Published reports dealing with tumor prosthesis have yet to establish a clear advantage of using either cemented or cementless implants. We examined the outcome and complications with modular cemented implants in 135 patients identified from our database to strengthen the argument for routine use of cemented constructs. The minimum followup was 1.4 months (mean, 57 months; median, 47 months; range, 1.4-157 months). The majority of patients (104) had sarcoma. The complications included: 11 infections, three of which underwent amputation and one a stem revision; eight local recurrences, five of which underwent amputation; three hip dislocations; and three incidents of shoulder instability. One periprosthetic femur fracture was stabilized operatively. There was no aseptic loosening or stem fracture. The 5-year survival rates for distal femoral and proximal humeral replacements were 84% and 70%; the 10-year survival rates were 79% and 59%. The 5-year survival rates for proximal femur and proximal tibia replacements were 78% and 37%. Average Musculoskeletal Tumor Society 1987 scores and Toronto Extremity Salvage Scores were 21.5 and 73% for proximal femur, 28.1 and 67% for distal femur, and 21 and 78% for proximal humerus. The survival of the endoprostheses related to site of bone resection. Cemented constructs of modern design in the context of tumor surgery provide good short-term results. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Multimodality treatment of primary soft tissue sarcoma by expert teams reportedly affords a low incidence of local recurrence. Despite advances, treatment of local recurrence remains difficult and is not standardized. We (1) determined the incidence of local recurrence from soft tissue sarcoma; (2) compared characteristics of the recurrent tumors with those of the primary ones; (3) evaluated local recurrences, metastases and death according to treatments; and (4) explored the relationship between the diagnosis of local recurrence and the occurrence of metastases. From our prospective database, we identified 618 soft tissue sarcomas. Thirty-seven of the 618 patients (6%) had local recurrence. Leiomyosarcoma was the most frequent diagnosis (eight of 37). The mean delay from original surgery was 22 months (range, 2–75 months). Mean size was 4.8 cm (range, 0.4–28.0 cm). Median followup after local recurrence was 16 months (range, 0–98 months). Recurrent tumors had a tendency toward becoming deeper seated and higher graded. Nineteen of the 37 patients with recurrence underwent limb salvage (nine free flaps) and six had an amputation. Twenty-two (59%) had metastases, including 10 occurring after the local recurrence event at an average delay of 21 months (range, 1–34 months). Six patients developed additional local recurrences, with no apparent difference in risk between amputation (two of six) and limb salvage (four of 19). Patients with a local recurrence of a soft tissue sarcoma have a poor prognosis. Limb salvage and additional radiotherapy remain possible but with substantial complications. Amputation did not prevent additional local recurrence or death. Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

BACKGROUND. DICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset lesions. Other susceptibility genes for familial forms of MNG likely exist. METHODS. Whole-exome sequencing of a kindred with early-onset MNG and schwannomatosis was followed by investigation of germline pathogenic variants that fully segregated with the disease. Genome-wide analyses were performed on 13 tissue samples from familial and nonfamilial DGCR8-E518K–positive tumors, including MNG, schwannomas, papillary thyroid cancers (PTCs), and Wilms tumors. miRNA profiles of 4 tissue types were compared, and sequencing of miRNA, pre-miRNA, and mRNA was performed in a subset of 9 schwannomas, 4 of which harbor DGCR8-E518K. RESULTS. We identified c.1552G>A;p.E518K in DGCR8, a microprocessor component located in 22q, in the kindred. The variant identified is a somatic hotspot in Wilms tumors and has been identified in 2 PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the DGCR8 locus, was found in all 13 samples harboring c.1552G>A;p.E518K. miRNA profiling of PTCs, MNG, schwannomas, and Wilms tumors revealed a common profile among E518K hemizygous tumors. In vitro cleavage demonstrated improper processing of pre-miRNA by DGCR8-E518K. MicroRNA and RNA profiling show that this variant disrupts precursor microRNA production, impacting populations of canonical microRNAs and mirtrons. CONCLUSION. We identified DGCR8 as the cause of an unreported autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter with schwannomatosis. FUNDING. Canadian Institutes of Health Research, Compute Canada, Alex’s Lemonade Stand Foundation, the Mia Neri Foundation for Childhood Cancer, Cassa di Sovvenzioni e Risparmio fra il Personale della Banca d’Italia, and the KinderKrebsInitiative Buchholz/Holm-Seppensen.