28 September 2005 Case of the Week #22


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We thank Drs. Elizabeth I. Johnston and Sanjay Logani, Emory University Department of Pathology, Atlanta, Georgia (USA) for contributing this case and the discussion. We invite you to contribute a Case of the Week by emailing NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case. Please only send cases with a definitive diagnosis.


Case of the Week #22


A 51 year old man presented to the Emergency Room with fatigue, shortness of breath and dizziness. A complete blood count demonstrated mild anemia and a stool guaiac test was positive for occult blood. Upper and lower gastrointestinal endoscopy showed polypoid gastric masses in the cardia, fundus, and antrum. Biopsies revealed the pathology described below. CT scan additionally demonstrated an enlarged lymph node in the gastrohepatic ligament, a 2.5 cm right adrenal mass, and an intramucosal lipoma in the jejunum. The patient had a subsequent gastrectomy, esophagojejunostomy, and proximal jejunum segmental resection.


Gross description:


The gastrectomy specimen revealed three soft, hemorrhagic, polypoid submucosal masses in the cardia, fundus, and antrum (figure 1). The masses ranged from 2.3 cm to 9.5 cm in greatest dimension.


Microscopic description:


On histopathologic examination, the masses were confined to the mucosa and submucosa (figure 2) and consisted of sheets and nests of large, polygonal, clear cells, with distinct cell borders, medium-sized round-to-irregular nuclei with moderate pleomorphism and prominent nucleoli (figure 3). Vascular invasion was present (figure 4). The surrounding gastric mucosa showed ulceration, reactive changes and chronic gastritis.


What is your diagnosis?


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Diagnosis: Metastatic Renal Cell Carcinoma, clear cell type




Metastatic tumors to the stomach are rare. The most common primary tumors are melanoma, carcinoma of the lung, breast, and esophagus1,2. The tumors generally spread by hematogenous route and result in submucosal masses, as in this case1. Metastatic tumors from breast or uterine primaries classically mimic linitis plastica; however, polypoid and ulcerated tumor masses may also be seen1,3. Patients with metastatic tumors to the stomach are often asymptomatic, and the lesions may be found on surveillance imaging. Symptomatic patients most frequently present with gastrointestinal bleeding and anemia.1


The most frequent sites of metastasis of renal cell carcinoma (RCC) include the lungs, bones, brain, and liver2,4. RCC has also been reported to metastasize to the small intestine, pancreas, and thyroid5,2,6. Although RCC has a propensity to metastasize to unusual sites, cases of metastatic RCC to the stomach are very rare. Previous cases of metastatic renal cell carcinoma to the stomach have been reported, and have presented as discrete and ulcerated gastric masses4, 7, 8.


The differential diagnosis of clear cell tumors in the stomach, especially in small endoscopic biopsies, can be challenging. Diagnoses to consider include paraganglioma, melanoma, clear cell carcinoid, clear cell carcinoma (metastatic or primary gastric adenocarcinoma with clear cell differentiation) and, rarely alveolar soft part sarcoma. A panel of immunohistochemical stains may differentiate between the various entities in small biopsy specimens. Paraganglioma is almost always positive for neuroendocrine markers such as neuron specific enolase, synaptophysin, and chromogranin, and S-100 protein highlights the sustentacular cells. Cytokeratins are generally negative, in contrast to clear cell carcinoid tumors, which express neuroendocrine markers9. Melanoma is one of the most common metastatic tumors to the stomach, and this diagnosis can be easily confirmed by positive expression for S-100, as well as the more specific markers such as HMB-45 and Melan-A. The rare alveolar soft part sarcoma may be S-100 positive; a more specific marker is the nuclear expression of TFE39,10. Finally, metastatic clear cell renal cell carcinoma is usually positive for epithelial membrane antigen (EMA), RCC antigen, and CD10.9,10




1. Kobayashi O, Murakami H, Yoshida T, et al. Clinical diagnosis of metastatic gastric tumors: clinicopathologic findings and prognosis of nine patients in a single cancer center. World Journal of Surgery 2004; 28:548-51.


2. Haberal I, Su S, Recant W, Michael E. Radiology quiz case 1. Metastatic renal cell carcinoma, clear cell type. Archives of Otolaryngology Head & Neck Surgery 2004; 130:892


3. Green LK. Hematogenous metastases to the stomach. A review of 67 cases. Cancer 1990; 65:1596-1600.


4. Odori T, Tsuboi Y, Katoh K, et al. A solitary hematogenous metastasis to the gastric wall from renal cell carcinoma four years after radical nephrectomy. Journal of Clinical Gastroenterology 1998; 26:153-4.


5. Chang WT, Chai CY, Lee KT. Unusual upper gastrointestinal bleeding due to late metastasis from renal cell carcinoma: a case report. Kaohsiung Journal of Medical Sciences 2004; 20:137-41.


6. Norton KS, Zibari GB. Body and distal pancreatectomy for metastatic renal cell carcinoma: case report and review of the literature. Journal of the Louisiana State Medical Society 2004; 156:40-1.


7. Mascarenhas B, Konety B, Rubin JT. Recurrent metastatic renal cell carcinoma presenting as a bleeding gastric ulcer after a complete response to high-dose interleukin-2 treatment. Urology 2001; 57:168


8. Blake MA, Owens A, O'Donoghue DP. Embolotherapy for massive upper gastrointestinal haemorrhage secondary to metastatic renal cell carcinoma: Report of three cases. Gut 1995; 37:835-837.


9. Weiss SW, Goldblum JR, eds. Enzinger and Weiss's Soft Tissue Tumors, 4th ed. St. Louis, MO: Mosby, Inc; 2001:1323-1355.


10. Bishop PW. An Immunohistochemical Vade Mecum. 2005 July 9. Website http://www.e-immunohistochemistry.info/



Nat Pernick, M.D.
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