Faculty Bibliography

BACKGROUND: Patients with a large congenital melanocytic nevus (LCMN) may have associated leptomeningeal melanocytosis with or without central nervous system (CNS) melanomas. These patients are considered to have neurocutaneous melanosis, a disorder that, when symptomatic or otherwise manifest neurologically, carries a poor prognosis even in the absence of malignancy. OBJECTIVE: Our purpose was to identify typical clinical features in patients who have manifest CNS melanosis in association with LCMN. METHODS: The records of 117 patients with LCMN in the New York University Registry of LCMN and the reports of 172 cases of LCMN in the world literature were included for features that might signal a high risk for the development of manifest CNS involvement. RESULTS: Of the 289 patients with LCMN, 33 had manifest CNS melanosis. In all 33 in whom symptomatic neurocutaneous melanosis was diagnosed, the LCMNs were present in a posterior axial location on the head, neck, back, and/or buttocks. 'Satellite' nevi were known to be present in 31 of the 33 patients. CONCLUSION: Patients with LCMN in a posterior axial location, especially when associated with 'satellite' melanocytic nevi, are at greater risk for the development of manifest neurocutaneous melanosis than patients with LCMN limited to the extremities or those who are lacking satellite nevi

OBJECTIVE: To define the spectrum of disease in cases of hypopigmentation and hyperpigmentation along the lines of Blaschko more accurately. Pigmentary anomalies along the lines of Blaschko, including hypomelanosis of Ito, linear and whorled nevoid hypermelanosis, and nevus depigmentosus, can be associated with notable abnormal systemic features. We believe that the incidence of associated abnormal features described in previous studies is exaggerated owing to referral and reporting bias. DESIGN: Retrospective review of case series. SETTING: An ambulatory, university hospital, pediatric dermatology practice and a large, city hospital, pediatric dermatology clinic. PATIENTS: Fifty-four children referred consecutively over a 5-year period for evaluation of segmental, linear, or swirled hypopigmentation and/or hyperpigmentation along the lines of Blaschko. MAIN OUTCOME MEASURE: Incidence of associated abnormal systemic features. RESULTS: Extracutaneous abnormal features were present in 16 (30%) of 54 children with aberrant pigmentation along the lines of Blaschko: in 9 (33%) of 27 with hypomelanosis of Ito, in 4 (31%) of 13 with linear and whorled nevoid hypermelanosis, in 1 (11%) of 9 with nevus depigmentosus, and in 2 (40%) of 5 with coexistent hypopigmentation and hyperpigmentation. CONCLUSIONS: Pigmentary anomalies along the lines of Blaschko are associated with abnormal systemic features far less often than has been reported previously. These pigmentary anomalies should not be considered distinct syndromes but rather grouped as a heterogeneous collection of disorders indicative of underlying genetic mosaicism. Such a classification will allow better understanding and evaluation of affected persons

BACKGROUND: The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to reflect the clinical overlap of 3 conditions previously described as separate entities, each inherited in an autosomal dominant fashion. They are the Riley-Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. OBSERVATIONS: We studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic cutaneous findings included multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Macrocephaly with normal ventricular size, mental retardation, central nervous system vascular malformations, intestinal polyposis, skeletal abnormalities, and thyroid tumors were the most common systemic featues. A striking clinical finding in 1 patient was widespread verrucous changes of both lips that histologically showed epidermal hyperplasia with papillomatosis and hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the epidermis with increased pigment in the basal layer and a slight increase in the number of melanocytes were seen in biopsy specimens of the penile lentigines. CONCLUSIONS: The histologic findings of both the facial lesions and the pigmented macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our knowledge, been reported previously. The similarities between the Bannayan-Riley-Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic pathogenesis for these 2 diseases

Melanomas exhibiting mutated ras genes are frequently invasive and amelanotic. Transfecting melanocytes with ras oncogenes causes transformation and a loss of visible pigmentation. We analyzed murine melanocytes rendered amelanotic by transfection with the v-rasHa oncogene. Consistent with previous reports, tyrosinase and tyrosinase-related protein-1 (TRP-1) were not expressed by transformed cells. In addition, lack of expression of TRP-2 and the product of the silver locus was documented. Levels of melanosomal matrix antigens, the pink-eyed dilution locus protein and lysosome-associated membrane protein-1 were markedly reduced. Residual matrix antigens were localized by immunofluorescence to large vacuoles distributed peri-nuclearly in transfected cells. Electron microscopy demonstrated the absence of typical melanosomes and the presence of large vacuolar structures, also in a peri-nuclear distribution. Although levels of lysosomal hydrolases, such as beta-glucuronidase and cathepsin D, were diminished, marked elevations were observed in the expression of cathepsins B and L, 2 thiol proteases implicated in the acquisition of invasiveness. Our data demonstrate that transfection of melanocytes with v-rasHa is sufficient to disrupt the biogenesis of melanosomes and to up-regulate thiol protease synthesis, providing insights into the amelanotic and invasive nature of melanomas exhibiting mutations in ras genes

CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) occurs, as a rule, exclusively in girls because the underlying X-linked gene exerts a lethal effect on male embryos. In this report the characteristic manifestations of CHILD syndrome are described in a 2-year-old boy with a normal chromosome constitution 46,XY. This exceptional case is best explained by the assumption of an early somatic mutation and thus compatible with the concept of X-linked dominant male-lethal inheritance of this trait

BACKGROUND AND DESIGN: Patients with large congenital melanocytic nevi have been described to have an increased risk for the development of malignant melanoma (MM). Ninety-two patients with large congenital melanocytic nevi were followed up prospectively for the development of MM. Matched individuals from the general population served as control subjects. RESULTS: Ninety-two patients (median age, 3 years) were followed up prospectively for an average of 5.4 years. In three patients (3%), MM developed in extracutaneous sites. The cumulative 5-year life-table risk for the development of MM was calculated to be 4.5% (95% confidence interval, 0% to 9.3%). In individuals in the general US population, matched for age, sex, and length of follow-up to the 92 study patients, 0.013 would be expected to develop MM. The standardized morbidity ratio (adjusted relative risk) was calculated to be 239, which was highly significant (P < .001). CONCLUSIONS: Patients with large congenital melanocytic nevi are at a significantly increased risk for the development of MM and should be kept under continuous surveillance for the development of cutaneous as well as noncutaneous primary MM