Highlights

This case focused on the treatment of Langerhans cell Histiocytosis of the cervical spine.
Main management of vertebral LCH is conservative method.
If there is nerological deficit due to mass effect, surgery must be considered.

Abstract

Langerhans cell histiocytosis (LCH) of the spine is a common benign disease in children and adolescents that rarely affects adults. Main management of single lesion (unifocal) vertebral LCH is conservative method, unless there is neurological deficit due to mass effect, surgery must be considered. This is an interesting and rare case report of the patient with LCH at C5 vertebral body who underwent fusion surgery.

1. Introduction

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by abnormal proliferation of Langerhans cells, which results in the formation of lesions primarily in the skin, bone, liver, spleen, and lymph nodes [1] and [2]. The incidence of spinal involvement varies from 6.5% to 25% of cases with LCH of the skeleton [3]. The disease seen mainly in children, but which can occur in any age group. The clinical presentation of the disease may range from a self-healing bone-lesion to multi-system life-threatening disease. The choice of appropriate therapy is therefore a significant challenge, with treatment options varying from watch-and wait to aggresive treatment [4] and [5]. In this case report, we share our 36-year old male with cervical spine LCH that had performed anterior cervical corpectomy and fusion.

2. Case report

This 36-year-old man, was first examined in the neurosurgical clinic because of a 6 months history of neck pain. The complaint followed by right arm radiating pain. Neurologic compromise does not respond to conservative treatment such as medication of non-steroidal anti-inflammatory drug and physical therapy. On examination, the patient was attentive and alert. The cranial nerves were intact, and the motor examination showed no focal weakness. The physiological reflex were normal. He was in a state of increasing appeal posterior neck pain and right arm radiating pain. The results of all laboratory investigations including white blood cell count, erythrocyte sedimentation rate, and serum chemistries were within normal limits. Including a magnetic resonance (MR) imaging of the cervical spine, revealed changes at C5 vertebral body. On contrast enhanced T1 weighted images, enhanced mass like lesion extended to anterior epidural space, subsequently central spinal stenosis was visualized (Fig. 1A & B). Computed tomography (CT) scans showed an expansile lytic lesion associated with erosive changes within the C5 vertebral body (Fig. 1C & D). We commissioned the oncologic team to CT guided biopsy, but the consensus was to perform surgical resection of the lesion. In 2011, the patient underwent C5 anterior cervical corpectomy and fusion with iliac bone graft. Microscopic examination of these specimens showed a prominent perivascular infiltrate consisting of pale-staining Langerhans histiocytes mixed with lymphocytes and plasma cells. The histological diagnosis was LCH. Immunohistochemistry staining was positive for CD1a and S-100 (Fig. 2). The neck pain and radiating pain were completely recover after surgery. The patient had normal gait and no other neurological findings. MR studies at 1 month after surgery revealed no sign of tumor growth at C5 vertebral body (Fig. 3A & B). Plain X Ray showed the cervical body has already fused (Fig. 3C). The patient routinely followed for five years. There were no history of complications or worsening of the symptoms were observed. Notably, serial MR studies revealed no lesion or tumor re-growth at C5 vertebral body (Fig. 3D).
Fig. 1
Fig. 1. 
Preoperative studies Magnetic Resonance (MR) imaging of the cervical spine, revealed changes in the vertebral body at C5. Contrast-enhanced T1-weighted image demonstrating homogeneous enhancement of the involved vertebra and paraspinal soft-tissue mass, which shows oversleeve-like sign, extend to anterior epidural space (A & B). Sagittal (C) and axial (D) computed tomography (CT) scans showing poorly defined osteolytic lesion involving C5 vertebral body.
Fig. 2
Fig. 2. 
Microscopically, there were sheets and scattered individual cells of characteristic tumor cells with various inflammatory cells, predominantly eosinophils. The tumor cells revealed folded and convoluted nuclei with occasional intranuclear groove and indistinct nucleoli, which was consistent with Langerhans cells. They were weakly positive for S-100 (A & B) and positive for Langerin (C) and CD1a (D).
Fig. 3
Fig. 3. 
Post operative MRI revealed no sign of tumor growth at C5 vertebral body. (A & B) Plain x-ray two years after surgery showed the cervical body has already fused (C); and MRI two years after surgery had no sign of tumor re-growth in the fusion construct (D).

3. Discussion

Langerhans cell histiocytosis (LCH) defines a group of disorders known as Histiocytosis X, eosinophillic granuloma, Abt-Letterer-Siwe disease and Hand–Schuller-Christian disease[3][6] and [7]. LCH has been reported to be caused by the proliferation and dysregulation of inflammatory cytokines such as interleukin-17A [8] and [9]. The incidence of LCH in adults is thought to 1–2 per million population, and in children of 2–10 cases per million, but this is likely to have underestimated the occurrence of the disease [7]. Previously reported that eighty-percent of the patients are younger than 10 years old [10]. However in our case, the patient was 36 years old, it might happen due to delayed diagnosis. The lesions often occurs in bone. The most frequently involving sites are skull (26%), vertebra (7%), ribs (12%), upper and mandible (9%), and bones of extremities (11%). Bunch et al. reported that only 14 (6.5%) of 214 cases were localized in the spine [10]. In the spine, LCH mainly involves the vertebral bodies, mostly with the thoracic spine (54%) followed by the lumbar (35%) and cervical spine (11%) [10]. Estimating of LCH that occurs as a single lesion in the cervical spine is difficult. Howarth et al. reported that spinal involvement, especially cervical vertebra was present in only 0.02% of 342 cases [9]. Our patient is a rare case of LCH in the adult cervical spine. Diagnosis of LCH is based on radiological changes and/or specific pathologic and immunohistochemical findings. We can find an osteolytic lesion often occurring in the metaphyseal area of long bones. Microscopically, a variable admixture of Langerhans cells with eosinophils, giant cells, neutrophils, foamy cells and fibrosis are visualized, as well as Langerhans cells that are positive for CD1a and S-100 protein [5]. The most controversial issue is to determine a treatment strategy. In the previous literature, the prognosis of the vertebral types is considered to be benign with a good result. There have not been any hazardous neurological deficit after involvement of the vertebral spine [11]. Even though the course of vertebral type of LCH is good, surgical treatment is also considered in selected cases. In our case, we had to perform extensive fusion surgery due to severe neurologic symptoms caused by cord compression, which threatened the patient's neurologic function. Many studies have reported resolution of LCH using variety of treatment options including observation, surgery, chemotherapy, radiation therapy. Treatment options should be guided by degree of disease. Patients with localized lesion have a good outcome and need minimal treatment. In contrast, multisystemic disease shows poor prognosis. In one study of about one hundred children with LCH, the overall survival rate was near 70% at 5 years respectively. Contrary, in patients with spleen or liver involvement, the 5-year survival was 25% [12]. Hence, factors affecting the prognosis of LCH must be diagnosed. In our case, further diagnostic evaluation included a bone scan, CT of the lungs, bone marrow biopsy, pituitary hormonal evaluation and brain CT and abdominal ultrasound evaluation was done. No other LCH infiltration was identified. And he is still managed with the hematologist and oncologist at our hospital annually. Postoperatively, our patient was free from posterior neck pain and arm radiating pain. MR studies at 2 years after surgery, there was no tumor re-growth and plain x-ray showed the cervical body has already fused. The patient routinely followed for every five years. There were no history of complications or worsening of the symptoms. Notably, serial MR studies revealed no lesion or tumor re-growth in the fusion construct. In conclusion, surgical decompression should be reserved for the uncommon cases with therapy refractory pain and neurologic compromise.

Patient consent

The patient and guardian have consented to the submission of this case report. (IRB of Chonnam National University Hospital)

Acknowledgements

This study was supported by a grant (CRI 13902-21) from the Chonnam National University Hospital Biomedical Research Institute.

References

    • [1]
    • S. Imashuku, Y. Shioda, R. Kobayashi, G. Hosoi, H. Fujino, S. Seto, H. Wakita, A. Oka, N. Okazaki, N. Fujita, T. Minato, K. Koike, Y. Tsunematsu, A. Morimoto
    • Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Japan LCH study group
    • Haematologica, 93 (4) (2008), pp. 615–618
    •  |   | 
    • [2]
    • E. Derenzini, M.P. Fina, V. Stefoni, C. Pellegrini, F. Venturini, A. Broccoli, L. Gandolfi, S. Pileri, S. Fanti, E. Lopci, P. Castellucci, C. Agostinelli, M. Baccarani, P.L. Zinzani
    • MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis: experience on seven patients
    • Ann. Oncol., 21 (6) (2010), pp. 1173–1178
    •  |   | 
    • [3]
    • X.S. Peng, T. Pan, L.Y. Chen, G. Huang, J. Wang
    • Langerhans' cell histiocytosis of the spine in children with soft tissue extension and chemotherapy
    • Int. Orthop., 33 (3) (2009), pp. 731–736
    •  |   | 
    • [4]
    • L. Porto, S. Schoning, E. Hattingen, J. Sorensen, A. Jurcoane, T. Lehrnbecher
    • Central nervous system imaging in childhood Langerhans cell histiocytosis - a reference center analysis
    • Radiol. Oncol., 49 (3) (2015), pp. 242–249
    • [5]
    • L. Gong, W.D. Zhang, Y.H. Li, X.Y. Liu, L. Yao, X.J. Han, S.J. Zhu, M. Lan, W. Zhang
    • Clonal status and clinicopathological features of Langerhans cell histiocytosis
    • J. Int. Med. Res., 38 (3) (2010), pp. 1099–1105
    •  |   | 
    • [6]
    • G. Dhall, J.L. Finlay, I.J. Dunkel, L.J. Ettinger, S.J. Kellie, J.C. Allen, R.M. Egeler, R.J. Arceci
    • Analysis of outcome for patients with mass lesions of the central nervous system due to Langerhans cell histiocytosis treated with 2-chlorodeoxyadenosine
    • Pediatr. Blood Cancer, 50 (1) (2008), pp. 72–79
    •  |   | 
    • [8]
    • G. Badalian-Very, J.A. Vergilio, B.A. Degar, L.E. MacConaill, B. Brandner, M.L. Calicchio, F.C. Kuo, A.H. Ligon, K.E. Stevenson, S.M. Kehoe, L.A. Garraway, W.C. Hahn, M. Meyerson, M.D. Fleming, B.J. Rollins
    • Recurrent BRAF mutations in Langerhans cell histiocytosis
    • Blood, 116 (11) (2010), pp. 1919–1923
    •  |   | 
    • [10]
    • S. Sayhan, D. Altinel, C. Erguden, C. Kizmazoglu, M. Guray, U. Acar
    • Langerhans cell histiocytosis of the cervical spine in an adult: a case report
    • Turk. Neurosurg., 20 (3) (2010), pp. 409–412
    •  | 
    • [11]
    • J.L. Jouve
    • Expert's comment concerning grand rounds case entitled “Langerhans cell histiocytosis of the atlas in an adult” (by Wo Quan Zhong, Liang Jiang, Qing Jun Ma, Zhong Jun Liu, Xiao Guang Liu, Feng Wei, Hui Shu Yuan, Geng Ting Dang)
    • Eur. Spine J., 19 (1) (2010), pp. 23–24
    •  |   | 
Corresponding author at: Department of Neurosurgery, Chonnam National University Hospital, 42, Jebong-ro, Donggu, Gwangju 501-757, Republic of Korea.