Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an “in-house” gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.

Background: Medulloblastoma has one of the highest rates of metastasis outside the central nervous system (CNS). Bone metastases are the most common lesions, although lymph node and visceral spread have also been reported. Objective: To present patients with bone metastasis in medulloblastoma and discuss their radiologic appearances and treatment approach. Patients and methods: From 1993 to 2008, 82 patients diagnosed with medulloblastoma were treated at the Institute for Oncology and Radiology of Serbia. Three (3.6%) developed extraneural metastasis (ENM). In primary treatment, patients were treated with surgery, craniospinal radiotherapy with local boost to tumor bed, and adjuvant chemotherapy [lomustine (CCNU) and vincristine]. Of the three patients with ENM, all developed bone metastases at the time of relapse. Relapse occurred within 17 to 42 months of initial diagnosis. Patients received secondary chemotherapy and palliative radiotherapy to the affected bone in two cases. Results: Among these three patients, case 1 had initially a solitary lytic lesion. Case 2 had diffuse blastic lesions and also bone marrow involvement. Case 3 had multiple mixed lytic-sclerotic lesions but later developed lymph node metastasis and metastases to both breasts, as well. All patients were without concurrent CNS involvement at the time of ENM. Unfortunately, after initial partial response, the three patients died at 24, 13, and 18 months after detection of metastases, respectively. Conclusion: With prolonged survival times in children with medulloblastoma, more emphasis should be placed on the possibility of systemic involvement. A greater understanding of the pathogenesis of the systemic metastases may be valuable in designing future, more aggressive multimodal therapy.

Background and Objectives: Before the introduction of griseofluvin, the use of X-ray radiation was the treatment of choice for tinea capitis. More than half a century later various types of tumors have been found to be associated with childhood irradiation due to tinea capitis, most commonly cancers of the head and neck, as well as brain tumors. The often unusually aggressive and recurrent nature of these tumors necessitates the need for repeated surgeries, while the atrophic skin with an impaired vascular supply due to radiation often poses an additional challenge for defect reconstruction. We present our experience in the surgical treatment of such patients. Materials and Methods: This is a retrospective cohort study. In this study, 37 patients treated for acquired defects of the scalp with a history of irradiation therapy due to tinea capitis in childhood were included in this study, 24 male and 13 female patients. The mean age at the first appointment was 60.6 ± 7.8, with the youngest included patient being 46 and the oldest being 75 years old. Patients’ characteristics, surgical treatment, and complications were analyzed and a reconstructive algorithm was developed. Results: Local flaps were used for reconstruction in 34 patients, direct sutures were used in 10 patients and 20 patients received split-thickness skin grafts for coverage of both primary and secondary defects for reconstruction of flap donor sites. One regional flap and one dermal substitute covered by an autologous skin graft were also used for reconstruction. Complications occurred in 43.2% of patients and were significantly associated with the presence of comorbidities (p = 0.001), aseptic bone necrosis (p = 0.001), as well as skin atrophy in frontal, occipital, and parietal region (p = 0.001, p = 0.042 and p = 0.001, respectively). A significant correlation between major complications and moderate skin atrophy was found only in the parietal region (p = 0.026). Conclusions: Unfortunately, many protocols developed for scalp reconstruction are not applicable in the setting of severe or diffuse scalp skin atrophy associated with high tumor recurrence rate and radiation-induced vascular impairment, such as in tinea capitis patients in Serbia. An algorithm has been developed based on the authors’ experience in managing these patients.