Childhood pulmonary Langerhans cell histiocytosis: a comprehensive clinical-histopathological and BRAFV600E mutation study from the French national cohort

Hum Pathol. 2019 Jul:89:51-61. doi: 10.1016/j.humpath.2019.04.005. Epub 2019 May 3.

Abstract

Childhood pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease. Its pulmonary histopathology, according to comprehensive clinical-radiological findings and BRAFV600E mutation status, has not yet been thoroughly documented. From the 167 childhood PLCH cases entered in the French National Histiocytosis Registry (1983-2016), we retrieved lung biopsies from a consecutive retrospective series of 17 patients, diagnosed when they were 2 weeks to 16 years old (median, 9.4 years), and report the clinical and histopathological findings herein. Histological analyses of biopsies (16 surgical and 1 postmortem) found the following features, alone or associated: Langerhans cell (LC) nodules with cavitation (9/17), cysts (14/17), fibrotic scars (2/17), peribronchiolar topographic distribution of the lesions (10/17), and accessory changes, like stretch emphysema (7/17). Those characteristics closely resemble those describing adult PLCH. However, unusual findings observed were 2 large nodules and a diffuse interstitial LC infiltrate. BRAFV600E mutation was detected in 4 of 12 samples tested, notably in the 3 with unusual features. In conclusion, childhood PLCH mostly shares the common histology features already described in adult PLCH, regardless of age. Because smoking is considered the major trigger in PLCH pathogenesis, the findings based on this series suggest other inducers of bronchiolar LC recruitment, especially in very young patients.

Keywords: BRAF(V600E); Childhood; Histopathology; Interstitial lung disease; Pulmonary Langerhans cell histiocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • France
  • Histiocytosis, Langerhans-Cell / genetics*
  • Histiocytosis, Langerhans-Cell / pathology*
  • Humans
  • Infant
  • Infant, Newborn
  • Lung Diseases / genetics*
  • Lung Diseases / pathology*
  • Male
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf