Antoine Italiano1, Ilaria Di Mauro2, Jocelyn Rapp2, Gaëlle Pierron3, Nathalie Auger4, Laurent Alberti5, Frédéric Chibon6, Fabienne Escande7, Anne-Claire Voegeli8, Jean-Pierre Ghnassia9, Frédérique Keslair2, Marick Laé10, Dominique Ranchère-Vince5, Philippe Terrier4, Sandrine Baffert11, Jean-Michel Coindre6, Florence Pedeutour2. 1. Early Phase Trials and Sarcoma Units, Bergonie Cancer Institute, Bordeaux, France. Electronic address: a.italiano@bordeaux.unicancer.fr. 2. Laboratory of Solid Tumor Genetics, Nice University Hospital, Nice, France; Institute for Research on Cancer and Aging of Nice (IRCAN), Faculty of Medicine, University of Nice-Sophia-Antipolis, CNRS, Nice, France. 3. Genetic Somatic Units, Institut Curie, Paris, France. 4. Department of Pathology and Medical Biology, Gustave-Roussy Institute, Villejuif, France. 5. Department of Pathology, Leon Bérard Center, Lyon, France. 6. Department of Pathology, Bergonié Cancer Institute, INSERM U916, University of Bordeaux, France. 7. Department of Biochemistry and Molecular Biology, Lille University Hospital, Lille, France. 8. Department of Biochemistry and Molecular Biology, Department of Pathology, Strasbourg University Hospital, Strasbourg, France. 9. Department of Pathology, Paul Strauss Institute, Strasbourg, France. 10. Department of Pathology, Institut Curie, Paris, France. 11. Institut Curie, Paris, France.
Abstract
BACKGROUND: Advances in molecular genetics of sarcoma have enabled the identification of type-specific aberrations. We aimed to assess the clinical effect of systematic implementation of molecular assays to improve sarcoma misdiagnosis. METHODS: In this multicentre, observational study, we recruited patients from 32 centres of the French Sarcoma Group/Reference Network in Pathology of Sarcomas. Eligibility criteria included: biopsy or surgical resection; suspicion of: dermatofibrosarcoma protuberans (cohort 1), dedifferentiated liposarcoma (cohort 2), Ewing's sarcoma family of tumours (cohort 3), synovial sarcoma (cohort 4), alveolar rhabdomyosarcoma (cohort 5), and myxoid or round cell liposarcoma (cohort 6); review by one sarcoma-expert pathologist; availability of frozen material (except for cohort 1 of patients with dermatofibrosarcoma protuberans because anti-CD34 immunohistochemistry is performed on paraffin-embedded tissue); and patient information. For each case, the pathologist made one primary diagnosis followed by up to two differential diagnoses, based on histological characteristics only. Each diagnosis was classified as certain, probable, or possible. For each case to determine the molecular classification, we did fluorescence in-situ hybridisation on paraffin-embedded samples. We also did comparative genomic hybridisation and quantitative PCR (cohort 2) or reverse transcriptase PCR (cohorts 3-6) on frozen and paraffin-embedded samples. We made a final diagnosis based on the molecular results. The clinical effect of diagnosis correction was assessed by a board of experts. FINDING: Between June 22, 2009, and Oct 30, 2012, 395 patients were enrolled in the study, of which 384 were eligible for inclusion. The diagnosis was eventually modified by molecular genetics for 53 patients: eight (16%) of 50 patients with dermatofibrosarcoma (cohort 1), seven (23%) of 30 patients with dedifferentiated liposarcoma (cohort 2), 13 (12%) of 112 with Ewing's sarcoma family of tumours (cohort 3), 16 (16%) of 97 patients with synovial sarcoma (cohort 4), seven (15%) of 46 patients with alveolar rhabdomyosarcoma (cohort 5), and two (4%) of 49 patients with myxoid or round cell liposarcoma (cohort 6), with an effect on primary management or prognosis assessment in 45 cases. INTERPRETATION: Molecular genetic testing should be mandatory for diagnostic accuracy of sarcoma and appropriate clinical management, even when histological diagnosis is made by pathologist experts in this field. FUNDING: French National Cancer Institute and Nice University Hospital.
BACKGROUND: Advances in molecular genetics of sarcoma have enabled the identification of type-specific aberrations. We aimed to assess the clinical effect of systematic implementation of molecular assays to improve sarcoma misdiagnosis. METHODS: In this multicentre, observational study, we recruited patients from 32 centres of the French Sarcoma Group/Reference Network in Pathology of Sarcomas. Eligibility criteria included: biopsy or surgical resection; suspicion of: dermatofibrosarcoma protuberans (cohort 1), dedifferentiated liposarcoma (cohort 2), Ewing's sarcoma family of tumours (cohort 3), synovial sarcoma (cohort 4), alveolar rhabdomyosarcoma (cohort 5), and myxoid or round cell liposarcoma (cohort 6); review by one sarcoma-expert pathologist; availability of frozen material (except for cohort 1 of patients with dermatofibrosarcoma protuberans because anti-CD34 immunohistochemistry is performed on paraffin-embedded tissue); and patient information. For each case, the pathologist made one primary diagnosis followed by up to two differential diagnoses, based on histological characteristics only. Each diagnosis was classified as certain, probable, or possible. For each case to determine the molecular classification, we did fluorescence in-situ hybridisation on paraffin-embedded samples. We also did comparative genomic hybridisation and quantitative PCR (cohort 2) or reverse transcriptase PCR (cohorts 3-6) on frozen and paraffin-embedded samples. We made a final diagnosis based on the molecular results. The clinical effect of diagnosis correction was assessed by a board of experts. FINDING: Between June 22, 2009, and Oct 30, 2012, 395 patients were enrolled in the study, of which 384 were eligible for inclusion. The diagnosis was eventually modified by molecular genetics for 53 patients: eight (16%) of 50 patients with dermatofibrosarcoma (cohort 1), seven (23%) of 30 patients with dedifferentiated liposarcoma (cohort 2), 13 (12%) of 112 with Ewing's sarcoma family of tumours (cohort 3), 16 (16%) of 97 patients with synovial sarcoma (cohort 4), seven (15%) of 46 patients with alveolar rhabdomyosarcoma (cohort 5), and two (4%) of 49 patients with myxoid or round cell liposarcoma (cohort 6), with an effect on primary management or prognosis assessment in 45 cases. INTERPRETATION: Molecular genetic testing should be mandatory for diagnostic accuracy of sarcoma and appropriate clinical management, even when histological diagnosis is made by pathologist experts in this field. FUNDING: French National Cancer Institute and Nice University Hospital.
Authors: Matthew R Avenarius; Cecelia R Miller; Michael A Arnold; Selene Koo; Ryan Roberts; Martin Hobby; Thomas Grossman; Yvonne Moyer; Richard K Wilson; Elaine R Mardis; Julie M Gastier-Foster; Ruthann B Pfau Journal: J Mol Diagn Date: 2020-08-01 Impact factor: 5.568
Authors: Lauren McConnell; Oisín Houghton; Peter Stewart; Jana Gazdova; Shambhavi Srivastava; Chang Kim; Mark Catherwood; Anna Strobl; Adrienne M Flanagan; Anca Oniscu; Leonie I Kroeze; Patricia Groenen; Philippe Taniere; Manuel Salto-Tellez; David Gonzalez Journal: Mod Pathol Date: 2020-02-11 Impact factor: 7.842