Occult clear cell carcinoma arising from oxidative stress‑exposed cystic adenomyosis: A case report

Hoshiba,Nao; Kayahashi,Kayo; Hayashi,Sakura; Nomura,Satoshi; Nakayama,Midori; Iizuka,Takashi; Fujiwara,Hiroshi

doi:10.3892/mco.2024.2748

Occult clear cell carcinoma arising from oxidative stress‑exposed cystic adenomyosis: A case report

Authors:
- Nao Hoshiba
- Kayo Kayahashi
- Sakura Hayashi
- Satoshi Nomura
- Midori Nakayama
- Takashi Iizuka
- Hiroshi Fujiwara
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Affiliations: Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan
Published online on: May 28, 2024 https://doi.org/10.3892/mco.2024.2748
Article Number: 50
Copyright: © Hoshiba et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although adenomyosis is a benign uterine disease, it can turn malignant in rare instances. Cystic adenomyosis is a rare variation of adenomyosis, arising from which 8 cases of clear cell carcinoma have been reported. However, to the best of our knowledge, there have been no previous reports describing the mechanism by which clear cell carcinoma develops from cystic adenomyosis. The present report documents a case of a 73‑year‑old woman who was referred to Kanazawa University Hospital (Kanazawa, Japan) because of cystic adenomyosis, with a solid part inside the cyst. The patient was diagnosed with cystic adenomyosis at Shonan Obstetrics and Gynecology Hospital (Hakusan, Japan) 17 years prior; however, the size of the cyst increased after menopause. Therefore, malignant transformation was suspected, which warranted simple abdominal hysterectomy and bilateral salpingo‑oophorectomy. The final diagnosis of the present case was uterine corpus cancer, clear cell carcinoma, stage IA. Immunohistochemical staining revealed that the normal and transitional atypical epithelial cells lining the cyst wall, in addition to the clear cell carcinoma cells (which were inside mural nodules located on the cyst wall), were positive for 8‑hydroxy‑20‑deoxyguanosine. This observation suggested the presence of chronic oxidative stress around the cystic adenomyosis. Therefore, the present case suggests the possible involvement of chronic oxidative stress in the malignant transformation of cystic adenomyosis to clear cell carcinoma. This mechanism of malignant transformation of cystic adenomyosis appears to be similar to that of the malignant transformation of endometriotic cysts. Therefore, if the size of the cystic adenomyosis increases after menopause or if the solid part appears in the cyst in future cases, then the possibility of malignant transformation should be considered.

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1	Peric H and Fraser IS: The symptomatology of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 20:547–555. 2006.PubMed/NCBI View Article : Google Scholar
2	Machida H, Maeda M, Cahoon SS, Scannell CA, Garcia-Sayre J, Roman LD and Matsuo K: Endometrial cancer arising in adenomyosis versus endometrial cancer coexisting with adenomyosis: Are these two different entities? Arch Gynecol Obstet. 295:1459–1468. 2017.PubMed/NCBI View Article : Google Scholar
3	Iizuka T, Ono M, Masumoto S, Mitani Y, Yamazaki R and Fujiwara H: Amniotic epithelial cells damage by oxidative stress in cases of diffuse chorioamniotic hemosiderosis. J Obstet Gynaecol Res. 45:2095–2099. 2019.PubMed/NCBI View Article : Google Scholar
4	Sampson JA: Endometrial carcinoma of the ovary, arising in endometrial tissue in that organ. Arch Surg. 10:1–72. 1925.
5	Colman HI and Rosenthal AH: Carcinoma developing in areas of adenomyosis. Obstet Gynecol. 14:342–348. 1959.PubMed/NCBI
6	Mori M, Furusawa A, Kino N, Uno M, Ozaki Y and Yasugi T: A rare case of endometrioid adenocarcinoma arising from cystic adenomyosis. J Obstet Gynaecol Res. 41:324–328. 2015.PubMed/NCBI View Article : Google Scholar
7	Taniguchi F: New knowledge and insights about the malignant transformation of endometriosis. J Obstet Gynaecol Res. 43:1093–1100. 2017.PubMed/NCBI View Article : Google Scholar
8	Sampson JA: Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into venous circulation. Am J Pathol. 3:93–110. 43. 1927.PubMed/NCBI
9	Leyendecker G, Herbertz M, Kunz G and Mall G: Endometriosis results from the dislocation of basal endometrium. Hum Reprod. 17:2725–2736. 2002.PubMed/NCBI View Article : Google Scholar
10	Leyendecker G, Wildt L and Mall G: The pathophysiology of endometriosis and adenomyosis: Tissue injury and repair. Arch Gynecol Obstet. 280:529–538. 2009.PubMed/NCBI View Article : Google Scholar
11	Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K and Fujii S: Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res. 14:32–40. 2008.PubMed/NCBI View Article : Google Scholar
12	Mandai M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J and Konishi I: Ovarian clear cell carcinoma as a stress-responsive cancer: Influence of the microenvironment on the carcinogenesis and cancer phenotype. Cancer Lett. 310:129–133. 2011.PubMed/NCBI View Article : Google Scholar
13	Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, et al: ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 363:1532–1543. 2010.PubMed/NCBI View Article : Google Scholar
14	Xu TX, Zhao SZ, Dong M and Yu XR: Hypoxia responsive miR-210 promotes cell survival and autophagy of endometriotic cells in hypoxia. Eur Rev Med Pharmacol Sci. 20:399–406. 2016.PubMed/NCBI
15	Niiro E, Kawahara N, Yamada Y, Yoshimoto C, Shimada K, Sudo T and Kobayashi H: Immunohistochemical expression of CD44v9 and 8-OHdG in ovarian endometrioma and the benign endometriotic lesions adjacent to clear cell carcinoma. J Obstet Gynaecol Res. 45:2260–2266. 2019.PubMed/NCBI View Article : Google Scholar
16	Tsuchimochi S, Wada-Hiraike O, Urano Y, Kukita A, Yamaguchi K, Honjo H, Taguchi A, Tanikawa M, Sone K, Mori-Uchino M, et al: Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma. Sci Rep. 13(20292)2023.PubMed/NCBI View Article : Google Scholar
17	Marí-Alexandre J, Carcelén AP, Agababyan C, Moreno-Manuel A, García-Oms J, Calabuig-Fariñas S and Gilabert-Estellés J: Interplay between MicroRNAs and oxidative stress in ovarian conditions with a focus on ovarian cancer and endometriosis. Int J Mol Sci. 20(5322)2019.PubMed/NCBI View Article : Google Scholar
18	Hsu JY, Reimann JD, Sørensen CS, Lukas J and Jackson PK: E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1). Nat Cell Biol. 4:358–366. 2002.PubMed/NCBI View Article : Google Scholar
19	Gütgemann I, Lehman NL, Jackson PK and Longacre TA: Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma. Mod Pathol. 21:445–454. 2008.PubMed/NCBI View Article : Google Scholar
20	Wang C, Liang Z, Liu X, Zhang Q and Li S: The association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer: Meta-Analyses. Int J Environ Res Public Health. 13(1138)2016.PubMed/NCBI View Article : Google Scholar
21	Mori Y, Inoue Y, Sakai K, Koizumi M, Okamura N, Sato K and Mizuuchi H: Primary clear cell carcinoma arising in cystic adenomyosis of the uterus-a case report. Nihon Sanka Fujinka Gakkai Zasshi. 46:915–917. 1994.PubMed/NCBI(In Japanese).
22	Shinozaki H, MR Ishizuka Y, Sugiura K, Nishii H, Watanabe A, Ochiai K and Tanaka T: A case of malignant transformation of cystic adenomyosis in which fine-needle aspiration cytology led to the diagnosis. Nihon Rinsho Saibo Gakkai Zasshi. 39(370)2000.(In Japanese).
23	Tsunota C, MK Motoyama T, Yasuda J and Tatebe A: A case of uterine corpus cancer thought to have arisen from cystic adenomyosis. Shojinkai Igaku Zasshi. 43:151–155. 2004.(In Japanese).
24	Ohta Y, Hamatani S, Suzuki T, Ikeda K, Kiyokawa K, Shiokawa A, Kushima M and Ota H: Clear cell adenocarcinoma arising from a giant cystic adenomyosis: A case report with immunohistochemical analysis of laminin-5 gamma2 chain and p53 overexpression. Pathol Res Pract. 204:677–682. 2008.PubMed/NCBI View Article : Google Scholar
25	Heo SH, Lee KH, Kim JW and Jeong YY: Unusual manifestation of endometrioid adenocarcinoma arising from subserosal cystic adenomyosis of the uterus: Emphasis on MRI and positron emission tomography CT findings. Br J Radiol. 84:e210–e212. 2011.PubMed/NCBI View Article : Google Scholar
26	Okuyama D, OM Kotani M and Suzuki A: A case of clear cell adenocarcinoma of the uterine corpus suspected to have developed from cystic adenomyosis. Tokyo J Ob-Gyn. 62:131–137. 2013.(In Japanese).
27	Ito M, SK Owada M, Suzuki H and Saito A: A case of clear cell adenocarcinoma suspected to have developed from cystic adenomyosis. Fukushima Journal of Medical Science. 64:29–33. 2014.(In Japanese).
28	Ohta Y, MK Yonezawa M and Mizuno K: A case of uterine corpus cancer arising from cystic adenomyosis. Kanto J Obst Gynec. 53:553–559. 2016.(In Japanese).
29	Baba A, Yamazoe S, Dogru M, Ogawa M, Takamatsu K and Miyauchi J: Clear cell adenocarcinoma arising from adenomyotic cyst: A case report and literature review. J Obstet Gynaecol Res. 42:217–223. 2016.PubMed/NCBI View Article : Google Scholar
30	Ueda M, KJ Okabe M, Morikawa K, Miyahara Y, Katayama Y, Matsuoka T, Sekino K, Masumoto K and Komatsu R: Two cases of uterine corpus cancer thought to have arisen from adenomyosis. Gendai Sanfujinka. 64:303–308. 2016.(In Japanese).
31	Amimoto S, UT Tohyama A, Atsui C, Kurita T, Kagami S, Kawagoe T, Matsuura Y and Hachisuka T: A case of uterine corpus cancer thought to have arisen from adenomyosis. Acta Obstetrica et Gynaecologica Japonica. 70(760)2020.(In Japanese).
32	Sakata K, YT Jingi A, Kawamura T, Hirata T and Kihira T: A case of clear cell adenocarcinoma suspected to have developed from cystic adenomyosis. The Tokai Journal of Obstetrics and Gynecology. 53:205–211. 2017.(In Japanese).
33	Okamoto S, HN Mizusaki M, Hamada K, Kita K, Ichikawa H, Takahashi T, Kato I, Katayama H and Sengoku K: A case of clear cell adenocarcinoma suspected to have developed from cystic adenomyosis. Journal of the Hokkaido Obstetrical and Gynecological Society. 64(106)2020.(In Japanese).
34	Gomez NF, Still MA, Akki AS, Carbajal-Mamani SL and Cardenas-Goicoechea J: Uterine clear cell carcinoma arising from cystic adenomyosis: A case report. J Obstet Gynaecol Res. 41:1175–1177. 2021.PubMed/NCBI View Article : Google Scholar
35	Dateki M, OA Yamaguchi T, Ueno N, Fujisaki A, Kawagoe Y and Samejima H: A case of endometrial cancer arising from cystic adenomyosis. Acta Obstetrica et Gynaecologica Japonica. 73(396)2021.(In Japanese).