Langerhans cell histiocytosis

Dr Jeremy Jones and A.Prof Frank Gaillard et al.

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

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

The disease is more common in the pediatric population, with a peak incidence between one and three years of age 5. Incidence is estimated at ~5 per million children, and 1-2 cases per million adults 8. There is also a male predilection (M:F  ~ 1.5:1) 5

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 multi-system disease). 

Historically, three eponymous forms have been recognized, although there is some confusion as to their definition 1-5:

  • Letterer-Siwe disease
    • disseminated multi-organ 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 4
      • other authors accept multi-organ involvement (e.g. bone and spleen) 6
    • confined to the one bone (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 4
      • other authors accept multiple lesions 6 
    • 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 3

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. 

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 1,3.  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

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

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 3-4:

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

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 9.

Bone tumours

The differential diagnosis for bone tumors is dependent on the age of the patient, with a very different set of differentials for the pediatric patient.

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Article information

rID: 1565
Synonyms or Alternate Spellings:
  • Langerhans cell histiocytosis (LCH)
  • LCH
  • Histiocytosis X

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Cases and figures

  • Eosinophilic gran...
    Case 1: eosinophilic granuloma of bone
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  • Case 2: LCH of lung
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  • Case 3: HSC of base of skull
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  • B101 004
    Case 4
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  • Case 5
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  • Case 6
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  • Case 7: lytic lesion on left iliac bone
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  • Case 8: with a vertebra plana
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  • Case 9: on nuclear imaging involving the right shoulder 
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  • Case 10: enhancing lesion in right iliac blade
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  • Case 11
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  • Case 12: punched out lytic lesions
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  • Case 13: in an adult
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  • Case 14
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