Abstract 17
Category: Clinical Science
At the end of the session, participants will be able to:
- Recognize the clinicopathologic features associated with malignant transformation of craniopharyngioma,
including histologic proliferation indices, and IHC signatures. - Evaluate the significance of management-related parameters (surgery, radiation, tumor size) in
influencing time to malignant transformation, based on pooled literature analysis. - Integrate the knowledge of molecular drivers such as CTNNB1 mutations and copy number alterations to
understand mechanisms of clonal evolution in long-standing craniopharyngiomas.
COI Disclosure:
None to disclose.
Presenter
Pramath Kakodkar is a final-year resident in Diagnostic and Clinical Pathology at the University of Saskatchewan and will be starting neuropathology fellowship at Northwestern University in Chicago in 2026. His interests include neurodegenerative disease, brain tumors, and how molecular tools and digital pathology can complement classic morphologic diagnosis.
Recent projects have ranged from using amyloid PET to study primary progressive aphasia, to mapping alpha-synuclein along the spinal axis in Parkinson’s disease, to exploring malignant transformation in craniopharyngioma. He is also leading a study comparing large language models in clinical neuroscience diagnostics, with a focus on neuropathology.
Pramath Kakodkar1, Gina Martin2, Julia Radic3, Vijayanada Kundapur4, Adrian B Levine5, Viktor Zherebitskiy1, and Roland N. Auer1
1Department of Pathology and Laboratory medicine University of Saskatchewan and Saskatchewan Health Authority, Saskatoon, SK, Canada
2Division of Pediatric Hematology-Oncology, Saskatoon Cancer Center, Saskatoon, SK, Canada
3Division of Neurosurgery, Dalhousie University, Halifax, NS, Canada
4Division of Radiation Oncology, Saskatoon Cancer Center, Saskatoon, SK, Canada
5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Target Audience:
Pathologists, Residents, Medical Students
CanMEDS:
Medical Expert (the integrating role), Communicator, Collaborator, Scholar
Malignant transformation of craniopharyngioma with spinal metastasis: A case report and comprehensive literature review.
Abstract
Malignant transformation of craniopharyngioma is exceedingly rare with few cases characterized by systemic spread or molecularly confirmed clonal progression. We present a pediatric case of adamantinomatous craniopharyngioma that evolved over 12 years into a high-grade epithelial neoplasm with clival extension and spinal metastases causing vertebral fracture and spinal cord compression; to our knowledge, this is the 3rd case of spinal dissemination in the literature. The transformed tumor demonstrated high-grade epithelial morphology (Ki-67: 100% vs 5% initially), strong pancytokeratin and vimentin expression, partial H3 K27me3 loss, and absence of glial or neuroendocrine differentiation. Molecular profiling confirmed the same CTNNB1 p.S33C mutation in both the initial and transformed tumor, along with a segmental 1p deletion acquired in the latter, supporting molecularly confirmed clonal evolution. A systematic review (n=35) on craniopharyngioma cases with malignant transformation revealed consistent epithelial immunophenotype, frequent p53 overexpression (89%, n=17), high mean Ki-67 (41±21%). More surgeries were significantly associated with longer time to transformation (r = 0.49, p = 0.005), suggesting that multiple surgical interventions delayed progression, while no significant correlation was observed with radiation dose (r = 0.01, p = 0.97) or tumor size (r = 0.40, p = 0.16). These findings support a clonal evolution model and highlight the importance of molecular surveillance in long-standing craniopharyngiomas.