1. Medulloblastomas associated with an APC germline pathogenic variant share the good prognosis of CTNNB1-mutated medulloblastomas
- Author
-
Marie-Bernadette Delisle, Anne-Isabelle Bertozzi-Salomon, Marc Polivka, Hélène Zattara, Aurore Surun, Laurence Brugières, Fabienne Prieur, Franck Bourdeaut, Alexandre Vasiljevic, Pierre Leblond, Pascale Varlet, Nicolas André, Françoise Desseigne, Dominique Figarella-Branger, Eric Sariban, Rosine Guimbaud, Christelle Dufour, Cécile Faure-Conter, Claire Alapetite, Florence Coulet, Léa Guerrini-Rousseau, Chrystelle Colas, François Doz, Sandra Raimbault, Claude-Alain Maurage, Brigitte Lacour, Claire Berger, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], and Hôpital de la Timone [CHU - APHM] (TIMONE)
- Subjects
Adult ,Male ,Cancer Research ,Adolescent ,Adenomatous polyposis coli ,[SDV]Life Sciences [q-bio] ,Adenomatous Polyposis Coli Protein ,Context (language use) ,medulloblastoma ,Germline ,Thyroid carcinoma ,WNT ,03 medical and health sciences ,0302 clinical medicine ,Gardner Syndrome ,Medicine ,Humans ,Cerebellar Neoplasms ,Child ,Gardner syndrome ,Osteoma ,neoplasms ,Germ-Line Mutation ,beta Catenin ,030304 developmental biology ,Retrospective Studies ,Medulloblastoma ,0303 health sciences ,biology ,business.industry ,Wnt signaling pathway ,Editorials ,medicine.disease ,familial adenomatosis polyposis ,3. Good health ,nervous system diseases ,APC ,stomatognathic diseases ,Oncology ,Adenomatous Polyposis Coli ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Female ,Neurology (clinical) ,business - 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.
- Published
- 2020