Purpose : Describe clinical characteristics and outcome of Li-Fraumeni-associated osteosarcomas. Methods : TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from the SEER (National Cancer Institute’s Surveillance, Epidemiology, and End Results) for patients of the same age group. Results : Median age at first osteosarcoma diagnosis was 13.7 years (range:5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients <10 years (23% versus 9%) and, when compared with osteosarcomas in patients <25 years were characterized by an excess of axial (16% versus 10%) and jaw sites (15% versus 3%) and histology with predominant chondroblastic component (35% versus 16%) and periosteal subtypes (17% versus 1%). Metastases incidence (25%) was as expected in unselected osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%[95%CI:42.6−71.1]) were as expected in unselected series of osteosarcomas whereas the 5-year event-free survival was 36.5%[95%CI: 25.3−52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 55.3%[95%CI:34.3-69.5]. Conclusion : In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up.

Botryoid growth pattern (BGP) is a polypoid mass growing into the renal pelvis, rarely seen in bilateral Wilms tumors (BWT) where it represents a surgical challenge. We report our experience of nephron sparing surgery (NSS) in three patients with BGP in BWT. Surgical en-bloc removal was performed after calyx opening with no complications. The histology of the BGP was Intra Lobar Nephrogenic Rest in all cases while all Wilms tumors were of intermediate risk. One patient early recurred. At a follow-up of 9 months, 22 and 23 years, all patients were alive with a moderate renal insufficiency and hypertension.

Background. Osteonecrosis (ON) is a long-known complication of acute leukemia (AL) management affecting 1 to 10% of young patients, leading to long-term morbidity. Widespread access to Magnetic Resonance Imagery (MRI) over the past ten years has allowed earlier detection and more accurate assessment. This study investigated clinical and radiological features of ON, among the large French cohort L.E.A (Leucémie Enfant Adolescent) Procedure. Patients with ON were retrospectively enrolled and risk factors for the onset, the multifocal involvement and severe damage were analyzed. Quality of life (QoL) was also evaluated. A sub-study described radiological features. Results. 129/4973 patients developed ON (2.5%) and were preferentially aged over 10 years at time of AL diagnosis (OR 22.46, p <10-6). Females were preferentially affected (OR 1.8, p=0.002) like patients treated for relapse (OR 1.81, p=0.041). Patients presenting ON suffered more frequently from other sequelae (p<10-6). Most of the necrosis were involving weight-bearing joints and multiple joints in 69% of cases. MRI of 39 patients with ON were double blinded reviewed. Overall, 14/39 suffered from severe impairment, preferentially on hips. QoL of adolescents and adults was poor and permanently affected once ON occurred. Conclusions. Age of over 10 years at diagnosis of AL, relapse and female sex were at risk of developing ON involving preferentially multiple joints. One third was severe and lasting poor QoL impacting several domains was found. Future studies should include prospective data on management and biological genetic features to build a targeted screening program to detect and manage ON earlier.