Introduction

Also known as solitary Langerhan's cell histiocytosis (LCH), eosinophilic granuloma is the most benign member of a group of disorders of the reticuloendothelial system, including Hand-Schuller-Christian disease and disseminated LCH.  Langerhans cell histiocytosis is a spectrum of diseases that primarily affects the skeleton but can involve the reticuloendothelial system and viscera. LCH is a self-limiting process that can lead to focal destruction of bone.

Langerhans cell histiocytosis in its simplest form, eosinophilic granuloma, involves the skeleton as either a single lesion or in multiple sites. In another form, Hand-Schüller-Christian disease, it is a combination of multiple osseous lesions, exophthalmos, and diabetes insipidus. The most extreme form of Langerhans cell histiocytosis is Letterer-Siwe disease, which occurs in infants as a combination of polyostotic lesions and multiple organ involvement.  Although etiology and pathogenesis remain unsettled, Langerhans cell histiocytosis is now considered a disorder of immune regulation, possibly in combination with a primary viral infection of bone, rather than a neoplastic process.

Clinical Findings

The most commonly involved site is the cranium. Many of the skull lesions probably are not diagnosed because the only abnormality is a painless, small, spontaneously resolving lump in the scalp. The long bones (particularly femur), pelvis, ribs, and vertebral bodies are the next most common sites of involvement. Lesions in long bones may weaken the bone sufficiently that the patient presents with activity-related pain suggestive of a fatigue fracture, or with a pathologic fracture. Patients with Langerhans cell histiocytosis may also have systemic symptoms such as fever and malaise.

Radiographic Features

The radiographic appearance of LCH is highly variable. Depending on the stage of the process that the radiographs are taken, the lesion may appear similar to a large number of benign and malignant processes and is appropriately referred to as the "great mimicker".  Radiographic appearance of LCH lesion ranges from a focal, well-marginated radiolucency to a permeative appearance with expansion of the overlying cortex, periosteal new bone formation, surrounding sclerosis, and an associated soft tissue mass. Spinal involvement usually results in variable compression of the vertebral body, known as vertebra plana when there is complete collapse.

On bone scan, most of the lesions show increased uptake, but as many as 25% of lesions will not be associated with abnormal bone scan. For this reason, some recommend a skeletal survey to look for other isolated bone lesions.

Histologic Features

Histologically, the lesion is characterized by a proliferation of lipid-laden histiocytes Langerhans cells in an inflammatory background. These cells often have ill-defined cytoplasmic boundaries and characteristically contain an oval or intended nucleus. Tennis racket-shaped cytoplasmic structures identified by electron microscopy, called 'Birbeck granules', are found within the histiocytes and are pathognomonic of LCH. Immunohistochemical phenotype shows that Langerhans cells react positively for S100, CD1a, CD11, and CD14.

Treatment

Patients with eosinophilic granuloma (EG) do not progress to Hand-Schüller-Christian or Letterer-Siwe diseases, but should be evaluated on presentation to exclude the presence of these syndromes. A skeletal survey and some urine and blood tests (e.g., liver enzymes) should be performed for all patients, and then the patient should be referred to a pediatric hematologist. Patients with solitary EG generally have a benign clinical course. They have a good chance of spontaneous remission and a favorable outcome over a period of months to years. The single bony lesion usually does not require treatment other than a biopsy to confirm the diagnosis. In the spine, no treatment is generally needed or recommended unless a neurologic deficit is present. Variable rates of vertebral body restoration are seen with time. Patients with Hand-Schüller-Christian disease should be treated with systemic corticosteroids and chemotherapy. An aggressive chemotherapy protocol is also required for Letterer-Siwe disease.