Identification of 5-S-cysteinyldopa by high performance liquid chromatography in biopsies from patients with dysplastic melanocytic nevi.

The appearance of 5-[(L)-S-cysteinyl]dopa, a major product in pheomelanogenesis was examined in affected and nonaffected skins from 20 patients with clinical signs of dysplastic melanocytic nevi. Analysis by high performance liquid chromatography and electrochemical detection showed that 20 of the 35 lesions had a pathological formation of 5-[(L)-S-cysteinyl]dopa (0.04-28.86 ng/micrograms acid soluble protein). 5-[(L)-S-cysteinyl]dopa was not detected in any of the normal uninvolved skin samples analyzed.

Pagetoid intraepidermal spread in Merkel cell (primary neuroendocrine) carcinoma of the skin.

Pagetoid intraepidermal spread of neoplastic cells was noted in six cases of Merkel (primary neuroendocrine) cell carcinoma of the skin. In two cases, the volume of the intraepidermal portion of the neoplasm was either equal to or more extensive than the dermal component. The intraepidermal component in all six cases was remarkable because of the following findings: the presence of cells with scant cytoplasm arranged both individually and as nests, sometimes along the dermoepidermal junction; splaying of the apical portions of basal keratinocytes by solitary neoplastic cells; incomplete rims of compressed basal keratinocytes at the peripheries of some junctional nests; and occasional contiguity of neuroendocrine carcinoma cells with those of Bowen's disease or solar keratosis. These features can be used to distinguish these Merkel cell carcinomas from other lesions that have a pagetoid pattern, even in superficial biopsies, and immunohistochemistry can confirm the diagnosis or resolve problematic cases. The occurrence of cutaneous neuroendocrine carcinoma situated largely in the epidermis raises the possibility that some of these tumors may arise from intraepidermal Merkel cells.

The inheritance pattern of dysplastic naevi in families of dysplastic naevus patients.

Dysplastic naevi (DN) are the major precursor lesions of malignant melanoma, yet the presumed mode of inheritance or genetic aetiology of DN remains controversial. The inheritance pattern of DN in families from a randomly selected population of 26 dysplastic naevus patients was investigated by estimating the segregation ratio in families ascertained through an offspring with DN (incomplete ascertainment). For families ascertained through a parent with DN (complete ascertainment) the transmission pattern was examined by comparing the observed number of affected offspring to the expected number using a chi 2 goodness-of-fit test. Results from the chi 2 tests and the estimated segregation ratio of 0.52 (95% confidence interval: 0.31, 0.73) suggest that the inheritance pattern for dysplastic naevi in these families is consistent with autosomal dominant transmission, although the present study was limited because of a small sample size. The findings, therefore, need to be confirmed by a much larger study that is able to test more rigorously specific genetic hypotheses.

Double-blind controlled crossover high-dose study of Azaribine in psoriasis.

Azaribine used in high doses of 200 mg/kg a day is an effective agent in inducing temporary remissions in patients with severe psoriasis but potentially serious neurotoxicity may occur. Therapy should be initiated at lower doses of 125 mg/kg a day and advanced carefully only if clinical response does not ensue at the lower level.

Dysplastic nevi and malignant melanoma.

The incidence of melanoma has been steadily increasing, with a trend for this tumor to develop at younger ages. The only satisfactory treatment for melanoma is early intervention; therefore, routine screening for melanoma and dysplastic nevi during the general physical examination is important. The prevalence of dysplastic nevi is estimated to be 2 to 5 percent. Patients with dysplastic nevi appear to have at least a 6 percent lifetime risk of melanoma. In the most severely affected patients (those with a family history of dysplastic nevi and more than one melanoma), the lifetime risk may exceed 50 percent. Patients with dysplastic nevi merit periodic follow-up. Since these nevi tend to be familial, close relatives of affected patients may also benefit from a screening examination. Individuals at increased risk for melanoma may display one or more of the following risk factors: dysplastic nevi, freckling, tendency to sunburn and numerous common nevi. Such individuals may benefit most from education in sunburn avoidance, sunscreen use and self-examination for changing nevi. A better informed public and heightened physician awareness are the most effective means of reducing mortality from this virulent malignancy.

Clinical diagnosis of dysplastic melanocytic nevi. A clinicopathologic correlation.

A prospective, community practice-based, clinicopathologic correlation was undertaken in 165 melanocytic nevi excised from a group of forty-three patients, each patient having previously had at least one clinically suspected and histologically confirmed dysplastic melanocytic nevus. Eighty-two percent of seventy-two lesions with histologic evidence of mild dysplasia had been diagnosed correctly as such clinically. The accuracy of clinical diagnosis of moderate dysplasia was low (20%); however, all cases of severe dysplasia with or without in situ melanoma were diagnosed correctly. In 75% of all cases in which dysplasia of any degree was diagnosed clinically, histologic evidence of dysplasia was found. In order to investigate further the clinical features of these nevi, 175 color enlargements of histologically confirmed dysplastic melanocytic nevi were examined. The following clinical features were found to be most common: ill-defined border (90%), irregularly distributed pigmentation (84%), maximum diameter greater than 5.0 mm (72%), erythema (64%), and accentuated skin markings (63%). Increasing darkness and confluence of pigmentation in these dysplastic melanocytic nevi correlated with increasing severity of dysplasia. We conclude that careful clinical examination of individual melanocytic nevi will separate severe dysplasia with or without in situ melanoma from low-grade (mild or moderate) dysplasia in a high percentage of nevi from patients with the dysplastic nevus syndrome. Clinical examination will yield a diagnosis of dysplasia in approximately 75% of nevi from such patients in whom histologic evidence of dysplasia is present. Clinical examination constitutes a practical and sufficiently reliable method for the assessment of melanocytic nevi in patients with the dysplastic nevus syndrome.

Familial and cutaneous features of dysplastic nevi: a case-control study.

BACKGROUND: Although dysplastic nevi are an important risk factor for melanoma, little is understood about the epidemiology of these nevi. To further characterize some of the correlates of dysplastic nevi, we reexamined patients from one of the original prevalence reports and their first-degree relatives. OBJECTIVE: Our purpose was to characterize the prevalence and correlates of dysplastic nevi. METHODS: We studied 25 persons originally diagnosed with dysplastic nevi in 1980 and 1981, 28 controls stratified by age, sex, race, and date of initial examination, and all willing first-degree relatives of both patients (n = 78) and control subjects (n = 76). Each study subject underwent a full skin examination and biopsy of nevi suspected of being dysplastic nevi, if willing. RESULTS: Eighty percent of the case kindreds were multiplex (2 members or more affected) for dysplastic nevi; the relative risk of having dysplastic nevi was 7.2 (95% confidence interval 2.1 to 24) if one or more relatives had dysplastic nevi. Three of the cases (12%) in multiplex families also had a first-degree relative with melanoma. Cases and relatives with dysplastic nevi of both patients and control subjects tended to have increased numbers of nevi. The risk of having dysplastic nevi rose 99-fold in persons with more than five nevi 4 mm or larger and/or scars on their back (p < 0.001). CONCLUSION: These data support the hypothesis that family members of unselected persons with dysplastic nevi are likely to have dysplastic nevi and may be at increased risk of melanoma.

Age distribution and histologic patterns of dysplastic nevi.

A total of 676 dysplastic moles collected from 487 patients over a 1-year period were reviewed together with demographic data. The associated nevus in 642 cases (95%) had a superficial, or "acquired," pattern within the papillary dermis, in comparison with the nevus in the remaining 34 cases (5%), which showed a deep, or "congenital," pattern. The dysplasia was graded in severity as mild, moderate, or severe (on a scale of 1 to 3). When patients with mild to severe dysplastic melanocytic nevi were compared with those patients showing atypical intraepidermal melanocytic hyperplasia (also called in situ malignant melanoma) or early invasive malignant melanoma associated with dysplasia, a progression of ages was noted. The average ages in the five diagnostic groups were as follows: 34.8 years, mild dysplasia (group 1); 35.1 years, moderate dysplasia (group 2); 41.5 years, severe dysplasia (group 3); 44.4 years, in situ malignant melanoma (group 4), and 46.9 years, early invasive malignant melanoma (group 5). Statistical analysis revealed that the two younger groups differed significantly in age from the three older groups. Men and women had an equal proportion of acquired and congenital pattern nevi, but men were older in each category and had more severe dysplasia, a greater tendency toward truncal lesions, and more regressive changes. Biopsy of trunk lesions was done in 275 cases (80%), of extremity lesions in 60 cases (17%), and in head and neck sites in 9 cases (3%).(ABSTRACT TRUNCATED AT 250 WORDS)