Definition/General
Introduction:
Kikuchi disease, also known as histiocytic necrotizing lymphadenitis, is a rare benign inflammatory condition affecting lymph nodes
It was first described by Kikuchi and Fujimoto in 1972
The disease is characterized by necrotizing inflammation with distinctive crescentic histiocytes
FNAC shows characteristic features that help distinguish it from other necrotizing lymphadenopathies.
Origin:
Etiology remains unknown but likely represents an abnormal immune response to viral infections
Proposed triggers include EBV, CMV, parvovirus B19, and HHV-6
Results in T-cell mediated cytotoxicity against infected cells
Apoptosis and cell-mediated immunity play key roles
Self-limited inflammatory response with spontaneous resolution.
Classification:
Histological classification: Proliferative phase (early stage with histiocytic proliferation)
Necrotizing phase (extensive necrosis with karyorrhectic debris)
Xanthomatous phase (resolution with foamy macrophages)
Clinical variants: Typical Kikuchi disease (isolated lymphadenopathy)
Systemic Kikuchi disease (with extranodal features)
SLE-associated variant.
Epidemiology:
Higher prevalence in East Asian populations (Japan, Korea, Taiwan)
Female predominance (male:female = 1:4)
Peak incidence in 2nd and 3rd decades (20-30 years)
Rare in children and elderly
Sporadic cases worldwide but endemic in certain regions
Seasonal clustering observed in some reports.
Clinical Features
Presentation:
Unilateral cervical lymphadenopathy (most common, 70-80%)
Posterior cervical triangle preferentially involved
Firm, mobile lymph nodes
Nodes may be tender (unlike malignancy)
Single or multiple nodes
Axillary and supraclavicular involvement less common
Bilateral involvement rare.
Symptoms:
Fever (30-50% of cases) - usually low-grade
Night sweats and malaise
Weight loss (10-20% of patients)
Arthralgia and myalgia
Skin rash (maculopapular) in 10% cases
Hepatosplenomegaly rare
Upper respiratory symptoms may precede lymphadenopathy.
Risk Factors:
Female gender (major risk factor)
Asian ethnicity (especially East Asian)
Young adult age group (20-40 years)
Recent viral infection history
Autoimmune predisposition
Genetic factors (HLA associations reported)
Environmental factors may play a role.
Screening:
No specific screening tests available
Complete blood count may show leukopenia or atypical lymphocytes
ESR and CRP may be elevated
LDH elevation in some cases
ANA testing to rule out SLE
Viral serology (EBV, CMV) may be helpful
FNAC is the primary diagnostic procedure.
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Gross Description
Appearance:
Enlarged lymph nodes (usually 1-6 cm)
Nodes are firm and mobile
Single or multiple nodes involved
Cut surface shows gray-white areas with focal necrosis
Areas of hemorrhage may be present
Capsular thickening common
Matting of nodes uncommon.
Characteristics:
FNAC aspirate shows variable cellularity
Hemorrhagic background common
Necrotic debris and karyorrhectic material
Thick, viscous aspirate due to necrosis
May be paucicellular in extensively necrotic areas
Granular, eosinophilic background
No purulent material.
Size Location:
Cervical lymph nodes most commonly affected (90%)
Posterior cervical triangle (levels II-V) preferentially involved
Supraclavicular nodes in 15-20% cases
Axillary nodes less common (10%)
Node size ranges from 1-8 cm
Unilateral involvement typical.
Multifocality:
Multiple nodes in same region common
Unilateral distribution characteristic (95% cases)
Bilateral involvement suggests systemic disease
Generalized lymphadenopathy rare
Extranodal involvement uncommon
Regional clustering of affected nodes.
Microscopic Description
Histological Features:
FNAC shows necrotizing inflammation with distinctive cellular features
Crescentic histiocytes (characteristic finding)
Abundant karyorrhectic debris
Plasmacytoid dendritic cells
Activated T-lymphocytes
Absence of neutrophils (important negative finding)
Tingible body macrophages may be present.
Cellular Characteristics:
Crescentic histiocytes: Kidney-shaped or crescentic nuclei with abundant cytoplasm
Plasmacytoid dendritic cells: Round to oval cells with eccentric nuclei, moderate cytoplasm
Immunoblasts: Large cells with vesicular nuclei and prominent nucleoli
Small lymphocytes: CD8+ T cells predominant
Apoptotic cells abundant
Karyorrhectic debris: Nuclear fragments.
Architectural Patterns:
Paracortical necrosis with preserved follicles initially
Progressive necrotizing inflammation
Geographic necrosis in advanced cases
Perinodal extension may occur
Zonal architecture: central necrosis, peripheral viable tissue
Absence of granulomas (helps differentiate from other conditions).
Grading Criteria:
Morphological phases: Phase I (Proliferative): Histiocytic proliferation with minimal necrosis
Phase II (Necrotizing): Extensive necrosis with crescentic histiocytes
Phase III (Xanthomatous): Resolution with foamy macrophages
Activity assessment based on necrosis extent and cellular composition
No formal grading system exists.
Immunohistochemistry
Positive Markers:
CD68 positive in histiocytes and crescentic cells
CD163 positive in macrophages
Lysozyme positive in histiocytes
CD8 positive in T-lymphocytes (predominant)
CD3 positive in T-cells
Perforin positive in cytotoxic T-cells
Granzyme B positive in activated T-cells.
Negative Markers:
CD15 and CD30 negative (excludes Hodgkin lymphoma)
Cytokeratin negative (excludes carcinoma)
CD20 decreased or absent
Neutrophil markers negative (MPO, neutrophil elastase)
CD1a and Langerin negative (excludes LCH)
ALK negative (excludes ALCL).
Diagnostic Utility:
IHC helps confirm histiocytic nature of crescentic cells
CD8 predominance characteristic
Useful to exclude malignancy (lymphoma, carcinoma)
Helps differentiate from other necrotizing lymphadenopathies
Absence of B-cells in necrotic areas
Cytotoxic marker expression supports diagnosis.
Molecular Subtypes:
Kikuchi disease shows T-cell mediated cytotoxicity pattern
High expression of perforin and granzyme B
Interferon-alpha pathway activation
Type I interferon signature
Apoptosis pathway activation
Complement system involvement
Autoimmune markers may be present.
Molecular/Genetic
Genetic Mutations:
No specific genetic mutations identified for Kikuchi disease
HLA associations reported (HLA-DPA1, HLA-DPB1)
Viral genome integration not demonstrated
Chromosomal abnormalities absent
Clonal gene rearrangements negative
Genetic susceptibility factors under investigation.
Molecular Markers:
Type I interferon signature prominent
High expression of ISG15 (interferon-stimulated gene)
MxA protein upregulation
CXCL10 elevation
TNF-alpha and IL-6 elevation
Complement C1q deposition
Viral nucleic acids rarely detected.
Prognostic Significance:
Excellent prognosis with spontaneous resolution in most cases
Self-limiting disease resolving in 3-6 months
Recurrence rate low (3-5%)
No malignant transformation
Associated SLE development in rare cases
Complete recovery expected without specific treatment.
Therapeutic Targets:
Supportive care is usually sufficient
NSAIDs for symptomatic relief
Corticosteroids for severe systemic symptoms
Immunosuppressive therapy rarely needed
Antiviral therapy not effective
Antibiotics not indicated unless secondary infection
Follow-up until resolution.
Differential Diagnosis
Similar Entities:
Systemic lupus erythematosus (SLE lymphadenopathy)
Tuberculosis (necrotizing lymphadenitis)
Lymphoma (especially T-cell lymphomas)
Cat scratch disease (necrotizing lymphadenitis)
Toxoplasmosis
Viral lymphadenitis (EBV, CMV)
Kawasaki disease
Drug-induced lymphadenopathy.
Distinguishing Features:
SLE: ANA positive, multi-system involvement, hematoxylin bodies
Tuberculosis: Caseating granulomas, AFB positive, epithelioid cells
Lymphoma: Atypical lymphoid cells, monoclonal population
Cat scratch disease: Stellate microabscesses, neutrophils present
Toxoplasmosis: Reactive follicular hyperplasia
Viral lymphadenitis: Polymorphic population, immunoblasts.
Diagnostic Challenges:
Distinguishing from T-cell lymphoma with necrosis
SLE-associated lymphadenopathy can be identical
Extensive necrosis may obscure cellular details
Secondary bacterial infection changes morphology
Sampling inadequacy in necrotic nodes
Atypical presentations without crescentic histiocytes.
Rare Variants:
Systemic Kikuchi disease with multi-organ involvement
Cutaneous Kikuchi disease
Kikuchi disease with SLE features
Recurrent Kikuchi disease
Kikuchi disease in children
Bilateral Kikuchi disease
Extranodal Kikuchi disease.
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
Fine needle aspiration cytology of [site] lymph node
Clinical History
Age: [age], Gender: [gender]. Duration: [duration]. Associated symptoms: [fever, malaise]. Unilateral/bilateral involvement
Adequacy
Adequate for evaluation despite necrotic background - sufficient cellular material for diagnosis
Morphological Features
Cellular smears showing necrotizing inflammation with characteristic crescentic histiocytes. Abundant karyorrhectic debris and apoptotic cells. Plasmacytoid dendritic cells present. Activated T-lymphocytes. Conspicuous absence of neutrophils
Special Features
Crescentic histiocytes with kidney-shaped nuclei. No granulomas identified. No organisms seen on routine stains. Background shows extensive karyorrhectic debris
Immunocytochemistry
CD68: Positive in histiocytes. CD8: Positive in T-lymphocytes (predominant). CD3: Positive. CD20: Decreased/absent. Perforin/Granzyme B: [if performed]
Cytological Diagnosis
Histiocytic necrotizing lymphadenitis, consistent with Kikuchi disease
Recommendations
Clinical correlation advised. ANA testing to rule out SLE. Conservative management with symptomatic treatment. Follow-up for spontaneous resolution expected in 3-6 months
Comments
The presence of crescentic histiocytes with necrotizing inflammation and absence of neutrophils is characteristic of Kikuchi disease. This is a benign, self-limiting condition with excellent prognosis