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Year : 2014  |  Volume : 57  |  Issue : 1  |  Page : 116-119
Hepatoid adenocarcinoma of stomach: Case report of a rare histological variant

1 Department of Pathology, IGMC, Shimla, Himachal Pradesh, India
2 Department of Internal Medicine, John H Stoger Hospital of Cook County, Chicago, IL, USA

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Date of Web Publication17-Apr-2014


Hepatoid adenocarcinoma of the stomach is a rare form of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. Here, we report a case of a 60-year-old male patient who presented in the outpatient department with pain abdomen and constitutional symptoms. Radiological examination revealed a growth involving the antrum of the stomach while the liver and spleen were normal. The serum alpha fetoproteins were 6590 ng/ml. The patient underwent a partial gastrectomy and microscopic examination of the growth showed two types of histological patterns. Majority of the tumor displayed hepatoid differentiation with adenocarcinomatous foci. Periodic acid Schiff positive intracytoplasmic hyaline globules were seen. The tumor was immunohistochemically positive for alpha fetoprotein. The patient underwent radical gastrectomy, received chemotherapy and has been on follow-up for the past 12 months. Though known to be an aggressive neoplasm early diagnosis of hepatoid adenocarcinoma can help improve the prognosis of the disease.

Keywords: Alpha fetoprotein, gastric cancer, hepatoid adenocarcinoma

How to cite this article:
Mahajan V, Gupta N, Gupta S, Sharma R. Hepatoid adenocarcinoma of stomach: Case report of a rare histological variant . Indian J Pathol Microbiol 2014;57:116-9

How to cite this URL:
Mahajan V, Gupta N, Gupta S, Sharma R. Hepatoid adenocarcinoma of stomach: Case report of a rare histological variant . Indian J Pathol Microbiol [serial online] 2014 [cited 2022 Jan 24];57:116-9. Available from: https://www.ijpmonline.org/text.asp?2014/57/1/116/130917

   Introduction Top

Hepatoid adenocarcinoma is a rare variant of gastric adenocarcinoma with a poor prognosis. It is characterized by a distinct morphology histologically and in many cases by increased alpha fetoprotein (AFP) levels. However, demonstration of AFP production is not a must for the diagnosis of these tumors. The presenting symptoms are similar to those that of conventional adenocarcinomas. Hepatoid adenocarcinoma is an adenocarcinoma primarily originating from gastric mucosa and contains distinctive foci of hepatocellular differentiation. Periodic acid Schiff (PAS) positive diastase resistant hyaline globules in the tumor cells is a common but not a specific finding seen in the hepatoid adenocarcinomas. [1] The incidence of this variant ranges from 0.38% to 0.73% of all gastric cancer. [2] Awareness of this rare entity would aid in better diagnosis by the pathologist and management by treating physicians.

   Case Report Top

This was a case report of a 60-year-old male patient who presented in the surgical out-patient department with pain abdomen for 2 months along with a history of loss of weight and decreased appetite. On physical examination, a non-tender firm lump was palpable in the gastric region. The liver function tests were within the normal range with serum AFP levels of 6590 ng/ml. On contrast enhanced computed tomography (CT) scan a 6 cm enhancing mass arising from the posterior aspect of the greater curvature of the stomach was noted [Figure 1]. The liver and spleen were within normal limits. Upper gastrointestinal endoscopy revealed an ulcerative growth in the antrum with a central depression. Histopathological report on biopsy was given as a poorly differentiated adenocarcinoma. Pre-operatively a growth of size (4 cm × 3 cm) in the antrum of the stomach involving the whole the circumference was seen. On gross examination, an ulceroinfiltrative growth measuring 3 cm × 2 cm extending up to the serosa was identified at antrum of the subtotal gastrectomy specimen [Figure 2]. Four lymph nodes were dissected out of the specimen. Microscopic examination of the growth revealed poorly differentiated adenocarcinoma with large areas showing hepatoid features comprising about 70% of the tumor. The tumor in these fields was composed of large polygonal cells arranged in sheets, aggregates, pseudoglandular and trabecular pattern having a well-defined cell boundaries, abundant eosinophilic cytoplasm, central nucleus with prominent nucleoli. The adjoining epithelium revealed dysplastic and reactive changes [Figure 3a,b]. Lymphovascular invasion was seen by the tumor cells. PAS positive diastase resistant intracytoplasmic hyaline globules were seen [Figure 3]c. Immunhistochemically the tumor revealed positivity for AFP in areas of the hepatoid differentiation [Figure 4]a. The tumor was also positive for cytokeratin (CK) 8, 18 and focally positive for carcinoembryonic antigen (CEA) [Figure 4]b. It was negative for Hep Par-1. Two of the four lymph nodes revealed tumor metastasis. The patient then underwent radical gastrectomy and received chemotherapy comprising of six cycles of 5-fluorouracil and cisplatin. The serum AFP levels reduced to 125 ng/ml after 6 months of treatment. The patient has been kept under close follow-up for the past 12 months and is still alive with no evident symptoms of recurrence or metastasis with further reductions in AFP levels.
Figure 1: Contrast enhanced computed tomography revealing gastric antral wall thickening with mucosal irregularity with the normal liver parenchyma

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Figure 2: Gross photograph revealing normal gastric mucosal folds with the antral area revealing the cut section of an ulceroinfiltrative growth extending up to the serosa

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Figure 3:

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Figure 4:

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   Discussion Top

Hepatoid adenocarcinoma of the stomach is a rare variant of gastric carcinoma. The disease frequently affects patients above the age of 60 years with a male to female ratio of 2.3:1. [3] The term hepatoid has been restricted to those extrahepatic carcinomas that show histologic features of hepatocytic differentiation. [1] The antrum of the stomach is one of the most commonly described sites for the occurrence of hepatoid adenocarcinomas. [3] Foregut derivation of both liver and the stomach could be the likely reason for this increased incidence. Hepatoid adenocarcinomas has also been reported in several different organs including the esophagus, colon, lung, pancreas, peritoneum and ovary. [4]

Ishikura proposed the term "hepatoid adenocarcinoma of the stomach" for the primary gastric carcinomas characterized by both hepatocytic differentiation and the production of large amounts of AFP. [5] AFP is an oncofetal glycoprotein and is found normally in large amounts during fetal development. AFP producing malignant tumors other than hepatocellular carcinoma and non seminomatous germ cell tumor have also been reported in several different organs such as the lung, pancreas, colon, ovary and urinary bladder. [1] Not all hepatoid adenocarcinomas produce AFP. Only 54% of the cases express AFP by immunohistochemistry and 63% reveal an elevated serum AFP levels. [6]

The diagnosis of hepatoid adenocarcinoma depends on recognition of characteristic histological features. The histological findings usually reveal intestinal adenocarcinoma with foci of hepatoid differentiation. The tumor can reveal a solid, trabecular and pseudoglandular arrangement mimicking the liver architecture. The tumor cells are large polygonal cells with abundant eosininophilic cytoplasm with prominent cell borders, central nuclei and prominent nucleoli. PAS positive hyaline globules within the tumor cells are another common but non-specific finding that has been correlated with production of AFP. [5] There is no consensus for the amount of hepatocellular differentiation required to classify a tumor as a hepatoid adenocarcinoma.

The immunohistochemical staining pattern has been variably reported in the literature. The tumor shows positivity for alpha fetoprotein, polyclonal CEA, CK 8, CK 18 while negativity for CK7 and Hep Par-1 is seen. [7] The tumor in this case showed positivity for AFP in the hepatoid areas and focal positivity for polyclonal CEA. Hep Par-1 was negative in the tumor population.

The main differential diagnosis for the hepatoid adenocarcinoma is the metastatic hepatocellular carcinoma. [8] The absence of an underlying disease such as liver cirrhosis and the use of imaging modalities such as endoscopy and CT in our case ruled out the presence of the a primary hepatocellular carcinoma.

Hepatoid adenocarcinomas 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. These tumors have a high proliferative activity, weak apoptosis and rich neovascularization indicating high grade malignant potential. [8]

A specific treatment protocol for this variant has not yet been defined with the majority of patients being detected in the metastatic stage and requiring palliative chemotherapy. The overall 5 year survival rate of hepatoid adenocarcinoma was 9% when compared to 44% of conventional gastric carcinoma. [9] Early diagnosis of this histological variant is essential for curative resection of the disease. The rarity and poor prognosis of this clinicopathological entity requires greater awareness for diagnosis and management.

   References Top

1.Roberts CC, Colby TV, Batts KP. Carcinoma of the stomach with hepatocyte differentiation (hepatoid adenocarcinoma). Mayo Clin Proc 1997;72:1154-60.  Back to cited text no. 1
2.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. 2
3.Nagai E, Ueyama T, Yao T, Tsuneyoshi M. Hepatoid adenocarcinoma of the stomach. A clinicopathologic and immunohistochemical analysis. Cancer 1993;72:1827-35.  Back to cited text no. 3
4.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. 4
5.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. 5
6.Kodama T, Kameya T, Hirota T, Shimosato Y, Ohkura H, Mukojima T, et al. Production of alpha-fetoprotein, normal serum proteins, and human chorionic gonadotropin in stomach cancer: Histologic and immunohistochemical analyses of 35 cases. Cancer 1981;48:1647-55.  Back to cited text no. 6
7.Terracciano LM, Glatz K, Mhawech P, Vasei M, Lehmann FS, Vecchione R, et al. Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: An immunohistochemical and molecular study of eight cases. Am J Surg Pathol 2003;27:1302-12.  Back to cited text no. 7
8.Ishikura H, Kishimoto T, Andachi H, Kakuta Y, Yoshiki T. Gastrointestinal hepatoid adenocarcinoma: Venous permeation and mimicry of hepatocellular carcinoma, a report of four cases. Histopathology 1997;31:47-54.  Back to cited text no. 8
9.Liu X, Cheng Y, Sheng W, Lu H, Xu X, Xu Y, et al. Analysis of clinicopathologic features and prognostic factors in hepatoid adenocarcinoma of the stomach. Am J Surg Pathol 2010;34:1465-71.  Back to cited text no. 9

Correspondence Address:
Vidisha Mahajan
Department of Pathology, IGMC, Shimla - 171 001, Himachal Pradesh, India

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.130917

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

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