eMedicine Specialties > Radiology > Musculoskeletal
Eosinophilic Granuloma, Skeletal
Updated: May 14, 2008
Introduction
Background
Eosinophilic granuloma (EG) is the benign form of the 3 clinical variants of Langerhans cell histiocytosis, which include Letterer-Siwe disease, Hand-Schüller-Christian disease, and EG (formerly termed histiocytosis X).
EG is characterized by single or multiple skeletal lesions, and it predominantly affects children, adolescents, and young adults. Solitary lesions are more common than multiple lesions. When multiple lesions occur, the new osseous lesions appear within 1-2 years. Any bone can be involved; the more common sites include the skull, mandible, spine, ribs, and long bones.1,2,3
Symptoms include localized pain, tenderness, swelling, fever, and leukocytosis. Lesions usually begin to regress after approximately 3 months, but they may take as long as 2 years to resolve.
Chest radiograph in a 9-year-old boy who presented with mid dorsal pain. Note the collapsed vertebra and paraspinal soft tissue mass.
Transaxial nonenhanced CT scans of the skull in a 28-year-old woman who presented with a palpable swelling over the calvarium. Scanogram of the patient's skull shows a geographic lytic lesion within the parieto-occipital region. Transaxial scan through the vertex, examined in a bone window, shows an expanding lytic lesion within the diploic space (see also Images 4-5 in Multimedia).
Radionuclide bone scans in a 28-year-old woman with a palpable swelling over the calvarium (same patient as in Images 3-4 in Multimedia) show a solitary lesion within the skull and a photon-deficient mass surrounded by a rim of intense activity. Biopsy results confirmed the diagnosis of eosinophilic granuloma.
External carotid angiogram in a 10-year-old boy with swelling of the left mandible (same patient as in Image 6 in Multimedia) shows an avascular mass within the mandible with stretching of the vessels around the lytic lesion. Biopsy results confirmed the diagnosis of eosinophilic granuloma.
T1-weighted nonenhanced sagittal MRI through the spine in a 9-year-old boy with mid dorsal pain (same patient as in Images 9-10 in Multimedia) shows the vertebra plana. Note the preserved disk spaces. Biopsy results confirmed the diagnosis of eosinophilic granuloma.
Pathophysiology
EG is a benign disorder that affects children and young adults, particularly males. The solitary bone lesion may be asymptomatic, or it may cause bone pain because of expansion of the medullary bone. Pathologic fractures may ensue.1,4,5
The distinctive morphologic lesions of the entire group of Langerhans histiocytosis disorders consist of expanding erosive accumulations of histiocytes, usually within the medullary cavity. Microscopically, proliferation of foamy and vacuolated histiocytes is associated with a variable admixture of neutrophils, eosinophils, lymphocytes, and plasma cells. The concentration of eosinophilic infiltrate varies from scattered mature cells to sheetlike masses of cells. Occasionally, areas of bone necrosis may interrupt the cellular infiltrate. The foamy cells may also be amassed in clumps, but because these clumps represent phagocytosis of lipid debris, they are of no clinical significance.
Any bone can be involved, but the calvarium, ribs, and femur are particularly common sites. Solitary lesions are more common than multiple ones. When the lesions are multiple, new osseous lesions occur within 1-2 years; the condition is still classified as EG. Radiologists need to be aware that additional EG of bone, occurring as long as 4 years after initial diagnosis, should be interpreted as a localized form of Langerhans cell histiocytosis. This differentiation is important because the prognosis is more favorable with focal disease with multifocal disseminated disease, which involves organs other than the skeletal system. Similar lesions may occur within the lungs, skin, and stomach, either as a unifocal lesion or as part of multifocal disease.4
Lung involvement occurs in 20% of patients with EG and in an older group (age, 20-40 y). Lung involvement has a strong association with smoking. Diffuse pulmonary infiltrates may be a manifestation of a covert osseous EG. In 50-75% of patients, the disease is monostotic. Skull involvement is seen in 50% of patients.6 Rarely, the growing epiphysis is involved with EG; in most such cases, transphyseal extension can be demonstrated, both by the radiologic findings and the histopathologic results.7
Frequency
United States
EG, or unifocal Langerhans cell histiocytosis, is the most common benign form in the Langerhans cell histiocytosis group. EG is found in 60-80% of patients with Langerhans cell histiocytosis.
International
The exact incidence of EG is unknown.
Mortality/Morbidity
The prognosis is usually excellent, with spontaneous resolution by fibrosis occurring within 1-2 years. In other instances, curettage, excision, or local irradiation leads to cure, although some authorities believe that the rate of spontaneous resolution of osseous and extraosseous lesions is unaffected by the mode of therapy.7
- Unifocal lesions occurring at certain sites may lead to complications. A lesion of the mastoid process may extend into the middle ear, destroy the ossicles, and lead to deafness, whereas a lesion in the mandible may lead to floating teeth and fractures.
- Pathologic fractures may complicate rib and long bone lesions and cause vertebra plana. The prognosis for patients with vertebra plana resulting from EG is favorable in terms of symptomatic improvement and the restoration of vertebral height. For patients with vertebra plana, conservative orthopedic treatment involving immobilization with a brace is usually sufficient to allow optimal vertebral remodeling.8
Sex
The male-to-female ratio is 3:2.
Age
The age range of patients with EG is 2-30 years. The highest frequency occurs in patients aged 5-10 years; 75% of patients with EG are younger than 20 years.
Presentation
Most patients have no symptoms. The diagnosis is usually based on radiographic demonstration of a destructive bone lesion arising from the marrow cavity and on characteristic morphologic findings. Localized bone pain and focal tenderness may occur as a result of bone erosion and, rarely, a pathologic fracture. A swelling or mass may be palpable at the site of osseous involvement. Rarely, children present with fever and leukocytosis. Involvement of the mastoid process may occur with intractable otitis media with a chronic discharge. Mandibular involvement may present as gingival and continuous soft tissue swelling.1
Eosinophilic granuloma may masquerade as an aggressive periodontitis.9 Eosinophilic granuloma should therefore be considered when an expanding lytic jaw lesion is encountered.
A spinal EG infrequently produces neurologic deficits in children, which may result in spinal instability.2,10,11
Preferred Examination
Plain radiography is the mainstay in the diagnosis of EG, although a specific diagnosis cannot always be made without bone biopsy because children and adolescents are not spared skeletal neoplasms. Radionuclide study, CT, MRI, and, occasionally, angiography are complementary examinations. Any or all may be used to arrive at a diagnosis.1,12,13
Limitations of Techniques
A wide variety of bone lesions may mimic EG; these include infections, traumatic lesions, and neoplasms. A false-negative diagnosis of EG is exceptional when plain radiographic findings are used, although difficulty may be encountered with lesions in areas with more complex anatomy, such as the posterior elements of the vertebral bodies. In these cases, conventional tomography or CT may useful. With radionuclide scanning, the false-negative rate is 30%.
Differential Diagnoses
| Aneurysmal Bone Cyst | Fibrous Dysplasia |
| Bone Infarct | Osteomyelitis, Acute Pyogenic |
| Bone Metastases | Osteomyelitis, Chronic |
| Eosinophilic Granuloma, Thoracic | Osteosarcoma, Variants |
Other Problems to Be Considered
Skull3
Venous lake
Meningocele, encephalocele, and cranium bifidum
Arachnoid granulation
Parietal foramen
Epidermoid cyst
Hemangioma
Cholesteatoma
Fibrous dysplasia
Metastasis
Surgical defect
Osteomyelitis
Vertebra plana
Fracture
Metastasis, lymphoma, leukemia, plasmacytoma, chordoma, aneurysmal bone cyst, and Ewing sarcoma
Hemangioma
Osteomyelitis
Long bones
Ewing sarcoma
Chronic osteomyelitis
Brodie abscess
Chondroblastoma
Lungs
Other interstitial lung diseases
More on Eosinophilic Granuloma, Skeletal |
 Overview: Eosinophilic Granuloma, Skeletal |
| Imaging: Eosinophilic Granuloma, Skeletal |
| Follow-up: Eosinophilic Granuloma, Skeletal |
| Multimedia: Eosinophilic Granuloma, Skeletal |
| References |
| Next Page » |
References
Azouz EM, Saigal G, Rodriguez MM, Podda A. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement. Pediatr Radiol. Feb 2005;35(2):103-15. [Medline].
Haouimi AS, Al-Hawsawi ZM, Jameel AN. Unusual location of eosinophilic granuloma. Saudi Med J. Oct 2004;25(10):1489-91. [Medline].
Park SH, Park J, Hwang JH, Hwang SK, Hamm IS, Park YM. Eosinophilic granuloma of the skull: a retrospective analysis. Pediatr Neurosurg. 2007;43(2):97-101. [Medline].
Vanhoenacker FM, De Beuckeleer LH, De Roeck F, et al. Metachronous eosinophilic granuloma of bone. JBR-BTR. Oct 2000;83(5):234-7. [Medline].
Greis PE, Hankin FM. Eosinophilic granuloma. The management of solitary lesions of bone. Clin Orthop. Aug 1990;(257):204-11. [Medline].
Yang JT, Chang CN, Lui TN, Ho YS. Eosinophilic granuloma of the skull--report of four cases. Changgeng Yi Xue Za Zhi. Dec 1993;16(4):257-62. [Medline].
Yanagawa T, Watanabe H, Shinozaki T, et al. The natural history of disappearing bone tumours and tumour-like conditions. Clin Radiol. Nov 2001;56(11):877-86. [Medline].
Raab P, Hohmann F, Kuhl J, Krauspe R. Vertebral remodeling in eosinophilic granuloma of the spine. A long- term follow-up. Spine. Jun 15 1998;23(12):1351-4. [Medline].
Silvestros SS, Mamalis AA, Sklavounou AD, Tzerbos FX, Rontogianni DD. Eosinophilic granuloma masquerading as aggressive periodontitis. J Periodontol. May 2006;77(5):917-21. [Medline].
Greenlee JD, Fenoy AJ, Donovan KA, Menezes AH. Eosinophilic granuloma in the pediatric spine. Pediatr Neurosurg. 2007;43(4):285-92. [Medline].
Fenoy AJ, Greenlee JD, Menezes AH, Donovan KA, Sato Y, Hitchon PW, et al. Primary bone tumors of the spine in children. J Neurosurg. Oct 2006;105(4 Suppl):252-60. [Medline].
Flores LG 2nd, Hoshi H, Nagamachi S, et al. Thallium-201 uptake in eosinophilic granuloma of the frontal bone: comparison with technetium-99m-MDP imaging. J Nucl Med. Jan 1995;36(1):107-10. [Medline].
Carrasco CH, Wallace S, Richli WR. Percutaneous skeletal biopsy. Cardiovasc Intervent Radiol. Jan-Feb 1991;14(1):69-72. [Medline].
Osenbach RK, Youngblood LA, Menezes AH. Atlanto-axial instability secondary to solitary eosinophilic granuloma of C2 in a 12-year-old girl. J Spinal Disord. Dec 1990;3(4):408-12. [Medline].
Further Reading
Keywords
EG, Langerhans cell histiocytosis, histiocytosis X, Letterer-Siwe disease, Hand-Schüller-Christian disease, skeletal eosinophilic granuloma, unifocal Langerhans cell histiocytosis, solitary skeletal lesions, bone lesions, multiple skeletal lesions, skeletal lesions, solitary bone lesions, multiple bone lesions
