Definition/General
Introduction:
Lymph node toxoplasmosis is a parasitic infection caused by Toxoplasma gondii, an obligate intracellular protozoan parasite
It typically presents as lymphadenopathy in immunocompetent individuals
Cats are the definitive host while humans are intermediate hosts
The condition is usually benign and self-limiting in healthy individuals but can cause severe disease in immunocompromised patients and pregnant women.
Origin:
Caused by Toxoplasma gondii, transmitted through multiple routes: ingestion of oocysts from cat feces or contaminated soil
Consumption of undercooked meat containing tissue cysts
Transplacental transmission (congenital toxoplasmosis)
Blood transfusion or organ transplantation (rare)
Laboratory exposure in healthcare workers
The parasite has complex life cycle involving sexual reproduction in cats and asexual reproduction in intermediate hosts.
Classification:
Clinical classification: Acquired toxoplasmosis (immunocompetent vs immunocompromised)
Congenital toxoplasmosis (maternal-fetal transmission)
Ocular toxoplasmosis (chorioretinitis)
Histological patterns: Early reactive phase (follicular hyperplasia)
Characteristic phase (epithelioid cell clusters)
Chronic phase (fibrosis and resolution).
Epidemiology:
Worldwide distribution with seroprevalence varying by region (10-80%)
Higher prevalence in tropical and subtropical regions
Age-related increase in seroprevalence
Cat ownership and raw meat consumption increase risk
Immunocompromised patients at risk for reactivation
Pregnant women risk vertical transmission
Occupational exposure in veterinarians and farm workers.
Clinical Features
Presentation:
Asymptomatic infection in 80-90% of immunocompetent individuals
Lymphadenopathy (most common symptomatic presentation)
Cervical lymph nodes most frequently involved
Posterior cervical triangle predilection
Unilateral or bilateral enlargement
Firm, non-tender lymph nodes
Generalized lymphadenopathy in some cases
Hepatosplenomegaly occasionally present.
Symptoms:
Flu-like syndrome: fever, malaise, myalgia
Sore throat and headache
Fatigue and weakness
Night sweats (less common than lymphoma)
Maculopapular rash (rare)
Atypical lymphocytosis on blood smear
Elevated liver enzymes possible
No weight loss typically (unlike malignancy).
Risk Factors:
Cat ownership or exposure to cat feces
Consumption of undercooked meat (lamb, pork, beef)
Gardening or contact with contaminated soil
Poor food hygiene practices
Immunocompromised state (HIV, transplant recipients)
Pregnancy (risk of congenital transmission)
Occupational exposure (veterinarians, butchers)
Geographic location (endemic areas).
Screening:
Toxoplasma-specific serology (IgG and IgM antibodies)
IgG avidity testing to determine timing of infection
PCR testing on blood or tissue
Complete blood count (atypical lymphocytes)
Liver function tests
Pregnancy screening in pregnant women
HIV testing in at-risk populations
Ophthalmologic examination for ocular involvement.
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Gross Description
Appearance:
Enlarged lymph nodes with smooth, intact capsule
Cut surface shows gray-white to tan coloration
Firm consistency without fluctuation
Prominent follicular pattern may be visible
No necrosis or caseation typically
Capsular thickening in chronic cases
Surrounding tissue may show reactive changes.
Characteristics:
Homogeneous cut surface without significant variegation
No suppuration or abscess formation
Preserved architecture grossly visible
Multiple lymph nodes may be affected
No calcification typically present
Vascular prominence in some cases
Fibrotic areas in chronic infection.
Size Location:
Size ranges from 1-4 cm in greatest dimension
Cervical lymph nodes most commonly affected (80-90%)
Posterior cervical triangle characteristic location
Supraclavicular and submandibular involvement
Axillary lymph nodes less commonly affected
Generalized lymphadenopathy in some cases
Mediastinal involvement rare.
Multifocality:
Regional lymphadenopathy following drainage patterns
Bilateral cervical involvement common
Multiple lymph node groups may be simultaneously affected
Asymmetric distribution possible
Progressive involvement over weeks to months
Spontaneous resolution typical in immunocompetent hosts.
Microscopic Description
Histological Features:
Triad of features: reactive follicular hyperplasia, epithelioid cell clusters, and monocytoid B-cell proliferation
Epithelioid cell clusters scattered throughout paracortex (characteristic feature)
Follicular hyperplasia with reactive germinal centers
Monocytoid B-cells in marginal zones and sinuses
Increased plasma cells and immunoblasts
Sinus histiocytosis may be present.
Cellular Characteristics:
Epithelioid cells in small clusters without giant cell formation
Monocytoid B-cells with abundant pale cytoplasm and round nuclei
Reactive germinal centers with tingible body macrophages
Increased plasma cells and immunoblasts in interfollicular areas
T-lymphocytes predominant in paracortex
Rare parasites may be identified in tissue sections
No significant atypia or mitotic activity.
Architectural Patterns:
Preserved lymph node architecture with reactive changes
Follicular hyperplasia pattern with expanded germinal centers
Paracortical expansion with epithelioid cell clusters
Marginal zone expansion with monocytoid B-cells
Sinus dilatation may be present
Interfollicular plasma cell infiltration
Capsular reactive changes.
Grading Criteria:
No standard grading system for toxoplasma lymphadenitis
Phase-based assessment: acute reactive, characteristic, chronic
Epithelioid cell cluster density
Degree of follicular hyperplasia
Monocytoid B-cell prominence
Plasma cell infiltration extent
Resolution assessment in follow-up biopsies
Parasite identification (rare but diagnostic when present).
Immunohistochemistry
Positive Markers:
CD20 highlights B-cell follicles and monocytoid B-cells
CD3 shows T-cells in paracortical areas
CD68 positive in epithelioid cells and histiocytes
CD138 demonstrates increased plasma cells
Ki-67 high in germinal centers
Lysozyme positive in epithelioid cells
BCL-6 positive in germinal center B-cells.
Negative Markers:
CD1a and Langerin negative (excludes Langerhans cell histiocytosis)
CD30 negative (excludes lymphoma)
Cyclin D1 negative (excludes mantle cell lymphoma)
BCL-2 negative in germinal centers
ALK-1 negative
S-100 negative in epithelioid cells
Melanoma markers negative.
Diagnostic Utility:
CD68 staining highlights epithelioid cell clusters
CD20 staining demonstrates monocytoid B-cell proliferation
Toxoplasma-specific immunostains may identify organisms (sensitivity varies)
Ki-67 shows reactive proliferation pattern
Light chain staining demonstrates polyclonal plasma cells
T-cell markers show preserved T-cell zones
No aberrant expression patterns.
Molecular Subtypes:
No molecular subtypes but strain variations exist
Type I strains (virulent, rare in humans)
Type II strains (intermediate virulence, common in Europe/North America)
Type III strains (less virulent)
Recombinant strains in some geographic regions
Genotyping available for epidemiological studies
Drug resistance markers under investigation.
Molecular/Genetic
Genetic Mutations:
No human genetic mutations specifically associated with toxoplasma susceptibility
HLA associations may influence disease severity
Cytokine gene polymorphisms affect immune response
Parasite genetic diversity influences virulence
Host immune response genes (IFN-γ, IL-12) important
No chromosomal abnormalities in infected lymph nodes.
Molecular Markers:
Toxoplasma-specific PCR targets multiple genes (B1, REP529, ITS-1)
Real-time PCR for quantitative detection
Genotyping markers for strain identification
Inflammatory cytokines (IFN-γ, IL-12, TNF-α) elevated
Th1 immune response pattern predominant
Antibody response (IgM followed by IgG)
T-cell activation markers.
Prognostic Significance:
Excellent prognosis in immunocompetent individuals
Self-limiting disease with resolution in 2-6 months
Immunocompromised patients risk severe complications
Congenital infection may cause severe fetal damage
Ocular involvement may lead to vision impairment
CNS involvement serious in immunocompromised
Lifelong latency with potential for reactivation.
Therapeutic Targets:
No treatment needed for typical lymphadenopathy in immunocompetent hosts
Sulfadiazine plus pyrimethamine for severe disease
Leucovorin (folinic acid) to prevent folate deficiency
Clindamycin alternative for sulfa-allergic patients
Atovaquone for refractory cases
Spiramycin for pregnant women
Prevention: proper food handling, cat hygiene.
Differential Diagnosis
Similar Entities:
Infectious mononucleosis (EBV, CMV)
Cat scratch disease (Bartonella henselae)
Reactive follicular hyperplasia (other causes)
Hodgkin lymphoma (mixed cellularity type)
Marginal zone lymphoma (monocytoid B-cells)
Sarcoidosis (epithelioid granulomas)
Kikuchi disease (necrotizing lymphadenitis)
Tuberculosis (epithelioid granulomas).
Distinguishing Features:
Toxoplasmosis: epithelioid cell clusters without giants, monocytoid B-cells, preserved architecture
EBV: atypical lymphocytes, Reed-Sternberg-like cells, EBER positive
Cat scratch: stellate abscesses, neutrophils, Warthin-Starry positive
Hodgkin: Reed-Sternberg cells, CD30+, CD15+
Marginal zone lymphoma: monoclonal B-cells, architectural effacement
Sarcoidosis: non-caseating granulomas, giant cells.
Diagnostic Challenges:
Epithelioid cell clusters may be focal or sparse
Monocytoid B-cells not always prominent
Parasite identification extremely rare in tissue sections
Serology correlation essential for diagnosis
Chronic cases may lack characteristic features
Immunocompromised patients may show atypical histology
PCR testing increasingly important.
Rare Variants:
Necrotizing lymphadenitis (immunocompromised patients)
Granulomatous variant (prominent epithelioid cell reaction)
Suppurative variant (secondary bacterial infection)
Chronic fibrosing variant
Ocular toxoplasmosis (chorioretinitis)
CNS toxoplasmosis (brain abscess)
Congenital variant (different pathology)
Disseminated variant (multiple organ 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 [cervical/axillary/other] region, measuring [X.X] cm in greatest dimension
Diagnosis
Toxoplasma lymphadenitis with characteristic histological features
Pattern Classification
Pattern: [reactive hyperplasia with epithelioid clusters], phase: [acute/characteristic/chronic]
Histological Features
Shows [characteristic triad] with [follicular hyperplasia/epithelioid cell clusters/monocytoid B-cell proliferation]
Size and Architecture
Size: [X.X] cm, architecture: [preserved with reactive changes], epithelioid clusters: [present/prominent]
Cellular Composition
Contains [epithelioid cell clusters without giant cells/monocytoid B-cells/reactive follicles] with [increased plasma cells]
Special Studies
IHC: CD20 [monocytoid B-cells], CD68 [epithelioid cells], CD3 [T-cells], Toxoplasma [positive/negative/not performed]
PCR: [if performed] Toxoplasma gondii [positive/negative/not performed]
Serology: [if available] Toxoplasma IgG/IgM [results/correlation recommended]
Final Diagnosis
Toxoplasma lymphadenitis, consistent with parasitic infection, clinical correlation with serology recommended