You are in: eMedicine Specialties > Radiology > MUSCULOSKELETAL Eosinophilic Granuloma, SkeletalArticle Last Updated: May 14, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia Ali Nawaz Khan is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England Coauthor(s): Muthusamy Chandramohan, MBBS, DMRD, FRCR, Consultant Radiologist, Bradford Teaching Hospitals, UK; Ian Turnbull, MD, Lecturer, Department of Radiology, University of Manchester; Consulting Neuroradiologist, Hope Hospital, Salford, Manchester and North Manchester Hospital; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute Editors: Michael A Bruno, MD, Associate Professor, Departments of Radiology and Medicine, Pennsylvania State University College of Medicine; Director, Radiology Quality Management Services, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Murali Sundaram, MBBS, FRCR, FACR, Consulting Staff, Department of Diagnostic Radiology, The Cleveland Clinic Foundation; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington Author and Editor Disclosure Synonyms and related 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 INTRODUCTIONSection 2 of 11
  BackgroundEosinophilic 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. PathophysiologyEG 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 FrequencyUnited StatesEG, 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. InternationalThe exact incidence of EG is unknown. Mortality/MorbidityThe 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
SexThe male-to-female ratio is 3:2. AgeThe 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. Clinical DetailsMost 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 Preferred ExaminationPlain 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 TechniquesA 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%. DIFFERENTIALSSection 3 of 11
Aneurysmal Bone Cyst Bone Infarct Bone Metastases Eosinophilic Granuloma, Thoracic Fibrous Dysplasia Osteomyelitis, Acute Pyogenic Osteomyelitis, Chronic Osteosarcoma, Variants Other Problems to Be ConsideredSkull3 Venous lake Vertebra plana Fracture Long bones Ewing sarcoma Lungs Other interstitial lung diseases RADIOGRAPHSection 4 of 11
Findings
Degree of ConfidencePlain radiography remains the mainstay of diagnosis in patients with EG, although a specific diagnosis cannot always be made without bone biopsy because children and adolescents are not spared skeletal neoplasms. False Positives/NegativesA wide variety of bone lesions may mimic EG, including infections, traumatic lesions, and neoplasms (see Differentials). A false-negative diagnosis of EG made by using plain radiographs is exceptional, 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. CT SCANSection 5 of 11
FindingsCT scans may be particularly useful in osseous lesions in areas with complex anatomy, such as the mastoids, atlantoaxial joints, and posterior elements of the vertebral bodies. Also, soft tissue components are better depicted with CT than with other imaging modalities. The destruction of the mastoid, petrous ridge, tegmen tympani, and lateral sinus plate and the destruction of the inner and external ear are depicted elegantly on CT scans (see Images 3-4). CT may demonstrate an isoattenuating and homogeneously enhancing mass in the hypothalamus/pituitary gland. Degree of ConfidenceCT is considerably better than plain radiography and conventional tomography in depicting an intracranial extension of EG. False Positives/NegativesCT appearances of EG are nonspecific, and a variety of inflammatory and neoplastic processes may mimic EG. MRISection 6 of 11
FindingsOn spin-echo MRIs, osseous lesions of EG reveal decreased signal intensity on T1-weighted images and high signal intensity on T2-weighted sequences. The lesion may enhance after the administration of a gadolinium-based contrast agent (see Image 11). Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. Degree of ConfidenceThe value of using MRI for patients with EG lies in the sensitivity of MRI; its specificity is low. However, the cost of the procedure and the procedural problems encountered in imaging young children confer no advantages over plain radiography. False Positives/NegativesThe soft tissue component around the osseous lesion has poor definition and shows signal inhomogeneity; the appearance may mimic that of a malignant tumor, infection, or stress fracture. NUCLEAR MEDICINESection 7 of 11
FindingsEG shows a variety of activity patterns on radionuclide bone scintigrams obtained by using technetium-99m (99mTc) diphosphonate. The bone lesions may be hot, cold, or cold with an area of increased surrounding reparative-ring activity. Areas of increased activity vary in intensity. In the lower limbs, EG lesions tend to appear more elongated and diffuse than bone metastasis. Recurrences are identified more readily with fewer false-negative findings (see Image 5). Bone lesions in all types of Langerhans cell histiocytosis are not gallium-67 (67Ga) citrate–avid, but 67Ga imaging may be helpful for detection of nonosseous lesions. Hence, it is useful in the initial assessment and serial follow-up imaging of patients with Langerhans cell histiocytosis. Thallous chloride-201 uptake detected on single-photon emission CT (SPECT) scans has been reported in a patient with skull EG, which was photon deficient on an 99mTc methylene diphosphonate uptake study.12 Degree of ConfidenceRadiographic examination and radionuclide bone imaging are complementary techniques in detecting bone lesions in bone marrow disorders, including EG. Scintigraphy is more useful in cases of unifocal EG than in cases of multifocal disease, in which radiography is superior. False Positives/NegativesNegative radionuclide findings occur in 35% of patients with known EG in whom plain radiographic findings are positive. ANGIOGRAPHYSection 8 of 11
FindingsEG shows no neovascularity, and angiography is usually not performed. Rarely, angiography may be performed in patients in whom staging is required before surgical intervention and to exclude other vascular lesions that can mimic EG, such as hemangioma and aneurysmal bone cyst. Degree of ConfidenceIn most instances, angiography has little or no role in the investigation of EG. False Positives/NegativesMost lesions included in the differential diagnosis of EG are avascular; therefore, differentiation on the basis of angiographic results is usually not possible. INTERVENTIONSection 9 of 11
Percutaneous biopsy is an accepted means of obtaining tissue for analysis to aid in the diagnosis of indeterminate metastatic disease.13 Needle biopsy for tissue sampling in primary osseous neoplasms is more controversial; however, needle biopsy is useful and may be diagnostic in the workup of patients with inflammatory bone lesions and EG. The diagnostic yield of a needle biopsy has been reported to be 50-94% in malignant bone lesions but is less accurate in benign disease. The low complication rate of 0.2% makes the percutaneous approach an attractive alternative to open surgical biopsy. 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.1, 5 Pathologic fractures may complicate rib and long bone lesions and cause vertebra plana. The prognosis in patients with vertebra plana resulting from EG is favorable in terms of symptomatic improvement and the restoration of vertebral height. Conservative orthopedic treatment of patients with vertebra plana through immobilization with a brace is usually sufficient to allow optimal vertebral remodeling. In cases with neurologic impairment (rarely seen in adults), surgical decompression and short fusion of the spine may be necessary. Rarely, the growing epiphysis may be involved by EG, in which case diagnosis demands accurate biopsy and histopathologic analysis so that treatment and prognosis can be individualized. Medical/Legal Pitfalls
Related Medscape topics: MULTIMEDIASection 10 of 11
REFERENCESSection 11 of 11
Eosinophilic Granuloma, Skeletal excerpt Article Last Updated: May 14, 2008 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
