Histiocitose das Células de Langerhans na criança: Revisão dos achados clínicos, anátomo-patológicos e imuno-histoquímicos dos casos diagnosticados no Hospital das Clínicas da UFMG 1988 a 2008

Abstract

Objectives: To review clinical, histopathological and immunohistochemical findings of children and adolescents with previous diagnosis of Langerhans cell histiocytosis (LCH), in order to establish the definitive diagnosis through CD1a antigen staining. To compare thedisease outcome according to age, sex, stage of the disease, treatment response and level of diagnostic accuracy. Material and methods: Retrospective analysis of data on 37 children with Langerhans cellhistiocytosis followed up at Hospital das Clínicas of Universidade Federal de Minas Gerais, Brazil, between 1988 and 2008. The study was carried out using the data abstracted from medical charts and by reviewing biopsies of the patients without previous definitive diagnosis. The definitive diagnosis was defined as that made possible through thedetection of Birbeck granules on electron microscopy, or CD1a antigen immunostaining of Langerhans cells. Results: Before the study, 13 (35,1%) of the 37 patients had definitive diagnosis, the highest level of diagnostic accuracy. The samples of twelve (50%) of the 24 patientswithout definitive diagnosis were located and reviewed. All reviewed cases were positive for CD1a antigen. By the end of the study, 25 of the 37 patients (67,5%) had a definitive diagnosis. The follow-up period ranged from 1 month to 20.9 years, with a median of 6.2 years. Age at diagnosis ranged from 1 month to 16.9 years, with a median of 2.4 years.Seventeen children were male (45,9%). The most common clinical manifestations at diagnosis were osteolytic lesions (67,6%). Multisystem disease was present in 19 patients (51%). The estimated overall survival (OS) probability was 88.5% (95%CI 72.1% to 95.5%). All deaths occurred in patients with multisystem disease and organ dysfunction at diagnosis. Those patients who had a better response to treatment in the sixth weekwere likely to have a significantly higher OS rate than those without response. OS rate was significantly higher for patients with single-system disease. The disease-free survival estimation for the whole group was 32.5% at 10 years (95%CI: 17.9% to 48.1%); it was significantly higher for patients with better response at six weeks of treatment and for patients with age 3 or more. There was no difference in OS and EFS when patients with definitive diagnosis were compared with the others. Reactivation episodes occurred in 75% of the patients with multisystem disease. Diabetes insipidus was the most common sequela, occurring in 21.6% of the patients. Conclusions: The study increased the level of diagnostic accuracy, with the majority of the patients having definitive diagnosis at the end of it. The overall survival and event-free survival rates were similar to international multicentric studies. Multisystem disease and absence of response at six weeks of treatment were the most important prognostic factors to predict worse outcome in overall survival. The frequency of reactivations for the patients with multisystem disease was higher than described in the literature