Extensive Pathologic Invasion and Prognostic Implication of Gastric-Type Cervical Adenocarcinoma

Gastric-type adenocarcinoma (GAS) is the most common subtype of human papillomavirus (HPV)-independent cervical adenocarcinomas and is associated with a poor prognosis. We used a gross morphologic classification system and imaging analysis to compare the clinicopathological features of GAS and HPV-associated adenocarcinoma (HPVA) and identify factors contributing to the poor prognosis of GAS. This retrospective 2-center study analyzed 33 patients with GAS and 70 with HPVA (stages IB-IVB) who underwent surgery between 1997 and 2023. GAS had a higher rate of positive surgical margins (21.2% vs. 0%, respectively, P <0.001) and unclear tumor boundaries on gross morphologic findings (47.8% vs. 8.8%, respectively, P <0.001). Discrepancies between clinical and pathologic T classifications were more common in GAS, leading to frequent upstaging (51.5% vs. 28.6%, respectively, P =0.029). Imaging analysis revealed that GAS was associated with a smaller median tumor cell area (19.8% vs. 55.7%, respectively, P <0.001), which was significantly correlated with unclear tumor boundaries. Perineural invasion (PNI) was significantly more frequent in GAS (69.7% vs. 10.0%, respectively, P <0.001). A Kaplan-Meier analysis showed that patients with PNI had significantly poorer overall survival ( P <0.001). A Cox multivariate analysis identified an advanced pathologic stage, positive peritoneal cytology, and positive surgical margins as independent risk factors. The present results indicate that GAS has a unique "stealth" invasion pattern, possibly caused by low tumor density, leading to undetectable tumor boundaries and positive surgical margins. This suggests a greater risk of incomplete resection than HPVA, leading to a poorer prognosis.