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<p>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) (<i>P</i> = 0.03). Patients with uMLAs had significantly shorter PFS and overall survival (OS) than those diagnosed with endometrial endometrioid carcinomas (EECs) (<i>P</i> &lt; 0.0001 and <i>P</i> &lt; 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, <i>P</i> = 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 <i>KRAS</i> hotspot mutation, 23 (79%) instances of endometriosis in the background had the same mutation. Among 36 uMLAs carrying the <i>KRAS</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月29日

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

摘要

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.