Langerhans Cell Histiocytoses

Snapshot

A 12-year-old boy presents to the emergency room for pain in in his right forearm with minimal trauma while playing tag. Radiography shows a fracture of the radius. A skeletal survey also shows 2 other lytic bone lesions on the cranium. He is referred to the pediatric oncologist for further workup and possible biopsy for a Langerhans cell histiocytosis.

Introduction

Overview
- Langerhans cell histiocytosis (LCH) describes a group of conditions caused by proliferation of dendritic (Langerhans) cells
  - traditionally classified by 4 subtypes, but more recent classification is based on extent of dissemination

Langerhans Cell Histiocytosis (LCH)
	Letterer-Siwe	Hand-Schuller-Christian	Hashimoto-Pritzker (Congenital Self-Healing Reticulohistiocytosis)	Eosinophilic Granuloma
Demographics	< 2 years of age	2-6 years of age	Neonatal period	7-12 years of agePulmonary involvement seen in ages 30-40 years
Involvement	Skin, bone, and viscerapulmonary infiltrates, lymph nodules, liver, and spleen	Skin, bone, and visceraliver, spleen, and lymph nodes	Skin-limited	Primarily bone > skinPulmonary involvemen
Prognosis	Poor prognosis with disseminated disease	Chronic and progressive	Rapid spontaneous resolution is likely	Good prognosis

Epidemiology
- incidence
  - rare
- demographics
  - males > females
- risk factor
  - smoking
    - pulmonary involvement
Pathogenesis
- mechanism
  - proliferation of Langerhans cells, which are immature and are unable to stimulate T-cells via antigen presentation
    - thought to be reactive or neoplastic
  - BRAF V600E mutation can be found in LCH
Prognosis
- worse with BRAF V600E mutation
- worse if there’s failure to respond to 6 weeks of treatment

Presentation

Clinical Presentation of LCH
	Letterer-Siwe	Hand-Schuller-Christian	Hashimoto-Pritzker (Congenital Self-Healing Reticulohistiocytosis)	Eosinophilic Granuloma
Symptoms	Acutely disseminated lesions affecting the skin, bone, and internal organsFeverBone pain	Triad of diabetes insipidus, osteolytic bone lesions (cranium), and exophthalmos	Skin lesions that crust and resolves spontaneously	Solitary indolent bone lesions (cranium most common) with spontaneous bone fractures
Physical exam	Pink papules, pustules, vesicles, petechiae, purpura, and erosions on the scalp, flexural surfaces, and trunkSecondary impetiginization common	Skin findings similar to Letterer-Siwe	Multipe red to brown papulonodules, some with erosions	Tenderness at site of bone lesions

Imaging

Bone radiograph
- views
  - cranium or other skeletal survey
- findings
  - punched out lytic lesions
Chest radiograph
- findings
may show pulmonary nodules or infiltrate

Studies

Serum studies
- liver function test
  - to evaluate for liver involvement
- baseline complete blood count
Urine studies
- to evaluate for diabetes insipidus
Pulmonary function test
- o evaluate for pulmonary involvement
Histology
- S100+, CD1a+, and Langerin+
- proliferation of histiocytes with mixed inflammatory infiltrate
Electron microscopy
Birbeck granules or “tennis rackets”

Differential

Multiple myeloma
- key distinguishing factors
  - may also have “punched out” lytic bone lesions
typically affects older adults, and protein electrophoresis of the serum (SPEP) will reveal monoclonal gammopathy

Treatment

Complications