Krukenberg tumours: diagnosis challenges, treatment approaches, and survival, sixteen-year experience at a single tertiary women’s hospital

Krukenberg tumours are rare metastatic ovarian tumour that originates primarily from the gastrointestinal tract. This study aimed to describe the diagnosis, treatment options, and survival outcomes in women with Krukenberg tumours treated in a single tertiary women’s hospital over a 16-year period. The case series included 15 patients diagnosed with Krukenberg tumours from 2008 to 2024. Data on pre-operative abdominal ultrasound and computed tomography scans, medical history, intraoperative history, treatment options, and laboratory parameters were collected from the hospital’s electronic database. None of the patients were preoperatively diagnosed with Krukenberg tumours, while 11 patients were suspected during surgery. Collaborating with gastroenterologists, oncologists, and pathologists confirmed these diagnoses as metastatic, with the primary sites identified. The other four patients with a history of gastrointestinal tumours (diagnosed 9 to 29 months prior) presented with gynaecological symptoms and were preoperatively diagnosed with primary ovarian tumours. However, Krukenberg tumours were confirmed intraoperatively in these cases as well. The primary tumour originated in the stomach for 10 patients and the colorectal region for 5 patients. Seven patients underwent cytoreductive surgery, while seven others underwent either a hysterectomy and bilateral salpingo-oophorectomy or bilateral salpingo-oophorectomy alone. One patient received palliative care. The median overall survival of all patients was 12 months, while the mean overall survival was 15 months. Among patients who underwent cytoreductive surgery, the median survival was 12.5 months, and the mean survival was 15 months. Pre-operative misdiagnosis of Krukenberg tumours is common. However, active collaboration with gastroenterologists, oncologists, and pathologists during surgery can help gynaecological oncologists overcome these diagnostic challenges. Similar content being viewed by others

Krukenberg tumour is a rare malignant growth in the ovary that primarily metastasises from the gastrointestinal tract, including the stomach and colon, affecting approximately 70% of patients [1], and develop during the reproductive age [2]. However, other sites, such as the breast, appendix, and biliary tract, can also be the origins [2]. The estimated annual incidence is approximately 0.16 per 100,000 women [3, 4]. Although the exact pathogenesis of Krukenberg tumour is not fully known, cancer cells from the origin metastasise to the ovary through the retrograde lymphatic or blood vessels, which are involved in the aetiology of this disease. These tumours are characterised by the presence of mucin-producing signet-ring cells. The overall survival rate is as low as 3 to 10 months after diagnosis [5]. A relatively higher incidence of Krukenberg tumours has been reported in Asian countries, including Japan, Korea, and China, due to the increased incidence of signet-ring cell gastric cancer [6]. There are no standardised clinical guidelines for effective treatment options for Krukenberg tumours, as the optimal treatment option is still controversial. However, cytoreductive surgery and systemic chemotherapy have been shown to extend overall survival in some patients [7, 8]. Additionally, in cases of widespread metastasis where curative surgery is not possible, palliative chemotherapy and supportive care can help manage symptoms and prolong survival [9]. The choice of systemic chemotherapy, including platinum, depends on the origin of primary tumours, though the effectiveness of chemotherapy remains conflicting (reviewed in [8]). Early diagnosis and surgical resection of the primary and metastatic lesions offer the best chance for prolonged survival. However, due to the non-specific clinical presentation, the metastatic nature, the complex diagnosis, and the difficulty of identifying the primary tumours, accurately identifying Krukenberg and their primary sites poses significant challenges for gynaecologic oncologists. In this case series, we present our sixteen-year experience from a single tertiary women’s hospital in treating and following up on women diagnosed with Krukenberg tumours, contributing to the available literature on treatment approaches and survival outcomes.

and materials This case series includes all patients diagnosed with Krukenberg tumours at Wuxi Maternity and Child Health Care Hospital of Jiangnan University, China, between January 2008 and January 2024. The study was approved by the Ethics Committee of Wuxi Maternity and Child Health Care Hospital (reference number: 2024-06-1025-53). The Ethics Committee waived the requirement for patient consent due to the nature of the retrospective study. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Fifteen women diagnosed with Krukenberg tumours at our specialised gynaecology hospital over a 16-year study period were included in this analysis. No cases were excluded. Following the surgical removal of the tumour lesions (Fig. 1), the final diagnosis of Krukenberg tumours was confirmed through histopathological examination, which showed typical signet-ring cells in the tumours (Fig. 2). All patients presented with gynaecological symptoms, and none of them initially presented with clinical suspicion of a non-gynaecological primary tumour when they were admitted to our hospital. Although two cases underwent gastrointestinal endoscopy before being admitted to our hospital, gastritis was diagnosed. Tumour markers, including serum levels of carbohydrate antigen (CA)-125, CA-199 and carcinoembryonic antigen (CEA), were measured. Due to the limitation of their specificity for exclusively diagnosing primary ovarian cancer, gastrointestinal endoscopy was not considered. All patients were managed under gynaecological disease protocols after admission to our hospital. Before surgery, all patients underwent abdominal ultrasound and computed tomography (CT) scans, and the gynaecologists made preliminary clinical diagnoses. It is referred to as the pre-operative diagnosis. Gastrointestinal primary was not observed in any of the cases by imaging. During operation, rapid histopathology using frozen sections was performed in all cases, allowing for immediate diagnostic evaluation and guiding surgical decision-making. After the operation, H&E stains and immunohistochemistry analysis, including CDX-2, SATB2, CEA, and CK20, were performed to confirm that the Krukenberg tumours originated from the gastrointestinal tract. Other general tumour markers, including p53, Ki-67, and PHH3, were also measured by immunohistochemistry. During surgery, when Krukenberg tumours were suspected/confirmed, gastroenterologists and oncologists were immediately called in for a consultation and performed surgery for the original cancerous mass as well, if it was possible. Data on detailed medical records, surgical history, clinical symptoms, imaging, and laboratory parameters, including preoperative serum levels of CA 125 or CA 199, or CEA at the time of diagnosis and during treatment, were collected from the hospital’s electronic database. Treatment options were also recorded. All patients were followed up through outpatient visits, repeat ultrasound evaluations, and telephone consultations until May 2024. Overall survival was measured from the time of Krukenberg tumour diagnosis. Statistical analysis The age at diagnosis was expressed as the mean and standard deviation (SD). In this retrospective case series study, only descriptive statistics were performed. Overall survival analysis was performed using Kaplan-Meier curves, and the median overall survival (with range) was calculated using GraphPad Prism (version 10.1.2). Missing data were handled using listwise deletion and excluded from analysis.

The mean age of 15 patients was 42 (± 13) years, and 13 were premenopausal. Clinical symptoms included abdominal pain in five patients and abdominal distension in seven patients (Table 1). Pelvic masses were detected in eight patients by either pre-operative ultrasound/CT or self-reported, and one patient presented with vaginal bleeding and one patient presented with hypomenorrhea (Table 1). Eleven patients were not previously diagnosed with gastrointestinal tumours. In contrast, four patients were previously diagnosed with gastrointestinal tumours between 9 and 29 months when they were admitted to our hospital. The tumours were initially presumed to be primary ovarian malignant or benign ovarian tumours in 11 patients by pre-operative radiological diagnosis (Table 2). Higher serum levels of CA-125 were observed in 10 cases, and 4 had unchanged levels (data on the remaining one case were missing). Higher serum levels of CEA were observed in 5 cases, and 8 had unchanged levels (data on the remaining two cases were missing). Excluding two cases with missing data, a higher ratio of CA125 and CEA (> 25) was observed in seven cases (55%). During surgery, when they were suspected to be Krukenberg tumours, gastroenterologists and oncologists were immediately consulted. In collaboration with gastroenterologists and pathologists, Krukenberg tumours were eventually confirmed in these patients (Table 2), and the primary tumours were identified as metastatic. Krukenberg tumours were presented in both ovaries in 13 patients and one ovary in 2 patients (Table 1). Histological examination confirmed the absence of metastasis in the opposite ovary in two cases with single-ovary metastasis (Table 1, cases 2 and 12). Additionally, during operation, ascites were observed in 4 cases, and peritoneal carcinomatosis was observed in 6 cases (Table 3), and an ovarian tumour metastasis was observed in all cases (Table 1). Residual tumour (R) 0 was achieved in 5 cases, and 2 cases were unresectable (Table 3). All patients present with a grade I or II score according to the Clavien-Dindo scoring system, after surgery. Four patients with a history of gastrointestinal tumours presented with gynaecological symptoms such as abdominal pain and pelvic masses, and were preoperatively diagnosed with primary ovarian tumours. However, they were eventually confirmed with Krukenberg tumours during and post-surgery. One of those four patients was suspected of spreading tumour cells to the omentum, and a gastroenterologist was immediately consulted for a surgical confirmation of tumour cell spread. The primary tumour site was the stomach in 10 patients and the colorectal region (excluding the appendix) in 5 patients. Only two patients had undergone a gastroscopy within the previous six months prior to admission to our hospital. Overall, based on pre-operative radiological diagnosis, four patients (27%) were diagnosed with primary ovarian carcinoma, six patients (60%) with benign ovarian tumour, and one case (6%) with uterine fibroids. Only four patients (27%) were diagnosed with metastatic ovarian carcinoma. However, intraoperative rapid histopathology confirmed Krukenberg tumours in eight patients (53%), metastatic tumour in three patients (20%), and primary ovarian tumour in four patients (27%) (Table 2). Only two patients received concurrent gastrectomies. The treatment options, primarily cytoreductive surgery, hysterectomy, and bilateral salpingo-oophorectomy, are summarised in Table 4. Seven patients (47%) underwent cytoreductive surgery, seven patients (47%) had either a hysterectomy and bilateral salpingo-oophorectomy or bilateral salpingo-oophorectomy alone, and one patient (6%) received palliative care. The overall survival details after the Krukenberg tumour diagnosis are summarised in Table 4, and the Kaplan-Meier curves were used for overall survival analysis (Fig. 3). Excluding one patient who has survived for more than 12 months since her Krukenberg tumour diagnosis and operation, the median overall survival of all patients was 12 months, ranging from 6 to 44 months, with a mean overall survival of 15 months. The median overall survival for patients with a primary tumour originating from the stomach was 13 months. For those diagnosed with Krukenberg tumours during surgery without knowing the primary tumour sites, the median overall survival was 9 months. The median overall survival for patients who underwent cytoreductive surgery (n = 6, excluding one patient still alive) was 12.5 months, with a mean overall survival of 15 months.

Since the first description of Krukenberg tumours in 1896, the incidence of Krukenberg tumours has increased, possibly due to the increased incidence of gastrointestinal tumours seen in young women [10]. Gastric and colorectal cancers together account for almost 90% of primary sites of Krukenberg tumours. Here, we describe a series of 15 patients diagnosed with Krukenberg tumours over a 16-year period. In our current study, the primary site of Krukenberg tumours in the stomach was observed in 10 patients (67%), and the colorectal region was seen in 5 patients (33%), which is consistent with the report in the literature [11]. We also found two patients with metastatic tumour cells spreading to multiple sites, including the Douglas pouch and omentum. Due to the nature of Krukenberg tumours, they are often discovered later, sometimes months or even years after the diagnosis of the primary tumours. This delay may be due to overlapping clinical symptoms, such as abdominal pain and abdominal distension, which can be similar to those of the primary tumours. As a result, an initial evaluation by a gastrointestinal tumour group is often required [12]. In our current study, 11 (73%) patients were not previously diagnosed with gastrointestinal tumours when they presented with gynaecological symptoms and were initially presumed to have primary ovarian malignant or benign tumours. However, they were suspected of having Krukenberg tumours during surgery and were finally confirmed to have Krukenberg tumours in collaboration with gastroenterologists, oncologists, and pathologists. Our experience in collaboration with gastroenterologists and oncologists helped our gyanecological oncologists ensure the comprehensive diagnosis of Krukenberg tumours and evaluation of possible primary tumour sites. In our study, only four patients were previously diagnosed with gastrointestinal tumours between 9 and 29 months. However, positron emission tomography (PET)-CT scans were not performed on these patients before surgery. Early detection of metastases can help guide treatment decisions and improve overall management. Given the metastatic nature of Krukenberg tumours, there are some similarities in clinical symptoms and the overlapping imaging characteristics between Krukenberg tumours and ovarian tumours. This results in difficulty in accurate diagnosis and distinguishing between the two tumours before surgery. In our current study, seven patients (47%) were incorrectly diagnosed preoperatively with benign ovarian tumours, uterine fibroids, or benign ovarian tumours based on ultrasound or CT imaging. However, intraoperative histopathology accurately diagnosed Krukenberg tumours in eight patients (54%). Pre-operative diagnostic errors with Krukenberg tumours are not uncommon. Although a high index of suspicion in patients with a history of gastrointestinal tumours in women suspected of ovarian tumours should be intensified, the possible reason for incorrect diagnosis in our study could be that 11 patients were not previously diagnosed with gastrointestinal tumours. The limitations in access to advanced diagnostic tools or biomarkers could be the factors that influence diagnostic accuracy, indicating that Krukenberg tumours must be differentiated from primary ovarian cancer. A study showed that biomarkers such as CA 125 or CEA, or the ratio of CA125 to CEA, have some diagnostic value for the diagnosis of Krukenberg tumours [13]. The CA-125 level is typically higher in primary ovarian cancer, with a median of 652 µg/ml, compared to Krukenberg tumours, which have a median of 43 µg/ml. In contrast, CEA levels are higher in Krukerberg tumours, with a median of 5.4 ng/ml, compared to primary ovarian cancer, which has a median of 1.4 ng/ml [13]. In our study, four patients did not show an increase in CA125, and eight patients showed no change in CEA levels. Six patients did not have a higher ratio of CA125 and CEA. This finding suggests a limited specificity of these serum tumour biomarkers in distinguishing between ovarian tumours and Krukenberg tumours. The lack of experience among our gynaecologic oncologists and radiologists in differentiating the imaging and clinical presentations may be another critical factor in the diagnostic challenges of Krukenberg tumours. Therefore, a continuing education program for gynaecologists focused on improving diagnostic skills and familiarity with the nuances of Krukenberg tumours could be beneficial in reducing diagnostic errors and enhancing patient outcomes. Although the survival rate of Krukenberg tumours depends on the original site and whether all visible cancer can be surgically removed (R0 resection), the overall median survival often ranges from 10 to 20 months. One study with a relatively large sample size showed a median survival of 16 months [14]. A recent review study also reported a mean overall survival is 14 months (StatPearls 2024). In our study, the overall median survival was 12 months (95% CI: 7–23), excluding one case that was at risk (over 12 months), although one case survived for 44 months. Collectively, these data indicate that the overall survival rate has remained unchanged over the last decades. There are currently no standardised treatment guidelines for Krukenberg tumours due to the heterogeneity of tumour biology. However, the basis for treatment includes R0 surgical removal and postoperative systemic chemotherapy with either as a monotherapy or in combination with taxanes and a platinum, depending on the tumour origin. Palliative surgery for Krukenberg tumours, including unilateral or bilateral salpingo-oophorectomy alone or total hysterectomy combined with bilateral salpingo-oophorectomy, resulted in a median overall survival of 17 months [9, 15]. Additionally, metastasectomy also improved overall survival for the Krukenberg tumours [16]. Recently, cytoreductive surgery has been shown to improve overall survival compared with chemotherapy alone [7, 8], which may be due to the fact that cytoreductive surgery enhances the responsiveness of chemotherapy for peritoneal carcinomatosis. In our series study, 7 (47%) patients received cytoreductive surgery. Excluding one patient still alive (at risk) for more than 12 months, the median survival for the six patients who underwent cytoreductive surgery was 12.5 months (mean survival was 15 months), which is slightly longer than that reported in other studies [5, 17]. Additionally, the overall survival rate may differ between primary sites because the progression of metastatic tumours can influence the overall survival of Krukenberg tumours. A study showed that 50% of patients diagnosed with Krukenberg tumours, originally from the colorectal region, survived for more than five years [18]. Due to the small sample size (we had only four cases with metastatic sites from the colorectal region), we were unable to directly compare our results with those of the study. However, our study did not see longer survival in Krukenberg tumours originating from colorectal tumours. Although a statistical comparison of overall survival between gastric and colorectal origins was not feasible in our current study, our data showed that the overall survival after diagnosis of Krukenberg tumours in these patients was similar. Our findings are consistent with a recent study showing no significant survival difference between Krukenberg tumours of gastric and colorectal origin [19]. The small number of patients is the main limitation of our study. For this reason, we were unable to determine whether cytoreductive surgery is the most effective option for Krukenberg tumours. Additionally, we could not statistically analyse the differences in overall survival between patients previously diagnosed with a gastrointestinal tumour and those not when they were admitted to our hospital. Future large sample-size studies are needed to analyse the effectiveness of cytoreductive surgery. In addition, all metastatic tumours in our cases originated from the gastrointestinal tract, specifically the stomach and colorectum. We had no cases of primary tumours arising from the breast or appendix. Survival outcomes may differ between these tumour origins and those observed in our cohort. Finally, none of the cases in our study underwent PET-CT, which could have improved diagnostic accuracy, particularly in patients with a history of malignancy. In conclusion, our 16-year case series study highlights the challenges in diagnosis and managing Krukenberg tumours, particularly the difficulty in preoperative diagnosis when the primary gastrointestinal tumour remains undiagnosed. The key take-home point from our experience is the necessity of adopting a robust, multidisciplinary and multimodal approach. Active collaboration with gastroenterologists, oncologists, and pathologists is essential to ensure accurate diagnosis, including the primary site of cancer. This interdisciplinary approach can ultimately benefit gynaecologic oncologists in overcoming the challenges of diagnosing Krukenberg tumours, as the treatment regimen, particularly chemotherapy, is based on the specific type and origin of the primary cancer. Data availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Abbreviations - CT: - Computed tomography - CA: - Carbohydrate antigen - CEA: - Carcinoembryonic antigen - SD: - Standard Deviation - PET: - Positron emission tomography

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N/A. Funding This study was supported by the Beijing Bethune Charitable Foundation (KY202301-14). Author information Authors and Affiliations Contributions All authors were involved in the drafting, editing, and approving the manuscript for publication. In addition to this, each author contributed to the following work. Conceptualization: QC, HC, DZ, and MZMethodology: LW, QC, and MZInvestigation: QC, HC, DZ, and MZData Curation: LWHistology: YYWriting - Original Draft: LW, QC, and MZWriting - Review & Editing: QC and MZFunding Acquisition: MZ. Corresponding author Ethics declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Wuxi Maternity and Child Health Care Hospital (reference number: 2024-06-1025-53). The Ethics Committee of Wuxi Maternity and Child Health Care Hospital waived the requirement for patient informed consent due to the nature of the retrospective study. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Consent for publication Not Applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Wang, L., Cao, H., Yin, Y. et al. Krukenberg tumours: diagnosis challenges, treatment approaches, and survival, sixteen-year experience at a single tertiary women’s hospital. BMC Cancer 26, 188 (2026). https://doi.org/10.1186/s12885-026-15578-2 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1186/s12885-026-15578-2