2025 Proffered Presentations
S061: SUCCINATE DEHYDROGENASE B EXPRESSION LOSS IN CHORDOMA: A CASE REPORT.
Kristen Marciniuk, MD, PhD; Luke Hnenny, MD; Viktor Zherebitskiy, MD; University of Saskatchewan
Background: Succinate dehydrogenase (SDH) is a mitochondrial enzyme with tumor suppressive effects. SDH inactivation is associated with metabolic and epigenetic mechanisms of tumorigenesis. In central and peripheral nervous system tumors, SDH inhibition is associated with familial paraganglioma/pheochromocytoma and has been reported in pituitary adenomas and hemangioblastomas. Other known SDH loss tumors would be gastrointestinal stromal tumor (GIST) and pulmonary chondroma. To our knowledge there are no reports of SDH loss in chordoma.
Case: We report a 69-year-old female who presented with a 3-week history of headaches and diplopia associated with a left oculomotor palsy. MRI demonstrated a large highly vascular and avidly enhancing mass centered within the left sphenoid bone with invasion into the pre-pontine cistern, sella, left cavernous sinus, sphenoid sinus, and nasopharynx. A preliminary transnasal biopsy was performed to guide further management. Findings were consistent with an SDH deficient neoplasm with neuroepithelial differentiation covering a broad differential. Recommended management included maximal safe resection followed by proton beam radiotherapy. Due to the significant vascularity of the lesion preoperative transarterial embolization was performed to reduce intraoperative blood loss. Endoscopic transsphenoidal maximal safe resection was then performed.
Results: The initial biopsy exhibited clusters of epithelioid looking tumor cells with ample amount of eosinophilic cytoplasm and sharp borders creating in some places impression of Zellballen pattern that would be more consistent with paraganglioma diagnosis. Although there were hints of focal cytoplasmic clearing, no physaliphorous cells or prominent myxoid stroma characteristic for chordoma were seen. SDH-B immunonegativity was found in the tumor tissue with positive internal control within the adjacent sinonasal mucosa which also would go along with the diagnosis of paraganglioma. However, synaptophysin negativity triggered more workup including use of brachyury and external consultation. The brachyury immunostain came back diffusely nuclear positive and based on that, external consultation favored a conventional chordoma over paraganglioma, pituitary adenoma and other options. Although molecular testing did not reveal TBXT gene mutations or EGFR (HER1) gene alterations common for chordomas, it did not show any other driving mutations including those related to paragangliomas (approximately 50% of sporadic chordomas have no known driver mutation). The histopathology of the subsequent resection specimen was much more consistent with the conventional chordoma appearance including presence of classic physaliphorous cells and the absence of features diagnostic for dedifferentiated or poorly differentiated chordomas. Yet SDH-B loss was maintained.
Conclusions: Loss of SDH-B immunohistochemical expression and its connection to SDH production as well as its role in chordoma tumorigenesis remains to be determined. The overall frequency of SDH inactivation in chordomas and associated prognostic or clinical significance requires further investigation. Importantly, misdiagnosis of chordoma due to atypical histological features and SDH-B loss on immunohistochemistry is a possibility in small biopsy specimens which has the potential to significantly influence management strategies and subsequent patient outcomes.