Bone Tumors
Eosinophilic Granuloma
James C. Wittig, MD
Sarcoma Surgeon
Orthopedic Oncologist
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
Radiology:
Permeative with periosteal reaction (lamellated)
Geographic
Rind of sclerosis
Soft tissue mass (5-10%)
Sequestrum (button-like); Hole in a Hole
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Skull: beveled edge; button sequestrum
Flat bone: hole in a hole
Spine: vertebra plana
Long bone:
Diaphysis: (58%)
Metadiaphysis (18%)
Metaphysis (28%)
Epiphysis (2%)
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X-Ray: Eosinophilic Granuloma of Skull
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Geographic Lesion with Periosteal Reaction |
Geographic Lytic Lesion
Periosteal Reaction | X-ray: Eosinophilic Granuloma of Femur
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Geographic Lesion
Lamellated Periosteal Reaction
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X-ray: Eosinophilic Granuloma of Femur
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Permeative Lesion of Diaphysis
Periosteal Reaction
Bone Scan is Variable
Uptake Intense, Mild or Cold |
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X-ray/Bone Scan: Eosinophilic Granuloma of Femur
MRI: Eosinophilic Granuloma
Marrow replacement on T1
High SI on T2
ST mass possible
Langerhans Cell Histiocytosis
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Geographic Lesion with Sclerotic Rim
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X-ray: Eosinophilic Granuloma of Femur
X-ray: Eosinophilic Granuloma of Clavicle
Permeative Lesion
Plain X-ray: Eosinophilic Granuloma of Humerus
Permeative Lesion
MRI T2: Eosinophilic Granuloma of Scapula Spine
X-ray: Eosinophilic Granuloma of Spine
Vertebra Plana
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
MICROSCOPIC PATHOLOGY
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
Microscopic Pathology: Eosinophilic Granuloma
Cells and No Matrix
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Eosinophils
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 | Microscopic Pathology: Eosinophilic Granuloma
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Eosinophils
Langerhans Cells
Coffee Bean
Indented Nucleus |
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Microscopic Pathology: Eosinophilic Granuloma
Microscopic Pathology: Eosinophilic Granuloma
Low Power
Langerhans Cells Mixed with Eosinophils
Microscopic Pathology: Eosinophilic Granuloma
Intermediate Power
Langerhans Cells Mixed with Eosinophils
Microscopic Pathology: Eosinophilic Granuloma
High power
Coffee Bean/Indented Nuclei of Langerhans Cells
Microscopic Pathology: Eosinophilic Granuloma
Touch Prep of Langerhans Cells with Bean Shaped Nuclei
Eosinophilic Granuloma: Vimentin Stain
Eosinophilic Granuloma: CD1a Stain
Eosinophilic Granuloma: S-100 Stain
Eosinophilic Granuloma: CD-10 Stain
Eosinophilic Granuloma: Birbeck Granules
Birbeck Granules
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 within6 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
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