Table of Contents  
Year : 2013  |  Volume : 23  |  Issue : 1  |  Page : 18-20

Alpha fetoprotein producing adenocarcinoma, a rare but unique subtype of gastric epithelial malignancy

Department of Pathology and Surgery, Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India

Date of Acceptance05-Aug-2013
Date of Web Publication14-Feb-2014

Correspondence Address:
Arijit Majumdar
Department of Pathology and Surgery, Institute of Post-Graduate Medical Education and Research, Vill-Duilya, Charaktala Andul District, Howrah - 711 302 West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1116-5898.127106

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Hepatoid adenocarcinoma is one of the rarest tumors of the stomach. These tumors produce alpha-fetoprotein (AFP), which can be used as a diagnostic marker. The prognosis is poor compared to conventional adenocarcinoma of the stomach. A case of AFP-producing hepatoid adenocarcinoma stomach in a 55-year-old woman is presented. The patient underwent partial gastrectomy. We focus on the clinical features, imaging, histopathological and biochemical characteristics of the hepatoid variety of adenocarcinoma stomach.

Keywords: Alpha fetoprotein, hepatoid adenocarcinoma, stomach

How to cite this article:
Majumdar A, Sarkar DK, Jana A, Jana A, Biswas S. Alpha fetoprotein producing adenocarcinoma, a rare but unique subtype of gastric epithelial malignancy. Niger J Surg Sci 2013;23:18-20

How to cite this URL:
Majumdar A, Sarkar DK, Jana A, Jana A, Biswas S. Alpha fetoprotein producing adenocarcinoma, a rare but unique subtype of gastric epithelial malignancy. Niger J Surg Sci [serial online] 2013 [cited 2023 Apr 1];23:18-20. Available from:

  Introduction Top

Hepatoid gastric adenocarcinoma is a distinct variant of gastric carcinoma, which represents a small percentage of gastric cancers. Compared to the reports obtained from the Far East the reports from Europe and North America are fewer. [1] Although some authors estimate hepatoid type adenocarcinomas of the stomach to represent 1.3 to 15% of gastric carcinomas, these percentages are, at least for Western countries an overestimation, and only a few hepatoid gastric adenocarcinomas have been reported in the recent literature. A minority of primary gastric carcinomas contain immunoreactive alpha fetoprotein (AFP), often accompanied by carcinoembryonic antigen. [2] Some of these have a morphology resembling hepatocellular carcinoma, some have a clear cell tubulopapillary variety of adenocarcinomatous pattern and others show combinations of the two. So, neither every AFP-producing gastric adenocarcinoma has hepatoid morphology nor all the hepatoid adenocarcinoma stomach produce AFP. There are very a few reported cases of AFP-producing hepatoid adenocarcinoma of stomach from South-East Asia including the country like India. In this report, we present non-specific clinical presentation of AFP-producing gastric hepatoid adenocarcinoma, which was confirmed by immunohistochemical staining.

  Case Report Top

A 55-year-old woman (origin Bangladesh) came to the hospital with complaints of fatigue, generalized weakness, dyspeptic symptoms for the last two months and one episode of hematemesis the previous night. There was a 2 kg weight loss over the last month but physical examination revealed no abnormality. The complete hemogram showed a hemoglobin 7 g/dl, biochemical parameters were within normal limits except AFP, which was elevated (10000 IU/mL). Upper GI endoscopy revealed an ulcerated mass in the gastric antrum. CT of the abdomen showed a 7 cm mass in the stomach. A partial gastrectomy specimen was sent for histopathological examination.

Sections showed sheets of polygonal tumor cells having abundant eosinophilic cytoplasm, some containing bile pigment, central nucleus with prominent nucleoli and increased mitotic activity. The majority of the cells were arranged in trabeculae but focal areas of glandular arrangement were also evident [Figure 1]. Immunohistochemically, the tumor cells showed diffused cytoplasmic AFP positivity [Figure 2].
Figure 1: Poorly differentiated gastric adenocarcinoma with hepatoid features, composed mainly of trabecular and focal glandular formations. (H and E stain ×400)

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Figure2: Immunohistochemical cytoplasmic positivity for a1-fetoprotein, ×100

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  Discussion Top

Alpha fetoprotein (AFP) levels in serum, initially elevated due to fetal liver, yolk sac and some fetal gastrointestinal cells production rapidly decrease after birth. [3] AFP level is, however, elevated in patients with hepatocellular carcinoma and in those with other liver diseases associated with liver regeneration. [4] AFP-producing tumors, other than hepatocellular carcinoma, have also been described. [5]

First reported in 1970 by Bourreille et al. [6] AFP-producing gastric adenocarcinoma has an incidence reported to be 1.3-15% of all gastric carcinomas. [7] Later Ishikura et al. proposed the term "hepatoid adenocarcinoma of the stomach" for primary gastric carcinomas that are characterized by both hepatoid differentiation and the production of large amounts of AFP. [8]

Depending on the immunohistochemical staining, Kodoma et al. described two histologic types of AFP-producing gastric carcinoma: a medullary type, characterized by polygonal cells arranged in solid nest or sheets, with scattered large pleomorphic or multinucleated giant cells, and well differentiated papillary or tubular type with clear cytoplasm. [9] The two types sometimes coexisted in a single tumor.

Ishikura et al. suggested that as the stomach and liver are both derived from primitive foregut of the embryo, some gastric carcinomas show hepatoid differentiation and produce AFP because of disturbances of differentiation. [10] Furthermore, there is sometimes confusion about whether hepatoid carcinoma originates from the stomach or the liver, because most patients show multiple liver metastasis preoperatively. [11]

Gastric hepatoid adenocarcinoma (GHAC) with elevated serum AFP, first described by Ishikura et al. 1985, [10] is a rare gastric cancer subtype seen more frequently in older patients, aged 60-70 years. The antrum is the most common site. There are no specific symptoms and signs, but generally, epigastric pain and fatigue are observed most frequently. [11]

Tumor cells in hepatoid foci histologically resemble the morphology of hepatocellular carcinoma (HCC), and immunohistochemically can be positive for AFP, alpha-1 antitrypsin, alpha-1 antichymotrypsin and albumin. The adenocarcinomatous component may be well or poorly differentiated, often with clear cells and a papillary pattern. [12]

GHAC, when present, need to be differentiated from HCC. Generally, in HCC, neighboring cirrhotic lesions can be seen and tumor cells are positive for Hep Par-1, a sensitive and specific immunohistochemical marker for hepatocyte differentiation, whereas in GHAC Hep Par-1 is often negative and neighboring cirrhotic lesions are seldom seen. [12] P53 protein immunohistochemical detection in GHAC has also been demonstrated. In classic adenocarcinoma of the stomach, p53 protein is frequently expressed and often correlates with a poor prognosis. In contrast, overexpression of p53 is a rare event in HCC. [13] A recent finding indicates the use of the palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) immunostaining as a novel marker that distinguishes GHAC from primary HCC. [2]

However, the presence of markers of hepatoid differentiation cannot be used as the sole diagnostic criteria for GHAC but must always be accompanied by a compatible morphological pattern. [14] The differential diagnosis includes other AFP-producing gastric tumors as well as metastatic germ cell tumor. [15]

In terms of treatment, there are only sparse data in the literature pertaining specifically to GHAC, and the disease should be treated similarly to common gastric adenocarcinoma.

  Conclusion Top

We present a case of AFP-producing gastric adenocarcinoma with hepatoid morphology. This histologic pattern is unique and the incidence is rare. The literature describes the clinical course of hepatoid adenocarcinoma stomach to be worse than that of conventional adenocarcinoma. This may be due to widespread metastases at the time of presentation. Thus distinction between these two entities is necessary, which can be accomplished histochemically and by measuring serum AFP levels.

  References Top

1.Inagawa S, Shimazaki J, Hori M, Yoshimi F, Adachi S, Kawamoto T, et al. Hepatoid adenocarcinoma of the stomach. Gastric Cancer 2001;4:43-52.  Back to cited text no. 1
2.Petrella T, Montagnon J, Roignot P, Van Nieuvenhuyse A, Matagrin C, Michiels-Marzais D, et al. Alphafetoprotein-producing gastric adenocarcinoma. Histopathology 1995;26:171-5.  Back to cited text no. 2
3.Gitlin D, Pericelli A, Gitlin GM. Synthesis of -fetorpotein by liver, yolk sac, and gastrointestinal tract of the human conceptus. Cancer Res 1972;32:979-82.  Back to cited text no. 3
4.Purves LR, Bersohn I, Geddes EW. Serum alpha-feto-protein and primary cancer of the liver in man. Cancer 1970;25:1261-70.  Back to cited text no. 4
5.Yamada K, Fujioka Y, Ebihara Y, Kiriyama I, Suzuki H, Akimoto M. Alpha-fetoprotein producing undifferentiated carcinoma of the bladder. J Urol 1994;152 : 958-60.  Back to cited text no. 5
6.Bourreille J, Metayer P, Sauger F, Matray F, Fondimare A. Existence of alpha feto protein during gastric-origin secondary cancer of the liver. Presse Med 1970;78:1277-8.  Back to cited text no. 6
7.McIntire KR, Waldmann TA, Moertel CG, Go VL. Serum alpha-fetoprotein in patients with neoplastic of the gastrointestinal tract. Cancer Res 1975;35:991-6.  Back to cited text no. 7
8.Ishikura H, Fukasawa Y, Ogasawara K, Natori T, Tsukada Y, Aizawa M. An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report. Cancer 1985;56:840-8.  Back to cited text no. 8
9.Takahashi Y, Mai O, Ogino T, Ueda H, Sawaguchi K, Ueno M. Clinicopathological study of AFP-producing gastric cancer-significance of AFP in gastric cancer. Nihon Geka Gakkai Zasshi 1987;88:696-700.  Back to cited text no. 9
10.Ishikura H, Kirimoto K, Shamoto M, Miyamoto Y, Ymagiwa H, Itho T, et al. Hepatoid adenocarcinoma of the stomach. An analysis of seven cases. Cancer 1986;58:119-26.  Back to cited text no. 10
11.Inagawa S, Shimazaki J, Hori M, Yoshimi F, Adachi S, Kawamoto T, et al. Hepatoid adenocarcinoma of the stomach. Gastric Cancer 2001;4:43-52.  Back to cited text no. 11
12.Gao YB, Zhang DF, Jin XL, Xiao JC. Preliminary study on the clinical and pathological relevance of gastric hepatoid adenocarcinoma. J Dig Dis 2007;8:23-8.  Back to cited text no. 12
13.Hishinuma M, Ohashi KI, Yamauchi N, Kashima T, Uozaki H, Ota S, et al. Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma. Histopathology 2006;49 : 479-86.  Back to cited text no. 13
14.Sentani K, Oue N, Sakamoto N, Arihiro K, Aoyagi K, Sasaki H, et al. Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach. Mod Pathol 2008;21 : 464-75.  Back to cited text no. 14
15.Supriatna Y, Kishimoto T, Uno T, Nagai Y, Ishikura H. Evidence for hepatocellular differentiation in alpha-fetoprotein-negative gastric adenocarcinoma with hepatoid morphology: A study with in situ hybridisation for albumin mRNA. Pathology 2005;37 : 211-5.  Back to cited text no. 15


  [Figure 1], [Figure 2]


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