Childhood Medulloblastoma in Latvia: Morphologic and Molecular Implications for Diagnostics and Personalised Treatment

Introduction. Medulloblastoma is among the most frequent childhood brain tumours. To the best of our knowledge, systematic studies of this entity have not been carried out in Latvia, and are scarce in the whole region. Aim of the study. The goal of the research was to characterise the incidence, demographic characteristics and morphologic scope of medulloblastomas in Latvia and to evaluate the immunophenotype for diagnostic, prognostic and future therapeutic role. Material and methods. Retrospective study design was applied. All consecutive patients with surgically treated and morphologically confirmed medulloblastoma (2000 - 2016) were identified by archive search in a single university clinic, providing neurosurgical and oncological treatment for children from the whole Latvia. The haematoxylin-eosin stained slides were reviewed by two authors to ensure diagnostic consistency. The diagnosis and histological type of medulloblastoma was detected in accordance to the classification and criteria, set by World Health Organisation (WHO). Ki-67, glial fibrillary acidic protein (GFAP), synaptophysin and p53 protein were assessed by immunohistochemistry. The expression of nuclear antigens (Ki-67, p53) was characterised by the mean fraction of positive cells within 400 sequential neoplastic cells. The levels of cytoplasmic antigens were scored semiquantitatively by intensity in 0 - 3 scale. Descriptive statistics, including the detection of the 95% confidence interval (CI); as well as non-parametric analytic assessment including Mann-Whitney test, Spearman correlation and Kruskal-Wallis analysis were applied. The diagnostic tests were characterised by sensitivity and specifity. Any differences were considered significant, if p < 0.05. Results. Medulloblastoma was verified in 26 cases, including 20 (76.9%; 95% CI: 57.6 - 89.3) boys and 6 (23.1%; 95% CI: 10.7 - 42.4) girls. This is consistent with the incidence of 0.5 per 100’000 children. The tumour was diagnosed at the mean age of 79.2 months (95% CI: 62.6 - 95.6), ranging 12 - 160 months. By the histological type, there were 20 cases of classic medulloblastoma, 4 cases of desmoplastic and nodular medulloblastoma and 2 cases of anaplastic and/ or large cell medulloblastoma. The mean proliferation fraction by Ki-67 was 36.8% (95% CI: 28.8 - 44.7), ranging 4.6 û 74.3%. The fraction of p53-expressing cells ranged 0.0 - 52.4%, yielding the mean value of 11.7% (95% CI: 6.4 - 17.1). There was no significant correlation