Maladie de Rosai-Dorfman cutanée pure (étude rétrospective de six cas)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Infection cutanée à scedosporium apiospermum au cours d'un traitement par anti-TNF alpha

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Posaconazole (une alternative thérapeutique dans la prise en charge des mucormycoses?)

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A case report of Muir-Torre syndrome in a woman with breast cancer and MSI-Low skin squamous cell carcinoma.

IF 1.590International audienceBackground: The tumor spectrum in the Lynch syndrome is well defined, comprising an increased risk of developing colonic and extracolonic malignancies. Muir-Torre syndrome is a variant with a higher risk of skin disease. Patients have been described carrying mutations in the mismatch repair genes and presenting tumors with unusual histology or affected organ not part of the Lynch syndrome spectrum. Hence, the real link between Lynch syndrome, or Muir-Torre syndrome, and these tumors remains difficult to assess.Case presentation: We present the case of a 45-year-old-woman, diagnosed with breast cancer at 39 years of age and skin squamous cell carcinoma (SCC) at 41 years of age, without personal history of colorectal cancer. The microsatellite instability analysis performed on the skin SCC showed a low-level of microsatellite instability (MSI-Low). The immunohistochemical expression analysis of the four DNA mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 showed a partial loss of the expression of MSH2 and MSH6 proteins. Germline deletion was found in MSH2 gene (c.1277-? _ 1661 + ?del), exon 8 to 10. Then, at 45 years of age, she presented hyperplastic polyps of the colon and a sebaceous adenoma.Conclusion: Squamous cell carcinomas have been described in Lynch syndrome and Muir- Torre syndrome in two studies and two case reports. This new case further supports a possible relationship between Lynch syndrome and squamous cell carcinoma

Clinical and Sociodemographic Characteristics Associated With Thick Melanomas: A Population-Based, Case-Case Study in France.

International audienceOBJECTIVE To identify clinical and sociodemographic factors associated with very thick melanoma (VTM) (Breslow thickness, ≥3 mm) in France. DESIGN Retrospective, population-based, case-case study using a survey of cancer registries and questionnaires to practitioners. SETTING Five regions covering 19.2% of the French territory and 8.2 million inhabitants. CASES Cases included all incident melanomas with a Breslow thickness of 3 mm or greater (ie, VTM), diagnosed between January 1 and December 31, 2008, in residents of the study area (Alsace, Bourgogne, Champagne-Ardenne, Franche-Comté, and Lorraine, France), and a randomly selected sample of melanomas thinner than 3 mm. MAIN OUTCOME MEASURES Circumstances of diagnosis, clinical and pathological characteristics of melanomas, and sociodemographic characteristics of patients (age, sex, residence, home and family life conditions, educational level, and smoking habits). RESULTS Among 898 melanomas, 149 (16.6%) were VTMs. Very thick melanomas were more often diagnosed in a general-practice setting than thinner melanomas. The rate of immediate clinical recognition by dermatologists was lower for VTMs than for thinner melanomas. In a multivariate logistic regression analysis, factors associated with VTM were the nodular and acrolentiginous types; the head and neck and lower limb locations; older age; male sex; and being single, separated, divorced, or widowed. When only factors related to patients were taken into account, older age, male sex, and living alone were independent risk factors for VTM. The most significant risk was observed for patients living alone. CONCLUSIONS Intrinsic factors related to the tumor and sociodemographic characteristics of patients contribute to the occurrence of VTM. These factors should be better targeted in future secondary prevention programs

French updated recommendations in Stage I to III melanoma treatment and management.

As knowledge continues to develop, regular updates are necessary concerning recommendations for practice. The recommendations for the management of melanoma stages I to III were drawn up in 2005. At the request of the Société Française de Dermatologie, they have now been updated using the methodology for recommendations proposed by the Haute Autorité de Santé in France. In practice, the principal recommendations are as follows: for staging, it is recommended that the 7th edition of AJCC be used. The maximum excision margins have been reduced to 2 cm. Regarding adjuvant therapy, the place of interferon has been reduced and no validated emerging medication has yet been identified. Radiotherapy may be considered for patients in Stage III at high risk of relapse. The sentinel lymph node technique remains an option. Initial examination includes routine ultrasound as of Stage II, with other examinations being optional in stages IIC and III. A shorter strict follow-up period (3 years) is recommended for patients, but with greater emphasis on imaging

Antibodies for flow cytometry analysis.

<p>PerCP: Peridinin chlorophyll; PE: Phycoerythrin; Cy7: Cyanine-7.</p><p>Antibodies for flow cytometry analysis.</p

BRAF inhibitor resistance of melanoma cells triggers increased susceptibility to natural killer cell-mediated lysis

Background Targeted therapies and immunotherapies are first-line treatments for patients with advanced melanoma. Serine–threonine protein kinase B-RAF (BRAF) and mitogen-activated protein kinase (MEK) inhibition leads to a 70% response rate in patients with advanced melanoma with a BRAFV600E/K mutation. However, acquired resistance occurs in the majority of patients, leading to relapse. Immunotherapies that activate immune cytotoxic effectors induce long-lasting responses in 30% of patients. In that context, combination of targeted therapies with immunotherapy (IT) is a promising approach. We considered boosting natural killer (NK) cell tumor immunosurveillance, as melanoma cells express stress-induced molecules and activate NK cell lysis.Methods Here we have generated vemurafenib (a BRAF inihibitor)-resistant (R) cells from BRAFV600E SK28 and M14-sensitive (S) melanoma cell lines and investigated how resistance interferes with immunogenicity to NK cells. We determined the levels of several soluble molecules including NK ligands in 61 melanoma patients at baseline and 6 months M post-treatment with targeted therapies or immunotherapies.Results Vemurafenib resistance involved activation of p-AKT in SK28R and of p-MEK/p-ERK in M14R cells and was accompanied by modulation of NK ligands. Compared with S cells, SK28R displayed an increased expression of natural killer group 2 D (NKG2D) receptor ligands (major histocompatibility complex class (MHC) I chain-related protein A (MICA) and UL16-binding protein 2 (ULBP2)) whereas M14R exhibited decreased ULBP2 . SK28R and M14R cells induced higher NK degranulation and interferon gamma secretion and were more efficiently lysed by donor and patient NK cells. SK28R showed increased tumor necrosis factor-related apoptosis-inducing ligand receptor II (TRAIL-RII) expression and TRAIL-induced apoptosis, and TRAIL-induced apoptosis of M14R was decreased. Combined BRAF/MEK inhibitors abrogated the growth of SK28S, M14S, and M14R cells, while growth of SK28R was maintained. BRAF/MEK inhibition attenuated NK activity but R cell lines activated polyfunctional NK cells and were lysed with high efficiency. We investigated the relationship of soluble NK ligands and response to treatment in a series of melanoma patients. Soluble NKG2D ligands known to regulate the receptor function have been associated to cancer progression. Serum analysis of patients treated with target therapies or IT indicates that soluble forms of NK ligands (MICA, B7H6, programmed cell death ligand 1, and carcinoembryonic antigen cell adhesion molecule 1) may correlate with clinical response.Conclusion These results support strategies combining targeted therapies and NK-based immunotherapies