The Risk Criteries of Central Nervous System Involvement and the Management of its Treatment in Patients with Langerhans Cell Histiocytosis

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Langerhans Cell Histiocytosis (LCH) is a rare disease of monocytic-macrophage system and it is characterized by reactive clonal proliferation and accumulation of pathologic dendritic cells. Therefore, LCH was suggested recently to be a neoplastic disease and BRAF-V600E mutation is seen 60% of patients with LCH. LCH affects various organs such as bone, lungs, skin, liver, spleen, lymph nodes and Central Nervous System (CNS). LCH CNS disease can be divided into two groups. One is focal mass lesions; other is lesions associated with progressive neurodegeneration. Focal, space-occupying mass lesions are localised in meninges, choroid plexus and brain parenchyma which may contain CD1a+ LCH cells, lymphocytes and macrophages with histology similar to extra cranial lesions. The most common involvement sites are the hypothalamic pituitary region which is leading to anterior and posterior pituitary involvement that results DI, growth hormone deficiency and thyroid function abnormalities. 

The other neurological findings of LCH are progressive neurodegeneration (ND-LCH) which is characterized by progressive radio logical and clinical abnormalities. The ND-CNS-LCH occurs mostly in children, but rarely in adult LCH patients. There are two stages in ND-CNS-LCH: an early neurologically symptom-free stage characterized by MRI abnormalities alone and a second stage that includes prominent neurological symptoms Typical T2-weighted MRI findings are the increased symmetrical MRI signal in the dentate nucleus of the cerebellum, basal ganglia, plexus choroideus and pons. LCH – associated abnormal clinical findings such as ataxia, tremor, abnormal cerebellar tests are characterized by absence of CD1a+ histiocytes, an inflammatory collection of CD8+ lymphocytes with neuronal and axonal degeneration and extensive demyelination, Purkinje cell loss, gliosis that is explained as ‘paraneo plastic phenomena’.

LCH patients known to have an increased risk for CNS complications have craniofacial involvement at the time of diagnosis (single skull lesions of the orbit, temporal, mastoid, sphenoid and ethmoid bones), Multi System (MS) involvements such as bone marrow, lung, liver and bone marrow involvements, children below the age of 2, carrying BRAF-V600E mutation in CD207+ cells, treatment-resistant cases to prednisolone plus in blastin therapy for 6 months and those patients with multisystem disease (with or without detectable BRAF-V600E mutation). LCH spread to CNS would be hematogeneous or lymphatic routes. Sometimes, CNS manifestations occur even in the absence of detectable disease elsewhere in the body.