Cancer Health Center

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Patients with multisystem disease and craniofacial involvement at the time of diagnosis, particularly of the orbit, mastoid, and temporal bones, carried a significantly increased risk of developing DI during their course (relative risk, 4.6), with 75% of patients with DI having these CNS-risk bone lesions.[33] This risk increased when the disease remained active for a longer period of time or reactivated. The risk for development of DI in this population was 20% at 15 years after diagnosis. Fifty-six percent of DI patients will develop anterior pituitary hormone deficiencies (growth, thyroid, or gonadal-stimulating hormones) within 10 years of the onset of DI. DI occurs in 11% of patients treated with multiagent chemotherapy and in up to 50% of patients treated less aggressively.[34,35]

Central nervous system

CNS disease manifestations

LCH patients may develop mass lesions of the choroid plexus, grey matter, or white matter.[36] These lesions contain CD1a-positive LCH cells and CD8-positive lymphocytes, and are, therefore, active LCH lesions.[37] These lesions may respond to chemotherapy.[38]

LCH CNS neurodegenerative syndrome

A chronic neurodegenerative syndrome that is manifested by dysarthria, ataxia, dysmetria, and sometimes behavior changes develops in 1% to 4% of LCH patients. These patients may develop severe neuropsychologic dysfunction. MRI scan results from these patients show hyperintensity of the dentate nucleus and white matter of the cerebellum on T2-weighted images or hyperintense lesions of the basal ganglia on T1-weighted images and/or atrophy of the cerebellum.[39] The radiologic findings may precede the onset of symptoms by many years or be found coincidently. A study of 83 LCH patients who had at least two MRI studies of the brain for evaluation of craniofacial lesions, DI, and/or other endocrine deficiencies of neuropsychological symptoms has been published.[40] Forty-seven of 83 patients (57%) had radiological neurodegenerative changes at a median time of 34 months from diagnosis. Of the 47 patients, 12 (25%) had clinical neurological deficits that presented 3 to 15 years after the LCH diagnosis. Fourteen of the 47 patients had subtle deficits in short-term auditory memory.

A study of CNS-related permanent consequences (neuropsychologic deficits) in 14 of 25 LCH patients followed for a median of 10 years has been published.[41] Seven of these patients had DI and five patients had radiographic evidence of LCH CNS neurodegenerative changes.[41] Patients with craniofacial lesions had lower performance and verbal intelligence quotient scores than those with other LCH lesions.

Histological evaluation of these neurodegenerative lesions shows a prominent T-cell infiltration, usually in the absence of the CD1a-positive dendritic cells along with microglial activation and gliosis. The neurodegenerative form of the disease has been compared to a paraneoplastic inflammatory response.[37]

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