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Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 133-137

Myelopathy secondary to isolated thoracic spine involvement mimicking metastasis in Erdheim–Chester disease: A case report and review of literature

Department of Spine Surgery, Ganga Medical Centre & Hospitals Pvt Ltd, Coimbatore, Tamil Nadu, India

Date of Submission14-Nov-2019
Date of Decision21-Jan-2020
Date of Acceptance31-May-2020
Date of Web Publication01-Oct-2020

Correspondence Address:
Ajoy P Shetty
Department of Spine Surgery, Ganga Medical Centre & Hospitals Pvt Ltd, Coimbatore 641043, Tamil Nadu.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ISJ.ISJ_78_19

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Erdheim–Chester disease (ECD) is a rare non-Langerhans histiocytosis. Appendicular skeleton involvement is more common whereas axial skeletal manifestation is very rare. Isolated thoracic spine involvement with myelopathy in ECD is reported extremely rarely. This case report aims to highlight the isolated axial skeletal involvement in the form of thoracic myelopathy, its diagnostic challenge, various treatment options and prognosis of the disease. We have managed our patient, presented with thoracic myelopathy, by posterior instrumented decompression followed by radiotherapy. This case report will contribute to increased awareness on isolated axial skeletal involvement in ECD.

Keywords: Axial skeletal involvement, Erdheim–Chester disease, non-Langerhans histiocytosis, thoracic myelopathy

How to cite this article:
Rajavelu R, Shetty AP, Kanna RM, Rajasekaran S. Myelopathy secondary to isolated thoracic spine involvement mimicking metastasis in Erdheim–Chester disease: A case report and review of literature. Indian Spine J 2021;4:133-7

How to cite this URL:
Rajavelu R, Shetty AP, Kanna RM, Rajasekaran S. Myelopathy secondary to isolated thoracic spine involvement mimicking metastasis in Erdheim–Chester disease: A case report and review of literature. Indian Spine J [serial online] 2021 [cited 2021 May 12];4:133-7. Available from: https://www.isjonline.com/text.asp?2021/4/1/133/308216

  Introduction Top

Erdheim–Chester disease (ECD) is a rare non-Langerhans histiocytosis, which involves different sites such as bone, retroperitoneum, lungs, skin, and central nervous system (CNS). Appendicular skeletal lesions are bilaterally symmetrical in nature and involve mainly the lower limbs. The axial skeleton is usually spared. Very few cases have been reported on spinal involvement in ECD, but as a part of multisystem involvement. Isolated spinal involvement with thoracic myelopathy due to ECD is rarely reported in the literature. Our case will contribute to increased awareness on axial skeletal involvement of the disease.

  Case Report Top

A 68-year-old individual, known diabetic and hypertensive, presented with progressively increasing gait instability for 2 months. He required assistance while walking since 2 weeks before presentation. He had urinary urge incontinence, weakness of bilateral lower limb, and significant weight loss (10 kg weight loss in 1 month). He was neither a smoker nor an alcoholic.

On examination, his gait was unstable without support. Neurological examination revealed a motor deficit of bilateral lower limbs (Medical Research Council grading [MRC]-3/5), exaggerated deep tendon reflexes with bilateral positive Babinski’s sign. Peri-anal sensation and voluntary anal contraction were normal.

Radiographs showed wedge compression at T7 and no other significant findings [Figure 1]. Magnetic resonance imaging [Figure 2] of the spine revealed a well-defined T1-weighted (T1W) and T2W hypointense lesion involving the body and posterior elements of T4 vertebra (3 × 4.0 × 2.5 cm) causing severe compression of the spinal cord. T5, T6, and T7 vertebral bodies were also minimally involved. On the basis of these MRI findings, osteoblastic metastasis was suspected and hence computed tomography (CT) of the thorax and abdomen were performed to find the site of the primary lesion. CT thorax [Figure 3] showed multiple lytic lesions in T4 and T5 vertebral bodies. CT abdomen and chest did not reveal any primary lesion. His long bone radiographs and MRI brain were normal. Bone marrow biopsy was negative for myeloma. Since the patient had progressive worsening of symptoms and MRI showed significant cord compression with CT of chest and abdomen negative for any primary lesion, we planned for urgent decompression and stabilization. A positron emission tomography with CT (PET-CT) scan is helpful to identify various sites of disease involvement; however, it could not be done in our case to avoid the delay for decompression. After a detailed evaluation, T2–T8 posterior instrumentation and T4–T5 decompression was performed [Figure 4]. Grayish-white, fibrous tumor tissue was excised and sent for histopathological examination. Post-operatively, radiotherapy of 10 Gy in five fractions was given. His postoperative period was uneventful and he got discharged on the seventh postoperative day, with improved motor power to MRC-4/5 and was able to ambulate independently. He returned to his routine activities by three months.
Figure 1: Antero-posterior and lateral radiograph of the thoracolumbar spine showing wedge compression of T7 vertebra and no sclerosis was noted

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Figure 2: (a) T1-weighted sagittal MRI shows a well-defined hypointense lesion of T4, T5, T6, and T7 vertebral bodies with the involvement of posterior elements of T4; (b) right para-sagittal T2W image; (c) mid-sagittal T2W image; (d) and (e) axial images showing maximal compression at T4

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Figure 3: (a) Sagittal CT image showing lytic lesion of T4 and T5 and wedge compression of T7 vertebra and (b) axial image demonstrating the involvement of vertebral body and posterior elements

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Figure 4: Antero-posterior (a) and lateral (b) radiographs of the postoperative thoracic spine showing T2–T8 instrumentation

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Histopathological examination [Figure 5] showed sheets of large round to polygonal cells with abundant histiocytes with granular eosinophilic cytoplasm and small round nucleus, and further immunohistochemistry confirmed the presence of ECD (CD68 positive, S-100, and CD1a negative). At a 2-year follow-up, the patient was self-ambulatory with complete neurological recovery.
Figure 5: Histopathological slides demonstrating sheets of large round to polygonal cells with abundant granular eosinophilic cytoplasm and small round nucleus resembling granular histiocytes characteristic of Erdheim–Chester disease

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  Discussion Top

ECD is a rare non-Langerhans histiocytosis and the underlying etiopathology remains unclear. Diagnosis is usually based on the histopathological evidence of foamy CD68 positive and CD1a negative histiocytic infiltration in combination with the clinical context. The pathological features of ECD include non-Langerhans histiocytes with foamy or eosinophilic cytoplasm, polymorphic granuloma, fibrosis, xanthogranulomatosis, proliferating fibroblasts, lymphocytic aggregates, and Touton giant cells.[1]

ECD affects multiple organs and presents with a wide clinical spectrum involving skeletal and extraskeletal systems. Neurological involvement in ECD is usually associated with other organ involvement such as bones, retroperitoneum, lungs, skin and cardiovascular system.[2],[3] Skeletal involvement usually affects the lower limbs involving femur, tibia, and fibula. On the contrary, there are only very few reports on upper limb involvement affecting ulna, radius, and humerus. Long bone lesions are characterized by symmetric sclerosis of the bilateral metaphysis, whereas the epiphysis and axial skeleton are usually spared.[4] In our case, there was no sclerosis of bone in plain radiograph but CT showed lytic lesions, as in certain cases it can be mixed lytic-sclerotic lesion or pure lytic lesions.[5] Several differential diagnoses are possible based on the presentation and it includes metastatic deposits, Langerhans cell histiocytosis, and juvenile xanthogranuloma (JXG). As there is no primary metastasis detected in our patient, the metastatic deposits were ruled out by radiological and histological examination. Langerhans cell histiocytosis shows a characteristic reniform nuclear morphology on histology and expresses CD1a, S100, and Langerin. ECD tumor cells lack central nuclear grooves and Birbeck granules that are typical of Langerhans cell histiocytosis and do not express CD1a or S100. JXG cells express factors VIIIa and CD68 and are negative for CD1a, Langerin, and S100. JXG occurs mainly in young children; however, the age and clinical presentation of our patient are different from that of JXG.

Spine- and spinal cord-associated lesions in ECD have been reported mostly as an association with other extraskeletal manifestation.[6] Klieger et al.[7] reported multiple lytic lesions in the thoracic spine as a manifestation of a patient with ECD during a routine workup for hemoptysis. Hwang et al.[6] reported cervical and thoracic compressive myelopathy due to spinal epidural lesions in a 25-year-old woman, who was diagnosed to have ECD two years earlier. She had initially presented with long-standing idiopathic diabetes insipidus and shoulder pain. Lim et al.[8] reported a case with skeletal involvement along with the involvement of bone marrow and axillary lymph nodes in a patient with exertional dyspnea. Takeuchi et al.[9] reported a case with thoracic extradural mass, intramedullary cervical lesion, and multiple intracranial lesions in a patient with a recurrent orbital tumor. Allmendinger et al.[10] reported epidural, pelvic, and proximal femoral lesions in a patient who presented with low back pain and was evaluated with suspicion of metastasis from prostate cancer. All these reported cases had axial skeletal involvement associated with appendicular or extraskeletal involvement. However, isolated spinal involvement in ECD is rarely reported.[11]

Three case reports classically define the MRI characteristics of the epidural masses as hypointense on T1W and hypo- or isointense on T2W images,[6] similar to our case who had hypointense lesion on both T1W and T2W images.

ECD being a very rare disease, numerous treatments have been attempted for this disease. Initiation of treatment is recommended for all patients except for asymptomatic disease.[12] Interferon-α, anticytokine-directed therapy, chemotherapeutic agents, radiotherapy, and targeted therapy for BRAF mutation are the various treatment options available apart from surgical intervention.

Interferon-α and pegylated interferon-α

High supportive evidence exists for the use of interferon-α and pegylated interferon-α (IFN-α/PEG-IFN-α) in ECD and is known to improve overall survival as compared to other agents.[13] Although the dose needs to be optimized, 3 million units (MIU) thrice a week have shown to decrease the lesional burden.[14],[15] High-dose IFN-α (IFN-α—18 MIU/week or PEG-IFN-α—180 µg/week) has been shown to have greater efficacy in patients with severe disease associated with CNS and cardiac involvement. Although the optimal duration of treatment is not clear, long-duration treatment with high-dose IFN-α was found to have disease stabilization or improvement in 64% of patients having ECD with CNS disease.[16] Adverse effects reported are constitutional symptoms, alopecia, pruritus, neuropsychiatric, transaminitis, gastrointestinal symptoms, and myelosuppression.[12] PEG-IFN-α is generally better tolerated and the dosage is determined by the severity and site of involvement.

Anticytokine-directed therapy: anakinra, infliximab, and tocilizumab

Anakinra, a recombinant IL-1R antagonist, was found effective at a dose of 1–2 mg/kg/day by reducing disease burden. It improves osseous, constitutional symptoms and benefits reported in cardiac and intracranial lesions.[17],[18],[19] Common side effects include injection site reactions, arthralgia, headache, and nasopharyngitis.

Infliximab, an anti-TNF-α antibody, provides clinical improvement in patients having cardiac involvement refractory to IFN-α.[20] Tocilizumab, a monoclonal antibody blocking the IL-6 receptor, is reported to have remarkable efficacy in difficult-to-treat disease manifestations with cardiac involvement; however, patients with CNS disease responded poorly to IL-6 inhibition.[21]

Many studies reported the usage of chemotherapeutic agents such as vinca alkaloids, anthracyclines, cladribine, cyclophosphamide, and corticosteroids and high-dose chemotherapy with autologous stem cell transplantation with variable results.[22],[23] Studies on radiotherapy in ECD reported that it prevents disease progression, however, it is mostly used for short-term palliation therapy.[24]

Targeted Therapy for BRAF Mutation

Since the establishment of BRAF mutation in ECD, frequency of which in ECD was reported to be more than 50%,[25] studies on inhibiting BRAF by vemurafenib and dabrafenib or in patients with wild-type BRAF, cobimetinib, a MEK inhibitor, have become the therapeutic target.[26] Vemurafenib in ECD demonstrated clinically meaningful long-term efficacy in patients with BRAF mutation,[25] and the most frequent side effects, when treated with BRAF inhibitors, are skin complications, ranging from pilar keratosis and photosensitivity to spinocellular carcinoma, and melanoma. The most frequent side effects of cobimetinib were nausea, acneiform rash, and rhabdomyolysis.[26] Though a high response rate was reported with targeted therapy, safety data should be considered as indefinite treatment is associated with the risk of increasing RAS-mediated neoplastic lesions.[27]

In our patient, the lesion causing compression was completely resectable and hence managed by posterior instrumented decompression followed by radiotherapy to prevent disease progression. The patient has recovered completely neurologically and has returned to his normal routine activities, and if any recurrence is found, IFN-α/targeted therapy is the therapeutic option to treat the patient.

Disease Surveillance and Prognosis

Patients should be evaluated every 3–6 months following the initiation of treatment and the interval can be increased once the disease has stabilized clinically and radiologically by (18F)-fluorodeoxyglucose-PET.[28] There is no specific serum biomarker available for ECD. It is recommended to continue treatment for a prolonged period if tolerated. However, on a case-to-case basis, with minimal disease burden or stable disease, attempting treatment cessation may be considered reasonable. The prognosis of ECD is poor, with only 43% of patients alive after an average follow-up of 32 months.[3] Worse survival was associated with CNS, retroperitoneal, and lung involvement.[29] However, recent studies reports on long-term survival are promising.[29] Survival analytical study describes an overall 1-year and 5-year survival rates as 96% and 68%, respectively, in patients treated with interferon therapy.[13] In a cohort of 165 patients with ECD, a 5-year survival rate of 82.7% was reported with an estimated median survival time of 13.5 years, and 34% of patients have received targeted therapy.[29]

  Conclusions Top

ECD is a rare multisystemic disease with predominant appendicular skeletal involvement. Thoracic spine involvement causing myelopathy is reported extremely rarely in the literature. There exists a diagnostic challenge in differentiating ECD with spinal metastasis radiologically, which also carries the inherent risk of dismal prognosis and lack of effective treatment. The surgically resectable tumor should be addressed appropriately and medical therapy is recommended for this multisystemic disease.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Lachenal F, Cotton F, Desmurs-Clavel H, Haroche J, Taillia H, Magy N, et al. Neurological manifestations and neuroradiological presentation of Erdheim–Chester disease: Report of 6 cases and systematic review of the literature. J Neurol 2006;253:1267-77.  Back to cited text no. 2
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Murray D, Marshall M, England E, Mander J, Chakera TM Erdheim–Chester disease. Clin Radiol 2001;56:481-4.  Back to cited text no. 4
Kumar P, Singh A, Gamanagatti S, Kumar S, Chandrashekhara SH Imaging findings in Erdheim–Chester disease: What every radiologist needs to know. Pol J Radiol 2018;83:e54-62.  Back to cited text no. 5
Hwang BY, Liu A, Kern J, Goodwin CR, Wolinsky JP, Desai A Epidural spinal involvement of Erdheim–Chester disease causing myelopathy. J Clin Neurosci 2015;22:1532-6.  Back to cited text no. 6
Klieger MR, Schultz E, Elkowitz DE, Arlen M, Hajdu SI Erdheim–Chester disease: A unique presentation with multiple osteolytic lesions of the spine and pelvis that spared the appendicular skeleton. AJR Am J Roentgenol 2002;178:429-32.  Back to cited text no. 7
Lim J, Kim KH, Suh KJ, Yoh KA, Moon JY, Kim JE, et al. A unique case of Erdheim–Chester disease with axial skeleton, lymph node, and bone marrow involvement. Cancer Res Treat 2016;48:415-21.  Back to cited text no. 8
Takeuchi T, Sato M, Sonomura T, Itakura T Erdheim–Chester disease associated with intramedullary spinal cord lesion. Br J Radiol 2012;85:e62-4.  Back to cited text no. 9
Allmendinger AM, Krauthamer AV, Spektor V, Aziz MS, Zablow B Atypical spine involvement of Erdheim–Chester disease in an elderly male. J Neurosurg Spine 2010;12:257-60.  Back to cited text no. 10
Caglar E, Aktas E, Aribas BK, Sahin B, Terzi A Erdheim–Chester disease in thoracic spine: A rare case of compression fracture. Spine J 2016;16:e257-8.  Back to cited text no. 11
Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim–Chester disease. Blood 2014;124:483-92.  Back to cited text no. 12
Arnaud L, Hervier B, Néel A, Hamidou MA, Kahn JE, Wechsler B, et al. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim–Chester disease: A multicenter survival analysis of 53 patients. Blood 2011;117:2778-82.  Back to cited text no. 13
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Suzuki HI, Hosoya N, Miyagawa K, Ota S, Nakashima H, Makita N, et al. Erdheim–Chester disease: Multisystem involvement and management with interferon-alpha. Leuk Res 2010;34:e21-4.  Back to cited text no. 15
Hervier B, Arnaud L, Charlotte F, Wechsler B, Piette JC, Amoura Z, et al. Treatment of Erdheim–Chester disease with long-term high-dose interferon-a. Semin Arthritis Rheum 2012;41:907-913.  Back to cited text no. 16
Aouba A, Georgin-Lavialle S, Pagnoux C, Martin Silva N, Renand A, Galateau-Salle F, et al. Rationale and efficacy of interleukin-1 targeting in Erdheim–Chester disease. Blood 2010;116:4070-6.  Back to cited text no. 17
Killu AM, Liang JJ, Jaffe AS Erdheim–Chester disease with cardiac involvement successfully treated with anakinra. Int J Cardiol 2013;167:e115-7.  Back to cited text no. 18
Diamond EL, Abdel-Wahab O, Durham BH, Dogan A, Ozkaya N, Brody L, et al. Anakinra as efficacious therapy for 2 cases of intracranial Erdheim–Chester disease. Blood 2016;128:1896-8.  Back to cited text no. 19
Dagna L, Corti A, Langheim S, Guglielmi B, De Cobelli F, Doglioni C, et al. Tumor necrosis factor α as a master regulator of inflammation in Erdheim–Chester disease: Rationale for the treatment of patients with infliximab. J Clin Oncol 2012;30:e286-90.  Back to cited text no. 20
Berti A, Cavalli G, Guglielmi B, Biavasco R, Campochiaro C, Tomelleri A, et al. Tocilizumab in patients with multisystem Erdheim–Chester disease. Oncoimmunology 2017;6:e1318237.  Back to cited text no. 21
Broccoli A, Stefoni V, Faccioli L, Agostinelli C, Spinardi L, Pastore Trossello M, et al. Bilateral orbital Erdheim–Chester disease treated with 12 weekly administrations of VNCOP-B chemotherapy: A case report and a review of literature. Rheumatol Int 2012;32:2209-13.  Back to cited text no. 22
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Diamond EL, Subbiah V, Lockhart AC, Blay JY, Puzanov I, Chau I, et al. Vemurafenib for BRAF V600-mutant Erdheim–Chester disease and Langerhans cell histiocytosis: Analysis of data from the histology-independent, phase 2, open-label VE-BASKET study. JAMA Oncol 2018;4:384-8.  Back to cited text no. 25
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Arnaud L, Malek Z, Archambaud F, et al. 18F-fluorodeoxyglucose-positron emission tomography scanning is more useful in follow up than in the initial assessment of patients with Erdheim–Chester disease. 2009;60:3128-38.  Back to cited text no. 28
Cohen YC, Saranga A, Gatt ME, Lavi N, Ganzel C, Magen H, et al. Treatment patterns and clinical outcomes in high-risk newly diagnosed multiple myeloma patients carrying the 17p deletion: An observational multi-center retrospective study. Am J Hematol 2018;93:810-5.  Back to cited text no. 29


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