Clinical Trial Summary
Adult Langerhans histiocytosis (LCH) is a rare disease of unknown etiology, characterized by
the activation of the MAPK (Mitogen-activated protein kinases) pathway, driven by various
somatic mutations in the specific lesions of involved organs/tissues. LCH is currently
classified as myeloid neoplasia with an inflammatory component. In patients with active
systemic LCH, MAPK mutations may also be identified in plasma free cell DNA in patients. In
contrast, circulating MAPK mutations seem more rarely detected in patients with LCH limited
to a single organ/tissue (single system disease), but this has not been accurately assessed
in a large series of patients.
The clinical presentation of LCH is very diverse, the prognosis variable, and the evolution
marked by the occurrence of flares of the disease. A definitive diagnosis of LCH warrants
histological confirmation obtained by a biopsy of an involved organ. In case of Pulmonary
Langerhans cell histiocytosis (PLCH), a presumptive diagnosis is often acceptable when
lung-computed tomography (CT) shows a nodulo-cystic pattern after excluding alternative
diagnoses. In contrast, in case of purely cystic lung CT pattern, PLCH may be difficult to
differentiate from other diffuse cystic lung diseases (mainly lymphangioléiomyomatose (LAM)
and BHD (Birt-Hogg-Dubé syndrom), and eventually other rare disorders). Advanced PLCH may
even be misdiagnosed as pulmonary emphysema that also occurs in smokers. In these situations,
confirmation of PLCH warrants lung tissue, obtained most often by surgical lung biopsy that
comprises significant morbidity or is not feasible in patients with altered lung function.
Thus, the identification of specific blood biomarkers of cystic PLCH would be very useful.
On another hand, personalized management of adult patients with LCH is limited given the
absence of predictive factors for prognosis or response to treatment.
The aim of this prospective study is to describe precisely the clinical phenotype at
diagnosis and during follow-up of a large cohort of adult LCH patients and to seek for blood
biomarkers eventually associated with prognosis or response to specific treatment. For
patients with cystic PLCH specific markers for non-invasive diagnosis will also be
investigated.
In the subgroup of patients with Single system (SS) LCH and specific driver MAPK mutation in
tissue lesions, we will also look for the identification of this mutation in plasma free DNA
at the time of a flare of the disease.
