Joaquim Marcoval

Angiogenesis and malignant melanoma. Angiogenesis is related to the development of vertical (tumorigenic) growth phase

To study angiogenesis in early steps of melanoma progression, 113 cutaneous melanomas 1mm or less in thickness were stained with Ulex europaeus lectin. Vascular density was determined in the areas of greatest vascularization. To avoid the effect of anatomic location, the quotient between vascular density at the tumor base and in normal skin (vascular ratio) was obtained in each case. Of these melanomas, 46 were immunohistochemically stained for the presence of vascular endothelial growth factor (VEGF). Positivity was scored from 1–4 by comparing staining of melanoma cells with keratinocytes. Vascular ratio values in vertical growth phase melanomas were higher than those in radial growth phase when counting per 200 or 400 magnification (2.29±1.3 and 2.48±1.5 for vertical growth phase and 1.34±0.62 and 1.41 ±0.83 for radial growth phase melanomas, respectively). This difference was statistically significant (p < 0.0001 and p<0.001 at × 200 and × 400, respectively). Also, VEGF staining was stronger in vertical growth phase melanomas when compared with radial growth phase melanomas (Chi square, p < 0.025).

Subcutaneous sarcoidosis--clinicopathological study of 10 cases.

Background  Subcutaneous sarcoidosis is a specific cutaneous lesion of sarcoidosis that is rarely reported.

Specific cutaneous lesions in patients with systemic sarcoidosis: relationship to severity and chronicity of disease

Background.  Specific (granulomatous) cutaneous lesions are seen in 9–37% of cases of systemic sarcoidosis, and are usually classified into maculopapules, plaques, lupus pernio (LP), scar sarcoidosis, and subcutaneous sarcoidosis. Their prognostic significance has not been fully established.

Calciphylaxis associated with alcoholic cirrhosis

Calciphylaxis is an uncommon disease characterized by calcification of dermal vessels that determines skin necrosis. Calciphylaxis has been almost exclusively reported in association with renal failure and altered phosphor–calcium metabolism. Only a few cases have been described in hyperparathyroidism, malignancies, and, recently, cirrhosis. We report a patient that developed calciphylaxis related to end‐stage alcoholic cirrhosis, without any alteration in the phosphocalcic and parathyroid hormone metabolisms. Possible contributing factors were repeated albumin infusions and low levels of protein C and S.

High expression of p21Waf1 in sarcoid granulomas: a putative role for long‐lasting inflammation

In sarcoid granulomas, apoptotic events are reduced, which explains their characteristic long‐lasting inflammation. We have described that interferon‐γ (IFN‐γ) inhibits apoptosis in macrophages through the expression of p21Waf1. Here, we explore the molecular mechanisms involved in the inhibition of apoptosis in sarcoid granulomas. We analyzed skin biopsies from 19 sarcoidosis patients and 16 controls. Total RNA was subjected to semiquantitative reverse transcriptase‐polymerase chain reaction analysis. There was no difference found in the expression of proapoptotic (Bax and Bcl‐Xs) or antiapoptotic (Bcl‐2 and Bcl‐XL) genes nor in the expression of the tumor suppressor gene p53. Furthermore, the expression of IFN‐γ and the cdk inhibitors p21Waf1 and p27Kip1 were analyzed. IFN‐γ was detected in 37% of the sarcoidosis patients, and controls were negative (P<0.02). In addition, a higher proportion of patients expressing p21Waf1 (58%) versus controls (12%) was found (P<0.005). There was a significant correlation between the expression of IFN‐γ and p21Waf1 (r=0.69) and between p21Waf1 and fibronectin (r=0.65). Finally, using immunohistochemistry, high p21Waf1 reactivity was observed inside the granuloma. We conclude that the high levels of p21Waf1 in sarcoidosis may explain the absence of apoptosis in the granuloma and the persistence of inflammation.

Evolución del melanoma maligno cutáneo en los últimos 19 años en un hospital terciario de la cuenca mediterránea

Resumen Introduccion La incidencia del melanoma ha aumentado mas que la de ninguna otra neoplasia maligna. Nuestro objetivo fue analizar la evolucion del melanoma cutaneo en los ultimos anos en una poblacion mediterranea. Material y metodos Los pacientes con melanoma diagnosticados entre 1988-2006 fueron incluidos en el estudio. Se comparan los datos de la primera mitad con la segunda mitad del periodo analizado. Resultados El numero de melanomas in situ paso de 36/302 casos (11,92 %) en la primera mitad del periodo a 224/724 (30,94 %) en la segunda. Los melanomas mayores de 4 mm pasaron de 29/302 casos (9,60 %) a 62/724 (8,56 %). La media de la profundidad maxima fue 1,91 mm y se mantuvo estable a lo largo del periodo. Conclusiones El aumento de incidencia del melanoma en nuestra poblacion se debe mayoritariamente al incremento de casos incipientes. Sin embargo, se mantiene estable la proporcion de melanomas mayores de 4 mm, y en numeros absolutos se ha duplicado el numero anual de melanomas con estas dimensiones. Consideramos que hay que seguir insistiendo en campanas de prevencion y deteccion precoz, especialmente dirigidas a la poblacion de mayor edad.

Calcinosis cutis following liver transplantation: a complication of intravenous calcium administration

Calcinosis cutis may be a complication of administration of intravenous calcium solutions. We report four patients who developed calcinosis cutis following orthotopic liver transplantation, all of whom had received calcium chloride solutions intravenously during surgery. There was no evidence of extravasation of the solutions. A gradual improvement of the lesions was seen in the subsequent months.

Kaposi‐like acroangiodermatitis induced by a suction‐socket prosthesis

concerning the incidence of skin cancer in the North Humberside area of England. The authors found that the age-standardized incidence of basal cell carcinoma per 100.000 population in 1978 was 38-8 among men and 37-1 among women. For 1991. the corresponding iigures were 115-6 and 103-7 for men and women, respectively. This corresponds to an increaseof 14% per year for males, and 12% per year for females. The authors also found an equal male/ female ratio (1:1). These findings correlate well with the results of our study** on the incidence of basal cell carcinoma in the Stockholm area. In 1971. the age-standardized incidence was 20-8 for men and 18-3 for women. In 1980 the corresponding figures were 48-8 and 44-4, respectively. The age-standardized incidence rate of basal cell carcinoma during the 10-year period between 1971 and 1980 increased 14% for men and 10% for women, annually. Overall, it increased 12% annually. We found no difference in the male/ female ratio, which was equal. The study was conducted in an area of Stockholm with a population of about 320,000. and a well-known migratory pattern. The steep Increase in the incidence of basal cell carcinoma in the years 1971-80 which we found in our study is in accordance with the findings of Ko ft ((/. concerning the change in the incidence of skin cancer between 1978 and 1991. Thus, it seems to be a true change in the incidence of basal cell carcinoma in Europe, and the reported iigures point to an alarming development in the near future. We can only agree with Ko et al. that skin cancer is a major health problem, and that the incidence of skin cancer is an important public health matter, which represents a challenge in preventive medicine.

Metastatic uveal melanoma: is there a role for conventional chemotherapy? - A single center study based on 58 patients.

Uveal melanoma metastases develop in 6.5–35% of patients, most commonly to the liver. Metastatic uveal melanoma (MUM) survival is poor, with 5–7 months of median survival. We reviewed retrospectively all patients with MUM diagnosed between January 1990 and December 2008 at our institution. We analyzed a total of 58 patients with a median age of 61 years (31–84 years). Median time for metastases development was 25.63 months (0.17–102.43 months). Fifty-six patients had hepatic involvement, 63.8% bilobar and 51.7% had more than or equal to five hepatic metastatic lesions. Sixteen patients (27.6%) had two or more organs involved. Six patients (10.71%) were treated with surgery, 25 patients (44.67%) received systemic chemotherapy, and 23 (41.07%) had best supportive care (BSC). The median overall survival (OS) for all the patients was 10.83 months [95% confidence interval (CI): 6.92–14.74]. Patients who had undergone chemotherapy presented 10.83 months (95% CI: 5.35–16.308) of median OS whereas the patients who did not undergo this treatment had an OS of 8.033 months (95% CI: 2.46–13.61). There were more patients with poor survival characteristics such as worse Eastern Cooperative Oncology Group performance status in the BSC group. OS was poor in treated and BSC patients. Differences in survival are more likely to be related to patient characteristics rather than to a chemotherapy effect. Patients with MUM should be included in clinical trials evaluating other options with newer agents.

Keratoacanthoma arising in hypertrophic lichen planus

Sir, We read with interest the recent report by Cox et al. on the association of atopic dermatitis with the beta subunit of the high-affinity IgE receptor (Fc1RI-b). The gene was originally identified as a candidate for atopy on human chromosome 11q. Fc1RI-b has been shown to be involved in the amplification of Fc1RI-mediated signalling that might be related to the pathogenesis of atopic disease. Because of the predominantly maternal transmission of atopy, it has been strongly suggested that the gene for Fc1RI-b may show a parent-of-origin effect such as genomic imprinting. One previous report consistent with this notion showed maternal transmission of the I181L allele in a British population, while another showed no parent-of-origin effect of the transmission of the E237G allele in an Australian population. The report by Cox et al. again raises this issue by demonstrating exclusive maternal transmission of Fc1RI-b alleles to offspring with atopic dermatitis. None the less, as far as we know, there has been no direct test of possible allele-specific expression of this gene. To study the possible involvement of a genomic imprinting mechanism, we have used the widely applicable mouse model system. We find, as detailed below, that the Fc1RI-b gene shows no parent-of-origin-specific expression, using F1 hybrids between a laboratory mouse strain (C57BL/6J) and wild mouse strains [either Mus musculus molossinus (MOLF/Ei) or M. spretus (SPRET/Ei)]. The parental mouse strains (C57BL/6J, MOLF/Ei, SPRET/ Ei) were purchased from Jackson Laboratory (Bar Harbor, ME, U.S.A.). Cloning, sequencing, total RNA extraction and reverse transcription±polymerase chain reaction (PCR) analysis of Fc1RI-b were done as described previously. Based on a human genomic DNA sequence (GenBank M89796) and a mouse cDNA sequence (GenBank J05019), we designed a PCR primer pair spanning exon 6, intron 6 and exon 7 of the Fc1RI-b gene, so that an intron could be included in the PCR target. This allowed us to measure the gene expression directly, without interference by possible contamination of genomic DNAs in RNA samples. Sequence polymorphisms among C57BL/6J, MOLF/Ei and SPRET/Ei were identified by sequencing PCR products from each strain (deposited in GenBank; accession numbers U90217±U90219). A 395-base pair (bp) fragment of the gene for Fc1RI-b was amplified from cDNAs with primers up6: 5 0-ATCCTGGCCTTTTGCAGTGC-3 0 and dn10: 5 0-TGTATGTGAAATTGTGACAC-3 0. To obtain enough DNA for analyses, a shorter fragment (361 bp) was reamplified from the PCR products with primers up6 and dn4: 5 0-GGAGTGAATGATATCCGCAA-3 0. Allele-specific expression in reciprocal crosses between C57BL/6J and MOLF/Ei was examined by using a Sau3AI restriction fragment length polymorphism (RFLP) in a 361-bp PCR product (Fig. 1A). For RFLP analysis, 3 mL of unpurified PCR products were digested with 5 U of Sau3AI in a 15-mL reaction mixture at 37 8C for 3 h, then electrophoresed in a 12% polyacrylamide gel. The gel was stained by ethidium bromide and photographed under ultraviolet radiation. Both paternally and maternally derived alleles were expressed in all examined tissues, i.e. embryo, placenta and yolk sac at 14 ́5 days postconception, whole body and skin at the newborn stage (Fig. 1B), and spleen, lung and colon in adults (not shown). The data clearly demonstrate the biallelic expression of the gene for Fc1RI-b. To confirm these data, interspecific hybrids between a laboratory mouse strain and M. spretus were used. In these crosses, the C57BL/6J-specific allele (296 bp) can be distinguished from the SPRET/Ei-specific allele (279 bp) by length