Sandbox: Langerhans

Microscopic Pathology

There are ongoing investigations to determine whether Langerhans cell histiocytosis is a reactive (non-cancerous) or neoplastic (cancerous) process. Arguments supporting the reactive nature of Langerhans cell histiocytosis include the occurrence of spontaneous remissions, the extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm) in the lesional tissue, favorable prognosis, and relatively good survival rate in patients without organ dysfunction.[14][15]

On the other hand, the infiltration of organs by monoclonal population of pathologic cells, and the successful treatment of subset of disseminated disease using chemotherapeutic regimens are all consistent with a neoplastic process.[16][17][18]

In addition, a demonstration, using X chromosome–linked DNA probes, of LCH as a monoclonal proliferation provided additional support for the neoplastic origin of this disease.[19] While clonality is an important attribute of cancer, its presence does not prove that a proliferative process is neoplastic. Recurrent cytogenetic or genomic abnormalities would also be required to demonstrate convincingly that LCH is a malignancy.

Activating mutation of a protooncogen in the Raf family, the BRAF gene, was detected in 35 of 61 (57%) LCH biopsy samples with mutations being more common in patients younger than 10 years (76%) than in patients aged 10 years and older (44%).[20] This study documented the first recurrent mutation in LCH samples. Two independent studies have confirmed this finding.[21][22] Presence of this activating mutation could support the notion to characterize LCH as myeloproliferative disorder.