Author: "Tony Petrella" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Tony Petrella"' showing total 132 results

Start Over Author "Tony Petrella"

132 results on '"Tony Petrella"'

1. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author: Francine Garnache-Ottou, Chrystelle Vidal, Sabeha Biichlé, Florian Renosi, Eve Poret, Maïder Pagadoy, Maxime Desmarets, Anne Roggy, Estelle Seilles, Lou Soret, Françoise Schillinger, Sandrine Puyraimond, Tony Petrella, Claude Preudhomme, Christophe Roumier, Elisabeth A. MacIntyre, Véronique Harrivel, Yohan Desbrosses, Bérengère Gruson, Franck Geneviève, Sylvain Thepot, Yuriy Drebit, Thibaut Leguay, François-Xavier Gros, Nicolas Lechevalier, Pascale Saussoy, Véronique Salaun, Edouard Cornet, Zehaira Benseddik, Richard Veyrat-Masson, Orianne Wagner-Ballon, Célia Salanoubat, Marc Maynadié, Julien Guy, Denis Caillot, Marie-Christine Jacob, Jean-Yves Cahn, Rémy Gressin, Johann Rose, Bruno Quesnel, Estelle Guerin, Franck Trimoreau, Jean Feuillard, Marie-Pierre Gourin, Adriana Plesa, Lucile Baseggio, Isabelle Arnoux, Norbert Vey, Didier Blaise, Romaric Lacroix, Christine Arnoulet, Blandine Benet, Véronique Dorvaux, Caroline Bret, Bernard Drenou, Agathe Debliquis, Véronique Latger-Cannard, Caroline Bonmati, Marie-Christine Bene, Pierre Peterlin, Michel Ticchioni, Pierre-Simon Rohrlich, Anne Arnaud, Stefan Wickenhauser, Valérie Bardet, Sabine Brechignac, Benjamin Papoular, Victoria Raggueneau, Jacques Vargaftig, Rémi Letestu, Daniel Lusina, Thorsten Braun, Vincent Foissaud, Jérôme Tamburini, Hind Bennani, Nicolas Freynet, Catherine Cordonnier, Magali Le Garff-Tavernier, Nathalie Jacques, Karim Maloum, Damien Roos-Weil, Didier Bouscary, Vahid Asnafi, Ludovic Lhermitte, Felipe Suarez, Etienne Lengline, Frédéric Féger, Giorgia Battipaglia, Mohamad Mohty, Sabrina Bouyer, Ouda Ghoual, Elodie Dindinaud, Caroline Basle, Mathieu Puyade, Carinne Lafon, Thierry Fest, Mikael Roussel, Xavier Cahu, Elsa Bera, Sylvie Daliphard, Fabrice Jardin, Lydia Campos, Françoise Solly, Denis Guyotat, Anne-Cécile Galoisy, Alice Eischen, Caroline Mayeur-Rousse, Blandine Guffroy, Christian Recher, Marie Loosveld, Alice Garnier, Vincent Barlogis, Maria Alessandra Rosenthal, Sophie Brun, Nathalie Contentin, Sébastien Maury, Mary Callanan, Christine Lefebvre, Natacha Maillard, Patricia Okamba, Christophe Ferrand, Olivier Adotevi, Philippe Saas, Fanny Angelot-Delettre, Delphine Binda, and Eric Deconinck
Subjects: Specialties of internal medicine, RC581-951
Abstract: Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.
Published: 2019
Full Text: View/download PDF

2. Refining diffuse large B-cell lymphoma subgroups using integrated analysis of molecular profiles

Author: Sydney Dubois, Bruno Tesson, Sylvain Mareschal, Pierre-Julien Viailly, Elodie Bohers, Philippe Ruminy, Pascaline Etancelin, Pauline Peyrouze, Christiane Copie-Bergman, Bettina Fabiani, Tony Petrella, Jean-Philippe Jais, Corinne Haioun, Gilles Salles, Thierry Jo Molina, Karen Leroy, Hervé Tilly, and Fabrice Jardin
Subjects: Medicine, Medicine (General), R5-920
Abstract: Background: Gene expression profiling (GEP), next-generation sequencing (NGS) and copy number variation (CNV) analysis have led to an increasingly detailed characterization of the genomic profiles of DLBCL. The aim of this study was to perform a fully integrated analysis of mutational, genomic, and expression profiles to refine DLBCL subtypes. A comparison of our model with two recently published integrative DLBCL classifiers was carried out, in order to best reflect the current state of genomic subtypes. Methods: 223 patients with de novo DLBCL from the prospective, multicenter and randomized LNH-03B LYSA clinical trials were included. GEP data was obtained using Affymetrix GeneChip arrays, mutational profiles were established by Lymphopanel NGS targeting 34 key genes, CNV analysis was obtained by array CGH, and FISH and IHC were performed. Unsupervised independent component analysis (ICA) was applied to GEP data and integrated analysis of multi-level molecular data associated with each component (gene signature) was performed. Findings: ICA identified 38 components reflecting transcriptomic variability across our DLBCL cohort. Many of the components were closely related to well-known DLBCL features such as cell-of-origin, stromal and MYC signatures. A component linked to gain of 19q13 locus, among other genomic alterations, was significantly correlated with poor OS and PFS. Through this integrated analysis, a high degree of heterogeneity was highlighted among previously described DLBCL subtypes. Interpretation: The results of this integrated analysis enable a global and multi-level view of DLBCL, as well as improve our understanding of DLBCL subgroups. Keywords: Diffuse large B-cell lymphoma, Independent component analysis, Transcriptomic variability, Gene signatures, prognosis
Published: 2019
Full Text: View/download PDF

3. Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape

Author: Loria Zalmaï, Pierre-Julien Viailly, Sabeha Biichle, Meyling Cheok, Lou Soret, Fanny Angelot-Delettre, Tony Petrella, Marie-Agnès Collonge-Rame, Estelle Seilles, Sandrine Geffroy, Eric Deconinck, Etienne Daguindau, Sabrina Bouyer, Elodie Dindinaud, Victor Baunin, Magali Le Garff-Tavernier, Damien Roos-Weil, Orianne Wagner-Ballon, Véronique Salaun, Jean Feuillard, Sophie Brun, Bernard Drenou, Caroline Mayeur-Rousse, Patricia Okamba, Véronique Dorvaux, Michel Tichionni, Johann Rose, Marie Thérèse Rubio, Marie Christine Jacob, Victoria Raggueneau, Claude Preudhomme, Philippe Saas, Christophe Ferrand, Olivier Adotevi, Christophe Roumier, Fabrice Jardin, Francine Garnache-Ottou, and Florian Renosi
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Neoplasms involving plasmacytoid dendritic cells (pDC) include blastic pDC neoplasms (BPDCN) and other pDC proliferations, where pDC are associated with myeloid malignancies: most frequently chronic myelomonocytic leukemia (CMML) but also acute myeloid leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDC in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DC (cDC) associated in the same sample, by phenotypic and molecular analyses (targeted next-generation sequencing, 70 genes). We compared 15 pDCAML at diagnosis with 21 BPDCN and 11 normal pDC from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDC (4-36%), monocytes in 14 cases (1-10%) and cDC (two cases, 4.8-19%). pDC in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56– in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a prepDC stage. In all cases, pDC, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite the low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.
Published: 2020
Full Text: View/download PDF

4. Lichenoid esophagitis presenting as fatal upper gastrointestinal bleeding in a 52 year-old woman: a case diagnosed by autopsy

Author: Andrew Mitchell and Tony Petrella
Subjects: Lichenoid, Esophagitis, Lichen planus, Autopsy, Case report, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Abstract Background “Lichenoid esophagitis” is a descriptive term for a lichenoid pattern of inflammation in the esophagus for which a precise histologic diagnosis cannot be established. The differential diagnosis includes lichen planus, a drug-related reaction, and viral infection. Lichenoid esophagitis causing death has not been reported previously. We describe a case, diagnosed by autopsy, of lichenoid esophagitis in which massive bleeding from generalized epithelial sloughing and a large longitudinal ulcer proved fatal. Case presentation A 52 year-old diabetic woman collapsed at her home in front of an acquaintance. “Bloody vomit” was noted. Despite resuscitation efforts, the patient died. A complete autopsy was performed. The middle portion of the esophagus showed a 9 cm longitudinal ulcer situated 12 cm from the esophago-gastric junction. Microscopic examination showed complete sloughing of the esophageal epithelium with a striking subepithelial lichenoid lymphocytic infiltrate extending into the muscularis mucosae. The findings were considered compatible with lichenoid esophagitis. Laboratory studies also showed the presence of diabetic ketoacidosis. Conclusions Lichenoid esophagitis is an appropriate diagnostic term when clinical, histologic and laboratory findings do not allow for specific categorization of lichenoid inflammation in the esophagus. As illustrated here for the first time, lichenoid esophagitis may cause ulceration and mucosal sloughing severe enough to result in massive upper gastrointestinal bleeding and death. Translating these autopsy findings to the clinical setting, it is possible that the endoscopic finding of a longitudinal mid-esophageal ulcer in the presence of proximal stricture may be indicative of underlying lichenoid esophagitis.
Published: 2017
Full Text: View/download PDF

5. Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets

Author: Laurence de Leval, Marie Parrens, Fabien Le Bras, Jean-Philippe Jais, Virginie Fataccioli, Antoine Martin, Laurence Lamant, Richard Delarue, Françoise Berger, Flavie Arbion, Céline Bossard, Marie-Christine Copin, Danielle Canioni, Frédéric Charlotte, Gandhi Damaj, Peggy Dartigues, Bettina Fabiani, Albane Ledoux-Pilon, Karine Montagne, Thierry Molina, Martine Patey, Patrick Tas, Michel Peoch, Barbara Petit, Tony Petrella, Jean-Michel Picquenot, Thérèse Rousset, Marie-Christine Rousselet, Isabelle Soubeyran, Sylvie Thiebault, Olivier Tournilhac, Luc Xerri, Christian Gisselbrecht, Corinne Haioun, Georges Delsol, and Philippe Gaulard
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2015
Full Text: View/download PDF

6. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial

Author: Nicolas Mounier, Taoufik El Gnaoui, Hervé Tilly, Danièle Canioni, Catherine Sebban, René-Olivier Casasnovas, Richard Delarue, Anne Sonet, Pauline Beaussart, Tony Petrella, Sylvie Castaigne, Serge Bologna, Gilles Salles, Alain Rahmouni, Philippe Gaulard, and Corinne Haioun
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: A previous pilot study with rituximab, gemcitabine and oxaliplatin showed promising activity in patients with refractory/relapsed B-cell lymphoma. We, therefore, conducted a phase II study to determine whether these results could be reproduced in a multi-institutional setting. This phase II study included 49 patients with refractory (n=6) or relapsing (n=43) diffuse large B-cell lymphoma. The median age of the patients was 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplantation in 17 (35%) patients. International Prognostic Index at enrollment was >2 in 34 patients (71%). The primary endpoint was overall response rate after four cycles of treatment. Patients were planned to receive eight cycles if they reached at least partial remission after four cycles. After four cycles 21 patients (44%) were in complete remission and 8 (17%) in partial remission, resulting in an overall response rate of 61%. Factors significantly affecting overall response rate were early (
Published: 2013
Full Text: View/download PDF

7. Twenty-five years of epidemiological recording on myeloid malignancies: data from the specialized registry of hematologic malignancies of Côte d’Or (Burgundy, France)

Author: Marc Maynadié, François Girodon, Ines Manivet-Janoray, Morgane Mounier, Francine Mugneret, François Bailly, Bernardine Favre, Denis Caillot, Tony Petrella, Michel Flesch, and Paule-Marie Carli
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background Epidemiological data on myeloid malignancies are very rare in the literature due to a lack of registration by cancer registries until 2000. The Registry of Hematologic Malignancies of the Côte d’Or Department in France has, however, steadfastly registered data on cases occurring in the Department since 1980, resulting, to date, in a database of over 5,000 cases classified according to the ICD-O-3 classification, following the most recent World Health Organization classification criteria.Design and Methods Twenty-five years of data on myeloid malignancies, including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes and myelodysplastic/myeloproliferative syndromes were analyzed. World population standardized incidence rates were calculated as were as observed and relative survival.Results Incidence rates per 100,000 inhabitants/year were 2.5 for acute myeloid leukemia, 1.3 for myelodysplastic syndromes, 3.2 for myeloproliferative neoplasms and 0.6 for myelodysplastic/myeloproliferative syndromes. It was found that the incidence rate of myelodysplastic syndromes increased significantly over the period. The median overall survival is 8.9 months for patients with acute myeloid leukemia, 33.8 months for patients with myelodysplastic syndromes, 91.7 months for those with myeloproliferative neoplasms and 26.6 months for patients with myelodysplastic/myeloproliferative syndromes. Observed and relative 20-year survival rates are, respectively, 12% and 13% in acute myeloid leukemia, 2% and 6% in myelodysplastic syndromes and 20% and 34% in myeloproliferative neoplasms.Conclusions These population-based data on myeloid malignancies are the first data collected over such a long period and provide interesting information for clinicians and public health authorities, particularly given the paucity of other long-term, population-based data from cancer registries.
Published: 2011
Full Text: View/download PDF

8. Clinical, histopathological and prognostic features of primary cutaneous acral <scp>CD8</scp> + T‐cell lymphoma and other dermal <scp>CD8</scp> + cutaneous lymphoproliferations: results of an <scp>EORTC</scp> Cutaneous Lymphoma Group workshop*

Author: Werner Kempf, Tony Petrella, Rein Willemze, Patty Jansen, Emilio Berti, Marco Santucci, Eva Geissinger, Lorenzo Cerroni, Eve Maubec, Maxime Battistella, John Goodlad, Emmanuella Guenova, Katariina Lappalainen, Annamari Ranki, Paul Craig, Eduardo Calonje, Blanca Martin, Sean Whittaker, Ilske Oschlies, Ulrike Wehkamp, Jan P. Nicolay, Marion Wobser, Julia Scarisbruck, Nicola Pimpinelli, Rudi Stadler, Katrin Kerl French, Pietro Quaglino, Jinran Lin, Lianjun Chen, Michaela Beer, Patrick Emanuel, Stephane Dalle, and Alistair Robson
Subjects: Dermatology
Published: 2022

9. Supplementary Data from Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Author: Fabrice Jardin, Karen Leroy, Hervé Tilly, Gilles Salles, Nicolas Ketterer, Marc André, André Bosly, Frédéric Peyrade, Richard Delarue, Bertrand Coiffier, Bettina Fabiani, Danielle Canioni, Tony Petrella, Josette Brière, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Thierry J. Molina, Martin Figeac, Pauline Peyrouze, Jean-Philippe Jais, Catherine Maingonnat, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Sylvain Mareschal, Pierre-Julien Viailly, and Sydney Dubois
Abstract: Supplementary methods, figures, and tables Figure S1: Variant filters applied to Lymphopanel NGS data. Figure S2: Validation of variants according to SIFT and CADD scores. Figure S3: PMBL samples harbor more mutations than other DLBCL subtypes. Figure S4: Role of AID-induced SHM in DLBCL. Figure S5: Mutation frequency by subtype. Figure S6: Clustering of gene mutations according to subtype. Figure S7: Protein representations of observed mutations. Figure S8: Correlations between age and specific gene mutations. Figure S9: Prognosis according to IPI and subtype. Figure S10: Prognostic impact of gene mutations among the Lymphopanel. Table S1: Clinical characteristics of patients in our cohort. Table S2: Overview of the Lymphopanel used for NGS analysis. Table S3: Overview of pathway selection Table S4: Validation of variant filtering by an independent study of seven non-tumoral samples from DLBCL patients Table S5: Validated variants. Table S6: Lymphopanel NGS detection of genes with high AID target frequencies. Table S7: Prognostic impact of mutations in Lymphopanel genes
Published: 2023

10. Data from Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Author: Fabrice Jardin, Karen Leroy, Hervé Tilly, Gilles Salles, Nicolas Ketterer, Marc André, André Bosly, Frédéric Peyrade, Richard Delarue, Bertrand Coiffier, Bettina Fabiani, Danielle Canioni, Tony Petrella, Josette Brière, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Thierry J. Molina, Martin Figeac, Pauline Peyrouze, Jean-Philippe Jais, Catherine Maingonnat, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Sylvain Mareschal, Pierre-Julien Viailly, and Sydney Dubois
Abstract: Purpose: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials.Experimental Design: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients. The tumor DNA of 215 patients with CD20+de novo DLBCL in the prospective, multicenter, and randomized LNH-03B LYSA clinical trials was sequenced to deep, uniform coverage with the Lymphopanel. Cell-of-origin molecular classification was obtained through gene expression profiling with HGU133+2.0 Affymetrix GeneChip arrays.Results: The Lymphopanel was informative for 96% of patients. A clear depiction of DLBCL subtype molecular heterogeneity was uncovered with the Lymphopanel, confirming that activated B-cell–like (ABC), germinal center B-cell like (GCB), and primary mediastinal B-cell lymphoma (PMBL) are frequently affected by mutations in NF-κB, epigenetic, and JAK–STAT pathways, respectively. Novel truncating immunity pathway, ITPKB, MFHAS1, and XPO1 mutations were identified as highly enriched in PMBL. Notably, TNFAIP3 and GNA13 mutations in ABC patients treated with R-CHOP were associated with significantly less favorable prognoses.Conclusions: This study demonstrates the contribution of NGS with a consensus gene panel to personalized therapy in DLBCL, highlighting the molecular heterogeneity of subtypes and identifying somatic mutations with therapeutic and prognostic impact. Clin Cancer Res; 22(12); 2919–28. ©2016 AACR.See related commentary by Lim and Elenitoba-Johnson, p. 2829
Published: 2023

11. Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis

Author: Christophe Ferrand, Philippe Saas, Etienne Daguindau, Anne Roggy, Sandrine Geffroy, Sabrina Bouyer, Pierre-Julien Viailly, Olivier Adotevi, Mary Callanan, Sabeha Biichle, Elizabeth Macintyre, Francine Garnache-Ottou, Tony Petrella, Jacques Colinge, Christophe Roumier, Florian Renosi, Véronique Harrivel, Véronique Salaun, Pascale Saussoy, Eric Deconinck, Ambre Giguelay, Fanny Angelot-Delettre, Jean Feuillard, Vahid Asnafi, Claude Preudhomme, Fabrice Jardin, Meyling Cheok, Pascal Fuseau, Lou Soret, UCL - (SLuc) Service de biologie hématologique, and UCL - SSS/IREC/SLUC - Pôle St.-Luc
Subjects: Myeloid, Carcinogenesis, Plasmacytoid dendritic cell, Biology, medicine.disease_cause, SOXC Transcription Factors, Immunophenotyping, CDKN2A, medicine, Humans, Lectins, C-Type, Receptors, Immunologic, Acute leukemia, Myeloid Neoplasia, Membrane Glycoproteins, Myeloproliferative Disorders, Dendritic Cells, Genomics, Hematology, ETV6, medicine.anatomical_structure, Cancer research, Transcriptome, SNP array
Abstract: Oncogenesis and ontogeny of blastic plasmacytoid dendritic cell neoplasm (BPDCN) remain uncertain, between canonical plasmacytoid dendritic cells (pDCs) and AXL+ SIGLEC6+ DCs (AS-DCs). We compared 12 BPDCN to 164 acute leukemia by Affymetrix HG-U133 Plus 2.0 arrays: BPDCN were closer to B-cell acute lymphoblastic leukemia (ALL), with enrichment in pDC, B-cell signatures, vesicular transport, deubiquitination pathways, and AS-DC signatures, but only in some cases. Importantly, 1 T-cell ALL clustered with BPDCN, with compatible morphology, immunophenotype (cCD3+ sCD3− CD123+ cTCL1+ CD304+), and genetics. Many oncogenetic pathways are deregulated in BPDCN compared with normal pDC, such as cell-cycle kinases, and importantly, the transcription factor SOX4, involved in B ontogeny, pDC ontogeny, and cancer cell invasion. High-throughput sequencing (HaloPlex) showed myeloid mutations (TET2, 62%; ASXL1, 46%; ZRSR2, 31%) associated with lymphoid mutations (IKZF1), whereas single-nucleotide polymorphism (SNP) array (Affymetrix SNP array 6.0) revealed frequent losses (mean: 9 per patient) involving key hematological oncogenes (RB1, IKZF1/2/3, ETV6, NR3C1, CDKN2A/B, TP53) and immune response genes (IFNGR, TGFB, CLEC4C, IFNA cluster). Various markers suggest an AS-DC origin, but not in all patients, and some of these abnormalities are related to the leukemogenesis process, such as the 9p deletion, leading to decreased expression of genes encoding type I interferons. In addition, the AS-DC profile is only found in a subgroup of patients. Overall, the cellular ontogenic origin of BPDCN remains to be characterized, and these results highlight the heterogeneity of BPDCN, with a risk of a diagnostic trap.
Published: 2021

12. Blastic Plasmacytoid Dendritic Cell Neoplasm

Author: Eric Deconinck, Tony Petrella, and Francine Garnache Ottou
Subjects: Pathology, medicine.medical_specialty, Myeloid, business.industry, Lineage markers, Hematology, Blastic plasmacytoid dendritic cell neoplasm, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Immunophenotyping, Oncology, 030220 oncology & carcinogenesis, Medicine, Immunohistochemistry, Interleukin-3 receptor, Bone marrow, Presentation (obstetrics), business, 030215 immunology
Abstract: Clinical and biological presentation of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) is depicted to highlight criteria that might alert physicians. Diagnosis of BPDCN is still challenging and requires (1) immunophenotyping of blood or bone marrow aspiration using several markers (CD4, CD56, HLA-DR, myeloid and lymphoid lineage markers) and should include pDC markers such as CD123, cTCL1, CD303, and CD304, and/or (2) pathologic analysis of cutaneous lesions, also with immunohistochemistry using markers specific to BPDCN.
Published: 2020

13. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author: Xavier Cahu, Maxime Desmarets, Thibaut Leguay, Philippe Saas, Victoria Raggueneau, Delphine Binda, Maria Alessandra Rosenthal, Chrystelle Vidal, Olivier Adotevi, Fanny Angelot-Delettre, Françoise Solly, Anne-Cécile Galoisy, Alice Garnier, Sylvie Daliphard, Estelle Guérin, Marie-Pierre Gourin, Karim Maloum, Véronique Harrivel, Edouard Cornet, Felipe Suarez, Jacques Vargaftig, Fabrice Jardin, Caroline Mayeur-Rousse, Sylvain Thepot, Maïder Pagadoy, Thorsten Braun, Bernard Drenou, Yuriy Drebit, Marc Maynadié, Caroline Basle, Zehaira Benseddik, Frédéric Féger, Jean Feuillard, Christian Recher, Etienne Lengliné, Catherine Cordonnier, Rémi Letestu, Mathieu Puyade, Isabelle Arnoux, Remy Gressin, Nathalie Contentin, Jerome Tamburini, Pascale Saussoy, Mary Callanan, Elodie Dindinaud, Pierre-Simon Rohrlich, Julien Guy, Hind Bennani, Tony Petrella, Vincent Foissaud, Johann Rose, Natacha Maillard, Lucile Baseggio, Magali Le Garff-Tavernier, Vincent Barlogis, Denis Guyotat, Yohan Desbrosses, Caroline Bonmati, Damien Roos-Weil, Michel Ticchioni, Sandrine Puyraimond, Norbert Vey, Adriana Plesa, Blandine Guffroy, Daniel Lusina, Bérengère Gruson, Anne Roggy, Véronique Salaun, Eric Deconinck, Jean-Yves Cahn, Nathalie Jacques, Caroline Bret, Florian Renosi, Marie-Christine Béné, Alice Eischen, Stefan Wickenhauser, Benjamin Papoular, Francine Garnache-Ottou, François-Xavier Gros, Vahid Asnafi, Celia Salanoubat, Blandine Bénet, Elisabeth Macintyre, Lou Soret, Orianne Wagner-Ballon, Mohamad Mohty, Elsa Bera, Nicolas Freynet, Ludovic Lhermitte, Franck Trimoreau, Claude Preudhomme, Christophe Roumier, Sébastien Maury, Sabrina Bouyer, Eve Poret, Mikael Roussel, Romaric Lacroix, Christine Arnoulet, Françoise Schillinger, Patricia Okamba, Christine Lefebvre, Didier Blaise, Nicolas Lechevalier, Sabine Brechignac, Christophe Ferrand, Estelle Seilles, Richard Veyrat-Masson, Giorgia Battipaglia, Denis Caillot, Véronique Latger-Cannard, Bruno Quesnel, Didier Bouscary, Sophie Brun, Agathe Debliquis, Marie Loosveld, Franck Geneviève, Carinne Lafon, Lydia Campos, Thierry Fest, Ouda Ghoual, Marie-Christine Jacob, Pierre Peterlin, Valérie Bardet, Anne Arnaud, Véronique Dorvaux, Sabeha Biichle, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: IC18CT980373, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de biologie hématologique, Garnache-Ottou, F., Vidal, C., Biichle, S., Renosi, F., Poret, E., Pagadoy, M., Desmarets, M., Roggy, A., Seilles, E., Soret, L., Schillinger, F., Puyraimond, S., Petrella, T., Preudhomme, C., Roumier, C., Macintyre, E. A., Harrivel, V., Desbrosses, Y., Gruson, B., Genevieve, F., Thepot, S., Drebit, Y., Leguay, T., Gros, F. -X., Lechevalier, N., Saussoy, P., Salaun, V., Cornet, E., Benseddik, Z., Veyrat-Masson, R., Wagner-Ballon, O., Salanoubat, C., Maynadie, M., Guy, J., Caillot, D., Jacob, M. -C., Cahn, J. -Y., Gressin, R., Rose, J., Quesnel, B., Guerin, E., Trimoreau, F., Feuillard, J., Gourin, M. -P., Plesa, A., Baseggio, L., Arnoux, I., Vey, N., Blaise, D., Lacroix, R., Arnoulet, C., Benet, B., Dorvaux, V., Bret, C., Drenou, B., Debliquis, A., Latger-Cannard, V., Bonmati, C., Bene, M. -C., Peterlin, P., Ticchioni, M., Rohrlich, P. -S., Arnaud, A., Wickenhauser, S., Bardet, V., Brechignac, S., Papoular, B., Raggueneau, V., Vargaftig, J., Letestu, R., Lusina, D., Braun, T., Foissaud, V., Tamburini, J., Bennani, H., Freynet, N., Cordonnier, C., Le Garff-Tavernier, M., Jacques, N., Maloum, K., Roos-Weil, D., Bouscary, D., Asnafi, V., Lhermitte, L., Suarez, F., Lengline, E., Feger, F., Battipaglia, G., Mohty, M., Bouyer, S., Ghoual, O., Dindinaud, E., Basle, C., Puyade, M., Lafon, C., Fest, T., Roussel, M., Cahu, X., Bera, E., Daliphard, S., Jardin, F., Campos, L., Solly, F., Guyotat, D., Galoisy, A. -C., Eischen, A., Mayeur-Rousse, C., Guffroy, B., Recher, C., Loosveld, M., Garnier, A., Barlogis, V., Rosenthal, M. A., Brun, S., Contentin, N., Maury, S., Callanan, M., Lefebvre, C., Maillard, N., Okamba, P., Ferrand, C., Adotevi, O., Saas, P., Angelot-Delettre, F., Binda, D., and Deconinck, E.
Subjects: Oncology, Vincristine, medicine.medical_specialty, Myeloid, Cyclophosphamide, Clinical Trials and Observations, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Plasmacytoid dendritic cell, Immunophenotyping, Clonal Evolution, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Neoplasm Metastasis, Neoplasm Staging, 030304 developmental biology, Chromosome Aberrations, 0303 health sciences, Leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Disease Management, Myeloid leukemia, Dendritic Cells, Hematology, Prognosis, medicine.disease, Blood Cell Count, 3. Good health, Transplantation, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Acute Disease, business, Biomarkers, medicine.drug
Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.
Published: 2019

14. Clinical, histopathological and prognostic features of primary cutaneous acral CD8

Author: Werner, Kempf, Tony, Petrella, Rein, Willemze, Patty, Jansen, Emilio, Berti, Marco, Santucci, Eva, Geissinger, Lorenzo, Cerroni, Eve, Maubec, Maxime, Battistella, John, Goodlad, Emmanuella, Guenova, Katariina, Lappalainen, Annamari, Ranki, Paul, Craig, Eduardo, Calonje, Blanca, Martin, Sean, Whittaker, Ilske, Oschlies, Ulrike, Wehkamp, Jan P, Nicolay, Marion, Wobser, Julia, Scarisbruck, Nicola, Pimpinelli, Rudi, Stadler, Katrin, Kerl French, Pietro, Quaglino, Jinran, Lin, Lianjun, Chen, Michaela, Beer, Patrick, Emanuel, Stephane, Dalle, and Alistair, Robson
Subjects: Skin Neoplasms, Humans, CD8-Positive T-Lymphocytes, Prognosis, Lymphoma, T-Cell, Cutaneous, Retrospective Studies
Abstract: The differential diagnosis of atypical dermal nonepidermotropic CD8To assess the clinical, histological and immunophenotypic features; outcomes of; and differences between dermal CD8Retrospective analysis of a series of 46 patients and biopsies by the international EORTC Cutaneous Lymphoma Group.The dermal CD8A constellation of distinct clinical, histopathological and phenotypic features allows discrimination and assignment of dermal CD8
Published: 2021

15. Refining diffuse large B-cell lymphoma subgroups using integrated analysis of molecular profiles

Author: Bettina Fabiani, Sylvain Mareschal, Pascaline Etancelin, Tony Petrella, Fabrice Jardin, Bruno Tesson, Sydney Dubois, Jean-Philippe Jais, Christiane Copie-Bergman, Gilles Salles, Elodie Bohers, Corinne Haioun, Pierre-Julien Viailly, Thierry Jo Molina, Philippe Ruminy, Karen Leroy, Hervé Tilly, Pauline Peyrouze, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Carnot CALYM [Pierre-Benite], Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Lille 2 - Faculté de Médecine, INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de pathologie, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département d'Hématologie, Institut Carnot Lymphome (CALYM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre de pathologie [Dijon]
Subjects: 0301 basic medicine, Male, Research paper, Key genes, Transcriptomic variability, DNA Copy Number Variations, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Locus (genetics), Computational biology, Independent component analysis, Biology, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], hemic and lymphatic diseases, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Copy-number variation, Gene signatures, prognosis, Genetic Association Studies, lcsh:R5-920, Gene Expression Profiling, lcsh:R, Gene signatures, Chromosome Mapping, Computational Biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Molecular Sequence Annotation, General Medicine, Diffuse large B-cell lymphoma, Gene signature, medicine.disease, Immunohistochemistry, Gene expression profiling, 030104 developmental biology, 030220 oncology & carcinogenesis, Affymetrix genechip, Female, prognosis, Lymphoma, Large B-Cell, Diffuse, lcsh:Medicine (General)
Abstract: Background: Gene expression profiling (GEP), next-generation sequencing (NGS) and copy number variation (CNV) analysis have led to an increasingly detailed characterization of the genomic profiles of DLBCL. The aim of this study was to perform a fully integrated analysis of mutational, genomic, and expression profiles to refine DLBCL subtypes. A comparison of our model with two recently published integrative DLBCL classifiers was carried out, in order to best reflect the current state of genomic subtypes. Methods: 223 patients with de novo DLBCL from the prospective, multicenter and randomized LNH-03B LYSA clinical trials were included. GEP data was obtained using Affymetrix GeneChip arrays, mutational profiles were established by Lymphopanel NGS targeting 34 key genes, CNV analysis was obtained by array CGH, and FISH and IHC were performed. Unsupervised independent component analysis (ICA) was applied to GEP data and integrated analysis of multi-level molecular data associated with each component (gene signature) was performed. Findings: ICA identified 38 components reflecting transcriptomic variability across our DLBCL cohort. Many of the components were closely related to well-known DLBCL features such as cell-of-origin, stromal and MYC signatures. A component linked to gain of 19q13 locus, among other genomic alterations, was significantly correlated with poor OS and PFS. Through this integrated analysis, a high degree of heterogeneity was highlighted among previously described DLBCL subtypes. Interpretation: The results of this integrated analysis enable a global and multi-level view of DLBCL, as well as improve our understanding of DLBCL subgroups. Keywords: Diffuse large B-cell lymphoma, Independent component analysis, Transcriptomic variability, Gene signatures, prognosis
Published: 2019

16. Gray Zone Lymphoma Arising in the Neck of a Teenager With a Germline Mutation in TP53

Author: Marie-Claude Quintal, Sonia Cellot, Sophie Gatineau-Sailliant, Sophie Turpin, Josette Champagne, Mathieu Roussy, Tony Petrella, Karine Turcotte, and Dorothée Bouron-Dal Soglio
Subjects: Vincristine, Pathology, medicine.medical_specialty, Lymphoma, B-Cell, Adolescent, Palatine Tonsil, Gray zone lymphoma, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Prednisone, hemic and lymphatic diseases, medicine, Humans, Germ-Line Mutation, Etoposide, business.industry, Hematology, Prognosis, medicine.disease, Combined Modality Therapy, Lymphoma, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Tonsil, Pediatrics, Perinatology and Child Health, Female, Rituximab, Tumor Suppressor Protein p53, business, Neck, 030215 immunology, medicine.drug
Abstract: Gray zone lymphoma is an aggressive disease for which appropriate management is still debated. We report a 15-year-old girl with a cervical mass, an enlarged ipsilateral tonsil, and anemia. Both sites showed hypermetabolism on F18-FG positron emission tomography/CT. Surgical resection was diagnostic of Epstein-Barr virus-negative gray zone lymphoma cervical and tonsillar involvement. No abnormality was found in cytogenetic analysis on tumor cells. However, exome sequencing in peripheral blood DNA revealed a germline mutation in TP53. Complete response was achieved after surgery and 6 cycles of rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin regimen.
Published: 2019

17. Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape

Author: Fabrice Jardin, Elodie Dindinaud, Meyling Cheok, Fanny Angelot-Delettre, Victor Baunin, Caroline Mayeur-Rousse, Victoria Raggueneau, Bernard Drenou, Christophe Ferrand, Patricia Okamba, Johann Rose, Marie-Thérèse Rubio, Etienne Daguindau, Véronique Dorvaux, Loria Zalmaï, Eric Deconinck, Florian Renosi, Claude Preudhomme, Pierre-Julien Viailly, Olivier Adotevi, Christophe Roumier, Michel Tichionni, Francine Garnache-Ottou, Damien Roos-Weil, Sabrina Bouyer, Sabeha Biichle, Sandrine Geffroy, Marie-Agnès Collonge-Rame, Marie Christine Jacob, Tony Petrella, Jean Feuillard, Philippe Saas, Magali Le Garff-Tavernier, Lou Soret, Véronique Salaun, Orianne Wagner-Ballon, Estelle Seilles, Sophie Brun, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Université de Montréal (UdeM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CH La Rochelle, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Limoges, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Strasbourg, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Le Mans (CH Le Mans), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier de Versailles André Mignot (CHV), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Myeloid, CD34, Chronic myelomonocytic leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Humans, Cell Proliferation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, hemic and immune systems, Hematology, Dendritic Cells, medicine.disease, 3. Good health, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Phenotype, RUNX1, chemistry, 030220 oncology & carcinogenesis, Mutation, Cancer research, Interleukin-3 receptor, CD5, 030215 immunology
Abstract: Neoplasms involving plasmacytoid dendritic cells (pDC) include blastic pDC neoplasms (BPDCN) and other pDC proliferations, where pDC are associated with myeloid malignancies: most frequently chronic myelomonocytic leukemia (CMML) but also acute myeloid leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDC in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DC (cDC) associated in the same sample, by phenotypic and molecular analyses (targeted next-generation sequencing, 70 genes). We compared 15 pDCAML at diagnosis with 21 BPDCN and 11 normal pDC from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDC (4-36%), monocytes in 14 cases (1-10%) and cDC (two cases, 4.8-19%). pDC in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56– in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a prepDC stage. In all cases, pDC, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite the low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.
Published: 2020

18. Primary cutaneous acral <scp>CD</scp> 8 + T‐cell lymphomas relapse more frequently in younger patients

Author: Liliane Laroche, Eduardo Marinho, Eve Maubec, Florent Grange, Tony Petrella, and Andrew Mitchell
Subjects: 030207 dermatology & venereal diseases, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, Primary (chemistry), business.industry, 030220 oncology & carcinogenesis, medicine, Cytotoxic T cell, Hematology, business, Dermatology
Published: 2018

19. CD28/4-1BB CD123 CAR T cells in blastic plasmacytoid dendritic cell neoplasm

Author: Philippe Saas, Frédéric Féger, Francis Bonnefoy, Julien Caumartin, Mohamad Mohty, Christophe Ferrand, Christophe Roumier, Maxime Fredon, Jean-René Pallandre, Marina Deschamps, Elizabeth Macintyre, Olivier Adotevi, Alizée Jenvrin, Yann Godet, Tony Petrella, Chloé Molimard, Maria Loustau, Frédéric Tsé, Francine Garnache-Ottou, Séverine Valmary-Degano, Etienne Daguindau, Kiave-Yune HoWangYin, François Anna, Florian Renosi, Eric Deconinck, Elodie Bole-Richard, Sabeha Biichle, Walid Warda, Jean-Marie Certoux, Pierre Langlade-Demoyen, Fanny Angelot-Delettre, Eolia Brissot, Maïder Pagadoy, Delphine Binda, and Margaux Poussard
Subjects: 0301 basic medicine, Cytotoxicity, Immunologic, Cancer Research, medicine.medical_treatment, T-Lymphocytes, Interleukin-3 Receptor alpha Subunit, HL-60 Cells, Immunotherapy, Adoptive, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, CD28 Antigens, Cell Line, Tumor, Medicine, Neoplasm, Animals, Humans, business.industry, CD28, Interleukin, Hematology, Immunotherapy, Dendritic Cells, medicine.disease, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Humanized mouse, Cancer research, Interleukin-3 receptor, business
Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is associated with a remarkably poor prognosis and with no treatment consensus. The identification of relevant therapeutic targets is challenging. Here, we investigated the immune functions, antileukemia efficacy and safety of CD28/4-1BB CAR T cells targeting CD123 the interleukin (IL)-3 receptor alpha chain which is overexpressed on BPDCN. We demonstrated that both retroviral and lentiviral engineering CD28/4-1BB CD123 CAR T cells exhibit effector functions against BPDCN cells through CD123 antigen recognition and that they efficiently kill BPDCN cell lines and BPDCN-derived PDX cells. In vivo, CD28/4-1BB CD123 CAR T-cell therapy displayed strong efficacy by promoting a decrease of BPDCN blast burden. Furthermore we showed that T cells from BPDCN patient transduced with CD28/4-1BB CD123 CAR successfully eliminate autologous BPDCN blasts in vitro. Finally, we demonstrated in humanized mouse models that these effector CAR T cells exert low or no cytotoxicity against various subsets of normal cells with low CD123 expression, indicating a potentially low on-target/off-tumor toxicity effect. Collectively, our data support the further evaluation for clinical assessment of CD28/4-1BB CD123 CAR T cells in BPDCN neoplasm.
Published: 2019

20. GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors

Author: Vincent Delwail, Jean-Ehrland Ricci, Isabelle Peyrottes, Celine Delpech-Debiais, Sandrine Marchetti, Julie Reverso-Meinietti, Jacqueline Lehmann-Che, Gabriel Brisou, Jozef P. Bossowski, Manuel Grima-Reyes, Christiane Copie-Bergman, Camila Rubio-Patiño, Konstantina Fragaki, Eric de Kerviler, Véronique Paquis-Flucklinger, Thierry Jo Molina, Frederic Peyrade, Annabelle Mouchotte, Tony Petrella, Emma Proïcs, Bertrand Nadel, Els Verhoeyen, Bruno Taillan, Richard Delarue, Catherine Thieblemont, Laetitia Shintu, Agnès Paquet, Rana Mhaidly, Johanna Chiche, Elodie Villa, Georges Garnier, Pascal Barbry, Josette Brière, Damien Ambrosetti, Nicolas Mounier, André Bosly, Jean-François Michiels, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Pasteur [Nice] (CHU), Hôpital Hôtel Dieu, INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Hôpital Princesse Grace [Monaco], Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Cliniques universitaires UCL de Mont-Godinne 5530 Yvoir, Centre de pathologie [Dijon], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Service hématologie Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'onco-hématologie [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Physiopathologie de la survie et de la mort cellulaire et infection virale, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de pathologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Antoine Lacassagne, Centre Antoine Lacassagne, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: 0301 basic medicine, Male, Physiology, Phenformin, Cohort Studies, chemistry.chemical_compound, Mice, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Glyceraldehyde 3-phosphate dehydrogenase, Cells, Cultured, Aged, 80 and over, Predictive marker, biology, GAPDH, Glyceraldehyde-3-Phosphate Dehydrogenases, OxPhos, Middle Aged, glycolysis, Prognosis, 3. Good health, Metformin, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Treatment Outcome, Vincristine, R-CHOP, mTOR, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymphoma, Large B-Cell, Diffuse, Rituximab, predictive marker, medicine.drug, Adult, Antimetabolites, Antineoplastic, Mice, Transgenic, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Young Adult, stomatognathic system, medicine, Animals, Humans, Molecular Biology, Cyclophosphamide, PI3K/AKT/mTOR pathway, B cell, Aged, Retrospective Studies, Glutaminolysis, business.industry, Cell Biology, medicine.disease, L-asparaginase, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, chemistry, Doxorubicin, DLBCL, biology.protein, Cancer research, Prednisone, business, Diffuse large B-cell lymphoma, 030217 neurology & neurosurgery
Abstract: International audience; Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease treated with anti-CD20-based immuno-chemotherapy (R-CHOP). We identified that low levels of GAPDH predict a poor response to R-CHOP treatment. Importantly, we demonstrated that GAPDH(low) lymphomas use OxPhos metabolism and rely on mTORC1 signaling and glutaminolysis. Consistently, disruptors of OxPhos metabolism(phenformin) or glutaminolysis (L-asparaginase) induce cytotoxic responses in GAPDH(low) B cells and improve GAPDH(low) B cell-lymphoma-bearing mice survival, while they are low or not efficient on GAPDH(high) B cell lymphomas. Ultimately, we selected four GAPDH(low) DLBCL patients, who were refractory to all anti-CD20-based therapies, and targeted DLBCL metabolism-using L-asparaginase (K), mTOR inhibitor (T), and metformin (M) (called KTM therapy). Three out of the four patients presented a complete response upon one cycle of KTM. These findings establish that the GAPDH expression level predicts DLBCL patients' response to R-CHOP treatment and their sensitivity to specific metabolic inhibitors.
Published: 2019

21. Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes

Author: Catherine Chassagne-Clément, A.M. Tasei, Laurence Lamant, Corinne Haioun, H. Chomarat, E. Menet, Nadia Amara, Georges Delsol, Luc Xerri, L. de Leval, Audrey Delas, L. Andrac-Meyer, Philippe Rochaix, P. Gaulard, Anne Moreau, V. Costes, Isabelle Quintin-Roue, Thérèse Rousset, Alexandra Traverse-Glehen, Tony Petrella, Jean-François Michiels, M.P. Chenard-Neu, Jean-François Emile, Pierre Brousset, and Camille Laurent
Subjects: Adult, STAT3 Transcription Factor, Pathology, medicine.medical_specialty, Breast Implants, Receptors, Antigen, T-Cell, Silicones, Ki-1 Antigen, Ki-1+ Anaplastic Large Cell Lymphoma, 030230 surgery, Implant removal, Immunophenotyping, law.invention, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, law, hemic and lymphatic diseases, medicine, Humans, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, skin and connective tissue diseases, Anaplastic large-cell lymphoma, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Lymphoma, T-Cell, Peripheral, Receptor Protein-Tyrosine Kinases, Original Articles, Hematology, Middle Aged, medicine.disease, Hodgkin Disease, Lymphoma, Oncology, 030220 oncology & carcinogenesis, Breast implant, Cancer research, Lymphoma, Large-Cell, Anaplastic, Female, business, T-Lymphocytes, Cytotoxic
Abstract: ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants.Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed.The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively.In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.
Published: 2016

22. Diagnostic d’un lymphome non hodgkinien mandibulaire primitif pour mobilités dentaires multiples : un cas

Author: Benoit-Luc Wajszczak, Tony Petrella, Julien Potier, and Victorin Ahossi
Subjects: Periodontics, Dentistry (miscellaneous), Oral Surgery
Abstract: Introduction : Les lymphomes primitifs osseux mandibulaires ont ete decrits pour la premiere fois par Parker et Jackson. Les lymphomes constituent le deuxieme cancer de la tete et du cou, apres les carcinomes epidermoides. Les localisations mandibulaires sont rares et ne representeraient que 0,6 % des cas. Observation : Nous exposons, a travers une observation, les caracteristiques cliniques et radiologiques du lymphome mandibulaire ainsi que ses modalites de prise en charge chez une patiente de 50 ans. Le traitement est medical par une chimiotherapie. Discussion : Les lymphomes de la tete et du cou sont presque toujours des lymphomes B a grandes cellules. Ils peuvent etre confondus avec une pathologie odontogene. Le chirurgien oral ne doit pas ignorer cette pathologie dont le taux de remission complete est de 60 a 80 % a un an.
Published: 2016

23. Indolent CD8-positive lymphoid proliferation of acral sites: three further cases of a rare entity and an update on a unique patient

Author: Alistair Robson, Stephen Morris, Dimitra Koch, Anneke Kai, Lorenzo Cerroni, Tony Petrella, Simon O'Connor, Saleem Taibjee, Mojca Persic, Sean Whittaker, Justine Kluk, and Werner Kempf
Subjects: Systemic disease, Pathology, medicine.medical_specialty, Histology, business.industry, Rare entity, Clinical course, Dermatology, Aggressive disease, Disease, medicine.disease, Cutaneous lymphoma, Pathology and Forensic Medicine, Lymphoma, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, business, CD8
Abstract: BACKGROUND: Primary cutaneous indolent CD8-positive lymphoid proliferation is an emerging entity characterised by slowly enlarging papules and nodules that are pathologically comprised of clonal non-epidermotropic medium-sized atypical CD8(+) T-cells. Although the majority of lesions are solitary and located on the ears, bilateral symmetrical presentations have been described and lesions may arise at other peripheral or "acral" sites. Patients follow a benign clinical course and systemic involvement has not yet been observed. Despite this, some medical practitioners classify such lesions as Peripheral T-cell Lymphoma, NOS, a category implying aggressive disease. OBJECTIVES: We present three cases seen in our institutions and provide an update on a previously reported unique patient who continues to develop recurrent and multifocal skin lesions. RESULTS: Systemic disease progression has not been observed, even in the presence of recurrent and multifocal cutaneous disease. CONCLUSIONS: Indolent CD8-positive lymphoid proliferation of acral sites is a distinctive and readily identifiable entity and should be included in the next consensus revision of cutaneous lymphoma classification. Although cases described thus far have followed an indolent clinical course, dermatologists should remain guarded about the prognosis and full staging and longitudinal observation are recommended until this condition is better understood.
Published: 2015

24. REFINEMENT OF MUM1 EXPRESSION THRESHOLD FOR DOUBLE POSITIVE CD10+ MUM1+ DIFFUSE LARGE B CELL LYMPHOMA ALLOWS A BETTER CELL OF ORIGIN CLASSIFICATION FOR GCB SUBTYPE

Author: Tony Petrella, W. El Alami Thomas, Danielle Canioni, Hervé Maisonneuve, O. Laghmari, A. Pavageau, P. Gaulard, Y. Le Bris, C. Copie Bergman, Antoine Bonnet, Josette Brière, P. Guerzider, Marie-Christine Béné, O. Casasnovas, Corinne Haioun, Gilles Salles, Thierry Jo Molina, H. Tilly, Anne-Sophie Moreau, Fabrice Jardin, Céline Bossard, Philippe Ruminy, Catherine Thieblemont, and S. Le Gouill
Subjects: Cancer Research, Oncology, Chemistry, Cell of origin, Double negative, medicine, Hematology, General Medicine, medicine.disease, Molecular biology, Diffuse large B-cell lymphoma
Published: 2019

25. Myelodysplasia Cutis Versus Leukemia Cutis

Author: Maxime Battistella, Wendy Cuccuini, M.-E. Noguera, Tony Petrella, Anne Janin, Emmanuel Raffoux, Vignon Pennamen, Jean-Paul Feugeas, and A. Osio
Subjects: medicine.medical_specialty, business.industry, Treatment outcome, Cutis, Leukemia cutis, Cell Biology, Dermatology, Biochemistry, Overall survival, %22">Fish , Medicine, medicine.symptom, Skin pathology, business, Molecular Biology
Published: 2015
Full Text: View/download PDF

26. Lymphoproliférations cutanées : proposition d’algorithmes diagnostiques à partir de l’expérience sur 2ans des réseaux INCa (LYMPHOPATH et GFELC) sur 2760 lymphoproliférations cutanées

Author: Eric Frouin, Nicolas Ortonne, Laurence Lamant, Tony Petrella, Émilie Laban, Anne de Muret, Brigitte Balme, Jean-Philippe Merlio, Maxime Battistella, Marie Beylot-Barry, Janine Wechsler, Béatrice Vergier, and A. Carlotti
Subjects: Pathology and Forensic Medicine
Abstract: Resume Introduction A partir de notre etude retrospective portant sur 2760 lymphoproliferations cutanees incluses dans les reseaux LYMPHOPATH et GFELC, nous avons analyse les cas douteux et discordants entre pathologiste expert et non expert, et l’apport diagnostique d’une confrontation anatomoclinique. Materiel et methodes Nous avons extrait les principales difficultes diagnostiques posees par les lymphoproliferations cutanees et avons concu et teste sur 20 cas tires au sort et grâce a 20 pathologistes, des algorithmes destines a tout pathologiste non specialiste en dermatopathologie. Resultats Les problematiques les plus frequentes sont les suivantes : MF ou dermatose reactionnelle ; lymphome sans autre precision ou infiltrat reactionnel ; lymphoproliferation B a petites cellules : lymphome ou reactionnel ; lymphoproliferation B a grandes cellules : phenotypage. Nous avons egalement etudie d’autres problematiques sur ou sous-diagnostiquees. Le test sur les 20 cas tires au sort a objective 72 % de reussite. L’utilisation de plusieurs algorithmes pour un meme cas est possible. Discussion Notre travail montre que la seconde lecture d’expert a un interet dans le domaine des lymphoproliferations cutanees. La relecture est utile pour distinguer un lymphome B a petites cellules d’un infiltrat reactionnel et dans l’aboutissement a un diagnostic apres envoi pour « doute entre lymphome et entite reactionnelle ». Nous montrons cependant que, pour la problematique MF ou dermatose reactionnelle, la confrontation anatomoclinique apporte plus de resultats, en premiere intention, que la seconde lecture. Conclusion Ceci est la premiere etude concernant les lymphoproliferations cutanees qui, sans exclure les infiltrats reactionnels, s’appuie sur les diagnostics douteux et discordants entre pathologistes non experts et experts pour aboutir a des algorithmes diagnostiques testes.
Published: 2015

27. Lichenoid esophagitis presenting as fatal upper gastrointestinal bleeding in a 52 year-old woman: a case diagnosed by autopsy

Author: Tony Petrella and Andrew Mitchell
Subjects: medicine.medical_specialty, Muscularis mucosae, Esophageal Mucosa, Autopsy, Case Report, Esophageal Diseases, Gastroenterology, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Esophagus, Fatal Outcome, Internal medicine, medicine, Esophagitis, Humans, lcsh:RC799-869, Esophageal disease, business.industry, Lichen Planus, General Medicine, Hepatology, Middle Aged, medicine.disease, stomatognathic diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Lichenoid, 030211 gastroenterology & hepatology, lcsh:Diseases of the digestive system. Gastroenterology, Female, Upper gastrointestinal bleeding, Differential diagnosis, business, Gastrointestinal Hemorrhage
Abstract: Background “Lichenoid esophagitis” is a descriptive term for a lichenoid pattern of inflammation in the esophagus for which a precise histologic diagnosis cannot be established. The differential diagnosis includes lichen planus, a drug-related reaction, and viral infection. Lichenoid esophagitis causing death has not been reported previously. We describe a case, diagnosed by autopsy, of lichenoid esophagitis in which massive bleeding from generalized epithelial sloughing and a large longitudinal ulcer proved fatal. Case presentation A 52 year-old diabetic woman collapsed at her home in front of an acquaintance. “Bloody vomit” was noted. Despite resuscitation efforts, the patient died. A complete autopsy was performed. The middle portion of the esophagus showed a 9 cm longitudinal ulcer situated 12 cm from the esophago-gastric junction. Microscopic examination showed complete sloughing of the esophageal epithelium with a striking subepithelial lichenoid lymphocytic infiltrate extending into the muscularis mucosae. The findings were considered compatible with lichenoid esophagitis. Laboratory studies also showed the presence of diabetic ketoacidosis. Conclusions Lichenoid esophagitis is an appropriate diagnostic term when clinical, histologic and laboratory findings do not allow for specific categorization of lichenoid inflammation in the esophagus. As illustrated here for the first time, lichenoid esophagitis may cause ulceration and mucosal sloughing severe enough to result in massive upper gastrointestinal bleeding and death. Translating these autopsy findings to the clinical setting, it is possible that the endoscopic finding of a longitudinal mid-esophageal ulcer in the presence of proximal stricture may be indicative of underlying lichenoid esophagitis.
Published: 2017

28. Cutaneous Apocrine Carcinoma With an In Situ Component and Histiocytoid and Signet-Ring Cells

Author: Delphine Désy, Tony Petrella, Yves E. Leclerc, Jérémie Berdugo, Josée Doyon, Sophie Brissy-Lachery, Vincent Dumont-Mackay, and Andrew Mitchell
Subjects: Male, Pathology, medicine.medical_specialty, Biopsy, Bone Neoplasms, Dermatology, Pathology and Forensic Medicine, Metastasis, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Fatal Outcome, Signet ring cell carcinoma, Carcinoma, Biomarkers, Tumor, Medicine, Humans, Apocrine Neoplasm, Aged, business.industry, Signet ring cell, Carcinoma in situ, Apocrine, Apocrine Carcinoma, Cell Differentiation, Histiocytes, General Medicine, medicine.disease, Immunohistochemistry, Neoplasms, Complex and Mixed, Sweat Gland Neoplasms, Apocrine Glands, 030220 oncology & carcinogenesis, business, Carcinoma, Signet Ring Cell, Carcinoma in Situ
Abstract: We present a case of cutaneous apocrine carcinoma arising in the axilla of a 71-year-old man. The tumor had a significant component of histiocytoid and signet-ring cells as well as in situ carcinoma within the apocrine glands. The cells expressed GATA3, gross cystic disease fluid protein 15, androgen receptor, and E-cadherin. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were negative. Clinical correlation was required to rule out a metastasis from the breast or the gastrointestinal tract. Although most cutaneous apocrine carcinomas do not behave aggressively, our patient developed bone metastases and eventually died of his disease. It is debated whether histiocytoid and signet-ring cell cutaneous carcinomas should be classified as apocrine neoplasm. The presence of in situ carcinoma associated with this kind of tumor has been reported only once in the literature. This characteristic and the immunohistochemical profile are in favor of apocrine differentiation.
Published: 2017

29. Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network

Author: Mylène Dandoit, Catherine Chassagne-Clément, Alexandra Traverse-Glehen, Gilles Salles, Marie Parrens, Peggy Dartigues, Marie-Pierre Chenard-Neu, Marc Maynadié, B. Fabiani, Pierre Brousset, Françoise Berger, Laurent Martin, Jean-François Michiels, Claire Bastien, Josette Brière, Michel Peoc'h, Patrick Tas, Diane Damotte, Philippe Gaulard, Martine Patey, Nadia Amara, Manuela Delage, Anne Moreau, Isabelle Quintin-Roue, Céline Bossard, Antoine de Mascarel, Marie-Christine Copin, Pierre Déchelotte, Henri Sevestre, Isabelle Soubeyran, Sylvie Thiebault, Luc Xerri, Camille Laurent, Jean-Michel Picquenot, Christiane Copie-Bergman, Antoine Martin, Frédéric Charlotte, Blandine Fabre, Béatrice Vergier, Georges Delsol, Flavie Arbion, Corinne Haioun, Tony Petrella, Marine Baron, Marie-Christine Rousselet, Thomas Filleron, Cécile Le Naoures, Thérèse Rousset, Nicole Brousse, and Thierry Jo Molina
Subjects: Cancer Research, Pathology, medicine.medical_specialty, Myeloid, Lymphoma, Newly diagnosed, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, Humans, Lymphoid neoplasms, Prospective Studies, Prospective cohort study, Referral and Consultation, Neoplasm Grading, Potential impact, Pathology, Clinical, business.industry, Lymphoma diagnosis, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Clinical Competence, France, business, Who classification, 030215 immunology
Abstract: Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.
Published: 2017

30. BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial

Author: Gilles Salles, Martin Figeac, Hervé Tilly, B. Fabiani, Josette Brière, Danielle Canioni, M. Parrens, Marc André, R. Delarue, Jean-Philippe Jais, C Thieblemont, Christiane Copie-Bergman, Karen Leroy, Corinne Haioun, P. Feugier, Philippe Ruminy, Fabrice Jardin, Tony Petrella, Thierry Jo Molina, P. Gaulard, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'études spatiales de la biosphère (CESBIO), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CHU Bordeaux [Bordeaux]
Subjects: 0301 basic medicine, Oncology, Male, Pathology, [SDV]Life Sciences [q-bio], Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Hazard ratio, Hematology, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Treatment Outcome, Proto-Oncogene Proteins c-bcl-2, Vincristine, 030220 oncology & carcinogenesis, Prednisolone, Rituximab, Female, Lymphoma, Large B-Cell, Diffuse, medicine.drug, medicine.medical_specialty, Disease-Free Survival, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Internal medicine, medicine, Biomarkers, Tumor, Humans, Progression-free survival, Cyclophosphamide, Aged, business.industry, medicine.disease, Lymphoma, 030104 developmental biology, Doxorubicin, Prednisone, business, Diffuse large B-cell lymphoma
Abstract: Background Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. Patients and methods We evaluated 285 paraffin-embedded samples from patients (60–80years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. Results The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). Conclusions Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. Clinical trial Number NCT00144755
Published: 2017

31. Subcutaneous Panniculitis-like T-cell Lymphoma: Immunosuppressive Drugs Induce Better Response than Polychemotherapy

Author: Christine Bodemer, Saskia Ingen-Housz-Oro, Tony Petrella, Olivier Hermine, Nathalie Franck, Sylvie Fraitag, Martine Bagot, David Michonneau, Maxime Battistella, Marie Beylot-Barry, Béatrice Vergier, Stéphane Barete, Nicole Brousse, Nicolas Ortonne, Marc Maynadié, Laboratoire d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maisonneuve-Rosemont Hospital Research Center, University of Montreal, CHU Henri Mondor [Créteil], Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie pathologique [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Dpt anatomie pathologique [CHU Bordeaux], Université de Bourgogne (UB), Service de dermatologie [CHU Necker], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [Saint-Louis], Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique Adulte [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Dpt Dermatologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Bourgogne ( UB ), Service de dermatologie [CHU Necker-Enfants malades], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Oncodermatologie, immunologie et cellules souches cutanées ( DIO U976 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Panniculitis, Time Factors, Biopsy, medicine.medical_treatment, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030207 dermatology & venereal diseases, 0302 clinical medicine, Subcutaneous Panniculitis-Like T-Cell Lymphoma, Antineoplastic Combined Chemotherapy Protocols, Child, medicine.diagnostic_test, Remission Induction, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, Immunosuppressive drug, Child, Preschool, 030220 oncology & carcinogenesis, Disease Progression, Female, France, Immunosuppressive Agents, Adult, medicine.medical_specialty, Adolescent, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Lymphoma, T-Cell, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Medical history, Pathological, Proportional Hazards Models, Retrospective Studies, business.industry, Autoantibody, Infant, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Lymphoma, business, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare condition usually considered to have a favourable prognosis. However, it is not known whether polychemotherapy or immunosuppressive-based therapy is the best approach for treating SPTCL. Using data collected between 2000 and 2012 in France, we analysed clinical, biological and pathological data of 27 patients with SPTCL. Medical history revealed that 40% of patients had been previously diagnosed with an autoimmune disorder and 22% with inflammatory panniculitis. Haemophagocytic syndrome was present in 37% of cases. Autoantibodies were positive in 65% of cases. Complete remission (CR) was reached in 74% of cases. Immunosuppressive drug treatment was given in 69.5% of patients (group 1) and polychemotherapy in 30.5% (group 2). CR was 81.2% and 28.5% (p?=?0.025), respectively. Progression rate was 6.2% and 42.8% (p?=?0.067), respectively. This study suggests that immunosuppressive drugs should be considered as the first-line treatment for SPTCL.
Published: 2017

32. Blastic Plasmacytoid Dendritic Cell Neoplasms

Author: Marie Dominique Vignon-Pennamen, Annie Levy, Stéphane Dalle, Valérie Costes-Martineau, Philippe Courville, Andrew Mitchell, Béatrice Vergier, Anne de Muret, Fanny Julia, Laurence Lamant, Gérard Duru, Agnès Carlotti, Nicolas Ortonne, Pierre Dechelotte, Claire Delattre, Tony Petrella, Sylvie Fraitag, Sophie Dalac, and Brigitte Balme
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Skin Neoplasms, Adolescent, Proliferative index, Kaplan-Meier Estimate, Plasmacytoid dendritic cell, Biology, Pathology and Forensic Medicine, Young Adult, Biomarkers, Tumor, medicine, Humans, Young adult, Child, Tropism, Aged, Aged, 80 and over, medicine.diagnostic_test, CD68, Dendritic Cells, Middle Aged, Immunohistochemistry, stomatognathic diseases, Hematologic Neoplasms, Skin biopsy, Female, Surgery, Interleukin-3 receptor, Anatomy
Abstract: Blastic plasmacytoid dendritic cell neoplasm is a rare clinicopathologic entity, characterized by strong skin tropism and a poor prognosis. The diagnosis is generally made by skin biopsy with appropriate immunohistochemical studies. To identify potential biological prognostic factors for blastic plasmacytoid dendritic cell neoplasm, we performed an extended clinico-immunohistochemical study on a series of 91 well-documented cases collected since 1995 by the French Study Group on Cutaneous Lymphomas. Skin biopsies were analyzed using a panel of 12 immunohistochemical markers (CD4, CD56, CD123, CD303, TCL1, CD68, CD2, CD7, TdT, Ki-67, S100, and MX-1). The results were correlated with survival. The 5 most characteristic markers of this entity (CD4, CD56, CD123, CD303, and TCL1) were expressed simultaneously in only 46% of patients. However, when 4 markers were expressed the diagnosis could still be reliably made without resorting to any additional stains. Expression of TdT and/or S100 correlated with varying degrees of maturation. Statistical survival analyses showed that CD303 expression and high proliferative index (Ki-67) were significantly associated with longer survival.
Published: 2014

33. Stroke associated with giant cell arteritis: a population-based study

Author: Jérôme Durier, Bernard Bonnotte, Maxime Samson, Benoit Daubail, Tony Petrella, Jean-François Besancenot, Yannick Béjot, Sylvain Audia, Hervé Devilliers, Laurent Martin, Agnès Jacquin, Bernard Lorcerie, and Maurice Giroud
Subjects: Male, medicine.medical_specialty, Pediatrics, Giant Cell Arteritis, Population, Vascular risk, Age Distribution, Sex Factors, immune system diseases, Internal medicine, Epidemiology, medicine, Humans, Prospective Studies, Registries, cardiovascular diseases, skin and connective tissue diseases, education, Stroke, Aged, Aged, 80 and over, education.field_of_study, business.industry, Incidence, Middle Aged, medicine.disease, Rheumatology, Population based study, Psychiatry and Mental health, Giant cell arteritis, cardiovascular system, Female, Surgery, France, Neurology (clinical), Vasculitis, business
Abstract: Background Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA. Methods All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptoms and 4 weeks after the start of treatment. Results Among the 57 biopsy-proven patients with GCA (incidence rate 10.9/100 000/year in individuals ≥50 years), 4 (7.0%) experienced a GCA-related stroke. Three were men and all had ≥2 vascular risk factors and were ≥80 years. The stroke was vertebrobasilar for 3/4 patients and undetermined for the remaining one. The incidence rate of GCA-related stroke in patients ≥50 years was 0.76/100 000/year (95% CI 0 to 2.47), 1.36/100 000/year in men (95% CI 0 to 3.63) and 0.33/100 000/year (95% CI 0 to 1.45) in women. Conclusions This population-based study demonstrated that GCA-related stroke essentially affects the vertebrobasilar territory and mainly occurs in old men with associated vascular risk factors. Although rare, GCA symptoms must be searched for in elderly patients with stroke, and optimal vascular prevention must be conducted carefully in patients with GCA with a high vascular risk before initiating GCA treatment.
Published: 2014

34. Extrafacial indolent CD8-positive cutaneous lymphoid proliferation with unusual symmetrical presentation involving both feet

Author: Matthias Goebeler, Hermann Kneitz, Marion Wobser, Eva Geissinger, Andreas Rosenwald, Andreas Kerstan, and Tony Petrella
Subjects: medicine.medical_specialty, Pathology, Histology, Proliferation index, Cutaneous T-cell lymphoma, Cancer, Dermatology, Biology, medicine.disease, World health, Pathology and Forensic Medicine, Lymphoma, medicine, Dermatopathology, Presentation (obstetrics), CD8
Abstract: Indolent CD8+ cutaneous lymphoid proliferation represents a recently described entity among cutaneous T-cell lymphomas that typically presents with solitary skin lesions on the face or at acral sites and usually follows an indolent clinical course. Histopathologically, this entity is characterized by a dense dermal infiltrate of non-epidermotropic, small- to medium-sized pleomorphic CD8+ T-cells of the non-activated cytotoxic phenotype showing a clear-cut grenz zone and a low proliferation index. Distinction from otherwise aggressive T-cell lymphomas bearing a cytotoxic CD8+ phenotype is fundamental. We herein present an unusual case of indolent CD8+ cutaneous lymphoid proliferation presenting in bilateral symmetrical distribution on both feet and lacking the otherwise described grenz zone. Our case widens the spectrum of possible clinical and histomorphological variations of this entity. Taking into account the distinctive and unique clinical and microscopic features of all hitherto published cases of indolent CD8+ cutaneous lymphoid proliferation we suppose that this lymphoma subtype has to be included as a new and distinct entity in the World Health Organisation (WHO)-/European Organisation for Research and Treatment of Cancer (EORTC)-classification of cutaneous lymphomas.
Published: 2013

35. Indolent CD8+lymphoid proliferation of acral sites: a clinicopathologic study of six patients with some atypical features

Author: Eduardo Calonje, Tony Petrella, Danielle Greenblatt, Fiona Child, Sean Whittaker, Mina S. Ally, Julia Scarisbrick, Alistair Robson, and Stephen Morris
Subjects: Pathology, medicine.medical_specialty, Histology, Proliferative index, biology, business.industry, Cancer, Dermatology, Disease, medicine.disease, Pathology and Forensic Medicine, Lymphoma, Granzyme B, Immunophenotyping, Granzyme, medicine, biology.protein, T-cell lymphoma, business
Abstract: The authors report six further cases of a cutaneous lymphoid proliferation that share many of the features of a case series previously described as indolent CD8-positive lymphoid proliferation of the ear. Previous reports of this entity have described the slow growth of cutaneous papules and nodules, with a predilection for the ear, associated with specific histopathologic and immunophenotypic features and a benign clinical course. These include the presence of a clear Grenz zone without epidermotropism, and a CD8(+) granzyme B- immunophenotype with a low proliferative index. The current case series presents some atypical clinical features, including site of disease beyond the ear and recurrent disease. Despite this, indolent clinical evolution is apparent. Histopathologically, three of the six cases showed a moderate-high proliferative index, while two cases had very focal epidermotropism and Pautrier collections. A single example had significant granzyme B expression. These previously unreported features add to our understanding of this rare entity, which is not currently recognized in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) classification.
Published: 2012

36. Alpha-Interferon Secreting Blastic Plasmacytoid Dendritic Cells Neoplasm

Author: Geneviève Hervé, John Andrew Carlson, François Girodon, Francine Mugneret, Pierre Lebon, Patrick Callier, Jean-Baptiste Bour, Bernard Bonnotte, and Tony Petrella
Subjects: Male, Pathology, medicine.medical_specialty, Skin Neoplasms, Myeloid, Genotype, Lymphoma, Karyotype, Alpha interferon, Dermatology, In situ hybridization, Biology, Pathology and Forensic Medicine, Antigen, Tumor Cells, Cultured, medicine, Humans, Neoplasm, In Situ Hybridization, Fluorescence, Aged, 80 and over, Comparative Genomic Hybridization, Interferon-alpha, Dendritic Cells, General Medicine, medicine.disease, ETV6, Leukemia, medicine.anatomical_structure, Bone marrow, Transcriptome
Abstract: We report a new case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) with extensive immunophenoptyping, genotyping (karyotype, array-comparative genomic hybridization, and fluorescent in situ hybridization), and long-term tumor cells culture. BPDCN is a very rare and aggressive disease clinically characterized by a skin revealing localization more or less rapidly disseminating to the bone marrow and other organs with or without and leukemia. The disease was initially phenotypically characterized by the expression of both CD4 and CD56 antigens, whereas lym- phoid and myeloid lineage antigens were negative. A phenotypic link with alpha-interferon (IFN-I)-producing plasmacytoid dendritic cells was demonstrated. The data collected in this case report provide additional biological and genotypical data on tumor cells of BPDCN. This study confirms the capability of tumor cells to secrete IFN-I, demonstrated by biological IFN-I activity of cultured cells and immunohistochemical expression of Mx-1 protein. Although a com- mon genetic profile involving chromosomes 5, 6, 9, 12, 13, and 15 has been identified, no specific genetic marker has been demon- strated that is specific to BPDCN. The demonstration of ETV6 gene deletion in this case deserves further investigations as a putative BPDCN marker.
Published: 2012

37. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study

Author: Danielle Canioni, Fabrice Jardin, Peggy Cuillière-Dartigues, Philippe Gaulard, Frederic Peyrade, Marie Parrens, Jean-Philippe Jais, Richard Delarue, Gilles Salles, Nicolas Ketterer, Reiner Siebert, Christian Recher, Karen Leroy, Hervé Tilly, Bettina Fabiani, Maryse Baia, Christiane Copie-Bergman, Tony Petrella, Corinne Haioun, Karim Belhadj, Inga Nagel, Josette Brière, Thierry Jo Molina, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), INSERM U955, équipe 9, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'anatomo-pathologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hématologie Biologique, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d’Hématologie [CHU Purpan, Toulouse], Centre Hospitalier Universitaire de Purpan (CHU Purpan), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Department of Oncology, Lausanne Hospital, Lausanne Hospital, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'hématologie clinique, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'informatique médicale et biostatistiques [CHU Necker], Hôpital Hôtel Dieu, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie [CHU Toulouse], CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Adult, Male, Immunoglobulin gene, Adolescent, [SDV]Life Sciences [q-bio], Immunology, Immunoglobulins, Chromosomal translocation, Biology, Biochemistry, Disease-Free Survival, Translocation, Genetic, Proto-Oncogene Proteins c-myc, Antibodies, Monoclonal, Murine-Derived, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Cyclophosphamide, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, Aged, 80 and over, Gene Rearrangement, 0303 health sciences, Cell Biology, Hematology, Gene rearrangement, Middle Aged, medicine.disease, BCL6, 3. Good health, Lymphoma, Survival Rate, Doxorubicin, Vincristine, 030220 oncology & carcinogenesis, Cancer research, Prednisone, Female, Lymphoma, Large B-Cell, Diffuse, Rituximab, Diffuse large B-cell lymphoma
Abstract: Diffuse Large B-Cell lymphoma (DLBCL) with MYC rearrangement ( MYC -R) carries an unfavorable outcome. We explored the prognostic value of MYC translocation partner gene in a series of MYC -R de novo DLBCL patients enrolled in first-line prospective clinical trials of the GELA/LYSA and treated with rituximab-anthracyclin-based chemotherapy. Seven hundred seventy four DLBCL cases characterized for cell of origin by the Hans classifier were analysed using fluorescence in situ hybridization (FISH) with BCL2 , BCL6 , MYC , IGK , IGL breakapart and IGH/MYC , IGK/MYC , IGL/MYC fusion probes. MYC rearrangement ( MYC -R) was observed in 51/574 (8.9%) evaluable DLBCL. MYC -R cases were predominantly of germinal centre B-cell-like subtype 37/51(74%) with no distinctive morphological and phenotypic features. Nineteen were MYC single-hit ( MYC -SH) and 32 MYC double-hit ( MYC -DH) ( MYC plus BCL2 and/or BCL6 ) DLBCL. MYC translocation partner was an immunoglobulin gene in 24 cases ( MYC-IG ) and a non-immunoglobulin gene ( MYC-non-IG ) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) ( P=.0002 ) compared to MYC -negative patients, whereas no survival difference was observed between MYC-non-IG and MYC -negative patients. In multivariate analyses MYC-IG predicted poor PFS ( P=.0051 ) and OS ( P=.0006 ) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC rearrangement is correlated to MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC rearrangement who should be routinely characterized according to MYC partner gene. Trials are individually registered with www.ClinicalTrials.gov numbers NCT00144807, NCT01087424, NCT00169143, NCT00144755, NCT00140660, NCT00140595 and NCT00135499.
Published: 2015

38. Immunologic effects of rituximab on the human spleen in immune thrombocytopenia

Author: Malika Trad, Bernard Lorcerie, Laurent Martin, Marion Ciudad, Nicolas Larmonier, V. Leguy, Bernard Bonnotte, Marc Maynadié, Serge Aho-Glélé, Jennifer Fraszczak, Sabine Berthier, Patrick Rat, Maxime Samson, Emmanuel Katsanis, Nicolas Cheynel, Tony Petrella, Julien Guy, Sylvain Audia, and Nona Janikashvili
Subjects: Adult, Male, medicine.medical_treatment, Immunology, Splenectomy, Spleen, T-Lymphocytes, Regulatory, Biochemistry, Antibodies, Monoclonal, Murine-Derived, Immune system, immune system diseases, hemic and lymphatic diseases, Humans, Immunologic Factors, Medicine, Immunobiology, Aged, Autoimmune disease, B-Lymphocytes, Purpura, Thrombocytopenic, Idiopathic, biology, business.industry, Cell Biology, Hematology, Middle Aged, Th1 Cells, medicine.disease, Lymphatic system, medicine.anatomical_structure, Monoclonal, biology.protein, Female, Rituximab, Antibody, business, medicine.drug
Abstract: Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug.
Published: 2011

39. Histologic and Immunohistologic Characterization of Skin Localization of Myeloid Disorders

Author: Claire Bénet, Aurélie Gomez, Claire Aguilar, Claire Delattre, Béatrice Vergier, Marie Beylot-Barry, Sylvie Fraitag, Agnès Carlotti, Pierre Dechelotte, Valérie Hospital, Michel d’Incan, Valérie Costes, Olivier Dereure, Nicolas Ortonne, Martine Bagot, Liliane Laroche, Astrid Blom, Sophie Dalac, and Tony Petrella
Subjects: Pathology, medicine.medical_specialty, Myeloid, biology, medicine.diagnostic_test, CD117, CD33, Chronic myelomonocytic leukemia, Myeloid leukemia, General Medicine, medicine.disease, Leukemia, medicine.anatomical_structure, Immunophenotyping, hemic and lymphatic diseases, Skin biopsy, biology.protein, medicine
Abstract: A retrospective analysis of 173 skin biopsy specimens of myeloid leukemia cutis (MLC) was performed to determine histologic and immunophenotypic criteria that could distinguish the varied myeloid disorders from one another. For the study, 11 relevant histologic items were scored and 12 antigens were studied (CD68 [KP1], CD163, CD14, CD4, myeloperoxidase [MPO], CD33, CD117, CD34, CD56, MIB-1, CD303, and CD123). Underlying myeloid disorders were essentially acute myeloid leukemias (65.3%), chronic myelomonocytic leukemias (11.0%), and refractory anemia (10.4%). Skin lesions were de novo in 7.5%, concurrent in 26.6%, and subsequent in 60.7%. Several morphologic characteristics (density, size of tumor cells, inflammatory background) were statistically useful in distinguishing between varied myeloid disorders. De novo MLCs displayed a specific morphologic profile. Association of CD68, CD33, and MPO could diagnose 100% of the cases of MLC. However, the immunohistochemical panel could not distinguish between the varied underlying myeloid disorders, with the exception that CD123 was particularly powerful in recognizing chronic myelomonocytic leukemia and also permitted reclassification of 4 cases as blastic plasmacytoid dendritic cell neoplasm.
Published: 2011

40. Tumoral aspects of plasmacytoid dendritic cells: What do we know in 2009?

Author: Fabio Facchetti and Tony Petrella
Subjects: Male, Skin Neoplasms, Myeloid, Follicular dendritic cells, Immunology, Interferon-alpha, Alpha interferon, hemic and immune systems, Dendritic Cells, Plasmacytoid dendritic cell, Dendritic cell, Blastic plasmacytoid dendritic cell neoplasm, Middle Aged, Biology, Lymphoma, T-Cell, medicine.anatomical_structure, medicine, Humans, Immunology and Allergy, Female, In patient, Lymph node
Abstract: Plasmacytoid dendritic cell (PDC) is a Th2-type dendritic cell precursor. It is an important professional effector cell characterized by its capacities to produce large amount of alpha interferon and to differentiate into dendritic cell. PDCs are scarce in normal condition. They circulate in the blood as veiled cells and enter the lymph node and mucosal site in response to immune stimulation. Besides the recent and wide-open field of the implication of PDCs in inflammatory diseases and in the microenvironment of solid or lymphoid tumours it has also been observed that PDCs can also be tumoral cells. In this paper, the authors present the different tumours thought to be originating from tumoral PDCs. To date, two kinds of tumoral conditions are recognized: the so-called PDCs proliferations in patients with myeloid disorders and the blastic plasmacytoid dendritic cell neoplasm. These two entities are exposed and discussed.
Published: 2010

41. Onychomatricoma: New Clinical and Histological Features. A Review of 19 Tumors

Author: Tony Petrella, Jean-François Michiels, Robert Baran, G Cannata, Bérangère Chignon-Sicard, Christophe Perrin, and Thierry Balaguer
Subjects: Adult, Male, Models, Anatomic, Pathology, medicine.medical_specialty, Skin Neoplasms, Thick nail, Nails, Malformed, Bowen's Disease, Fibroma, Dermatology, Pathology and Forensic Medicine, Diagnosis, Differential, Nail Diseases, Young Adult, Imaging, Three-Dimensional, Onychomatricoma, Biomarkers, Tumor, Humans, Medicine, Aged, business.industry, Superficial acral fibromyxoma, General Medicine, Anatomy, Middle Aged, Nail plate, medicine.disease, Immunohistochemistry, medicine.anatomical_structure, Nail disease, Pleomorphic fibroma, Carcinoma, Squamous Cell, Nail (anatomy), Female, Warts, business
Abstract: To further define the clinicopathological spectrum of onychomatricoma (OM). We report the clinical feature, histological, and immunophenotypic characteristics of 19 cases of OM diagnosed between 2002 and 2007. The characteristic histologic appearance of OM is sometimes difficult to grasp because of 3 main factors: the anatomic particularities of the nail apparatus, the often fragmented aspect of the tissue specimen, and the choice of the section planes, which strongly modified the morphologic appearances observed. To prevent these difficulties, we built a tridimensional model using serial, transverse, and longitudinal sections. This reconstitution gives us a better understanding of the apparent diversity of the morphologic aspects observed in linking them to the anatomic site of the tumor. OM of the matrix is characterized by a thick nail plate with porch roof. OM of the ventral aspect of the proximal nail fold (PNF) is characterized by a nail plate without porch roof, exhibiting either a woodworm-like appearance or multiple cavities. In this second category, the fibrous base becomes elongated in shape, taking the shape of the anatomic contour of the PNF. The stroma gives rise to numerous fibroepithelial digitations. This pattern is different from the classical OM visualized in longitudinal sections, which appears as a single and large fibroepithelial tumor, that is, the multiple distal epithelial digitations arranged along a transversal plane are not seen. In the PNF variant, the characteristic clinical signs of OM fail to appear. We individualize 3 misleading clinical variants: tumor with a verrucous surface that is located in the lateral nail fold, as a band pattern suggesting wart or Bowen disease; a total dystrophy of the nail unit mimicking a squamous cell carcinoma; and pseudofibrokeratoma type. In the OM located on the ventral matrix, 3 new specific histologic variants were noted: pleomorphic OM, OM with a predominantly collagenous stroma, and superficial acral fibromyxoma-;like OM. OM is a benign tumor with a broader morphologic spectrum than previously thought. When the nail plate is not available, the immunohistochemistry can aid diagnosis by highlighting the peculiar immunophenotyping of OM, which expresses CD34 but not CD99, epithelial membrane antigen, S-100 protein, actin, and desmin.
Published: 2010

42. Plasmacytoid (CD68+CD123+) Monocytes May Play a Crucial Role in the Pathogenesis of Hydroa Vacciniforme: A Case Report

Author: J. Andrew Carlson, Tony Petrella, Mitchel Singer, and Neal Varughese
Subjects: Epstein-Barr Virus Infections, Pathology, medicine.medical_specialty, Adolescent, CD30, Photodermatosis, Dermatology, Biology, medicine.disease_cause, Monocytes, Herpesviridae, Immunophenotyping, Pathology and Forensic Medicine, Lymphocytic Infiltrate, Antigens, CD, Interferon, medicine, Humans, Cytotoxic T cell, CD68, General Medicine, medicine.disease, Immunology, Hydroa Vacciniforme, Hydroa vacciniforme, Female, medicine.drug
Abstract: Hydroa vacciniforme (HV) is a rare, blistering, childhood photodermatosis that heals with smallpox-like scars, is associated with latent Epstein-Barr virus (EBV) infection, and spontaneously resolves by early adulthood. Cytotoxic T cells are suspected to mediate the histologic hallmark of HV-dense, perivascular, lymphocytic infiltrates and reticular degeneration and necrosis of the epidermis. We report a case of 13-year-old white girl with EBV-associated HV, whose lesional skin harbored a predominate CD6 + , CD123 + infiltrate of plasmacytoid monocytes (PMs). Other significant pathologic attributes included abundant non-neutrophilic nuclear debris, necrosis of adnexal structures, lymphocytic vasculitis, and clusters of CD30 + cells. PMs produce large amounts of type I interferon during viral infection, which induces apoptosis of some cell types and promotes the survival of others. This antiviral response can explain these aforementioned pathologic findings representing wide spread cell death and lymphoid proliferation, as well as eventual resolution of HV with time, via elimination of latent EBV-infected cells. The destruction of adnexal structures can account for the depressed circinate scars characteristic of HV The validity of this proposed mechanism must be evaluated by first examining the prevalence and number of PMs in future case series of HV.
Published: 2009

43. Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome

Author: Thierry Jo Molina, Aspasia Stamatoullas, Anne Vekhoff, F. Morschhauser, Marie Christine Copin, Olivier Casasnovas, Reda Bouabdallah, Daniel Birnbaum, Bruno Chetaille, Pierre Feugier, Jean Michel Picquenot, Benjamin Esterni, François Bertucci, Luc Xerri, Tony Petrella, Daniel Olive, Pascal Finetti, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancérologie (Inserm U599/IPC), Université de la Méditerranée - Aix-Marseille 2-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de Recherche Interdiscipinaire Innovation et Optimisation Thérapeutique - EA 4481 (GRIIOT), Université de Lille, Droit et Santé, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Dijon, Département de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Centre de Recherche en Cancérologie de Marseille (CRCM / U891 Inserm)
Subjects: Adult, Male, Epstein-Barr Virus Infections, Stromal cell, Adolescent, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Biology, medicine.disease_cause, Biochemistry, Disease-Free Survival, T-Lymphocyte Subsets, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, polycyclic compounds, medicine, Humans, Reed-Sternberg Cells, Child, Oligonucleotide Array Sequence Analysis, CD20, B-Lymphocytes, Tumor microenvironment, Gene Expression Profiling, Remission Induction, food and beverages, FOXP3, Cell Biology, Hematology, Middle Aged, Th1 Cells, Prognosis, medicine.disease, Hodgkin Disease, Survival Analysis, Epstein–Barr virus, Neoplasm Proteins, Lymphoma, Gene Expression Regulation, Neoplastic, Gene expression profiling, Treatment Outcome, Cancer research, biology.protein, Immunohistochemistry, Female, Stromal Cells
Abstract: The outcome of classical Hodgkin lymphoma (cHL) patients may be related to the tumor microenvironment, which in turn may be influenced by Epstein-Barr virus (EBV) infection. To characterize the cHL microenvironment, a set of 63 cHL tissue samples was profiled using DNA microarrays. Their gene expression profile differed from that of histiocyte T cell–rich B-cell lymphoma (H/TCRBCL) samples that were used as controls, mainly due to high expression of PDCD1/PD-1 in H/TCRBCL. EBV+ cHL tissues could be distinguished from EBV− samples by a gene signature characteristic of Th1 and antiviral responses. Samples from cHL patients with favorable outcome overexpressed genes specific for B cells and genes involved in apoptotic pathways. An independent set of 146 cHL samples was analyzed using immunohistochemistry. It showed a significant adverse value in case of high percentage of either TIA-1+-reactive cells or topoisomerase-2+ tumor cells, whereas high numbers of BCL11A+, FOXP3+, or CD20+ reactive cells had a favorable influence. Our results suggest an antitumoral role for B cells in the cHL microenvironment and a stronger stromal influence of the PD1 pathway in H/TCRBCL than cHL. The observation of Th1/ antiviral response in EBV+ cHL tissues provides a basis for novel treatment strategies.
Published: 2009

44. Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases

Author: José L. Rodriguez Peralto, Patty M. Jansen, M.L. Geerts, Marco Paulli, Werner Kempf, Emilio Berti, Marco Santucci, Leila Jeskanen, Marijke R. Canninga-van Dijk, Maarten H. Vermeer, Alistair Robson, Lorenzo Cerroni, Chris J.L.M. Meijer, Michael Hummel, Nancy J. Senff, Sonja Hahtola, Pablo L. Ortiz-Romero, Rein Willemze, Janine Wechsler, Chalid Assaf, Annamari Ranki, Agnes Carlotti, Cesare Massone, Tony Petrella, Sean Whittaker, Willemze, R, Jansen, P, Cerroni, L, Berti, E, Santucci, M, Assaf, C, Canninga van Dijk, M, Carlotti, A, Geerts, M, Hahtola, S, Hummel, M, Jeskanen, L, Kempf, W, Massone, C, Ortiz Romero, P, Paulli, M, Petrella, T, Ranki, A, Peralto, J, Robson, A, Senff, N, Vermeer, M, Wechsler, J, Whittaker, S, Meijer, C, Pathology, and CCA - Disease profiling
Subjects: Male, Pathology, Panniculitis, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, panniculitis like T-cell lymphoma, Biochemistry, Gastroenterology, Cutaneous lymphoma, 030207 dermatology & venereal diseases, 0302 clinical medicine, Subcutaneous Panniculitis-Like T-Cell Lymphoma, Antineoplastic Combined Chemotherapy Protocols, MED/35 - MALATTIE CUTANEE E VENEREE, T-cell lymphoma, Child, Microfilament Proteins, Receptors, Antigen, T-Cell, gamma-delta, Hematology, Middle Aged, Chemotherapy regimen, CD56 Antigen, 3. Good health, Lymphoma, T-Cell, Cutaneous, Survival Rate, Phenotype, 030220 oncology & carcinogenesis, CD4 Antigens, Female, Lupus erythematosus panniculitis, Adult, medicine.medical_specialty, Adolescent, CD8 Antigens, Immunology, Disease-Free Survival, Education, Diagnosis, Differential, 03 medical and health sciences, Internal medicine, medicine, Humans, Survival rate, Aged, business.industry, Cell Biology, medicine.disease, Lymphoma, Transplantation, business, Carrier Proteins
Abstract: In the WHO classification, subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a distinct type of T-cell lymphoma with an aggressive clinical behavior. Recent studies suggest that distinction should be made between SPTL with an α/β T-cell phenotype (SPTL-AB) and SPTL with a γδ T-cell phenotype (SPTL-GD), but studies are limited. To better define their clinicopathologic features, immunophenotype, treatment, and survival, 63 SPTL-ABs and 20 SPTL-GDs were studied at a workshop of the EORTC Cutaneous Lymphoma Group. SPTL-ABs were generally confined to the subcutis, had a CD4-, CD8+, CD56-, βF1+ phenotype, were uncommonly associated with a hemophagocytic syndrome (HPS; 17%), and had a favorable prognosis (5-year overall survival [OS]: 82%). SPTL-AB patients without HPS had a significantly better survival than patients with HPS (5-year OS: 91% vs 46%; P < .001). SPTLGDs often showed (epi)dermal involvement and/or ulceration, a CD4-, CD8-, CD56 +/-, βF1- T-cell phenotype, and poor prognosis (5-year OS: 11%), irrespective of the presence of HPS or type of treatment. These results indicate that SPTL-AB and SPTL-GD are distinct entities, and justify that the term SPTL should further be used only for SPTL-AB. SPTL-ABs without associated HPS have an excellent prognosis, and multiagent chemotherapy as first choice of treatment should be questioned. © 2008 by The American Society of Hematology.
Published: 2008

45. Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets

Author: Fabien Le Bras, Corinne Haioun, Richard Delarue, Laurence de Leval, Albane Ledoux-Pilon, Sylvie Thiebault, Flavie Arbion, Michel Peoc'h, Frédéric Charlotte, Marie Parrens, Gandhi Damaj, Marie-Christine Rousselet, Patrick Tas, Peggy Dartigues, Philippe Gaulard, Tony Petrella, Marie-Christine Copin, Jean-Michel Picquenot, Karine Montagne, Isabelle Soubeyran, Laurence Lamant, Georges Delsol, Christian Gisselbrecht, Thierry Jo Molina, Danielle Canioni, Olivier Tournilhac, Antoine Martin, Thérèse Rousset, Barbara Petit, Françoise Berger, Martine Patey, Bettina Fabiani, Luc Xerri, Céline Bossard, Jean-Philippe Jais, Virginie Fataccioli, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Henri Mondor, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital avicenne, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'immuno-hématologie pédiatrique [CHU Necker], Service d'Anatomopathologie [Tours], CHRU Tours-CHU Trousseau [APHP], Service d'anatomie pathologique [CHU Necker], Centre de référence des mastocytoses, CHU Necker - Enfants Malades [AP-HP], APHP, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut Gustave Roussy ( IGR ), Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service d'Anatomo-Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP), Service de Biologie, CRLCC Eugène Marquis ( CRLCC ), Service de neuropathologie, CHU Saint-Etienne, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'anatomie cytologie pathologiques, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Laboratoire HIFIH, PRES Université Nantes Angers Le Mans ( UNAM ) -IFR132-UPRES 3859, Department de pathologie cellulaire et tissulaire, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ) -PRES Université Nantes Angers Le Mans ( UNAM ), Génétique tumorale - Pathologie, CHU Bordeaux [Bordeaux]-Centre Régional de Lutte Contre le Cancer Institut Bergonié (Bordeaux), Service d'Hématologie Clinique Adulte et de Thérapie Cellulaire, Centre Hospitalier Universitaire de Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I ( UdA ), Laboratoire DIAG, GELA, Groupe d'Etude des Lymphomes de l'Adulte, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de pathologie [Mondor], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Henri Mondor [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de référence des mastocytoses (CEREMAST), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I (UdA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Centre de Physiopathologie Toulouse Purpan (CPTP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux]-Institut Bergonié [Bordeaux], and UNICANCER-UNICANCER
Subjects: Oncology, Male, Databases, Factual, Female, France/epidemiology, Humans, Immunoblastic Lymphadenopathy/epidemiology, Immunoblastic Lymphadenopathy/pathology, Lymphoma, T-Cell/epidemiology, Lymphoma, T-Cell/pathology, medicine.medical_specialty, Angioimmunoblastic T-cell lymphoma, Lymphoma, Epidemiology, T cell, [SDV]Life Sciences [q-bio], Lymphoma, T-Cell, angioimmunoblastic T-cell lymphoma, Databases, Lymphoma t-cell, hemic and lymphatic diseases, Internal medicine, medicine, Prevalence, T-cell lymphoma, Online Only Articles, peripheral T-cell lymphoma, ComputingMilieux_MISCELLANEOUS, Factual, [ SDV ] Life Sciences [q-bio], business.industry, Cancer, Hematology, medicine.disease, T-Cell, Information data, Peripheral T-cell lymphoma, 3. Good health, medicine.anatomical_structure, Immunoblastic Lymphadenopathy, Immunology, France, business
Abstract: Reliable information regarding the current prevalence of peripheral T-cell lymphoma (PTCL) entities is missing. Herein we report on the frequency of PTCL entities in France between 2010 and 2013. Using Lymphopath , a national lymphoma network established by the French National Cancer Agency, which
Published: 2015

46. Indolent CD8-positive lymphoid proliferation of acral sites: three further cases of a rare entity and an update on a unique patient

Author: Justine, Kluk, Anneke, Kai, Dimitra, Koch, Saleem M, Taibjee, Simon, O'Connor, Mojca, Persic, Stephen, Morris, Sean, Whittaker, Lorenzo, Cerroni, Werner, Kempf, Tony, Petrella, and Alistair, Robson
Subjects: Adult, Male, Skin Neoplasms, Humans, Lymphoma, T-Cell, Peripheral, Female, CD8-Positive T-Lymphocytes, Middle Aged, Cell Proliferation, Lymphoma, T-Cell, Cutaneous
Abstract: Primary cutaneous indolent CD8-positive lymphoid proliferation is an emerging entity characterized by slowly enlarging papules and nodules that are pathologically comprised of clonal nonepidermotropic medium-sized atypical CD8(+) T-cells. Although the majority of lesions are solitary and located on the ears, bilateral symmetrical presentations have been described and lesions may arise at other peripheral or 'acral' sites. Patients follow a benign clinical course and systemic involvement has not yet been observed. Despite this, some medical practitioners classify such lesions as peripheral T-cell lymphoma, NOS, a category implying aggressive disease.We present three cases seen in our institutions and provide an update on a previously reported unique patient who continues to develop recurrent and multifocal skin lesions.Systemic disease progression has not been observed, even in the presence of recurrent and multifocal cutaneous disease.Indolent CD8-positive lymphoid proliferation of acral sites is a distinctive and readily identifiable entity and should be included in the next consensus revision of cutaneous lymphoma classification. Although cases described thus far have followed an indolent clinical course, dermatologists should remain guarded about the prognosis and full staging and longitudinal observation are recommended until this condition is better understood.
Published: 2015

47. Cutaneous Rosai-Dorfman Disease Located on the Breast: Rapid Effectiveness of Methotrexate After Failure of Topical Corticosteroids, Acitretin and Thalidomide

Author: Laurent Machet, Marie-Christine Machet, Tony Petrella, Marion Nadal, and Thibault Kervarrec
Subjects: medicine.medical_specialty, Systemic disease, Anti-Inflammatory Agents, Dermatology, Administration, Cutaneous, Skin Diseases, Acitretin, Breast Diseases, Keratolytic Agents, Biopsy, medicine, Humans, Angiosarcoma, Treatment Failure, Rosai–Dorfman disease, Aged, Clobetasol, integumentary system, medicine.diagnostic_test, business.industry, Sinus Histiocytosis with Massive Lymphadenopathy, General Medicine, medicine.disease, Thalidomide, Histiocytosis, Methotrexate, Skin biopsy, Retreatment, Female, Dermatologic Agents, Histiocytosis, Sinus, business, Immunosuppressive Agents, medicine.drug
Abstract: An erythematous cutaneous plaque on the breast with no signs of infection requires a skin biopsy to rule out dermal extension of an underlying mammary adenocarcinoma, primary skin tumour (e.g. angiosarcoma or malignant lymphoma) (1), or inflammatory lymphoedema of the breast (2). It can more rarely reveal location on the skin of systemic disease. Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a benign proliferative disorder of histiocytes first described in 1965 by Destombes on nodal biopsy (3). It was subsequently recognised as a distinct clinicopathologic entity by Rosai & Dorfman (4). Cases of RDD located solely on the skin have rarely been reported, and thus treatment is not well-codified (5). We report a case of RDD on the breast which showed rapid partial response to methotrexate.
Published: 2015

48. Aggressive epidermotropic cutaneous CD8+ lymphoma: A cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC Cutaneous Lymphoma Task Force Workshop

Author: Alistair Robson, Christine Castillo, Maria Geerts, Sean Whittaker, Chalid Assaf, Nicola Pimpinelli, Rein Willemze, Tony Petrella, Joclim Roewert, Mattias Steinhoff, Marco Santucci, Frederic Franck, Emilio Berti, Robin Russell-Jones, Lorenzo Cerroni, Janine Wechsler, Robert Knobler, Pierre Dechelotte, Nicola Chimenti, Cesare Massone, Chris J.L.M. Meijer, John R. Goodlad, Werner Kempf, Sylke Gellrich, Eduardo Calonje, Wolfram Sterry, Martine Bagot, Pablo Ortiz, Günter Burg, Robson, A, Assaf, C, Bagot, M, Burg, G, Calonje, J, Castillo, C, Cerroni, L, Chimenti, N, Dechelotte, P, Franck, F, Geerts, M, Gellrich, S, Goodlad, J, Kempf, W, Knobler, R, Massone, C, Meijer, C, Ortiz, P, Petrella, T, Pimpelli, N, Roewert, J, Russell-Jones, R, Santucci, M, Steinhoff, M, Sterry, W, Wechsler, J, Whittaker, S, Willemze, R, Berti, E, Pathology, and CCA - Innovative therapy
Subjects: Adult, Male, mycosis fungoide, Pathology, medicine.medical_specialty, Histology, Lymphoma, diagnosis, Prognosi, CD8-Positive T-Lymphocytes, Cutaneous lymphoma, Pathology and Forensic Medicine, Immunophenotyping, hemic and lymphatic diseases, Medicine, Neoplasm, Humans, Lymphomatoid papulosis, Pathological, Aged, Aged, 80 and over, Mycosis fungoides, business.industry, mycosis fungoides, CD8 antigen, lymphoma, diagnosis, mycosis fungoides, prognosis, General Medicine, CD8 antigen, Middle Aged, medicine.disease, Lymphoma, T-Cell, Cutaneous, diagnosi, Pagetoid, Female, prognosis, business, CD8
Abstract: AIMS: Aggressive epidermotropic cutaneous CD8+ lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8+ lymphomas.METHODS & RESULTS: Sixty-one CD8+ cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed & recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8+ lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and have striking pagetoid epidermotropism histologically. A CD8+ CD45RA+ CD45RO- CD2- CD5- CD56- phenotype, with 1 or more cytotoxic markers was found in 7/18 with a very similar phenotype in the remainder.. The tumours seldom involve lymph nodes but mucosae and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8+ mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp presented the typical features well documented in the CD4+ forms of those diseases.CONCLUSIONS: Aggressive Epidermotropic Cutaneous CD8+ Lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications. This article is protected by copyright. All rights reserved.
Published: 2015

49. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B

Author: Hervé Tilly, Olivier Casasnovas, Nicolas Mounier, Francoise Berger, Catherine Thieblemont, Corinne Haioun, Marie-Christine Copin, Karen Leroy, Jean-Philippe Jais, Danielle Canioni, Philippe Gaulard, Christiane Copie-Bergman, Bertrand Coiffier, Franck Morschauser, Tony Petrella, Christian Recher, Gilles Salles, Fabrice Jardin, Thierry Jo Molina, Josette Brière, Bettina Fabiani, and Christophe Fermé
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Vincristine, Pathology, Vindesine, Prednisolone, Kaplan-Meier Estimate, CHOP, Disease-Free Survival, Proto-Oncogene Proteins c-myc, Antibodies, Monoclonal, Murine-Derived, Bleomycin, International Prognostic Index, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Biomarkers, Tumor, Humans, Cyclophosphamide, Chemokine CCL2, Proportional Hazards Models, business.industry, Middle Aged, BCL6, medicine.disease, Immunohistochemistry, Lymphoma, DNA-Binding Proteins, Treatment Outcome, Doxorubicin, Interferon Regulatory Factors, Proto-Oncogene Proteins c-bcl-6, Prednisone, Rituximab, Female, Neprilysin, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, Germinal center B-cell like diffuse large B-cell lymphoma, business, Algorithms, medicine.drug
Abstract: Purpose To determine whether any tumor biomarkers could account for the survival advantage observed in the LNH 03-2B trial among patients with diffuse large B-cell lymphoma (DLBCL) and low-intermediate risk according to the International Prognostic Index when treated with dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) compared with standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Patients and Methods Using immunohistochemistry, expression of CD10, BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were examined. The interaction effects between each biomarker and treatment arm on survival were studied in a restricted model and a full model incorporating clinical parameters. Results Among the 379 patients analyzed in the trial, 229 tumors were evaluable for germinal center B-cell–like (GCB)/non-GCB subclassification according to the Hans algorithm. Among all the biomarkers, only the interaction between the Hans algorithm and the treatment arm was significant for progression-free survival (PFS) and overall survival (OS) in univariable (PFS, P = .04; OS, P = .01) and multivariable (PFS, P = .03; OS, P = .01) analyses. Non-GCB tumors predicted worse PFS (hazard ratio [HR], 3.21; 95% CI, 1.29 to 8.00; P = .01) and OS (HR, 6.09; 95% CI, 1.37 to 27.03; P = .02) among patients treated with R-CHOP compared with patients who received R-ACVBP, whereas there were no significant survival differences between these regimens among patients with GCB tumors. Conclusion The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to improved survival among patients with non-GCB DLBCL. Therefore, the Hans algorithm could be considered a theragnostic biomarker for selecting young patients with DLBCL who can benefit from an intensified R-ACVBP immunochemotherapy regimen.
Published: 2014

50. Immune response and alteration of pulmonary function after primary human metapneumovirus (hMPV) infection of BALB/c mice

Author: Magali Darniot, Pierre Pothier, Serge Aho, Catherine Manoha, and Tony Petrella
Subjects: viruses, Antibodies, Viral, Virus, BALB/c, Mice, Human metapneumovirus, Chlorocebus aethiops, medicine, Animals, Lung, Vero Cells, Mice, Inbred BALB C, Paramyxoviridae Infections, General Veterinary, General Immunology and Microbiology, medicine.diagnostic_test, biology, Public Health, Environmental and Occupational Health, virus diseases, respiratory system, Airway obstruction, medicine.disease, biology.organism_classification, Virus Shedding, respiratory tract diseases, Airway Obstruction, Disease Models, Animal, Pneumonia, Infectious Diseases, Bronchoalveolar lavage, medicine.anatomical_structure, Immunology, Cytokines, Molecular Medicine, Female, Metapneumovirus, Bronchial Hyperreactivity, Respiratory tract
Abstract: Human metapneumovirus (hMPV), a recently identified virus, causes upper and lower respiratory tract diseases. In this study, we show that BALB/c mice inoculated with hMPV exhibited significant morbidity on 1–2 days post-infection, when airway obstruction was found. Increased airway hyper-responsiveness to metacholine was found on day 4 concurrent with lung viral replication. Both IgG1 and IgG2a hMPV-specific antibodies were found in sera, while interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were found in bronchoalveolar lavage. Lung histology showed parenchymal pneumonia and increased lymphocytic infiltration. We present here an animal model that may be helpful in studying hMPV pathogenesis and evaluating the effects of vaccines.
Published: 2005

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

132 results on '"Tony Petrella"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources