Langerhans cell histiocytosis of the cervical spine: a post traumatic presentation.

J Aw1, K Wheeler2, TAD Cadoux-Hudson3 and A Jones4

1Diagnostic Department, Bristol Royal Infirmary, United Healthcare Trust Hospital, Marlborough St, Bristol, BS2 8HW

2Paediatric Haematology/Oncology Unit, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU

3Oxford John Radcliffe Hospital, Radcliffe Infirmary NeuroSurgical Division, Woodstock Rd, Oxford, Oxfordshire OX2 6HE

4The Great Western Hospital, Diagnostic Department, Malborough Rd, Swindon, Wiltshire SN3 6AA

SMJ 2008 53(1): 60

 

Abstract

Langerhans cell histiocytosis occurring at critical sites can cause both diagnostic difficulty and risk for morbidity. We present a case report of a 17 year old male who presented with neck pain following a sports injury. He was initially treated with analgesia but due to persistent pain he presented to the emergency department. A plain radiograph revealed a pathological fracture with osteolytic destruction of C4. Further investigations and surgical spinal stabilisation under orthopaedic care revealed a biopsy proven diagnosis of solitary histiocytosis of C4. He recovered completely with normal function. This case report contributes to the clinical experience of this rare entity and gives a review of the literature on this rare but highly significant disease.

 

Introduction

Langerhans cell histiocytosis (LCH) is a poorly understood disorder characterised by clonal proliferation of Langerhans cells. Formerly known as Histiocytosis X it was subdivided into three clinical categories: Letterer-Siwe disease (disseminated histiocytosis), Hand-Schuller-Christian disease (multifocal histiocytosis) and Eosinophilic Granuloma (solitary histiocytosis). These presentations are now believed to represent different ends of the same spectrum of disease. The proliferating cell in all forms is the Langerhans cells of marrow origin.1 They are dendritic cells whose main role is in presenting antigens, normally responsible for the first line immunologic defence in the skin. These cells are normally found in the epidermis however they are also present in smaller numbers throughout the body. The aetiology of LCH is still unknown but it is considered to be a non-neoplastic condition. The most common bony locations in order of decreasing frequency are the skull, femur, mandible, pelvis, ribs and spine where it is classically known as vertebral plana.2 When it occurs within the cervical spine it presents a substantial risk for morbidity and mortality. Bertram et al3 performed a meta-analysis of all cases and reported on eosinophilic granuloma of the cervical spine, 53 cases in total (43 paediatric cases and 9 adult cases). Ngu et al4 found only 5 published cases of eosinophilic granuloma of the atlas in children. This report describes a patient presenting with symptoms after a sports injury who was found to have an isolated deposit of LCH in the fourth cervical vertebrae.

 

Case Report

A 17-year-old Caucasian male presented with a history of neck injury whilst playing football 2 weeks prior to re-attending the emergency department. Following the initial sports injury, he had experienced an increase in neck stiffness and pain. He was normally fit and well with an unremarkable past medical history.

 

Physical examination reveals tenderness at C6/7 level and a mild rotational deficit to the right (limited to 20 degrees forward rotation). No apparent external injury of the cervical spine was evident. Neurological deficits were not detected. Laboratory investigations were within normal limits.   

 

An initial plain lateral cervical spine radiograph revealed an isolated osteolytic lesion with collapse of the C4 vertebral body and normal appearance of the soft tissue planes (Figure 1).

 

Magnetic resonance imaging (MRI) (protocol: T1W, T2W Sagital and axial) of the cervical spine confirmed collapse of C4 vertebral body with an abnormal marrow signal, high signal on T2-weighted (Figure 2.0 and 2.1) and low to isointense compared to muscle on T1-weighted sequences (Figure 3.0, and 3.1). High signal in the para-vertebral soft tissues and normal signal and configuration of the intervertebral discs with no evidence of any associated soft tissue lesion. The T2W sequence also revealed high intramedullary signal over the length of several vertebral bodies at lower level to the marrow changes of C4, consistent with a syrinx (Figure 2.0). The cervico-medullary junction and posterior fossae were normal; the absence of a Chairi 1 malformation is in keeping with a traumatic aetiology of the syrinx.

The patient was transferred to a neurosurgical tertiary centre with a concern of a diagnosis of a malignant process such as Ewing’s sarcoma, osteosarcoma, leukaemia, or lymphoma. Surgical management consisted of an autologous bone transplantation: a C4 corporectomy iliac bone graft and Condam Onlay plate for spinal stabilization. The histology of tissue taken at the corportectomy confirmed a diagnosis of Langerhans cell histiocytosis. Because of the high frequency of multiple skeletal lesions, it is recommended that a skeletal survey which is more sensitive for LCH than a technetium bone scan is performed.12 In our case further investigations did not reveal any other lesions on a skeletal survey and brain MRI showed a normal pituitary fossa. Postoperative recovery was uneventful, with relief of the neck pain and recovery of a full range of movements. Long term follow up care will be under the orthopaedic team and subsequent removal of the titanium plate is anticipated.

 

Discussion

Formerly known as eosinophilic granuloma (either uni-focal or multi-focal) this variant of LCH was characterised by expanding, erosive accumulations of Langerhans cells within the medullary cavities of bones.1 Uni-focal lesions usually affected the skeletal system without infiltration of normal tissue or development of metastasis.  It is thought to be a benign osteolytic lesion with an indolent course.1

 

Uni-focal LCH of the cervical spine in the paediatric population is uncommon with a bimodal distribution. Uni-focal LCH of the cervical spine affects children or young adolescent (mean age at the time of diagnosis for cervical LCH was 7.4+/-4.5 years) and adults (mean age at the time of diagnosis for cervical LCH was 35+/-13.8 years).3, 5 The diagnosis of an eosinophilic granuloma is even rarer in adults as compared to the paediatric population.20

 

Eighty percent of uni-focal LCH present before the age of 10 years [5, 13] and with an estimated male: female ratio of 2-5:1 (5, 12). A mean age (8.2 years) at the time of diagnosis was found if you encompass LCH of the spine [12]. The skull is the most frequent location, then in descending order the femur, mandible, pelvis, ribs and spine.2 A meta-analysis of cervical LCH reported cases in the literature found that children had lesions in C3-5 in 60% of cases compared with C2-3 involvement in 54% of adult cases.3 Consistent with our case, LCH localised in the skeleton usually presents with local pain, tenderness, and a restricted range of movement developing over several weeks to months2, 3, 6 and carries a favourable prognosis.

 

Plain radiography, CT and MRI encompass the radiological assessment. Radiography is useful to assess the entire skeletal axis; CT is used to fully delineate the extent of local bony destruction and any soft tissue involvement. Fluid-levels and dural extension of spinal involvement are rarer features on CT and MRI.5

 

The classic radiographic findings of LCH in the spine are vertebral collapse with preserved disc spaces and lack of extra-spinal or soft tissue involvement.7, 12 This helps to differentiate from osteomyelitis. MRI is non-specific for histiocytosis, but is able to differentiate an active from an inactive lesion. Active lesions show a low signal on T1W and a high signal on T2W in the marrow compared to low on T1 & T2W in the case of an old lesion.2, 5 MRI is also an excellent guide for biopsy where biopsy is required as MRI is able to differentiate active from healing lesions and thus guide needle biopsies.

 

Presentation of histiocytosis as a solitary vertebral lesion is uncommon, and even more so in an isolated lesion of C2. 4, 7, 8

 

Treatment of LCH of the cervical spine has been variable. The different standard treatment strategies are: no treatment, resection, intra-lesion infiltration with steroids, systemic steroids, NSAIDs, pamidronate, and radiation therapy. Various case reports advocate their own specific therapies however each case is quite individual in the site involved, morphology, soft tissue component, and skeletal maturity of the patient. Historically radiation therapy was used7, 14 but is now not advocated due to the risk of late effects within the radiotherapy field, both impaired tissue growth and the risk of secondary malignant lesions. Local and/or systemic treatment should be considered for either symptomatic localised disease or multi-focal disease. The current recommended treatment for multi-focal bone disease is systemic treatment with oral steroids with IV venous vinblastine in a 6 months schedule as well as specific orthopaedic measures indicated by virtue of the site of disease. Surgical intervention may be indicated for a lesion which is extensive, compromises spinal stability or has neurological deficit.4 In multisystem LCH, the most recent randomized clinical trial suggests that intravenous vinblastine and etoposide, both with one dose of corticosteroids, are equally effective treatments. If these patients do not respond within 6 weeks they are at increased risk for treatment failure and may require different therapy.19

 

Currently although there are new potential therapies for LCH such as antiCD52 antibody- alemtuzumab, Vascular Endothelial Growth Factor, Thalidomide and TNF-alpha antagonists15, 16, 17, 18 they would not be indicated in a case of isolated or multi-focal bone disease.

 

A series of 4 cases of LCH in the cervical spine at a single institution concluded good clinical results with prednisolone monotherapy.9 Bertram et al3 advocated immobilisation alone in a Minerva jacket with excellent clinical results. Surgery was reserved for cases with neurological defects or instability. Long-term follow up of LCH involving the posterior elements of the cervical spine in a skeletally immature patient with a short course of chemotherapy and steroids, and conservative care showed excellent resolution.4 Several authors have concluded that low dose chemotherapy is safe and effective for patients with solitary LCH.4, 8, 10

 

In conclusion solitary LCH of the cervical spine is uncommon in the paediatric population but has excellent long term prognosis. Imaging studies and biopsy were useful for diagnosing LCH at an early stage and to differentiate this rare entity from other sinister causes.

References

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