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El carcinoma epidermoide cutaneo (CEC) o espinocelular, el segundo en frecuencia de los carcinomas queratinociticos, puede producirse de novo o derivar de precursores. El queratoacantoma comparte con el carcinoma epidermoide una histogenesis y una epidemiologia comunes, pero se caracteriza por la capacidad de involucionar de forma espontanea. Los principales factores causales son la exposicion cronica a los rayos ultravioletas para las lesiones cutaneas y los virus del papiloma humano (VPH) para las lesiones de las zonas anogenitales. La mayoria de los carcinomas espinocelulares no compromete el pronostico vital, pero este carcinoma esta dotado de un potencial metastasico responsable de la mayoria de las muertes imputables a los canceres cutaneos, con excepcion del melanoma. La clasificacion tumor-ganglios-metastasis (TNM) de estos canceres no tiene en cuenta la mayoria de los criterios pronosticos citados en las publicaciones. Una clasificacion pronostica reciente incorpora estos criterios, pero todavia falta perfeccionarla. El tratamiento de eleccion es la cirugia, con margenes de exeresis definidos en funcion del pronostico. La radioterapia externa y la braquiterapia intersticial se pueden utilizar si la cirugia esta contraindicada. La prevencion primaria se basa en la identificacion de las personas de riesgo, la comunicacion reiterada sobre las medidas de proteccion y la educacion para la autoexploracion. La prevencion del cancer del cuello uterino con las vacunas anti-VPH deberia influir en la incidencia de los carcinomas epidermoides genitales y sus precursores. La prevencion secundaria de los CEC y sus precursores consiste en el control de las personas de riesgo, la identificacion y el tratamiento de las lesiones sospechosas.

Resume Introduction L’angiome en touffe et l’hemangioendotheliome kaposiforme sont deux tumeurs vasculaires rares, benignes mais agressives decrites essentiellement chez l’enfant. Observation Un homme de 72 ans avait depuis 10 ans une tumeur vasculaire de l’epaule droite qui augmentait de taille progressivement et atteignait, lors de la consultation, 50 cm de grand axe. L’examen histologique montrait que cette tumeur vasculaire associait par place des aspects d’angiome en touffe et d’hemangioendotheliome kaposiforme. Discussion La tumeur chez ce malade etait atypique par sa taille tres importante et jusqu’alors jamais decrite. L’association histologique d’aspects pouvant relever a la fois d’un angiome en touffe et d’un hemangioendotheliome kaposiforme va dans le sens des publications recentes qui tendent a reunir ces deux lesions et a en faire des stades evolutifs d’une meme entite.

To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life.

The management of patients presenting with metastatic malignant melanoma (MM) is hampered by the substantial variability in survival of these patients and the lack of prognostic markers. In the search for a reliable predictive parameter, we have investigated the expression of the nm23 gene, considered to be a major regulator of the metastatic process. We have analysed by Northern blot the nm23 mRNA level in tumour tissue obtained from metastases of 20 stage II and ten stage III patients with MM. Normal human tissues and benign naevi were simultaneously examined. The level of nm23 expression was highly heterogeneous in MM metastases, with a mean value which was higher than the mean level in normal tissues and naevi. Correlative study was focused on the overall survival following resection of the metastasis in which nm23 Northern blot analysis was performed. Patients displaying higher nm23 expression in metastatic tissue (above the mean level) tended to have a longer survival than others (P = 0.08), and this difference was significant for patients presenting with isolated regional lymph node involvement (P = 0.035). The time from biopsy of the primary MM to the appearance of the first lymph node metastasis also showed a positive correlation with the nm23 mRNA level in this metastasis. The present study is not only in accordance with previous reports showing that the nm23 gene may be implicated in MM progression, but also suggests the reliable value of nm23 expression as a prognostic marker for patients presenting with metastatic MM. Images Figure 1

One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.

A case of extensive skin necrosis following intramuscular injections of sisomycin is described. Eight cases of necrosis following subcutaneous injections of aminoside antibiotics have been reported in elderly females under anticoagulant therapy, but the pathogenic mechanisms of these lesions have not been investigated. Defective fibrinolysis and abnormalities of oxidative metabolism of neutrophils were noted in our patient. Four major mechanisms are discussed: an Arthus reaction, a thrombotic process, a direct toxicity of aminosides for subcutaneous tissue, or a pyoderma-like neutrophilic reaction. Subjects with a tendency to thrombosis and/or abnormalities of neutrophil functions may be predisposed to these skin necroses.

Tufted angioma and kaposiform hemangioendothelioma are two rare benign but aggressive vascular tumours that occur mainly in children.A 72 year-old man consulted for a 50 cm wide vascular tumour of the right shoulder which was increasing for 10 years. On histological examination there were features of tufted angioma and kaposiform hemangioendothelioma.The tumour of this patient was atypical because of its big size never described before. The histological association of aspects which could correspond to tufted angioma and kaposiform hemangioendothelioma seems to confirm recent publications which support the hypothesis that these two tumours are two evolutive stages of one and only entity.

Only ablative methods lead to long term remission of areas affected by Hailey-Hailey disease: excision/skin graft, cryosurgery, dermabrasion... The method using the CO2 laser is a recent addition in the management of this dermatitis. We report our experience with this technique in 4 patients.Carbon dioxide laser vaporization was proposed to 4 patients exhibiting Hailey-Hailey disease resistant to classical treatments. A test under local anesthesia was performed beforehand in all the patients. A 60 year-old man had an immediate reaction and refused to continue treatment. In the other 3 cases, the result of the test at 6 months was considered satisfactory. These patients were treated under general anesthesia in a single area of 50 to 70 cm2, and a half-body for comparison. The CO2 laser was used in pulse mode, with successive irradiations, until a homogenous, whitish-yellow aspect with first retraction was obtained.Although the healing delays were long (a mean of 1 month) and required major analgesics over the first few days, the cosmetic results were satisfactory and no abnormal scarring was observed. After a median follow-up of 27 months, no relapse of the disease other than punctiform elements was noted. All the patients wanted treatment of the other remaining affected areas be continued. In 2 patients, CO2 laser vaporization permitted treatment of areas not easily accessible to other ablative methods (around the mouth, the anus and the vulva) with anatomy and normal function spared.These results are globally good. Although the time to healing was long, the cosmetic and functional results were always satisfactory, without abnormal scarring. Moreover, in 2 of the patients, CO2 laser was able to treat areas inaccessible to other methods. The reason for the efficacy of ablative methods is debated. Re-epidermization with keratinocytes of appendices and not expressing the molecular defect, and the constitution of dermal cicatricial tissue, are two currently proposed hypotheses.

We describe a previously unreported complication after anterior surgery of the cervical spine for melanoma. Ten days after the surgical procedure, a 51-year-old man presented a huge cystic cervical metastasis along the surgical route. The pathophysiology and the surgical risk of the procedure are discussed.

Using the trial demonstrating that interferonα-2a (IFNα-2a) is efficacious as adjuvant therapy in stage II melanoma, we evaluate its outcomes and economic consequences. Using rates observed in the 5-year trial and published figures, survival and Q-TWIST (Time Without Symptoms and Toxicity) were extrapolated to a 10-year and lifetime horizon. Cost analysis was performed using the trial's data, published literature and experts' opinions from the perspective of the French Sickness Funds. Patients in the IFNα-2a-group have an additional 0.26 years in life-expectancy over a 5-year time period ( P =0.046), 0.67 years over a 10-year period and 2.59 years over a lifetime. Cost per life-year-gained was estimated at approximately 14 400 after 5 years, 6635 after 10 years and 1716 over a lifetime. Assuming that there is an improvement in disease-free survival only, cost is 26 147 per Q-TWIST. Cost-effectiveness of IFNα-2a in stage II melanoma compares favourably with estimates for widely used therapies in the oncological field.

Angioneurotic edema (AE) is a rare but severe disease. Hereditary AE is the more well-known form. The acquired form is exceptional: the symptoms are the same but there are some biologic and treatment differences. We investigated the clinical and biochemical features in nine patients with acquired angioneurotic edema (AAE).Four of the patients with type I AAE presented an accelerated metabolism of C1Inh, associated with a hematology disease. Their C4, C1q and C1Inh plasma levels were low. Four patients had type II AAE associated with an autoantibody to C1Inh. Their C1Inh plasma levels were normal or low but the functional levels were low in all four. One patient had AAE induced by oral contraceptives. The C1Inh plasma level was normal but the functional level was very low; there were no autoantibodies. Symptoms resolved when oral contraceptives were withdrawn and the C1Inh level returned to normal.Treatment of AAE is a difficult matter. For type I AAE, it consists in treating the associated disease. For type II AAE, the treatment goal is to lower the autoantibody level. Management of these diseases requires close collaboration between clinicians and biologists.

In this report we describe a case of bowenoid papulosis (BP) on the face of a 44 year old Algerian man. To our knowledge this is the first reported case of isolated extragenital BP. The presence of type 16 human papilloma virus was demonstrated by in situ hybridisation. This case underscores that multiple HPV-induced severe intraepithelial neoplasia, the so-called BP, is not restricted to the anogenital area.

Quality of life (QoL) assessment is crucial to assess the severity of dermatological diseases.To construct and validate the first dermatology-specific instrument in French.Items were generated from the interview of patients. The final self-administered questionnaire, the VQ-Dermato, included 28 questions. Validity in terms of content and construct, reliability in terms of reproducibility and internal consistency, responsiveness and acceptability were tested in a population of 231 patients with 12 categories of chronic skin disorders, who were recruited and followed in hospital and private practice in France.Item analysis revealed that discrimination indices were high. After factor analysis, 7 dimensions were retained, which accounted for 72% of the total variance. Cronbach's alpha coefficient ranged between 0. 67 and 0.88. A strong correlation was found between dimensions of the VQ-Dermato and the corresponding dimensions of the SF36. Scores were significantly different in each category of chronic skin disease and significantly higher when there was a function restriction or when the lesions were visible to others. The scale was proven to be stable by test-retest correlation. The VQ-Dermato was more responsive to clinical improvement after a 1- or 2-month treatment than the SF36. The percentage of missing responses was under 10 and the time for completing the questionnaire always under 13 min.The VQ-Dermato is the first valid and reliable dermatology-specific QoL instrument in French, and the first based on the concept of 'chronic skin disorders'. It is acceptable for routine use and has a better responsiveness than a general health instrument.

To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life.

Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with low doses of interferon alpha could be effective in patients with localised melanoma.After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval.499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon alpha-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life.Adjuvant therapy of high-risk melanoma with low doses of interferon alpha-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop.

The aim of this double-blind, placebo-controlled, randomized, cross-over pilot study was to assess the antiinflammatory properties of cetirizine. A group of 27 patients with a positive patch test to an allergen consecutively received cetirizine 10 mg o.d. or placebo during a 14-day period, respectively. At day 11 of each period, patch testing was performed with the allergen. The image analysis showed a skin reaction significantly reduced under cetirizine (p = 0.03), but the clinical recording and the standardized chromatometry did not show any difference between groups. In the cross-over analysis the results of image analysis were influenced by the period, but this effect disappeared after adjustment of the ambient temperature during the 3 days of the test. These results demonstrate that cetirizine has an impact on the inflammatory process in a clinical model of cell-mediated allergic reaction, although this effect is only detected with a very sensitive technique. They also show that it is useless to stop antihistamines before patch testing, since clinical evaluation of tests is not hampered by a potent antihistamine. Additionally this study suggests that ambient temperature has an influence on the results of tests.

Melanoma is theoretically an ideal model for prevention campaigns. However a detailed analysis of this model shows that we do not yet have reliable tools to identify the high risk population and that prevention campaigns have a limited impact. However, any campaign which can increase the notoriety of melanoma in the public can probably improve early diagnosis. Detailed evaluation of messages and cost-effectiveness ratio of campaigns is needed.

Fibroblast growth factor 2 (FGF2) has been implicated in the pathogenesis of malignant melanoma (MM), but the role of other FGFs and their receptors (FGFRs) is not elucidated. To determine whether FGF1 and FGFR1 may be involved in MM growth in vivo, we have studied the expression of the FGF1 and FGFR1 genes in 77 fresh MM biopsy samples, using RT-PCR analysis. Samples of benign nevi, normal skin and carcinoma cell lines were included as controls. Using RT-PCR analysis, expression of FGF1 and FGFR1 was observed in 69/77 and 68/77 cases, respectively. Immunohistochemical detection of the FGFR1 protein was positive in reactive stromal cells and at a much lower level in neoplastic cells. In situ hybridization experiments demonstrated FGFR1 mRNA mainly located in the stromal component. Southern blot analysis of genomic DNA prepared from MM tumors did not show any structural alteration of the FGFR1 gene. There was no correlation between FGF1/FGFR1 expression and the usual clinicopathological parameters of MM. We conclude that FGF1 and FGFR1 are frequently co-expressed in MM, a situation that may contribute to aberrant autocrine and paracrine pathways. Due to the absence of correlation with clinico-pathological parameters, this expression cannot be used as a marker of prognosis in the management of MM patients.

The principal causative agent of cat scratch disease (CSD) is Bartonella henselae, and the natural host of the bacteria is the domestic cat, with the bacteria located in erythrocytes (6). Another species, B. clarridgeiae, can be isolated from the blood of healthy cats, and based on serological evidence, this species has been associated with CSD in humans (3). A newly described species, B. koehlerae, was recovered for the first time in the United States during a prevalence study of Bartonella sp. bacteremia in domestic cats (2). It is not known whether this new Bartonella species can infect humans.

Cysts and canals found on the ventral surface of the penis have been ascribed to minor dysembryoplasia of the male genitalia. These lesions occur almost exclusively on the ventral surface of the penis along the median raphe and can extend from the urethral meatus to the anus. They are lined by stratified urothelium or squamous epithelium and they do not communicate with the urethra. Most cases are noted in early adulthood, they are usually asymptomatic but may become infected. Surgical removal is the adapted treatment. In this report we describe a case in which the urothelial origin of the cyst was documented by immunohistochemistry for cytokeratin 13.

These studies were designed to assess the influence of sun exposure on nevi in white people. To eliminate the confounding effect of age, sex, and phenotype, two parallel studies were conducted on people of the same age (17 to 24 years; median, 20 years old), sex (male), and phenotype: one in people with "red" phenotype (red or red-blond hair, white complexion on the inner part of the arm, and inability to tan) and one in people with "dark" phenotype (brown or black hair, dark complexion on the inner part of the arm, absence of freckles, and easy tanning without burning).In both groups, comparison of nevus counts on the inner and outer side of the upper extremities and comparison of mean density of nevi (number per square meter) in always-exposed and never-exposed skin show that the number of nevi is higher in sun-exposed areas. The density of large and atypical nevi was maximal on intermittently sun-exposed skin while the density of small nevi was maximal on always-exposed skin. The number of large nevi on intermittently exposed skin correlated with cumulative intensive exposure during beach recreation in the red phenotype group. The number of large nevi was significantly higher in red phenotypes who repeatedly experienced severe sunburns in their first 20 years of life.The number of nevi at the end of the second decade is influenced by cumulative sun exposure from birth. "Traumatizing" sun exposure, which is more frequent in the red phenotype than in the dark phenotype, has an influence on the number of large nevi and is therefore likely to make small nevi grow.

Genetically, Klinefelter's syndrome is characterized by a super-numerary chromosome X in male subjects presenting with clinical and biochemical hypoandrogenism and relative hyperoestrogenism. The association of Klinefelter's syndrome with chronic leg ulcer has given rise to numerous publications. The cause of the trophic disorders is unclear. We report two cases of this syndrome associated with chronic leg ulcers and anomalies of haemostasis. One of these two patients had platelet hyperaggregability followed by disorders of fibrinolysis, while the other had disorders of fibrinolysis. We reviewed the literature concerning the various aetiopathogenic hypotheses put forward to explain the cause of these leg ulcers, as well as their interactions and relationship with the hormonal anomalies. The position occupied by disorders of haemostasis is particularly developed.

Small erythematous or cyanotic lesions on the hands and feet of four patients with antiphospholipid antibodies are described. These discrete lesions outline capillaries and do not disappear when pressure is applied. The histologic features are identical to those described in skin thrombotic syndrome associated with antiphospholipid antibodies, that is, microthrombi in dermal vessels without inflammation. In addition to indicating antiphospholipid antibodies in apparently healthy patients, this sign could be a marker of risk for large-vessel thrombosis.

A study of 207 consecutive white patients older than 18 years of age with nonfamilial nodular and superficial spreading melanoma and 295 controls was conducted in southeast France. Controls were recruited in a public health center. They were matched for sex and age to the overall population older than 18 years of age according to the last census. Melanocytic nevi were counted over the entire body, and data on sun exposure and skin type were collected. A multiple logistic model was used to determine the variables best predicting the risk of melanoma. In order of entry into the model, these variables were number of nevi from 5 to less than 10 mm (N5/10), outdoor leisure per year, frequency of sunburn in the last years, depth of suntan, number of nevi less than 5 mm in diameter (N1/5), age, social level, and hair color. Nevi counts were shown to be indispensable to the construction of a good predictive model for nonfamilial melanoma. After adjustment, estimated relative risks for nonfamilial melanoma rose with increasing number of N1/5, N5/10, and clinically atypical nevi (CAN) on the whole body. Compared with baseline groups the presence of more than 120 N1/5 was associated with a RR of 19.6, the presence of at least five N5/10 with a RR of 10, and the presence of more than one CAN with a RR of 2.77. The number of nevi on the buttocks seemed to be a strong risk factor of melanoma and may provide a simple technique for mass screening. The association between CAN and nonfamilial melanoma could be explained largely by the association between this tumor and the number of large nevi (greater than or equal to 5 mm). It is suggested that when using number of nevi as risk markers, their size might be more important than the other features of clinical atypia. Phenotypic traits and sun exposure, on the one hand, and number of nevi, on the other, seem to be independent risk factors. On the basis of nevus count alone, high-risk subgroups can be identified, which represent only a small part of the overall population older than 18 years of age and from which a large proportion nonfamilial melanoma would theoretically derive.

Local anesthesia for ambulatory phlebectomy makes it necessary to inject a considerable quantity of lidocaine. This study involved 50 operations. The doses of lidocaine containing 1% adrenaline and injected after cooling (between 2 and 5 degrees C) ranged from 200 mg to nearly 900 mg in a single administration. The assays of lidocaine in the peripheral venous blood were carried out by means of F.P.I.A. (Fluorescence Polarization Immuno Assay) at times 0, 30 min 60 min, 90 min., 24 hours and 48 hours. The peak concentration obtained (1.8 micrograms/ml) for a dose of 700 mg in a subject weighting 65 kg, i.e. 10.9 mg/kg, was only one-half the concentration considered to be neurologically toxic (4 to 12 micrograms/ml) or one-twelfth of the toxic levels with regard to the cardiovascular system (24 micrograms/ml). The performance of local anesthesia in the physician's office is devoid of major risks, even though the doses used during AP are much higher than those usually administered in routine dematological surgery.

Fifty patients suffering from histologically proven metastatic melanoma were treated with a combination of DTIC (400 mg/m2 i.v. every 28 days) and recombinant alpha 2A interferon (Roferon-A) 10 x 10(6) U/m2 daily, administered intramuscularly or subcutaneously for 2 months followed by 7 x 10(6) U/m2 3 times a week. Treatment was carried out for a period of 12 months unless progressive disease was noted after 3 months. Among the 49 evaluable patients, 6 achieved a complete response (CR) and 4 a partial response (PR) (response rate, 20%) at 2 months, 8 CR and 3 PR (25%) and 8 CR and 2 PR (23%; 95% confidence limits, 13-40%) occurred at month 6 and 12 respectively These responses occurred notably in patients with cutaneous (3 cases) or lymph node metastases (4 cases), but 3 responses included visceral sites: lung (1 CR), liver (1CR and 1PR). Average response duration was 16.5 months (range 4-29 + months). The time required for objective response can be up to 6 months, which suggest that treatment should receive a reasonable trial period (at least 3 months). Clinical toxicity consisted mainly of a flu-like syndrome, anorexia and fever, and occurred in more than 50% of patients; hematologic and hepatic toxicities required a dose reduction in 54% of patients but in only one case did treatment have to be terminated because of this. Seventeen (35%) of the patients are still alive, 4 with metastases (follow-up period: 18-34 + months) and 13 without metastases (follow-up period: 13-32 + months). A combined regimen of r-IFN alpha 2A and dacarbazine is effective in treating patients with metastatic melanoma, with acceptable toxicities and a reasonable quality of life (out-patient treatment or district nurse care). The objective response rate (23% at 12 months) compares favourably with those of earlier trials using the same combination of drugs, and occurred not only in cutaneous and lymph node metastases but also in visceral metastases.