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      Clinicopathologic characteristics and treatment outcomes of hepatoid adenocarcinoma of the stomach, a rare but unique subtype of gastric cancer

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          Abstract

          Background

          Gastric hepatoid adenocarcinoma (HAC) is a special type of gastric cancer that morphologically mimics hepatocellular carcinoma. In this study, we performed an evaluation of clinicopathologic characteristics, treatment outcome, and prognosis in patients with gastric HAC.

          Methods

          We consecutively enrolled patients with pathologically proven gastric HAC at Seoul National University Hospital between January 1996 and December 2008 and conducted a retrospective review. Among 15,253 patients with gastric cancer, 26 patients (0.17%) were diagnosed as gastric HAC.

          Results

          Among 26 patients, 22 were male and the median age was 63. Stage at diagnosis was stage IB in 3 patients, stage II in 6 patients, stage III in 7 patients, and stage IV in 10 patients. Eight patients out of 18 patients with stage IB, II, III, and IV relapsed after curative surgery. Relapse-free survival for these patients was 16.67 months. The most common metastatic site was intraabdominal lymph nodes (n = 9), followed by the liver (n = 8). Thirteen patients received palliative chemotherapy. The most commonly used regimen was a combination of fluoropyrimidine and platinum. Partial response was observed in one patient and stable disease in 5 patients. Median overall survival and progression free survival of these patients were 8.03 (95% CI: 6.59-9.47) and 3.47 months (95% CI: 0.65-6.29), respectively.

          Conclusions

          Gastric HAC is a very rare but unique type of stomach cancer. Early detection of this type of cancer is of critical importance to patient prognosis. Additional studies to reveal the biology of this tumor are warranted.

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          Most cited references21

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          Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial.

          Y-K Kang, W.-K. Kang, D-B. Shin … (2009)
          To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer (AGC). In this randomised, open-label, phase III study, patients received cisplatin (80 mg/m(2) i.v. day 1) plus oral capecitabine (1000 mg/m(2) b.i.d., days 1-14) (XP) or 5-FU (800 mg/m(2)/day by continuous infusion, days 1-5) (FP) every 3 weeks. The primary end point was to confirm noninferiority of XP versus FP for progression-free survival (PFS). A total of 316 patients were randomised to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point was met with an unadjusted hazard ratio (HR) of 0.81 [95% confidence interval (CI) 0.63-1.04, P < 0.001 versus noninferiority margin of 1.25]. Median overall survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95% CI 0.64-1.13, P = 0.008 versus noninferiority margin of 1.25). The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis (2% versus 6%). XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC. XP can be considered an effective alternative to FP.
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            An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report.

            Y Akishima-Fukasawa, M. Aizawa, H Ishikura … (1985)
            A patient with primary gastric adenocarcinoma with extremely high serum alpha-fetoprotein (AFP) levels (12,000 ng/ml) is described. Histologically, foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Within tumor cells, AFP was identified with both light and electron microscopy, showing the production of AFP by tumor cells themselves. Furthermore, 88% of serum AFP combined with Concanavalin A (ConA), revealing that it was hepatic-type AFP and not germ-cell-type. Localization of alpha-1-antitrypsin within tumor cells was also noted. Ultrastructural study showed that there were two types of structures corresponding to periodic acid-Schiff (PAS)-positive globules, one of which, the proteinaceous material in intracytoplasmic lumina, was found to contain AFP. Among gastric adenocarcinomas with a high serum AFP level (several thousand or more ng/ml of AFP), foci resembling hepatocellular carcinomas have been reported by several investigators. Those gastric carcinomas, together with the current case, may constitute a clinicopathologic entity, hepatoid adenocarcinoma of the stomach.
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              Hepatoid adenocarcinoma of the stomach. A clinicopathologic and immunohistochemical analysis.

              T Ueyama, E Nagai, T Yao … (1993)
              The clinicopathologic and immunohistochemical features of the primary gastric hepatoid adenocarcinomas still remain unclear. The authors evaluated 28 hepatoid adenocarcinomas (HC) of the stomach on the basis of characteristic histologic features resembling hepatocellular carcinoma, which were selected from the 7200 cases of primary gastric carcinoma in their files. Additionally, 22 alpha-fetoprotein (AFP)-positive adenocarcinomas without hepatoid features (APC) were also selected. The HC cases fell into the following two groups: HC with AFP-positive tumor cells (Group 1; 15 cases) and HC without AFP-positive cells (Group 2; 13 cases). Histologically, the glycogen granules and hyaline globules were common features in HC. The incidence of a venous invasion of HC (Groups 1 and 2) was higher than that of APC (Group 3). There were no significant differences among the three groups regarding clinical features, macroscopic features, and the incidence of lymphatic permeation. An immunohistochemical study showed that HC had differentiation into various directions. As for the advanced carcinomas, the 5-year survival rates of patients with HC (Groups 1 and 2) and those with APC (Group 3) were 11.9% (21.4%, 8.3%) and 38.2%, respectively. The prognosis of Group 1 was similar to that of Group 2, but was poorer than that of Group 3. The findings suggested that HC, as shown by its characteristic histologic features, had a poor prognosis whether producing AFP or not, and that HC should therefore be distinguished from AFP-positive carcinoma without hepatoid features.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMC Gastroenterol
                Title: BMC Gastroenterology
                Publisher: BioMed Central
                ISSN (Electronic): 1471-230X
                Publication date Collection: 2011
                Publication date (Electronic): 19 May 2011
                Volume: 11
                Page: 56
                Affiliations
                [1 ]Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
                [2 ]Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
                [3 ]Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Korea
                Article
                Publisher ID: 1471-230X-11-56
                DOI: 10.1186/1471-230X-11-56
                PMC ID: 3136411
                PubMed ID: 21592404
                SO-VID: babff0a9-13f5-48d1-b77c-89869d3ac48a
                Copyright © Copyright ©2011 Baek et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 14 December 2010
                Date accepted : 19 May 2011
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: clinicopathologic,gastric hepatoid adenocarcinoma,treatment outcome,prognosis
                Data availability:
                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: clinicopathologic, gastric hepatoid adenocarcinoma, treatment outcome, prognosis

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