Ovarian serous carcinoma with stomach metastasis: a rare case report and literature review

Abstract

Ovarian cancer is a common tumor among women. It is often asymptomatic in the early stages, with most cases already at stage III to IVE at the time of diagnosis. Direct spread and lymphatic metastasis are the primary modes of metastasis, whereas hematogenous spread is rare. An initial diagnosis of ovarian cancer that has metastasized to the stomach is also uncommon. Therefore, clear treatment methods and prognostic data for such metastasis are lacking. In our hospital, we encountered a patient with an initial imaging diagnosis of a gastric tumor and a history of an ovarian tumor with endoscopic abdominal metastasis. Based on the characteristics of the case, the two tumors were considered to be the same. After chemotherapy, a partial response was observed in the stomach and pelvic lesions, suggesting the effectiveness of the treatment. Through three treatments of recurrence, gastroscopy confirmed the stomach to be a metastatic site. Therefore, determining the primary source of advanced tumors is crucial in guiding treatment decisions. Clinicians must approach this comprehensively, relying on thorough evaluation and personal experience.

Introduction

Ovarian cancer (OC) is one of the most common gynecological tumors; nevertheless, it has the highest fatality rate among all gynecologic tumors.^1–3 Epithelial tumors are the predominant type of OC and include serous carcinoma, mucinous carcinoma, endometrioid carcinoma, undifferentiated carcinoma, and clear cell carcinoma. ⁴ Abdominal implantation metastasis is the primary route of OC metastasis, and the cancer mainly spreads to the peritoneum, uterus, fallopian tubes, lymph nodes, or pelvic peritoneum. Ovarian epithelial carcinoma can also metastasize to distant organs, with the chest, liver, abdominal wall, abdominal lymph nodes, and brain being the most common sites.^5,6 Gastric metastasis (GM) of OC is extremely rare. Distant lymph node metastasis has shown a relatively favorable prognosis.^7,8 Approximately 80% of patients with OC are diagnosed at a late stage, with a recurrence rate ranging from 70% to 80%. The overall prognosis is poor; the 5-year survival rate is 47.3%. ⁹ Gastric secondary cancer is clinically rare, with an incidence of approximately 0.2% to 0.7%. ¹⁰ The primary source of GM is breast cancer, followed by malignant melanoma and lung cancer. ¹⁰ GM of ovarian serous carcinoma is exceptionally uncommon, accounting for only 0.013% to 1.600% of all gastric metastatic tumors. ¹¹ According to the worldwide literature, diagnosis of the primary tumor and GM tumor is typically achieved after 32 months (range, 14–84 months). The main symptoms of GM include indigestion, anemia, bleeding, vomiting, and perforation. ¹² Pathologic examination is required for a definitive diagnosis. We herein report a case of ovarian serous carcinoma combined with GM in our hospital. This case suggests the possibility of other abdominal organ sources of gastric lesions, helps to fill the knowledge gap in the diagnosis of ovarian cancer and gastric metastasis, and provides a reference for clinical doctors to treat platinum-sensitive ovarian cancer. The reporting of this study conforms to the CARE guidelines. ¹³

Case presentation

An approximately 70-year-old woman who had been diagnosed with ovarian serous cystadenocarcinoma 4 years previously presented with a 5-month history of abdominal distension and a 1-month history of a pelvic mass. The patient had no relevant family history, and this was her first medical visit to our institution. Positron emission tomography–computed tomography (CT) revealed thickening of the gastric sinus wall along with enlarged abdominal, retroperitoneal, and right superior phrenic lymph nodes. Peritoneal implant metastasis and abdominal and pelvic effusion were also observed. The serum levels of cancer antigen 125 (CA125) and cancer antigen 153 (CA153) were high at 1983.0 U/mL and 121.4 U/mL, respectively. The patient underwent laparoscopic exploration, and exploratory and pathological biopsies were performed. There were no obvious abnormalities in the appearance of the gastric tissue under laparoscopy. However, endoscopy showed a space-occupying lesion in the stomach. Multiple biopsies revealed mainly negative pathology, indicating lesions confined to the submucosal layer. Positron emission tomography–CT showed no adnexal or ovarian masses. The pelvic tumor was diagnosed as metastatic. Immunohistochemical analysis confirmed that the pelvic metastasis had originated from ovarian serous cystadenocarcinoma. The immunohistochemical results were as follows: pan-cytokeratin +, cytokeratin 7 +, cytokeratin 20 −, villin +, CDX2 −, SATB2, CerbB2 (0), vimentin (−), Alcian blue + / periodic acid–Schiff −, CAM5.2 (+) in pelvic region, Ki67 (approximately 60% positive), estrogen receptor (−), and progesterone receptor (focal point +). According to the FIGO Cancer Report 2018, the clinical stage was IVB. The patient showed a partial response after six cycles of chemotherapy (paclitaxel plus carboplatin).

One year later, the patient presented to our hospital with abdominal pain. Gastroscopy revealed a mass in the gastric cardia, and the mass was confirmed to be tumor-free through gastric biopsy. The CA125 and CA153 concentrations had decreased to 417.9 U/mL and 43.23 U/mL, respectively. A breast cancer susceptibility gene test result was negative. The patient then underwent five cycles of chemotherapy (cyclophosphamide plus bevacizumab) and showed a partial response. Another year later, abdominal enhanced CT examination showed that the lesion occupied the lesser curvature of the gastric cardia and that the retroperitoneal lymph nodes had become enlarged (Figure 1(a)). The CA125 and CA153 concentrations had increased to 629.2 U/mL and 75.5 U/mL, respectively. Gastroscopy revealed an ulcer in the cardia, erosion of the gastric body, and neoplastic lesions of the stomach (Figure 1(b), (c)). Stomach biopsy confirmed GM of ovarian serous cystadenocarcinoma through hematoxylin and eosin and immunohistochemical staining (Figure 2(a)–(d)). The morphologic features and immunoprofile were consistent with the previous diagnosis of ovarian tumor. The patient underwent two cycles of chemotherapy (paclitaxel plus carboplatin), resulting in a partial response with a significant decrease in the size of the retroperitoneal lymph nodes. However, the treatment was discontinued when the patient developed COVID-19. Six months later, the patient developed disease progression due to a new occurrence in the left ovarian adnexal area. After one cycle of chemotherapy, she developed grade IV myelosuppression characterized by granulocyte deficiency syndrome, fever, and thrombocytopenia. The anti-tumor therapy was discontinued, and the patient died of gastrointestinal bleeding due to severe thrombocytopenia.

Figure 1.

Imaging examinations. (a) Enhanced computed tomography and (b, c) electronic gastroscopy revealed a gastric mass.

Figure 2.

Histological examination of the tumors. (a) Hematoxylin and eosin staining of the gastric metastases. Immunohistochemistry showed (b) PAX8 positivity, (c) WT1 positivity, and (d) 70% Ki67 positivity.

Discussion

Secondary gastric cancer is rare in clinical practice, with an overall incidence of only 0.2% to 0.7%. ⁴ The majority of GMs originate from breast cancer, followed by malignant melanoma and lung cancer.^14–16 GM from ovarian serous cancer is extremely rare, accounting for only 0.013% to 1.600% of all gastric metastatic tumors. ⁶ The most common symptom is indigestion, followed by anemia, bleeding, vomiting, and perforation. One study revealed a median interval of 32 months (range, 14–84 months) for diagnosis of GM from ovarian serous cancer. ¹² A definitive diagnosis requires clear pathology. In our patient, a gastric mass was discovered. Gastroscopy revealed lesions beneath the mucosa, which were not visually apparent. Because of difficulties in obtaining mucosal surface biopsies, the diagnosis remained inconclusive despite multiple repeated endoscopies. After receiving comprehensive treatment at another hospital, the patient returned to our hospital with abdominal pain. Enhanced CT and endoscopic examinations were performed, leading to a final diagnosis of GM from ovarian serous cancer. In clinical practice, when encountering a patient diagnosed with OC who presents with a gastric mass, it is necessary to determine whether the gastric tumor is a primary tumor or a metastasis from OC.

Advanced OC is associated with a poor prognosis, with a 5-year survival rate of approximately 47.5%. ⁹ Treatment of advanced OC primarily involves comprehensive approaches such as surgery, chemotherapy, targeted therapy, and immunotherapy. However, despite these interventions, the prognosis remains unfavorable. ¹⁷ The primary route of metastasis of OC is direct dissemination. Ovarian epithelial cancers commonly metastasize to the peritoneum, uterus, fallopian tubes, lymph nodes, or pelvic peritoneum. Hematogenous metastasis to distant organs, including the chest, liver, abdominal wall, abdominal lymph nodes, and brain, occurs in 2% to 3% of patients. Although the pathogenesis of GM from OC has not been fully elucidated, there are reports suggesting the existence of specific pathways that facilitate tumor metastasis between the stomach and ovaries. Estrogen likely serves as the primary catalyst, fostering the distal spread of OC by triggering the induction of epithelial–mesenchymal transition. ¹⁸ An analysis of tumor occurrence and metastasis in vivo revealed that MUC4 enhanced the metastasis of OC cells by upregulating N-cadherin, resulting in a heightened occurrence of metastasis to abdominal organs, particularly the stomach. ¹⁹ Furthermore, extracellular vesicles (or exosomes) released by OC cells have the ability to disseminate to the abdominal cavity, fostering gastrointestinal metastasis. ²⁰ Alterations in the tumor microenvironment, encompassing factors such as estrogen, exosomes, and MUC4, are likely to be influential contributors to the metastatic process of OC.

Metastasis of primary OC to the gastric parenchyma is even rarer. Reports have described cases in which patients presented with gastric and ovarian masses simultaneously. The general surgeons initially believed that the ovarian mass was a GM, leading to gastric sinus resection and mass removal surgery. However, immunohistochemical staining later revealed that the tumor had originated from the ovary, resulting in complete remission after anti-tumor treatment for OC. ²¹ Another report also described a case of a gastrointestinal tumor and OC occurring simultaneously. ²² This suggests that although the likelihood of GM from OC is low, we should not disregard the possibility in clinical practice. One study concluded that a clear diagnosis of GM could be achieved through ultrasound-guided fine needle aspiration of the gastric mass. ²³ In our particular case, the patient presented with abdominal distension and lower abdominal pain. The ovary was confirmed as the primary source, whereas the origin of the gastric mass remained unknown. Empirical medical therapy partially alleviated the gastric and ovarian lesions, leading to consideration of a homologous tumor. Ultimately, the pathological diagnosis was confirmed through repeated gastroscopy. Appropriate systemic therapy should be administered for the treatment of GM in such cases. ²⁴ Therefore, determining the source of advanced tumors is crucial in guiding treatment decisions and necessitates a comprehensive and detailed overall evaluation based on clinical experience.

Because of the rarity of GM from OC, no studies have analyzed the prognosis of this condition. In the present case, we analyzed our treatment experience of GM from OC. The GM was identified concurrently with the OC, but no pathologic diagnosis from gastroscopy was initially obtained. A pathologic diagnosis was eventually obtained after multiple gastroscopic interventions, emphasizing the importance of multi-point biopsy during gastroscopy. No standard treatment has been established for recurrent OC, and chemoresistance is a significant factor contributing to treatment failure in patients with recurrent ovarian epithelial cancer. Poly(ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in platinum-sensitive relapse therapy, but their role is limited in patients with platinum-resistant recurrent ovarian epithelial carcinoma. ²⁵ Our patient tolerated maintenance therapy with PARP inhibitors despite subsequently developing myelosuppression. However, because she lacked a breast cancer mutation and the estimated duration of PARP inhibitor maintenance is short, alternative therapeutic approaches needed to be considered. The continuous research and development of new therapeutic agents, such as antibody–drug conjugates, DNA damage response inhibitors, mechanistic target of rapamycin inhibitors, Src inhibitors, and DNA methyltransferase inhibitors,^26,27 holds promise for improving treatment outcomes in patients with OC. The findings in this case report may provide valuable therapeutic insights into the treatment of other patients with GM from OC.