Anna Paioli1, Silvia Stacchiotti2, Domenico Campanacci3, Emanuela Palmerini4, Anna Maria Frezza2, Alessandra Longhi4, Stefano Radaelli5, Davide Maria Donati6, Giovanni Beltrami3, Giuseppe Bianchi6, Marta Barisella7, Alberto Righi8, Stefania Benini8, Marco Fiore5, Piero Picci8,9, Alessandro Gronchi5. 1. Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. anna.paioli@ior.it. 2. Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 3. Department of Orthopedic Oncology, Azienda Ospedaliera Careggi, Florence, Italy. 4. Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 5. Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 6. Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 7. Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 8. Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 9. Italian Sarcoma Group (I.S.G.), San Lazzaro di Savena, Bologna, Italy.
Abstract
BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain origin, marked by specific chromosomal translocations involving the NR4A3 gene, and usually characterized by an indolent course. Surgery (with or without radiotherapy) is the treatment of choice in localized disease. The treatment for advanced disease remains uncertain. In order to better evaluate prognostic factors and outcome, a retrospective pooled analysis of patients with EMC treated at three Italian Sarcoma Group (ISG) referral centers was carried out. METHODS: All patients with localized EMC surgically treated from 1989 to 2016 were identified. Diagnosis was centrally reviewed according to WHO 2013. Only patients with NR4A3 rearrangement were included. RESULTS: Sixty-seven patients were identified: 13 (20%) female, 54 (80%) male. Median age was 56 years (range 18-84). Numbers and type of translocation were: 50 (80%) NR4A3-EWS, 10 (16%) NR4A3-TAF15, 1 (2%) NR4A3-TCF12, and 1 (2%) NR4A3-TFG. Median follow-up was 55 months (range 2-312). Five- and ten-year overall survival rates were 94% (86-100 95%CI) and 84% (69-98 95%CI). Thirty-five (52%) patients relapsed: 9 had local recurrence (LR) and 26 had distant metastasis (5 with concomitant LR). The 5- and 10-year disease-free survival rates (DFS) were 51% (38-65 95%CI) and 20% (7-33 95%CI). Size of the primary tumor was significantly related to distant metastasis-free survival (DMFS) (p = 0.004). Patients carrying the NR4A3-EWS translocation had a trend in favor of better DFS (p = 0.08) and DMFS (p = 0.09) compared with the patients with NR4A3-TAF15. CONCLUSIONS: Prolonged survival can be expected in patients with EMC, in spite of a high rate of recurrence. Size is significantly associated with distant relapse. The type of NR4A3 translocation could influence outcome.
BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain origin, marked by specific chromosomal translocations involving the NR4A3 gene, and usually characterized by an indolent course. Surgery (with or without radiotherapy) is the treatment of choice in localized disease. The treatment for advanced disease remains uncertain. In order to better evaluate prognostic factors and outcome, a retrospective pooled analysis of patients with EMC treated at three Italian Sarcoma Group (ISG) referral centers was carried out. METHODS: All patients with localized EMC surgically treated from 1989 to 2016 were identified. Diagnosis was centrally reviewed according to WHO 2013. Only patients with NR4A3 rearrangement were included. RESULTS: Sixty-seven patients were identified: 13 (20%) female, 54 (80%) male. Median age was 56 years (range 18-84). Numbers and type of translocation were: 50 (80%) NR4A3-EWS, 10 (16%) NR4A3-TAF15, 1 (2%) NR4A3-TCF12, and 1 (2%) NR4A3-TFG. Median follow-up was 55 months (range 2-312). Five- and ten-year overall survival rates were 94% (86-100 95%CI) and 84% (69-98 95%CI). Thirty-five (52%) patients relapsed: 9 had local recurrence (LR) and 26 had distant metastasis (5 with concomitant LR). The 5- and 10-year disease-free survival rates (DFS) were 51% (38-65 95%CI) and 20% (7-33 95%CI). Size of the primary tumor was significantly related to distant metastasis-free survival (DMFS) (p = 0.004). Patients carrying the NR4A3-EWS translocation had a trend in favor of better DFS (p = 0.08) and DMFS (p = 0.09) compared with the patients with NR4A3-TAF15. CONCLUSIONS: Prolonged survival can be expected in patients with EMC, in spite of a high rate of recurrence. Size is significantly associated with distant relapse. The type of NR4A3 translocation could influence outcome.
Authors: Milena Urbini; Annalisa Astolfi; Maria Abbondanza Pantaleo; Salvatore Serravalle; Angelo Paolo Dei Tos; Piero Picci; Valentina Indio; Marta Sbaraglia; Stefania Benini; Alberto Righi; Marco Gambarotti; Alessandro Gronchi; Chiara Colombo; Gian Paolo Dagrada; Silvana Pilotti; Roberta Maestro; Maurizio Polano; Maristella Saponara; Giuseppe Tarantino; Andrea Pession; Guido Biasco; Paolo Giovanni Casali; Silvia Stacchiotti Journal: Genes Chromosomes Cancer Date: 2017-05-04 Impact factor: 5.006
Authors: Alex D Drilon; Sanjay Popat; Gauri Bhuchar; David R D'Adamo; Mary Louise Keohan; Cyril Fisher; Cristina R Antonescu; Samuel Singer; Murray F Brennan; Ian Judson; Robert G Maki Journal: Cancer Date: 2008-12-15 Impact factor: 6.860
Authors: C Filion; T Motoi; A B Olshen; M Laé; R J Emnett; D H Gutmann; A Perry; M Ladanyi; Y Labelle Journal: J Pathol Date: 2009-01 Impact factor: 7.996
Authors: Geraldine O'Sullivan Coyne; Shivaani Kummar; James Hu; Kristen Ganjoo; Warren A Chow; Khanh T Do; Jennifer Zlott; Ashley Bruns; Lawrence Rubinstein; Jared C Foster; Lamin Juwara; Robert Meehan; Richard Piekarz; Howard Streicher; Elad Sharon; Naoko Takebe; Andrea Regier Voth; Donald Bottaro; Rene Costello; John J Wright; James H Doroshow; Alice P Chen Journal: Clin Cancer Res Date: 2021-10-29 Impact factor: 13.801
Authors: Michael P Fice; Linus Lee; Pavan Kottamasu; Abdullah Almajnooni; Matthew R Cohn; Charles A Gusho; Steven Gitelis; Alan T Blank Journal: Rare Tumors Date: 2022-02-25