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Axial osseous sarcoidosis: rare clinical presentation and radiological findings
Clinical Radiology 65 (2010) 167–171
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.elsevierhealth.com/journals/crad
Case Report
Axial osseous sarcoidosis: rare clinical presentation and radiological findings S. Yanny a, *, A.P. Toms a, D. MacIver a, T. Barker b, A. Wilson c a
Department of Radiology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, Norfolk, UK Department of Pathology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, Norfolk, UK c Department of Respiratory Medicine, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, Norfolk, UK b
art icl e i nformat ion Article history: Received in revised form 4 November 2009 Accepted 8 November 2009
Introduction Skeletal sarcoidosis is most frequently peripheral involving the phalanges of the hands and feet and usually occurs late in the course of the disease when there is typically a long history of lung involvement.1 Although bone involvement can be the earliest manifestation, it usually accompanies skin lesions, such as lupus pernio.2 Vertebral sarcoidosis is rare and is even less common in the absence of lung disease. Diagnosis is made by a combination of clinical, radiological, and pathological findings where noncaseating granuloma is the hallmark of the disease. We report a case of a 36-year-old man with extensive axial sarcoidosis presenting with constitutional symptoms but no evidence of lung disease. The extent of spinal disease was unusually diffuse in this patient and associated with a rare location in the sternum. The radiological features [plain film, computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy] of this rare
* Guarantor and correspondent: S. Yanny, Department of Radiology, Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk, NR4 7UY, UK. Tel.: þ44 1603 286140; fax: þ44 1603 286077. E-mail address: [email protected] (S. Yanny).
presentation of sarcoidosis are described with histopathological confirmation.
Case report A 36-year-old man presented with a 1 year history of drenching night sweats, rigors, exertional chest pain, and back stiffness. He had documented pyrexia between 38 and 39 C. He complained of an unproductive cough and malaise, but there was no history of weight loss. He did not complain of back pain. Prior to this he was fit and well with no relevant past medical history and had run the London marathon 1 year previously. He was an ex-smoker of one to two cigarettes a day for 5 years. His grandmother had a history of bronchogenic carcinoma. Physical examination was unremarkable with no clubbing or adenopathy. Erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at 91 mm/h and 67 mg/l, respectively. Serum calcium was normal. A chest radiograph demonstrated bilateral hilar enlargement and multifocal rib abnormalities (Fig. 1). Pulmonary function tests were normal. A highresolution CT chest examination demonstrated normal lung parenchyma with no evidence of peribronchovascular or subpleural nodules (Fig. 2a), but there was bilateral hilar
0009-9260/$ – see front matter Ó 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2009.11.002
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S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
Figure 1 Posteroanterior (PA) chest radiograph demonstrating bilateral hilar enlargement and multifocal lace-like reticular pattern of rib involvement (magnified view).
lymphadenopathy (Fig. 2b). On CT there were abnormalities of the pelvis (Fig. 3), vertebrae, ribs, and sternum. These consisted of relatively well-circumscribed areas of osteolysis and reticular (lace-like) trabeculae, often with cortical destruction, and patchy areas of sclerosis. No extra-osseous soft-tissue masses were identified. Technetium 99m radionuclide bone scintigraphy revealed multiple foci of intense abnormal increased tracer uptake in the skull, scapulae, sternum, ribs, cervical and thoracic spine, and pelvis (Fig. 4), corresponding to areas of bony abnormality on CT. The lesions seen in the lumbar spine did not accumulate tracer and there was no radiotracer uptake in the limbs. MRI of the spine and pelvis was non-specific (Figs. 5 and 6). Patchy bone marrow changes, in the vertebral bodies and posterior elements, were present, which were hyperintense on T2weighted and short-tau inversion recovery (STIR) sequences, and hypointense on T1-weighted imaging. It was not possible to appreciate the lace-like trabeculae when comparing CT with MRI (Fig. 6). Bone biopsy from the iliac crest showed epithelioid cell granulomata within which were occasional small multinucleated giant cells (Fig. 7). The granulomata were noncaseating and ‘‘naked,’’ without significant numbers of accompanying inflammatory cells. Stains for micro-organisms, including fungi and both typical and atypical mycobacteria, were negative. There was no evidence of malignancy.
Discussion Osseous sarcoidosis is not infrequent and is reported on radiographs in 1–13% of patients with the disease.2,3 The phalanges of the hands and feet are most often affected, although the spine, ribs, pelvis, nasal bones, and skull may be involved. Vertebral sarcoidosis is an extremely rare form of osseous sarcoidosis and is associated with mediastinopulmonary disease in 80–90% of cases.4,5 Vertebral sarcoidosis is usually localized, most commonly to the
lower thoracic and upper lumbar spine6; however, all areas of the vertebral column can be involved. Although osseous sarcoidosis is usually an incidental finding, axial disease is almost always symptomatic, manifesting as radicular back pain. Vertebral disease may be purely osteosclerotic,7 osteolytic, or mixed with variable CT and MRI patterns. Extension into the pedicles and epidural space may be seen. Disc spaces are characteristically preserved. Spinal cord and cauda equina involvement are rare. There are several distinct types of bony lesions in sarcoidosis.8 They may be lytic cortical punched out defects, permeative lesions with cortical tunnelling, and progressive trabecular remodelling, which results in a reticular pattern, destructive lesions with propensity for pathological fracture, and periosteal reaction. Lytic lesions may develop a sclerotic rim with healing. Plain radiographs and CT may be normal or reveal lytic lesions with or without marginal sclerosis. The radiographic appearance can simulate osteomyelitis or neoplasm. In this case the disease in the sternum and the pelvis appeared to be aggressive with areas of cortical destruction, but reassuringly, no associated extra-osseous soft-tissue mass. MRI usually demonstrates multifocal vertebral lesions that are low signal on T1-weighted images, high signal on T2-weighted images and enhance strongly, depending on the nature of the lesion and disease activity.9 On bone scintigraphy, radiotracer uptake is usually confined to areas of active inflammation.10 In this case the lesions in the lumbar spine did not accumulate tracer. This is due to the planar nature of the study. Single photon-emission CT (SPECT) is more sensitive in detecting low levels of spinal involvement due to increased signal-to-noise ratio and would have been more likely to detect all the axial disease. As in the present case report, the MRI and radionuclide findings are nonspecific and similar findings may be present with metastatic disease, granulomatous infection, multiple myeloma, lymphoma, and Paget’s disease.11 Radiological diagnosis of osseous sarcoidosis is usually straightforward if typical bone lesions are seen on a background of multisystem
S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
169
Figure 3 Axial CT image through the pelvis demonstrating mixed lytic and sclerotic lesions, with lace-like trabeculation and areas of cortical destruction (arrow).
disease. Diagnosis of osseous sarcoidosis in the absence of significant disease elsewhere is best made with plain radiographs or CT, but almost always requires biopsy to exclude other conditions, in particular malignancy and infection. Given its rarity, there are few guidelines for the treatment of vertebral sarcoidosis. Indications for treatment include pain, hypercalcaemia, and bony destruction. Corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDS), or other disease modifying agents may be used for pain control, to reduce swelling, and suppress granulomatous inflammation. In the present case, there was a good response to steroid therapy with resolution of night sweats and constitutional symptoms, and
Figure 2 High-resolution axial CT image of the chest demonstrating normal lung parenchyma (a), bilateral hilar lymphadenopathy (b), and an ill-defined destructive lytic lesion in the sternum (c).
Figure 4 Technetium 99m bone scintigraphy image demonstrating extensive tracer uptake in the skull, scapulae, sternum, ribs, cervical and thoracic vertebrae, and the anterior pelvis (between anterior superior and inferior iliac spines). There is also bilateral symmetrical uptake in the sacro-iliac joints. No radiotracer uptake demonstrated in the lumbar spine or appendicular skeleton.
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S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
Figure 5 Sagittal T2-weighted, T1-weighted, and STIR images of the cervical spine demonstrate multifocal ill-defined lesions within the vertebral bodies, which are mildly hypointense on T1-weighted and hyperintense on T2-weighted and STIR sequences.
improvement of back stiffness. Treatment does not usually normalize the bone abnormalities,12 and it becomes more difficult to reverse radiographic changes with increasing duration of disease. Chronic osseous disease is normally associated with multisystem disease and hence a poor prognosis. In summary, we present the imaging findings in a patient who presents with extensive axial sarcoidosis, sparing the
appendicular skeleton, in the absence of lung involvement. Although osseous sarcoidosis usually occurs secondary to manifestations elsewhere, axial disease may rarely be the presenting feature. The MRI and radionuclide imaging of vertebral sarcoidosis is non-specific, but CT and plain radiographs can reveal characteristic lace-like reticular lesions. Histological confirmation of the diagnosis is usually required.
Figure 6 Sagittal CT image of the thoracolumbar spine demonstrates multiple lytic vertebral body lesions with sclerotic margins (a). Sagittal T2-weighted (b), T1-weighted (c), and STIR (d) MRI images of the lumbar spine demonstrate little correlation with the lesions defined on CT (arrow). In particular, the lytic components and surrounding sclerosis are difficult to identify on MRI. Involvement of the posterior elements of L3 and L4 is observed on the STIR images.
S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
Figure 7 Iliac crest bone biopsy demonstrating a non-caseating epithelioid and multinucleate cell granuloma (arrows).
References 1. Mangino D, Stover DE. Sarcoidosis presenting as metastatic bony disease. A case report and review of the literature on vertebral body sarcoidosis. Respiration 2004;71:292–4.
171
2. James DG, Neville E, Carstairs LS. Bone and joint sarcoidosis. Semin Arthritis Rheum 1976;6:53–81. 3. Jelinek JS, Mark AS, Barth WF. Sclerotic lesions of the cervical spine in sarcoidosis. Skeletal Radiol 1998;27:702–4. 4. Koyama T, Ueda H, Togashi K, et al. Radiologic manifestations of sarcoidosis in various organs. Radiographics 2004;24:87–104. 5. Resnik CS, Young JW, Aisner SC, et al. Case report 594: osseous sarcoidosis (osteolytic) of lumbar spine and pelvis. Skeletal Radiol 1990;19:79–81. 6. Sartoris DJ, Resnick D, Resnik C, et al. Musculoskeletal manifestations of sarcoidosis. Semin Roentgenol 1985;20:376–86. 7. Poyanli A, Poyanli O, Sencer S, et al. Vertebral sarcoidosis: imaging findings. Eur Radiol 2000;10:92–4. 8. Neville E, Carstairs LS, James DG. Sarcoidosis of bone. Q J Med 1977;46:215–27. 9. Nanda S, Bhatt SP, Steinberg D, et al. Unusual cause of generalized osteolytic vertebral lesions: a case report. J Med Case Reports 2007;1:33. 10. Clarencon F, Silbermann-Hoffman O, Lebreton C, et al. Diffuse spine involvement in sarcoidosis with sternal lytic lesions: two case reports. Spine (Phila Pa 1976) 2007;32:E594–7. 11. Waanders F, van Hengel P, Krikke A, et al. Sarcoidosis mimicking metastatic disease: a case report and review of the literature. Neth J Med 2006;64:342–5. 12. Hyzy MD, Kroon HM, Watt I, et al. Chronic osseous sarcoidosis. JBR-BTR 2007;90:194–5.
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.elsevierhealth.com/journals/crad
Case Report
Axial osseous sarcoidosis: rare clinical presentation and radiological findings S. Yanny a, *, A.P. Toms a, D. MacIver a, T. Barker b, A. Wilson c a
Department of Radiology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, Norfolk, UK Department of Pathology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, Norfolk, UK c Department of Respiratory Medicine, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, Norfolk, UK b
art icl e i nformat ion Article history: Received in revised form 4 November 2009 Accepted 8 November 2009
Introduction Skeletal sarcoidosis is most frequently peripheral involving the phalanges of the hands and feet and usually occurs late in the course of the disease when there is typically a long history of lung involvement.1 Although bone involvement can be the earliest manifestation, it usually accompanies skin lesions, such as lupus pernio.2 Vertebral sarcoidosis is rare and is even less common in the absence of lung disease. Diagnosis is made by a combination of clinical, radiological, and pathological findings where noncaseating granuloma is the hallmark of the disease. We report a case of a 36-year-old man with extensive axial sarcoidosis presenting with constitutional symptoms but no evidence of lung disease. The extent of spinal disease was unusually diffuse in this patient and associated with a rare location in the sternum. The radiological features [plain film, computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy] of this rare
* Guarantor and correspondent: S. Yanny, Department of Radiology, Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk, NR4 7UY, UK. Tel.: þ44 1603 286140; fax: þ44 1603 286077. E-mail address: [email protected] (S. Yanny).
presentation of sarcoidosis are described with histopathological confirmation.
Case report A 36-year-old man presented with a 1 year history of drenching night sweats, rigors, exertional chest pain, and back stiffness. He had documented pyrexia between 38 and 39 C. He complained of an unproductive cough and malaise, but there was no history of weight loss. He did not complain of back pain. Prior to this he was fit and well with no relevant past medical history and had run the London marathon 1 year previously. He was an ex-smoker of one to two cigarettes a day for 5 years. His grandmother had a history of bronchogenic carcinoma. Physical examination was unremarkable with no clubbing or adenopathy. Erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at 91 mm/h and 67 mg/l, respectively. Serum calcium was normal. A chest radiograph demonstrated bilateral hilar enlargement and multifocal rib abnormalities (Fig. 1). Pulmonary function tests were normal. A highresolution CT chest examination demonstrated normal lung parenchyma with no evidence of peribronchovascular or subpleural nodules (Fig. 2a), but there was bilateral hilar
0009-9260/$ – see front matter Ó 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2009.11.002
168
S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
Figure 1 Posteroanterior (PA) chest radiograph demonstrating bilateral hilar enlargement and multifocal lace-like reticular pattern of rib involvement (magnified view).
lymphadenopathy (Fig. 2b). On CT there were abnormalities of the pelvis (Fig. 3), vertebrae, ribs, and sternum. These consisted of relatively well-circumscribed areas of osteolysis and reticular (lace-like) trabeculae, often with cortical destruction, and patchy areas of sclerosis. No extra-osseous soft-tissue masses were identified. Technetium 99m radionuclide bone scintigraphy revealed multiple foci of intense abnormal increased tracer uptake in the skull, scapulae, sternum, ribs, cervical and thoracic spine, and pelvis (Fig. 4), corresponding to areas of bony abnormality on CT. The lesions seen in the lumbar spine did not accumulate tracer and there was no radiotracer uptake in the limbs. MRI of the spine and pelvis was non-specific (Figs. 5 and 6). Patchy bone marrow changes, in the vertebral bodies and posterior elements, were present, which were hyperintense on T2weighted and short-tau inversion recovery (STIR) sequences, and hypointense on T1-weighted imaging. It was not possible to appreciate the lace-like trabeculae when comparing CT with MRI (Fig. 6). Bone biopsy from the iliac crest showed epithelioid cell granulomata within which were occasional small multinucleated giant cells (Fig. 7). The granulomata were noncaseating and ‘‘naked,’’ without significant numbers of accompanying inflammatory cells. Stains for micro-organisms, including fungi and both typical and atypical mycobacteria, were negative. There was no evidence of malignancy.
Discussion Osseous sarcoidosis is not infrequent and is reported on radiographs in 1–13% of patients with the disease.2,3 The phalanges of the hands and feet are most often affected, although the spine, ribs, pelvis, nasal bones, and skull may be involved. Vertebral sarcoidosis is an extremely rare form of osseous sarcoidosis and is associated with mediastinopulmonary disease in 80–90% of cases.4,5 Vertebral sarcoidosis is usually localized, most commonly to the
lower thoracic and upper lumbar spine6; however, all areas of the vertebral column can be involved. Although osseous sarcoidosis is usually an incidental finding, axial disease is almost always symptomatic, manifesting as radicular back pain. Vertebral disease may be purely osteosclerotic,7 osteolytic, or mixed with variable CT and MRI patterns. Extension into the pedicles and epidural space may be seen. Disc spaces are characteristically preserved. Spinal cord and cauda equina involvement are rare. There are several distinct types of bony lesions in sarcoidosis.8 They may be lytic cortical punched out defects, permeative lesions with cortical tunnelling, and progressive trabecular remodelling, which results in a reticular pattern, destructive lesions with propensity for pathological fracture, and periosteal reaction. Lytic lesions may develop a sclerotic rim with healing. Plain radiographs and CT may be normal or reveal lytic lesions with or without marginal sclerosis. The radiographic appearance can simulate osteomyelitis or neoplasm. In this case the disease in the sternum and the pelvis appeared to be aggressive with areas of cortical destruction, but reassuringly, no associated extra-osseous soft-tissue mass. MRI usually demonstrates multifocal vertebral lesions that are low signal on T1-weighted images, high signal on T2-weighted images and enhance strongly, depending on the nature of the lesion and disease activity.9 On bone scintigraphy, radiotracer uptake is usually confined to areas of active inflammation.10 In this case the lesions in the lumbar spine did not accumulate tracer. This is due to the planar nature of the study. Single photon-emission CT (SPECT) is more sensitive in detecting low levels of spinal involvement due to increased signal-to-noise ratio and would have been more likely to detect all the axial disease. As in the present case report, the MRI and radionuclide findings are nonspecific and similar findings may be present with metastatic disease, granulomatous infection, multiple myeloma, lymphoma, and Paget’s disease.11 Radiological diagnosis of osseous sarcoidosis is usually straightforward if typical bone lesions are seen on a background of multisystem
S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
169
Figure 3 Axial CT image through the pelvis demonstrating mixed lytic and sclerotic lesions, with lace-like trabeculation and areas of cortical destruction (arrow).
disease. Diagnosis of osseous sarcoidosis in the absence of significant disease elsewhere is best made with plain radiographs or CT, but almost always requires biopsy to exclude other conditions, in particular malignancy and infection. Given its rarity, there are few guidelines for the treatment of vertebral sarcoidosis. Indications for treatment include pain, hypercalcaemia, and bony destruction. Corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDS), or other disease modifying agents may be used for pain control, to reduce swelling, and suppress granulomatous inflammation. In the present case, there was a good response to steroid therapy with resolution of night sweats and constitutional symptoms, and
Figure 2 High-resolution axial CT image of the chest demonstrating normal lung parenchyma (a), bilateral hilar lymphadenopathy (b), and an ill-defined destructive lytic lesion in the sternum (c).
Figure 4 Technetium 99m bone scintigraphy image demonstrating extensive tracer uptake in the skull, scapulae, sternum, ribs, cervical and thoracic vertebrae, and the anterior pelvis (between anterior superior and inferior iliac spines). There is also bilateral symmetrical uptake in the sacro-iliac joints. No radiotracer uptake demonstrated in the lumbar spine or appendicular skeleton.
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S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
Figure 5 Sagittal T2-weighted, T1-weighted, and STIR images of the cervical spine demonstrate multifocal ill-defined lesions within the vertebral bodies, which are mildly hypointense on T1-weighted and hyperintense on T2-weighted and STIR sequences.
improvement of back stiffness. Treatment does not usually normalize the bone abnormalities,12 and it becomes more difficult to reverse radiographic changes with increasing duration of disease. Chronic osseous disease is normally associated with multisystem disease and hence a poor prognosis. In summary, we present the imaging findings in a patient who presents with extensive axial sarcoidosis, sparing the
appendicular skeleton, in the absence of lung involvement. Although osseous sarcoidosis usually occurs secondary to manifestations elsewhere, axial disease may rarely be the presenting feature. The MRI and radionuclide imaging of vertebral sarcoidosis is non-specific, but CT and plain radiographs can reveal characteristic lace-like reticular lesions. Histological confirmation of the diagnosis is usually required.
Figure 6 Sagittal CT image of the thoracolumbar spine demonstrates multiple lytic vertebral body lesions with sclerotic margins (a). Sagittal T2-weighted (b), T1-weighted (c), and STIR (d) MRI images of the lumbar spine demonstrate little correlation with the lesions defined on CT (arrow). In particular, the lytic components and surrounding sclerosis are difficult to identify on MRI. Involvement of the posterior elements of L3 and L4 is observed on the STIR images.
S. Yanny et al. / Clinical Radiology 65 (2010) 167–171
Figure 7 Iliac crest bone biopsy demonstrating a non-caseating epithelioid and multinucleate cell granuloma (arrows).
References 1. Mangino D, Stover DE. Sarcoidosis presenting as metastatic bony disease. A case report and review of the literature on vertebral body sarcoidosis. Respiration 2004;71:292–4.
171
2. James DG, Neville E, Carstairs LS. Bone and joint sarcoidosis. Semin Arthritis Rheum 1976;6:53–81. 3. Jelinek JS, Mark AS, Barth WF. Sclerotic lesions of the cervical spine in sarcoidosis. Skeletal Radiol 1998;27:702–4. 4. Koyama T, Ueda H, Togashi K, et al. Radiologic manifestations of sarcoidosis in various organs. Radiographics 2004;24:87–104. 5. Resnik CS, Young JW, Aisner SC, et al. Case report 594: osseous sarcoidosis (osteolytic) of lumbar spine and pelvis. Skeletal Radiol 1990;19:79–81. 6. Sartoris DJ, Resnick D, Resnik C, et al. Musculoskeletal manifestations of sarcoidosis. Semin Roentgenol 1985;20:376–86. 7. Poyanli A, Poyanli O, Sencer S, et al. Vertebral sarcoidosis: imaging findings. Eur Radiol 2000;10:92–4. 8. Neville E, Carstairs LS, James DG. Sarcoidosis of bone. Q J Med 1977;46:215–27. 9. Nanda S, Bhatt SP, Steinberg D, et al. Unusual cause of generalized osteolytic vertebral lesions: a case report. J Med Case Reports 2007;1:33. 10. Clarencon F, Silbermann-Hoffman O, Lebreton C, et al. Diffuse spine involvement in sarcoidosis with sternal lytic lesions: two case reports. Spine (Phila Pa 1976) 2007;32:E594–7. 11. Waanders F, van Hengel P, Krikke A, et al. Sarcoidosis mimicking metastatic disease: a case report and review of the literature. Neth J Med 2006;64:342–5. 12. Hyzy MD, Kroon HM, Watt I, et al. Chronic osseous sarcoidosis. JBR-BTR 2007;90:194–5.