Neurocutaneous melanosis presenting with intracranial amelanotic melanoma.
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We describe imaging findings in a 2-year-old girl with neurocutaneous melanosis and malignant cerebral melanoma. Because the cerebral melanoma in this child was of the amelanotic type, high-signal intensity on unenhanced T1-weighted images was not present. The cutaneous lesions played a crucial role in establishing a correct (presumed) histopathologic diagnosis on the basis of the imaging findings. To our knowledge this is the first report describing an intracranial amelanotic malignant melanoma in association with neurocutaneous melanosis. (+info)
Genetics of risk factors for melanoma: an adult twin study of nevi and freckles.
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BACKGROUND: We sought by use of an adult twin study to investigate the relative contribution of genetic and environmental effects on the expression of nevi and freckles, which are known risk factors for melanoma, and to determine if age and sun exposure influence the heritability of nevi. DESIGN AND METHODS: Total nevus and freckle counts were conducted on 127 monozygotic twin pairs and 323 dizygotic twin pairs. Intraclass correlations were calculated by use of analysis of variance. Model-fitting analyses were performed to quantify the genetic and environmental components of the variance for nevus and freckle counts. RESULTS: The intraclass correlation for total nevus counts was.83 in monozygotic pairs compared with.51 in dizygotic pairs. Quantitative genetic analyses showed that the contribution of genetic factors on nevi expression varied according to age. For twins less than 45 years old, the additive genetic variance on total nevus count was 36% (95% confidence interval [CI] = 0.8%-63%), with 38% (95% CI = 14%-61%) and 26% (95% CI = 16%-42%) of the remaining variance attributed to common environment and unique environmental effects, respectively. In twins aged 45 years or older, common environmental effects on total nevus count became negligible, with the additive genetic variance increasing to 84% (95% CI = 77%-88%). Body site was also found to affect the heritability estimates for nevus counts, with a statistically significant difference between sun-exposed and sun-protected sites. The polychoric correlation (i.e., the correlation in liability within twins for more than two categories) for total freckle counts was.91 in monozygotic twin pairs compared with.54 in dizygotic twin pairs. Additive genetic effects explained 91% (95% CI = 86%-94%) of the variance in freckle counts. CONCLUSION: The contribution of genetic factors on the variance for total nevus counts increased with age, and sun exposure appears to influence the expression of nevi. The results of this study highlight the need to take into account the age and site of nevus counts for future genetic linkage or association studies in the search for new melanoma genes. (+info)
An unbalanced submicroscopic translocation t(8;16)(q24.3;p13.3)pat associated with tuberous sclerosis complex, adult polycystic kidney disease, and hypomelanosis of Ito.
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We report on a familial submicroscopic translocation involving chromosomes 8 and 16. The proband of the family had a clinical picture suggestive of a large deletion in the chromosome 16p13.3 area, as he was affected with tuberous sclerosis complex (TSC) and had alpha thalassaemia trait, and his half brother, who also had TSC, may have suffered additionally from polycystic kidney disease (PKD). FISH studies provided evidence for a familial translocation t(8;16)(q24.3;p13.3) with an unbalanced form in the proband and a balanced form in the father and in a paternal aunt. The unbalanced translocation caused the index patient to be deleted for the chromosome 16p13.3-pter region, with the most proximal breakpoint described to date for terminal 16p deletions. In addition, FISH analysis showed a duplication for the distal 8q region. Since the index patient also had hypomelanosis of Ito (HI), either of the chromosomal areas involved in the translocation may be a candidate region for an HI determining gene. Furthermore, it is noteworthy that both carriers of the balanced translocation showed a nodular goitre, while the proband has hypothyroidism. (+info)
Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study.
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BACKGROUND: Anthranoid laxatives are the most commonly used purgatives in the therapy of acute and chronic constipation. Recent experimental data and a prospective cohort study provide evidence of a possible risk of anthranoid use for the development of colorectal neoplasms. MATERIALS AND METHODS: We performed a prospective case control study at the University of Erlangen to investigate the risk of anthranoid laxative use for the development of colorectal adenomas or carcinomas. A total of 202 patients with newly diagnosed colorectal carcinomas, 114 patients with adenomatous polyps, and 238 patients (controls) with no colorectal neoplasms who had been referred for total colonoscopy were studied. The use of anthranoid preparations was assessed by standardised interview, and endoscopically visible or microscopic melanosis coli was studied by histopathological examination. RESULTS: There was no statistically significant risk of anthranoid use for the development of colorectal adenomas (unadjusted odds ratio 1.0; 95% CI 0.5-1.9) or carcinomas (unadjusted odds ratio 1.0; 95% CI 0.6-1.8). Even after adjustment for the risk factors age, sex, and blood in the stools by logistic regression analysis the odds ratio for adenomas was 0.84 (95% CI 0. 4-1.7) and for carcinomas 0.93 (95% CI 0.5-1.7). Also, there were no differences between the patient and control groups for duration of intake. Macroscopic and high grade microscopic melanosis coli were not significant risk factors for the development of adenomas or carcinomas. CONCLUSION: Neither anthranoid laxative use, even in the long term, nor macroscopic or marked microscopic melanosis coli were associated with any significant risk for the development of colorectal adenoma or carcinoma. (+info)
Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins.
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Human papillomavirus (HPV) survives by reactivating DNA replication in post-mitotic cells. In the present study, we describe a mouse model of HPV-dependent disease. In these mice, DNA synthesis is activated in suprabasal keratinocytes, leading to acanthosis, parakeratosis and enhanced desquamation. The full-length E6/E7 transcript and two alternately spliced products are produced and in most lines the predominant product is E6*. In the present study, we examine the effects of E6/E7 on cell cycle regulatory protein expression. E6/E7 expression in mouse epidermis is correlated with increased levels of the p53, p21, p27, cdk2, cdk4, cdk6, cyclin D1 and cyclin E regulatory proteins. Hyperproliferation is also observed in the buccal mucosa and the tongue epithelia of E6/E7 mice, and p53 levels are markedly increased in these epithelia. These results suggest that the major changes in cell cycle regulatory protein expression are in response to the presence of E7 and that E6 has a lesser impact. (+info)
The dramatic rise in incidence of malignant melanoma experienced by populations both within the United States and throughout the world over the last several decades has been attributed to enhanced exposure to the UV spectrum of sunlight radiation. This hypothesis can now be tested using genetically engineered mouse models predisposed to malignant melanoma. Here we use melanoma-prone transgenic mice inappropriately expressing hepatocyte growth factor/scatter factor (HGF/SF) in the skin as an experimental model system to ascertain the consequences of a chronic regimen of suberythemal UV radiation on melanoma genesis. HGF/SF is a multifunctional regulator capable of stimulating growth, motility, invasiveness, and morphogenetic transformation in cells, including melanocytes, expressing its receptor tyrosine kinase Met. HGF/SF transgenic mice demonstrate ectopic interfollicular localization and accumulation of melanocytes within the truncal dermis, epidermis, and junction and if untreated develop primary cutaneous melanoma with a mean onset age of approximately 21 months. Transgenic mice and their wild-type littermates subjected to UV radiation three times weekly using FS40 sunlamps (60% UVB and 40% UVA), with daily UV doses graded from 2.25 to 6.0 kJ/m2, developed skin tumors with a mean onset age of 26 and 37 weeks, respectively (P < 0.001, Kaplan-Meier log rank test). However, the repeated doses of suberythemal UV radiation used in this study failed to accelerate melanoma genesis, instead inducing the development of nonmelanoma tumors that included squamous cell carcinomas, squamous papillomas, and sarcomas. The conspicuous absence of melanocytic tumors occurred despite the immunohistochemical detection of a significant stimulation (P < 0.001) in melanocyte-specific bromodeoxyuridine incorporation in response to only 2 weeks of UV irradiation (total UV dose of 13.5 kJ/m2), resulting in 2.6- and 4.6-fold increases in the number of melanocytes in the dermis and epidermis, respectively. These data indicate that chronic suberythemal UV radiation preferentially favors the development of nonmelanocytic over melanocytic neoplasms in this transgenic animal, consistent with the pathogenesis proposed for sun exposure-associated skin cancer based on retrospective studies in the human population. Our findings suggest that the HGF/SF transgenic mouse will be useful as an experimental model for determining the consequences of exposure to various regimens of UV radiation and for elucidating the mechanisms by which such consequences are realized. (+info)
Benign atypical junctional melanocytic hyperplasia associated with intradermal nevi: a common finding that may be confused with melanoma in situ.
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Over the past few years, consultation cases thought to represent melanoma in situ have been received that consisted of otherwise normal intradermal nevi with an abnormal but benign junctional proliferation of melanocytes that we have termed benign atypical junctional melanocytic hyperplasia. In order to evaluate the incidence of this feature, 400 cases of intradermal nevi were reviewed. Of these, 25 (6.2%) qualified for inclusion, making this a rather common phenomenon. Clinically, patient ages ranged from 18 to 64 years (mean, 35 years), with a male to female ratio of 1:1. Face (40%) and back (32%) were the most common locations. Histologically, the lesions were predominantly dome-shaped with an intradermal component consisting of conventional nevus cells. Most importantly, each lesion exhibited prominent individual nevomelanocytic cells dispersed at uneven intervals along the dermoepidermal junction in insufficient numbers to be considered compound nevi. The cells exhibited abundant pale to clear cytoplasm, an increased nuclear:cytoplasmic ratio, and often exhibited prominent nucleoli. However, these lesions could be distinguished from melanoma in situ by the lack of several features including lateral spread, upward epidermal migration, marked cytologic atypia, finely granular "smoky" melanin pigment, mitotic figures, and a subjacent host inflammatory response. All cases behaved in a benign fashion. Although benign atypical junctional melanocytic hyperplasia is a relatively common histological curiosity, it is a potential pitfall in the diagnosis of pigmented lesions. (+info)
Evolutionary dynamics of declining melanism in the peppered moth in the Netherlands.
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Populations of Biston betularia in the region of The Netherlands around Leiden and Rotterdam were resampled. A comparison of three sets of data for 1969-1973, 1988 and 1999 enabled a further examination of declines in melanism. Unlike parallel changes for the black carbonaria form of this species in urban regions of Britain, those inThe Netherlands involve substantial changes in frequencies of at least two of the intermediate insularia morphs as well as an increase in the non-melanic typica morph. The darkest of the three insularia morphs has shown a transitory pulse of increased frequency in The Netherlands. The dynamics are discussed in relation to the history of air pollution and to straightforward predictions about selection. (+info)