BACKGROUND AND PURPOSE:Extension of malignant melanoma along cranial nerves is a little-known complication of malignant melanoma of the head and neck. We describe the clinical and MR imaging findings of perineural spread of malignant melanoma to cranial nerves, emphasizing that this entity occurs more commonly with desmoplastic histology and may have a long latent period following primary diagnosis.METHODS: At two institutions, we identified and retrospectively reviewed eight cases of malignant melanoma of the head and neck that had MR imaging evidence of perineural spread of disease. All patients underwent confirmatory tissue sampling.RESULTS: Seven patients had melanomas of the facial skin or lip, and one patient had a primary sinonasal lesion. By histopathology, these melanomas included five desmoplastic, two mucosal, and one poorly differentiated melanotic spindle-cell tumor. All patients developed symptomatic cranial neuropathy an average of 4.9 years from the time of initial diagnosis. MR imaging demonstrated postgadolinium enhancement of at least one branch of the trigeminal nerve in all cases and of at least one other cranial nerve in five cases. Other findings included abnormal contrast enhancement and soft tissue thickening in the cavernous sinus, Meckel's cave, and/or the cisternal segment of the trigeminal nerve.CONCLUSION: Although perineural spread of disease occurs most commonly with squamous cell carcinoma and adenoid cystic carcinoma, malignant melanoma must also be included in this differential diagnosis, particularly if the patient's pathology is known to be desmoplastic. Similarly, any patient with malignant melanoma of the head and neck who undergoes MR imaging should receive an imaging assessment focused on the likely routes of perineural spread.

In response to acute disruption of the permeability barrier of aged mammals there is a diminished capacity for barrier recovery, analogous to other aged organs when stressed. Acute barrier disruption increases levels of epidermal cytokines, and cytokines are known regulators of keratinocyte mitogenesis, as well as lipid synthesis in extracutaneous tissues. Underlying the sluggish barrier recovery in aged skin are diminished mRNA and protein levels for the interleukin-1 cytokine family, and its receptors. To further elucidate the role of the interleukin-1 family of cytokines in the barrier repair response, cytokine production was stimulated in aged murine skin with topical imiquimod application. Imiquimod accelerated barrier recovery after acute insults to aged and young skin. These functional results correlated temporally with increased interleukin-1 alpha production in the epidermis following topical imiquimod administration to murine skin. Furthermore, intracutaneous injections of interleukin-1 alpha accelerated barrier recovery in aged mice. Finally, we showed that interleukin-1 alpha added to cultured human keratinocytes stimulates epidermal lipid synthesis. These studies provide further evidence for the role of reduced interleukin-1 alpha signaling in the decline of permeability barrier function in aged skin, and point to the potential use of cytokine augmentation in barrier dysfunction of the aged.

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Cholesterol sulfate is a multifunctional sterol metabolite, produced in large amounts in squamous keratinizing epithelia. Because patients with recessive x-linked ichthyosis display not only a 10-fold increase in cholesterol sulfate, but also a 50% reduction in cholesterol, we assessed here whether cholesterol sulfate accumulation and/or cholesterol deficiency produce abnormal barrier function in recessive x-linked ichthyosis. Patients with recessive x-linked ichthyosis display both an abnormal barrier under basal conditions, and a delay in barrier recovery after acute perturbation, which correlate with minor abnormalities in membrane structure and extensive lamellar-phase separation. Moreover, both the functional and the structural abnormalities were corrected by topical cholesterol. Yet, topical cholesterol sulfate produced both a barrier abnormality in intact skin and extracellular abnormalities in isolated stratum corneum, effects largely reversed by coapplications of cholesterol. Together, these results suggest that cholesterol sulfate accumulation rather than cholesterol deficiency is responsible for the barrier abnormality. Despite the apparent importance of cholesterol sulfate-to-cholesterol processing for normal barrier homeostasis, neither steroid sulfatase activity nor mRNA levels are upregulated following acute perturbations. These results demonstrate both a potential role for cholesterol sulfate-to-cholesterol processing in normal permeability barrier homeostasis, and that basal levels of steroid sulfatase are sufficient to accommodate acute insults to the permeability barrier.