Definition/General
Introduction:
Kimura disease is a chronic inflammatory disorder of unknown etiology characterized by lymphadenopathy and eosinophilic infiltration
First described in China in 1937 and later detailed by Kimura in Japan in 1948
It primarily affects young Asian males and involves head and neck region
The condition shows angiolymphoid hyperplasia with prominent eosinophilia.
Origin:
Etiology remains unknown but likely represents an aberrant immune response with Th2 predominance
Allergic or hypersensitivity reaction to unknown antigen suggested
Autoimmune component supported by elevated IgE levels and eosinophilia
Genetic susceptibility in Asian populations
Environmental triggers may include trauma, infection, or allergens
Chronic antigenic stimulation leads to persistent inflammatory response.
Classification:
Classified based on anatomical involvement: Lymph node predominant (lymphadenopathy with systemic features)
Soft tissue predominant (subcutaneous masses)
Mixed pattern (both lymph node and soft tissue involvement)
Systemic form with renal involvement
Localized form limited to head and neck
Generalized form with widespread involvement.
Epidemiology:
Strong male predominance with M:F ratio of 10:1
Peak incidence in 2nd and 3rd decades (20-40 years)
Geographic clustering in East Asia (China, Japan, Korea)
Rare in Western populations
Familial clustering occasionally reported
Association with atopic conditions (asthma, eczema)
Renal involvement in 10-16% of cases.
Clinical Features
Presentation:
Unilateral cervical lymphadenopathy (most common presentation)
Subcutaneous nodules in head and neck region
Painless, slowly growing masses
Auricular involvement characteristic (preauricular, postauricular)
Salivary gland enlargement (parotid, submandibular)
Pruritus commonly associated
Bilateral involvement in advanced cases.
Symptoms:
Peripheral eosinophilia (>90% of cases)
Elevated IgE levels (>80% of cases)
Pruritus and skin changes
Proteinuria (renal involvement)
No constitutional symptoms typically
Seasonal exacerbations in some patients
Growth retardation in children with chronic disease
Recurrent skin infections due to eosinophilia.
Risk Factors:
Asian ethnicity (strong predisposing factor)
Male gender (10:1 male predominance)
Young age (peak in 20-40 years)
Atopic background (asthma, allergic rhinitis, eczema)
Family history rarely reported
Trauma history to affected area
Previous allergic reactions
Geographic residence in endemic areas.
Screening:
Complete blood count with differential (eosinophil count)
Total IgE levels (typically elevated >100 IU/mL)
Specific IgE testing for common allergens
Renal function tests (serum creatinine, urinalysis)
Imaging studies: ultrasound, CT, MRI for extent assessment
Fine needle aspiration may suggest diagnosis but excisional biopsy preferred.
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Gross Description
Appearance:
Enlarged lymph nodes with smooth, intact capsule
Firm consistency with rubbery texture
Cut surface shows gray-white to tan coloration
Prominent follicular pattern visible grossly
Vascular prominence with dilated vessels
No necrosis or caseation
Fibrotic areas in chronic cases
Associated soft tissue nodules may be present.
Characteristics:
Well-circumscribed but not encapsulated masses
Homogeneous cut surface without variegation
Increased vascularity apparent on sectioning
Fibrotic bands in longstanding lesions
No calcification typically present
Capsular thickening common
Adherence to surrounding tissues may occur.
Size Location:
Size ranges from 1-10 cm in greatest dimension
Cervical lymph nodes most commonly involved (80-90%)
Preauricular and postauricular locations characteristic
Submandibular and parotid region involvement
Axillary lymph nodes less commonly affected
Generalized lymphadenopathy in systemic disease
Bilateral involvement in advanced cases.
Multifocality:
Unilateral cervical involvement typical initially
Regional spread to adjacent lymph node groups
Bilateral neck involvement in chronic cases
Associated subcutaneous nodules in same anatomical region
Systemic spread to distant lymph nodes rare
Soft tissue involvement without lymphadenopathy possible.
Microscopic Description
Histological Features:
Follicular hyperplasia with reactive germinal centers
Prominent eosinophilic infiltration throughout lymph node parenchyma
Vascular proliferation with endothelial swelling
Fibrosis in interfollicular areas
Plasma cell infiltration with Russell bodies
Tingible body macrophages in germinal centers
Sclerosis in chronic cases.
Cellular Characteristics:
Abundant eosinophils (hallmark feature) throughout all compartments
Reactive lymphoid follicles with prominent germinal centers
Plasma cells with polyclonal immunoglobulin production
Histiocytes and immunoblasts scattered
Endothelial cell proliferation in vessels
Fibroblast proliferation in sclerotic areas
Mast cells increased in some cases.
Architectural Patterns:
Preserved lymph node architecture with follicular hyperplasia pattern
Interfollicular expansion with eosinophilic infiltrate
Vascular proliferation pattern with capillary proliferation
Fibrotic pattern in chronic stages
Paracortical hyperplasia with T-cell expansion
Sinus histiocytosis may be present
Subcapsular involvement common.
Grading Criteria:
No standard grading system for Kimura disease
Eosinophil count assessment (>20% of inflammatory cells)
Degree of fibrosis indicates chronicity
Vascular proliferation extent
Germinal center activity assessment
IgE+ plasma cell quantification
Sclerosis staging (early vs advanced)
Activity assessment based on inflammatory intensity.
Immunohistochemistry
Positive Markers:
CD20 highlights reactive B-cell follicles
CD3 shows T-cell infiltration
CD68 positive in histiocytes and tingible body macrophages
Tryptase highlights increased mast cells
CD34 demonstrates vascular proliferation
IgE positive in plasma cells
CD138 shows polyclonal plasma cells
Ki-67 high in germinal centers.
Negative Markers:
CD30 negative (excludes lymphoma)
ALK-1 negative
CD1a and Langerin negative (excludes Langerhans cell histiocytosis)
S-100 negative in most cells
Cyclin D1 negative
BCL-2 negative in germinal centers
EBV/EBER typically negative.
Diagnostic Utility:
IgE immunostaining shows increased IgE+ plasma cells
Tryptase staining demonstrates mast cell increase
CD34 staining highlights vascular proliferation
Eosinophil markers (major basic protein) confirm eosinophilic infiltration
Polyclonal light chains (kappa and lambda)
T-helper cell markers show Th2 predominance
No clonal markers present.
Molecular Subtypes:
No molecular subtypes recognized for Kimura disease
Th2-dominant immune response pattern
Polyclonal B-cell population
No clonal gene rearrangements
Cytokine expression profile shows IL-4, IL-5, IL-13 elevation
IgE isotype switching prominent
Eosinophil activation markers present.
Molecular/Genetic
Genetic Mutations:
No specific genetic mutations identified in Kimura disease
HLA associations reported in some studies
Cytokine gene polymorphisms may influence susceptibility
IgE receptor gene variants possible association
Eosinophil-related gene expression altered
T-helper cell differentiation genes involved
No oncogene activation or tumor suppressor loss.
Molecular Markers:
Elevated Th2 cytokines (IL-4, IL-5, IL-13)
Increased IgE production markers
Eosinophil activation markers (ECP, EDN)
VEGF overexpression causing vascular changes
Mast cell mediators (histamine, leukotrienes)
Fibroblast activation markers in chronic cases
Complement activation products.
Prognostic Significance:
Benign condition with no malignant potential
Chronic, relapsing course typical
Renal involvement affects long-term prognosis
Response to treatment variable
Recurrence common after incomplete excision
No mortality directly related to disease
Quality of life impacted by chronic symptoms
Long-term monitoring required for renal complications.
Therapeutic Targets:
Corticosteroids (first-line therapy)
Antihistamines for symptomatic relief
Immunosuppressive agents (azathioprine, methotrexate)
Biological agents (anti-IL-5, anti-IgE)
Surgical excision for localized disease
Radiation therapy for refractory cases
Cyclosporine for severe cases
Renal protective measures when indicated.
Differential Diagnosis
Similar Entities:
Angiolymphoid hyperplasia with eosinophilia (ALHE)
Reactive eosinophilic lymphadenitis
Hodgkin lymphoma (eosinophil-rich variant)
Parasitic infections with eosinophilia
Drug-induced eosinophilic lymphadenitis
Hypereosinophilic syndrome
Eosinophilic granuloma
Allergic granulomatosis.
Distinguishing Features:
Kimura disease: Asian male predominance, systemic eosinophilia, elevated IgE, chronic course
ALHE: older patients, superficial lesions, no systemic eosinophilia
Hodgkin lymphoma: Reed-Sternberg cells, CD30+, clonal population
Parasitic: travel history, specific organism identification
Drug-induced: medication history, resolution with discontinuation
HES: organ dysfunction, different criteria.
Diagnostic Challenges:
Distinction from ALHE (overlapping histology but different demographics)
Eosinophil-rich Hodgkin lymphoma requires careful morphologic and immunophenotypic evaluation
Parasitic infections need thorough organism search
Early stages may lack characteristic features
Systemic vs localized forms require clinical correlation
Renal involvement assessment challenging.
Rare Variants:
Renal variant with glomerulonephritis
Cutaneous variant without lymphadenopathy
Conjunctival variant (ocular involvement)
Oral cavity variant
Generalized systemic variant
Pediatric variant (different clinical behavior)
Familial variant (rare familial clustering)
Post-transplant variant in immunosuppressed patients.
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/preauricular/other] region, measuring [X.X] cm in greatest dimension
Diagnosis
Kimura disease (chronic eosinophilic lymphadenitis) with angiolymphoid hyperplasia
Classification
Pattern: [lymph node predominant/mixed pattern], activity: [active/chronic/sclerotic]
Histological Features
Shows [follicular hyperplasia] with [prominent eosinophilic infiltration] and [vascular proliferation/interfollicular fibrosis]
Size and Pattern
Size: [X.X] cm, eosinophilia: [prominent/extensive], architecture: [preserved with hyperplasia]
Cellular Composition
Shows [abundant eosinophils/reactive follicles/polyclonal plasma cells] with [vascular proliferation/fibroblast proliferation]
Special Studies
IHC: CD20 [B-cells], CD3 [T-cells], IgE [positive plasma cells], CD138 [polyclonal plasma cells], CD30 [negative]
Eosinophil markers: Major basic protein [positive], tryptase [increased mast cells]
Molecular: [if performed] Gene rearrangement studies [polyclonal]
Final Diagnosis
Kimura disease (chronic eosinophilic lymphadenitis), consistent with benign inflammatory condition requiring clinical correlation