Background: Perineural invasion (PNI) is a recognized pathway for cancer spread and is associated with poor outcomes in gastric cancer. However, the initial morphological characteristics of tumor–nerve interactions in early gastric cancer, particularly at the ultrastructural level, remain insufficiently defined. Case Presentation: We report a case of a 49-year-old man diagnosed with type IIc early gastric cancer. Histological examination revealed a combined poorly cohesive carcinoma (PCC)-NOS/signet-ring cell (SRC) histotype. Tumor invasion reached the middle third of the submucosa and was accompanied by a mature desmoplastic reaction, with metastases identified in two perigastric lymph nodes (pT1bN1M0). Transmission electron microscopy (TEM) revealed unmyelinated nerve fibers embedded within the submucosal desmoplastic stroma, in close proximity to infiltrating neoplastic cells. Several tumor cells exhibited cytoplasmic projections ranging from single extensions to multiple prominent pseudopods, resulting in an amoeboid morphology. Notably, an unmyelinated nerve process was observed within a cytoplasmic invagination of an individual tumor cell. Conclusions: Taken together, these ultrastructural findings provide novel and previously undescribed morphological evidence of a specific interaction between amoeboid tumor cells and peripheral unmyelinated nerve fibers within the submucosal desmoplastic stroma of early gastric cancer. The biological and clinical significance of this interaction in the early stages of perineural invasion warrants further investigation.
Caruso et al. (Tue,) studied this question.