Sandbox: Langerhans

• Several cellular markers have been associated with poor disease prognosis, including expression of certain metalloproteinases and gelosin, a regulatory protein involved in the disassembly of actin microfilaments.41 Other factors for poor prognosis include extensive organ involvement and younger patient age at diagnosis.8 Younger age at diagnosis is associated with multisystem disease.

Prognostic factors in LCH have been identified and can be categorized as follows:

   Age at diagnosis: Although age younger than 2 years was once thought to portend a worse prognosis, data from the LCH-II study showed that patients aged 2 years or younger without high-risk organ involvement had the same response to therapy as older patients.[16] By contrast, the OS was poorer in neonates with risk-organ involvement compared with infants and children with the same extent of disease when patients were treated for only 6 months.[16]
   Response to treatment: Response to therapy at 6 to 12 weeks has been shown to be a more important prognostic factor than age.[19] The overall response to therapy is influenced by the duration and intensity of treatment.[15,16]
   Organ involvement: Involvement of craniofacial bones including orbital, mastoid, and temporal bones is associated with an increased risk of diabetes insipidus and an increased frequency of anterior pituitary hormone deficiencies and neurologic problems. (Refer to the Endocrine system subsection in the Multisystem Disease Presentation section of this summary for more information on diabetes insipidus.)

• The table below lists prognostic factors for Langerhans cell histiocytosis patients:

Prognostic Factor	Description
Age	A younger age at the time of diagnosis is associated with a worse prognosis.
Organ involvement	A more extensive organ involvement is associated with a worse prognosis.
Response to treatment	A low response rate after 6 weeks of therapy is associated with a worse prognosis.
Cellular markers	The expression of metalloproteinases and gelosin on a cellular level is associated with a worse prognosis.