Paired molecular profiling of malignant transformation of an epidermoid cyst for potential genetic drivers: illustrative case.

Abstract

Background: Malignant transformation of an intracranial epidermoid cyst (EC) into squamous cell carcinoma (SCC) is an exceedingly rare occurrence that is typically diagnosed on postoperative histology. The mechanisms underlying transformation remain poorly understood, with limited characterization of genetic changes associated with progression.

Observations: A 55-year-old female presented with a large cerebellopontine angle EC with an enhancing nodule in the left tectum, for which she underwent resection. Three months following surgery, rapid enlargement of the residual tectal component required reoperation, with pathology showing SCC. Paired next-generation sequencing of the EC and SCC revealed multiple shared variants, including a pathogenic TP53 mutation. Additionally, the SCC contained a pathogenic PTEN variant absent in the EC, suggesting a second driver mutation contributing to malignant transformation of an EC (MTEC). Her SCC was resistant to volumetric modulated arc therapy, requiring subsequent chemotherapy and pembrolizumab combined with stereotactic radiosurgery. Despite a favorable initial response, she died 26 months following MTEC diagnosis.

Lessons: To the authors' knowledge, this represents the first use of paired molecular profiling to link intracranial SCC to an EC precursor, enhancing precision of this rare diagnosis. Additionally, this case identifies specific genetic alterations associated with transformation, providing insight into the largely unknown mechanisms underlying MTEC. https://thejns.org/doi/10.3171/CASE24849.