The risk of hereditary cutaneous malignant melanoma was evaluated in 401 members of 14 families with an autosomal dominant form of melanoma. We documented 127 primary melanomas in 69 famil...

High Risk of Malignant Melanoma in Melanoma-Prone Families with Dysplastic Nevi

Malignant melanoma in renal-transplant recipients

We studied 30 patients with juvenile neuronal ceroid lipofuscinosis (JNCL). The patients (aged 6–25 years) and 43 age-matched healthy volunteers underwent MRI. After visual assessment, the signal intensity was measured on T2-weighted images in numerous locations. The thickness of the cortex and corpus callosum and the dimensions of the brain stem were measured. Mild to moderate cerebral atrophy was found in 14 of 30 patients, most of them over 14 years of age; 5 older patients had mild to moderate cerebellar atrophy. There was reduction in the size of the corpus callosum and brain stem. The thalamus, caudate nucleus and putamen appeared to give low signal in patients from the ages of 7, 11 and 11 years, respectively. In contrast, the signal intensity measured from the thalamus in these patients showed only a slight (insignificant) decrease compared with controls. The most significant alteration, an increase in measured signal intensity, was found in the white matter (P<0.0001), even in the youngest patients. The MRI findings correlated significantly with decreased intelligence, speech disturbances and motor problems. Although MRI findings in JNCL do not appear very specific and the visual changes develop relatively late, the absence of pathological MRI findings in the very early stage of the disease may play a part in differential diagnosis of the different types of NCL. Furthermore, the MRI findings may be used in assessing severity and prognosis, particularly in young patients.

MRI of neuronal ceroid lipofuscinosis. I. Cranial MRI of 30 patients with juvenile neuronal ceroid lipofuscinosis.

RAB7 Controls Melanoma Progression by Exploiting a Lineage-Specific Wiring of the Endolysosomal Pathway

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). Although environmental exposures, especially solar UV-irradiation, have been implicated as risk factors in sporadic melanoma, the role of such exposures in the pathogenesis of HCMM is unknown. We have studied the in vitro radiation responses of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. All six HCMM/DNS strains were found to show some degree of enhanced cell killing sensitivity, compared with normal controls, following 254 nm UV-irradiation. The abnormal survival responses appeared to relate to specific characteristics of HCMM/DNS cells since the six strains had essentially normal sensitivity to gamma-radiation. The enhanced photosensitivity was not associated with abnormal patterns in either DNA repair synthesis or UV-induced inhibition and recovery of de novo DNA synthesis. The survival results are consistent with the hypothesis that the genetically determined predisposition to malignant melanoma may directly or indirectly be the consequence of increased susceptibility to UV-induced cellular damage.

Abnormal sensitivity to UV-radiation in cultured skin ibroblasts from patients with hereditary cutaneous malignant melanoma and dysplastic nevus syndrome

Immune reactivity to melanoma extracts was measured by the leukocyte adherence inhibition (LAI) test in 40 members of 3 melanoma-prone families. The melanoma patients had a wide range of responsiveness to the extract, the highest responder being a 10-year survivor. As a group, family members (including spouses) without disease had significantly elevated LAI responses compared to those of unrelated controls (P less than 0.01). Within the families, members with close exposure to melanoma patients for 10 years or more had a significantly higher response to melanoma antigen than did members with 0-5 years of close exposure (P less than 0.05). Responses of spouses and members at high risk of developing melanoma (B-K mole syndrome) also correlated with length of exposure to patients, which suggests that the elevated LAI response was not genetically determined. The high frequency of positive responses to melanoma antigens in these families, particularly in spouses, suggests the presence of transmissible melanoma-associated material capable of immunizing persons in contact with melanoma patients.

Immune Response to Melanoma Extracts In Three Melanoma-Prone Families

Two patients with Charco-Marie-Tooth disease subsequently developed cutaneous malignant melanoma. This constellation of diseases may be due to chance, but raises the possibility of a shared neural crest defect or genetic linkage.

Ronald R. Reimer

Papers

Immune Response to Melanoma Extracts In Three Melanoma-Prone Families

Malignant melanoma and Charcot-Marie-Tooth disease.

Chemotherapy of Recurrent Breast Cancer