title: Intimal sarcoma is the most frequent primary cardiac sarcoma: clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomas.
abstract: We report novel molecular and pathologic features of sarcomas involving the heart. Intimal sarcoma appears as the most frequent primary cardiac sarcoma within the largest described series of 100 primary cardiac sarcomas. Immunohistochemical analysis, fluorescence in situ hybridization, real-time polymerase chain reaction, and array-comparative genomic hybridization were performed on materials from 65 women and 35 men, aged 18 to 82 years (mean 50 y), retrieved from the French Departments of Pathology, between 1977 and early 2013. Right and left heart was involved in 44 and 56 cases, respectively. There were 42 intimal sarcomas, 26 angiosarcomas, 22 undifferentiated sarcomas, 7 synovial sarcomas, 2 leiomyosarcomas, and 1 peripheral neuroectodermal tumor. All but 1 angiosarcomas originated from the right heart, whereas 83% of the intimal sarcomas and 72% of the undifferentiated sarcomas were from the left heart. MDM2 overexpression was immunohistochemically observed in all intimal sarcomas, as well as in 10 of the 22 undifferentiated sarcomas and in 5 of the 26 angiosarcomas. MDM2 amplification was only demonstrated in intimal sarcomas. Genomic analysis showed a complex profile, with recurrent 12q13-14 amplicon involving MDM2, 4q12 amplicon involving KIT and PDGFRA, 7p12 gain involving EGFR, and 9p21 deletion targeting CDKN2A. Immunohistochemical detection of MDM2 overexpression can easily detect intimal sarcoma, provided that molecular aberration is proved. As resections are limited to the left atrium, this histologic subtype could benefit from therapies targeting PDGFRA or MDM2.
authors.affiliation: *University of Bordeaux †INSERM U916 ‡Department of Biopathology, Institut Bergonié, Bordeaux §Department of Pathology, Centre Georges-François Leclerc, Dijon ∥Department of Pathology, Hôpital Européen Georges Pompidou, Paris ¶Department of Pathology, Hôpital du Haut-Lévèque, Pessac #Department of Pathology, Hôpital Universitaire, Lyon **Department of Pathology, Hôpital Rangueil, Toulouse ††Department of Pathology, Institut Gustave Roussy, Villejuif ‡‡Department of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson §§Department of Pathology, Hôpital Universitaire, Rennes, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Neuville
authors.forename: Françoise
authors.initials: F
authors.lastname: Collin
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Marie
authors.initials: M
authors.lastname: Parrens
authors.forename: Françoise
authors.initials: F
authors.lastname: Thivolet
authors.forename: Anne
authors.initials: A
authors.lastname: Gomez-Brouchet
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.forename: Vincent Thomas
authors.initials: VT
authors.lastname: de Montpreville
authors.forename: François
authors.initials: F
authors.lastname: Le Gall
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hostein
authors.forename: Pauline
authors.initials: P
authors.lastname: Lagarde
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chibon
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002877:Chromosomes, Human; D055028:Comparative Genomic Hybridization; D005260:Female; D006338:Heart Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor