Multi-institutional study of mesonephric-like adenocarcinoma: its clinicopathological characteristics and histogenetic association with ectopic endometrium

To explore the clinicopathological features and origin of mesonephric-like adenocarcinomas (MLAs), 83 cases diagnosed or suspected to be MLAs were collected from various institutions in Japan. We clearly classified 78 as MLAs (uterus: 47, ovary: 31) and 5 as non-MLAs (all ovary) based on our morphological and immunohistochemical criteria. In uterine MLAs (uMLAs), lymphovascular space invasion was an independent prognostic factor for progression-free survival (PFS) (P = 0.03). Patients with uMLAs had significantly shorter PFS and overall survival (OS) than those diagnosed with endometrial endometrioid carcinomas (EECs) (P < 0.0001 and P < 0.001, respectively) and comparable PFS and OS to those with copy number-high tumors. PFS and OS of ovarian MLAs (oMLAs) were similar to those of ovarian endometrioid carcinomas (OECs) overall but worse for patients with stage II-IV. Endometriosis was observed with oMLAs as often as with OECs (94% vs 93%, respectively). Adenomyosis was more frequently observed with uMLAs than with EECs (62% vs 28%, respectively, P = 0.0005). Six uMLAs were confined to the myometrium and adjacent to adenomyosis. In an analysis of molecularly speculated origin, among 29 oMLAs harboring a KRAS hotspot mutation, 23 (79%) instances of endometriosis in the background had the same mutation. Among 36 uMLAs carrying the KRAS hotspot mutation, common mutations were observed in 12 (33%) instances of adjacent adenomyosis (12/21 [67%] of adenomyosis). These findings suggest a histogenetic link between MLAs and ectopic endometrium, implicating both ovarian endometriosis and adenomyosis in MLA pathogenesis, with potential clinical significance.

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Journal
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Published
2025-10-29
DOI
https://doi.org/10.1007/s00428-025-04286-0
Primary Topic
Endometriosis Research and Treatment
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article
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article

Multi-institutional study of mesonephric-like adenocarcinoma: its clinicopathological characteristics and histogenetic association with ectopic endometrium

Morihiro Higashi, Junichi Shiraishi, Fumi Kawakami, Yu Miyama et al.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Endometriosis Research and Treatment
article

Multi-institutional study of mesonephric-like adenocarcinoma: its clinicopathological characteristics and histogenetic association with ectopic endometrium

Morihiro Higashi, Junichi Shiraishi, Fumi Kawakami, Yu Miyama, Kousuke Uranishi, Yoshinobu Maeda, Takako Kiyokawa, Eiji Kudo, Akiko Tonooka, Kozue Ito, Masataka Hirasaki, Masanori Yasuda, Yohei Kawasaki, Sachiko Minamiguchi, Yumiko Yasuhara, Hiroshi Kajiwara, Kosei Hasegawa, Tetsuya Shimada, Yoshiaki Kawano, Yoshiki Mikami, Yuzuru Kondo, Nasa Okazaki
article en

Abstract

To explore the clinicopathological features and origin of mesonephric-like adenocarcinomas (MLAs), 83 cases diagnosed or suspected to be MLAs were collected from various institutions in Japan. We clearly classified 78 as MLAs (uterus: 47, ovary: 31) and 5 as non-MLAs (all ovary) based on our morphological and immunohistochemical criteria. In uterine MLAs (uMLAs), lymphovascular space invasion was an independent prognostic factor for progression-free survival (PFS) (P = 0.03). Patients with uMLAs had significantly shorter PFS and overall survival (OS) than those diagnosed with endometrial endometrioid carcinomas (EECs) (P < 0.0001 and P < 0.001, respectively) and comparable PFS and OS to those with copy number-high tumors. PFS and OS of ovarian MLAs (oMLAs) were similar to those of ovarian endometrioid carcinomas (OECs) overall but worse for patients with stage II-IV. Endometriosis was observed with oMLAs as often as with OECs (94% vs 93%, respectively). Adenomyosis was more frequently observed with uMLAs than with EECs (62% vs 28%, respectively, P = 0.0005). Six uMLAs were confined to the myometrium and adjacent to adenomyosis. In an analysis of molecularly speculated origin, among 29 oMLAs harboring a KRAS hotspot mutation, 23 (79%) instances of endometriosis in the background had the same mutation. Among 36 uMLAs carrying the KRAS hotspot mutation, common mutations were observed in 12 (33%) instances of adjacent adenomyosis (12/21 [67%] of adenomyosis). These findings suggest a histogenetic link between MLAs and ectopic endometrium, implicating both ovarian endometriosis and adenomyosis in MLA pathogenesis, with potential clinical significance.

Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Jikei University School of Medicine (JP), Tokai University (JP), University of the Ryukyus (JP), National Defense Medical College Hospital (JP), Tokyo Medical Center (JP), Tokushima Prefectural Central Hospital (JP), Sakai Municipal Hospital (JP), Japanese Red Cross Kumamoto Hospital (JP), Toyama City Hospital (JP), Niigata Prefectural Niigata Minami High School (JP), Kyushu Hospital (JP), Matsuyama Red Cross Hospital (JP), Kumamoto University Hospital (JP), Saitama International Medical Center (JP), Japan Community Healthcare Organization (JP), National Hospital Organization (JP), Kasumigaura Medical Center (JP), Toyama University Hospital (JP), Kyoto University Hospital (JP), Social Insurance Saitama Chuo Hospital (JP), Japanese Foundation For Cancer Research (JP), Saitama Medical University (JP)
Openalex Percentile: Top 59%
Endometriosis Research and Treatment
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