Aurore Surun1,2, Pascale Varlet2,3, Laurence Brugières4, Brigitte Lacour5, Cécile Faure-Conter6, Pierre Leblond7, Anne-Isabelle Bertozzi-Salomon8, Claire Berger9, Nicolas André10, Eric Sariban11, Sandra Raimbault4, Fabienne Prieur12, Françoise Desseigne13, Hélène Zattara14, Rosine Guimbaud15, Marc Polivka16, Marie-Bernadette Delisle17, Alexandre Vasiljevic18, Claude-Alain Maurage19, Dominique Figarella-Branger20, Florence Coulet21, Léa Guerrini-Rousseau4, Claire Alapetite22, Christelle Dufour4, Chrystelle Colas23, François Doz1,2, Franck Bourdeaut1. 1. Curie Institute, SIREDO Cancer Center (Care, Innovation and Research in Pediatric, Adolescents, and Young Adults Oncology), Paris, France. 2. Paris Descartes University, Sorbonne Paris Cité, Paris, France. 3. Sainte Anne Hospital, Department of Neuropathology, Paris, France. 4. Gustave Roussy Cancer Center, Department of Pediatric and Adolescent Oncology, Paris-Saclay University, Villejuif, France. 5. CRESS Equipe 7 UMRS 1153, INSERM, Paris Descartes University, Paris, and National Registry of Solid Tumors, Nancy University Hospital, Vandoeuvre-les-Nancy, France. 6. Centre Leon Berard, Pediatric Hemato-oncology Institute (IHOP), Lyon, France. 7. Centre Oscar Lambret, Pediatric Oncology Department, Lille, France. 8. Toulouse University Hospital, Pediatric Hemato-oncology Department, Toulouse, France. 9. Saint-Etienne University Hospital, Pediatric Hemato-oncology Department, Saint-Etienne, France. 10. Aix Marseille University, La Timone, Pediatric Hemato-oncology Department, AP-HM, Marseille, France. 11. Hôpital des Enfants, Unité Cancer, Bruxelles, Belgique. 12. Saint-Etienne University Hospital, Genetic Department, Saint-Etienne, France. 13. Centre Leon Berard, Department of Medical Oncology, Lyon, France. 14. Marseille University, La Timone, Genetic Department, Marseille, France. 15. Centre Claudius Regaud, Oncogenetic Department, Toulouse, France. 16. University Hospital Lariboisière, Department of Pathology, Paris, France. 17. Toulouse University Hospital, Department of Pathology, Toulouse, France. 18. Hospices Civils de Lyon, Department of Pathology, Lyon, France. 19. Lille University Hospital, Department of Pathology, Lille, France. 20. Marseille University Hospital, Department of Pathology, Marseille, France. 21. Pitié Salpêtrière hospital, Genetic Department, Paris, France. 22. Curie Institute, Department of Radiation Oncology, Paris, France. 23. Curie Institute, Genetic Department, Paris, France.
Abstract
BACKGROUND: Medulloblastomas may occur in a predisposition context, including familial adenomatosis polyposis. Medulloblastomas related to a germline pathogenic variant of adenomatous polyposis coli (APC) remain rare and poorly described. Their similarities with sporadic WNT medulloblastomas still require description. METHODS: We performed a multicentric retrospective review of 12 patients treated between 1988 and 2018 for medulloblastoma with an identified or highly suspected (personal or familial history) APC germline pathogenic variant. We report personal and familial history APC gene pathogenic variants whenever available: clinical and histologic characteristics of the medulloblastoma, treatments, and long-term outcome, including second tumor and late sequelae. RESULTS: Medulloblastomas associated with APC pathogenic variants are mainly classic (11/11 patients, 1 not available), nonmetastatic (10/12 patients) medulloblastomas, with nuclear immunoreactivity for ß-catenin (9/9 tested cases). Ten of 11 assessable patients are disease free with a median follow-up of 10.7 years (range, 1-28 y). Secondary tumors included desmoid tumors in 7 patients (9 tumors), 1 thyroid carcinoma, 2 pilomatricomas, 1 osteoma, 1 vertebral hemangioma, and 1 malignant triton in the radiation field, which caused the only cancer-related death in our series. CONCLUSIONS: Medulloblastomas associated with an APC pathogenic variant have an overall favorable outcome, even for metastatic tumors. Yet, long-term survival is clouded by second tumor occurrence; treatment may play some role in some of these second malignancies. Our findings raise the question of applying a de-escalation therapeutic protocol to treat patients with APC germline pathogenic variants given the excellent outcome, and reduced intensity of craniospinal irradiation may be further evaluated.
BACKGROUND:Medulloblastomas may occur in a predisposition context, including familial adenomatosis polyposis. Medulloblastomas related to a germline pathogenic variant of adenomatous polyposis coli (APC) remain rare and poorly described. Their similarities with sporadic WNT medulloblastomas still require description. METHODS: We performed a multicentric retrospective review of 12 patients treated between 1988 and 2018 for medulloblastoma with an identified or highly suspected (personal or familial history) APC germline pathogenic variant. We report personal and familial history APC gene pathogenic variants whenever available: clinical and histologic characteristics of the medulloblastoma, treatments, and long-term outcome, including second tumor and late sequelae. RESULTS:Medulloblastomas associated with APC pathogenic variants are mainly classic (11/11 patients, 1 not available), nonmetastatic (10/12 patients) medulloblastomas, with nuclear immunoreactivity for ß-catenin (9/9 tested cases). Ten of 11 assessable patients are disease free with a median follow-up of 10.7 years (range, 1-28 y). Secondary tumors included desmoid tumors in 7 patients (9 tumors), 1 thyroid carcinoma, 2 pilomatricomas, 1 osteoma, 1 vertebral hemangioma, and 1 malignant triton in the radiation field, which caused the only cancer-related death in our series. CONCLUSIONS:Medulloblastomas associated with an APC pathogenic variant have an overall favorable outcome, even for metastatic tumors. Yet, long-term survival is clouded by second tumor occurrence; treatment may play some role in some of these second malignancies. Our findings raise the question of applying a de-escalation therapeutic protocol to treat patients with APC germline pathogenic variants given the excellent outcome, and reduced intensity of craniospinal irradiation may be further evaluated.
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