Peculiar pathological, radiological and clinical features of skull base dedifferentiated chordomas. Results from a referral Center case series and literature review

BACKGROUND: Dedifferentiated chordoma is an uncommon and incompletely characterized aggressive neoplasm. Only few cases originating from the skull base have been reported. MATERIAL & METHODS: All consecutive cases of skull base dedifferentiated chordomas treated surgically in a referral Center from January 1990 to June 2019 were retrospectively evaluated to assess peculiar pathological, radiological and clinical features. Patient data were retrieved from paper and electronic records. RESULTS: Six cases (4 F; mean age at surgery 46 years, range 35-64), treated surgically at our Institution were identified. Transformation to dedifferentiated chordomas occurred after radiation therapy in 3 cases (mean 13.6 years after treatment, range 5-25), 2 during tumor progression, while one was de-novo. Magnetic resonance imaging and surgical examination revealed the presence of two different tumor components, corresponding to the conventional and dedifferentiated portion at histological examination. The de novo case presented a PIK3CA mutation. DNA methylation analysis revealed consistent epigenetic changes in TERT, MAGEA11 and UXT. Prognosis was poor as 5 out of 6 patients died after surgery and radiation therapy, with a mean overall survival of 29 months (range 11-52). CONCLUSIONS: Skull base dedifferentiated chordomas are extremely rare and aggressive neoplasms with characteristic magnetic resonance imaging, surgical and histological features. Therefore, an early and accurate histological diagnosis is of paramount relevance. Molecular analysis appears promising to define mechanisms involved in tumor dedifferentiation.