Diagnosis and treatment of Langerhans cell histiocytosis in adults
Langerhans cell histiocytosis (LCH) is a rare hematologic disorder that affects patients of all ages. While most of our current understanding of LCH comes from studies of pediatric patients, data on adult cases remain limited. The discovery of the BRAFV600E mutation in approximately 50% of LCH samples established LCH as a neoplastic disease, and subsequent research has identified additional activating mutations in the mitogen-activated protein kinase (MAPK) pathway. Recent advances in our understanding of the disease’s pathogenesis and treatment, combined with its rarity, have highlighted the need for comprehensive guidelines for diagnosing and treating LCH in adults.
Clinical features of LCH in adults
The clinical manifestations and disease progression of LCH exhibit remarkable heterogeneity, encompassing a spectrum from localized single-system disease with isolated involvement (SS-s) to multiple sites within a single system (SS-m) and potentially progressing to multisystem (MS) disease with severe organ dysfunction. In adult patients, the predominant sites of involvement include the pulmonary system, skeletal structures, and the pituitary gland.
Pulmonary manifestations: pulmonary LCH can manifest either as a component of MS disease or as isolated single-system pulmonary involvement (SS-p). Tobacco use has been identified as a significant etiologic factor in pulmonary LCH, particularly in SS-p cases. The clinical presentation may include dyspnea, chest pain, chronic cough, or spontaneous pneumothorax. High-resolution computed tomography (HRCT) typically reveals characteristic patterns, including cystic changes, nodular lesions, ground-glass opacities, emphysematous changes, reticular patterns, honeycomb formation, or pneumothorax. Notably, the majority of pulmonary lesions demonstrate minimal to no hypermetabolic activity on 18F-FDG positron emission tomography (PET).
Skeletal manifestations: patients typically present with skeletal pain, and diagnostic imaging reveals characteristic osteolytic lesions detectable through radiography or CT. 18F-FDG PET demonstrates high sensitivity in detecting osseous involvement.
Pituitary manifestations: central diabetes insipidus constitutes the primary clinical presentation in patients with pituitary involvement. 18F-FDG PET findings are variable, ranging from hypermetabolic lesions to normal metabolic activity.
Hepatic manifestations: liver involvement in adult patients with LCH is frequently asymptomatic. Laboratory investigations typically reveal elevated alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) levels as the primary biochemical abnormalities. Hyperbilirubinemia generally manifests in advanced disease stages. Notably, approximately two-thirds of patients exhibit no hypermetabolic hepatic lesions on 18F-FDG PET at initial diagnosis.
