In adults, the most common presenting symptoms are local pain from bony involvement, weight loss, and fever. Bony lesions most often occur in the skull, especially in the jaw. Long bones are less frequently involved, with lesions occurring in the long bones in approximately 17% of patients.3 The rib has also been reported as a common site of involvement in adults.5 Similar to children, diabetes insipidus remains a classic manifestation of LCH because of pituitary gland involvement. Other common symptoms of LCH in adults are cough, dyspnea, and chest pain from pulmonary involvement. Up to 20% to 30% of adult LCH patients have isolated pulmonary lesions, although pulmonary LCH may also occur as part of multisystem disease (risk group).3,4,20
Eosinophilic granuloma bone lesions have a variety of radiographic appearances but most commonly appear as lytic lesions. They often mimic aggressive lesions with permeative bone destruction, periostitis, ill-defined borders, and cortical erosion. Most lesions arise in the medullary space but can present as a destructive, cortically based lesion, as it did in our patient’s first femoral lesion. The differential diagnosis for a lytic medullary bone lesion includes benign entities, such as nonossifying fibromas, bone cysts, or osteomyelitis, but also includes malignant tumors, such as metastases, Ewing sarcoma, and lymphoma. A destructive, cortically based lesion in an adult should raise a very high suspicion for metastatic carcinoma until proven otherwise. Other diagnostic considerations for a cortically based lesion include chondromyxoid fibroma and surface bone lesions, such as surface chondroma and osteoma, or osteosarcoma (parosteal and periosteal). In the skull, lesions commonly erode the outer table more than the inner table (the typical “beveled-edge” appearance). Skull lesions also may have a small, central, dense focus within the lytic lesion (“button sequestrum”).
Bone scanning is often not as sensitive in detecting EG lesions compared with other bone tumors, although in our patient the bone scan was positive. In patients with a negative bone scan but a high index of suspicion, a radiographic skeletal survey should be obtained to rule out other lesions. MRI typically shows T2-hyperintense, T1-hypointense lesions with surrounding bone marrow edema and variable contrast enhancement, which is relatively nonspecific. The high sensitivity of MRI allows accurate delineation of the extent of the lesions and evaluates for the presence of an extraosseous soft-tissue component. Biopsy is generally necessary to establish a definitive histologic diagnosis. In our patient, despite her history of biopsy-proven EG, the aggressive appearance of a destructive, cortically based lesion made obtaining a biopsy critical to establish a definitive diagnosis in this case.
The histopathologic examination of the tissue from our patient was typical of that seen in patients with EG. It revealed tissue fragments with diffuse sheets of histiocytes displaying nuclear grooves, admixed numerous eosinophils with eosinophilic microabscesses, and scattered lymphocytes (Figures 6A, 6B). There were areas of necrosis, raising the possibility of osteomyelitis. However, the presence of classic histomorphologic features of LCH in the majority of the tissue fragments, along with CD1a- and S100-positivity in the histiocytes, confirmed the diagnosis of LCH (Figures 6C, 6D). Although not highly specific, a positive CD1a immunostain with the described histomorphologic findings in the proper clinical setting is often considered sufficient for LCH diagnosis. S100 is an important adjunct immunostain in the evaluation of histiocytic disorders. A positive S100 immunostain helps identify histiocytes, which are also CD1a-positive, because the latter immunostain can also be positive in some lymphomas and thymomas.21
After diagnosis of LCH has been confirmed, staging includes radiographs of any suspicious bone lesions, chest radiograph, bone scan, abdominal ultrasound, routine laboratory studies, and chest CT if pulmonary LCH is suspected.
The optimal treatment strategy for adult patients has not been clearly defined, and current strategies for LCH vary depending on organ involvement and extent of disease. Therapeutic options include observation, local treatment with steroids, local excision with curettage with or without bone grafting, chemotherapy, immunomodulation, irradiation, and stem cell transplantation in advanced disease. In general, patients who benefit from systemic therapy, such as chemotherapy or immunomodulation, include those with multisystem disease, refractory or recurrent lesions, and multifocal skeletal involvement.22
Patients with more limited disease, such as EG of bone, may undergo observation or local intralesional treatment. Eosinophilic granuloma of bone may resolve spontaneously and commonly does so when it is located in the pediatric spine. However, the therapeutic approach in adults with EG is controversial, given that spontaneous resolution is less likely to occur in the skeletally mature. Plasschaert and colleagues23 reported a recurrence rate of 26% in skeletally mature patients with EG of bone treated with biopsy followed by curettage with or without grafting. In the skeletally immature group, there were no clinical or radiographic signs of recurrence in the 2-year follow-up period.23 Thus, treatment in the adult population must be considered separate from the skeletally immature and in the appropriate clinical context. Depending on the location of the lesion, patients may become symptomatic or be at risk for pathologic fracture. In such circumstances, curettage with or without bone grafting and prophylactic internal fixation may be indicated. Other treatments, such as intralesional infiltration with corticosteroids, have been reported, but the role of such treatment in adults is undetermined.24,25 Radiation is typically not recommended in single-system disease unless a vital organ is threatened.26 Overall, patients with single-system disease have an excellent prognosis, and treatment should be determined on an individual basis.3