Are gastric metastases of renal cell carcinoma really rare? A case report and systematic review of the literature

Highlights • Solitary gastric metastasis of RCC are scarce.• When feasible, surgical or endoscopic treatment of gastric metastasis should be performed.• Risk of metastatic recurrence is significant and must be taken into consideration in the therapeutic strategy.


Introduction
Renal cell carcinoma (RCC) represents above 3 % of all cancers, with the highest incidence occurring in Western countries [1]. At diagnosis, above 25 % of patients with RCC present an advanced disease, including locally invasive or metastatic cancer [2,3]. The mean survival time of patient with metastatic RCC is approximately 13 months [1].
The most common metastatic RCC sites are the lung and bone (up to 60 % and 40 % of patients with metastases) [4]. However, unusual sites of metastasis are characteristics of RCC and any organ site can be involved, including the thyroid, pancreas, skeletal muscle and skin.
Gastric metastasis of RCC has been described  and it is associated with poor outcome, with only a third of patients being alive after one year [23]. Usually, gastric metastases are asymptomatic, single and located in the gastric body or fundus [23,33].
Thus, these metastases are diagnosed on routine CT scans as part of the monitoring of RCC after local treatment. Gastrointestinal bleeding and anemia are the most common presentations of symptomatic gastric metastasis [23,33].
We herein report the case of a patient, who underwent a wedge resection for a gastric metastasis of RCC, which is healthy at 2-years of follow-up. Furthermore, we conducted a systematic review of the literature to report all published cases of RCC patients with gastric metastasis.

Case report
In December 2010, a 61-year-old man was referred to our academic center for the management of a localized right clear cell RCC, without synchronous metastases. It was an upper polar lesion, measuring 2.5 cm long axis, essentially exophytic, posterior, entirely above the polar lines, without vascular contact, classified 5p RENAL score.
An open right partial nephrectomy was performed by an experienced surgeon and histological results highlighted a 2.5 cm clear cell RCC, Furhman grade III, classified pT3aN0R0 due to the extension to perinephric tissues, but not beyond Gerota Fascia. According to EAU (European Association of Urology) guidelines [40], a surveillance has been validated including semi-annual monitoring by CT scan in the 1 st year, then annual monitoring by CT scan in the following 2 years and every 2 years thereafter.
In Mars 2012, a localized homolateral recurrence has been highlighted at CT scan. It was a lower polar lesion, measuring 4.3 cm long axis, essentially endophytic, anterior, close to the collecting system, with polar line crosses and venous contact, classified 9 ah RENAL score, Supplemental Fig. 1. There was no evidence of metastasis on this CT scan.
An open right radical nephrectomy was performed and histological examination reported a 3.5 cm clear cell RCC, Furhman grade III, classified pT3aN0R0 due to the extension to the renal sinus fat. According to EAU guidelines [40], a surveillance has been validated.
In September 2018, a metachronous gastric metastasis was found on CT scan. The lesion was located on the lesser curvature of the stomach, measuring 4.5 cm long axis. No other secondary lesions were identified, Supplemental Fig. 2. The patient had no digestive symptoms, no hematemesis, no melena.
A surgical procedure has been validated: a laparoscopic wedge resection, converted to laparotomy has been performed.
Histological examination reported a proliferation of atypical cells containing round clear nuclei and irregularly shaped nuclei with prominent nucleoli using hematoxylin-eosin staining. Immunostaining revealed negativity for all epithelial markers (CK7, CK20) and positivity for proximal tubular epithelial markers (CD10, Vimentine). These characteristics led to the conclusion of gastric metastasis of a clear cell RCC with 30 % sarcomatoid contingent, with negative resection margins.
The patient had an uneventful postoperative course and was discharged on the 8th day.
Two years later, in September 2020, a CT scan was performed, revealing a 17 mm adenopathy behind the hepatic hilum and a surgical management was performed, by an experienced surgeon, including a lymph node dissection of the hepatic hilum and the hepatic artery. Histological examination reported a node metastasis of the clear cell RCC, in hepatic artery lymph node dissection. Actually, he remains healthy.
This case has been reported in line with the SCARE 2020 criteria [41].

Systematic review
Literature about gastric metastasis of RCC was realized using electronic database Medline via PubMed .
Key terms used included "renal cell carcinoma," "stomach metastasis," and "gastric metastasis" (Fig. 1). References in the identified articles were used to identify more relevant studies.
RCC with solitary gastric metastasis cases (n = 11) are summarized in Table 1. RCC with multiple or unspecified metastatic sites (including stomach) cases (n = 31) are summarized in Table 2.
At RCC gastric metastasis diagnosis, 73 % of the patients presented multiple metastatic sites, mainly lungs and bones.

Discussion
Renal cell carcinoma is the most common solid lesion within the kidney and accounts approximately 90 % of all kidney malignancies [1]. It comprises different RCC subtypes with specific histopathological characteristics [42]. Clear cell RCC is the most common histopathological entities of RCC [40] and clear cell RCC has worse prognosis compared to other histopathological entities [43,44], even after stratification for stage and grade [45].
Indeed, clear cell RCC has an abundant blood supply and can metastasize to several organs [46]. Metastasis routes include hematogenous, lymphogenous, renal capsule, renal pelvis and ureteric routes [37], which explains the wide variety of organs that can be RCC metastatic sites.
Currently, EAU guidelines [40] and French ccAFU (comité de cancérologie de l'Association Franç aise d'Urologie) guidelines [47] on management of kidney cancer recommends using MSKCC and IMDB prognostic models to establish the prognosis of patients with metastatic RCC, in order to select the appropriate therapy. Thus, EAU [40] and French ccAFU guidelines [47] recommend offering surgical treatment, when technically feasible, of metastases in patients with oligo-metastatic RCC, in order to defer the initiation of systemic treatment.
Our systematic review suggests that solitary gastric metastasis of RCC are scarce. Herein, we report the 12th case of solitary gastric metastasis, discovered 6 years after local treatment of RCC. For the  Our case has a similar age. The location of the metastasis was the middle body of the stomach. The median time between diagnosis of RCC and metachronous gastric metastasis was 6 years, lower than median time reported by the 11th cases. Two years after gastric metastasis surgical treatment, a hepatic hilum adenopathy recurrence occurred, treated by surgery and our median patient survival was higher (26 months versus 9 months). However, in case of multiple metastatic sites, the stomach is a frequent localization of metastases. Thus, at gastric metastases diagnosis, 80 % of patients presented multiple metastatic sites, mainly lungs and bones. The median time between RCC diagnosis and metachronous gastric metastasis diagnosis was shorter in case of multiple metastatic sites (5.0 years versus 8.5 years in case of solitary gastric metastasis).
Surgical treatment, when it is feasible remains the best therapeutic option for a solitary gastric metastasis, resulting in significant survival prolongation in eligible patients. Indeed, median patient survival was higher after surgical treatment of gastric metastasis (9 months (3.4-15.8) versus 6 months (2.5-24.0) in case of solitary and multiple metastatic sites).
However, after surgical treatment of solitary gastric metastases, the risk of metastatic recurrence is significant. Among the 11 cases of solitary gastric metastasis reported in the literature, 3 patients presented a metastasis recurrence. Our case presented a hepatic hilum adenopathy recurrence, treated by surgery, two years after gastric metastasis surgical treatment.

Conclusion
Our systematic review suggests that solitary gastric metastasis of RCC are scarce. In comparison of patients with multiple metastatic sites, the median survival of patients with solitary gastric metastasis is longer. When it is feasible, surgical or endoscopic treatment of the solitary gastric metastasis should be performed, whenever the patient is fit for surgery, in order to delay the initiation of systemic treatment. Nevertheless, the risk of metastatic recurrence is significant and must be taken into consideration in the therapeutic strategy.

Declaration of Competing Interest
None.

Funding
None.

Ethical approval
According to French legislation, retrospective studies are not subject to an ethics committee.

Consent
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 Editor-in-Chief of this journal on request.

Registration of research studies
Not applicable.

Provenance and peer review
Not commissioned, externally peer-reviewed.

Appendix A. Supplementary data
Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.ijscr.2021. 105867.