Definition/General
Introduction:
Cat scratch disease is a bacterial infection caused by Bartonella henselae, a gram-negative, fastidious bacterium
It typically presents as regional lymphadenopathy following cat scratch or bite
First described by Debré in 1950 and later characterized by Parinaud
The disease is self-limiting in immunocompetent hosts but can cause severe complications in immunocompromised patients.
Origin:
Caused by Bartonella henselae, transmitted primarily through cat scratches or bites
Cat fleas (Ctenocephalides felis) serve as vectors between cats
Cats are asymptomatic carriers with bacteremia lasting months
Direct inoculation through broken skin leads to local infection
Hematogenous spread to regional lymph nodes occurs
Zoonotic transmission from infected felines to humans.
Classification:
Clinical classification includes typical cat scratch disease (regional lymphadenopathy)
Atypical presentations: Parinaud oculoglandular syndrome
Neuroretinitis
Encephalopathy
Osteomyelitis
Endocarditis
Histological patterns: Early inflammatory phase
Necrotizing granulomatous phase
Suppurative phase with stellate abscesses.
Epidemiology:
Seasonal peak in autumn and winter (kitten season)
Higher incidence in children and young adults
Warm, humid climates favor flea vectors
Pet ownership major risk factor
Immunocompromised patients at risk for severe disease
Global distribution with higher prevalence in developed countries
Estimated 24,000 cases annually in United States.
Clinical Features
Presentation:
Primary skin lesion at inoculation site (papule, vesicle, or pustule)
Regional lymphadenopathy develops 1-2 weeks later
Unilateral lymph node enlargement (90% of cases)
Axillary lymph nodes most commonly affected (upper extremity scratches)
Cervical lymphadenopathy (head/neck scratches)
Inguinal involvement (lower extremity scratches)
Tender, enlarged lymph nodes.
Symptoms:
Low-grade fever (60% of cases)
Malaise and fatigue
Headache and myalgia
Anorexia and weight loss
Nausea and vomiting (less common)
Parinaud syndrome (conjunctivitis with preauricular lymphadenopathy)
No significant constitutional symptoms in typical cases.
Risk Factors:
Cat exposure (especially kittens <1 year old)
Cat scratches or bites within 3 weeks of symptom onset
Flea-infested cats (higher bacterial load)
Immunocompromised state (risk for severe disease)
Seasonal exposure (autumn/winter peak)
Outdoor cats higher risk than indoor cats
Geographic location (warm, humid climates).
Screening:
History of cat exposure (scratch, bite, or close contact)
Clinical examination for primary skin lesion and lymphadenopathy
Bartonella henselae serology (IgG and IgM)
PCR testing on tissue or aspirate
Warthin-Starry silver stain on histological sections
Bacterial culture (difficult, specialized media required)
Fine needle aspiration for cytological examination.
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Gross Description
Appearance:
Enlarged lymph nodes with intact, thickened capsule
Cut surface shows gray-white areas alternating with yellow-tan necrotic foci
Firm to fluctuant consistency depending on stage
Central softening may be present in suppurative phase
Multiple small abscesses visible grossly
Capsular thickening and adhesions
Surrounding tissue inflammation.
Characteristics:
Multinodular appearance with areas of necrosis and fibrosis
Central necrosis surrounded by inflammatory tissue
No typical caseous material (unlike tuberculosis)
Purulent material in advanced cases
Fibrotic areas in healing phase
Vascular prominence in capsule
Adherence to surrounding tissues common.
Size Location:
Size ranges from 1-6 cm in greatest dimension
Axillary lymph nodes most commonly affected (50-60%)
Cervical lymph nodes (25-30%)
Inguinal lymph nodes (10-15%)
Epitrochlear lymph nodes occasionally involved
Usually single lymph node group affected
Bilateral involvement rare.
Multifocality:
Regional lymphadenopathy following lymphatic drainage pattern
Multiple lymph nodes within same anatomical region commonly affected
Unilateral involvement typical (>90%)
Proximal spread along lymphatic chains
Generalized lymphadenopathy rare except in immunocompromised
Extranodal involvement (liver, spleen) in severe cases.
Microscopic Description
Histological Features:
Three-phase inflammatory response: early lymphoid hyperplasia, granulomatous inflammation, and suppurative necrosis
Stellate abscesses (pathognomonic feature) with central neutrophilic necrosis surrounded by epithelioid cells and lymphocytes
Microabscesses with surrounding granulomatous inflammation
Reactive follicular hyperplasia in early stages
Capsular thickening and fibrosis.
Cellular Characteristics:
Central neutrophilic necrosis in stellate abscesses
Epithelioid cells surrounding necrotic centers
Multinucleated giant cells (foreign body and Langhans type)
Lymphocytes and histiocytes in surrounding areas
Plasma cells in chronic stages
Eosinophils may be present
Endothelial proliferation in granulation tissue.
Architectural Patterns:
Necrotizing granulomatous pattern with stellate morphology
Geographic necrosis with irregular, star-shaped outline
Preserved nodal architecture in early stages
Progressive architectural distortion with abscess formation
Paracortical hyperplasia pattern
Sinus histiocytosis may be present
Capsular involvement with pericapsular inflammation.
Grading Criteria:
Stage-based assessment: lymphoid hyperplasia, granulomatous, necrotizing/suppurative
Early stage: reactive follicular hyperplasia with minimal necrosis
Intermediate stage: granulomatous inflammation with microabscesses
Advanced stage: extensive necrosis with stellate abscesses
Resolution stage: fibrosis and healing
No malignant potential grading.
Immunohistochemistry
Positive Markers:
CD68 positive in epithelioid cells and histiocytes
CD3 highlights T-lymphocytes around abscesses
CD20 shows B-cells in preserved follicular areas
Lysozyme positive in histiocytes
S-100 may be positive in Langerhans cells
CD15 positive in neutrophils within abscesses
Ki-67 high in reactive areas.
Negative Markers:
Mycobacterial markers (AFB stain negative)
Fungal markers (GMS, PAS negative)
CD1a and Langerin negative (excludes LCH)
CD30 negative (excludes lymphoma)
Cytokeratin negative (excludes carcinoma)
Melanoma markers negative
EBV/EBER negative.
Diagnostic Utility:
Warthin-Starry silver stain may demonstrate Bartonella organisms (sensitivity 10-20%)
Steiner stain alternative for bacterial visualization
Immunohistochemistry limited utility for organism detection
CD68 staining highlights granulomatous component
Negative AFB and GMS stains exclude mycobacterial and fungal infections
PCR more sensitive than histochemical stains.
Molecular Subtypes:
No molecular subtypes but different Bartonella species may cause similar disease
Bartonella henselae most common cause
Bartonella clarridgeiae less common
Bartonella quintana causes similar syndrome
PCR identification can distinguish species
Genotyping available for epidemiological studies
Antibiotic susceptibility generally similar across species.
Molecular/Genetic
Genetic Mutations:
No human genetic mutations specifically associated with cat scratch disease susceptibility
Bacterial virulence genes include outer membrane proteins
Type IV secretion system important for pathogenesis
Bartonella adhesin genes (badA, vomp)
Immune evasion genes
Host immune response genes may influence disease severity
No chromosomal abnormalities in infected tissues.
Molecular Markers:
Bartonella-specific PCR targets 16S rRNA gene
ITS region amplification for species identification
Real-time PCR for quantitative detection
Inflammatory cytokines (IL-1β, TNF-α, IL-6) elevated
T-helper 1 immune response pattern
Interferon-γ production important for bacterial clearance
Antibody response (IgM followed by IgG).
Prognostic Significance:
Excellent prognosis in immunocompetent hosts (self-limiting disease)
Resolution within 2-4 months typical
Immunocompromised patients may develop severe complications
Parinaud syndrome has good prognosis with conservative treatment
Neuroretinitis usually resolves completely
Rare complications: endocarditis, osteomyelitis, encephalopathy
Mortality extremely rare in immunocompetent individuals.
Therapeutic Targets:
Supportive care for typical disease (observation, analgesics)
Antibiotics controversial for typical lymphadenopathy
Azithromycin may reduce lymph node size and duration
Doxycycline alternative antibiotic
Clarithromycin or trimethoprim-sulfamethoxazole for severe cases
Surgical drainage rarely needed
Prevention: avoid cat scratches, flea control.
Differential Diagnosis
Similar Entities:
Tuberculosis (caseating granulomas)
Atypical mycobacterial infection
Tularemia (Francisella tularensis)
Toxoplasmosis (epithelioid cell clusters)
Lymphogranuloma venereum (Chlamydia)
Kikuchi disease (necrotizing lymphadenitis)
Sarcoidosis (non-caseating granulomas)
Hodgkin lymphoma (mixed cellularity type).
Distinguishing Features:
Cat scratch disease: stellate abscesses, neutrophilic centers, cat exposure history, Warthin-Starry positive
Tuberculosis: caseous necrosis, Langhans giant cells, AFB positive
Tularemia: ulceroglandular syndrome, different exposure history
Toxoplasmosis: epithelioid cell clusters, different serology
Kikuchi: absence of neutrophils, crescentic histiocytes
Sarcoidosis: non-caseating granulomas, systemic involvement.
Diagnostic Challenges:
Early stages may lack characteristic stellate abscesses
Chronic cases may show extensive fibrosis obscuring features
Bacterial staining sensitivity low (10-20% with Warthin-Starry)
Serology may be negative in early infection
Atypical presentations in immunocompromised patients
PCR testing increasingly important for diagnosis
Clinical correlation essential including exposure history.
Rare Variants:
Parinaud oculoglandular syndrome (conjunctivitis with preauricular lymphadenopathy)
Neuroretinitis (optic nerve involvement)
Encephalopathy (CNS complications)
Fournier gangrene-like syndrome
Osteomyelitis (bone involvement)
Endocarditis (cardiac complications)
Bacillary angiomatosis (in immunocompromised)
Peliosis hepatis (liver involvement).
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 [axillary/cervical/inguinal] region, measuring [X.X] cm in greatest dimension
Diagnosis
Cat scratch disease (necrotizing granulomatous lymphadenitis), [stage/phase]
Stage Classification
Stage: [lymphoid hyperplasia/granulomatous/necrotizing-suppurative], pattern: [stellate abscesses/microabscesses]
Histological Features
Shows [necrotizing granulomatous inflammation] with [stellate abscesses/microabscesses] and [epithelioid cell reaction]
Size and Pattern
Size: [X.X] cm, necrosis: [stellate pattern/geographic], inflammation: [granulomatous/mixed]
Cellular Composition
Contains [neutrophilic necrosis/epithelioid cells/giant cells] with [surrounding lymphocytes/plasma cell infiltrate]
Special Studies
Special stains: Warthin-Starry [positive/negative for bacteria], AFB [negative], GMS [negative]
PCR: [if performed] Bartonella henselae [positive/negative/not performed]
Serology: [if available] Bartonella IgG/IgM [results]
Final Diagnosis
Cat scratch disease (Bartonella henselae infection), necrotizing granulomatous lymphadenitis, consistent with bacterial infection