Abstract Background: The incidence and mortality of melanoma is increasing in many countries, including Brazil. Survival studies are still scarce in our country, but much needed to know and address this problem better. Objective: To analyze the disease-specific survival of patients with invasive melanoma and to correlate it with clinical and histopathological variables. Methods: Retrospective cohort analysis of 565 cases of invasive melanoma in a tertiary hospital with the objective of testing variables that could be associated with a worse prognosis, such as gender, phototype, thickness, histological type and presence of pre-existing clinical lesion at the site of the tumor. Results: The worst survival rates were significantly associated with thicker tumors (p < 0.001), male sex (p = 0.014), high phototype (p = 0.047), nodular melanoma (p = 0.024) and "de novo" lesions (p = 0.005). When all variables were adjusted for melanoma thickness, male patients (p = 0.011) and "de novo" melanomas (p = 0.025) remained associated with worse survival. Study limitations: Retrospective study of a single tertiary hospital. Conclusions: Although the causes are still unknown, melanoma-specific survival was statistically worse for males and for "de novo" melanomas even after adjustment of tumor thickness.
Abstract: The oncogenic role of high-risk HPV in anogenital, head and neck, and cervical cancer is well recognized, but not in skin cancer in the general population. Some authors have demonstrated their appearance mainly on the hands and feet, particularly in the area of the nail bed, which could be due to contamination with HPV types from anogenital regions. Here, we describe a case of genital HPV associated with SCC on the nose tip in an immunocompetent young man, which was confirmed by histopathological findings and in situ hybridization. The importance of this report is to highlight the potential role of HPV in the etiology of skin cancer in an immunocompetent individual.
Abstract: In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy. In this article, we will review the molecular bases for these new metastatic melanoma therapeutic agents cited above and also analyze new molecular discoveries in melanoma study, as Cancer-Testis antigens (CT). They are capable of induce humoral and cellular immune responses in cancer patients and because of this immunogenicity and their restrict expression in normal tissues, they are considered an ideal candidate for vaccine development against cancer. Among CT antigens, NY-ESO-1 is the best characterized in terms of expression patterns and immunogenicity. It is expressed in 20-40% of all melanomas, more in metastatic lesions than in primary ones, and it is very heterogeneous inter and intratumoral. Breslow index is associate with NY-ESO-1 expression in primary cutaneous melanomas, but its relation to patient survival remains controversial.
Abstract: BACKGROUND: Angiosarcoma is an aggressive, malignant neoplasm of vascular or lymphatic origin. Herpes virus 8 (HHV-8) is a member of the herpes family with a tropism for endothelial cells and it has been proven to induce vascular neoplasms, such as Kaposi's sarcoma. The role of HHV-8 in the pathogenesis of angiosarcoma has not been well defined. OBJECTIVE: To investigate the relationship between the presence of HHV-8 and angiosarcoma. METHODS: In this study, the team investigated the relationship between the presence of HHV-8, as determined by polymerase chain reaction, and angiosarcoma, using samples from patients with epidemic Kaposi's sarcoma as controls. RESULTS: While all control cases with epidemic Kaposi's sarcoma were positive for HHV-8, none of the angiosarcoma cases was. CONCLUSION: These findings support most previous studies that found no association between HHV-8 and angiosarcoma.
Abstract: Inflammasomes are intracellular multiprotein complexes that comprise part of the innate immune response. Since their definition, inflammasome disorders have been linked to an increasing number of diseases. Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA). Concepts from other pathologies have also been reviewed in recent years, such as psoriasis, after the recognition of a combined contribution of innate and adaptive immunity in its pathogenesis. Inflammasomes are also involved in the response to various infections, malignancies, such as melanoma, autoimmune diseases, including vitiligo and lupus erythematosus, atopic and contact dermatitis, acne, hidradenitis suppurativa, among others. Inhibition of the inflammasome pathway may be a target for future therapies, as already occurs in the handling of CAPS, through the introduction of IL-1 inhibitors. This study presents a literature review focusing on the participation of inflammasomes in skin diseases.
Abstract: Background: Knowledge of epidemiological data on skin diseases is important in planning preventive strategies in healthcare services. Objective: To assess data from patients admitted to a triage dermatology clinic. Methods: A retrospective study was performed of patients admitted over a one-year period to the Triage Dermatology Clinic at the Hospital das Clínicas of the University of São Paulo Medical School. Data were obtained from record books. The variables analyzed were: patient age, gender, dermatologic disease (initial diagnosis), origin (from where the patient was referred) and destination (where the patient was referred to). Results: A total of 16,399 patients and 17,454 diseases were identified for analysis. The most frequent skin disorders were eczema (18%), cutaneous infections (13.1%), erythematous squamous diseases (6.8%) and malignant cutaneous neoplasms (6.1%). Atopic dermatitis was the most common disease in children. Acne was more common among children and adults, as were viral warts. Basal cell carcinoma and squamous cell carcinoma were more common in the elderly. Contact dermatitis and acne predominated in women. The most frequent origins were: the primary/secondary health system (26.6%), other outpatient specialties (25.5%), emergency care (14.9%); while the destinations were: discharged (27.5%), follow-up in our Dermatology Division (24.1%), return (14.1%) and the primary/secondary health system (20.7%). Conclusion: Understanding the incidence of skin diseases is fundamental in making decisions regarding resource allocation for clinical care and research. Thus, we believe our findings can contribute to improving public health policies.
Abstract Phaeohyphomycosis is an infection caused by a filamentous fungus that contains pigment melanin in its cell wall. We report two cases caused by Exophiala sp. emphasizing the clinical variability of the disease, as well as diagnostic and therapeutic difficulties of this opportunistic infection in immunosuppressed patients (kidney transplant).
The concept of "field cancerization" was first introduced by Slaughter in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular studies support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. An important clinical implication is that fields often remain after the surgery for the primary tumor and may lead to new cancers, designated presently as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding pre-neoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed. The most important etiopathogenetic, clinical, histopathological and therapeutic aspects of field cancerization are reviewed in this article.
O conceito de campo de cancerização foi empregado, pela primeira vez, por Slaughter em 1953, estudando o tecido alterado peri-tumoral de carcinoma espinocelular, através da histopatologia. O conceito foi proposto para explicar o desenvolvimento de múltiplos tumores primários e recorrentes na mesma área onde já havia alterações histopatológicas. Os órgãos que apresentam campo de cancerização, até hoje descritos são: cavidade oral, orofaringe, pulmão, vulva, esôfago, cérvix uterino, pele, mama, cólon e bexiga. Os resultados obtidos a partir da biologia molecular sustentam o modelo de carcinogênese, onde um campo com células geneticamente alteradas têm papel fundamental. Uma importante implicação clínica é o fato de que campos com células mutadas geralmente permanecem após a cirurgia para a remoção de um tumor primário, podendo originar novos tumores, designados como segundo tumor primário ou recorrência local, dependendo do local exato e do intervalo entre a cirurgia e a detecção deste novo tumor. O desenvolvimento de campos com células mutadas é considerado uma etapa crítica na carcinogênese, com importante repercussão clínica. Assim, o diagnóstico e tratamento das lesões malignas epiteliais deve abordar não somente o tumor isolado mas sim, todo o campo onde se desenvolveu. Neste artigo, revisamos aspectos importantes da etiopatogenia, clínica, histopatologia e da terapêutica do campo de cancerização.
BACKGROUND: The objective of this study was to estimate the prevalence of depression and anxiety disorders in hospitalized patients at the dermatology ward at a university hospital in São Paulo, Brazil. OBJECTIVE: To assess the prevalence of mood and anxiety disorders in hospitalized patients at the dermatology ward at a university hospital in São Paulo. METHOD: A total of 75 patients, men and women, aged between 18 and 76 years, took part in the research. The study employed a descriptive, cross sectional and correlational method. The data was collected by means of a social demographic questionnaire and the PRIME-MD. RESULTS: It was found that 45.3 percent of the subjects presented with depressive symptoms, and 52 percent presented with symptoms of anxiety and that this survey showed moderate and high significant correlations (p<0,01; r= 0,616) for depression and anxiety. CONCLUSION: These facts could evidence the relationship between physical and psyche, just as the literature presents.
FUNDAMENTOS: O presente estudo teve como objetivo verificar a freqüência de depressão e ansiedade em pacientes internados na Divisão da Clínica de Dermatologia de um hospital universitário de São Paulo. OBJETIVO: Avaliar a prevalência de depressão e ansiedade em pacientes hospitalizados na enfermaria da clínica de dermatologia de um hospital universitário em São Paulo. MÉTODO: Participaram da pesquisa 75 sujeitos, homens e mulheres, entre 18 e 76 anos. O delineamento do estudo foi transversal e descritivo. Os instrumentos utilizados foram Entrevista Sócio Demográfica e PRIME-MD. RESULTADOS: Identificou-se a presença de depressão em 45,3% e de ansiedade em 52% dos pacientes avaliados. CONCLUSÃO: Verificou-se correlação moderada e altamente significativa (p<0,01; r =0,616) para os índices de depressão e ansiedade, que pode evidenciar a relação entre adoecimento físico e psíquico muito encontrada na literatura.
OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and squamous cell carcinomas indicate the presence of a spectrum of malignant progression.
INTRODUCTION: Dermatology is primarily an outpatient specialty, but it also plays an important role in the care of inpatients. METHODS: We conducted a prospective study that recorded data from inpatient dermatology consultation request forms over a period of four months. The study evaluated 313 requests that led to 566 visits, 86 biopsies, 35 laboratory exams, 41 direct microscopic studies, 18 direct immunofluorescence analyses, 14 skin cultures and a few other exams. RESULTS: The most frequent requesting service was internal medicine (24%), followed by neurology (12%), cardiology (11%), infectious diseases and pediatrics (8% each) and psychiatry and general surgery (6% each). The most frequent diagnostic groups were infectious diseases (25%, divided into fungal infections (13%), bacterial infections (7%) and viral infections (5%)), eczemas (15%) and drug reactions (14%). To our knowledge, this is the first study to attempt to evaluate the impact of the consultations by asking multiple-choice questions that were analyzed by the authors. In 31% of the cases, the consultation was considered extremely relevant because it aided in managing the disease that led to admission or treated a potentially severe dermatological disease. In 58% of the cases, the consultation was considered important because it facilitated diagnosis and/or treatment of a dermatological disease that was unrelated to the reason for admission.
Photodynamic therapy involves the administration of a photosensitizing drug and its subsequent activation by light at wavelengths matching the absorption spectrum of the photosensitizer. Currently, topical photodynamic therapy has received approval for the treatment of cutaneous oncologic conditions such as actinic keratoses, Bowen’s disease and superficial basal cell carcinoma in many countries in the world. Multicenter randomized controlled studies have demonstrated high efficacy and superior cosmetic outcome over standard therapies. For many non-oncologic dermatological diseases such as acne vulgaris, viral warts and localized scleroderma, case reports and small series have confirmed the potential of photodynamic therapy. After the development of topical photosensitizers 5-aminolevulinic acid (ALA) or its methyl ester (MAL), photodynamic therapy has gained worldwide popularity in dermatology, as these drugs do not induce prolonged phototoxicity as the systemic photosensitizing hematoporphyrin derivatives do. The production of reactive oxygen intermediates such as singlet oxygen depends on the concentration and localization of the photosensitizer in the diseased tissue as well as the applied light dose. Either incoherent lamps or LED arrays are suitable for the cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving inflammatory condition.
A terapia fotodinâmica envolve a administração de uma droga fotossensibilizante e sua ativação subsequente pela luz de comprimento de onda correspondente ao espectro de absorção do fotossensibilizador. Atualmente, a terapia fotodinâmica tópica é aprovada para o tratamento de condições oncológicas cutâneas como queratoses actínicas, doença de Bowen e carcinoma basocelular superficial em diversos países do mundo. Estudos multicêntricos controlados e randomizados demonstram a alta eficácia e resultado cosmético final superior dessa modalidade terapêutica em relação aos tratamentos convencionais. Para condições cutâneas não oncológicas, como acne vulgar, verrugas virais e esclerodermia localizada, há também relatos e série de casos confirmando o potencial terapêutico da terapia fotodinâmica. O desenvolvimento de fotossensibilizantes tópicos, ácido 5-aminolevulínico (ALA) ou seu metiléster (MAL), frente aos derivados da hematoporfirina de aplicação sistêmica, permitiu um grande avanço na popularidade da TFD na dermatologia, uma vez que tanto ALA quanto MAL tópicos não induzem mais fotossensibilidade generalizada prolongada. A produção de intermediários reativos de oxigênio, como oxigênio singlet, depende da concentração, da localização do fotossensibilizante no tecido alvo, assim como da dose de luz utilizada. Tanto as lâmpadas de amplo espectro quanto os LEDs (do inglês light emitting diodes) constituem fontes de luz adequadas para que os efeitos citotóxicos da terapia fotodinâmica resultem na destruição do tumor ou seus efeitos imunomodulatórios atuem melhorando as condições inflamatórias cutâneas.
INTRODUCTION: There are various approaches to the treatment of cutaneous tumors; one of them is treatment with imiquimod, a synthetic toll-like receptor agonist with a low molecular weight that offers a topical, noninvasive, and non-surgical therapeutic option. The main objective of our study was to provide data on 89 patients who used a 5% imiquimod cream for the treatment of cutaneous tumors at the Cutaneous Oncology Group of the Dermatology Department of Hospital das Clinicas from 2003 to 2008. MATERIALS AND METHODS: Here, we present our experience in the treatment of 123 cutaneous tumors of various types, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease, erythroplasia of Queyrat, Paget's disease, and trichoepithelioma, with 5% imiquimod cream from 2003 to 2008 in the Cutaneous Oncology Group of the Dermatology Department of Hospital das Clinicas. Patients were divided into two separate groups according to their diagnosis and comorbidities; these comorbidities included epidermodysplasia verruciformis, xeroderma pigmentosum, albinism, basal cell nevus syndrome, Brooke-Spiegler syndrome, HIV, chronic lymphocytic leukemia, B-cell lymphoma, and kidney transplantation. Treatment duration, response to imiquimod, follow-up, recurrence, and local and systemic reactions associated with use of the drug were analyzed. Epidemiological data were obtained and cure rates were calculated. RESULTS: The ratio of women to men was 1.28:1, and the mean age was 63.1 years. Tumors were located mainly on the face, back, trunk, and legs. For patients with comorbidities, the overall cure rate was 38%. These specific patients demonstrated cure rates of 83.5% for superficial BCC and 50% for Bowen's disease. Aggressive BCC and superficial and nodular BCC did not present a good response to treatment. Trichoepitheliomas and nodular BCC showed a partial response, and erythroplasia of Queyrat showed a complete response. For patients without comorbidities, the overall cure rate was 73%. For these patients, the cure rates were 85.7% for superficial and nodular BCC, 88% for superficial BCC, 57% for Bowen's disease, 50% for nodular BCC, and 50% for aggressive BCC. One SCC lesion demonstrated a complete response, and tumors caused by Paget's disease and erythroplasia of Queyrat presented a partial response. None of the tumors considered as clinically cured recurred. Thirty-seven lesions demonstrated no response to imiquimod. Having a cutaneous comorbidity, high-risk tumors such as mixed aggressive BCC (sclerodermiform or micronodular), nodular BCC, or Bowen's disease, and presenting no local reaction to imiquimod were considered as risk factors for a worse prognosis. We demonstrate that patients with no response to imiquimod, even when they demonstrated no local reaction, can undergo another cycle of six weeks of imiquimod treatment and show a complete response. The healing pattern led to good cosmetic outcomes, and the side effects were tolerable. CONCLUSIONS: Our experience confirms imiquimod as an effective treatment option for several types of cutaneous tumors, especially in patients without the cutaneous comorbidities cited above and with low-risk tumors. Imiquimod has a relatively low cost compared to other therapeutic options and can be delivered via ambulatory care to patients with surgery contraindications, and its side effects are tolerable.