|Ahead of print publication
Gastric fundic gland metastasis of renal cell carcinoma 14 years after the primary diagnosis
Mahmut S Degerli1, Abdulhak H Karayagiz2
1 Department of General Surgery, Istanbul Esenler Gynecology and Pediatrics State Hospital, Istanbul, Turkey
2 Department of General Surgery, Istanbul Esenyurt Necmi Kadioglu State Hospital, Istanbul, Turkey
|Date of Submission||07-Dec-2021|
|Date of Decision||02-Apr-2022|
|Date of Acceptance||12-Apr-2022|
|Date of Web Publication||04-Oct-2022|
Mahmut S Degerli,
Department of General Surgery, Istanbul Esenler Gynecology and Pediatrics State Hospital, Istanbul
Source of Support: None, Conflict of Interest: None
Gastric metastasis from renal cell carcinoma (RCC) is rare and associated with poor outcomes. In this case, we report gastric fundic gland metastasis presenting with upper gastrointestinal bleeding in a patient who had a history of nephrectomy due to RCC 14 years ago. Metastasis of any cancer to the stomach is relatively uncommon. Gastric metastasis from RCC, especially isolated fundic gland metastasis, is extremely rare. However, although rare, metastatic RCC to the stomach should be suspected in any patient with a history of RCC who presents with gastrointestinal symptoms.
Keywords: Gastrointestinal Bleeding, gastric metastasis, renal cell carcinomas
| > Introduction|| |
Renal cell carcinoma (RCC) represents 3% of all malignant tumors. The management of metastatic RCC has evolved rapidly with several immunotherapy-based combinations of strategies. With new treatment options for metastatic RCC, life expectancy has been approximately 32 months in recent years. While the metastatic disease is detected in 15%–17% of patients with newly diagnosed kidney tumors, RCC metastasis is expected to be detected in 30% of patients who underwent radical nephrectomy due to localized disease in their 5-year follow-up. The common sites of RCC metastasis are bone, lung, liver, adrenal glands, and lymph nodes. Gastric metastasis has rarely been reported in RCC (only 0.2% of the literature). Metastatic tumors in the stomach often appear as submucosal tumors or deep ulcers. There are a few reported cases with metastatic RCC presenting gastric fundic gland polyp.
In this study, we report the case of a 73-year-old man who has advanced RCC with gastric fundic gland metastasis and presented with gastrointestinal bleeding.
| > Case Report|| |
The patient, a 73-year-old man, had a history of tobacco smoking and hypertension. Fourteen years ago, a right radical nephrectomy was performed due to a large solid hypervascular mass identified in his right kidney by ultrasound. Histological examination demonstrated a clear cell RCC, Fuhrman nuclear grade 3. The tumor was 13 cm in size and limited to the kidney, and the renal capsule was intact. There were no metastatic lymph nodes. The pathologic stage was pT2bN0. In the follow-up, bilateral lung metastatic nodules were detected 7 years later. Mediastinal lymph nodes biopsy by endobronchial ultrasound (EBUS) showed that it was RCC metastasis, and interferon therapy was started. Because the patient did not tolerate interferon therapy. So, sunitinib 50 mg/day (4 weeks use, 2 weeks break) was started. Under sunitinib treatment, complete response was achieved for 5 years. After that, sunitinib was stopped, and the patient followed up without any drugs.
Two years later, the patient was admitted to the emergency with upper gastrointestinal bleeding. Gastric fundic gland polyp was detected in gastroscopy, and polypectomy was performed. In histological examination, RCC metastasis was detected. The tumor consisted of large, clear cytoplasm cells with a round nucleus, which infiltrated the lamina propria and showed acinar (tubular) and alveolar growth patterns on the gastric fundus mucosa [Figure 1]. The lumens of the tubular structures had varying diameters, some of which had extra erythrocytes. Around the tubular and alveolar structures, there were numerous thin-walled veins and ulcers on the surface of some tissue pieces. Tumor cells were immunohistochemically Pax-8 positive and cytokeratin 7 and CD68 negative [Figure 2]. The pathology was found to have the same morphology as the initial nephrectomy specimens. The patient was scanned with positron emission tomography/computed tomography (PET/CT). While there was no pathological recurrence in the right nephrectomy location, new increased FDG (18-F Fluorodeoxyglucose) involvement was detected in the left adrenal gland. In addition, there was a metastatic mass at the ninth right rib. Minimal progression was detected in stabilized metastatic lesions previously present in the lung. Furthermore, the patient was asymptomatic. Therefore, it was decided to start sunitinib treatment again.
|Figure 1: Clear cell renal cell carcinoma infiltration in gastric fundus mucosa (H&E, ×100). H&E = hematoxylin and eosin|
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| > Discussion|| |
RCC accounts for approximately 90% of all kidney cancers. There are many histopathologic subtypes. Clear cell RCC is the most common histopathologic subtype of RCC and has a worse prognosis than other histopathologic subtypes. Clear cell renal carcinoma can metastasize by hematogenous, lymphomatous, and direct invasion. Aggressive and typical metastasis is characteristic of clear cell renal carcinoma. Metastatic tumors to the stomach are infrequent (0.2%–0.7%). Metastasis of primary lung, breast, and malignant melanoma to the stomach is a known condition, whereas gastric metastasis of clear cell RCC is rare. There are approximately 50 cases reported in the literature.
There is a long interval between primary RCC diagnosis and gastric metastasis. The mean interval between the diagnoses of the primary tumor and gastric metastasis is 1.3 years at the other cancers (e.g., breast, lung). However, gastric metastasis can be seen after many years at RCCs. The mean interval is 6.7 years at the RCC. The presenting symptoms in patients with gastric metastasis from RCC are upper gastrointestinal bleeding, gastroesophageal reflux, anemia, melena, and epigastric pain or it may be asympt omatic. Gastric metastases often occur as solitary, single, large ulcerated lesions. There are rare case reports of metastatic RCC presenting as a solitary subcentimeter gastric lesion., The present patient had a small (0.4 cm) gastric polyp. He presented with gastrointestinal bleeding. The histology of the polyp was a clear cell type. In the literature, histologically, metastatic RCC is predominantly of clear cell type. Vimentin and PAX-3 are useful ımmunohistochemistry tools. Vimentin is a filament protein expressed in normal renal tissues and 87% of clear cell RCC. PAX-2 or PAX-8 is a transcription factor protein expressed in 85% of metastatic clear cell RCC.
Molecularly targeted therapies, including sunitinib, effectively manage advanced or metastatic RCC. RCC treatment for gastric metastasis includes gastrectomy (total or subtotal), endoscopic resection, embolization, targeted therapy, or immunotherapy. Optimal treatment is controversial. We recommend surgical procedures such as polypectomy and resection for solitary gastric metastasis in symptomatic RCC patients.
It should be kept in mind that although many years have passed since the primary diagnosis, gastric metastases, albeit rare, can be seen in patients diagnosed with RCC. Especially in a patient presenting with upper gastrointestinal bleeding, as in our case, the treatment should not be terminated with only bleeding control. Biopsy should be performed for histological examination, and, if necessary, metastatic focus scanning should be performed with advanced imaging methods.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Cairns P. Renal cell carcinoma. Cancer Biomark 2010;9:461-73.
Powles T; ESMO Guidelines Committee. Electronic address: [email protected]
Recent eUpdate to the ESMO Clinical Practice Guidelines on renal cell carcinoma on cabozantinib and nivolumab for first-line clear cell renal cancer: Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2021;32:422-3.
Eggener SE, Yossepowitch O, Pettus JA, Snyder ME, Motzer RJ, Russo P. Renal cell carcinoma recurrence after nephrectomy for localized disease: Predicting survival from time of recurrence. J Clin Oncol 2006;24:3101-6.
Sakurai K, Muguruma K, Yamazoe S, Kimura K, Toyokawa T, Amano R. et al.
Gastric metastasis from renal cell carcinoma with gastrointestinal bleeding: A case report and review of the literature. Int Surg 2014;99:86-90.
Namikawa T, Hanazaki K. Clinicopathological features and treatment outcomes of metastatic tumors in the stomach. Surg Today 2014;44:1392-9.
Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al
. Renal cell carcinoma. Nat Rev Dis Primers 2017;3:17009. doi: 10.1038/nrdp. 2017.9.
Muglia VF, Prando A. Renal cell carcinoma: Histological classification and correlation with imaging findings. Radiol Bras 2015;48:166-74.
Green LK. Hematogenous metastases to the stomach. A review of 67 cases. Cancer 1990;65:1596-600.
Namikawa T, Munekage M, Kitagawa H, Okabayashi T, Kobayashi M, Hanazaki K. Metastatic gastric tumors arising from renal cell carcinoma: Clinical characteristics and outcomes of this uncommon disease. Oncol Lett 2012;4:631-6.
Martín-Pérez JA, Torres-Silva C, Tenorio-Arguelles R, García-Corona DA, Silva-González S, Dominguez-Rodriguez JA, et al.
Gastric carcinoma and renal cell carcinoma as an atypical presentation of multiple primary malignancies: A case report and review of the literature. J Med Case Rep 2020;14:234.
Pollheimer MJ, Hinterleitner TA, Pollheimer VS, Schlemmer A, Langner C. Renal cell carcinoma metastatic to the stomach: Single-centre experience and literature review. BJU Int 2008;102:315-9.
Kim MY, Jung HY, Choi KD, Song HJ, Lee JH, Kim DH, et al.
Solitary synchronous metastatic gastric cancer arising from t1b renal cell carcinoma: A case report and systematic review. Gut Liver 2012;6:388-94.
Saidi RF, Remine SG. Isolated gastric metastasis from renal cell carcinoma 10 years after radical nephrectomy. J Gastroenterol Hepatol 2007;22:143-4.
Yamamoto D, Hamada Y, Okazaki S, Kawakami K, Kanzaki S, Yamamoto C, et al.
Metastatic gastric tumor from renal cell carcinoma. Gastric Cancer 2009;12:170-3.
Gokden N, Gokden M, Phan DC, McKenney JK. The utility of PAX-2 in distinguishing metastatic clear cell renal cell carcinoma from its morphologic mimics: An immunohistochemical study with comparison to renal cell carcinoma marker. Am J Surg Pathol 2008;32:1462-7.
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