International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults

Abstract

Langerhans cell histiocytosis (LCH) can affect children and adults with wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography based imaging for staging and response assessment in majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with emerging role of targeted (BRAF- and MEK-inhibitor) therapies. Despite documented response to treatments, many patients struggle with high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.

Pituitary Stalk Thickening: Causes and Consequences. The Children’s Memorial Health Institute Experience and Literature Review

“…LCH is classified as unifocal LCH (solitary lesion), single-system multifocal disease (>1 lesions), multisystem LCH (≥2 organs/organ systems involved) and may affect any organ or system of the human body: the bones (78.7%), skin (36.7%), lung (25%), liver (25%), spleen (25%), hypothalamus and pituitary gland (25%), lymph nodes (15%) and other soft tissues ( 52 , 53 ). In the CNS LCH exhibits a predilection for the HPR, leading to permanent posterior and/or anterior pituitary hormone deficiencies in a subset of patients.…”

“…The optimal treatment of HPR LCH remains challenging to define because of the very low incidence of disease and a paucity of prospective studies. According to the consensus recommendation for treatment of LCH, simple observation, surgery, low-dose radiation and chemotherapy are considered in the treatment planning ( 53 ). Limited literature data showed that low-dose irradiation (≤22 Gy) was usually the first-line therapy adequate for most cases of isolated HPR LCH with a sporadic recurrence of illness ( 60 ).…”

Langerhans cell histiocytosis in adolescent patients: a single-centre retrospective study

“…Another study in paediatric patients showed that the median age of diagnosis of patients with risk organ involvement was younger than that of patients without risk organ involvement[ 6 , 7 ]. Liver and spleen involvement can occur in 10–15% of adult cases[ 8 ]. In our previous study, adult patients rarely had haematopoietic system involvement[ 9 ].…”

“…In our previous study, adult patients rarely had haematopoietic system involvement[ 9 ]. However, studies and guidelines in children with LCH mainly included patients under 14 years old[ 10 – 12 ], while studies in adults mainly included patients 18 years or older[ 8 ]. With relatively low disease frequency, adolescent LCH patients (14–17 years old) have not been reported separately from younger patients in previous studies.…”

Bronchoalveolar Lavage as a Diagnostic Tool in an Atypical Pulmonary Langerhans Cell Histiocytosis

“…In some cases, the use of molecular evaluations such as that of the BRAF -V600E mutation on the BAL cytology specimen and/or whole blood NGS for mutations and fusions in genes of the MAPK-ERK and related pathways provide supplementary diagnostic evidence, especially for atypical PLCH, and could stratify different pathological phenotypes [ 18 ]. The limitation specifically in our case was the fact that we did not perform an 18F-fluorodeoxyglucose positron emission tomography-based (18F-FDG PET/CT) imaging for staging as recommended by the new international expert consensus recommendations for the diagnosis and staging of adult LCH [ 18 ]. Unfortunately, 18F-FDG PET/CT was not provided in our hospital at the time of admission of the patient, and externalization for this imaging technic was not covered by the patient’s insurance.…”