Malignant craniopharyngiomas: Institutional experience and literature review

Malignant craniopharyngiomas, de novo or via malignant transformation, are exceedingly rare with a dismal prognosis and unclear treatment standards. Little is known about the factors involved in their pathogenesis. A natural language search, performed in our institutional CoPath system, identified 65 adamantinomatous craniopharyngiomas from 56 patients (25 males, 31 females; median age at initial diagnosis = 22 years). Among those, a unique case of malignant craniopharyngioma was identified in a 36-year-old male initially diagnosed with a benign adamantinomatous craniopharyngioma 16 years prior. A literature review identified 44 cases of malignant craniopharyngiomas (current case included) with a median age of 28 years and a median overall survival of 6 months, independent of sex, age, histologic variant, tumor size, or radiation therapy. Eighteen (41%) malignant craniopharyngiomas occurred in patients without a history of radiation, suggesting mechanisms other than radiation contribute to their pathogenesis. Since BRCA1-Associated Protein 1 (BAP1) and TP53 mutations have recently been reported in a case of malignant craniopharyngioma, we assessed these genes in the current case. Next-generation sequencing identified variants in BAP1 (c.1850delGinsCA;p.R617fs), TP53 (c.428delT;p.V143fs), and CTNNB1 (c.110C>T;p.S37F). In conclusion, our results demonstrate that malignant craniopharyngioma tends to occur in young adults with a median overall survival of only 6 months. The current case is the second reported to harbor BAP1 and TP53 mutations by sequencing. BAP1 and TP53 mutations may play an important role in the pathogenesis of malignant craniopharyngioma and may offer potential targets for therapeutic intervention.