Ultrastructural pathological features and clinical significance of recurrent chordoma

Chordoma is a low-grade malignant osseous neoplasm characterized by an exceedingly high postoperative recurrence rate. Conventional histopathological assessment cannot identify early subcellular alterations that drive tumor recurrence, and the ultrastructural mechanisms mediating chordoma recurrence and malignant progression remain poorly delineated. This study was designed to characterise the distinct subcellular pathological features of recurrent chordoma and evaluate their clinical value in prognostic assessment and risk stratification. 50 surgically resected recurrent chordoma specimens were included as the recurrent cohort, with 50 contemporaneously collected primary chordoma specimens serving as the primary control cohort. Among these, 16 pairs consisted of matched TEM specimens from the same patient's primary and recurrent chordomas, while the remaining 34 pairs comprised non-matched primary and recurrent chordomas from different patients.; Transmission electron microscopy (TEM) was employed to systematically compare ultrastructural differences across cytoplasmic vacuolar patterns, organellar architecture, intercellular junctional complexes, nuclear morphology, and stromal microvascular ultrastructure, and the prevalence of each ultrastructural abnormality was analysed statistically. Compared with primary chordoma, recurrent lesions displayed extensive and progressive subcellular pathological remodelling, including atypical cytoplasmic vacuolation with giant cystic fusion, diffuse mitochondrial injury and rough endoplasmic reticulum degranulation, widespread disintegration of mitochondria-associated endoplasmic reticulum membrane (MAM) complexes, marked nuclear atypia, loss of intercellular desmosomal junctions, activation of invasive invadopodia, and stromal microvascular dysplasia. The prevalence of all these ultrastructural aberrations was significantly higher in the recurrent cohort than in the primary control cohort (all P < 0.001), and the severity of ultrastructural damage was positively correlated with the frequency of prior tumor recurrence. In this cross-sectional series, recurrent chordoma presents characteristic progressive ultrastructural lesions, in which organellar remodelling, loss of intercellular junctions, stromal microvascular abnormalities and nuclear atypia co-segregate with recurrent disease. These findings describe a subcellular morphological correlate of recurrence; because the present cohort was cross-sectional and did not correlate ultrastructural scores with survival, the value of TEM for recurrence-risk prediction, malignant grading or individualised treatment remains a hypothesis to be tested prospectively.