Orthopaedic Surgery - Eosinophilic Granuloma

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Basics

Eosinophilic granuloma is the osseous manifestation of Langerhans cell histiocytosis (LCH) and is the most common skeletal presentation of this disease spectrum.

LCH is now regarded as a clonal disorder of Langerhans-type cells rather than a group of entirely separate diseases.

Bone involvement may occur as a solitary lesion, as multifocal skeletal disease without visceral involvement, or as multisystem disease involving bone together with other organs.

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Sites of Involvement

Commonly affected bones include the skull, ribs, pelvis, vertebral column, mandible, and diaphyses of long bones.

However, virtually any bone can be involved.

A single skeletal lesion is more common than multifocal bone disease.

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Historical Classification of LCH

Historically, LCH was divided into three separate clinical entities: eosinophilic granuloma, Hand–Schüller–Christian disease, and Letterer–Siwe disease.

These names are now largely considered historical descriptions along a spectrum of LCH severity.

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Eosinophilic Granuloma

The term eosinophilic granuloma traditionally referred to a localized or solitary skeletal lesion without significant visceral disease.

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Hand–Schüller–Christian Disease

This historical term described multifocal skeletal involvement with systemic disease affecting organs such as the skin, lymph nodes, liver, or spleen.

The classic but uncommon triad consists of lytic skull lesions, exophthalmos, and diabetes insipidus.

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Letterer–Siwe Disease

Letterer–Siwe disease was the historical name for an aggressive multisystem form occurring predominantly in very young children, particularly those younger than 2 years.

Features may include lymphadenopathy, hepatosplenomegaly, skin involvement, and pulmonary disease, and the condition can be life-threatening.

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Synonyms

Older terminology includes histiocytosis X and reticuloendotheliosis.

The preferred current term is Langerhans cell histiocytosis.

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Epidemiology

LCH is rare.

Skeletal disease is seen most frequently in patients younger than 30 years, with peak presentation commonly between approximately 5 and 10 years of age.

Males are affected more often than females, with a reported ratio of approximately 2:1.

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Etiology

The precise initiating cause is not fully understood.

LCH is characterized by abnormal accumulation and proliferation of pathologic Langerhans-type cells, accompanied by a prominent inflammatory response.

This process can cause focal bone resorption and lytic destruction.

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Diagnosis

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General Principles

Diagnosis is based on the combination of clinical presentation, imaging, and histopathologic confirmation when required.

Because eosinophilic granuloma may mimic infection or malignancy, biopsy is often necessary unless the clinical and radiographic appearance is highly characteristic.

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Spinal LCH

A characteristic spinal presentation may include vertebral body collapse, preservation of the adjacent intervertebral disc spaces, and absence of a significant paraspinal soft-tissue mass.

This pattern is highly suggestive of LCH.

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Percutaneous Biopsy

Percutaneous needle biopsy is an effective means of establishing the diagnosis in uncertain lesions and can often avoid a larger open procedure.

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Signs and Symptoms

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Pain

Localized bone pain is one of the most common symptoms.

Pain may be gradual or relatively acute and is generally centered over the involved bone.

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Swelling and Tenderness

The lesion may produce localized swelling, tenderness, and warmth.

These inflammatory features can cause the condition to resemble osteomyelitis.

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Fever

Low-grade fever may occasionally be present, particularly with more active or multifocal disease.

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Physical Examination

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Skeletal Examination

The skull and accessible skeleton should be palpated for tender areas, swelling, or palpable bony defects.

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Orbital Involvement

Orbital lesions may occur, often in the superolateral orbit.

Patients may develop a visible mass, proptosis, ptosis, erythema, or visual disturbance, and the appearance can sometimes be mistaken for infection.

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Spine Examination

The spine should be inspected and gently percussed for focal tenderness.

Any evidence of deformity or neurologic abnormality should prompt further assessment.

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Gait

The patient’s gait should be observed for limping or reluctance to bear weight, particularly when the pelvis or lower extremity is involved.

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Laboratory Tests

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Inflammatory Markers

The erythrocyte sedimentation rate may be elevated, although the finding is nonspecific.

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Peripheral Eosinophilia

Peripheral eosinophilia may occur but is neither required nor diagnostic.

Normal laboratory results do not exclude LCH.

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Imaging

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Plain Radiographs

Radiographs commonly demonstrate well-defined, sharply marginated lytic lesions, often described as “punched-out.”

The appearance varies according to location and stage of healing.

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Healing Response

As the lesion heals, a rim of reactive or sclerotic bone may form along the periphery.

This represents reparative bone formation.

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Cortical Changes

The lesion may produce endosteal scalloping, cortical destruction, expansion, or periosteal reaction.

Because the cortex may be eroded unevenly from within, some skull lesions develop a characteristic beveled or “hole-within-a-hole” appearance.

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Skull Lesions

Calvarial lesions are classically sharply defined and lytic.

Asymmetric destruction of the inner and outer tables may produce a beveled-edge appearance.

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Vertebra Plana

In the spine, severe collapse of the vertebral body may produce vertebra plana, in which the vertebral body becomes a thin, flattened wafer of bone.

The adjacent disc spaces are usually preserved.

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Mandibular and Maxillary Lesions

In the jaws, loss of supporting alveolar bone may make the teeth appear suspended within the lesion.

This produces the classic “floating tooth” appearance.

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Bone Scan

Bone scintigraphy is not the most reliable screening study because some LCH lesions may demonstrate little or no increased tracer uptake.

A negative bone scan therefore does not exclude disease.

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Pathological Findings

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Langerhans Cells

Histologically, the lesion contains sheets of abnormal Langerhans cells with abundant pale cytoplasm.

The nuclei often demonstrate longitudinal grooves, producing a characteristic coffee-bean appearance.

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Immunohistochemistry

Langerhans cells characteristically express CD1a and S-100, and contemporary diagnosis also commonly uses langerin, or CD207.

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Inflammatory Background

The abnormal cells are surrounded by a mixed inflammatory infiltrate.

Eosinophils are often prominent, although lymphocytes, neutrophils, macrophages, and multinucleated giant cells may also be present.

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Differential Diagnosis

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Ewing Sarcoma

Ewing sarcoma may present with bone pain, fever, and an aggressive lytic lesion.

Clinical and imaging overlap may be substantial, making biopsy necessary in suspicious cases.

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Lymphoma

Primary lymphoma of bone can produce pain and a destructive lesion and should be considered, particularly when the radiographic appearance is atypical.

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Osteomyelitis

Osteomyelitis is one of the most important mimics because both conditions may present with pain, warmth, fever, elevated inflammatory markers, and bone destruction.

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Great Imitator

Eosinophilic granuloma has historically been called a “great imitator” because its clinical and radiographic features may resemble both infection and neoplasm.

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Treatment

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General Principles

Many solitary bone lesions are self-limiting and may heal spontaneously.

Treatment therefore depends on symptoms, anatomic location, structural risk, and whether multisystem disease is present.

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Observation

Observation is appropriate for selected patients with a characteristic solitary lesion, mild symptoms, and no impending fracture or danger to a joint surface.

Serial radiographs are used to confirm healing.

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Curettage

Curettage may be performed when the diagnosis is uncertain, symptoms are persistent, or the lesion is structurally significant.

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Bone Grafting

Bone grafting may be added after curettage if a large defect remains or if mechanical support is required.

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Steroid Injection

Intralesional corticosteroid injection has been used successfully for selected solitary lesions.

Methylprednisolone acetate is one commonly used agent and may promote symptom resolution and bone healing.

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Impending Pathologic Fracture

If the lesion significantly weakens the bone and a pathologic fracture appears imminent, operative curettage with bone grafting, with or without fixation, may be required.

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Articular Surface at Risk

Lesions threatening a joint surface may also warrant surgical treatment to prevent collapse or structural damage.

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Treatment of Multifocal or Systemic Disease

Patients with multiple skeletal lesions or visceral involvement require assessment by a multidisciplinary team.

Systemic treatment may be necessary, with therapy tailored to the extent of disease and organs involved.

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Chemotherapy

Historically, agents such as corticosteroids, methotrexate, and doxorubicin have been used in multisystem disease.

Modern systemic treatment depends on disease extent, risk-organ involvement, age, and current hematology-oncology protocols.

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Vertebra Plana

Vertebral collapse caused by LCH often has a favorable natural history in children.

The lesion may heal spontaneously, and partial restoration of vertebral body height can occur over time.

Neurologic compromise is uncommon when there is no epidural extension or instability.

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Surgery

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General Role

Surgery is unnecessary in most uncomplicated solitary lesions.

Its role is primarily diagnostic or mechanical rather than oncologic.

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Indications

Operative treatment may be considered when there is failure of nonoperative management, diagnostic uncertainty, impending pathologic fracture, substantial structural weakness, articular involvement, or neurologic compression.

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Curettage and Fixation

Curettage with bone grafting and internal fixation may be used when the involved bone is at substantial risk of fracture or has already fractured in an unstable pattern.

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Follow-Up

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Prognosis

The prognosis for isolated skeletal LCH is generally excellent.

Many lesions resolve with observation or limited treatment.

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Pathologic Fracture

Pathologic fractures can occur through weakened bone.

These fractures generally heal well with appropriate nonoperative or surgical treatment.

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Patient Monitoring

When the diagnosis is secure and there is no structural danger, the lesion can be followed with serial plain radiographs until healing is evident, often over several months.

Clinical follow-up should assess pain, swelling, function, skeletal stability, and development of new lesions or systemic symptoms.

Persistent pain, progressive destruction, new masses, neurologic findings, or evidence of multisystem disease should prompt reassessment and specialist referral.