langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a rare multisystem disease with a wide and heterogeneous clinical spectrum and variable extent of involvement.

Terminology

Langerhans cell histiocytosis was previously known as histiocytosis X. The newer term is preferred as it is more descriptive of its cellular background, and removes the ambiguity of the connotation "X".

Epidemiology

The disease is more common in the pediatric population, with a peak incidence between one and three years of age . Incidence is estimated at ~5 per million children, and 1-2 cases per million adults . There is also a male predilection (M:F  ~ 1.5:1) .

Clinical presentation

Essentially any part of the body can be affected and as such, clinical presentation will depend on specific involvement. The course of the disease ranges from those that spontaneously regress to those that have a rapidly progressive course (the latter is especially common in young children with multisystem disease).

Historically, three (two eponymous) forms have been recognized, although there is some confusion as to their definition :

  • Letterer-Siwe disease
    • disseminated multiorgan disease
    • typically young children/infants less than one year old
    • fulminant course with poor prognosis
  • Hand-Schüller-Christian disease
    • multiple lesions
      • some authors confine the term to patients with solitary organ involvement
      • other authors accept multi-organ involvement (e.g. bone and spleen) 
    • confined to the one location (usually bone)
    • typically children
    • intermediate prognosis
  • eosinophilic granuloma (EG)
    • lesions are confined to one organ system
      • some authors confine the term to patients with a solitary lesion
      • other authors accept multiple lesions  
    • 70% of cases affect bone
    • typically children
    • best prognosis

A more useful and less controversial classification, which roughly correlates to the eponymous diseases above, is as follows:

  • multiple organ systems, multiple sites involved 
  • single organ system, multiple sites involved
  • single lesion

Additionally, in 2008 the WHO recommended distinguishing LCH from a more pleomorphic variant known as Langerhans cell sarcoma .

As well as systemic disease, individual organ systems may be involved, which will be discussed separately:

The remainder of this article concerns a general overview of LCH.

Pathology

Langerhans cell histiocytosis is due to uncontrolled monoclonal proliferation of Langerhans cells (distinctive cells of monocyte-macrophage lineage) and should be considered a malignancy although its biological behavior is very variable . An immune-mediated mechanism has been postulated. This proliferation is accompanied by inflammation and granuloma formation. Electron microscopy may reveal characteristic Birbeck granules. Immunohistochemistry reveals expression of the following antigens:

  • HLA-DR
  • CD1a
  • CD207 (langerin)
  • S100

Radiographic features

Imaging features are often not pathognomonic and tissue diagnosis is usually required for definitive diagnosis. As langerhans cell histiocytosis can affect most organ systems, radiographic appearances are discussed separately (see above).

Treatment and prognosis

The prognosis can be extremely variable with eosinophilic granuloma carrying the best and Letterer-Siwe disease carrying the worst prognosis. The prognosis is more closely related to the disease burden rather than histological features, although frankly malignant features (Langerhans cell sarcoma) do also have an impact on survival :

  • unifocal disease (eosinophilic granuloma): >95% survival
  • two organ involvement: 75% survival
  • Langerhans cell sarcoma: 50% survival

History and etymology

The Langerhans cell was discovered within the epidermis by German physician Paul Langerhans (1847-1888) in 1865 when he was a medical student and working under famed Professor Rudolf Virchow .

See also