Neurocutaneous melanosis presenting with hydrocephalus and malignant transformation: case-based update.

INTRODUCTION: Neurocutaneous melanosis (NCM) is a sporadic condition characterised by congenital melanocytic nevi and melanocytic thickening of the leptomeninges. It is believed to result from congenital dysplasia of melanin-producing cells within the skin and leptomeninges. The management of cutaneous manifestations remains controversial; for neurological manifestations, outcome remains poor even with the use of radiotherapy and chemotherapy. PATIENTS AND METHODS: We describe the case of a 5-month-old boy who presented with giant congenital melanocytic nevus and hydrocephalus. MR imaging and CSF immunohistochemistry confirmed leptomeningeal melanosis. We discuss the diagnosis, treatment and prognosis of this rare disorder in the light of recent published literature. RESULTS: Patient required placement of right-sided ventriculoperitoneal shunt to control hydrocephalus. The patient tolerated the procedure well and was discharged home with normal neurological function. A presumptive diagnosis of NCM was made based on the MR characteristics, CSF cytology and clinical presentation. He received trametinib, a MAPK/Erk kinase inhibitor for 7 months. At 30 months of age, he developed left-sided weakness and status epilepticus requiring paediatric intensive care unit admission and ventilator support. The patient eventually succumbed to malignant transformation of leptomeningeal disease. CONCLUSION: Cutaneous manifestations of NCM are usually congenital, and neurological manifestations develop early in life. Patients with large or multiple congenital nevi should therefore be investigated early to facilitate treatment. MR imaging is the investigation of choice which can further assist in performing biopsy. Symptomatic NCM is refractory to radiotherapy and chemotherapy and has a poor prognosis. A multidisciplinary approach is necessary in the management of NCM patients.

Controlled hypertension, a transgenic toggle switch reveals differential mechanisms underlying vascular disease.

A novel inbred rat model with inducible hypertension has been generated using a renin transgene under the transcriptional control of the cytochrome P450, Cyp1a1 promoter. The degree and duration of hypertension are regulated tightly by administration of the natural xenobiotic indole-3 carbinol and can be readily reversed. Induction experiments reveal distinct temporal and mechanistic responses to hypertensive injury in different vascular beds, which is indicative of differential susceptibility of organs to a hypertensive stimulus. The mesentery and heart exhibited the greatest sensitivity to damage, and the kidney showed an adaptive response prior to the development of malignant hypertensive injury. Quantitative analysis of morphological changes induced in mesenteric resistance arteries suggest eutrophic remodeling of the vessels. Kinetic evidence suggests that locally activated plasma prorenin may play a critical role in mediating vascular injury. This model will facilitate studies of the cellular and genetic mechanisms underlying vascular injury and repair and provide a basis for the identification of novel therapeutic targets for vascular disease.

Neuropathological findings after intracerebral implantation of microdialysis catheters.

The neuropathological and immunocytochemical changes in the sheep forebrain following 7 days of microdialysis, using a catheter approved for human use, are described. There was no behavioural dysfunction and light microscopy revealed mild astrogliosis and patchy macrophage infiltration immediately adjacent to the catheter track. The surrounding neuropil was normal. There was one small subcortical haemorrhage (10 x 1.5 mm). These findings are similar to those following microdialysis in rodents and suggest that the risk of significant damage to the human brain is low, that neuropathological changes in the brain around the catheter should not interfere with local brain metabolism, and that the catheter should be affixed in such a way as to minimize movement-induced damage to the brain.

Expression of c-kit and kit ligand proteins in normal human tissues.

The c-kit receptor and its cognate ligand, KL, play a critical role in melanogenesis, gametogenesis, and hematopoiesis. Studies on the expression of c-kit and KL have been primarily focused on mouse development. We undertook the present study to characterize the pattern of expression of these molecules in normal adult human tissues. Using immunohistochemistry and consecutive tissue sections from the same block, we evaluated a variety of well-preserved normal tissues for c-kit and KL microanatomic distribution. c-kit protein was identified in tissue mast cells, melanocytes, glandular epithelial cells of breast, parotid, dermal sweat, and esophageal glands. Scattered c-kit immunoreactivity was also observed for testicular and ovarian interstitial cells. A striking regional distribution of c-kit was detected in the central nervous system, particularly in the cerebellum, hippocampus, and dorsal horn of the spinal cord. KL protein was identified in cells complementary to staining for the receptor, such as glandular myoepithelium of breast and sweat glands. Intense KL immunoreactivity was observed in smooth muscle cells of the bladder, cervix, uterus, and gastrointestinal tract, as well as in striated and cardiac muscle. Strong KL staining was also detected in prostate fibromuscular stroma cells. In the central nervous system, KL expression was confined to Golgi and Purkinje cells in the cerebellum. These results suggest a role for this receptor and its ligand in the maintenance of a variety of fully differentiated tissues.