Histopathological and molecular predictors of growth patterns and recurrence in craniopharyngiomas: a systematic review

Craniopharyngiomas (CPs) are rare, benign tumors derived from Rathke's pouch, known for their high recurrence rates and associated morbidity and mortality. Despite significant investigation on risk factors for recurrence, a lack of consensus persists. Recent research suggests that specific histopathological and molecular characteristics are prognostic for disease progression. In this systematic review, we analyzed and consolidated key features of CPs that contribute to increased recurrence rates. This systematic review was performed in accordance with PRISMA guidelines. A search string was created with the keywords craniopharyngioma, histology, histopathology, molecular, and recurrence. Literature was collected from 2006 to 2016 on the PubMed/Medline and Web of Science databases. The initial search resulted in 242 papers, examined with inclusion and exclusion criteria. The final review included a total of 37 studies, 36 primary studies covering a total of 1461 patients and 1 previous meta-analysis. Cystic lesions and whorl-like arrays were found to be associated with increased recurrence, while previously considered reactive gliosis and finger-shaped protrusions were not. The genetic elements found to be associated with increased risk of recurrence were Ki-67, Ep-CAM, PTTG-1, survivin, and certain RAR isotypes, as well as the glycoproteins osteonectin and chemokines CXCL12/CXCR4. The effects of VEGF, HIF-1 alpha, and p53, despite extensive study, yielded conflicting results. Certain histopathological and molecular characteristics of CPs provide insight into their pathogenesis, likelihood of recurrence, and potential novel targets for therapy.