Uterine Serous Carcinoma Following the Insertion of Levonorgestrel Intrauterine System: A Case Report and Literature Review

Hu Q, Yao Y, Xie X, Zhong X, Luo Y, Huang X
In: International Journal of Women's Health, Vol Volume 17, Iss Issue 1, Pp 4177-4185 (2025) · 2025 · W7104183631
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This case report and literature review describe the first documented instance of uterine serous carcinoma developing in a patient with adenomyosis following long-term levonorgestrel intrauterine system therapy.

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This case report and literature review describe the first documented instance of uterine serous carcinoma developing in a 44-year-old woman with adenomyosis who had used a levonorgestrel-releasing intrauterine system for five years. The authors note that while previous cases linked to this device were exclusively endometrioid adenocarcinomas, this patient presented with irregular bleeding and an enlarged uterine cavity, leading to a diagnosis of serous endometrial intraepithelial carcinoma after diagnostic curettage. Following oncological staging surgery and adjuvant chemoradiation, the patient remained in complete remission at six-month follow-up, prompting recommendations for vigilant biopsy protocols in similar clinical scenarios. Relevance to endometriosis: not mentioned; Relevance to adenomyosis: the patient’s underlying condition was adenomyosis, which served as the indication for the LNG-IUS therapy that preceded the cancer diagnosis.

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Abstract

QiuXia Hu,1,* Yi Yao,2,* XiaoHui Xie,1 XiaoMei Zhong,1 Yong Luo,1 Xiaoqin Huang1 1Department of Gynecology, The First People’s Hospital of Neijiang, Sichuan, 641000, People’s Republic of China; 2Department of Cardiothoracic Surgery, The First People’s Hospital of Neijiang, Sichuan, 641000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqin Huang, Department of Gynecology, The First People’s Hospital of Neijiang, No. 1866 West Section of Han’an Avenue, Shizhong District, Neijiang, Sichuan, 641000, People’s Republic of China, Tel +86-0832-2155661, Email [email protected]: The levonorgestrel-releasing intrauterine system (LNG-IUS) is now widely used for the treatment of heavy menstrual bleeding and endometrial hyperplasia, and its clinical application has been extended to adenomyosis. By releasing levonorgestrel directly into the uterine cavity, the LNG-IUS induces endometrial atrophy and thinning, effectively reversing hyperplastic changes, thereby conferring a distinct protective effect on the endometrium. Nevertheless, even under this potent progestogenic protection, malignant transformation remains an exceedingly rare event. To date, only 11 cases of endometrial carcinoma arising after LNG-IUS placement have been reported worldwide. The majority of these patients were perimenopausal women who presented with variable degrees of vaginal bleeding after LNG-IUS insertion; all lesions were subsequently confirmed as endometrioid adenocarcinoma, and no cases of uterine serous carcinoma (USC) were documented. Herein, we report the first documented case of a 44-year-old patient with adenomyosis and menorrhagia who, despite long-term LNG-IUS therapy, progressed to USC.Case Presentation: A 44-year-old woman was admitted to the hospital due to “irregular vaginal bleeding for over 1 month”. Five years earlier, the patient had an LNG-IUS inserted at our institution for menorrhagia secondary to adenomyosis. Pre-insertion transvaginal ultrasound showed no endometrial abnormality, and endometrial biopsy was not performed. On the current admission, diagnostic curettage revealed a markedly enlarged uterine cavity. Histopathologic examination was consistent with serous endometrial intraepithelial carcinoma (SEIC). The patient underwent complete oncological staging surgery according to International Federation of Gynecology and Obstetrics (FIGO) guidelines, followed by adjuvant platinum-based chemoradiation. Surveillance at 6 months post-treatment confirmed continued complete remission.Conclusion: Through a systematic review and analysis of this case, special caution is warranted in patients presenting with abnormal uterine bleeding—especially when the uterine cavity is enlarged; ideally, endometrial biopsy should be performed before LNG-IUS placement to rule out endometrial pathology. Any alteration in vaginal bleeding patterns in LNG-IUS users should prompt vigilance for possible endometrial pathology, and repeat endometrial biopsy should be performed. This case provides valuable evidence to help reduce the risk of missed diagnosis of endometrial cancer in such patients.Keywords: endometrial cancer, levonorgestrel-releasing intrauterine system, uterine serous carcinoma, case report
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International Journal of Women's Health (Nov 2025) Uterine Serous Carcinoma Following the Insertion of Levonorgestrel Intrauterine System: A Case Report and Literature Review Abstract QiuXia Hu,1,* Yi Yao,2,* XiaoHui Xie,1 XiaoMei Zhong,1 Yong Luo,1 Xiaoqin Huang1 1Department of Gynecology, The First People’s Hospital of Neijiang, Sichuan, 641000, People’s Republic of China; 2Department of Cardiothoracic Surgery, The First People’s Hospital of Neijiang, Sichuan, 641000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqin Huang, Department of Gynecology, The First People’s Hospital of Neijiang, No. 1866 West Section of Han’an Avenue, Shizhong District, Neijiang, Sichuan, 641000, People’s Republic of China, Tel +86-0832-2155661, Email [email protected]: The levonorgestrel-releasing intrauterine system (LNG-IUS) is now widely used for the treatment of heavy menstrual bleeding and endometrial hyperplasia, and its clinical application has been extended to adenomyosis. By releasing levonorgestrel directly into the uterine cavity, the LNG-IUS induces endometrial atrophy and thinning, effectively reversing hyperplastic changes, thereby conferring a distinct protective effect on the endometrium. Nevertheless, even under this potent progestogenic protection, malignant transformation remains an exceedingly rare event. To date, only 11 cases of endometrial carcinoma arising after LNG-IUS placement have been reported worldwide. The majority of these patients were perimenopausal women who presented with variable degrees of vaginal bleeding after LNG-IUS insertion; all lesions were subsequently confirmed as endometrioid adenocarcinoma, and no cases of uterine serous carcinoma (USC) were documented. Herein, we report the first documented case of a 44-year-old patient with adenomyosis and menorrhagia who, despite long-term LNG-IUS therapy, progressed to USC.Case Presentation: A 44-year-old woman was admitted to the hospital due to “irregular vaginal bleeding for over 1 month”. Five years earlier, the patient had an LNG-IUS inserted at our institution for menorrhagia secondary to adenomyosis. Pre-insertion transvaginal ultrasound showed no endometrial abnormality, and endometrial biopsy was not performed. On the current admission, diagnostic curettage revealed a markedly enlarged uterine cavity. Histopathologic examination was consistent with serous endometrial intraepithelial carcinoma (SEIC). The patient underwent complete oncological staging surgery according to International Federation of Gynecology and Obstetrics (FIGO) guidelines, followed by adjuvant platinum-based chemoradiation. Surveillance at 6 months post-treatment confirmed continued complete remission.Conclusion: Through a systematic review and analysis of this case, special caution is warranted in patients presenting with abnormal uterine bleeding—especially when the uterine cavity is enlarged; ideally, endometrial biopsy should be performed before LNG-IUS placement to rule out endometrial pathology. Any alteration in vaginal bleeding patterns in LNG-IUS users should prompt vigilance for possible endometrial pathology, and repeat endometrial biopsy should be performed. This case provides valuable evidence to help reduce the risk of missed diagnosis of endometrial cancer in such patients.Keywords: endometrial cancer, levonorgestrel-releasing intrauterine system, uterine serous carcinoma, case report

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