Pediatric chordoma associated with tuberous sclerosis complex: A rare case report with a thorough analysis of potential therapeutic molecular targets.

Chordoma associated with tuberous sclerosis complex (TSC) is an extremely rare tumor that was described only in 13 cases since 1975. Сhordoma itself is a malignant slow-growing bone tumor thought to arise from vestigial or ectopic notochordal tissue. Chordoma associated with TSC differs from chordoma in the general pediatric population in the median age, where the diagnosis of TSC-associated chordoma is 6.2 months, whereas for chordoma in the general pediatric population it is set to 12 years. The majority of TSC-associated chordomas are localized in skull-based and sacrum regions, and rare in the spine. Chordomas are genetically heterogeneous tumors characterized by chromosomal instability (CIN), and alterations involving PI3K-AKT signaling pathway genes and chromatin remodeling genes. Here we present the 14th case of chordoma associated with TSC in a 1-year-old pediatric patient. Alongside biallelic inactivation of the TSC1 gene, molecular genetic analysis revealed CIN and involvement of epigenetic regulation genes. In addition, we found the engagement of CBX7 and apolipoprotein B editing complex (APOBEC3) genes that were not yet seen in chordomas before. Amplification of CBX7 may epigenetically silence the CDKN2A gene, whereas amplification of APOBEC3 genes can explain the frequent occurrence of CIN in chordomas. We also found that KRAS gene is located in the region with gain status, which may suggest the ineffectiveness of potential EGFR monotherapy. Thus, molecular genetic analysis carried out in this study broadens the horizons of possible approaches for targeted therapies with potential applications for personalized medicine.

Testing of Actual Scanner Performance in a High-loaded UNIM Laboratory Environment.

BACKGROUND: Scanners are the main tool in digital pathology. The technical abilities of scanners determine the workflow logic in the pathology laboratory. Its performance can be restricted by the divergence between the scanning time presented by the manufacturer and the actual scanning time. This could lead to critical deviations from the established business processes in a 24/7 laboratory. AIM: Our investigation is focused in exploring the performance of three main models of high-performance scanners available on the Russian market: 3DHistech, Hamamatsu и Leica. OBJECTIVES: We compared the performance of the scanners on the samples of a given size with the manufacturer's stated specifications and evaluated the speed of the scanners on the reference and routine laboratory material. SUBJECTS AND METHODS: We examined 3DHistech Pannoramic 1000, Hamamatsu NanoZoomer s360 and Leica AT2 with default settings and automatic mode. Two sets of glasses were used (glass slide): Group 1 included 120 slides with 15 mm × 15 mm slices, Group 2 included 120 workflow slides. RESULTS: The average slide scan times in Groups 1 and 2 for the C13220 (156 ± 1.25 s and 117 ± 4.17 s) and Pannoramic 1000 (210 ± 1.64 s and 183 ± 3.78 s) differ statistically significantly (P < 0.0001). Total scanning time including rack reloading was shorter for the workflow slide set group for the modern C13220 and Pannoramic 1000 scanner models. CONCLUSIONS: The scanner specifications provided by manufacturers are not sufficient to evaluate the performance. The guidelines and regulations concerning scanner selection should be consented by the digital pathology community. We suggest discussing criteria for evaluating scanner performance.