Recurrent giant neurofibroma of the posterior neck and upper back with failed primary grafting and salvage reconstruction: a case report.

Niemann-Pick type C (NPC) disease is an autosomal recessive neurodegenerative disease caused by mutations in the gene (in 95% of patients) or 2 gene. Both genes encode proteins required for cholesterol export from lysosomes. The NPC1 glycoprotein is involved in the efflux of low-density lipoprotein (LDL) derived unesterified cholesterol from late endosomes and lysosomes to other intracellular compartments. The NPC2 protein binds cholesterol and mutations in gene produce accumulations of unesterified cholesterol, sphingolipids, and complex gangliosides in late endosomes and lysosomes of most cell types of the body indistinguishable from those of mutations. Loss-of-function mutations in either of these proteins lead to deficient lipid trafficking, abnormal regulation of cholesterol biosynthesis, and intracellular accumulation of unesterified cholesterol and gangliosides GM2 and GM3 (sialic acid-containing sphingolipids, major constituents of neuronal membranes) in late endosomes/lysosomes, due to impaired mobilization and re-esterification of LDL cholesterol throughout the body, especially in liver, spleen, lung, and brain. The most prevalent mutation in the gene, I1061T, accounts for approximately 15–20% of all disease-associated alleles in humans. This variant leads to the misfolding of the NPC1 protein, which is subsequently directed toward ER-associated degradation. This mutation predisposes patients to the classic NPC1 disease clinical phenotype, which includes hepatosplenomegaly, ataxia, dystonia, and progressive neurodegeneration (in late-infantile and juvenile forms between 3 and 15 years of life, 60–70% of cases). Neurodegeneration can even appear later with onset in adolescence and adulthood, when it is characterized by cognitive, auditory, and coordination impairments. Animal models for NPC1 disease reported age-dependent neuronal loss in the prefrontal cortex, thalamus, and brainstem, as well as degeneration of cerebellar Purkinje cells, astrogliosis, upregulation of inflammatory genes, and accumulation of cholesterol-derived compounds and sphingolipids within hepatic and neural tissues. These changes closely parallel those described in human NPC1 disease.