Treatment and outcome of vertebral langerhans cell histiocytosis at the Children's Hospital of Eastern Ontario

Langerhans cell histiocytosis (LCH) is a relatively uncommon disorder involving the reticuloendothelial system in children and young adults. Although it was discovered by Hand in 1893, the etiology remains unknown,1 but viruses, bacteria and genetic factors have been implicated. Familial occurrence is very rare.2 LCH is now used to designate various clinicopathologic conditions previously known as Hand–Schuller –Christian disease, Abt–Letterer–Siwe disease, Hashimoto–Pritzker disease, eosinophilic granuloma of bone and histiocytosis X. LCH was agreed upon by the Writing Group of the Histiocyte Society in 1987 in order to acknowledge the central role of the Langerhans cell in these diseases. Although the classification system is in continual flux, the most contemporary nomenclature divides the disorder into a malignant form (malignant disorders) or a nonmalignant form, which ranges from self-limited to lethal (disorders of varied biological behaviour). LCH is classified as a disorder of varied biological behaviour and is dendritic-cell-related. Furthermore, LCH has been stratified on clinical grounds as single-system involving a single solitary site, single system affecting multiple sites or multisystem disease.3 LCH is characterized by an abnormal proliferation of histiocytes with a variable granulomatous and inflammatory component. The histologic picture is one of reactive rather than neoplastic proliferation.4 Multi-system LCH generally presents with a triad of exophthalmos, diabetes insipidus and lytic bone lesions.5 The clinical spectrum of LCH is broad, depending on the number and location of the lesions. Bone involvement is almost always present with the lesions usually located in the skull or long bones (or both)5 as well as the viscera. Other common anatomical locations (and findings) of LCH involvement include skin (rash), lungs (dysfunction), liver (dysfunction), gastrointestinal tract, hematologic system (dysfunction), the pituitary gland (diabetes insipidus) and the nervous system. Sites such as the spleen (dysfunction), lymph nodes, subcutaneous tissues overlying a bony lesion (pain), urinary tract, eye (uveitits, exophthalmos) and ear (chronic infections or discharge) may also be involved. General symptoms like fever, weakness and failure to thrive may be present.6,7 Not all children have all of these involvements, and although no single prognostic indicator is accepted, factors predicting a poor prognosis appear to be young age (<1 yr), signs of organ dysfunction (liver, bone-marrow, lung or digestive involvement), or dysfunction of one of the vital organs (liver, lung or bone marrow) or involvement of more than 3 organs, or a combination of these.1,6,7 Solitary bone involvement in contrast to the multisystem form, has the best prognostic result. LCH involving bone at a single site (formerly eosinophilic granuloma) tends to be self-limiting. LCH accounts for less than 1% of bone tumours, and up to 80% of children will present before they reach the age of 10 years. Involvement of the spine has been reported to occur in 7%–10% of cases.8,9,10 Despite the relative infrequency of LHC, solitary LCH is the commonest form, accounting for 60%–80% of cases. Detection is important to manage solitary LCH properly.11 Acute awareness is required for diagnosis, and the Langerhans cell is essential for the diagnosis of LCH, particularly in its solitary form. The Langerhans cell is thought to be derived from the bone marrow and is related to the mononuclear phagocyte.9 Definitive diagnosis of LCH is made by histopathological evidence of Birbeck granules and immunohistochemical detection of S-100 and CD1a antigens in the tissue samples.3,11 In addition to a clinical examination, the investigations, usually dictated by the organ system(s) involved, consist of laboratory investigations (complete blood count, hepatic function testing, inflammatory markers, measurement of blood and urine osmolarities, and hormone levels such as antidiuretic hormone, thyroid stimulating hormone and growth hormone).6 To help confirm the diagnosis, multiple imaging modalities have been recommended, such as CT and MRI, a skeletal survey and tissue diagnosis.1,4 Myelography has also been used in the past.10 Technetium bone scintigraphy is not recommended as a screening tool because of its poor sensitivity.1 Treatment methods for vertebral involvement have been variable, yet all have had successful outcomes.12 The goals of treatment include spinal stability, preservation of neurologic function and eradication of the lesion. Some authors recommend conservative treatment with biopsy and immobilization and the use of steroids when there is no neurologic deficit.9,10,12 However, the treatment of children with neurologic deficit is more controversial. Some have advocated that immobilization and radiation are appropriate in children with mild neurologic deficit.12 Others believe that the neural elements should be decompressed and then fused, with the debatable addition of radiation or chemotherapy. Still others believe that radiation is unnecessary except when the disease continues to progress,1 and there are those who believe that chemotherapy is justified for multiple lesions or involved visceral organs, or when surgery and radiation have failed, but it is not recommended in cases of solitary LCH.1,10,12 Several studies of solitary osseous LCH have shown that resolution occurred at a rate unaffected by the mode of treatment and this reinforces the opinion that solitary LCH is a self-limiting process.1 Hence there is no clear evidence that treatment affects the natural history of this entity.4 In this study we compare the treatment regimen and outcome of children with vertebral LCH at a tertiary care pediatric centre and compare it to those reported in the literature.