Definition/General
Introduction:
Lymph node sinus histiocytosis is a reactive condition characterized by expansion of lymph node sinuses with increased numbers of histiocytes (macrophages)
It represents a non-specific reactive pattern seen in response to various stimuli including infections, inflammatory conditions, and malignancies
The condition reflects enhanced immune surveillance and phagocytic activity within lymph nodes.
Origin:
Results from increased antigenic load requiring enhanced phagocytic clearance
Infectious stimuli (bacterial, viral, fungal) commonly trigger the response
Inflammatory conditions (autoimmune diseases, drug reactions)
Malignancy-associated (tumor antigens, necrotic debris)
Foreign material exposure
Metabolic disorders (storage diseases)
Drainage of infected or inflamed tissues leads to histiocyte accumulation.
Classification:
Classified by underlying etiology: Infectious sinus histiocytosis (bacterial, viral, parasitic)
Inflammatory sinus histiocytosis (autoimmune, drug-induced)
Neoplasm-associated sinus histiocytosis
Idiopathic sinus histiocytosis
By pattern: Simple sinus histiocytosis
Sinus histiocytosis with erythrophagocytosis
Pigmented sinus histiocytosis (melanin, hemosiderin).
Epidemiology:
Common reactive pattern seen across all age groups
No gender predilection
Associated with underlying conditions that stimulate immune response
Geographic variation based on endemic infections
Higher prevalence in immunocompromised patients
Seasonal variation following infectious disease patterns
Often accompanies other reactive lymph node changes.
Clinical Features
Presentation:
Lymphadenopathy as part of underlying condition
Usually painless unless associated with acute infection
Variable size depending on stimulus intensity
Multiple lymph node groups may be involved
Associated symptoms related to underlying cause
Fever if infectious etiology
Regional lymphadenopathy following drainage patterns.
Symptoms:
Constitutional symptoms variable depending on cause
Fever and malaise in infectious cases
Weight loss uncommon unless chronic stimulation
Night sweats rare
Fatigue may be present
Symptoms of underlying disease (skin rash, joint pain, respiratory symptoms)
No specific B-symptoms.
Risk Factors:
Chronic infections (tuberculosis, histoplasmosis, toxoplasmosis)
Autoimmune diseases (rheumatoid arthritis, SLE)
Malignancy (carcinoma, lymphoma)
Immunodeficiency states
Drug therapy (phenytoin, allopurinol)
Occupational exposures (dusts, chemicals)
Geographic location (endemic infectious diseases).
Screening:
Clinical examination for lymphadenopathy and underlying disease
Laboratory studies: CBC, inflammatory markers (ESR, CRP)
Infectious workup when indicated
Autoimmune markers if suspected
Imaging studies for extent assessment
Fine needle aspiration may show increased histiocytes
Excisional biopsy for definitive diagnosis.
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Gross Description
Appearance:
Enlarged lymph nodes with preserved overall architecture
Cut surface shows prominent trabecular pattern due to dilated sinuses
Gray-white to tan coloration
Soft to firm consistency
No necrosis typically present
Prominent vascular pattern
Capsule intact without adherence to surrounding tissues.
Characteristics:
Spongy appearance due to sinus dilatation
Honeycomb pattern visible on cut surface
Homogeneous appearance without focal lesions
No calcification or fibrosis typically
Variable pigmentation (melanin, hemosiderin) in some cases
Multiple lymph nodes may show similar changes
Size proportional to degree of stimulation.
Size Location:
Variable size from 1-5 cm typically
Regional lymph nodes following drainage patterns
Cervical lymph nodes (head/neck infections)
Axillary lymph nodes (upper extremity, breast conditions)
Inguinal lymph nodes (lower extremity, pelvic conditions)
Mediastinal involvement (pulmonary conditions)
Generalized involvement in systemic conditions.
Multifocality:
Multiple lymph nodes in drainage region commonly affected
Bilateral involvement possible in systemic conditions
Progressive involvement along lymphatic chains
Regression possible with resolution of underlying stimulus
Chronic persistence with ongoing stimulation
Associated tissue changes in drainage area.
Microscopic Description
Histological Features:
Marked dilatation of lymph node sinuses (subcapsular, medullary, and cortical)
Increased numbers of histiocytes within dilated sinuses
Preserved lymphoid follicles and paracortical areas
Histiocytes with abundant cytoplasm and vesicular nuclei
Phagocytic activity evident (erythrophagocytosis, debris)
Variable inflammatory infiltrate
Intact sinus endothelium.
Cellular Characteristics:
Large histiocytes with abundant eosinophilic to foamy cytoplasm
Vesicular nuclei with prominent nucleoli
Phagocytosed material (red blood cells, debris, pigment)
Multinucleated histiocytes occasionally present
Mixed inflammatory cells (lymphocytes, plasma cells)
Neutrophils if acute inflammation
No significant atypia in histiocytes.
Architectural Patterns:
Sinus expansion pattern with preserved nodal architecture
Subcapsular sinus dilatation most prominent
Medullary cord preservation between dilated sinuses
Follicular structure maintained
Paracortical areas may show reactive changes
Capsular thickening minimal
No architectural effacement.
Grading Criteria:
No standard grading system for sinus histiocytosis
Degree of sinus expansion (mild, moderate, marked)
Histiocyte density within sinuses
Phagocytic activity assessment
Associated inflammatory changes
Pigment accumulation (when present)
Underlying etiology determines significance
Resolution potential with treatment of cause.
Immunohistochemistry
Positive Markers:
CD68 positive in histiocytes (KP1 clone variable)
CD163 strongly positive in macrophages
Lysozyme positive in histiocytes
S-100 may be positive in some histiocytes
CD14 positive in monocytes/macrophages
Factor XIIIa positive in some histiocytes
Smooth muscle actin negative in histiocytes.
Negative Markers:
CD1a and Langerin negative (excludes Langerhans cell histiocytosis)
CD30 negative (excludes lymphoma)
Cytokeratin negative in histiocytes
Melanoma markers negative (unless melanin phagocytosis)
CD21 and CD23 highlight follicular dendritic cells
CD34 negative in histiocytes.
Diagnostic Utility:
CD68 and CD163 confirm histiocytic nature
Negative CD1a/Langerin exclude Langerhans cell histiocytosis
CD21/CD23 staining demonstrates preserved follicular dendritic cell networks
Ki-67 shows low proliferation in histiocytes
Special stains may identify phagocytosed organisms
Iron stain demonstrates hemosiderin deposition.
Molecular Subtypes:
No molecular subtypes for reactive sinus histiocytosis
Polyclonal histiocyte population
No clonal gene rearrangements
Cytokine expression studies show inflammatory profile
Marker expression varies with activation state
Functional studies may assess phagocytic capacity
Normal chromosomal complement.
Molecular/Genetic
Genetic Mutations:
No specific genetic mutations associated with reactive sinus histiocytosis
Normal chromosomal complement in histiocytes
Activation-related gene expression changes
Cytokine receptor upregulation
Phagocytosis-related gene activation
No clonal genetic alterations
Inflammatory pathway activation.
Molecular Markers:
Inflammatory cytokines (IL-6, TNF-α, IL-1β) elevated
Chemokines (MCP-1, RANTES) increased
Complement activation products
Acute phase reactants
Phagocytosis markers (CD68, CD163)
Activation markers (CD69, CD25)
Antigen processing markers (cathepsins, proteases).
Prognostic Significance:
Excellent prognosis as reactive condition
Resolution expected with treatment of underlying cause
Persistent stimulation leads to chronic changes
No malignant potential
Indicates active immune response
May mask underlying pathology
Follow-up needed if persistent after treatment.
Therapeutic Targets:
Treatment of underlying condition primary approach
Anti-inflammatory agents for symptomatic relief
Antibiotics for bacterial infections
Antifungal therapy when indicated
Immunosuppressive therapy for autoimmune causes
Supportive care generally sufficient
No specific therapy for sinus histiocytosis itself.
Differential Diagnosis
Similar Entities:
Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy)
Langerhans cell histiocytosis
Hemophagocytic lymphohistiocytosis
Storage diseases (Gaucher, Niemann-Pick)
Metastatic carcinoma (sinus involvement)
Reactive follicular hyperplasia
Dermatopathic lymphadenopathy.
Distinguishing Features:
Simple sinus histiocytosis: mild sinus expansion, normal histiocyte morphology, no emperipolesis
Rosai-Dorfman: massive lymphadenopathy, S-100+ histiocytes, emperipolesis
LCH: CD1a/Langerin positive, coffee-bean nuclei, eosinophilic infiltrate
HLH: hemophagocytosis, systemic symptoms, cytopenias
Storage disease: specific enzyme deficiency, characteristic inclusions.
Diagnostic Challenges:
Mild sinus histiocytosis may be subtle finding
Distinguishing from Rosai-Dorfman disease when histiocytes prominent
Underlying malignancy may be obscured by reactive changes
Chronic stimulation may lead to architectural distortion
Infectious organisms may be difficult to identify
Clinical correlation essential for interpretation.
Rare Variants:
Pigmented sinus histiocytosis (melanin, hemosiderin, anthracotic pigment)
Lipid-laden sinus histiocytosis
Crystal-storing histiocytosis
Xanthogranulomatous sinus histiocytosis
Erythrophagocytic sinus histiocytosis
Giant cell-rich sinus histiocytosis
Necrotizing sinus histiocytosis (associated with infection).
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 in greatest dimension
Diagnosis
Lymph node showing sinus histiocytosis, [degree] expansion
Pattern Classification
Pattern: [simple sinus histiocytosis/with erythrophagocytosis/pigmented], degree: [mild/moderate/marked]
Histological Features
Shows [dilated sinuses] with [increased histiocytes] and [preserved nodal architecture]
Size and Architecture
Size: [X.X] cm, sinus expansion: [prominent/moderate/mild], architecture: [preserved]
Cellular Composition
Histiocytes show [normal morphology/phagocytic activity/pigment deposition] without atypia
Special Studies
IHC: CD68 [positive histiocytes], CD163 [positive], CD1a/Langerin [negative]
Special stains: [if performed] [organism stains/iron stain/PAS]
Clinical correlation: [underlying condition/symptoms/laboratory findings]
Final Diagnosis
Lymph node sinus histiocytosis, reactive pattern, clinical correlation recommended for underlying etiology