Sandbox: Langerhans

Pathogenesis

• Langerhans cell histiocytosis arises from epidermal dendritic cells, which are normally involved in the process of antigen presentation to lymphocytic cells.
• Langerhans cells originally arise from the bone marrow, then the cells migrate to other organs such as:

• Skin
• Lymph nodes
• Lungs
• Hypothalamic pituitary axis
• Gastrointestinal tract
• CNS
• Oral cavity

• The malignant organ involvement is variable among patients with Langerhans cell histiocytosis. The disease process may range from an isolated cutaneous or bone involvement to a life-threatening multi-system condition.
• The skeletal distribution of Langerhans cell histiocytosis involves the following sites:

• The skull (most common bone involved)
• Ribs
• Humerus
• Vertebra

• The exact pathogenesis of Langerhans cell histiocytosis is not fully understood. It is thought that Langerhans cell histiocytosis is the result of either a true neoplastic process or a reactive immune condition.
• Facts consistent with the neoplastic process hypothesis include the following:

• The infiltration of organs by monoclonal population of pathologic cells
• The presence of specific recurrent cytogenetic and genomic abnormalities
• The successful treatment of a subset of disseminated Langerhans cell histiocytosis using chemotherapeutic regimens

• Facts consistent with the reactive immune condition hypothesis include the following:

• The evidence of spontaneous remissions that may occur among certain cases of Langerhans cell histiocytosis
• The extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm)
• The favorable prognosis and relatively good survival rate among patients with no organ dysfunction

• The excessive Langerhans cells clonal proliferation will initiate a non-specific inflammatory response, which will lead to the accumulation of various immune system cells such as:

• Eosinophils
• Macrophages
• Lymphocytes
• Multinucleated giant cells

• Langerhans cell histiocytosis may result in bone marrow failure due to malignant cell infiltration of the bone marrow. This can manifest as:

• Anemia
• Recurrent bleeding
• Recurrent Infections

• The infiltration of the hypothalamic pituitary axis by malignant Langerhans cells will lead to a deficiency in both anterior and posterior pituitary hormones, which may result in:

• Central diabetes insipidus
• Growth retardation
• Delayed puberty