Calcifying pseudoneoplasm of the neuraxis progressing to G5/PDGFRA subgroup glioblastoma in a United States Army veteran with a history of head trauma and germline POT1 and EPHB2 mutations: illustrative case.

Background: Trauma-associated glioblastoma has been previously described, albeit without molecular characterization.

Observations: The authors show the integrated clinical/pathologic/molecular analysis of a glioblastoma developing 43 years after head trauma sustained by a United States veteran. An epileptogenic benign lesion developed at the trauma site, followed 34 years later by a calcified lesion diagnosed as calcifying pseudoneoplasm of the neuraxis (CAPNON) that recurred 9 years later as glioblastoma with heterotopic/metaplastic ossification. Genomic analysis showed novel germline mutations in the telomere maintenance factor POT1 p.W184* and receptor tyrosine kinase (RTK) EPHB2 p.W792*. The somatic alterations included second-hit POT1 p.D163Y mutation, CDKN2A/2B homozygous loss, DNMT3A mutation and PDGFRA amplification, classifying this glioblastoma in the G5/PDGFRA molecular subgroup. Proliferation markers, PDGFRA, MAPK feedback inhibitors, and EPHB1 showed high expression, whereas EPHB3 and EPHA7 showed the highest expression of all glioblastomas. Following gross-total resection, the patient received adjuvant radiotherapy and temozolomide and died 16.3 months later.

Lessons: This is the first report of CAPNON progression to glioblastoma and of molecularly characterized glioma occurring decades after head trauma. A multifactorial etiology including genetic predisposition and posttraumatic repair is hypothesized. The discussion presents possible roles of EPH RTKs in posttraumatic repair and CAPNON, and of POT1 and PDGFRα in subsequent progression to glioblastoma. https://thejns.org/doi/10.3171/CASE25152.