Langerhans cell histiocytosis
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Langerhans cell histiocytosis (LCH) is a rare multisystem disease with a wide and heterogeneous clinical spectrum and variable extent of involvement.
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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".
Historically, the condition was also subdivided into three distinct entities, Letterer-Siwe disease, Hand-Schüller-Christian disease and eosinophilic granuloma, see below.
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 multisystem disease).
Historically, three forms (two with eponymous names) have been recognized, although there is some confusion as to their definition 1-5:
disseminated multiorgan disease
typically young children/infants less than one year old
fulminant course with poor prognosis
some authors confine the term to patients with solitary organ involvement 4
other authors accept multiorgan involvement (e.g. bone and spleen) 6
confined to the one location (usually bone)
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
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
Additionally, in 2008 the WHO recommended distinguishing Langerhans cell histiocytosis 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 Langerhans cell histiocytosis.
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:
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 3,4:
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 the famed Professor Rudolf Virchow (1821-1902) 9,10.
Erdheim-Chester Disease: a non-Langerhans cell histiocytosis
Rosai-Dorfman disease: sinus histiocytosis
- 1. Wolfgang Dähnert. Radiology Review Manual. (2003) ISBN: 9780781738958 - Google Books
- 2. Schmidt S, Eich G, Geoffray A et al. Extraosseous Langerhans Cell Histiocytosis in Children. Radiographics. 2008;28(3):707-26; quiz 910-1. doi:10.1148/rg.283075108 - Pubmed
- 3. Gatter K, Delsol G, Warnke R. The Diagnosis of Lymphoproliferative Diseases. Wiley-Blackwell. (2011) ISBN:1119971748. Read it at Google Books - Find it at Amazon
- 4. Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues (World Health Organization Classification of Tumours). (2003) ISBN: 9283224116 - Google Books
- 5. Robert J. Arceci, Ian M. Hann, Owen P. Smith. Pediatric Hematology. (2006) ISBN: 9781405134002 - Google Books
- 6. Walter Siegenthaler. Differential Diagnosis in Internal Medicine. (2007) ISBN: 9781588905512 - Google Books
- 7. Paul Shreve, David W. Townsend. Clinical PET-CT in Radiology. (2010) ISBN: 9780387489001 - Google Books
- 8. Allen C, Ladisch S, McClain K. How I Treat Langerhans Cell Histiocytosis. Blood. 2015;126(1):26-35. doi:10.1182/blood-2014-12-569301 - Pubmed
- 9. Coppes-Zantinga A & Egeler R. The Langerhans Cell Histiocytosis X Files Revealed. Br J Haematol. 2002;116(1):3-9. doi:10.1046/j.1365-2141.2002.03232.x - Pubmed
- 10. Schultz M. Rudolf Virchow. Emerg Infect Dis. 2008;14(9):1480-1. doi:10.3201/eid1409.086672