Relationship between type 2 diabetes mellitus and markers of cutaneous melanoma aggressiveness: an observational multicentric study in 443 patients with melanoma.

BACKGROUND: Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are under way to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis. OBJECTIVES: To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma. METHODS: We conducted a cross-sectional multicentric study in 443 patients diagnosed with cutaneous melanoma. At diagnosis, all patients completed a standardized protocol, and a fasting blood sample was extracted to analyse their glucose levels, glycated haemoglobin concentration and markers of systemic inflammation. Melanoma characteristics and aggressiveness factors [Breslow thickness, ulceration, tumour mitotic rate (TMR), sentinel lymph node (SLN) involvement and tumour stage] were also recorded. RESULTS: The mean (SD) age of the patients was 55·98 (15·3) years and 50·6% were male. The median Breslow thickness was 0·85 mm. In total, 48 (10·8%) patients were diagnosed with T2DM and this finding was associated with a Breslow thickness > 2 mm [odds ratio (OR) 2·6, 95% confidence interval (CI) 1·4-4·9; P = 0·004)] and > 4 mm (OR 3·6, 95% CI 1·7-7·9; P = 0·001), TMR > 5 per mm2 (OR 4·5, 95% CI 1·4-13·7; P = 0·009), SLN involvement (OR 2·3, 95% CI 1-5·7; P = 0·038) and tumour stages III-IV (vs. I-II) (OR 3·4, 95% CI 1·6-7·4; P = 0·002), after adjusting for age, sex, obesity, alcohol intake and smoking habits. No significant associations emerged between glycated haemoglobin levels, metformin treatment and melanoma aggressiveness. CONCLUSIONS: T2DM, rather than glycaemic control and metformin treatment, is associated with increased cutaneous melanoma aggressiveness at diagnosis.

Determination of minimal erythema dose and anomalous reactions to UVA radiation by skin phototype.

BACKGROUND: Phototesting is a technique that assesses the skin's sensitivity to UV radiation by determining the smallest dose of radiation capable of inducing erythema (minimal erythema dose [MED]) and anomalous responses to UV-A radiation. No phototesting protocol guidelines have been published to date. METHODOLOGY: This was a multicenter prospective cohort study in which 232 healthy volunteers were recruited at 9 hospitals. Phototests were carried out with solar simulators or fluorescent broadband UV-B lamps. Each individual received a total of 5 or 6 incremental doses of erythemal radiation and 4 doses of UV-A radiation. The results were read at 24hours. RESULTS: At hospitals where solar simulators were used, the mean (SD) MED values were 23 (8), 28 (4), 35 (4), and 51 (6) mJ/cm(2) for skin phototypes i to iv, respectively. At hospitals where broadband UV-B lamps were used, these values were 28 (5), 32 (3), and 34 (5) mJ/cm(2) for phototypes ii to iv, respectively. MED values lower than 7, 19, 27, and 38 mJ/cm(2) obtained with solar simulators were considered to indicate a pathologic response for phototypes I to IV, respectively. MED values lower than 18, 24, and 24mJ/cm(2) obtained with broadband UV-B lamps were considered to indicate a pathologic response for phototypes ii to iv, respectively. No anomalous responses were observed at UV-A radiation doses of up to 20J/cm(2). CONCLUSIONS: Results were homogeneous across centers, making it possible to standardize diagnostic phototesting for the various skin phototypes and establish threshold doses that define anomalous responses to UV radiation.

[Eruptive pseudoangiomatosis: study of 7 cases]. / Pseudoangiomatosis eruptiva: 7 casos clínicos.

INTRODUCTION: Eruptive pseudoangiomatosis consists in the acute development of small vascular lesions in the face and extremities that resolve in several weeks without scarring. Lesions are described as 3-4 mm asymptomatic macules and papules with peripheral whitish halo that blanch upon pressure. Initially it was considered a disease limited to children but it has also been described in adults. It overlaps with the entity known in Japan as <>, possibly caused by an insect named Culex pipiens pallens. METHODS: We report a serie of 7 patients that consulted for lesions compatible with eruptive pseudoangiomatosis. We performed a detailed clinical history and histological, microbiological and serological studies. Follow-up time was up to 4 years. RESULTS: Eighty-five percent of patients were women and the mean age was 62 years. All cases appeared in spring/summer and 71 % relapsed. Lesions predominated in the face and extremities and the outbreak lasted 2-4 weeks. The anamnesis did not disclose any specific etiologic agent in any of the cases. Complete laboratory tests including serologies and cultures were negative or within normal limits. Histological study revealed vascular dilatation in all cases with endothelial cell protrusion and a peripheral lymphohistiocytic infiltrate. CONCLUSIONS: Currently, the etiology of this entity is not well established although it probably represents a reactive disorder to different etiologic processes.

Interleukin-2 enhances the growth of human melanoma cells derived form primary but not from metastatic tumours.

Previously, we demonstrated that in vitro treatment of B16F10 murine melanoma cells with interleukin-2 (IL-2) enhances proliferation and metastasis. To further investigate the role played by IL-2 in human melanomas, we studied the expression of IL-2/IL-2 receptor and the effect of IL-2 on the proliferation of melanoma cell lines derived from primary (A375 and RMS cell lines) and metastatic (Hs294T cell line) tumours. We found a constitutive expression of cytoplasmic IL-2 and alpha, beta and gamma-subunits of the IL-2R on the surface of the three melanoma cell lines. The presence of IL-2 in the culture increased the proliferation rate in A375 and RMS cell lines, but no effect was observed in Hs294T metastatic cells. Biologically active IL-2 could be found in the supernatant of the three melanoma cell lines, particularly in A375 and RMS cells, in which an inhibition of the proliferation rate was observed when IL-2 was blocked. Moreover, the combination of anti-IL-2R beta and anti-IL-2R gamma blocking antibodies induced a significant down-regulation of cell proliferation in the three melanoma cell lines, and the combination of anti-IL-2R alpha, anti-IL-2R beta and anti-IL-2R gamma blocking antibodies inhibited IL-2-mediated growth stimulation in A375 and Hs294T cell lines. In RMS cells, a more significant effect was observed when only IL-2R gamma was blocked. Finally, exogenous IL-2 modulated the IL-2 endogenously produced by melanoma cells. These data show that IL-2 may modulate the growth of melanoma cells through autocrine or/and paracrine mechanisms.

Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma.

Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma.

Serum-soluble IL-2 receptor and IL-6 levels in patients with melanoma.

Elevated soluble IL-2 receptor (sIL-2R) and IL-6 serum concentrations have been reported as adverse prognostic factors in several types of cancer. In order to determine whether these factors are predictive of metastatic progression in melanoma, sIL-2R and IL-6 levels were measured in sera from 172 patients with melanoma and 60 in healthy controls. Mean sIL-2R values were significantly higher in the patients than in normal controls and the highest values were observed in those that developed metastasis during follow-up. However, no correlation was found with the stage of the disease. Serum IL-6 levels were found to be correlated with age and sex, but not correlated with sIL-2R levels. Statistical analysis was based on logistic and Cox regression models. The factors considered were age, sex, stage, disease-free interval and serum sIL-2R and IL-6 levels. The analysis showed that only the sIL-2R value is significantly linked to metastatic progression. This finding suggests that high serum levels of sIL-2R could be a predictive factor of metastatic progression in malignant melanoma.

A case of the elephant man phenotype with giant rhinophyma and benign symmetric lipomatosis.

We described an unusual male patient with two disfiguring diseases, benign symmetric lipomatosis and giant rhinophyma, which gave him a grotesque appearance. His physical appearance had isolated him from the rest of society and was probably the main reason for his alcohol abuse.

[Familial eosinophilic fascitis induced by toxic oil]. / Fascitis eosinofílica familiar inducida por aceite tóxico.

Three of four family members in husband, wife and one of two daughters developed in a short time interval (eleven months) eosinophilic fasciitis. The clinical, analytical and histopathological changes were characteristic of this disease. Familial cases of eosinophilic fasciitis have not been previously published. The process of these patients was probably caused by the ingestion of denatured oil (toxic oil syndrome), although the clinical picture begun two and a half years after the epidemic phase of the toxic oil syndrome declined.

[Bowenoid papulosis in a patient with AIDS]. / Papulosis bowenoide en paciente de SIDA.

A patient with a acquired immunodeficiency syndrome (AIDS) and Kaposi's angiosarcoma developed bowenoid papulosis of the genitalia (BP). The clinical and histopathological criteria were both characteristic of BP. With vinblastine treatment a moderate improvement of Kaposi's lesions was observed, but no significant changes of the BP lesions were noted during this treatment.