General Information

• This is a benign proliferation of Langerhans cells usually accompanied with eosinophils, lymphocytes, neutrophils and scattered plasma cells.
• There may be solitary or multiple lesions confined to bone
• 70% of cases consist of a solitary lesion
• Seldom leads to disseminated systemic disease
• Viewed as disorder of immune regulation or reactive process rather than neoplasm
• All organ systems may be affected with disseminated forms

• Hand-Schuller-Christian Disease (1-5 years): chronic disseminated histiocytosis
• Letterer-Siwe disease (<1 year): acute or subacute disseminated histiocytosis Uniformly fatal
• Solitary EG is twice as common as multifocal EG
• May arise from any bone and any site within a bone (epiphyseal, metaphyseal, diaphyseal)
• Radiographically variable appearance: may appear benign (geographic) or malignant (permeative or moth eaten)

Hand-Schuller-Christian Disease

Triad:

• Destructive skeletal lesions
• Exophthalmos
• Diabetes Insipidus
• 10% of patients with unifocal EG develop multifocal and extraskeletal disease
• Usually <5 years old
• Hepatosplenomegaly, adenopathy, anemia, fever, neurological complaints
• Fatal in 15%
• Any bone but 90% have skull involvement

Letterer-Siwe Disease

• Develops in 1st year of life
• Disseminated disease and small bone lesions
• Fatal in 95% who develop before 1 year of life

Clinical Presentation

Signs/Symptoms:

• Pain and soft tissue swelling
• Temporal bone disease is clinically indistinguishable from otitis media or mastoiditis
• May have a fever
• Mild peripheral eosinophilia (5%-10% of patients)
• Prevalence: Male predilection (2:1)

Age:

• 1 month – 71 years
• Most common age 5-15 years old
• 85% within first 3 decades
• 60% within first decade

Sites:

• Flat Bones (most common—70%)
• Skull
• Pelvis
• Femur
• Humerus
• Hands and Feet are rare in solitary disease

Radiographic Presentation

Roll over the images for more information

Gross Pathology

• Gross appearance not distinctive
• Depending on mixture of cells, may be yellow, gray, or brown
• Older lesions are yellow due to regression and accumulation of lipid in histiocytes and Langerhans cells
• Intralesional hemorrhage exists

• Langerhans cell is diagnostic and clonal proliferation
• Nuclei show prominent nuclear groove (coffee-bean)
• Also composed of eosinophils and other inflammatory cells (non diagnostic component)
• Ratio of inflammatory cells to Langerhans cells varies
• Mitotic activity low
• Eosinophils dominate some areas forming diffuse sheets, excluding Langerhans cells
• Birbeck Granules: Electron Microscopy demonstrates granules that often take the form of a tennis raquet and form from complex invaginations of the cell membrane
• Vimentin, CD1 and S-100 positivity

Roll over the images for more information

Differential Diagnosis

• Osteomyelitis
• Granulomatous Inflammation
• • Tuberculosis
  • Fungus
• Hodgkin Disease

Biological Behavior

• Typically acts as a benign disorder
• Individual lesions may undergo partial or complete spontaneous resolution
• Patients with solitary lesions are at risk for developing additional bony lesions within 6 months to 2 years
• Adult patients with more than 3 bone lesions are at risk for visceral involvement although death due to EG in adults is rare
• Children with multiple bone lesions are at risk for visceral involvement that may cause death. Children less than 2 who develop disseminated disease are at highest risk for death

Treatment

• Majority of patients are cured by curettage or intralesional injection of a steroid
• Curettage and bone grafting for long bones and weight bearing bones at risk for fracture
• Intralesional steroids for non weightbearing bones
• Complete healing may take a year
• Low dose radiation may be valuable for inaccessible lesions
• Vertebral plana is braced and observed

Prognosis

• Complete healing after surgery may take 1 year
• Patients with intraosseous EG are at risk for developing additional lesions
• Pateints who develop additional bony lesions are at risk for organ involvement.
• Death is rare of adults, regardless of extend of lesions although children, especially when less than 2 years of age, more readily die from disseminated disease