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Case Report |
1 Department of Pediatrics, SUNY Downtown Medical Center, New York, NY.
2 Present address: 400 E 71st St., Apt. 11K, New York, NY 10021.
3 Department of Radiology, Nuclear Medicine Section, NYU Medical Center and
Tisch Hospital, 550 First Ave., 2nd Floor, New York, NY 10016.
4 Department of Medicine, NYU Medical Center, 550 First Ave., Ste. 9N, New York,
NY 10016.
5 Present address: 34 Francine Dr. N, Massapequa, NY 11758.
Received June 17, 2003; accepted after revision August 29, 2003.
Address correspondence to F. Ponzo.
Case Report
A previously healthy 43-year-old man was seen in the emergency department after sustaining a broken rib in a fall. Chest radiography performed at admission showed mediastinal widening. Blood tests were remarkable for minimal elevations in the liver function enzymes (aspartate aminotransferase, 64 U/L [normal, 15–46 U/L]; and alanine aminotransferase, 111 U/L [normal, 8–50 U/L]) and an elevated erythrocyte sedimentation rate (34 mm/hr).
Helical CT of the chest showed mediastinal lymphadenopathy involving the paratracheal compartment; the aorticopulmonary window; and the precarinal, subcarinal, and epicardial compartments. A 2-cm nodule was seen in the right middle lobe, and multiple small pulmonary nodules were seen in all lobes of the lung parenchyma. Because lymphoma was suspected, the patient was referred for whole-body FDG PET.
Whole-body PET was performed 45 min after the IV administration of 9.7 mCi (359 mBq) of FDG using an Advance PET scanner (General Electric Medical Systems). Transmission images were acquired for 5 min per table position and emission images for 3 min per table position. Images were corrected for attenuation, and standardized uptake values were calculated using the commercially available algorithm.
PET showed increased uptake in the right lower lung lobe corresponding to the nodules seen on the CT scan (maximum standardized uptake value, 9.3) (Fig. 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H). In addition, we saw increased uptake in the bilateral supraclavicular, paratracheal, prevascular, hilar, subcarinal, and abdominal paraaortic nodes. Focal bone uptake was seen in the spine, a coracoid process, a humerus, a rib, and the bony pelvis (maximum standardized uptake values of 5.9 in the right iliac crest and 9.3 in the lumbar spine) (Fig. 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H). The elevated uptake value of the lesions and their pattern of distribution were not suggestive of benign disease, so the findings were interpreted as suspicious for malignancy.
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Bone marrow biopsy and aspiration showed extensive involvement of the marrow by well-formed epithelioid granulomas with multinucleated giant cells and focal caseation. Mediastinoscopic lymph node biopsy revealed noncaseating granulomata, confirming a diagnosis of sarcoidosis. The patient remains asymptomatic without treatment.
Discussion
Sarcoidosis is a chronic inflammatory disease of unknown cause characterized histologically by noncaseating granulomas in affected tissues. The reported incidence of skeletal involvement with sarcoidosis ranges from 3% to as much as 36% in patients with musculoskeletal complaints [1, 2]. Bone lesions occur most frequently in the phalanges of the fingers and toes. Less commonly affected areas include the skull, vertebrae, and pelvis [2]. Clinically, skeletal sarcoidosis is usually tolerated well and produces few symptoms. Medical treatment often involves corticosteroid therapy or methotrexate, but in some cases spontaneous regression occurs. The degree of inflammatory activity and systemic distribution of the disease helps in determining appropriate treatment.
Radiographic evaluation of the skeleton often shows normal findings but can reveal focal osteosclerosis and osteolysis [2]. The relatively innocuous presentation of these findings can make the radiographic diagnosis of skeletal sarcoidosis difficult and probably results in a substantial underdiagnosis of the disease. CT of the skeleton may show focal sclerotic lesions. MRI is sensitive for detection of osseous sarcoidosis but is nonspecific.
Bone scintigraphy has shown greater sensitivity than radiography in locating bone involvement in sarcoidosis [1, 3]. Scanning with gallium-67 has been widely used for studies of sarcoidosis. These studies have described a typical pattern of 67Ga uptake in sarcoidosis known as a "lambda" pattern of mediastinal lymphadenopathy that relates to right paratracheal and bilateral hilar involvement. Although 67Ga uptake in bone lesions has also been reported [3], the sensitivity of 67Ga for detecting osseous sarcoidosis is less than that of bone scintigraphy [4]. In most cases, the diagnosis requires confirmation with biopsy.
FDG PET is useful in the diagnosis and treatment of a variety of malignancies. PET can also play a major role in the diagnosis of patients with suspected infection and inflammation [5]. The uptake of FDG increases when metabolic activity is increased by inflammatory cells. In sarcoidosis, macrophages are activated and play an important role in the formation of granulomas, which may explain why the granulomatous lesions of sarcoidosis show strong FDG uptake. In sarcoidosis, the degree of FDG uptake has been related both to activity of disease [5] and to treatment responsiveness [6]. Other researchers have described the intense uptake of FDG in sarcoidosis [5], particularly in the associated lymphadenopathy. To our knowledge, bone involvement seen on FDG PET has been reported only once before [7].
The patient we describe was asymptomatic and underwent evaluation only because pulmonary lymphadenopathy was found incidentally on chest radiography. CT of the chest showed a pattern that was thought to be consistent with a malignancy, possibly lymphoma. Whole-body FDG PET showed both a lambda sign and multiple bone foci in our patients. Although these findings were suspicious for disseminated malignancy, lymph node biopsies in each patient showed noncaseating granulomas, consistent with sarcoidosis. The kinetics of FDG may be used to characterize inflammatory foci on PET. Recently, we proposed that sarcoidosis may show characteristic patterns of uptake on FDG PET (Ponzo et al., presented at the 2002 annual meeting of the Society of Nuclear Medicine). The pattern and distribution of the FDG uptake may provide more information than the quantification of activity in single lesions. The recognition of characteristic patterns may help to differentiate sarcoidosis from malignant conditions.
In conclusion, our case shows that FDG PET may be a sensitive tool for evaluating the extent of sarcoidosis in bone involvement. Intense focal bone involvement, particularly in long bones, associated with the lambda pattern of mediastinal FDG uptake, may be helpful in differentiating sarcoidosis from lymphoma on FDG PET.
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