Elsevier

The Journal of Pediatrics

Volume 165, Issue 5, November 2014, Pages 990-996
The Journal of Pediatrics

Original Article
Differentiating Skin-Limited and Multisystem Langerhans Cell Histiocytosis

Portions of this study were presented as an abstract at the Histiocyte Society annual meeting, Washington, DC, October 19-21, 2013.
https://doi.org/10.1016/j.jpeds.2014.07.063Get rights and content

Objective

To identify features associated with multisystem involvement and therapeutic failure in patients with skin Langerhans cell histiocytosis (LCH).

Study design

We reviewed medical records of 71 consecutive patients with LCH with skin involvement evaluated at Texas Children's Hospital and analyzed clinical features, laboratory results, and the presence of circulating cells with the BRAF-V600E mutation with respect to initial staging and clinical outcomes.

Results

Skin disease in patients older than 18 months of age at diagnosis was associated with the presence of multisystem disease (OR, 9.65; 95% CI, 1.17-79.4). Forty percent of patients referred for presumed skin-limited LCH had underlying multisystem involvement, one-half of these with risk-organ involvement. Patients with skin-limited LCH had a 3-year progression-free survival of 89% after initial therapy, and none developed multisystem disease. Patients with skin/multisystem involvement had a 3-year progression-free survival of 44% with vinblastine/prednisone therapy, and risk-organ involvement did not correlate with failure to achieve nonactive disease. Circulating cells with BRAF-V600E were detected at higher frequency in patients with multisystem involvement (8 of 11 skin/multisystem vs 1 of 13 skin-limited; P = .002).

Conclusion

Skin-limited LCH necessitates infrequent therapeutic intervention and has a lower risk of progression relative to skin plus multisystem LCH. The less-aggressive clinical course and lack of circulating cells with the BRAF-V600E mutation in skin-limited LCH suggest a different mechanism of disease origin compared with multisystem or risk-organ disease.

Section snippets

Methods

Medical records of 71 consecutive patients who presented with any LCH skin lesions, either as skin-limited disease or as multisystem disease, at the Texas Children's Cancer and Hematology Centers between March 2005 and October 2011 were reviewed. Patients who presented either with de novo disease or from referral after diagnosis were included in this study. The age, date of diagnosis, date of symptom onset, location of LCH involvement, type of therapy, response to therapy, and time to

Results

Seventy-one patients presented with LCH skin lesions between March 2005 and August 2012 (Table). Of these patients, 21 were determined to have skin-limited disease, and 43 patients had multisystem involvement. Seven patients with multisystem disease, referred late in the course of treatment, could not be categorized due to incomplete information at diagnosis, and these patients were not included in subsequent analyses.

The majority of patients with skin-limited and skin plus multisystem disease

Discussion

LCH occurs in 2-10 per million children and 1-2 per million adults per year, with extreme clinical heterogeneity.26, 27, 28 Involvement of risk organs (liver, spleen, and bone marrow) and failure to respond to the first 12 weeks of therapy predict increased mortality risk.5, 8 Accurate staging is essential to determine optimal therapy, because observation or curettage may be appropriate for single-system disease, whereas systemic chemotherapy is required for multisystem LCH. Survival of

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    Supported by the HistioCure Foundation (Texas Children's Cancer Center Histiocytosis Program), National Institutes of Health (R01 CA154489 [to C.A. and K.M.], P50CA126752 [to C.A.], and NIH K12 CA090433 [to S.S.]), and Dan L. Duncan Cancer Center (P30CA125123). The authors declare no conflicts of interest.

    Contributed equally.

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