Isolated gastric metastasis of endometrioid carcinoma: a case report and literature review
Highlight box
Key findings
• Endometrial endometrioid carcinoma may manifest as isolated gastric metastasis characterized by a large ulcer, which is managed through radical resection. In patients with a history of ovarian and endometrial cancer, gastric lesions may signify secondary metastases from these malignancies.
What is known and what is new?
• Common sources of gastric metastases include breast cancer, lung cancer, esophageal cancer, renal cell carcinoma, and malignant melanoma. Isolated gastric metastasis from ovarian and endometrial cancers is exceedingly rare, and the mechanisms underlying this metastasis remain unclear.
• Our novel finding indicates that the postoperative pathology diagnosed the patient with isolated gastric metastasis originating from endometrial endometrioid carcinoma. If surgery is feasible and safe, cytoreductive surgery followed by adjuvant chemotherapy represents an effective and widely endorsed treatment approach, significantly improving patient prognosis and enhancing long-term survival rates.
What is the implication, and what should change now?
• This is the first reported case in the English literature of isolated gastric metastasis from endometrioid carcinoma characterized by a giant ulcer, managed through radical resection. Patients with isolated gastric metastases may derive significant benefit from complete cytoreductive surgery. This case report aims to augment clinicians’ understanding of this condition, thereby facilitating early diagnosis and treatment.
Introduction
Isolated gastric metastatic carcinoma is exceedingly rare; in three large autopsy series, the incidence of gastric metastatic carcinoma was reported to be as low as 0.54–1.7%, whereas the antemortem diagnosis through clinical endoscopic studies was even lower at 0.2% (1). In this case, the synchronous occurrence of low-grade endometrioid carcinoma in the endometrium and ovary remains controversial; however, the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging provides clear guidance on this matter (2). Nevertheless, isolated gastric metastases from primary ovarian or endometrial cancer are exceedingly rare. This article presents a case of isolated gastric metastasis originating from endometrioid carcinoma, manifesting as a giant ulcer infiltrating liver tissue. The diagnosis was confirmed through histological and immunohistochemical analyses conducted post-surgery. This case report aims to augment clinicians’ understanding of this condition, thereby facilitating early diagnosis and treatment. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-217/rc).
Case presentation
As the timeline shows (Figure 1), in May 2024, a 60-year-old female was admitted to the hospital due to nonspecific upper abdominal pain accompanied by melena. Six years earlier, the patient had undergone total hysterectomy, bilateral salpingectomy, pelvic lymphadenectomy, para-aortic lymph node dissection, and omentectomy for ovarian and endometrial cancer. Histological examination revealed moderately to poorly differentiated endometrioid carcinoma (stage IA) of the endometrium, with shallow myometrial invasion; the right ovary had moderately differentiated endometrioid carcinoma [stage IC (2009 FIGO)], with extension into the left ovary. There was no evidence of cancer invasion in either fallopian tube, and no lymph node metastasis was detected (0/17). The patient received four cycles of adjuvant chemotherapy with a paclitaxel and carboplatin regimen. Follow-up examinations revealed no tumor recurrence.
Current laboratory tests revealed mild anemia hemoglobin (HGB): 9.5 g/dL, and upper gastrointestinal endoscopy revealed a large, irregular ulcerative lesion in the gastric body, with a necrotic base and surrounding mucosal elevation (Figure 2). Endoscopic biopsy pathology revealed adenocarcinoma components, with immunohistochemical staining indicative of a gynecological origin. The immunohistochemistry results were as follows: cytokeratin 7 (CK7+), cytokeratin 20 (CK20−), Wilms’ tumor 1 (WT1−), cancer antigen 125 (CA125+), estrogen receptor (ER+), paired box 8 (PAX-8 +), Villin (+), and caudal type homeobox 2 (CDX2−). The test results revealed the following—carcinoembryonic antigen (CEA): 0.329 ng/mL, CA125: 12.0 U/mL, and cancer antigen 153 (CA153): 5.34 U/mL. To rule out systemic metastasis, an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan was performed, which revealed localized thickening of the gastric wall on the lesser curvature of the gastric body with intense FDG uptake and a maximum standardized uptake value (SUV) of 23.23 (Figure 3A). Abdominal transverse CT revealed irregular thickening of the gastric wall, with the thickest part measuring approximately 2.1 cm. The enhanced scan revealed mild persistent enhancement (Figure 3B), with no evidence of metastatic disease elsewhere.
The tumor was located in the upper part of the gastric body, near the cardia, and was characterized by infiltrative growth and extensive involvement. The patient subsequently underwent total gastrectomy, Roux-en-Y esophagojejunostomy, partial hepatectomy, and D2 lymphadenectomy. Intraoperatively, we found that both the mucosa and serosa of the gastric wall were involved, with tumor infiltration into the left hepatic lobe (Figure 4), without the detection of enlarged lymph nodes in the gastric antrum. Postoperative paraffin pathology revealed a large ulcerative tumor on the anterior gastric wall measuring 8 cm × 7.5 cm × 1.2 cm, with a gray-white firm cut surface infiltrating the full thickness of the gastric wall. Microscopic examination (Figure 5A,5B) and immunohistochemical marker analysis supported the diagnosis of metastatic low-grade endometrioid adenocarcinoma. No lymph node metastasis was found (0/25). The immunohistochemistry results were as follows: CK7 (partial+, Figure 5C), PAX-8 (+, Figure 5D), ER (partial+, Figure 5E), progesterone receptor (PR, partial+, Figure 5F), CK20 (−, Figure 5G), GATA binding protein 3 (GATA3 scattered weak+, Figure 5H), P53 (50%+, Figure 5I), Villin (−), Ki67 (60%+), CDX2 (−), Cadherin17 (−), WT1 (−), and P16 (partial+). Both the gastric tumor and the ovarian and endometrial cancers were positive for CK7, ER, PR, PAX-8, P53, and P16 but negative for CK20, WT1, and CDX2. The immunohistochemical staining results supported the final diagnosis of metastatic endometrioid carcinoma to the stomach. A postoperative review on day 7 revealed HGB 98 g/L, CEA 0.8 ng/mL, CA125 35.40 U/mL, and CA153 4.20 U/mL. The postoperative course was uneventful, and the patient was discharged on postoperative day 11. To date, no signs of recurrence or metastasis have been observed during the 3-month postoperative follow-up. The patient has a favorable prognosis and has undergone subsequent chemotherapy. All procedures performed in this study were in accordance with the ethical standards of the national research committees and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Discussion
There is debate regarding synchronous primary tumors of the endometrium and ovary. The distinction between low-grade endometrioid carcinoma (stage IA3) involving the endometrium and ovary and endometrial carcinoma with extensive ovarian metastasis (stage IIIA1) is crucial. The 2023 FIGO staging provides clear criteria: low-grade endometrioid adenocarcinoma can be classified as stage IA3 if it meets the following criteria: (I) myometrial invasion <1/2; (II) no extensive lymphovascular space invasion (LVSI); (III) no other metastases; and (IV) a unilateral ovarian tumor confined to the ovary in the absence of capsular invasion or rupture. Patients who do not meet these criteria are classified as having widespread ovarian metastasis of endometrial carcinoma (stage IIIA1) (2). This patient was diagnosed with ovarian and endometrial cancer six years ago. According to the 2009 FIGO staging, stage IA is defined as a tumor confined to the endometrium or with <1/2 myometrial invasion (3). However, under the updated 2023 FIGO staging system, this patient was classified as having stage IIIA1 endometrial endometrioid carcinoma.
This article describes a case of isolated gastric recurrence six years after the initial diagnosis of primary ovarian and endometrial cancer. The patient presented with chronic melena and underwent gastroscopy, revealing a large ulcerative lesion in the gastric body. Biopsy pathology and immunohistochemistry supported a diagnosis of endometrioid carcinoma with metastasis to the stomach. PET/CT confirmed isolated gastric metastasis. Postsurgical histology and immunohistochemistry [ER(+), PR(+), CK7(+), and PAX-8(+)] further supported the diagnosis of endometrioid carcinoma. This case met the diagnostic criteria for isolated gastric metastasis from primary endometrial endometrioid carcinoma. Gastric metastases are most commonly observed in patients with breast cancer, lung cancer, esophageal cancer, renal cell carcinoma, and malignant melanoma. The incidence rates of gastric metastasis from breast and lung cancer are 3.6% and 1.3%, respectively (4,5). The extreme rarity of isolated gastric metastases from ovarian and endometrial cancer has led to a limited number of reported clinical cases, and no studies have analyzed their incidence and mechanisms of metastasis.
We conducted a comprehensive review of all reported cases of isolated gastric metastasis from ovarian and endometrial cancer. As of September 2024, 10 English-language case reports have been identified in PubMed (Table 1). In this case, and the 10 reported cases, the age of onset ranged from 42 to 72 years (median: 60 years). Histologically, serous adenocarcinoma accounted for the majority of tumors (6 patients), with only 3 cases of endometrioid carcinoma. Besides this case, the other 2 cases had gastric metastasis from endometrial cancer (5,6), and most had FIGO stage III disease. The time from initial surgery to recurrence ranged from 0 to 144 months (median: 36 months). Two patients had lesions in the upper third of the stomach, one had lesions in the middle third, and seven had lesions in the lower third. The average survival time after the diagnosis of isolated gastric metastasis was 8 months. Ovarian and endometrial cancers may metastasize to other organs, including the stomach, via hematogenous spread without evidence of peritoneal metastasis. Despite the rich blood supply to the stomach, there are no reports clearly detailing hematogenous metastasis of the stomach from distant organs (7). Gastric metastatic tumors are usually located in the submucosa, where they form nodules or plaques with clear borders. Ulceration occurs only when the lesion enlarges, resulting in diminished blood supply to the center, mucosal involvement, or erosion of the overlying mucosa (8). Gastric metastatic tumors are usually located in the submucosa, where they form nodules or plaques with clear borders. Ulceration occurs only when the lesion enlarges, resulting in diminished blood supply to the center, mucosal involvement, or erosion of the overlying mucosa (5,9-11). Early diagnosis has become an essential part of treatment. Elevated serum CA125 levels and abnormal imaging findings can provide diagnostic clues for tumor recurrence. FDG PET/CT scans can detect the site of recurrence and systemic metastasis early on. In this case, FDG PET/CT imaging revealed a hypermetabolic lesion in the gastric body, and the literature supports the use of FDG PET/CT in postoperative surveillance (12). However, the final distinction between primary gastric cancer and metastatic gastric cancer still relies on biopsy pathology and immunohistochemistry.
Table 1
| Authors | Age (years) | Histological type | Stage | IPM (months) | Symptoms | Tumor size (cm) | Ulcer | Serum CA125 | Immunohistochemistry | Tumor location | Follow up after gastric metastasis |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Zhou et al. (4) | 61 | Serous, G3 | NA | 144 | Asymptomatic | 2.4×3 | + | high | CA125+, ER+, CK7+, WT1+, PR−, CK20−, CDX2− | L | 5 months, NED |
| Lundeberg et al. (5) | 72 | Endometrial endometrioid adenocarcinoma | IIIA | 36 | Fatigue, melena | NA | − | high | NA | U | 8 months, DOD |
| Cui et al. (6) | 42 | Endometrial endometrioid adenocarcinoma, FIGO 3 | I | 3 | Asymptomatic | 4.4 | NA | NA | AE1/3+, CAM2+, S100−, LAC−, CDX2−, PAX-8+, ER+, PR+ | NA | 2 months, NED |
| Jung et al. (7) | 49 | Serous | ≥IIB | 52 | Asymptomatic | 2.5×2.5 | − | high | NA | L | 18 months, NED |
| De Wide et al. (8) | 55 | Serous | ≥IIIb | 20 | Asymptomatic | 1.5 | − | NA | NA | L | NA |
| Sangha et al. (9) | 62 | Poorly differentiated carcinoma | NA | 84 | Belching, reflux, discomfort | 4 | + | high | CA125+, CK7-AE1/AE3+, CK7+, CK20−, vimentin−, CD117−, CEA− | U | NA |
| Yang et al. (10) | 47 | Serous | IIA | 25 | Abdominal pain | 3.6×2.8 | − | N | NA | L | 8 months, NED |
| Namikawa et al. (11) | 63 | Serous | NA | 72 | Asymptomatic | NA | + | NA | CA125+, ER+, PR+ | L | 9 months, DOD |
| Pernice et al. (12) | 42 | Serous, G3 | IIIC | 15 | Asymptomatic | 7 | NA | high | NA | L | 12 months, NED |
| Nikas et al. (13) | 61 | Adult type granulosa cell tumors | NA | 0 | Asymptomatic | NA | − | NA | α-inhibin+, calretinin+, CD56+, chromogranin−, synaptophysin−, CD117−, DOG1− | L | NA |
| Present case | 60 | Endometrial endometrioid adenocarcinoma | IIIA | 144 | Epigastric pain, melena | 8×7.5 | + | N | CK7+, CK20−, Villin−, Ki67 (60%+), PAX8+, CDX2−, Cadherin17−, WT1−, ER+, PR+, GATA3+, P16+, P53 (50%+) | M | 3 months, NED |
CA125, cancer antigen 125; CEA, carcinoembryonic antigen; CK, cytokeratin; DOD, died of disease; ER, estrogen receptor; IPM, interval between the treatment of the primary tumor and the diagnosis of metastatic tumor in the stomach; L, lower third of the stomach; M, middle third of the stomach; NA, not available; N, normal; NED, no evidence of disease; PR, progesterone receptor; U, upper third of the stomach; WT1, Wilms’ tumor 1; FIGO, International Federation of Gynecology and Obstetrics.
Histological and immunohistochemical evaluations are instrumental in distinguishing metastatic gastric cancer from gastric adenocarcinoma. Endometrioid carcinoma typically stains positive for PAX-8, ER, PR, and vimentin and negative for p53, p16, CK20, CEA, and HNF-1B. On the other hand, gastric adenocarcinoma usually stains positive for CK20, CDX2, MUC2, MUC5AC, and CK5/6, and negative for ER, PR, GATA3, and E-cadherin (5). Positive expression of PAX-8 is indicative of metastatic endometrioid carcinoma, and its value in distinguishing between endometrioid carcinoma and gastric cancer has been confirmed in the literature (6). Positive staining for CK14 and CK18 is indicative of squamous cell carcinoma and adenocarcinoma of the lung, respectively. Additionally, positive thyroid transcription factor 1 (TTF1) staining is associated with a thyroid or lung tumor origin (14). Commonly utilized markers for identifying breast origin include mammaglobin, gross cystic disease fluid protein 15 (GCDFP-15), and GATA3 (15).
Endoscopy can be used to monitor gastrointestinal metastasis, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive method for diagnosing metastatic gastric cancer. It provides high accuracy in the preoperative histological diagnosis and staging of gastrointestinal cancer, aiding in the correct diagnosis of submucosal gastric lesions. However, these lesions must be differentiated from low-grade malignant neoplasms that arise in the submucosal or muscular layers, including gastric neuroendocrine tumors (NETs), gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas (13). Early submucosal tumors (SMT) without ulcer formation in metastatic gastric cancer can be treated with endoscopic submucosal dissection (ESD) and enucleation (7). The optimal long-term survival approach for patients with metastatic ovarian cancer is complete cytoreductive surgery. Cytoreductive surgery for recurrent ovarian cancer is an independent prognostic factor (10). For breast cancer with gastric metastasis, both chemotherapy and hormonal therapy have been shown to improve survival outcomes and quality of life (16). For patients with resectable primary lung cancer accompanied by solitary gastric metastasis, surgical resection is a viable option that should be considered (14). Cytoreductive surgery followed by adjuvant chemotherapy represents an effective and widely recommended treatment strategy for confirmed solitary gastric metastasis. To our knowledge, this is the first case in the English literature to report isolated gastric metastasis from endometrioid carcinoma with a giant ulcer treated by radical resection.
Conclusions
In conclusion, although gastric metastasis of endometrioid carcinoma is extremely rare, clinicians should remain vigilant. For patients with a history of ovarian and endometrial cancer, gastric lesions may represent secondary metastasis from these malignancies. For solitary metastatic gastric lesions, early diagnosis and treatment are critical. If surgery is feasible and safe, cytoreductive surgery followed by adjuvant chemotherapy represents an effective and widely endorsed treatment approach, significantly improving patient prognosis and enhancing long-term survival rates.
Acknowledgments
The authors would like to thank all the reviewers who participated in the review.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-217/rc
Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-217/prf
Funding: This study was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-217/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the national research committees and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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Cite this article as: Zhu W, Sun L, Song X, Hou R, Gao S. Isolated gastric metastasis of endometrioid carcinoma: a case report and literature review. AME Case Rep 2025;9:58.
