Langerhans cell histiocytosis (skeletal manifestations)

The skeleton is the most commonly involved organ system in Langerhans cell histiocytosis (LCH) and is by far the most common location for single-lesion LCH, often referred to as eosinophilic granuloma (EG) (the terms are used interchangeably in this article). For a general discussion of this disease please refer to the article on Langerhans cell histiocytosis (LCH).

Epidemiology

The skeletal system is the most common site of Langerhans cell histiocytosis involvement, and in 60-80% of cases is the only organ system involved. It primarily occurs in older children and young adults, with a male to female ratio of 2:1.

Clinical presentation

The lesions may be asymptomatic and discovered as an incidental radiographic finding.

When symptomatic, patients complain of pain, swelling and tenderness around the lesion. Systemic symptoms may also be present, including general malaise and, on occasion, fever with leukocytosis.

Pathology

There is proliferation of Langerhans cells with an abundance of eosinophils, lymphocytes and neutrophils. These cells produce prostaglandins which result in medullary bone resorption: this is what causes the symptoms.

Location/distribution

Patients may have one or, less commonly, many lesions. The most common locations are the skull and long bones ^5,6:

• skull: ~50%

• pelvis: 23%

• femur: 17%

• spine: ~15% (range 6.5-25%) ⁷

• ribs: 8% (most common in adults)

• humerus: 7%

• mandible: 7%

Radiographic features

Plain radiographs

Skull

• solitary or multiple punched out lytic lesions without sclerotic rim

• double contour or beveled edge appearance may be seen due to asymmetrical involvement of the inner and outer tables (hole within a hole) sign ⁸

• button sequestrum representing residual bone

• geographic skull

Mandible

• irregular radiolucent areas mostly involving superficial alveolar bone

• floating tooth: loss of lamina dura

Spine

• vertebra plana: most common cause of vertebra plana in children; more often in thoracic spine

Long bones

• depends on phase of disease which is imaged

• permeative and aggressive appearing lesion

• mainly involves diaphysis or metadiaphysis and respects growth plates

• endosteal scalloping, periosteal reaction (in healing phase it can appear as solid benign periosteal reaction), cortical thinning, intracortical tunneling, and associated soft tissue mass

Ultrasound

Skull

• seen as a solid mass lesion

• minimal vascularity

• originating from the diploic surface, extending through to the outer table 

• local subperiosteal spread

CT

Similar to plain film findings with better demonstration of cortical erosion and soft tissue involvement. Excellent for biopsy and surgical planning.

MRI

Signal characteristics include:

• T1: typically hypointense to isointense ⁹

• T2: hyperintense ⁹

• STIR: hyperintense

• T1 C+ (Gd): often shows diffuse contrast enhancement

Nuclear medicine

There is a variable appearance on bone scintigraphy, with lesions showing an increased or decreased tracer uptake depending on the histological picture. Nonetheless, bone scans are helpful in other asymptomatic lesions.

Treatment and prognosis

Prognosis is excellent when disease is confined to the skeleton, especially if it is a solitary lesion, with the majority of such lesions spontaneously resolving by fibrosis within 1-2 years. However, where symptoms persist, other treatment options may be considered:

• excision and curettage ³

• steroid therapy: intralesional injection

• chemotherapy

• radiofrequency ablation ⁴

• radiotherapy for spinal lesion

History and etymology

The term eosinophilic granuloma was coined by Lichtenstein and Jaffe in 1940 ².

Differential diagnosis

General imaging differential considerations include:

• osteomyelitis

• round blue cell tumors

• metastases

• primary bone tumors

• lymphoma

• leukemia