# Unique pattern of endometrial invasion in gastric-type adenocarcinoma of the uterine cervix: a report of two cases

## TL;DR

This paper reports two cases of aggressive cervical cancer with a unique way of invading the endometrium, which may explain its poor prognosis and resistance to treatment.

## Contribution

The study identifies a novel 'symbiotic' invasion pattern in gastric-type cervical adenocarcinoma and links it to an immunologically 'cold' tumor environment.

## Key findings

- GAS exhibited a 'symbiotic' endometrial invasion pattern without disrupting normal tissue architecture.
- CD8-positive TILs were reduced at the tumor–endometrium interface, indicating an immunologically 'cold' microenvironment.
- This pattern may explain the extensive spread of GAS and its resistance to treatment.

## Abstract

Gastric-type cervical adenocarcinoma (GAS), the most prevalent subtype of human papillomavirus (HPV)-independent cervical adenocarcinoma, is an aggressive malignancy with a poor prognosis. We herein present two cases of GAS with a unique endometrial infiltration pattern. Both cases were 37-year-old nulligravid women presenting with advanced GAS. A pathological examination revealed HPV-independent GAS that was positive for claudin 18 and negative for p16, with extensive invasion, including the myometrium and endometrium. Endometrial infiltration was characterized by a distinctive “symbiotic” pattern of invasion. In these areas, GAS glands intermingled with normal endometrial glands without disrupting the native architecture, and there was no distinct tumor border or stromal reaction. An immunohistochemical analysis revealed fewer CD8-positive tumor-infiltrating lymphocytes (TILs) around invasive GAS glands in the endometrium than in the normal endometrium and both the tumor center and invasive margin of the primary cervical lesion. These results are consistent with relative T-cell exclusion at the tumor–endometrium interface. This “symbiotic” invasion pattern differs from typical cervical adenocarcinoma, which forms distinct boundaries with desmoplastic stromal reactions. The observed pattern may contribute to the unexpectedly extensive spread of GAS frequently discovered only after surgical resection. The reduction in CD8-positive TILs density around invasive GAS glands indicates an immunologically “cold” tumor microenvironment that may contribute to treatment resistance. The present results provide novel insights into the pathology of GAS that may inform more effective diagnostic approaches and therapeutic strategies for this aggressive malignancy.