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Melanoma: HELP
Articles by Arnaud de la Fouchardiere
Based on 43 articles published since 2010
(Why 43 articles?)
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Between 2010 and 2020, A. De La Fouchardière wrote the following 43 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline French updated recommendations in Stage I to III melanoma treatment and management. 2017

Guillot, B / Dalac, S / Denis, M G / Dupuy, A / Emile, J F / De La Fouchardiere, A / Hindie, E / Jouary, T / Lassau, N / Mirabel, X / Piperno Neumann, S / De Raucourt, S / Vanwijck, R. ·Dermatology Department, CHU Montpellier. · Dermatology Department, CHU Dijon. · Laboratory of Biochemistry, CHU Nantes. · Dermatology Department, CHU Rennes. · Laboratory of Pathology, AP-HP Ambroise Paré Hospital, Boulogne, France. · Laboratory of Pathology, Centre Léon Bérard Lyon. · Department of Nuclear medicine, CHU Bordeaux. · Dermatology Department, CH Pau. · Department of Radiology, Institut Gustave Roussy Villejuif. · Department of Radiotherapy, Centre Oscar Lambret Lille. · Institut Curie, Paris, France. · 1 Avenue du 6 Juin, 1945, 14000 Caen, France. · Louvain Catholic University, Brussels, Belgium. ·J Eur Acad Dermatol Venereol · Pubmed #28120528.

ABSTRACT: 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.

2 Guideline [Update to the recommendations for management of melanoma stages I to III]. 2016

Guillot, B / Dalac, S / Denis, M G / Dupuy, A / Emile, J-F / De La Fouchardière, A / Hindie, E / Jouary, T / Lassau, N / Mirabel, X / Piperno Neumann, S / De Raucourt, S / Vanwijck, R. ·Département de dermatologie, hôpital Saint-Éloi, CHU de Montpellier, 34295 Montpellier cedex 5, France. Electronic address: b-guillot@chu-montpellier.fr. · Service de dermatologie, hôpital du Bocage sud, CHU de Dijon, BP 1542, 21079 Dijon cedex, France. · Laboratoire de biochimie, institut de biologie, 9, quai Moncousu, 44093 Nantes cedex, France. · Service de dermatologie, CHU de Rennes, Rennes, France. · Service d'anatomie pathologique, CHU Ambroise-Paré-Boulogne, 92104 Boulogne cedex, France. · Centre anticancéreux Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. · Service de médecine nucléire Sud et Pellegrin, CHU de Bordeaux, Bordeaux, France. · Service de médecine, centre hospitalier de Pau, 64000 Pau, France. · Service d'imagerie médicale, institut Gustave-Roussy, 94800 Villejuif, France. · Centre Oscar-Lambret, 3, rue Fréderic-Combemale, 59000 Lille, France. · Institut Curie, 26, rue d'Ulm, 75005 Paris, France. · 1, avenue du 6-Juin, 14000 Caen, France. · Université catholique de Louvain, 10, avenue Hippocrate, 1200 Bruxelles, Belgique. ·Ann Dermatol Venereol · Pubmed #27527567.

ABSTRACT: 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 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 2cm. 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 (3years) is recommended for patients, but with greater emphasis on imaging.

3 Guideline [Guidelines for stage I to III melanoma]. 2016

Guillot, Bernard / Dalac, Sophie / Denis, Marc / Dupuy, Alain / Emile, Jean François / De La Fouchardiere, Arnaud / Hindie, Elif / Jouary, Thomas / Lassau, Nathalie / Mirabel, Xavier / Piperno Neumann, Sophie / De Raucourt, Sixtine / Vanwijck, Romain. ·Département de dermatologie, hôpital Saint-Eloi, CHU de Montpellier, 34295 Montpellier cedex 5, France. Electronic address: b-guillot@chu-montpellier.fr. · Service de dermatologie, hôpital du Bocage sud, CHU de Dijon, BP 1542, 21079 Dijon cedex, France. · Laboratoire de biochimie, institut de biologie, 9, quai Moncousu, 44093 Nantes cedex, France. · Service de dermatologie, CHU de Rennes, Rennes, France. · Service d'anatomie pathologique, CHU Ambroise-Paré Boulogne, 92104 Boulogne cedex, France. · Centre anticancéreux Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. · Service de médecine nucléire sud et pellegrin, CHU de Bordeaux, Bordeaux, France. · Service de médecine, CH de Pau, 64000 Pau, France. · Service d'imagerie médicale, institut Gustave-Roussy, 94800 Villejuif, France. · Centre Oscar-Lambret, 3, rue Fréderic-Combemale, 59000 Lille, France. · Institut Curie, 26, rue d'Ulm, 75005 Paris, France. · Sixtine, 1, avenue du 6 juin, 14000 Caen, France. · Université catholique de Louvain, avenue Hippocrate, 10 B-1200 Bruxelles, Belgique. ·Bull Cancer · Pubmed #27456259.

ABSTRACT: -- No abstract --

4 Review Unclassified sclerosing malignant melanomas with AKAP9-BRAF gene fusion: a report of two cases and review of BRAF fusions in melanocytic tumors. 2018

Perron, Emilie / Pissaloux, Daniel / Neub, Angela / Hohl, Daniel / Tartar, Marie Dominique / Mortier, Laurent / Alberti, Laurent / de la Fouchardiere, Arnaud. ·Département de Biopathologie, Centre Leon Bérard, Lyon, France. emilie.perron.1@ulaval.ca. · Département de Biologie médicale, Service d'anatomopathologie, Centre hospitalier universitaire de Québec-Université Laval, 11 Côte du Palais, Québec, QC, G1R 2J6, Canada. emilie.perron.1@ulaval.ca. · Département de Biologie Moléculaire, de Biochimie Médicale et de Pathologie, Faculté de Médecine de l'Université Laval, Québec, Canada. emilie.perron.1@ulaval.ca. · Département de Biopathologie, Centre Leon Bérard, Lyon, France. · Service de Dermatologie et Vénérologie, Centre hospitalier universitaire vaudois (CHUV), Lausanne, Switzerland. · Service de Pathologie, Hôpital Jean Bernard, Valenciennes, France. · Service de Dermatologie, Université de Lille, INSERM U 1189, CHU Lille, F-59000, Lille, France. ·Virchows Arch · Pubmed #29464327.

ABSTRACT: The current classification of melanocytic tumors includes clinical, pathological, and molecular data. A subset of lesions remains difficult to classify according to these complex multilayer schemes. We report two cases of deeply infiltrating melanomas with a sclerosing background. The first case occurred on the back of a middle-aged man appearing clinically as a dermatofibroma. The architectural and cytological aspects resembled those of a desmoplastic melanoma but the strong expression of both melanA and HMB45, two stainings usually reported as negative in this entity, raised the question of an alternate diagnosis. The second case was a large, slowly growing, perivulvar tumor in a middle-aged woman. The morphology was complex with a central junctional spitzoid pattern associating an epidermal hyperplasia with large nests of large spindled melanocytes. The dermal component was made of deeply invasive strands and nests of nevoid unpigmented melanocytes surrounded by fibrosis; a perineural invasion was present at the periphery of the lesion. In both cases, aCGH found, among many other anomalies, a chromosomal breakpoint at the BRAF locus. RNA sequencing identified in both an AKAP9-BRAF gene fusion. A complementary resection was performed and no relapses have been observed in the respectively 15 and 6 months of follow-up. Both of these melanomas remained unclassified. We further review the variety of melanocytic tumors associated with such BRAF fusions.

5 Review [Gallbladder metastasis of melanoma: Immunohistochemical and molecular data of a case and review of the literature]. 2017

Tauziède-Espariat, Arnault / Raffoul, Johnny / Sun, Shan-Rong / Monnin, Christine / de la Fouchardière, Arnaud / Lassabe, Catherine. ·Service d'anatomie et cytologie pathologiques, centre hospitalier Belfort-Montbéliard, 2, rue du Docteur-Flamand, 25200 Montbéliard, France. Electronic address: arnault.tauziedeespariat@gmail.com. · Service d'anatomie et cytologie pathologiques, centre hospitalier Belfort-Montbéliard, 2, rue du Docteur-Flamand, 25200 Montbéliard, France. · Département de biopathologie, centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. ·Ann Pathol · Pubmed #29153887.

ABSTRACT: We report the case of a 57-year-old man, who is hospitalized for the surgery of a gallbladder mass associated by an increase in fluorodeoxyglucose-activity on positron emission tomography/computed tomography scan. This is an incidental finding occurring during monitoring of a skin melanoma. A cholecystectomy is performed. Microscopic examination identified an infiltration of the gallbladder wall by a proliferation of atypical pigmented spindled melanocytes with numerous mitoses. The immunohistochemical analysis confirmed the melanocytic nature of this proliferation with the staining of HMB-45, S100 protein and Melan-A. A complementary immunohistochemical (p16, desmin and BRAFV600E) and molecular (BRAF sequencing) study is performed. The results are consistent with the hypothesis of a gallbladder metastasis of a cutaneous melanoma is proposed. Gallbladder metastases of melanoma are exceptional. The aim of our work is to describe a new case with immunohistochemical and molecular characterization, to review the literature on this topic and to consider the main differential diagnosis (primary malignant melanoma of the gallbladder).

6 Review [Cutaneous melanocytic tumors. Case 4]. 2016

de la Fouchardière, Arnaud. ·Département de biopathologie, centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. Electronic address: arnaud.delafouchardiere@lyon.unicancer.fr. ·Ann Pathol · Pubmed #27641820.

ABSTRACT: -- No abstract --

7 Article CRTC1-TRIM11 fusion defined melanocytic tumors: A series of four cases. 2019

Ko, Jennifer S / Wang, Lin / Billings, Steven D / Pissaloux, Daniel / Tirode, Franck / Berry, Ryan / De La Fouchardiere, Arnaud. ·Department of Pathology, Cleveland Clinic, Cleveland, Ohio. · Department of Pathobiology, Centre Léon Bérard, Lyon, France. · Univ Lyon, Université Claude Bernard Lyon 1, Research Cancer Center of Lyon, Lyon, France. ·J Cutan Pathol · Pubmed #31237704.

ABSTRACT: A cutaneous melanocytic tumor with morphologic overlap with clear cell sarcoma, but defined by CRTC1-TRIM11 gene fusion, was recently described in a series of five adult patients. Here, we expand the clinicopathologic features of this entity by four additional cases which include pediatric presentation, exophytic growth, and propensity to occur on the head. Patients (2F; 2M) had a median age of 41 years (range 11-59). Sites of involvement included leg, ear, and face. Tumors were circumscribed, unencapsulated, mostly limited to the dermis, and varied from 5 to 35 mm. One case was exophytic. Lesional cells were arranged in nests and fascicles, and were monomorphic and fusiform with moderate pale to clear cytoplasm, occasional nuclear pseudo-inclusions, and small to prominent nucleoli. Mitotic rate was variable (rare to 12/10 HPF, median 3/10 HPF). The pediatric case showed increased nuclear pleomorphism, tumor necrosis, and mitotic figures. All cases showed strong, diffuse nuclear staining for SOX10, but were negative or focal for S100 protein, HMB45 and Melan-A expression. Cases were positive by FISH technique and/or RNA sequencing for a TRIM11 rearrangement/fusion, and negative for EWSR1 rearrangement. This series is presented to aid in further characterization of this novel melanocytic tumor.

8 Article Filigree-like Rete Ridges, Lobulated Nests, Rosette-like Structures, and Exaggerated Maturation Characterize Spitz Tumors With NTRK1 Fusion. 2019

Yeh, Iwei / Busam, Klaus J / McCalmont, Timothy H / LeBoit, Philip E / Pissaloux, Daniel / Alberti, Laurent / de la Fouchardière, Arnaud / Bastian, Boris C. ·Departments of Dermatology and Pathology, UCSF, San Francisco, CA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Biopathology, Centre Léon Bérard. · INSERM, Léon Bérard Center, Cancer Research Center of Lyon, University of Lyon, Claude Bernard University, Lyon, France. ·Am J Surg Pathol · Pubmed #30844834.

ABSTRACT: Activating NTRK1 fusions have been described as oncogenic events across the spectrum of Spitz tumors. Herein we report a series of 38 Spitz tumors with NTRK1 fusion. These Spitz tumors have distinctive histopathologic features characterized by filigree-like rete ridges which are elongated, thin and branched, dermal melanocytes arranged in a rosette-like configuration, and marked diminishment of melanocyte size with descent into the dermis. These features are distinct from those of other genetically defined subtypes of Spitz tumors and can aid in microscopic diagnosis and help prioritize in case selection for molecular testing in the rare patients that need targeted therapy.

9 Article β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors. 2019

de la Fouchardière, Arnaud / Caillot, Claire / Jacquemus, Julien / Durieux, Emeline / Houlier, Aurélie / Haddad, Véronique / Pissaloux, Daniel. ·Departement de Biopathologie, Centre Léon Bérard, 28, rue Laennec, 69008, Lyon, France. arnaud.delafouchardiere@lyon.unicancer.fr. · Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Université de Lyon, Lyon, France. arnaud.delafouchardiere@lyon.unicancer.fr. · Departement de Biopathologie, Centre Léon Bérard, 28, rue Laennec, 69008, Lyon, France. · Department of Pathology, Centre Hospitalier Lyon-Sud, 69310, Lyon, France. · Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Université de Lyon, Lyon, France. ·Virchows Arch · Pubmed #30756182.

ABSTRACT: Recent advances in genomics have improved the molecular classification of cutaneous melanocytic tumors. Among them, deep penetrating nevi (DPN) and plexiform nevi have been linked to joint activation of the MAP kinase and dysregulation of the β-catenin pathways. Immunohistochemical studies have confirmed cytoplasmic and nuclear expression of β-catenin and its downstream effector cyclin D1 in these tumors. We assessed nuclear β-catenin immunohistochemical expression in a large group of DPN as well as in the four most frequent differential diagnoses of DPN: "blue" melanocytic tumors, Spitz tumors, nevoid and SSM melanomas, and pigmented epithelioid melanocytomas (PEM). Nuclear β-catenin expression was positive in 98/100 DPN and 2/16 of melanomas (one SSM and one nevoid melanoma with a plexiform clone) and was negative in all 30 Spitz, 26 blue, and 6 PEM lesions. In 41% DPN, β-catenin expression was positive in more than 30% nuclei. No differences were observed in cytoplasmic and nuclear cyclin D1 expression between these tumor groups, suggesting alternate, β-catenin-independent, activation pathways. We have subsequently studied nuclear β-catenin expression in a set of 13 tumors with an ambiguous diagnosis, for which DPN was part of the differential diagnosis. The three out of four patients showing canonical DPN mutation profiles were the only β-catenin-positive cases. We conclude that nuclear β-catenin expression, independently from CCND1 expression, in a dermal melanocytic tumor is an argument for its classification as DPN. In ambiguous cases and in early combined DPN lesions, this antibody can be helpful as a screening tool. β-Catenin is also potentially expressed in a subset of malignant melanomas with CTNNB1 mutations.

10 Article Tspan8-β-catenin positive feedback loop promotes melanoma invasion. 2019

El Kharbili, Manale / Agaësse, Gweltaz / Barbollat-Boutrand, Laetitia / Pommier, Roxane M / de la Fouchardière, Arnaud / Larue, Lionel / Caramel, Julie / Puisieux, Alain / Berthier-Vergnes, Odile / Masse, Ingrid. ·Université de Lyon, F-69003, Lyon, France. · Université Lyon 1, Lyon, F-69003, France. · CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, F-69622, France. · Department of Dermatology, University of Colorado Anschutz Medical Campus, 12800 E. 19th Avenue, P18-8132, Aurora, CO, 80045, USA. · Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université de Lyon, Université Lyon 1, 69000, Lyon, France. · Département de Biopathologie, Centre Leon Bérard, Lyon, France. · Institut Curie, PSL Research University, INSERM U1021, Normal and Pathological Development of Melanocytes, Orsay, France. · Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France. · Equipe Labellisée Ligue Contre le Cancer, Orsay, France. · Université de Lyon, F-69003, Lyon, France. ingrid.masse@univ-lyon1.fr. · Université Lyon 1, Lyon, F-69003, France. ingrid.masse@univ-lyon1.fr. · CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, F-69622, France. ingrid.masse@univ-lyon1.fr. · Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université de Lyon, Université Lyon 1, 69000, Lyon, France. ingrid.masse@univ-lyon1.fr. ·Oncogene · Pubmed #30679790.

ABSTRACT: Due to its high proclivity to metastasize, and despite the recent development of targeted and immune therapy strategies, melanoma is still the deadliest form of skin cancer. Therefore, understanding the molecular mechanisms underlying melanoma invasion remains crucial. We previously characterized Tspan8 for its ability to prompt melanoma cell detachment from their microenvironment and trigger melanoma cell invasiveness, but the signaling events by which Tspan8 regulates the invasion process still remain unknown. Here, we demonstrated that β-catenin stabilization is a molecular signal subsequent to the onset of Tspan8 expression, and that, in turn, β-catenin triggers the direct transcriptional activation of Tspan8 expression, leading to melanoma invasion. Moreover, we showed that β-catenin activation systematically correlates with a high expression of Tspan8 protein in melanoma lesions from transgenic Nras; bcat* mice, as well as in deep penetrating naevi, a type of human pre-melanoma neoplasm characterized by a combined activation of β-catenin and MAP kinase signaling. Overall, our data suggest that β-catenin and Tspan8 are part of a positive feedback loop, which sustains a high Tspan8 expression level, conferring to melanoma cells the invasive properties required for tumor progression and dissemination.

11 Article Clinical and dermoscopic features of cutaneous BAP1-inactivated melanocytic tumors: Results of a multicenter case-control study by the International Dermoscopy Society. 2019

Yélamos, Oriol / Navarrete-Dechent, Cristián / Marchetti, Michael A / Rogers, Tova / Apalla, Zoe / Bahadoran, Philippe / Blázquez-Sánchez, Nuria / Busam, Klaus / Carrera, Cristina / Dusza, Stephen W / de la Fouchardière, Arnaud / Ferrara, Gerardo / Gerami, Pedram / Kittler, Harald / Lallas, Aimilios / Malvehy, Josep / Millán-Cayetano, José F / Nelson, Kelly C / Quan, Victor Li / Puig, Susana / Stevens, Howard / Thomas, Luc / Marghoob, Ashfaq A. ·Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Dermatology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, and CIBER de Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain. Electronic address: oyelamos@gmail.com. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Dermatology, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · First Department of Dermatology, Aristotle University, Thessaloniki, Greece. · Dermatology Department, Centre Hospitalier Universitaire de Nice, Nice, France. · Dermatology Department, Hospital Costa del Sol, Marbella, Spain. · Pathology Department, Memorial Sloan Kettering Cancer Center, New York, New York. · Dermatology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, and CIBER de Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain. · Département de Biopathologie, Centre Léon Bérard, Lyon, France. · Anatomic Pathology Unit, Hospital of Macerata, Macerata, Italy. · Dermatology Department, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. · Dermatology Department, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Skin Care Network, Barnet, London, United Kingdom. · Department of Dermatology, Lyon 1 University, Centre Hospitalier Lyon Sud and Lyon's Cancer Research Center INSERM U1052 - CNRS UMR5286, Lyon, France. ·J Am Acad Dermatol · Pubmed #30244062.

ABSTRACT: BACKGROUND: Multiple BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) have been associated with a familial cancer syndrome involving germline mutations in BAP1. OBJECTIVES: We sought to describe the clinical and dermoscopic features of BIMTs. METHODS: This was a retrospective, multicenter, case-control study. Participating centers contributed clinical data, dermoscopic images, and histopathologic data of biopsy-proven BIMTs. We compared the dermoscopic features between BIMTs and control patients. RESULTS: The dataset consisted of 48 BIMTs from 31 patients (22 women; median age 37 years) and 80 control patients. Eleven patients had a BAP1 germline mutation. Clinically, most BIMTs presented as pink, dome-shaped papules (n = 24). Dermoscopically, we identified 5 patterns: structureless pink-to-tan with irregular eccentric dots/globules (n = 14, 29.8%); structureless pink-to-tan with peripheral vessels (n = 10, 21.3%); structureless pink-to-tan (n = 7, 14.9%); a network with raised, structureless, pink-to-tan areas (n = 7, 14.9%); and globular pattern (n = 4, 8.5%). The structureless with eccentric dots/globules pattern and network with raised structureless areas pattern were only identified in BIMT and were more common in patients with BAP1 germline mutations (P < .0001 and P = .001, respectively). LIMITATIONS: Limitations included our small sample size, retrospective design, the absence of germline genetic testing in all patients, and inclusion bias toward more atypical-looking BIMTs. CONCLUSIONS: Dome-shaped papules with pink-to-tan structureless areas and peripheral irregular dots/globules or network should raise the clinical suspicion for BIMT.

12 Article Primary malignant melanoma of the esophagus, treated with immunotherapy: a case report. 2018

Rochefort, Pauline / Roussel, Juliette / de la Fouchardière, Arnaud / Sarabi, Matthieu / Desseigne, Françoise / Guibert, Pierre / Cattey-Javouhey, Anne / Mastier, Charles / Neidhardt-Berard, Eve-Marie / de la Fouchardière, Christelle. ·Department of Medical Oncology, Centre Leon Berard, Claude Bernard University, Lyon, France. · Department of Biopathology, Centre Leon Berard, Claude Bernard University, Lyon, France. · Departement of Radiology, Centre Leon Berard, Claude Bernard University, Lyon, France. ·Immunotherapy · Pubmed #30073896.

ABSTRACT: Primary malignant melanoma of the esophagus is rare, accounting for less than 0.1-0.2% of all esophageal malignancies. It is associated with a poor outcome due to late detection and high metastatic potential. Here, we report a case of esophageal cancer, which was initially diagnosed as an adenocarcinoma and finally was confirmed as a primary malignant melanoma. This 75-year-old Caucasian male had a history of dysphagia and recent lingering abdominal pain. First biopsy showed a poorly-differentiated adenocarcinoma. He was then treated with neoadjuvant radiochemotherapy. Biopsies were repeated because of an incomplete tumor response, evaluated by endoscopic and imaging studies. The final diagnosis was a malignant melanoma. The patient has been treated with immune-checkpoint inhibitor, nivolumab, an anti-PD1 antibody.

13 Article Expression of the serotonin receptor 2B in uveal melanoma and effects of an antagonist on cell lines. 2018

Weidmann, Cindy / Bérubé, Julie / Piquet, Léo / de la Fouchardière, Arnaud / Landreville, Solange. ·Axe Médecine régénératrice and Centre Universitaire d'Ophtalmologie (CUO)-Recherche, Centre de recherche du CHU de Québec, Quebec City, QC, Canada. · Centre de recherche sur le cancer de l'Université Laval, Quebec City, QC, Canada. · Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Quebec City, QC, Canada. · Département d'ophtalmologie, Faculté de médecine, Université Laval, Quebec City, QC, Canada. · Département de biopathologie, Centre Léon Bérard, Lyon, France. · Axe Médecine régénératrice and Centre Universitaire d'Ophtalmologie (CUO)-Recherche, Centre de recherche du CHU de Québec, Quebec City, QC, Canada. Solange.Landreville@fmed.ulaval.ca. · Centre de recherche sur le cancer de l'Université Laval, Quebec City, QC, Canada. Solange.Landreville@fmed.ulaval.ca. · Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Quebec City, QC, Canada. Solange.Landreville@fmed.ulaval.ca. · Département d'ophtalmologie, Faculté de médecine, Université Laval, Quebec City, QC, Canada. Solange.Landreville@fmed.ulaval.ca. ·Clin Exp Metastasis · Pubmed #29696577.

ABSTRACT: Uveal melanoma (UM) is the most common primary tumor in the adult, and disseminates to the liver in half of patients. A 15-gene expression profile prognostic assay allows to determine the likelihood of metastasis in patients using their ocular tumor DNA, but a cure still remains to be discovered. The serotonin receptor 2B represents the discriminant gene of this molecular signature with the greatest impact on the prognosis of UM. However, its contribution to the metastatic potential of UM remains unexplored. The purpose of this study was to investigate the effects of a selective serotonin receptor 2B antagonist on cellular and molecular behaviours of UM cells. UM cell lines expressing high level of serotonin receptor 2B proteins were selected by Western blotting. The selective serotonin receptor 2B antagonist PRX-08066 was evaluated for its impact on UM cells using viability assays, phosphorylated histone H3 immunostainings, clonogenic assays, migration assays, invasion assays and membrane-based protein kinase phosphorylation antibody arrays. The pharmacological inhibition of the serotonin receptor 2B reduced the viability of UM cells and the population in mitosis, and impaired their clonogenicity and potential of migration. It also decreased the phosphorylation of kinases from signaling pathways classically activated by the serotonin receptor 2B, as well as kinases β-catenin, Proline-rich tyrosine kinase 2, and Signal transducer and activator of transcription 5. Our findings support a role for the serotonin receptor 2B in the proliferation and migration of UM cells, through activation of many signaling pathways such as WNT, Focal adhesion kinase and Janus kinase/STAT.

14 Article Atypical cutaneous melanocytic tumours arising in two patients with Li-Fraumeni syndrome. 2017

Jacquemus, Julien / Perron, Emilie / Pissaloux, Daniel / Alberti, Laurent / de la Fouchardière, Arnaud. ·Département of Biopathology, Centre Leon Bérard, Lyon, France. · Département of Biopathology, Centre Leon Bérard, Lyon, France; Service d'anatomopathologie, Centre Hospitalier Universitaire de Québec-Université Laval, Canada; Département de Biologie Moléculaire, de Biochimie Médicale et de Pathologie, Faculté de Médecine, Université Laval, Québec, Canada. · Département of Biopathology, Centre Leon Bérard, Lyon, France. Electronic address: arnaud.delafouchardiere@lyon.unicancer.fr. ·Pathology · Pubmed #29108654.

ABSTRACT: -- No abstract --

15 Article Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi. 2017

Yeh, Iwei / Lang, Ursula E / Durieux, Emeline / Tee, Meng Kian / Jorapur, Aparna / Shain, A Hunter / Haddad, Veronique / Pissaloux, Daniel / Chen, Xu / Cerroni, Lorenzo / Judson, Robert L / LeBoit, Philip E / McCalmont, Timothy H / Bastian, Boris C / de la Fouchardière, Arnaud. ·Department of Dermatology, University of California, San Francisco, 94143, CA, USA. Iwei.Yeh@ucsf.edu. · Department of Pathology, University of California, San Francisco, 94143, CA, USA. Iwei.Yeh@ucsf.edu. · Department of Pathology, University of California, San Francisco, 94143, CA, USA. · Department of Pathology, Centre Hospitalier Lyon-Sud, Lyon, 69310, France. · Department of Dermatology, University of California, San Francisco, 94143, CA, USA. · Department of Biopathology, Centre Léon Bérard, Lyon, 69008, France. · Department of Dermatology, Medical University of Graz, Graz, 8036, Austria. ·Nat Commun · Pubmed #28935960.

ABSTRACT: Deep penetrating nevus (DPN) is characterized by enlarged, pigmented melanocytes that extend through the dermis. DPN can be difficult to distinguish from melanoma but rarely displays aggressive biological behavior. Here, we identify a combination of mutations of the β-catenin and mitogen-activated protein kinase pathways as characteristic of DPN. Mutations of the β-catenin pathway change the phenotype of a common nevus with BRAF mutation into that of DPN, with increased pigmentation, cell volume and nuclear cyclin D1 levels. Our results suggest that constitutive β-catenin pathway activation promotes tumorigenesis by overriding dependencies on the microenvironment that constrain proliferation of common nevi. In melanoma that arose from DPN we find additional oncogenic alterations. We identify DPN as an intermediate stage in the step-wise progression from nevus to melanoma. In summary, we delineate specific genetic alterations and their sequential order, information that can assist in the diagnostic classification and grading of these distinctive neoplasms.Deep penetrating nevi (DPN) are unusual melanocytic neoplasms with unknown genetic drivers. Here the authors show that majority of DPN harbor activating mutations in the β-catenin and the MAP-kinase pathways; this characteristic can help in the classification and grading of these distinctive neoplasms.

16 Article Tetraspanin 8 is a novel regulator of ILK-driven β1 integrin adhesion and signaling in invasive melanoma cells. 2017

El Kharbili, Manale / Robert, Clément / Witkowski, Tiffany / Danty-Berger, Emmanuelle / Barbollat-Boutrand, Laetitia / Masse, Ingrid / Gadot, Nicolas / de la Fouchardière, Arnaud / McDonald, Paul C / Dedhar, Shoukat / Le Naour, François / Degoul, Françoise / Berthier-Vergnes, Odile. ·Université de Lyon, Lyon, France. · Université Lyon 1, Lyon, France. · CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaire et Cellulaire, Villeurbanne, France. · Current address: Department of Dermatology, University of Colorado, Aurora, Colorado, USA. · Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, Clermont-Ferrand, France. · Inserm, U990, Clermont-Ferrand, France. · Laboratoire CarMeN (INSERM 1060, INRA1397, INSA), Université Lyon 1, Lyon, France. · Université Lyon 1, Fédération de Recherche Santé Lyon-Est, ANIPATH, Faculté Laennec, Lyon, France. · Département de Biopathologie, Centre Léon Bérard, Lyon, France. · Department of Integrative Oncology, British Columbia Cancer Research Center, Vancouver, Canada. · INSERM U602, Villejuif, France. · Current address: INSERM U1193, Hôpital Paul Brousse, Villejuif, France. ·Oncotarget · Pubmed #28188308.

ABSTRACT: Melanoma is well known for its propensity for lethal metastasis and resistance to most current therapies. Tumor progression and drug resistance depend to a large extent on the interplay between tumor cells and the surrounding matrix. We previously identified Tetraspanin 8 (Tspan8) as a critical mediator of melanoma invasion, whose expression is absent in healthy skin. The present study investigated whether Tspan8 may influence cell-matrix anchorage and regulate downstream molecular pathways leading to an aggressive behavior. Using silencing and ectopic expression strategies, we showed that Tspan8-mediated invasion of melanoma cells resulted from defects in cell-matrix anchorage by interacting with β1 integrins and by interfering with their clustering, without affecting their surface or global expression levels. These effects were associated with impaired phosphorylation of integrin-linked kinase (ILK) and its downstream target Akt-S473, but not FAK. Specific blockade of Akt or ILK activity strongly affected cell-matrix adhesion. Moreover, expression of a dominant-negative form of ILK reduced β1 integrin clustering and cell-matrix adhesion. Finally, we observed a tumor-promoting effect of Tspan8 in vivo and a mutually exclusive expression pattern between Tspan8 and phosphorylated ILK in melanoma xenografts and human melanocytic lesions. Altogether, the in vitro, in vivo and in situ data highlight a novel regulatory role for Tspan8 in melanoma progression by modulating cell-matrix interactions through β1 integrin-ILK axis and establish Tspan8 as a negative regulator of ILK activity. These findings emphasize the importance of targeting Tspan8 as a means of switching from low- to firm-adhesive states, mandatory to prevent tumor dissemination.

17 Article A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8-mediated melanoma invasion. 2017

Agaësse, G / Barbollat-Boutrand, L / Sulpice, E / Bhajun, R / El Kharbili, M / Berthier-Vergnes, O / Degoul, F / de la Fouchardière, A / Berger, E / Voeltzel, T / Lamartine, J / Gidrol, X / Masse, I. ·Université de Lyon, Lyon, France. · Université Lyon 1, Lyon, France. · CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, France. · Université Grenoble-Alpes, Grenoble, France. · CEA, BIG-BGE, Biomics, Grenoble, France. · Inserm, BGE, Grenoble, France. · Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP, Clermont-Ferrand, France. · Inserm, U 990, Clermont-Ferrand, France. · Département de Biopathologie, Centre Léon Bérard, Lyon, France. · Laboratoire CarMeN (INSERM 1060, INRA 1397, INSA), Université de Lyon, Lyon, France. · Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université de Lyon, Université Lyon 1, Lyon, France. ·Oncogene · Pubmed #27375018.

ABSTRACT: Melanoma is the deadliest form of skin cancer owing to its proclivity to metastasise, and recently developed therapies have not yielded the expected results, because almost all patients relapse. Therefore, understanding the molecular mechanisms that underlie early invasion by melanoma cells is crucial to improving patient survival. We have previously shown that, whereas the Tetraspanin 8 protein (Tspan8) is undetectable in normal skin and benign lesions, its expression arises with the progression of melanoma and is sufficient to increase cell invasiveness. Therefore, to identify Tspan8 transcriptional regulators that could explain the onset of Tspan8 expression, thereby conferring an invasive phenotype, we performed an innovative RNA interference-based screen, which, for the first time, identified several Tspan8 repressors and activators, such as GSK3β, PTEN, IQGAP1, TPT1 and LCMR1. LCMR1 is a recently identified protein that is overexpressed in numerous carcinomas; its expression and role, however, had not previously been studied in melanoma. The present study identified Tspan8 as the first LCMR1 target that could explain its function in carcinogenesis. LCMR1 modulation was sufficient to positively regulate endogenous Tspan8 expression, with concomitant in vitro phenotypic changes such as loss of melanoma cell-matrix adherence and increase in invasion, and Tspan8 expression promoted tumourigenicity in vivo. Moreover, LCMR1 and Tspan8 overexpression were shown to correlate in melanoma lesions, and both proteins could be downregulated in vitro by vemurafenib. In conclusion, this study highlights the importance of Tspan8 and its regulators in the control of early melanoma invasion and suggests that they may be promising new therapeutic targets downstream of the RAF-MEK-ERK signalling pathway.

18 Article Effects of Long-term Serial Passaging on the Characteristics and Properties of Cell Lines Derived From Uveal Melanoma Primary Tumors. 2016

Mouriaux, Frédéric / Zaniolo, Karine / Bergeron, Marjorie-Allison / Weidmann, Cindy / De La Fouchardière, Arnaud / Fournier, Frédéric / Droit, Arnaud / Morcos, Mohib W / Landreville, Solange / Guérin, Sylvain L. ·Centre universitaire d'ophtalmologie-Recherche (CUO-Recherche), Axe médecine régénératrice, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada 2Département d'ophtalmologie, Faculté de Médecine, Université Laval, Québec, Canada 3CNRS, UMR 6301 ISTCT, CERVOxy. GIP CYCERON, Caen, France 4CHU de Rennes, Service d'Ophtalmologie, France. · Centre universitaire d'ophtalmologie-Recherche (CUO-Recherche), Axe médecine régénératrice, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada 5Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, Canada. · Département de biopathologie, Centre Léon Bérard, Lyon, France. · Département de médecine moléculaire, CHUL, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada. · Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, Canada 8Service de pathologie, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada. · Centre universitaire d'ophtalmologie-Recherche (CUO-Recherche), Axe médecine régénératrice, Hôpital du Saint-Sacrement, Centre de Recherche FRQS du CHU de Québec-Université Laval, Québec, Canada 2Département d'ophtalmologie, Faculté de Médecine, Université Laval, Québec, Canada 5Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, Canada. ·Invest Ophthalmol Vis Sci · Pubmed #27723895.

ABSTRACT: Purpose: Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). A few cell lines cultured from primary UM tumors have been used widely to investigate the pathobiology of UM. However, the translation of basic knowledge to the clinic for the treatment of the metastatic disease has remained incremental at best. In this study, we examined whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors. Methods: Gene expression profiling by microarray was performed on UM primary tumors and derived cell lines cultured at varying passages. Expression of UM protein markers was monitored by immunohistochemical analyses and Western blotting. The in vivo tumorigenic properties of UM cultures were evaluated using athymic nude mice. Results: Cell passaging severely reduced the expression of genes encoding markers typical of UM, including those of the prognostic gene signature. Marked differences between gene expression profiles of primary tumors and cell lines could be linked to the infiltrating immune and stromal cells in situ. In addition, the tumorigenic properties of UM cell lines also increased with cell passaging in culture as evaluated by their subcutaneous injection into athymic mice. Conclusions: Together, these findings demonstrate that the short-term UM primary cultures exhibit molecular features that resemble the respective surgical material and, thus, represent the best model for in vitro-assessed cancer treatments.

19 Article ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors. 2016

Richard, Geoffrey / Dalle, Stéphane / Monet, Marie-Ambre / Ligier, Maud / Boespflug, Amélie / Pommier, Roxane M / de la Fouchardière, Arnaud / Perier-Muzet, Marie / Depaepe, Lauriane / Barnault, Romain / Tondeur, Garance / Ansieau, Stéphane / Thomas, Emilie / Bertolotto, Corine / Ballotti, Robert / Mourah, Samia / Battistella, Maxime / Lebbé, Céleste / Thomas, Luc / Puisieux, Alain / Caramel, Julie. ·Cancer Research Center of Lyon, INSERM U1052, Lyon, France Cancer Research Center of Lyon, CNRS UMR 5286, Lyon, France Université de Lyon, Lyon, France ISPB Université Lyon 1, Lyon, France Centre Léon Bérard, Lyon, France. · Cancer Research Center of Lyon, INSERM U1052, Lyon, France Cancer Research Center of Lyon, CNRS UMR 5286, Lyon, France Université de Lyon, Lyon, France ISPB Université Lyon 1, Lyon, France Centre Léon Bérard, Lyon, France Dermatology Unit, Hospices Civils de Lyon CH Lyon Sud, Pierre Bénite Cedex, France. · Cancer Research Center of Lyon, INSERM U1052, Lyon, France Cancer Research Center of Lyon, CNRS UMR 5286, Lyon, France Université de Lyon, Lyon, France ISPB Université Lyon 1, Lyon, France Centre Léon Bérard, Lyon, France Department of Biopathology, Centre Léon Bérard, Lyon, France. · Department of Biopathology, Hospices Civils de Lyon CH Lyon Sud, Pierre-Bénite Cedex, France. · Fondation Synergie Lyon Cancer, Centre Léon Bérard, Lyon, France. · INSERM U1065 Equipe 1 Biologie et pathologies des mélanocytes: de la pigmentation cutanée au mélanome Equipe labellisée Ligue 2013 Centre Méditerranéen de Médecine Moléculaire, Nice, France Université de Nice Sophia-Antipolis UFR Médecine, Nice, France CHU Nice Service de Dermatologie, Nice, France. · APHP INSERM U976 Saint Louis Hospital Pharmacology-Genetic Laboratory Paris, Paris, France. · Department of Pathology, INSERM U1165 Université Paris Diderot AP-HP Hôpital Saint-Louis, Paris, France. · Department of Dermatology, APHP Saint Louis Hospital, Paris, France INSERM U976 University Paris 7 Diderot, Paris, France. · Cancer Research Center of Lyon, INSERM U1052, Lyon, France Cancer Research Center of Lyon, CNRS UMR 5286, Lyon, France Université de Lyon, Lyon, France ISPB Université Lyon 1, Lyon, France Centre Léon Bérard, Lyon, France Institut Universitaire de France, Paris, France alain.puisieux@lyon.unicancer.fr julie.caramel@lyon.unicancer.fr. · Cancer Research Center of Lyon, INSERM U1052, Lyon, France Cancer Research Center of Lyon, CNRS UMR 5286, Lyon, France Université de Lyon, Lyon, France ISPB Université Lyon 1, Lyon, France Centre Léon Bérard, Lyon, France alain.puisieux@lyon.unicancer.fr julie.caramel@lyon.unicancer.fr. ·EMBO Mol Med · Pubmed #27596438.

ABSTRACT: Targeted therapies with MAPK inhibitors (MAPKi) are faced with severe problems of resistance in BRAF-mutant melanoma. In parallel to the acquisition of genetic mutations, melanoma cells may also adapt to the drugs through phenotype switching. The ZEB1 transcription factor, a known inducer of EMT and invasiveness, is now considered as a genuine oncogenic factor required for tumor initiation, cancer cell plasticity, and drug resistance in carcinomas. Here, we show that high levels of ZEB1 expression are associated with inherent resistance to MAPKi in BRAF

20 Article Proliferative Nodules vs Melanoma Arising in Giant Congenital Melanocytic Nevi During Childhood. 2016

Vergier, Béatrice / Laharanne, Elodie / Prochazkova-Carlotti, Martina / de la Fouchardière, Arnaud / Merlio, Jean-Philippe / Kadlub, Natacha / Avril, Marie-Françoise / Bodemer, Christine / Lacoste, Caroline / Boralevi, Franck / Taieb, Alain / Ezzedine, Khaled / Fraitag, Sylvie. ·Department of Pathology and Molecular Pathology, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Pessac, France2Institut National de la Santé et de la Récherche Médicale U1053-UMR, Bordeaux Research In Translational Oncology, Bordeaux University, Bordeaux, France. · Department of Pathology, Centre Léon Bérard, Lyon, France. · Unit of Maxillofacial and Plastic Surgery, Necker-Enfants Malades Hospital, Paris, France. · Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France. · Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France6Department of Dermatology, Necker-Enfants Malades Hospital, Paris, France. · Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France7Department of Pathology, Necker-Enfants Malades Hospital, Paris, France. · Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux University, Pessac, France. ·JAMA Dermatol · Pubmed #27486690.

ABSTRACT: Importance: The differential diagnosis between proliferative nodules (PNs) and melanoma arising in congenital melanocytic nevi (CMN) is crucial, as patients with PNs most often experience no increased risk of melanoma with metastases and death. Objective: To analyze the utility of immunohistochemistry and fluorescence in situ hybridization (FISH) in distinguishing PNs from childhood and adult-onset melanoma arising in CMN. Design, Setting, and Participants: A case series was conducted from June 29, 1989, to November 12, 2009, of 13 children with PNs arising in CMN in childhood and 5 children with melanomas arising in CMN in childhood. Five patients with giant CMN with no nodules were included as negative controls, and 6 patients with melanomas arising in CMN in adulthood were included as positive controls. Follow-up ranged from 3 to 21 years in all children (mean, 9.9 years) and from 3 months to 7 years in adults. Specimens were selected for immunohistochemistry and FISH. All histopathologic sections were reviewed by 2 dermatopathologists who examined all nodules arising at different ages in the same patient and, in the case of melanoma, all locations. Data analysis was performed from January 1, 2013, to January 31, 2015. Main Outcomes and Measures: The ability to distinguish melanoma from PN using immunohistochemistry and/or FISH. Results: Of the 13 patients (5 boys and 8 girls) with PNs present at birth, all PNs were stable (mean follow-up, 9 years). Eight patients with PNs and 4 of 5 patients with childhood-onset melanoma showed homogeneous staining for HMB45, while heterogeneous staining for HMB45 was seen in 3 of 6 patients with adult-onset melanoma. Expression of p16 was strongly positive in most patients with childhood-onset PNs (10 of 11 patients) and melanoma (all patients) but negative in 4 patients with adult-onset melanoma. Patients with PNs and the 5 patients with childhood-onset melanoma had numerical chromosomal aberrations never observed in the adjacent CMN. The 2 children with FISH-positive PNs are melanoma free after 7 and 4 years. Only 1 patient with childhood-onset melanoma had a FISH aberration compared with 4 patients with adult-onset melanoma. Conclusions and Relevance: Immunohistochemistry and the 4-probe FISH melanoma analysis are not useful for distinguishing PN from childhood-onset melanoma as opposed to adult-onset melanoma. Numerical anomalies seen in PNs but not in the adjacent CMN could be the result of a chromosomal segregation malfunction resulting in the development of nodules.

21 Article Melanomas Associated With Blue Nevi or Mimicking Cellular Blue Nevi: Clinical, Pathologic, and Molecular Study of 11 Cases Displaying a High Frequency of GNA11 Mutations, BAP1 Expression Loss, and a Predilection for the Scalp. 2016

Costa, Sebastian / Byrne, Michelle / Pissaloux, Daniel / Haddad, Veronique / Paindavoine, Sandrine / Thomas, Luc / Aubin, Francois / Lesimple, Thierry / Grange, Florent / Bonniaud, Bertille / Mortier, Laurent / Mateus, Christine / Dreno, Brigitte / Balme, Brigitte / Vergier, Beatrice / de la Fouchardiere, Arnaud. ·*Department of Biopathology, Leon Berard Center, Lyon †Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia ‡Department of Dermatology, Lyon Sud Hospital Center, Pierre-Benite, CRCL and CHU of Lyon, Lyon §Department of Dermatology, CHU Besançon, Besançon ∥Department of Medical Oncology, Eugene Marquis Center, Rennes ¶Department of Dermatology, Robert Debre´ University Hospital, Reims #Department of Dermatology, CHU of Dijon, Dijon **Department of Dermatology CHRU of Lille, Lille ††Department of Dermatology, Institut Gustave Roussy, Villejuif ‡‡Department of Dermatocancerology, Hotel Dieu, Nantes §§Department of Pathology, Lyon Sud Hospital Center, Pierre-Benite ∥∥Department of Pathology, CHU of Bordeaux, Hospital Haut-Leveque, Pessac, France. ·Am J Surg Pathol · Pubmed #26645730.

ABSTRACT: Melanomas associated with blue nevi (MABN) or mimicking cellular blue nevi (MMCBN) represent exceptional variants of malignant cutaneous melanocytic tumors. Uveal and leptomeningeal melanomas frequently have somatic mutations of GNAQ or GNA11, which are believed to be early driver mutations. In uveal melanomas, monosomy 3, linked to the BAP1 gene, is an adverse prognostic factor. We have studied the clinical, histologic, BAP1 expression profile, and molecular data of 11 cases of MABN/MMCBN and 24 cellular blue nevi. Most of the cases of MABN/MMCBN occurred on the scalps of adult patients and presented as rapidly growing nodules, typically >1 cm, often arising at the site of a preexisting melanocytic lesion. The MABN/MMCBN were composed of dense nests of large dermal atypical melanocytes, in some cases lying adjacent to a blue nevus. Four patients developed metastatic disease, and 2 died from their disease. A GNA11 mutation was found in 8/11 cases and a GNAQ mutation in 1 case. Seven of 11 cases showed loss of nuclear BAP1 immunohistochemical (IHC) expression in the malignant component, sparing the adjacent nevus. Array comparative genomic hybridization revealed recurrent deletions of chromosomes 1p, 3p, 4q, 6q, 8p, 16q, and 17q and recurrent gains of chromosomes 6p, 8q, and 21q. The 24 cases of cellular blue nevi frequently occurred on the sacrum, had GNAQ mutations, and showed normal positive IHC staining for BAP1. These results underscore overlapping features in all blue-like malignant melanocytic tumors. Loss of BAP1 IHC expression was restricted to melanomas, including all metastatic cases.

22 Article Combined cutaneous tumors with a melanoma component: A clinical, histologic, and molecular study. 2015

Amin, Sapna M / Cooper, Chelsea / Yélamos, Oriol / Lee, Christina Y / Sholl, Lauren M / de la Fouchardiere, Arnaud / Guitart, Joan / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Département de Biopathologie, Centre Léon Bérard, Lyon, France. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: pgerami@nmff.org. ·J Am Acad Dermatol · Pubmed #26209219.

ABSTRACT: BACKGROUND: The histogenesis and clinical behavior of combined cutaneous tumors (CCTs) in which the mesenchymal component consists of melanoma remain unclear. OBJECTIVE: We sought to characterize the clinical, histologic, and molecular findings in CCTs with an epithelial and a melanoma component. METHODS: We retrospectively reviewed the records from 2 institutions for CCTs. Fluorescence in situ hybridization was performed to assess chromosomal copy number alterations in both components. RESULTS: Sixteen CCTs were included. The most common subtype was the squamomelanocytic tumor (11), followed by the basomelanocytic tumor (3) and the trichoblastomelanoma (2). CCTs were more common in men (87%), on the head and neck (57%), and had extensive solar elastosis (81%). The median follow-up was 25 months (range, 8-167 months). One case had an adverse outcome. Fluorescence in situ hybridization revealed chromosomal alterations in approximately 55% of the cases. Five cases showed chromosomal gains only in the melanocytic component. One case showed 11q13 gains in both the epithelial and melanocytic components. LIMITATIONS: Our study is retrospective and the sample is small. CONCLUSIONS: The low incidence of adverse outcomes suggests that CCT may be more indolent than noncombined tumors. 11q13 amplification in both components supports the theory of dual differentiation from a common progenitor cell.

23 Article Activating MET kinase rearrangements in melanoma and Spitz tumours. 2015

Yeh, Iwei / Botton, Thomas / Talevich, Eric / Shain, A Hunter / Sparatta, Alyssa J / de la Fouchardiere, Arnaud / Mully, Thaddeus W / North, Jeffrey P / Garrido, Maria C / Gagnon, Alexander / Vemula, Swapna S / McCalmont, Timothy H / LeBoit, Philip E / Bastian, Boris C. ·1] Departments of Dermatology and Pathology, and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA [2] Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA. · Département de Biopathologie, Centre Léon Bérard, 69008 Lyon, France. · Departments of Dermatology and Pathology, and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA. ·Nat Commun · Pubmed #26013381.

ABSTRACT: Oncogenic gene fusions have been identified in many cancers and many serve as biomarkers or targets for therapy. Here we identify six different melanocytic tumours with genomic rearrangements of MET fusing the kinase domain of MET in-frame to six different N-terminal partners. These tumours lack activating mutations in other established melanoma oncogenes. We functionally characterize two of the identified fusion proteins (TRIM4-MET and ZKSCAN1-MET) and find that they constitutively activate the mitogen-activated protein kinase (MAPK), phosphoinositol-3 kinase (PI3K) and phospholipase C gamma 1 (PLCγ1) pathways. The MET inhibitors cabozantinib (FDA-approved for progressive medullary thyroid cancer) and PF-04217903 block their activity at nanomolar concentrations. MET fusion kinases thus provide a potential therapeutic target for a rare subset of melanoma for which currently no targeted therapeutic options currently exist.

24 Article [Recommendations for genetic testing and management of individuals genetically at-risk of cutaneous melanoma]. 2015

Avril, M-F / Bahadoran, P / Cabaret, O / Caron, O / de la Fouchardière, A / Demenais, F / Desjardins, L / Frébourg, T / Hammel, P / Leccia, M-T / Lesueur, F / Mahé, E / Martin, L / Maubec, E / Remenieras, A / Richard, S / Robert, C / Soufir, N / Stoppa-Lyonnet, D / Thomas, L / Vabres, P / Bressac-de Paillerets, B. ·Service de dermatologie, groupe hospitalier Cochin-Saint-Vincent-de-Paul, AP-HP, pavillon Tarnier, 89, rue d'Assas, 75006 Paris, France. · Inserm U895, service de dermatologie, hôpital Archet 2, CHU, 151, route Saint-Antoine-Ginestiere, BP 79, 06200 Nice cedex 3, France. · Service de génétique, département de biologie et pathologie médicales, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Consultation d'oncogénétique, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France. · Département de biopathologie, centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. · Inserm, UMR946, variabilité génétique et maladies humaines, fondation Jean-Dausset, CEPH, 27, rue Juliette-Dodu, 75010 Paris, France. · Service d'ophtalmologie, institut Curie, 26, rue d'Ulm, 75231 Paris cedex 05, France. · Inserm U1079, service de génétique, CHU de Rouen, IRIB, faculté de médecine et de pharmacie, 22, boulevard Gambetta, 76183 Rouen cedex, France. · Service de gastro-entérologie-pancréatologie, hôpital Beaujon, AP-HP, 100, boulevard du Général-Leclerc, 92118 Clichy cedex, France. · Service de dermatologie, CHU Michallon, BP 217, 38043 Grenoble cedex 9, France. · Inserm U900, équipe épidémiologie génétique des cancers, institut Curie, 26, rue d'Ulm, 75248 Paris cedex 05, France. · Service de dermatologie, centre hospitalier Victor-Dupouy, 69, rue du Lieutenant-Colonel-Prud'hon, 95107 Argenteuil cedex, France. · Service de dermatologie, CHU d'Angers, université d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France. · Inserm, UMR946, variabilité génétique et maladies humaines, fondation Jean-Dausset, CEPH, 27, rue Juliette-Dodu, 75010 Paris, France; Service de dermatologie, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France. · Département d'oncologie génétique, institut Paoli-Calmettes, 232, boulevard Saint-Marguerite, 13273 Marseille cedex 9, France. · Service d'urologie, hôpital Bicêtre, Centre expert national cancers rares INCa PREDIR, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France. · Service de dermatologie, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France. · Inserm U976, laboratoire de génétique moléculaire, unité fonctionnelle de génétique, hôpital Xavier-Bichat-Claude-Bernard, AP-HP, Paris 7 université, 75018 Paris, France. · Inserm U830, service de génétique, département de biologie des tumeurs, institut Curie, 26, rue d'Ulm, 75231 Paris cedex 05, France. · Service de dermatologie, centre hospitalier Lyon Sud, université Lyon 1, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite cedex, France. · Service de dermatologie, CHU de Dijon, BP 77908, 21079 Dijon cedex, France. · Service de génétique, département de biologie et pathologie médicales, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. Electronic address: brigitte.bressac@gustaveroussy.fr. ·Ann Dermatol Venereol · Pubmed #25600792.

ABSTRACT: Cutaneous melanoma is a multifactorial disease resulting from both environmental and genetic factors. Five susceptibility genes have been identified over the past years, comprising high-risk susceptibility genes (CDKN2A, CDK4, and BAP1 genes) and intermediate-risk susceptibility genes (MITF, and MC1R genes). The aim of this expert consensus was to define clinical contexts justifying genetic analyses, to describe the conduct of these analyses, and to propose surveillance recommendations. Given the regulatory constraints, it is recommended that dermatologists work in tandem with a geneticist. Genetic analysis may be prescribed when at least two episodes of histologically proven invasive cutaneous melanoma have been diagnosed before the age of 75 years in two 1st or 2nd degree relatives or in the same individual. The occurrence in the same individual or in a relative of invasive cutaneous melanoma with ocular melanoma, pancreatic cancer, renal cancer, mesothelioma or a central nervous system tumour are also indications for genetic testing. Management is based upon properly managed photoprotection and dermatological monitoring according to genetic status. Finally, depending on the mutated gene and the familial history, associated tumour risks require specific management (e.g. ocular melanoma, pancreatic cancer). Due to the rapid progress in genetics, these recommendations will need to be updated regularly.

25 Article Malignant Melanoma Arising in Patients with a Large Congenital Melanocytic Naevus: Retrospective Study of 10 Cases with Cytogenetic Analysis. 2015

Lacoste, Caroline / Avril, Marie-Françoise / Frassati-Biaggi, Annonciade / Dupin, Nicolas / Chrétien-Marquet, Bertrand / Mahé, Emmanuel / Bodemer, Christine / Vergier, Béatrice / de la Fouchardière, Arnaud / Fraitag, Sylvie. ·Department of Pathology, Necker-Enfants Malades Hospital, APHP, Paris Descartes - Sorbonne Paris Cité university, Institut Imagine, 75015 Paris, France. ·Acta Derm Venereol · Pubmed #25594732.

ABSTRACT: Large congenital melanocytic naevi (LCMN) represent the main risk factor for development of melanoma in childhood. This retrospective study of 10 cases of melanoma in patients with LCMN used fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) (6 cases) to elucidate the clinical, histological, and cytogenetic characteristics of this rare disorder. Six melanomas were found within the LCMN, the others in lymph nodes, subcutis and brain. The LCMN was located on the trunk in 8 cases, with satellite naevi in 6 cases. Two distinct groups emerged: 5 melanomas that developed before the age of 10 years and the other after 20 years. The mortality rate was 60% and clearly correlated with clinical stage at diagnosis. Histological diagnosis was difficult in only 2 patients in whom neither immunohistochemistry nor FISH were helpful. Otherwise, CGH showed a high number of chromosomal aberrations leading to a formal diagnosis.

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