Medulloblastomas associated with an APC germline pathogenic variant share the good prognosis of CTNNB1-mutated medulloblastomas

authors

• Surun Aurore
• Varlet Pascale
• Brugières Laurence
• Lacour Brigitte
• Faure-Conter Cécile
• Leblond Pierre
• Bertozzi-Salomon Anne-Isabelle
• Berger Claire
• André Nicolas
• Sariban Eric
• Raimbault Sandra
• Prieur Fabienne
• Desseigne Françoise
• Zattara Hélène
• Guimbaud Rosine
• Polivka Marc
• Delisle Marie-Bernadette
• Vasiljevic Alexandre
• Maurage Claude-Alain
• Figarella-Branger Dominique
• Coulet Florence
• Guerrini-Rousseau Léa
• Alapetite Claire
• Dufour Christelle
• Colas Chrystelle
• Doz François
• Bourdeaut Franck

document type

abstract

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.

more information