [Langhans giant cells], and [lymphocytic infiltrate]
Acid-Fast Bacilli Stain
AFB stain: [positive/negative] for acid-fast bacilli
Molecular Studies
Gene Xpert: [positive/negative]. PCR for M. tuberculosis: [positive/negative]
Diagnosis
Splenic tuberculosis with necrotizing granulomatous inflammation
Drug Susceptibility
[Susceptible/resistant] to [first-line drugs] - [specific resistance pattern if known]
Recommendations
Recommend [anti-TB therapy] for [duration] and clinical correlation with systemic evaluation