Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases. Endocrine glands: Hypothalamic pituitary axis  commonly involved. Diabetes insipidus is most common. Anterior pituitary hormone deficiency is usually permanent. Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others experience chronic cough and shortness of breath. Less frequently gastrointestinal tract, central nervous system, and oral cavity. Pathophysiology
The pathogenesis of Langerhans cell histiocytosis (LCH) is a matter of debate. There are ongoing investigations to determine whether LCH is a reactive (non-cancerous) or neoplastic (cancerous) process. Arguments supporting the reactive nature of LCH 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 or risk organ involvement.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. 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. 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.An activating somatic mutation of a proto-oncogene 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%). This study documented the first recurrent mutation in LCH samples. Two independent studies have confirmed this finding. Presence of this activating mutation could support the notion to characterize LCH as myeloproliferative disorder. Diagnosis
Diagnosis is confirmed histologically by tissue biopsy. Hematoxylin-eosin stain of biopsy slide will show features of Langerhans Cell e.g. distinct cell margin, pink granular cytoplasm. Presence of Birbeck granules on electron microscopy and immuno-cytochemical features e. g. CD1 positivity are more specific. Initially routine blood tests e.g. full blood count, liver function test, U&Es, bone profile are done to determine disease extent and rule out other causes.Imaging may be evident in chest X-rays with micronodular and reticular changes of the lungs with cyst formation in advanced cases. MRI and High-resolution CT may show small, cavitated nodules with thin-walled cysts. MRI scan of the brain can show three groups of lesions such as tumourous/granulomatous lesions, nontumourous/granulomatous lesions, and atrophy. Tumourous lesions are usually found in the hypothalamic-pituitary axis with space-occupying lesions with or without calcifications. In non-tumourous lesions, there is a symmetrical hyperintense T2 signal with hypointense or hyperintense T1 signal extending from grey matter into the white matter.