Saudi Journal of Gastroenterology
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CASE REPORT Table of Contents   
Year : 2003  |  Volume : 9  |  Issue : 1  |  Page : 23-25
Hepatoid gastric adenocarcinoma

Department of Medicine, Histopathology and Surgery, College of Medicine, King Faisal University, Dammam, Saudi Arabia

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Date of Submission04-Jan-2002
Date of Acceptance29-Oct-2002

How to cite this article:
Yasawy MI, Tamimi DM, Al-Quorain A, Wosornu L, Al-Mulhim A, Zakaria H. Hepatoid gastric adenocarcinoma. Saudi J Gastroenterol 2003;9:23-5

How to cite this URL:
Yasawy MI, Tamimi DM, Al-Quorain A, Wosornu L, Al-Mulhim A, Zakaria H. Hepatoid gastric adenocarcinoma. Saudi J Gastroenterol [serial online] 2003 [cited 2021 Sep 16];9:23-5. Available from:

In 1970, Bourreille et al reported the first case of stomach cancer producing Alpha fetoprotein (AFP) [1]. Later, Masuzawa and Okito demonstrated the presence of AFP in gastric cancer cells using immuno-flourescence. Ishikura proposed a new linicopathologic entity, "hepatoid adenocarcinorna of the stomach", which produces a large amount of AFP and shows morphologically and immunohisto chemically distinctive foci of hepatic differentiation [2] .

Until 1997, only 59 cases were reported, and to the present, less than 100 cases has been recorded in the world literature[3] . In this report, we present non­specific clinical presentation of AFP-producing gastric hepatoid adenocarcinoma, which was confirmed by immunohistochemical staining. The patient had normal liver in terms of enzymes, computerized tomography (CT) and histology. To our knowledge, we think this is the first case of hepatoid gastric adenocarcinoma reported from the gulf area.

   Case Report Top

A 47-year old Saudi male presented to the gastrointestinal (GI) clinic with dyspeptic symptoms of three months duration. There was no documented weight loss and the physical examination revealed no abnormality. The complete blood count, coagulation, liver function tests, urea and electrolytes were in the normal range. Hepatitis markers for both hepatitis BsAg and hepatitis C antibody were negative. CEA was 16.6ng/ml (normal below 3) AFP was significantly elevated (1961ng/ml.) Chest radiography was normal. Upper GI endoscopy showed 5cm antral ulcerative growth with central excavation. Biopsy was reported, as "poorly differentiated adenocarcinoma". Abdominal ultrasound and CT chest and abdomen were normal.

Partial gastrectomy was performed and the resected specimen was sent for histological examination. At surgery, the liver was grossly inspected and found to be free of metastasis. However, liver biopsy was obtained and was normal. The microscopic examination of gastric specimen showed focal replacement of the gastric mucosa by intestinal metaplasia of the incomplete type. The tumor invaded the submucosa and muscularis propria and consisted of two histological patterns. The first and the most predominant was an adenocarcinoma showing tubulopapillary pattern with prominent glandular differentiation [Figure - 1]. The second morphological pattern consisted of sheets and islands of carcinoma cells with hepatoid differentiation separated by thin fibrous stroma [Figure - 2].

The primary gastric tumor stained positive for keratin, EMA, CEA, alpha antitrypsin and AFP. The staining for AFP was diffuse and strongly positive in the cells showing hepatoid features and less intense but diffusely positive in the malignant tubules and glands [Figure - 3],[Figure - 4]. In contrast, the staining for CEA was strongly positive in the tubulo-gladular areas and weakly positive in the carcinoma cells with the hepatoid differentiation.

During the first post-operative week, the level of both CEA and AFP dropped markedly and were normalized within two months. Patients' recovery was uneventful and he was discharged and followed up for the last ten months. His tumor markers, abdominal ultrasonography and CT scan remained normal. The dramatic drop in AFP was pursued and the slides were reviewed. The samples were also examined immunohistochemically with antibodies against keratin, epithelial membrance-antigen (EMA), CEA, alpha-1 antitrypsin and AFP.

   Discussion Top

Gastric carcinomas secreting AFP are rare. Alpha­fetoprotein (AFP) is a mammalian embryonal serum protein first described in the human fetus in 1956 [4] . Synthesis of AFP by the developing liver begins in the second gestational month and stops either at or near birth.

The presence of elevated serum AFP in patients older than one year of age indicates cancerous or non-cancerous liver disease. AFP production has been reported in germ cell tumors, gastric, pancreatic, colorectal carcinomas, urogenital tumors and lung carcinoma [5],[6],[7],[8],[9] .

These tumors tend to be large, nodular and polypoid, the antrum and the pylorus of the stomach are the most common primary sites. Kodama et al described two histological types [10] . The first is the medullary type characterized by polygonal cells and the second is well-differentiated papillary or tubular type. This differentiation is based on the immunohistochemical staining. Tumors that stained positive for AFP were of the medullary type and others, of the well-differentiated adenocarcinoma.

Ishikura et al proposed a new entity; 'hepatoid adenocarcinoma of the stomach' and suggested that the medullary type is associated with hepatocellular carcinoma morphology and produces high levels of AFP, while the well-differentiated adenocarcinomatous type revealed intestinal morphology and is associated with low AFP levels [11] . Later, the term 'hepatoid carcinoma' was defined on the basis of the characteristic histologic features resembling hepatocellular carcinoma, irrespective of AFP production [12] . Some authors also reported AFP-producing gastric carcinoma that consisted of well-differentiated adenocarcinoma and lacked the hepatoid features [12],[13] . Our case had well-differentiated adenocarcinomatous pattern with areas of undifferentiated carcinomatous cells showing hepatoid features.

The cells of the hepatoid differentiation are generally strongly positive for AFP. But sometimes the cells of glandular differentiation are also positive [11] . In our case, the AFP staining was diffusely positive in the solid carcinomatous cells with hepatoid features, and in the well-differentiated tubulopapillary and glandular areas, although it was stronger in the former. CEA staining was diffusely and strongly positive in the differentiated adenocarcinomatous areas but focal and less intense in the hepatoid cells.

Why some gastric carcinomas show hepatoid differentiation and secrete AFP, has been the subject of debate? Two main theories have been considered regarding the morphogenesis of AFP-producing gastric cancer. These theories are based on the morphological similarity between AFP-producing gastric carcinoma and other tumors that produce AFP [2],[14] . Ishikura et al has suggested that AFP­producing gastric cancers are differentiated morphologically and functionally along hepatocyte, which may be due to the fact that the stomach and liver are both derived from primitive foregut.

AFP-producing gastric carcinomas are reported to have aggressive behavior. Deep invasion of the gastric wall, frequent metastasis to regional lymph nodes, and high incidence of liver metastasis have been observed [2],[10],[15] . Negai et al found that five-year survival rate in 24 patients with hepatoid adenocarcinoma was 11.9%. While in 19 patients with AFP-producing adenocarcinoma without hepatoid features, the figure was 38.2% [12]. Koide et al histochemically investigated cell proliferation, apoptosis and angiogenesis in APP-producing gastric cancers to evaluate its malignant potential [16] . They concluded that these tumors have high proliferative activity, weak apoptosis and rich neovascularization indicating that they behave biologically as a high-grade malignancy. The rarity and poor prognosis of this clinicopathological entity requires greater awareness for diagnosis and management. Immunohistochemical studies and serum AFP pattern remain the sole diagnostic tool.

   References Top

1.Bourreile J, Metayer P, Sauger F, Matray F, Fondimare A: Existence d'a-foeto protein au cours Tun cancer secondaire du foie d'origin gastrique. Presse Med 1970; 78: 1277-8.  Back to cited text no. 1    
2.Ishikura H, Fukusawa Y, Ogasawara K, Natori T, Tsukada Y. Aizawa N: An AFP- producing gastric carcinoma with features of hepatic differentiation: A case report. Cancer 1985; 56: 840-8.  Back to cited text no. 2    
3.Roberts, Catherine C, Colby, Thomas V, Batts, Kenneth P: Carcinoma of the stomach with hepatocyte differentiation (Hepatoid adenocarcinoma) subject review. Mayo Clinic Proc 1997; 72: 1154-60.  Back to cited text no. 3    
4.Bergstrand CG, Czar D. Demonstration of a new protein fraction in the serum from the human fetus. Scand J Clin Lab Invest 1956; 8:174  Back to cited text no. 4    
5.Okamoto T, Hirabayashi K, Ishiguro T. Immunohistochemical type distinction of alpha­fetoprotein in various alpha-fetoprotein secreting tumors. Jpn J Cancer Res 1993; 84:360-3  Back to cited text no. 5  [PUBMED]  
6.Kato K. Matsuda M, Ingu A, et al. Colon cancer with a high serum alpha-fetoprotein level. Am J Gastroenterol 1996; 91: 1045.  Back to cited text no. 6    
7.Tokoro K, Chiba Y. Ohtani T, Abe H, Yogishita S. Pineal ganglioglioma in a patient with familial basal ganglia calcification and elevated serum alpha­fetoprotein: Case report, Neurosurgery 1993; 33: 506­-11.  Back to cited text no. 7    
8.Hammad A, Jasnosz KM, Olson PR. Expression of alpha protein by ovarian sertoli - leydig cell tumors: Case report and review of the literature. Arch Pathol Lab Med 1995; 119: 1075-9.  Back to cited text no. 8  [PUBMED]  
9.Okunaka T, Kato H, Konaka C, Yamamoto H, Furukawa K. Primary lung cancer producing alpha­fetoprotein. Ann Thorac Surg 1992; 53: 152.  Back to cited text no. 9    
10.Kodama T, Kameya T, Hirota T, et al: Production of fetoprotein, normal serum proteins, and human chorionic gonadotropin in stomach cancer: Histologic and immunohistochemical analysis of 35 cases. Cancer 1981; 4:1647-55.  Back to cited text no. 10    
11.Ishikura H, Kirimoto K, Shamoto M, et al. Hepatoid adenocarcinoma of the stomach: An analysis of seven cases. Cancer 1986; 58: 119-26.  Back to cited text no. 11  [PUBMED]  
12.Nagai E, Ueyama T, Yao T, Tsuneyoshi M. Hepatoid adenocarcinoma of the stomach : A clinico­pathological and immunohistochernical analysis cancer 1993; 72: 1827-35.  Back to cited text no. 12    
13.Matsunou H, Konishi F. Jalal R, Yamamichi N, Mukawa A: AFP producing gastric carcinoma with enteroblastic differentiation. Cancer 1994; 73: 534-40.  Back to cited text no. 13    
14.Motoyama T, Saito K, Jwafuchi M, Watanabe H: Endodermal sinus tumor of the stomach. Acta pathol Jpn 1985; 35: 497-505.  Back to cited text no. 14    
15.Chang YC, Nagasue N, Kohno H, et al. Clinico­pathologic features and long term results of­fetoprotein producing gastric cancer. Am J Gastroenterol 1990: 85: 1480-5.  Back to cited text no. 15    
16.Koide N, Nishio A, Igarashi J. Kajikawa S, Adachi W, Amano J. Protein producing gastric cancer: Histochemical analysis of cell proliferation, apoptosis and angiogenesis. Am J Gastrocnterol 1999; 94: 1658-63.  Back to cited text no. 16    

Correspondence Address:
Mohamed Ismail Yasawy
Department of Medicine, King Fahad Hospital of the University, P. O. Box 40143, Al Khobar 31952
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 19861807

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]


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