Abstract
Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia in which somatic mutations in components of the MAPK/ERK pathway have been identified. Osseous involvement is evident in approximately 80% of all patients and may present as a single osteolytic lesion, as a multi-ostotic single system disease or as part of multisystem disease. Both exogenous, such as treatment with glucocorticoids, and endogenous parameters, such as anterior pituitary hormone deficiencies and inflammatory cytokines, may severely affect bone metabolism in LCH. Computed tomography (CT) or magnetic resonance imaging (MRI) are usually required to precisely assess the degree of bone involvement; 18F-fluorodeoxyglucose (FDG) positron emission tomography—CT can both detect otherwise undetectable LCH lesions and differentiate metabolically active from inactive or resolved disease, while concomitantly being useful in the assessment of treatment response. Treatment of skeletal involvement may vary depending on location, extent, size, and symptoms of the disease from close observation and follow-up in unifocal single-system disease to chemotherapy and gene-targeted treatment in cases with multisystem involvement. In any case of osseous involvement, bisphosphonates might be considered as a treatment option especially if pain relief is urgently needed. Finally, a patient-specific approach is suggested to avoid unnecessary extensive surgical interventions and/or medical overtreatment.
Highlights
Langerhans cell histiocytosis (LCH) is an orphan disease characterized by clonal proliferation of abnormal CD1a+/CD207+ myeloid precursors cells
We have previously shown that 20% of all adult patients with LCH have a bone mineral density (BMD) measurement below the expected age range (Z-score ≤ −2.0)
Whole-body magnetic resonance imaging (MRI) could prove very useful in the detection of small, otherwise undetectable, vertebral lesions [37]. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (FDG-PET/Computed tomography (CT)) could detect LCH lesions not detectable with other imaging modalities (CT, MRI) and could differentiate metabolically active from inactive or resolved disease, information that would preclude biopsy or treatment in metabolically inactive lesions and is essential for prognosis [38]
Summary
Langerhans cell histiocytosis (LCH) is an orphan disease characterized by clonal proliferation of abnormal CD1a+/CD207+ myeloid precursors cells. The recent identification of somatic mutations in components of the MAPK/ERK pathway point towards a neoplastic rather than a reactive process and the World Health Organization has recently recognized LCH as a hematopoietic neoplasm. The LCH cells are characterized by activation of the MAPK/ERK pathway secondary to a cancer-associated mutation (BRAFV600E) in approximately 60% of LCH lesions [1,2]. In addition to this BRAF mutation, a high prevalence of somatic MAP2K1 mutations has been reported in BRAF V600E–negative Langerhans cell histiocytosis [3]. Recent studies suggest BRAF V600E mutation as a significant predictor of disease progression and as a candidate for targeted therapy in patients with disease relapse or multisystem disease [4]
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