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. 2025 Jul 29.
doi: 10.1097/PGP.0000000000001128. Online ahead of print.

Origin of Endometrioid Carcinoma Adjacent to Extraovarian Endometriosis: Detailed Molecular Analyses

Tomo Yamagata  1 , Koichi Watanabe  1   2 , Koji Yamanoi  1 , Nobuyuki Kakiuchi  2   3 , Rin Mizuno  1 , Mana Taki  1 , Ryusuke Murakami  1 , Ken Yamaguchi  1 , Junzo Hamanishi  1 , Hiroaki Itoh  4 , Seishi Ogawa  2   5 , Masaki Mandai  1
Affiliations

Origin of Endometrioid Carcinoma Adjacent to Extraovarian Endometriosis: Detailed Molecular Analyses

Tomo Yamagata et al. Int J Gynecol Pathol. .

Abstract

A well-differentiated endometrioid carcinoma at the site of extra-uterine/ovarian endometriosis complicates the differentiation between an uncommon metastatic pattern from a corpus cancer and a synchronous primary tumor originating from adjacent endometriosis. Herein, we present 2 cases of well-differentiated uterine endometrial carcinoma metastasizing to the intestinal tract and uterosacral ligament, which were adjacent to surrounding endometriosis. Case 1: a well-differentiated endometrioid carcinoma was identified in the uterus and the uterosacral ligament. Genetic analysis revealed shared driver gene mutations between the uterine corpus tumor and uterosacral ligament tumor, indicating a common clonal origin. Case 2: an endometrioid carcinoma was identified in the intestinal tract, with adjacent ectopic endometriosis. Furthermore, the patient had a history of treatment for early-stage uterine well-differentiated endometrial carcinoma 7 yr prior. Genetic analysis demonstrated shared genetic alterations between the uterine corpus tumor, treated 7 yr earlier, and the intestinal tumor, strongly supporting a shared clonal origin. Although clinical and pathologic findings suggested that these tumors could originate from endometriosis, detailed genetic analysis confirmed that they shared genetic alterations with the primary uterine endometrioid carcinoma, indicating a common clonal origin in both cases. When well-differentiated adenocarcinoma is identified at an extrauterine/ovarian site adjacent to endometriosis, the tumor can be considered to be derived from the surrounding endometriosis. However, if a uterine endometrial carcinoma is present concurrently or has a history of existing, metastasis from the uterine endometrial carcinoma should be considered first, even if its clinical malignant potential is not high.

Keywords: Endometrioid carcinoma; Endometriosis; Extraovarian endometriosis; Uterus cancer; Whole exome sequencing.

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Conflict of interest statement

K.Y. and M.M. receive grants from the company DUMSCO Inc. The remaining authors declare no conflict of interest.

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