Adult Langerhans Cell Histiocytosis and the Skeleton

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.

Keywords: Langerhans cell histiocytosis (LCH); bone; skeleton; treatment.

Figure 1

Factors affecting bone metabolism in LCH. GM-CSF: granulocyte-macrophage colony-stimulating factor; OPG: osteoprotegerin; RANKL: receptor activator of nuclear factor kappa-Β ligand; IFN-γ: interferon gamma; TNFs: tumor necrosis factors; IL-: interleukin -; HP: hypothalamus-pituitary; GH: growth hormone; PRL: prolactine.

Figure 2

(a) Sagittal T1-weighted MR scan showing a 1.5 cm lytic lesion with soft mass tissue extension (arrow) which disrupts the cortex of the left acromion and extents mainly to the supraspinatus muscle; (b) appearance of lytic bone lesion in CT: (b1) transverse CT scan section showing an extensive lytic lesion of the right scapula (arrow); (b2) different transverse CT scan section of the previous lytic lesion of the right scapula, one year later and following treatment with denosumab, depicting now scleroting margins (arrow) suggestive of the healing process. R: right; L: left.