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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.

Medulloblastoma may occur in a context of APC germline mutation and familial adenomatous polyposis. We aimed to describe clinical features of patients with medulloblastoma occurring in this context. We performed a multicentric retrospective review of French and Belgian patients treated for medulloblastoma with identified or highly suspected (personal or familial history) APC germline mutation. Genetic status, clinical and histological characteristics, treatments and outcome were reported. Eleven patients with known or suspected APC germline mutation, mostly on exon 15 (N=6/9 available data), were diagnosed with medulloblastoma at a median age of 10.6 years [6-32]. Medulloblastomas were mainly non-metastatic (N=9/11), classic (N=9/9 available data, central review ongoing), with no significant residual tumor after surgery (N=9/11). All patients underwent radiotherapy (median craniospinal dose: 35 Gy), combined with chemotherapy for 10 patients. No relapse was noticed (median follow-up: 11 years). Secondary tumors (N=8) occurred in 7 patients, including 1 lethal malignant Triton tumor in the irradiation field, 1 thyroid carcinoma, and 6 desmoid tumors (5 abdominal tumors, 1 occipital tumor in the irradiation field). Pre-symptomatic polyposis was diagnosed for 9 patients at a median age of 15.5 years, prior to medulloblastoma for 2 of them. Medulloblastomas associated with APC germline mutation have favorable clinical outcome, even for metastatic tumors, with no relapse in this small series of patients, in line with WNT-medulloblastomas’ profile. Yet, long-term survival is clouded by second tumor occurrence, with potential radiation-induced tumors. These findings raise the question of applying de-escalation therapeutic protocol for these patients with reduced intensity craniospinal irradiation.