Genetic alterations in CDKN2A, PIK3CA, SMAD4, and TP53 can serve as biomarkers for detecting advanced neoplasia, with sensitivities of 11%, 10%, 9%, and 42%, and specificities of 97%, 97%, 98%, and 95%, respectively, based on 666 surgically resected PCLs [50,59,96]. Here, SMAD4 is linked to neoplasm.