Abstract

Ovarian cancer has the highest mortality rate among gynecological malignancies. Metastatic sites are most commonly found in the peritoneum, pelvic organs, and lymph nodes, followed by the liver, distant lymph nodes, lungs, bones, and brain. There have only been a few reports of distant metastases in the stomach.

Herein, we present a rare case of a 59-year-old woman with high-grade serous ovarian carcinoma with a single metastasis in the stomach. The post-surgery follow-up was performed with 18F-FDG PET/CT. The patient remained recurrence-free for 3 years. On a routine follow-up PET/CT scan, an intramural hypermetabolic lesion in the stomach, suggestive of GIST, was detected. A biopsy confirmed a metastasis from high-grade serous ovarian carcinoma. A “Reverse Krukenberg” tumor—a gastric metastasis from ovarian cancer—is extremely uncommon. The exact mechanism of spreading to the stomach is still unknown. Even though gastric metastasis from ovarian carcinoma is uncommon, we advise clinicians to stay mindful of the potential for gastric metastasis in patients with a history of ovarian cancer.

18F-FDG PET/CT, gastric metastasis, ovarian carcinoma

Ovarian cancer is the 8th most common cancer type in women and the deadliest one among the gynecological malignancies. Due to its late clinical presentation, it is often diagnosed in a late stage, when the 5-year survival rate is under 30%. Despite the commonly observed initial good response to chemotherapy, chemo-resistant tumor cells can remain in metastatic sites and lead to a relapse or progressive disease.^[1,2]

Ovarian carcinoma (OC) is a broad term that encompasses both epithelial and non-epithelial subtypes. Epithelial tumors are the most common form of OC and consist of serous, endometrioid, clear-cell, mucinous, and undifferentiated carcinomas, representing about 90% of all cases.‌^[3] The main pathway for OC metastasis is through abdominal implantation, with the cancer primarily spreading to the peritoneum, pelvic organs, and lymph nodes. OC also disseminates to distant organs—liver, distant lymph nodes, lung, bones, and brain being the most frequent sites.^[4] Gastric metastases are rare in clinical practice and autopsy analyses, with an incidence ranging from about 0.2% to 0.7%, with the main origin being breast cancer, followed by malignant melanoma and lung cancer.^[2,5] Gastric metastasis from OC is extremely rare, accounting for only 0.013% to 1.6% of all gastric metastatic tumors.^[2,5-7] We herein present a rare case of single submucosal gastric metastasis from OC without ulcerations, mimicking gastrointestinal stromal tumor (GIST). The tumor was detected on a follow-up 18F-FDG PET/CT in a patient with a history of ovarian cancer. The histological diagnosis was confirmed after endoscopic ultrasound (EUS) examination and biopsy.

A 59-year-old female with a history of arterial hypertension presented to another hospital with postmenopausal vaginal bleeding. This case report was conducted at Acibadem City Clinic Tokuda Hospital in Sofia, Bulgaria, with appropriate ethical oversight and patient consent obtained. Initial imaging, including abdominal and transvaginal ultrasound, revealed a cystic tumor formation in the pelvis. Given the findings, the patient underwent diagnostic and staging laparoscopic surgery, which included total hysterectomy, bilateral adnexectomy, total omentectomy, appendectomy, and paraaortic lymph node dissection. Pathological reports showed poorly differentiated ovarian carcinoma. Six weeks after surgery, the patient underwent a diagnostic CT scan in our hospital, which revealed no evidence of distant metastases. The patient was staged as pT3N1M0. Pre-therapy CA-125 levels were in the reference range. Therapy with paclitaxel, carboplatin, and bevacizumab was initiated after a cardiac ultrasound showed no abnormalities in the heart function and kinetics. After 6 cycles of combined chemo- and targeted therapy, the patient underwent a restaging with 18F-FDG PET/CT. It showed no signs of recurrent or metastatic disease and was assessed as stable disease according to RECIST 1.1 (Fig. 1) .

Figure 1.

Normal PET/CT scan. A. A maximum intensity projection (MIP) from the fused PET/CT showing normal biodistribution with physiologically high glucose uptake in the brain, heart, kidney, and bladder and moderately high glucose uptake in the spleen and liver; B. An axial CT slice from the hybrid PET/CT with no pathology present; C. A fused axial PET/CT image of the abdomen demonstrates physiologic distribution of FDG with no abnormal focal uptake. No corresponding CT abnormalities are identified.

A non-avid FDG lesion in the brain was revealed (not shown). As indicated by the findings, an MRI brain scan was performed and ruled out a metastasis from the oncologic disease; the lesion was assessed as meningioma. The therapy was continued in the same regimen. A restaging 18F-FDG PET/CT scan was performed after 16 cycles and showed stable disease. The patients continued maintenance therapy with bevacizumab in a stable clinical condition, remaining asymptomatic. Tumor marker CA-125 levels remained in the normal range. The following two routinely performed PET/CTs showed stable disease.

She was free of disease for 3 years until a routine follow-up PET/CT form January 2024 revealed a newly detected FDG-avid lesion in the stomach measuring 12×23 mm with SUVmax 6.45. The hypermetabolic intramural formation was smoothly compressing the posterior wall of the gastric body, bulging into the gastric cavity. The metabolic activity and morphological characteristics of the lesion raised the suspicion for a neoplastic process, suggestive of a gastric submucosal tumor such as a gastrointestinal stromal tumor (GIST) (Fig. 2) .

Figure 2.

A. An MIP image from the combined PET/CT demonstrates a focal area of increased FDG uptake medially from the left kidney. B. An axial CT slice from the hybrid PET/CT reveals a well-rounded infrastructural mass, gently pressing against the posterior wall of the gastric body and protruding into the lumen. C. A fused axial PET/CT image demonstrates a hypermetabolic lesion of the stomach with malignant characteristics.

At that time the patient reported no symptoms, exhibited overall well-being, and had no elevation in serum levels of CA-125. Based on the findings, EUS (endoscopic ultrasound) with biopsy was performed. The pathological report showed a metastasis of high-grade serous ovarian carcinoma (Fig. 3) .

Figure 3.

Microscopically, infiltration of metastatic serous adenocarcinoma cells into normal gastric tissues was observed. (H&E, 4×).

A clinical tumor board stated the necessity of a subtotal gastrectomy. In March 2024 a Billroth I partial gastrectomy was performed. The resected tissue was submitted for final pathological analysis, which excluded GIST and confirmed the surgically excised mass as metastatic ovarian cancer (Fig. 4) .

Figure 4.

Microscopic findings. Microscopically, infiltration of metastatic serous adenocarcinoma cells into normal gastric tissues was observed. A. H&E, 4×; B. H&E, 10×; C. The tumor cells’ immunohistochemical staining value was PAX8 positive (4×); D. The tumor cells’ immunohistochemical staining was WT1 positive (4×).

The postoperative period was well-tolerated, and the patient remained stable. A diagnostic CT in April 2024 showed no abnormalities. The patient continued targeted therapy with olaparib. Our patient successfully managed maintenance therapy with the PARP inhibitor with no adverse effects. The last PET/CT scan was performed in January 2025 and showed no signs of recurrent disease and no new metabolically active lesions (Fig. 5) .

Figure 5.

Normal PET/CT scan after Billroth I resection. A. No pathological findings seen on the MIP image; B. An axial postsurgical anatomy of the stomach with no evidence of residual or recurrent pathology seen on the CT slice from the hybrid PET/CT; C. A fused metabolic and morphological image showing no signs of abnormal activity or complications.

A Krukenberg tumor is a metastatic “signet ring” subtype of metastatic tumor to the ovary, which typically originates from the stomach in 70% of the cases with an incidence of 1% to 21%, with a higher frequency in Asian countries due to the greater prevalence of gastric cancer.^[8] A “Reverse Krukenberg” tumor—a gastric metastasis from ovarian cancer—is ever rarer, with few cases published.^[9] A systematic review published in 2016 described only 18 cases of gastric metastases originating from ovarian carcinoma, most of the patients being in advanced disease stages.^[10] Two additional case reports, published in 2021 and 2024, detailed newly identified patients with gastric metastasis originating from primary ovarian cancer.^[2,11]

Distant hematogenous spread has been reported in 2% to 3% of the patients.^[2] Even though the exact mechanism of gastric metastasis is not fully understood, it can be accounted for by the blood supply of the stomach, making it a potential target for metastasis. Gastric metastasis presents with nonspecific symptoms, which can include epigastric pain, melena, anemia, nausea, and vomiting. In this case, however, the patient was asymptomatic. Although the exact mechanisms of gastric metastasis from ovarian cancer remain unclear, some studies suggest specific pathways that facilitate tumor spread between the stomach and ovaries. Estrogen is likely a key factor, promoting the distant spread of ovarian cancer.^[12] Research on tumor development and metastasis in vivo found that MUC4 accelerates the metastasis of ovarian cancer cells by increasing N-cadherin expression, leading to more frequent metastasis to abdominal organs, especially the stomach.^[13] Changes in the tumor microenvironment, including MUC4, estrogen, and exosomes, are likely significant factors in the metastatic spread of ovarian cancer.^[2]

Although gastric metastasis from ovarian carcinoma is uncommon, we advise clinicians to stay mindful of the potential for gastric metastasis in patients with a history of ovarian cancer.

The clinical presentation of gastric metastasis from ovarian carcinoma can be nonspecific or vary, as presented in the current case. The combination of imaging modality plus biopsy can be a helpful tool in accurately diagnosing gastric lesions.

Ethical statement

• This case report was conducted at Acibadem City Clinic Tokuda Hospital in Sofia, Bulgaria, with the appropriate approval from the local Ethics Committee.
• The authors declared that no clinical trials were used in the present study.
• The authors declared that no experiments on humans or human tissues were performed for the present study.
• Informed consent was obtained from the patient for the publication of this case report.
• The authors declared that no experiments on animals were performed for the present study.
• The authors declared that no commercially available immortalized human and animal cell lines were used in the present study.

Conflict of interest

The authors have declared that no competing interests exist.

Artificial Intelligence (AI) use

The authors accept full responsibility for the content of the manuscript, including the disclosure of any use of AI. No AI tools were used in the preparation of this manuscript.

Funding

No funding was reported.

Author contributions

TS wrote the manuscript’s initial draft and finished it. EP wrote the first draft of the manuscript. SS did the report writing. BR conducted the patient’s initial examination and follow-up. The pathology studies and figures were completed by AF and BI. The final draft of the manuscript was examined and approved by all authors.

Author ORCIDs

Teodor Sofiyanski https://orcid.org/0009-0001-8838-9975

Data availability

All of the data that support the findings of this study are available in the main text.