A Rare Case of Endometrioid Cancer with Lymph Node Metastasis and Endometriosis

A Rare Case of Endometrioid Cancer with Lymph Node Metastasis and Endometriosis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 9 July 2025 V1 Latest version Share on A Rare Case of Endometrioid Cancer with Lymph Node Metastasis and Endometriosis Authors : Zhipeng Wang , wenmei He 0009-0003-9716-4158 , Ying Li [email protected] , Weiquan Lu , and Gongke li Authors Info & Affiliations https://doi.org/10.22541/au.175204879.90929142/v1 207 views 91 downloads Contents Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share A Rare Case of Endometrioid Cancer with Lymph Node Metastasis and Endometriosis Zhipeng Wang 1 , Wenmei He 1 ,Gongke li 1 ,Weiquan Lu 1 ,Ying Li 1, * Zhipeng Wang, Department of Pathology, Sanya Central Hospital (Hainan Third People’s Hospital), Sanya,Hainan, China. Wenmei He,Department of Ultrasound,Sanya Central Hospital (Hainan Third People’s Hospital), Sanya,Hainan, China. Zhipeng Wang and Wenmei He should be considered joint first author Gongke li,Department of Radiology,Sanya Central Hospital (Hainan Third People’s Hospital), Sanya,Hainan, China. Weiquan Lu,Department of Radiology,Sanya Central Hospital (Hainan Third People’s Hospital), Sanya,Hainan, China. *, Corresponding author: Ying Li, Department of Pathology, Sanya Central Hospital (Hainan Third People’s Hospital), Sanya, Hainan,China, Email: [email protected] . Endometriosis and endometrioid carcinoma share high morphological similarity, which can lead to misdiagnosis, and both exhibit a propensity for lymphatic metastasis; however, the mechanism underlying their coexistence remains unclear. This report presents a rare and complex case of a 54-year-old woman with endometrioid carcinoma (G2), concurrently exhibiting lymph node metastasis and endometriosis. For the first time, both carcinoma tissue (Ki-67 50%, PAX-2 negative) and ectopic endometrium (Ki-67 3%, PAX-2 positive) were simultaneously identified in metastatic lymph nodes, along with loss of MMR protein expression (MLH1/PMS2 negative), suggesting that microsatellite instability may drive metastasis. The clinical and pathological features of this case are notably uncommon. It provides crucial insights into the potential molecular mechanisms and metastatic pathways of disease coexistence, underscoring the necessity of combined immunohistochemical markers (PAX-2/Ki-67/MMR) for accurate differential diagnosis. Summary The coexistence of endometrioid carcinoma and endometriosis with lymph node metastasis can lead to difficulties in pathological diagnosis and even misdiagnosis. Endometrioid carcinoma and endometriosis share potential molecular mechanisms and metastatic pathways, emphasizing the necessity of combined immunohistochemical staining (PAX-2/Ki-67/MMR) for accurate differential diagnosis. 1 Introduction Endometrioid carcinoma (EC) is the most common histopathological subtype of endometrial cancer, whereas endometriosis (EM) is a hormone-dependent chronic gynaecological disorder. Although benign in nature, EM lesions frequently exhibit invasive behaviour and distant spread. Both conditions share significant similarities in tissue morphology and immunophenotypic characteristics(1). Studies have shown that EC and EM can co-exist within metastatic lymph nodes, complicating pathological diagnosis and even leading to misdiagnosis(2). Moreover, a proportion of EC patients exhibit loss of mismatch repair (MMR) proteins, resulting in microsatellite instability (MSI), which has been closely associated with increased tumour aggressiveness and lymphatic dissemination(3, 4). In the present case, the patient was found to have both EC and EM, with histological evidence of both tissue types within metastatic lymph nodes—a phenomenon considered exceedingly rare in clinical practice. Immunohistochemical analysis revealed a markedly elevated Ki-67 index and negative PAX-2 expression in carcinoma tissue, whereas ectopic endometrial tissue showed low Ki-67 expression and positive PAX-2 staining, thus facilitating the distinction between the two origins(5, 6). Notably, the carcinoma exhibited loss of MLH1 and PMS2 expression, indicative of the MSI-high (MSI-H) subtype, which has gained considerable attention in recent research for its prognostic and metastatic implications in endometrial carcinoma. Recent advances in high-throughput sequencing have identified oncogenic mutations —such as in ARID1A, PIK3CA, and KRAS—in some EM lesions, suggesting that EM may, in certain contexts, serve as a precancerous condition. These findings further support the hypothesis of a shared molecular pathogenesis between EC and EM(7). Therefore, this case is not only of exceptional academic rarity, but also offers new theoretical insights into the potential pathological and metastatic interplay between endometrioid carcinoma and endometriosis. 2 Case Presentation 2.1 Presenting Complaints and Disease History The patient was a 54-year-old female with a complaint of abnormal vaginal bleeding. Medical History: Outpatient ultrasound examination suggested multiple uterine leiomyomas, and computed tomography performed after admission revealed that the presence of calcified uterine leiomyomas. Moreover, the patient’s endometrium was thickened, and her right iliac lymph nodes were slightly enlarged (Figure 1). A subsequent pathological biopsy of the endometrium revealed endometrioid carcinoma (G2) (Figure 2、3). 2.2 Diagnosis: The diagnosis of endometrioid carcinoma (G2) was established. 2.3 Treatment Plan: Surgical treatment. Ten days after admission, the patient underwent total hysterectomy, bilateral adnexal resection, pelvic lymphadenectomy, and abdominal para-aortic lymphadenectomy. During surgery, multiple hard tumors protruded from the uterine surface, but the appearance and morphology of the bilateral adnexa were not abnormal. The pelvic, para-aortic, and retroperitoneal lymph nodes were not enlarged. After surgical intervention, the patient received two cycles of paclitaxel-carboplatin chemotherapy. 2.4 Postoperative Care The patient received routine postoperative care for endometrioid cancer. During the 3-month follow-up, the patient underwent regular examinations of blood tumor markers. The results indicated a significant decrease in the CA125 level, which dropped from 60.2 U/mL before the operation to 23.7 U/mL after treatment. 3 Discussion Diagnostic Challenges: Several studies have reported on endometriosis and cancer development in endometriotic lesions(8-10). Dimoulios et al. reported a patient with colon cancer associated with endometriosis. Due to the similarities in structures and morphologies between colorectal adenocarcinoma and endometriosis, they are often misdiagnosed(11). The current case involves a patient with endometrioid carcinoma complicated by endometriosis, with metastasis detected in two lymph nodes. However, only endometriosis was found in the other lymph nodes. Based on our literature search, this case is exceptionally rare. Notably, under microscopic examination, compared with colon adenocarcinoma, endometrioid carcinoma has a morphology more similar to that of endometriosis. Therefore, misdiagnosis is common, and determination of the pathological stage is challenging. Thus, accurately distinguishing between endometriosis and endometrioid carcinoma was the key focus in the differential diagnosis of the patient reported in this study. Microscopic HE images showed that the endometrioid carcinoma with lymph node metastasis featured obvious cellular atypia, nuclear division, and necrosis (Figure 4). IHC is an effective tool for distinguishing endometrioid carcinoma from endometriosis(12). Endometrioid carcinoma showed higher Ki-67, p53, and ER expression levels than endometriosis. Moreover, PAX-2 was expressed in endometriotic tissues but not in endometrioid carcinoma tissues (Figure 5). It was also found that metastatic lymph nodes and endometrioid carcinoma in the uterine cavity did not express MLH1 and PMS2 proteins, but normally expressed MSH2 and MSH6 proteins. This suggests that the patient may have had microsatellite instability and that MLH1, PMS2, MSH2, and MSH6 proteins are normally expressed in endometrial tissues in the same lymph node (Table 1). Riedinger et al. performed a full transcriptome analysis of large sample data obtained with next-generation sequencing ( NGS ) of endometrioid carcinoma samples and, found that endometrioid carcinoma with microsatellite instability had more aggressive characteristics and that its DNA expression was associated with tumor metastasis. MMR-deficient tumor cells may drive tumor metastasis(13). Endometriosis involves the ovaries, peritoneum, and the sigmoid colon. At present, our understanding of endometriosis remains limited, owing to the non-specificity of symptoms in patients with lymph node endometriosis or because it is difficult to diagnose this disease preoperatively. A previous study reported that up to 42.3% of the patients with rectosigmoid endometriosis had lymph node involvement (14). In addition, endometriosis and endometrial cancer have many similarities; both exhibit features of distant and lymph node metastasis and cause pain. In some studies(15), NGS has been used to detect cancer driver mutations (CAMs) in the glandular cells of endometriosis. Mutations in CAMs, such as ARID1A, PIK3CA, KRAS, and PPP2R1A, occur in some patients. Future research should focus on whether the simultaneous occurrence of endometriosis and metastatic endometrioid carcinoma in lymph nodes is related to similarities between the two diseases and whether the diseases share the same lymph node metastasis pathway or similar CAMs. Comprehensive Treatment Strategy: After surgical intervention, the patient received two cycles of paclitaxel-carboplatin chemotherapy. At the 3-month follow-up, regular blood tumor marker examinations were conducted, showing a decrease in the CA125 level. Prognosis Assessment: A large-scale study showed that female patients with both endometrial cancer and endometriosis had better overall survival than those with only endometrial cancer(16). After careful review of this study, it was found that, compared with those with only endometrial cancer, female patients with both endometrial cancer and endometriosis were younger and overall exhibited earlier disease stage, with better tumor differentiation. Therefore, improved OS of the female patients was unrelated to endometriosis. Another large-scale study on the surgical treatment of patients with endometriosis verified that active surgical treatment failed to significantly relieve pain in these patients (17). Rossini et al. conducted a retrospective study involving 140 patients with colorectal endometriosis and found that lymph node endometriosis was significantly associated with intestinal stenosis, infiltration rate, depth, and intestinal recurrence rate. Lymph node endometriosis does not alter the natural course of the disease(18) . Clinical Significance and Insights: There are a few reports of simultaneous lymph node metastasis and endometriosis in patients with endometrioid carcinoma. In this study, we reported a rare case of endometrioid carcinoma accompanied by endometriosis. Owing to its rarity, this case provides valuable insights into the co-occurrence of these conditions. This case report suggests that the mechanisms underlying lymph node metastasis in endometrioid carcinoma and endometriosis may be interrelated. However, further research on the mechanisms underlying lymph node metastasis in endometrioid carcinoma and endometriosis is needed. 4 Conclusions Herein, we reported a rare case of endometrioid carcinoma complicated by endometriosis, with metastasis detected in two lymph nodes; however, only endometriosis was found in other lymph nodes. The findings emphasize the importance of careful differential diagnosis in similar cases, as the morphological similarities can lead to misinterpretation. Author Contributions Conceptualization: Zhipeng Wang，Wenmei He. Methodology: Gongke li、Weiquan lu. Supervision:Ying Li. Writing–original draft: Zhipeng Wang、Wenmei He. Writing–review & editing: Ying Li. Acknowledgments The author would like to thank the patient in this case for providing clinical information and the Department of Pathology at Sanya Central Hospital for providing pathological diagnosis information. Ethics Statement As a single-case report with the patient’s signed consent, no other ethical review was required. Consent Written informed consent was obtained from the patient for the publication of this case report. Conflicts of Interest The author declares no conflicts of interest. Data Availability Statement The data used in this article are available upon request from the authors. Figure 1. A single slightly enlarged lymph node in the right ilium (indicated by the red arrow) Figure 2. A: Pathological image of endometrial biopsy under the microscope; B: Local magnification of A Figure 3. Multiple vessels invaded by endometrioid carcinoma on the myometrium wall. A: HE staining image under the microscope; B: Immunohistochemical CD31 staining image under the microscope; C: IHC D2-40 staining image under the microscope. All images on the right side are detail views of the images on the left side. Figure 4. A: Ectopic endometrial tissue in the upper part of the lymph node and metastatic endometrioid carcinoma in the lower part of the lymph node, accompanied by tumor necrosis (B and C are detail views). Table 1 IHC Endometriosis tissue Endometrioid carcinoma Ki-67 3% 50% P53 5% 25% PAX-2 + - PTEN + + ER 1% 95% CD10 + + PAX-8 + + MLH1 + - PMS2 + - MSH2 + + MSH6 + + Figure 5. Compared with endometriosis, endometrioid carcinoma showed higher expression levels of Ki-67, p53 and ER, and no expression of PAX-2. In both endometriosis and endometrioid carcinoma tissues , the mullerian duct system transcription factor PAX-8 was expressed. Therefore, it can be used in the diagnosis of female reproductive tract epithelial tumors(19). 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Hermens M, van Altena AM, van der Aa M, Bulten J, van Vliet H, Siebers AG, et al. Endometrial cancer prognosis in women with endometriosis and adenomyosis: A retrospective nationwide cohort study of 40 840 women. Int J Cancer. 2022;150(9):1439-46.17. Bafort C, Beebeejaun Y, Tomassetti C, Bosteels J, Duffy JM. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev. 2020;10(10):Cd011031.18. Rossini R, Monsellato D, Bertolaccini L, Pesci A, Zamboni G, Ceccaroni M, et al. Lymph Node Involvement in Deep Infiltrating Intestinal Endometriosis: Does It Really Mean Anything? J Minim Invasive Gynecol. 2016;23(5):787-92.19. Ordóñez NG. Value of PAX 8 immunostaining in tumor diagnosis: a review and update. Adv Anat Pathol. 2012;19(3):140-51. Supplementary Material File (figures.doc) Download 3.76 MB Information & Authors Information Version history V1 Version 1 09 July 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords family planning/reproductive health oncology Authors Affiliations Zhipeng Wang Sanya Central Hospital View all articles by this author wenmei He 0009-0003-9716-4158 Sanya Central Hospital View all articles by this author Ying Li [email protected] Sanya Central Hospital View all articles by this author Weiquan Lu Sanya Central Hospital View all articles by this author Gongke li Sanya Central Hospital View all articles by this author Metrics & Citations Metrics Article Usage 207 views 91 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Zhipeng Wang, wenmei He, Ying Li, et al. A Rare Case of Endometrioid Cancer with Lymph Node Metastasis and Endometriosis. Authorea . 09 July 2025. DOI: https://doi.org/10.22541/au.175204879.90929142/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. 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