Ovarian endometriosis associated with significantly elevated CA19-9: a case report

Background: Carbohydrate antigen 19-9 (CA19-9) is a well-established tumour marker primarily associated with pancreaticobiliary and gastrointestinal malignancies. Its elevation in benign gynaecological conditions, particularly in isolated ovarian endometriosis (OE) without malignancy, is rare and can pose a significant diagnostic challenge. Case presentation: In this case report, a 44-year-old female was found to have significantly elevated CA19-9 (up to 2453.1 U/mL), accompanied by left lower abdominal dull pain and weight loss. She was first diagnosed with an ovarian cyst more than 20 years ago, which resolved during pregnancy and recurred postpartum with no special intervention due to the absence of clinical symptoms. Extensive workup, including gastroenterological endoscopy and abdominal magnetic resonance imaging (MRI), excluded gastrointestinal malignancies. Laparoscopy followed by pathological examination confirmed the diagnosis of an ovarian endometriotic cyst (chocolate cyst). Postoperatively, the patient received standardised endocrine therapy, and follow-up assessments showed that serum CA19–9 levels returned to the normal range with no evidence of lesion recurrence.

For female patients with elevated CA19−9 combined with a long−standing ovarian cyst and pelvic symptoms, ovarian malignancy should be suspected after excluding gastrointestinal lesions. However, benign diseases should also be considered. The final diagnosis should be based on comprehensive clinical evaluation, additional laboratory and imaging findings, and ultimately confirmed by pathological biopsy. Clinicians need to strengthen the cognitive understanding of this atypical manifestation to reduce misdiagnosis. 1 Introduction Carbohydrate antigen 199 (CA19-9), a sialylated Lewis antigen, is weakly expressed in the epithelial cells of the pancreas, bile duct, gastrointestinal tract, and other tissues in the normal human body (). Its serum levels are frequently significantly elevated in gastrointestinal malignancies (e.g., pancreatic cancer, gastric cancer, colorectal cancer) and pancreatic diseases (e.g., acute pancreatitis, chronic pancreatitis) (, ), serving as an important indicator for the diagnosis, disease assessment, and prognostic monitoring of these disorders. Several studies have demonstrated that CA19–9 is expressed in both benign and malignant ovarian tumours (), and it has a high reference value for the diagnosis and differential diagnosis of malignant ovarian tumours, especially ovarian mucinous carcinoma. However, a significant elevation of CA19–9 in ovarian endometriosis is rare, and its exact pathophysiological mechanism remains incompletely elucidated, which poses great challenges for clinical diagnosis and differential diagnosis. In accordance with the CARE guidelines (), this paper details a case of ovarian endometriosis with significantly elevated CA19-9 (2453.1 U/mL; normal reference value < 43 U/mL) and reports the patient’s clinical characteristics, diagnosis, treatment, and follow-up outcomes. This case aims to provide new clinical evidence for the differential diagnosis of benign and malignant ovarian lesions and the clinical interpretation of elevated CA19–9 levels. This case report was approved by the Research Ethics Committee of Shenzhen Hospital of Traditional Chinese Medicine (Approval No.: K2022-165). The patient signed a written informed consent for the publication of this case report and any accompanying images. 2 Case presentation 2.1 Patient history The clinical course is illustrated in the Supplementary Figure 1. Twenty years ago, the patient was found to have an ovarian cyst measuring approximately 5 cm in size during a routine physical examination; the exact nature of the cyst was unclear. At that time, she had regular menstrual cycles with no dysmenorrhea, no lower abdominal pain, dyspareunia, or bowel and bladder dysfunction. No further tests were conducted to confirm the diagnosis, and she did not receive any hormonal medication. In 2009, the patient conceived naturally. Prenatal examinations revealed no ovarian cyst, and she delivered her first child vaginally. A postpartum follow-up transvaginal ultrasound detected the ovarian cyst again; however, as she had no specific symptoms, she did not undergo regular follow-ups or treatment. 2.2 Clinical findings At age 44 (Table 1 for her basic information), she sought medical attention due to an abnormally elevated CA19–9 level (453.03 U/mL; normal < 43 U/mL, Luteal phase). Other symptoms included occasional left lower abdominal pain, occasional heartburn, and occasional frequent urination. She had lost 2.5 kg in weight over the past six months unintentionally. Given the elevated tumour marker, abdominal pain, heartburn, and unintentional weight loss, a gastrointestinal malignancy was suspected; therefore, upper abdominal MRI and gastrointestinal endoscopy were recommended. During the examinations conducted by the gastroenterology team, the upper abdominal MRI revealed no significant abnormalities, whilst the gastrointestinal endoscopy confirmed chronic non-atrophic gastritis with bile reflux and colonic polyps. A follow-up CA19–9 test showed a progressive increase (932.83 U/mL, Follicular phase). Given her history of ovarian cysts, she was referred to the gynaecology department. Table 1 | Categories | Details | |---|---| | Gender | Female | | Age | 44 years | | Reproductive history | Married with children, G1P1A0; conceived naturally in 2009 and gave birth to one child vaginally. | | Fertility requirements | Contraception; currently no desire to conceive | | Age at menarche | 12 years | | Duration of menstrual period | 6 days | | Menstrual cycle length | 27–28 days | | Date of last menstrual period | 3 October 2025 | | Usual Menstrual Pattern | Menstruation is usually regular, with normal flow and colour, no dysmenorrhoea, and normal vaginal discharge. | | Have you ever received any form of hormone therapy? | No | | Results of most recent cervical screening | The patient reports that her cervical cancer screening in 2024 showed no abnormalities. | | Medical history | Breast nodules, thyroid nodules, chronic non-atrophic gastritis with bile reflux, and colon polyps (resected). | | Personal history | Denies smoking or alcohol consumption; no other significant lifestyle factors. | | Family history | Her father died of lung cancer. | Patient Information. A transvaginal ultrasound revealed: heterogeneous echogenicity of the uterine muscle layer; several hypoechoic areas visible in the uterine wall, the largest measuring approximately 13 × 8 mm (anterior wall) with poorly defined margins; the endometrial line was central, and the endometrial thickness was approximately 8.8 mm. Multiple anechoic areas were observed in the cervix, the largest measuring 8 × 6 mm with clear margins. In the left adnexal region, a cystic echo measuring 69 × 46 mm was observed, with clear margins, a thick, irregular wall, poor internal acoustic transmission, and dense punctate hypoechoic foci. No significant abnormalities were noted in the right adnexal region (Figure 1). Follow-up CA125 levels were 74.7 U/ml and CA19–9 levels were 2453.1 U/ml(Luteal phase). Given the persistently elevated CA-19–9 levels and the possibility of a malignant tumour, the patient and her family were informed of the situation. Following their consent, laparoscopic exploratory surgery was performed. Figure 1 2.3 Diagnostic assessment Microscopic findings (Figure 2): A small amount of dark red fluid in the pelvic cavity; multiple scattered chocolate-coloured nodules on the peritoneum of the pelvic and abdominal cavities, the omentum, and the surface of the intestinal tract; a chocolate-coloured, patchy protrusion on the peritoneum of the posterior wall of the bladder, measuring approximately 2 cm × 2 cm. The uterus is anteverted and of normal size; a myoma-like mass protruding from the surface of the anterior wall is visible, measuring approximately 1 cm in diameter. The left ovary is cystic and enlarged, measuring approximately 7 cm × 6 cm × 5 cm, with dense adhesions to the left pelvic wall. A chocolate-coloured cystic mass protruding from the surface of the right ovary is visible, measuring approximately 1 cm in diameter. No abnormalities are observed in the appearance of the bilateral fallopian tubes. Endometriosis classification: [Peritoneal type (SUP), Ovarian type (OMA)], rAFS score/ASRM classification: Stage III, ENZIAN(s): P3, O2/1, T1/0. Figure 2 2.4 Surgical intervention Adhesions throughout the pelvic cavity were released to fully expose the left ovary. The surface cortex of the left ovary was incised using an electrosurgical hook, and the space between the internal mass and the ovarian cortex was carefully dissected. The mass was completely excised(bilateral ovarian cystectomy); during the dissection, chocolate-like fluid was observed to drain. The cyst wall was removed and sent for frozen section analysis. Results: preliminary diagnosis of an endometriotic cyst. The cyst on the surface of the right ovary was managed using the same technique and sent for postoperative pathology. Multiple chocolate-like nodules in the pelvic and abdominal cavities were treated with electrocautery. A chocolate-like, patchy protrusion measuring approximately 2 cm × 2 cm on the peritoneum of the posterior bladder wall was excised. The mass on the anterior uterine wall was exposed. A vertical incision was made with an electrosurgical knife through the seromuscular layers of the anterior uterine wall to reach the pseudocapsule of the tumour. No hysterectomy or bilateral salpingo-oophorectomy was performed. The space between the mass and the uterine muscle layer was dissected using both blunt and sharp instruments, and the uterine mass was completely excised and sent for examination. Postoperative pathological examination confirmed the diagnoses of bilateral ovarian endometriotic cysts, intramural uterine leiomyomas, pelvic endometriosis (Figure 3), pelvic adhesions, breast nodules, thyroid nodules, and chronic non-atrophic gastritis with bile reflux. Figure 3 2.5 Postoperative course The patient initially received postoperative treatment with goserelin acetate (3.6 mg every 4 weeks for 3 months) as a GnRH agonist to suppress residual endometriotic lesions. The original plan was to follow this with long−term maintenance therapy with dienogest(2mg qd), but the patient declined this treatment for personal reasons after completing the goserelin course. During the goserelin treatment, the patient experienced temporary amenorrhea, which is an expected pharmacological effect. Despite the absence of maintenance therapy, at the most recent follow−up (10 March 2026, more than six months post−surgery), serum tumour markers (Figure 4) remained well within the normal range (CA125: 20.3 U/mL, CA19−9: 7.5 U/mL), and transvaginal ultrasound showed no evidence of pelvic mass recurrence. These findings support the durable remission of the endometrioma. Figure 4 3 Discussion and conclusion This case report describes a patient with a long-standing ovarian mass who presented with significantly elevated serum CA19-9, accompanied by left lower abdominal dull pain and weight loss. Malignant disease was ruled out via laparoscopic surgery, and the final diagnosis of ovarian endometriotic cyst was confirmed. After treatment with surgery combined with endocrine therapy, the serum CA19–9 level gradually returned to the normal range. CA19–9 is a sialylated Lewis A blood group antigen first discovered by Koprowski et al. in 1979; it was initially widely used as an adjunct in the early diagnosis of pancreatic cancer (). The distribution of CA19–9 is not limited to tumour cells; trace amounts are also present in the epithelial cells of the pancreas, bile ducts, stomach, and intestines in healthy individuals, as well as in normal secretions (such as saliva and digestive fluids).In healthy individuals, serum CA19–9 levels typically remain at a low level of <37 U/mL; in some individuals, levels may never rise due to genetic Lewis antigen negativity. When CA19–9 levels rise abnormally, the mechanisms are primarily divided into two categories: firstly, abnormal proliferation of malignant tumour cells, leading to a significant increase in the synthesis and secretion of CA19–9 and its massive release into the bloodstream; secondly, benign inflammatory stimuli (such as pancreatitis or cholecystitis) cause metabolic changes in the relevant epithelial cells, resulting in a transient increase. Consequently, elevated CA19–9 levels are strongly associated with malignant tumours such as pancreatic cancer (with a positive rate of up to 85–95%), cholangiocarcinoma and gastric cancer (), but are also commonly observed in benign conditions such as cholelithiasis, cirrhosis and diabetes. An elevated level of this single marker does not, in itself, have definitive diagnostic significance; however, a substantial and persistent rise may indicate a higher degree of malignancy (). Endometriosis is a common gynaecological condition, primarily characterised by progressively worsening dysmenorrhoea, chronic pelvic pain, dyspareunia, and infertility. The ‘gold standard’ for diagnosis is laparoscopy combined with a pathological biopsy, whilst the initial clinical diagnosis relies mainly on a typical medical history, gynaecological examination, and imaging assessments such as ultrasound; consequently, diagnostic delays are common (, ). Elevated levels of certain tumour markers have been associated with endometriosis, including CA125, CA19-9, CEA, and HE4 (). Among these, CA125 has demonstrated good predictive value as an indicator of incomplete treatment or disease recurrence (, ).CA19-9, on the other hand, shows a high correlation with overall survival (OS) and advanced disease (, ); its elevation is primarily associated with secretion by ectopic endometrial glands, chronic pelvic inflammation, activation of peritoneal mesothelial cells, and local barrier disruption caused by recurrent bleeding (, ). Specifically, ectopic endometrial glands possess the ability to secrete CA19-9, and concentrations of CA19–9 in cyst fluid can reach several thousand to tens of thousands of units, far exceeding serum levels. When cysts enlarge, cyst wall tension increases, or microleaks occur, high concentrations of the antigen are absorbed through the peritoneum into the systemic circulation. Pelvic endometriosis is a chronic inflammatory condition in which local levels of pro-inflammatory factors such as IL-6 and TNF-α are elevated. These factors can upregulate the expression of fucosyltransferase, enhancing the ability of ectopic endometrial cells to synthesise CA19–9 and creating a positive feedback loop; dense adhesions surrounding the cyst and recurrent intra-cystic haemorrhage further compromise the integrity of the cyst wall, promoting the continuous release of the antigen. Although this benign, reactive elevation may reach levels commonly seen in malignant tumours, it often declines rapidly following complete resection of the lesion, consistent with the dynamic changes observed in this case, where levels fell significantly one month post-surgery and returned to normal by three months. There was no recurrence within six months (Figure 4). There are already numerous case reports in the existing literature concerning endometriosis associated with significantly elevated CA19–9 levels (Table 2). It can be observed that there is a complex clinical association between elevated serum CA19–9 levels and ovarian cysts, which holds significant diagnostic and differential diagnostic value. In some cases, CA19–9 levels may reach as high as 7, 000–15, 000 U/mL (, ), significantly exceeding the 2, 453 U/mL observed in this case; however, there are also reports of only mild elevations (50–100 U/mL) (). Extremely elevated CA19–9 levels are highly suggestive of ovarian malignancy and are often accompanied by a concurrent rise in CA125, massive ascites, or acute abdomen resulting from cyst rupture; these ‘malignant’ signs further complicate the diagnosis. In contrast, tumour markers in benign conditions rapidly return to normal levels post-surgery. Khodaverdi S et al. () provide an important diagnostic approach: when HE4 and the ROMA index are normal, benign conditions such as endometriosis should be considered first, even in the presence of extremely high CA19-9/CA125 ratios. Furthermore, blood sampling during menstruation may lead to transient elevations (, ). Excluding benign ovarian cysts such as endometriomas and mucinous cysts (MCTs). Elevated CA19–9 levels have been reported in various types of ovarian cancer, including mucinous carcinoma/borderline tumours, clear cell carcinoma, carcinoid tumours, as well as rare sarcomas and metastatic tumours. In these cases, CA19–9 is frequently used as a serological marker for diagnostic guidance, monitoring treatment response, and predicting recurrence. Table 2 | Article title and DOI | First author | Publication Date | Patient’s age | Primary Diagnosis | Benign/Malignant | Serological markers | Imaging findings | Case summary | |---|---|---|---|---|---|---|---|---| | Ovarian chocolate cyst with markedly elevated serum CA19–9 levels: a case report. DOI: 10.1016/0028-2243(91)90229-e () | Takemori M | 1991 | 39 years | Ovarian chocolate cyst (endometrioma) | Benign | CA125: 380 U/ml, CA19-9: 2380 U/ml, CEA: 4. 3 ng/ml, TPA: 25 U/ml or less, and AFP: 5 ng/ml or less. | A multilocular cystic mass measuring approximately 12 × 8 cm, showing septal echoes, was observed on the left to posterior wall of the uterus. The interior of the mass was mostly anechoic or hypoechoic, but focal granular echoes were noted in some parts, indicating the presence of solid components | The patient presented with acute lower left abdominal pain and was found to have an o cyst; serum CA19–9 levels were significantly elevated. Immunohistochemical results showed that CA19–9 was expressed on the epithelium of the endometrioma, whereas no expression was observed in the endometrium or adenomyotic tissue. Postoperatively, serum CA19–9 levels returned to normal within 12 weeks. | | Unusually elevated serum carbohydrate antigen 125 (CA125) and CA19–9 levels as a result of unruptured bilateral endometrioma. DOI: 10.1046/j.0004-8666.2003.00088.x () | Yilmazer M | 2003 | 22 | Bilateral unruptured ovarian endometriomas | Benign | Serum samples taken on the 23rd day of the menstrual cycle: CA125: 134 U/mL and CA19-9: 61.96 U/mL. Repeat serum markers on the second day of menstruation were CA125: 1741.8 U/mL and CA19-9: 170.9 U/mL | Transabdominal ultrasonography revealed bilateral adnexal cystic masses measuring 44 × 35 mm and 56 × 42 mm, with solid internal components. | The patient presented with abdominal pain and was found to have bilateral ovarian cysts, with abnormally elevated CA125 and CA19–9 levels, raising a strong suspicion of malignancy. Surgery and histopathological examination confirmed bilateral endometriomas; post-operative tumour markers returned to normal levels. | | Massive peritoneal fluid and markedly elevated serum CA125 and CA19–9 levels associated with an ovarian endometrioma. DOI: 10.1111/j.1447-0756.2009.01122.x () | Park BJ | 2009 | 34 years | Ovarian endometrioma with massive ascites | Benign | CA125: 548.1 IU/mL. CA19-9: 7604, IU/mL. | A pelvic ultrasound revealed a large amount of peritoneal fluid containing echogenic material and a 10-cm complex cystic structure, which appeared to be an enlarged left ovary. | A young woman was admitted to hospital presenting with abdominal distension, massive ascites and significantly elevated tumour markers, raising a strong suspicion of ovarian cancer. The final pathological diagnosis was rupture of an endometrioma, and the markers declined rapidly following surgery. | | Elevated serum CA125 and CA19–9 due to the spontaneous rupture of an ovarian endometrioma. DOI: 10.1016/s0301-2115(02)00139-2 () | Kurata H | 2002 | 23 | Spontaneous rupture of an ovarian endometrioma | Benign | CA125: 9, 537: IU/ml, CA19-9: 15, 653 IU/ml | A pelvic examination revealed an elastic mass which appeared to be large (8 cm × 10 cm and 7 cm × 7 cm in diameter) bilateral ovarian cysts on vaginal ultrasound. | The patient presented with intermittent abdominal pain; tests revealed significantly elevated CA125 and CA19–9 levels. Surgery confirmed a ruptured ovarian endometriotic cyst, and post-operative levels returned to normal. | | Adnexal mass with extremely high levels of CA-125 and CA19–9 but normal Human Epididymis Protein 4 (HE4) and Risk of Ovarian Malignancy Algorithm (ROMA): Endometriosis or ovarian malignancy? A case report. PMID: 30123870 () | Khodaverdi S | 2018 | 18 | Pelvic endometriosis | Benign | CA-125: 6484 IU/ml, CA 19-9: 1309– IU/ml | Abdominopelvic ultrasonography revealed a, 14×10 cm complex, multiseptate cystic mass containing solid components in the right ovary and a small amount of free fluid in the cul-de-sac. The right ovary and uterus were normal. | The patient’s CA125 and CA19–9 levels were markedly elevated (), but HE4 and the ROMA index were normal. Surgical confirmation ultimately revealed pelvic endometriosis, suggesting that combined testing aids in differential diagnosis. | | Drastic elevation of serum CA125, CA72–4 and CA19–9 levels during menses in a patient with probable endometriosis. DOI: 10.1016/s0301-2115(98)00003-7 () | Imai A | 1998 | 25 | Probable endometriosis (menstruation) | Benign | CA125 >1000 U/ml, CA72-4 >10 U/ml and CA19-9 >150 U/ml during but not after menstruation (P<0.01). In the luteal and premenstrual phases, the levels of these markers appeared to return with -normal ranges, although CA125 remained above the upper normal limit. | An ultrasound examination and magnetic resonance imaging revealed a right adnexal cystic mass measuring 5 × 3 × 4 cm; the cyst had a regular surface wall and an inhomogeneous, haemorrhagic content, indicating a ‘chocolate cyst’. | A patient experienced a sharp rise in multiple tumour markers (CA125, CA72-4, CA19-9) during her menstrual period, which rapidly declined after the period ended, suggesting that the activity of endometriotic lesions during menstruation may have caused the elevation in marker levels. | | Bilateral Endometriotic Cystic Ovaries and a Huge Splenic Epithelial Cyst with Elevated CA-125 and CA19-9: A Report of a Rare Case. DOI: 10.7759/cureus.44256 () | Abdulla MR | 2023 | 26 | Bilateral endometriotic cysts of the ovaries combined with a giant splenic cyst | Benign | CA-125 and CA19–9 were 204.1 U/mL and 70.64 IU/mL | Her left ovary contained two unilocular thick-walled cystic masses with numerous small papillary projections, and vascularity was only detected in the wall of the largest mass (75×76×60 mm). Her right ovary contained a single unilocular thick-walled cyst measuring 77×60 mm, and her abdominal and pelvic ultrasounds revealed a well-defined, regular-outlined solid mass measuring 136×112×114 mm with obvious vascularity, which was pushing up the spleen. | The patient was found to have bilateral ovarian cysts and a giant splenic cyst, accompanied by elevated CA125 and CA19–9 levels. Postoperative pathology confirmed that the ovarian cysts were endometriotic cysts and the splenic mass was an epithelioid cyst. | | Clear Cell Carcinoma Arising From an Adenomyotic Cyst: A Case Report. DOI: 10.7759/cureus.71503 () | Morishita Y | 2024 | 38 years old | Malignant transformation of an adenomyotic cyst into clear cell carcinoma | Malignant | CA125: 1, 200 U/mL, CA19-9: 8, 178 U/mL | Pelvic magnetic resonance imaging (MRI) revealed a 12-cm solid uterine tumour. | The patient presented to the obstetrics and gynaecology department with lower abdominal pain. Her serum CA125 and CA19–9 levels were elevated, and imaging revealed a cystic lesion. Postoperative pathology confirmed a rare clear cell carcinoma arising from an adenomyotic cyst, demonstrating endometriosis-related malignancy. | | Rapid growth of an ovarian clear cell carcinoma expressing LH/hCG receptor arising from endometriosis during early pregnancy. DOI: 10.1006/gyno.19-96.0233 () | Kobayashi F | 1996 | 31 | Malignant transformation of endometriosis into clear cell carcinoma of the ovary during pregnancy | Malignant | CA125 and CA19–9 were 106 and 51 U/ml | She was diagnosed at 5 weeks’ gestation in June, and at, an ovarian tumour measuring 5 cm in diameter was identified. As the tumour had grown rapidly and measured 9 cm in diameter one week later, she was referred to our hospital. Upon admission to our hospital at 9 weeks’ gestation, the tumour measured 14 cm in diameter and we identified a solid component within the ovarian tumour. | A pregnant woman presented with a rapidly enlarging ovarian cyst in early pregnancy; postoperative pathology revealed clear-cell carcinoma of the ovary, originating from an endometriotic cyst, with immunohistochemical staining showing expression of LH/hCG receptors. | | A case of diaphragmatic clear cell carcinoma in a patient with a medical history of ovarian endometriosis. DOI: 10.1007/s10147-010-0052-y () | Fujiu K | 2010 | 65 years old | Transparent cell carcinoma of the diaphragm (history of ovarian endometriosis) | Malignant | The levels of carcinoembryonic antigen (CEA), CA19-9, PIVKA-II, and alpha- -fetoprotein (AFP) were normal. However, the CA-125 level was 48 U/ml (normal range, 0–35 U/ml). | During a routine medical examination of a 65-year-old woman, ultrasonography revealed a 2.5-cm nodule on the surface of the liver. She had undergone a hysterectomy for the treatment of a uterine myoma at the age of 51. The left ovary was not resected. No malignant lesions were found in the resected uterus. | The patient presented with elevated CA19–9 and CA125 levels and a history of surgery for ovarian endometrioma (). A diaphragmatic mass was ultimately identified; histopathological examination revealed clear cell carcinoma, which is considered to be associated with the malignant transformation of endometriosis. | | The Great Mimicker: Extragonadal Endometriosis Presenting as an Appendiceal Mass and Acute Appendicitis.DOI: 10.7759/cureus.88718 () | Ha J | 2025 | 45 | Appendiceal endometriosis | Benign | CA19-9, CA-125, and CEA were tested, of which only CA-125 was elevated at 92.7 U/mL (reference range: 0–35 U/mL). | A CT scan of the abdomen and pelvis revealed an enlarged structure in the right lower quadrant along the medial border of the caecum, suggestive of acute appendicitis with a retained rupture. | Endometriosis implanted in the appendix caused symptoms of acute appendicitis and elevated CA19–9 levels, demonstrating a rare site of endometriosis. | Summary of reported CA19–9 levels in endometriosis-associated cases from the literature. Serum CA19–9 is a broad-spectrum tumour-associated antigen with low specificity but high sensitivity. In ovarian-related diseases, an isolated elevation in CA19–9 levels cannot serve as the gold standard for diagnosing malignancy. Clinical decision-making must take into account the patient’s age, symptoms, signs, imaging findings, and other ancillary investigations. In young patients with a high suspicion of endometriotic cysts, if CA19–9 levels are markedly elevated, prompt surgical exploration to confirm the pathology is crucial. Postoperative monitoring of CA19–9 is of significant value in assessing treatment efficacy and detecting recurrence. 4 Limitations The single case nature of this report limits generalisability. Regarding the limitation of short follow−up, we are pleased to report that we have now extended the observation period to over six months, showing normal CA125 and CA19−9 levels (20.3 U/mL and 7.5 U/mL, respectively). Nevertheless, we acknowledge that longer−term follow−up remains desirable, and we will continue to monitor the patient.HE4 and ROMA index data were not obtained, which represents a missed opportunity to further strengthen the benign diagnosis. The patient’s Lewis blood group status was not assessed; this is relevant because CA19–9 expression is dependent on the Lewis antigen system.CA19–9 levels in the cyst fluid were not measured, which would have provided direct evidence of the source of elevation. The retrospective design is an inherent limitation of a case report. Statements Data availability statement The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author. Ethics statement This case report involving a human participant was approved by the Research Ethics Committee of Shenzhen Hospital of Traditional Chinese Medicine (Approval No. K2022-165). The study was conducted in accordance with the Declaration of Helsinki and its later amendments. Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report. Author contributions YH: Writing – original draft, Writing – review & editing. JR: Conceptualization, Investigation, Writing – original draft, Writing – review & editing. XD: Funding acquisition, Writing – review & editing. Funding The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Sanming Project of Medicine in Shenzhen (Grant No.: SZZYSM202211006). Acknowledgments The authors thank the patient and staff participating in the study. Conflict of interest The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Generative AI statement The author(s) declared that generative AI was used in the creation of this manuscript. Generative AI was used. This article used artificial intelligence to help with language polishing. Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us. Publisher’s note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2026.1846804/full#supplementary-material Supplementary Figure 1The course of the patient’s illness. Abbreviations CA19-9, Carbohydrate antigen 19-9; CA125, Cancer antigen 125; OE, Ovarian endometriosis; CEA, Carcinoembryonic antigen; CT, Computed tomography; HE4, Human epididymis protein 4; MRI, Magnetic resonance imaging; rAFS, Revised American Fertility Society; ASRM, American Society for Reproductive Medicine; ENZIAN, Endometriosis classification system; ROMA, Risk of Ovarian Malignancy Algorithm; MCT, Mucinous Cystic Tumour; HE, Hematoxylin and Eosin; GnRH, Gonadotropin−releasing hormone.

1 ScaràSBottoniPScatenaR. CA 19-9: Biochemical and Clinical Aspects. Adv Exp Med Biol. (2015) 867:247–60. doi: 10.1007/978-94-017-7215-0_15 2 TengDWuKSunYZhangMWangDWuJet al. Significant increased CA199 levels in acute pancreatitis patients predicts the presence of pancreatic cancer. Oncotarget. (2018) 9:12745. doi: 10.18632/oncotarget.23993 3 AMCKKAGBRPEBet al. Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer. HPB (Oxford). (2015) 17:942–52. doi: 10.1111/hpb.12448 4 LiTHouNMaoLLiuFMaZWangLet al. Tumor markers in differential diagnosis of benign ovarian masses. IJWH. (2024) 16:1517–31. doi: 10.2147/IJWH.S471058 5 RileyDSBarberMSKienleGSAronsonJKvon Schoen-AngererTTugwellPet al. CARE guidelines for case reports: explanation and elaboration document. J Clin Epidemiol. (2017) 89:218–35. doi: 10.1016/j.jclinepi.2017.04.026 6 LuoGJinKDengSChengHFanZGongYet al. Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter. Biochim Biophys Acta Rev Cancer. (2021) 1875:188409. doi: 10.1016/j.bbcan.2020.188409 7 YangJXuRWangCQiuJRenBYouL. Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review. Cancer Commun (Lond). (2021) 41:1257–74. doi: 10.1002/cac2.12204 8 FarzanehFSalimnezhadMHosseiniMSAshraf GanjoueeTArabMTalayehM. D-dimer, fibrinogen and tumor marker levels in patients with benign and Malignant ovarian tumors. Asian Pac J Cancer Prev. (2023) 24:4263–8. doi: 10.31557/APJCP.2023.24.12.4263 9 TaylorHSKotlyarAMFloresVA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. (2021) 397:839–52. doi: 10.1016/S0140-6736(21)00389-5 10 VercelliniPViganòPSomiglianaEFedeleL. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. (2014) 10:261–75. doi: 10.1038/nrendo.2013.255 11 Ramírez-PavezTNMarín-SánchezPNebotAGarcía-IzquierdoLNieto-MecaLSánchezRet al. Systemic immune and tumor marker profiles in ovarian and deep infiltrating endometriosis: associations with disease severity and symptom burden. Int J Mol Sci. (2025) 26:9581. doi: 10.3390/ijms26199581 12 MuyldermansMCornillieFJKoninckxPR. CA125 and endometriosis. Hum Reprod Update. (1995) 1:173–87. doi: 10.1093/humupd/1.2.173 13 AbrãoMSPodgaecSPinottiJAde OliveiraRM. Tumor markers in endometriosis. Int J Gynaecol Obstet. (1999) 66:19–22. doi: 10.1016/s0020-7292(99)00046-6 14 ShenAXuSMaYGuoHLiCYangCet al. Diagnostic value of serum CA125, CA19-9 and CA15-3 in endometriosis: A meta-analysis. J Int Med Res. (2015) 43:599–609. doi: 10.1177/0300060515583076 15 StovallDWHalmeJ. Endometriosis and associated pathology. Curr Opin Obstet Gynecol. (1991) 3:853–8. doi: 10.1097/00001703-199112000-00019 16 Rosendo-ChalmaPDíaz-LandyENAntonio-VéjarVOrtiz TejedorJGReytor-GonzálezCSimancas-RacinesDet al. Endometriosis: challenges in clinical molecular diagnostics and treatment. Int J Mol Sci. (2025) 26:3979. doi: 10.3390/ijms26093979 17 ParkBJKimTEKimYW. Massive peritoneal fluid and markedly elevated serum CA125 and CA19-9 levels associated with an ovarian endometrioma. J Obstet Gynaecol Res. (2009) 35:935–9. doi: 10.1111/j.1447-0756.2009.01122.x 18 KurataHSasakiMKaseHYamamotoYAokiYTanakaK. Elevated serum CA125 and CA19-9 due to the spontaneous rupture of ovarian endometrioma. Eur J Obstet Gynecol Reprod Biol. (2002) 105:75–6. doi: 10.1016/s0301-2115(02)00139-2 19 AbdullaMRSaeedYAAbdul AzizJMAhmedSAAbdullahYASabirAAet al. Bilateral endometriotic cystic ovaries and huge splenic epithelial cyst with elevated CA-125, CA19-9: A report of a rare case. Cureus. (2023) 15:e44256. doi: 10.7759/cureus.44256 20 KhodaverdiSAmini-MoghaddamSAlmassi NokianiFHashemiNMohammad BeigiR. Adnexal mass with extremely high levels of CA-125 and CA19-9 but normal Human Epididymis Protein 4 (HE4) and Risk of Ovarian Malignancy Algorithm (ROMA): Endometriosis or ovarian Malignancy? A case report. Int J Reprod BioMed. (2018) 16:413–6. doi: 10.29252/ijrm.16.6.413 21 YilmazerMSonmezerMGungorMFenkciVCevriogluS. Unusually elevated serum carbohydrate antigen 125 (CA125) and CA19-9 levels as a result of unruptured bilateral endometrioma. Aust N Z J Obstet Gynaecol. (2003) 43:329–30. doi: 10.1046/j.0004-8666.2003.00088.x 22 ImaiAHoribeSTakagiATakagiHTamayaT. Drastic elevation of serum CA125, CA72-4 and CA19-9 levels during menses in a patient with probable endometriosis. Eur J Obstet Gynecol Reprod Biol. (1998) 78:79–81. doi: 10.1016/s0301-2115(98)00003-7 23 TakemoriMSugimuraK. Ovarian chocolate cyst with markedly elevated serum CA19-9 level: a case report. Eur J Obstet Gynecol Reprod Biol. (1991) 42:241–4. doi: 10.1016/0028-2243(91)90229-e 24 MorishitaYYagiHOnoyamaIYahataHKatoK. Clear cell carcinoma arising from adenomyotic cyst: A case report. Cureus. (2024) 16:e71503. doi: 10.7759/cureus.71503 25 KobayashiFMonmaCNanbuKKonishiISagawaNMoriT. Rapid growth of an ovarian clear cell carcinoma expressing LH/hCG receptor arising from endometriosis during early pregnancy. Gynecol Oncol. (1996) 62:309–13. doi: 10.1006/gyno.1996.0233 26 FujiuKMiyamotoHHashimotoSSuzukiNTakanoYTeranishiYet al. A case of diaphragmatic clear cell carcinoma in a patient with a medical history of ovarian endometriosis. Int J Clin Oncol. (2010) 15:489–92. doi: 10.1007/s10147-010-0052-y 27 HaJHamidFAhnJAfuapeNAzharE. The great mimicker: extragonadal endometriosis presenting as an appendiceal mass and acute appendicitis. Cureus. (2025) 17:e88718. doi: 10.7759/cureus.88718 Summary

CA19-9, case report, endometriosis, ovarian endometrioma, tumor marker Citation Hu Y, Ruan J and Du X (2026) Ovarian endometriosis associated with significantly elevated CA19-9: a case report. Front. Oncol. 16:1846804. doi: 10.3389/fonc.2026.1846804 Received 07 April 2026 Revised 29 June 2026 Accepted 30 June 2026 Published 21 July 2026 Volume 16 - 2026 Edited by Anthony Taylor, University of Leicester, United Kingdom Reviewed by Fengyi Xiao, Fudan University, China Francesco Giuseppe Martire, University of Rome Tor Vergata, Italy Updates Copyright © 2026 Hu, Ruan and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Xuelian Du, [email protected] †These authors share first authorship Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.