Melanoma: tumor microenvironment and new treatments.

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.

Inflammasomes and dermatology.

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.

Profile of patients admitted to a triage dermatology clinic at a tertiary hospital in São Paulo, Brazil.

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.

Angiosarcoma in HIV-negative patients is not associated with HHV-8.

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.

Epidermodysplasia verruciformis associated with myelodysplastic syndrome: an intriguing association.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by massive infection with human papillomaviruses (HPVs) and development of skin cancer. Myelodysplastic syndromes (MDSs) are a group of chronic conditions that involve dysplastic hematopoiesis, peripheral blood cytopenias, and a high incidence of progression into leukemia. METHODS: We describe the intriguing association of these two premalignant conditions (EV and MDS) in one patient. These diagnoses were confirmed by histopathologic examination and cytogenetic abnormalities of bone marrow cells. RESULTS: The patient presented initially with clinical features typical of EV and impairment of cell-mediated immunity. In the skin lesions, HPVs 23 and 25 were identified by nested polymerase chain reaction. Six years later, he had recurrent episodes of mucosal bleeding with fever, weakness, and fatigue. At this time, severe refractory anemia and neutropenia were observed, and bone marrow smears showed hypercellularity with abnormal dysplastic megakaryocytes. The cytogenetic pattern showed abnormalities involving trisomy of chromosomes 8 and 21. The patient received a diagnosis of the indolent subtype of MDS. CONCLUSIONS: Through the observation of our patient and review of the literature, we hypothesized that the pathomechanisms, including the role of oncogenes and cytokines, are connected to the progression to malignancy in these settings.

Pioderma gangrenoso: revisión de 29 casos clínicos / Pyoderma gangrenosum: a review of 29 patients

Una revisión de 29 pacientes con diagnóstico de Pioderma Gangrenoso es analizado en cuanto a la clínica, forma de presentación, asociaciones, respuesta al tratamiento y recaidas, entre otros; comparándolo finalmente con lo reportado en la literatura (AU)