Sarcoidosis, also called Morbus Boeck disease, is a potentially systemic disease defined by noncaseating granulomatous inflammation of uncertain etiology1. The natural history of sarcoidosis is unpredictable as it can involve one or multiple organ systems and it can be progressive or resolve spontaneously. While sarcoidosis has been described as affecting most organ systems, the lungs are involved in >90% of cases2. Skeletal involvement is much less frequent; the prevalence has been reported to range from <1% to 13%2,3. The small bones of the hands and feet are most often involved, whereas spinal disease is rare4. Most patients with spinal sarcoidosis present with axial pain that resolves either on its own or after the administration of corticosteroids. However, pathologic fractures have been reported with associated neurologic sequelae5,6.
We report the clinicopathologic features of five patients with sarcoidosis involving the spine.
The Massachusetts General Hospital Institutional Review Board reviewed and approved this study. We searched our bone sarcoma registry to identify all patients diagnosed with sarcoidosis of the spine from 1980 through 2007. In addition, we utilized our Department of Pathology database to search for pertinent cases. Inclusion criteria were the diagnosis of sarcoidosis, confirmed with a bone biopsy of the spine, and a minimum duration of follow-up of two years. The initial group included thirteen patients. One patient was excluded because there was no histological evidence of bone sarcoidosis. We also excluded five patients who had bone sarcoidosis but not of the spine. Two patients were excluded because of a lack of sufficient follow-up. This left a cohort of five patients with sarcoidosis of the spine who formed the final study group, and we reviewed their medical records, radiographs, and pathology reports.
The tissue specimen from each case had been reviewed by a bone pathologist. The pathologic features considered consistent with sarcoidosis included the presence of noncaseating granulomas composed of aggregates of epithelioid histiocytes with or without Langerhans multinucleated giant cells.
When appropriate, the patients had undergone skin tests to rule out infection with Mycobacterium tuberculosis. Lymph-node biopsies had been performed to help exclude lymphoma and infection, and, at the discretion of the pathologist, special stains for acid-fast and fungal organisms had been performed on tissue specimens.
All available radiographs had been reviewed by an experienced musculoskeletal radiologist, and the number of lesions and the specific sites had been recorded. In addition, the lesions had been characterized according to whether they were lytic, blastic, or mixed in appearance. Encroachment on the spinal canal was also noted.
We attempted to determine whether the spine was the initial site of manifestation or if it was detected after the sarcoidosis had presented in another organ system. We reviewed the symptoms of each patient as they related to spinal involvement and recorded the treatment rendered as well as the outcome. Table I presents a summary of the five cases as well as cases reported in the literature.
Case 1. A forty-eight-year-old man was seen with neck pain and numbness in his hands. He had been diagnosed with pulmonary sarcoidosis and had been treated with oral corticosteroids fifteen years earlier. Cervical spine radiographs demonstrated mild spondylosis. A magnetic resonance image (MRI) demonstrated scattered, diffuse signal abnormalities in the cervical spine. No soft-tissue mass was noted. A bone scan showed increased radioisotope uptake in the cervical spine, both shoulders, the right femur, and the right ilium. A needle biopsy of the iliac lesion revealed non-necrotizing granulomas consistent with sarcoidosis. The patient was treated with 10 mg of oral prednisone daily for three months, and the neck and hand symptoms completely resolved during treatment. The symptoms recurred two more times during the next seven years. Eventually, the symptoms did not respond to oral corticosteroids; subsequently, an intrathecal pain pump allowed the patient to remain pain-free.
Case 2. A forty-six-year-old man with a three-year history of pulmonary sarcoidosis presented with increasing thoracolumbar pain. An MRI demonstrated scattered, diffuse intraosseous signal abnormalities in the thoracolumbar spine, ilium, and sacrum. In addition, his hilar lymphadenopathy had worsened, as evident on chest radiographs. A biopsy of a thoracic spine lesion revealed noncaseating granulomas (Fig. 1). The patient was treated with a tapered dose of oral prednisone, starting with 40 mg daily. He was symptom-free after four months of treatment and was still symptom-free after sixty-three months of follow-up.
Case 3. A forty-one-year-old man with known pulmonary sarcoidosis presented with paresthesias on the plantar surface of his feet. Four months later, he developed Lhermitte signs. An MRI of the spine showed T2-weighted hyperintense signal abnormalities throughout the axial skeleton with a normal-appearing spinal cord. He was treated with 40 mg of prednisone, and the neurologic signs and symptoms resolved. A follow-up MRI acquired two years later revealed progression of the osseous lesions. The patient had no clinical symptoms, but prednisone therapy was restarted because of the radiographic progression of disease. A follow-up MRI acquired one year later revealed resolution of many of the signal abnormalities seen on the previous MRI (Figs. 2-A and 2-B). He did not develop any neurologic symptoms, and there was no pain. After forty-nine months, he remained symptom-free and the lesions remained stable as indicated by their MRI appearance.
Case 4. A fifty-one-year-old woman with known pulmonary sarcoidosis presented with thoracic back pain. Computed tomography (CT) revealed multifocal lytic lesions within the vertebral bodies of the thoracic spine. In addition, there were lytic lesions in the pelvis and liver as well as signal abnormalities in the spleen. A CT-guided biopsy of a pelvic lesion revealed noncaseating granulomas (Figs. 3-A and 3-B). The patient refused oral corticosteroid treatment. Subsequent CT images did not reveal progression of the lytic lesions. The thoracic back pain resolved over the next several months, and she was symptom-free after seventy months of follow-up.
Case 5. A fifty-seven-year-old man presented with mild back pain and lytic lesions in the thoracic spine, evident on a chest radiograph, which also revealed hilar lymphadenopathy. A biopsy of one of the osseous lesions revealed noncaseating granulomas. He received 15 mg of prednisone daily, but the corticosteroid therapy was subsequently stopped because of side effects. The sarcoidosis progressed over the next six months as he developed worsening hilar lymphadenopathy, skin rashes, and dyspnea as well as new lytic lesions in the scapula and ribs. Oral bisphosphonate therapy was started and oral prednisone therapy was restarted, but the dose was lowered to 10 mg daily. The dyspnea and skin rashes resolved, and the lytic lesions stabilized. He remained on low-dose corticosteroids and was symptom-free after 118 months.
Sarcoidosis is an idiopathic, inflammatory condition that occurs more commonly in females and black individuals7. Involvement of the spine by sarcoidosis is extraordinarily uncommon; it can be the first manifestation of the disorder or a harbinger of disease progression. The true prevalence of spinal disease is unknown as it can be asymptomatic and remain undetected. Spinal sarcoidosis usually involves the thoracolumbar region8. The radiographic appearance of vertebral-based sarcoidosis has not been well-defined. In our series, the lesions generally were lytic with well-defined borders, but some of the lesions were mixed lytic and sclerotic. The MRI demonstrated multifocal, hyperintense signal abnormalities on T2-weighted images, which were hypointense to isointense on T1-weighted images. The posterior elements are usually spared, as are the intervertebral discs8,9. Neurologic symptoms can be present even though overt stenosis may not be evident on MRI.
Only one patient in our series presented with radicular pain. As we cannot fully explain why this patient would have Lhermitte signs without clear evidence of compression, we postulate that there are two possible explanations. One is that there was nerve irritation occurring from the regional inflammatory response caused by the sarcoidosis. Another plausible explanation is that the spinal cord was involved by the sarcoidosis but the changes were undetected with MRI. Abnormal MRI signal changes within the parenchyma of the spinal cord associated with sarcoidosis have been reported in other series10,11.
The diagnosis of sarcoidosis is based in part on histological analysis of biopsy specimens from the lesions. Characteristic noncaseating granulomas must be present, although this alone is not sufficient to make the diagnosis. One must rule out other diseases that can present with noncaseating granulomas, including mycobacterial and fungal infection, brucellosis, lymphoma, foreign bodies, occupational beryllium exposure, malignant tumors, and common variable immunodeficiency.
The changes noted on CT and MRI in our series were nonspecific. If these lesions are discovered incidentally, then the patient should be evaluated as one would investigate a lesion of unknown origin12. When these lesions present in a patient over the age of forty, metastatic carcinoma should be considered. CT of the chest, abdomen, and pelvis as well as serum protein electrophoresis and measurements of serum calcium levels should be performed. Patients with bone sarcoidosis commonly have elements of pulmonary sarcoidosis, which are seen on CT of the chest. The radiographic findings are nonspecific, and a biopsy of the lesion is needed to help make the diagnosis. In addition to metastatic carcinoma and myeloma, lymphoma, histoplasmosis, coccidioidomycosis, and tuberculosis should all be considered.
Treatment of sarcoidosis is based on the clinical presentation of the disease. It is important to remember that many cases are identified incidentally and more than half will resolve spontaneously without treatment. Oral corticosteroids can be helpful in patients with pain, paresthesias, or dyspnea. Other systemic agents are also being used to treat sarcoidosis, although the level of evidence supporting their use is low2,13–15.
The surgical management of spinal sarcoidosis should be reserved for cases of spinal cord compression or instability secondary to fracture. This is an uncommon catastrophic manifestation of spinal involvement with sarcoidosis. Patients with lytic lesions, however, should be monitored for signs of disease progression to identify those who may be at risk for fractures.
Hem
E. [Multiple benign sarcoid of the skin—100 years since Caesar Boeck’s pioneering article]. Tidsskr Nor Laegeforen.
1999;119:4567-9. .
Dempsey
OJ;
Paterson
EW;
Kerr
KM;
Denison
AR. Sarcoidosis. BMJ.
2009;339:b3206.
Neville
E;
Carstairs
LS;
James
DG. Bone sarcoidosis. Ann N Y Acad Sci.
1976;278:475-87.
Wendling
D;
Desmurs
H;
Royer
F;
Gil
H;
Dupond
JL. Inaugural cervical vertebral sarcoidosis. J Rheumatol.
2008;35:362-5.
Tzagarakis
GP;
Papagelopoulos
PJ;
Sapkas
GS;
Tsarouchas
JK. Surgical management for instability and paraplegia caused by spinal sarcoidosis. A case report. Spine (Phila Pa 1976).
1998;23:1711-4.
Engle
EA;
Cooney
FD. Tetraplegia secondary to cervical sarcoidosis. Case report. J Neurosurg.
1979;50:665-7.
Rybicki
BA;
Major
M;
Popovich
J
Jr;
Maliarik
MJ;
Iannuzzi
MC. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol.
1997;145:234-41.
Marymont
JV;
Murphy
DA. Sarcoidosis of the axial skeleton. Clin Nucl Med.
1994;19:1060-2.
Brembilla
C;
Signorelli
A;
Lamartina
C;
Biroli
F. Surgical management in spinal sarcoidosis: case report. Spine (Phila Pa 1976).
2009;34:E258-61.
Bhagavati
S;
Choi
J. Intramedullary cervical spinal cord sarcoidosis. Spinal Cord.
2009;47:179-81. .
Varron
L;
Broussolle
C;
Candessanche
JP;
Marignier
R;
Rousset
H;
Ninet
J;
Sève
P. Spinal cord sarcoidosis: report of seven cases. Eur J Neurol.
2009;16:289-96.
Rougraff
BT;
Kneisl
JS;
Simon
MA. Skeletal metastases of unknown origin. A prospective study of a diagnostic strategy. J Bone Joint Surg Am.
1993;75:1276-81.
Lynch
JP
3rd;
McCune
WJ. Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders. Am J Respir Crit Care Med.
1997;155:395-420.
Moller
DR. Treatment of sarcoidosis—from a basic science point of view. J Intern Med.
2003;253:31-40.
Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med.
1999;160:736-55.
Bundens
DA;
Rechtine
GR. Sarcoidosis of the spine. Case report and literature review. Spine (Phila Pa 1976).
1986;11:209-12.
Bushara
KO;
Petermann
G;
Waclawik
AJ;
Brown
WD;
Schutta
HS. Sarcoidosis of the spinal cord with extensive vertebral involvement: a case report. Comput Med Imaging Graph.
1995;19:443-6.
Ginsberg
LE;
Williams
DW
3rd;
Stanton
C. MRI of vertebral sarcoidosis. J Comput Assist Tomogr.
1993;17:158-9.
Goobar
JE;
Gilmer
WS
Jr;
Carroll
DS;
Clark
GM. Vertebral sarcoidosis. JAMA.
1961;178:1162-3.
Heijckmann
AC;
Drent
M;
Dumitrescu
B;
De Vries
J;
Nieuwenhuijzen Kruseman
AC;
Wolffenbuttel
BH;
Geusens
P;
Huijberts
MS. Progressive vertebral deformities despite unchanged bone mineral density in patients with sarcoidosis: a 4-year follow-up study. Osteoporos Int.
2008;19:839-47.
Ito
M;
Motomiya
M;
Abumi
K;
Shirado
O;
Kotani
Y;
Kadoya
K;
Murota
E;
Minami
A. Vertebral osteonecrosis associated with sarcoidosis. Case report. J Neurosurg Spine.
2005;2:222-5.
Jelinek
JS;
Mark
AS;
Barth
WF. Sclerotic lesions of the cervical spine in sarcoidosis. Skeletal Radiol.
1998;27:702-4.
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.
Perlman
SG;
Damergis
J;
Witorsch
P;
Cooney
FD;
Gunther
SF;
Barth
WF. Vertebral sarcoidosis with paravertebral ossification. Arthritis Rheum.
1978;21:271-6.
Resnik
CS;
Young
JW;
Aisner
SC;
Levine
A. Case report 594: osseous sarcoidosis (osteolytic) of lumbar spine and pelvis. Skeletal Radiol.
1990;19:79-81.
Rúa-Figueroa
I;
Gantes
MA;
Erausquin
C;
Mhaidli
H;
Montesdeoca
A. Vertebral sarcoidosis: clinical and imaging findings. Semin Arthritis Rheum.
2002;31:346-52.
Sundaram
M;
Place
H;
Shaffer
WO;
Martin
DS. Progressive destructive vertebral sarcoid leading to surgical fusion. Skeletal Radiol.
1999;28:717-22.
Young
DA;
Laman
ML. Radiodense skeletal lesions in Boeck’s sarcoid. Am J Roentgenol Radium Ther Nucl Med.
1972;114:553-8.
Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.