Definition/General
Introduction:
Necrotizing lymphadenitis represents a heterogeneous group of conditions characterized by tissue necrosis within lymph nodes
It encompasses various entities including Kikuchi disease, systemic lupus erythematosus (SLE) lymphadenitis, and infectious necrotizing lymphadenitis
The condition demonstrates inflammatory cell infiltration with tissue destruction and requires careful differentiation from malignancy.
Origin:
Results from various inflammatory and infectious processes leading to tissue necrosis
Autoimmune mechanisms (SLE, Kikuchi disease)
Infectious agents (bacteria, viruses, fungi, parasites)
Drug-induced necrosis (chemotherapy, immunosuppressants)
Malignancy-related necrosis (lymphoma, metastatic disease)
Ischemic necrosis (vascular compromise)
Unknown etiology (idiopathic necrotizing lymphadenitis).
Classification:
Classified by underlying etiology: Kikuchi disease (histiocytic necrotizing lymphadenitis)
SLE-associated necrotizing lymphadenitis
Infectious necrotizing lymphadenitis (bacterial, viral, fungal)
Drug-induced necrotizing lymphadenitis
Malignancy-associated necrosis
By pattern: Geographic necrosis
Focal necrosis
Extensive necrosis.
Epidemiology:
Variable epidemiology depending on underlying cause
Kikuchi disease: young Asian females predominance
SLE lymphadenitis: follows SLE demographics
Infectious causes: all age groups, geographic variation
Overall rare condition requiring careful evaluation
Seasonal variation for some infectious causes.
Clinical Features
Presentation:
Painful or painless lymphadenopathy depending on cause
Fever common in infectious and autoimmune causes
Constitutional symptoms: weight loss, night sweats, malaise
Skin manifestations (SLE, infections)
Rapid progression may suggest malignancy or severe infection
Regional or generalized lymph node involvement.
Symptoms:
Fever (60-80% of cases)
Fatigue and malaise
Weight loss and anorexia
Night sweats
Skin rash (autoimmune, infectious causes)
Arthralgia (SLE, other autoimmune)
Respiratory symptoms (pulmonary involvement)
Neurological symptoms (rare, CNS involvement).
Risk Factors:
Autoimmune disease predisposition (SLE, other connective tissue diseases)
Immunocompromised state (increased infection risk)
Recent infections (viral, bacterial)
Drug therapy (chemotherapy, immunosuppressants)
Geographic location (endemic infections)
Age and gender (specific to underlying condition)
Family history of autoimmune disease.
Screening:
Complete blood count with differential
Comprehensive metabolic panel
Inflammatory markers (ESR, CRP)
Autoimmune serology (ANA, anti-dsDNA, complement levels)
Infectious workup (cultures, serology)
Imaging studies (CT, MRI, PET-CT)
Tissue biopsy essential for diagnosis.
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Gross Description
Appearance:
Enlarged lymph nodes with areas of yellow-white necrosis
Firm to fluctuant consistency depending on extent of necrosis
Cut surface shows geographic areas of necrosis
Hemorrhagic areas may be present
Capsular thickening and possible rupture
Surrounding tissue inflammation.
Characteristics:
Geographic pattern of necrosis with irregular borders
Central softening in extensive necrosis
Peripheral viable tissue around necrotic areas
Variable consistency from firm to cystic
No typical caseous appearance (unlike tuberculosis)
Hemorrhagic discoloration possible.
Size Location:
Variable size from 1-8 cm
Location depends on underlying cause
Cervical lymph nodes (Kikuchi disease, SLE)
Generalized involvement (systemic conditions)
Regional involvement (localized infections)
Mediastinal involvement (systemic disease, malignancy).
Multifocality:
Single or multiple lymph nodes depending on etiology
Bilateral involvement in systemic conditions
Progressive spread possible
Associated organ involvement (spleen, liver)
Extranodal extension in severe cases.
Microscopic Description
Histological Features:
Geographic areas of necrosis with coagulative pattern
Karyorrhectic debris abundant in necrotic areas
Mixed inflammatory infiltrate around necrotic foci
Histiocytes and macrophages prominent
Absence of neutrophils (Kikuchi pattern) or presence (infectious pattern)
Vascular changes including thrombosis.
Cellular Characteristics:
Coagulative necrosis with loss of cellular detail
Karyorrhectic debris (fragmented nuclei)
Histiocytes with crescentic nuclei (Kikuchi pattern)
Plasmacytoid dendritic cells (CD123+)
Hematoxylin bodies (SLE pattern)
Variable inflammatory cells depending on cause.
Architectural Patterns:
Geographic necrosis pattern with sharp demarcation
Paracortical involvement predominant
Preserved follicular architecture in viable areas
Capsular involvement and possible rupture
Vascular involvement with thrombosis
Fibrosis in healing areas.
Grading Criteria:
Extent of necrosis (focal, extensive, near-total)
Inflammatory pattern (histiocytic, neutrophilic, mixed)
Associated features (vasculitis, hematoxylin bodies)
Cellular composition in viable areas
Degree of karyorrhexis
Healing vs active pattern.
Immunohistochemistry
Positive Markers:
CD68 positive in histiocytes and macrophages
CD163 positive in M2 macrophages
CD123 highlights plasmacytoid dendritic cells
Lysozyme positive in histiocytes
MPO may be positive in neutrophils (infectious pattern)
CD8 often predominant T-cell population
Ki-67 variable depending on activity.
Negative Markers:
CD15 negative (absence of neutrophils in Kikuchi pattern)
CD30 negative (excludes lymphoma)
ALK-1 negative
EBV/EBER typically negative (unless EBV-associated)
CD1a and Langerin negative
Cytokeratin negative.
Diagnostic Utility:
CD68/CD163 confirm histiocytic infiltrate
CD123 identifies plasmacytoid dendritic cells (characteristic of Kikuchi)
CD15 helps distinguish patterns (neutrophilic vs histiocytic)
EBV studies important in appropriate clinical context
SLE markers (complement, DNA) in tissue
Organism detection by special stains.
Molecular Subtypes:
Etiology-specific patterns: Kikuchi disease, SLE lymphadenitis, infectious causes
No universal molecular classification
Viral detection by PCR when indicated
Autoantibody patterns in autoimmune causes
Cytokine profiles vary by etiology.
Molecular/Genetic
Genetic Mutations:
No specific mutations but underlying disease genetics important
HLA associations in autoimmune causes
Viral integration in infectious causes
p53 pathway activation in necrotic tissue
Apoptosis pathway dysregulation
Inflammatory pathway activation.
Molecular Markers:
Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)
Type I interferons (autoimmune causes)
Apoptosis markers (caspases, TUNEL)
Complement activation products
Viral nucleic acids when applicable
Autoantibodies in tissue (SLE).
Prognostic Significance:
Variable prognosis depending on underlying cause
Kikuchi disease: excellent prognosis, self-limiting
SLE lymphadenitis: depends on systemic disease control
Infectious causes: depends on organism and treatment response
Malignancy-associated: poor prognosis
Drug-induced: reversible with discontinuation.
Therapeutic Targets:
Etiology-specific treatment essential
Supportive care (Kikuchi disease)
Immunosuppression (SLE, autoimmune causes)
Antimicrobial therapy (infectious causes)
Drug discontinuation (drug-induced)
Malignancy treatment when applicable.
Differential Diagnosis
Similar Entities:
Malignant lymphoma with necrosis
Metastatic carcinoma with necrosis
Infectious lymphadenitis (tuberculosis, cat scratch disease)
Kikuchi disease vs SLE lymphadenitis
Drug-induced lymphadenitis
Autoimmune lymphadenopathy.
Distinguishing Features:
Kikuchi disease: absence of neutrophils, crescentic histiocytes, CD123+ cells, young Asian females
SLE: hematoxylin bodies, complement deposits, ANA positive
Lymphoma: malignant cells, monoclonal population, specific markers
Tuberculosis: caseous necrosis, epithelioid granulomas, AFB positive
Infectious: neutrophils present, organism identification.
Diagnostic Challenges:
Extensive necrosis may obscure underlying pathology
Overlap between Kikuchi and SLE patterns
Secondary infection in necrotic tissue
Sampling issues in predominantly necrotic nodes
Clinical correlation essential
Special stains and molecular studies often required.
Rare Variants:
EBV-associated necrotizing lymphadenitis
Parvovirus B19-associated
Systemic juvenile idiopathic arthritis lymphadenitis
Still disease lymphadenitis
Drug-induced (immune checkpoint inhibitors)
Post-vaccination necrotizing 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 [anatomical location], measuring [X.X] cm, with areas of necrosis
Diagnosis
Necrotizing lymphadenitis, [pattern/etiology when determinable]
Pattern Classification
Pattern: [histiocytic/neutrophilic/mixed], extent: [focal/extensive], type: [Kikuchi-type/infectious-type/other]
Histological Features
Shows [geographic necrosis] with [karyorrhectic debris] and [inflammatory infiltrate pattern]
Size and Necrosis
Size: [X.X] cm, necrosis: [extent and pattern], viable tissue: [description]
Inflammatory Pattern
Inflammatory infiltrate shows [histiocytes/neutrophils/mixed] with [specific features like crescentic nuclei/hematoxylin bodies]
Special Studies
Special stains: AFB [negative/positive], GMS [negative/positive], Gram [results]
IHC: CD68 [histiocytes], CD123 [plasmacytoid cells], CD15 [neutrophils], organism-specific markers
Molecular: [if performed] PCR for viruses/bacteria, autoimmune markers
Final Diagnosis
Necrotizing lymphadenitis, [specific type when determinable], clinical correlation recommended for underlying etiology