Rare Case of Metachronous Gastric Metastasis from Primary Ovarian Carcinoma

Abstract

Metastasis of ovarian cancer to the stomach is extremely rare. The tumors most commonly metastasizing to the stomach include melanoma, breast, lung, and oesophageal carcinoma, while ovarian cancer comprises only 0.013–1.6% of all gastric metastatic tumors. The aim of this study was to present a rare case of an isolated metachronous gastric metastasis from an ovarian carcinoma, in a 59-year-old lady. A 59-year-old lady presented with a right adnexal mass on MRI imaging of the abdomen and pelvis and an elevated serum CA 125 of 4240 IU/ml. She underwent a primary cytoreductive surgery comprising of omentectomy, peritoneal biopsies, pelvic peritonectomy and peritoneal washing cytology, hysterectomy and bilateral salpingo-oophorectomy, and a retroperitoneal and pelvic nodal dissection. The surgical Peritoneal Carcinomatosis Index (PCI) was 5. The final histopathology showed a high-grade serous adenocarcinoma involving the right adnexa. She received six cycles of adjuvant chemotherapy. On a 3-monthly follow-up, the PET scan revealed that a gastric fundic lesion was noted. Investigations revealed a metachronous metastasis from the serous carcinoma of the ovary, confirmed by histopathological evaluation. The patient was treated with surgical resection of the metastasis and systemic chemotherapy to achieve disease control. Gastric metastasis from ovarian cancer should be considered a differential diagnosis in any patient presenting with a gastric mass and a history of ovarian cancer.

Introduction

Ovarian cancer is one of the commonest gynecological malignancies. The majority of ovarian cancer patients are diagnosed at an advanced stage (stages III–IV) [1]. Ovarian cancer has a propensity to metastasize to the peritoneal cavity and the pelvic and retroperitoneal lymph nodes. Metastasis to distant organs such as the lung, liver, and bones is extremely rare [2]. In the natural course of the disease, gastrointestinal involvement may be seen in ovarian cancer due to the direct invasion of metastatic tumor implant over bowel serosal surfaces [3, 4].

Metastasis of ovarian cancer to the stomach is extremely rare. The tumors most commonly reported to metastasize to the stomach include melanoma, breast, lung, and oesophageal carcinoma, while ovarian cancer comprises only 0.013–1.6% of all gastric metastatic tumors [3, 5–8]. They most commonly present as a synchronous metastasis which is usually associated with advanced disease and concurrent peritoneal metastasis. They can also present as an isolated solitary gastric metastasis. However, isolated metachronous gastric metastasis in the absence of peritoneal disease is extremely rare, with very few cases reported in literature.

The aim of this study was therefore to present a rare case of an isolated metachronous gastric metastasis from an ovarian carcinoma, in a 59-year-old lady.

Case Summary

In this article, we discuss the case of a 59-year-old lady who presented with complaints of deep vein thrombosis (DVT) for which she was started on oral anticoagulants. An ultrasonography (USG) of the abdomen and pelvis performed for the workup of DVT showed an incidental right adnexal mass 6.5 × 6 × 4 cm which was confirmed subsequently by a Magnetic Resonance Imaging (MRI) of the abdomen and pelvis, which in addition to the adnexal mass also showed enhancing retroperitoneal and pelvic lymph nodes. There was no evidence of ascites or peritoneal disease (Fig. 1). During this time, serum tumor markers were evaluated which were found to be elevated. The serum CA 125 was 4240 µ/ml. The CEA and the CA 19.9 values were within the normal range.

Fig. 1.

MRI scan (red arrow) showing enhancing right adnexal mass

With the above background of an elevated serum CA 125 and adnexal mass on imaging, a working diagnosis of carcinoma of the ovary was made and the patient was planned for a primary cytoreductive surgery. However, during this time, prior to the surgery, the patient developed hematemesis and a fall in hemoglobin to 3 mg/dl. She was resuscitated and once stable, underwent an Upper Esophagogastroduodenoscopy (EGD), which did not reveal any mass or specific cause of bleed (Fig. 2). Subsequently, with the bleeding under control and improved general condition, she underwent primary cytoreductive surgery comprising of omentectomy, peritoneal biopsies, pelvic peritonectomy and peritoneal washing cytology, hysterectomy and bilateral salpingo-oophorectomy, and a retroperitoneal and pelvic nodal dissection. The surgical Peritoneal Carcinomatosis Index (PCI) was 5.

Fig. 2.

Upper GI endoscopy prior to adjuvant chemotherapy prior to TAH + BSO + PLND

The final histopathology showed a high-grade serous adenocarcinoma involving the right adnexa. Immunohistochemistry was positive for p53, CK7, and PAX8. Two out of 18 nodes showed metastatic disease without any perinodal extension (PNE), but positivity for lymphovascular emboli (LVE), pelvic peritoneum, and omentum was involved by the disease. The pathological PCI was 5.

She received six cycles of adjuvant chemotherapy. The chemotherapeutic medication administered was 3 weekly carboplatin and paclitaxel. The patient was followed up with the PETCT scan at 3 months (Fig. 3) which showed isolated uptake in the stomach. PETCT scan though not a routine investigation for ovarian cancer is requested by several medical oncologists in our institute as part of a follow-up protocol after treatment completion. The Ca 125 was 14 IU/ml at a 3-month follow-up. In view of the fundic growth on the PETCT scan, an UGI endoscopy was advised which showed fundic growth (Fig. 4). The biopsy from the fundic mass showed a poorly differentiated adenocarcinoma with IHC positive for CK7, PAX8, and P53 and negative for CK20, CDX2, and WT1.

Fig. 3.

PET scan showing FDG avid focal thickening seen involving gastric fundus and cardia at 3-month follow-up post adjuvant chemotherapy

Fig. 4.

Upper GI endoscopy post adjuvant chemotherapy

In view of the isolated fundic metastasis, good performance status of the patient, she was planned for a surgical resection. She underwent a proximal gastrectomy for the same. The post-operative course was uneventful. The final histopathology (Fig. 5) of gastric growth showed a serous adenocarcinoma consistent with metastasis from ovarian cancer and confirmed on IHC. She received six additional cycles of second-line chemotherapy comprising cisplatin and gemcitabine. At 24 months post-treatment, she remains disease-free.

Fig. 5.

Histopathology: 3 × 2 × 2 cm tumor, in submucosal and muscle layer, focal ulceration of the mucosa, resection margin free, 2 cm away. No LVE/PNI

Discussion

Ovarian cancer has a proclivity to metastasize and disseminate within the peritoneal cavity in the majority of cases during the natural history of disease progression. The non-cohesive, exfoliated tumor cells implant throughout the peritoneal cavity with a predilection to the parietal peritoneum to develop metastasis as compared to the visceral peritoneum. This predilection is explained by Yonemura’s model describing the distribution of lymphatic stomata and milky spots, which seem to be heterogeneously distributed over the peritoneal surface, with greater concentration, not only in the structures like the omentum, or pelvic or subdiaphragmatic peritoneum, but also in the parietal peritoneum. Therefore the intraperitoneal route of dissemination is considered to be the commonest route of metastasis [9–11].

Gastrointestinal involvement in advanced ovarian cancer is usually superficial and is limited to the seromuscular layer, primarily of the small and large bowel and its mesentery. The mechanism of involvement has been attributed to lymphatic spread or direct tumor invasion [3, 4, 11]. The stomach, therefore, is an unusual site for metastasis from primary ovarian cancer. The mechanisms underlying gastric metastasis have not been clearly elucidated. But owing to the rich vascularity of the stomach, the most common pathway that may be involved in the metastatic spread to the stomach is the hematogenous route [12, 13]. A number of cases of metastatic ovarian cancer to the stomach have been reported in literature. Zhou and Miao reviewed all recorded cases of gastric metastasis from ovarian carcinoma and found that among 1010 patients with malignant tumors, 17 (1.7%) had metastases to the stomach. Another series of autopsies discovered 92 cases of gastric metastases among a total of 7165 cases, which is a rate of 1.28% [12, 14, 15].

Most patients either present with synchronous metastases with advanced peritoneal disease or other distant metastasis or as an isolated metachronous gastric mass (Table 1). In our study, the patient presented with a metachronous fundic mass, detected on a follow-up PETCT scan after treatment completion. Although the PETCT scan is not a common first-line imaging modality for ovarian cancer, it is not uncommon to consider follow-up imaging on treatment completion with a PET CT scan, as was done in our case. Other case series in literature have reported the use of PETCT scan in aiding diagnoses of metastatic disease [12]. Since in our case, this was a finding detected at follow-up in an otherwise asymptomatic patient with normal serum CA 125 levels, the fundic mass was further evaluated by an Upper Esophagogastroduodenoscopy (EGD) and biopsy.

Table 1.

Literature review of cases of ovarian cancer with metastases to stomach

Author (year)	Ovarian tumour pathology	Stage metastasis (synchronous/metachronous)	Treatment of primary	Treatment of secondary
Our study (2021)	High-grade Serous carcinoma	Stage IIIc, metachronous	Cytoreductive surgery + adjuvant chemotherapy	Proximal gastrectomy + maintenance chemotherapy
Yang (2018) [24]	Serous adenocarcinoma	Stage IIa, metachronous	Cytoreductive surgery + adjuvant chemotherapy	Laparoscopic resection of gastric metastasis + chemotherapy
Antonini et al. 2017 [26]	Serous adenocarcinoma	Stage IV, metachronous	Chemotherapy + cytoreductive surgery	Palliative chemotherapy
Kim et al. 2015 [20]	3 cases of adenocarcinoma	Resembled advanced gastric cancer III and IV, synchronicity not mentioned	Not mentioned	Palliative chemotherapy and supportive care
Kim et al. (2014) [13]	Serous adenocarcinoma	Stage IIIb, metachronous	TAH + BSO + PLND + para-aortic LND + total omentectomy + adjuvant chemotherapy	Curative subtotal gastrectomy + lymphadenectomy + chemotherapy
Namikawa et al. (2013) [22]	Serous adenocarcinoma	Stage not described, metachronous	TAH + BSO + PLND + adjuvant chemotherapy	Distal gastrectomy + chemotherapy
Obeidat et al. (2013) [25]	Poorly differentiated papillary serous cystadenocarcinoma	Stage IIIc, metachronous	TAH + BSO + Omentectomy	Subtotal gastrectomy + Adjuvant chemotherapy
Zhou et al. (2012) [12]	Serous adenocarcinoma	Stage not described, metachronous	Cytoreductive surgery + adjuvant chemotherapy	Local gastrectomy + chemotherapy
Akce et al. (2012) [3]	Papillary serous adenocarcinoma	Stage IIIc, metachronous	Abdominal hysterectomy + BSO + omentectomy + adjuvant chemotherapy	Chemotherapy
Carrara et al. (2011) [23]	Adenocarcinoma	Not described	Not described	Not described

^*TAH, total abdominal hysterectomy

^# BSO, bilateral salpingo-oophorectomy

^$ PLND, pelvic lymph node dissection

The clinical presentation of metastatic tumors in the stomach is often indistinguishable from that of primary gastric cancer. Endoscopic, radiological, and histological evaluations are essential to distinguish between primary gastric cancer and metastatic tumors to the stomach. Besides histological morphological features, immunohistochemistry (IHC) evaluation plays an important role in establishing diagnosis. For most gastric adenocarcinomas, the most commonly expressed IHC markers are CK7 and CK20 with a variable expression on CDX2 [16, 17]. In the case of ovarian adenocarcinomas, there is almost never an expression of CDX2 PAX8-positive; calretinin-negative staining appears to be highly specific and sensitive for detecting metastatic ovarian serous carcinoma in cytological preparations and may prove useful for distinguishing these cells from mesothelial cells in fluid cytology. Tong et al. [18] reported that PAX8 was detected in 70 and 68.8% of metastatic carcinomas of the ovary and endometrium in serous effusions, respectively.

In our case, the biopsy of gastric growth showed a high-grade serous adenocarcinoma with IHC positive for CK7, PAX8, and P53 and negative for CK20, CDX2, and WT1.

Because the presence of synchronous gastric metastasis is usually associated with advanced disease, the overall survival outcome is poor, and hence, treatment for such metastatic tumors in the stomach usually consists of systemic therapy rather than surgery [19, 20]. However, in patients with a solitary metachronous gastric metastasis, surgical resection or wherever possible endoscopic resection of metastatic gastric tumors may be recommended, either for symptomatic control such as bleeding or for disease control [20, 21]. In the present study, surgical resection, in the form of a partial (proximal) gastrectomy, was performed to achieve disease control (Table 1).

Conclusion

Gastric metastasis from ovarian cancer should be considered a differential diagnosis in any patient presenting with a gastric mass and a history of ovarian cancer.

Declarations

Conflict of interest

The authors declare no competing interests.