Hepatoid adenocarcinoma of the stomach: A case report of a rare type of gastric cancer

  • Authors:
    • Zhihong Shen
    • Xibo Liu
    • Baochun Lu
    • Minfeng Ye
  • View Affiliations

  • Published online on: December 10, 2015     https://doi.org/10.3892/ol.2015.4023
  • Pages: 1077-1080
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Abstract

Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric cancer with an extremely poor prognosis. The current study reports a rare case of HAS, characterized by gastric cancer and infiltration of cancer cells into the left liver lobe, as well as lymphadenectasis. The expression of α‑fetoprotein (AFP) was markedly increased in the tumor cells of the liver neoplasms. A gastric biopsy indicated highly, moderately and poorly differentiated papillary adenocarcinoma. The patient underwent two cycles of chemotherapy with oxaliplatin (130 mg; day 1) and capecitabine (2 mg, twice daily; days 1‑14). At 7 weeks after the chemotherapy, an expanded gastrectomy and radical resection of left lung lobe were performed on the operable lesion. AFP expression was significantly decreased following the procedure. A literature review was also conducted by searching PubMed/Medline, indicating that surgery and chemotherapy may positively affect the outcomes of HAS patients.

Introduction

Hepatoid adenocarcinoma is an extrahepatic tumor with an incidence of 0.38–0.73% (1). The occurrence of this malignancy has been described in several organs, including the lungs, gallbladder, esophagus, uterus and stomach (2). Hepatoid adenocarcinoma of stomach (HAS) refers to a rare type of gastric carcinoma characterized by a distinct morphology and elevated α-fetoprotein (AFP) levels (3). The diagnosis of HAS is largely depend on the pathological analysis. In 1981, Kodama et al (4) initially described two histologic types of AFP-producing gastric carcinoma with medullary or papillotubular arrangements. Subsequently, Ishikura et al (5) proposed the term ‘hepatoid adenocarcinoma of the stomach’ for primary gastric carcinomas characterized by hepatoid differentiation and the production of large amounts of AFP. At present, the prognosis of HAS is rather poor and according to a literature search of PubMed/Medline between January 2001 and December 2013, only a few cases of this disease have been reported (Table I) (68). The current study reports a case of HAS, and summarizes the treatment and outcome for the disease.

Table I.

Literature review from January 2001 to December 2013a.

Table I.

Literature review from January 2001 to December 2013a.

Author (reference no.)GenderAge (years)AFPTreatmentFollow-up
Gálvez-Muñoz et al (7)Male75PositivePalliative total gastrectomy; palliative chemotherapy with cisplatin and capecitabine (6 cycles)Alive at 8 months post surgery
Ahn et al (6)Male68PositiveBillroth type II subtotal gastrectomy; palliative chemotherapy with cisplatin and capecitabine; second-line palliative chemotherapy with fluororacil, leucovorin and irinotecanAlive during 21 months of follow-up
Ye et al (8)Male58PositiveDistal gastrectomy; epirubicin, oxaliplatin and fluorouracil (6 cycles)Alive at 20 months post surgery
Male54PositiveTotal gastrectomy with lymph node dissection; oxaliplatin plus fluorouracil adjuvant chemotherapy (6 cycles); paclitaxel and capecitabine (2 cycles)Deceased at 18 months post surgery
Female61PositiveChemotherapy with oxaliplatin plus S-1Deceased at 8 months after treatment
Present studyMale70PositiveExpanded gastrectomy and radical resection of left lung lobe; chemotherapy using oxaliplatin and capecitabineAlive during 7 months of follow-up

a Search of Pubmed/Medline for English language articles using terms ‘hepatoid adenocarcinomas of stomach’, ‘AFP-producing tumor’ and ‘AFP-producing gastric cancer’. AFP, α-fetoprotein.

Case report

A 70-year-old male patient presented to Shaoxing People's Hospital (Shaoxing, China) due to muscle weakness and palpitations lasting for 2 months. No abnormalities were noted during the physical examination. During laboratory tests, fecal occult blood was noted, and the patient's AFP level was 14,399.9 ng/ml (normal range, 0–13.4 ng/ml). Ultrasound examination indicated an occupying lesion in right upper quadrant. Computed tomography imaging was performed, revealing gastric cancer and infiltration of cancer cells into the left lobe of the liver, as well as lymphadenectasis of the group 1 and 3 nodes (Fig. 1A). Gastroscopy and pathological tests revealed irregular bulges in the gastric antrum and oedema in the peripheral mucous membrane. In addition, highly-differentiated adenocarcinoma cells were observed. On this basis, the patient was diagnosed with adenocarcinoma of the gastric antrum (Figs. 1B and 2A). The diagnosis of HAS was primarily based on the presence of the following aspects: papillary adenocarcinoma of high, moderate or low grade; mucinous adenocarcinoma; undifferentiated carcinoma and poorly differentiated hepatocellular carcinoma combined with presence of hyaline bodies; poorly differentiated hepatocellular carcinoma and hyaline body-like structures in the liver cancer specimen. Two cycles of chemotherapy with oxaliplatin (130 mg; day 1) and capecitabine (2 mg, twice daily; days 1–14) were administered.

At 7 weeks after chemotherapy, resection of the stomach and external lobe of the left liver were conducted, during which a tumor mass measuring ~2.0×1.5×1.0 cm was observed in gastric corpus. Meanwhile, a gastric biopsy revealed an ulcerating tumor (4.0×3.0×1.5 cm) from the gastric angle to the gastric antrum, and infiltration of cancer cells into left liver (4.0×3.0×3.0 cm). No postoperative complications were reported. Biopsy of liver indicated adenoid carcinoma with no infiltration of cancer cells in the incisal margins, and no lymph node metastasis (Fig. 2B and C). The immunohistochemistry results were AFP(+), cytokeratin (CK) 19(+), CK7(−) and CK20(−). Biopsy of gastric samples indicated adenocarcinoma (Fig. 2D); the immunohistochemistry results were AFP(−), c-erbB-2(+), E-cadherin(+), epidermal growth factor receptor(+), Ki-67 (+65%), CK7(+) and CK20(+). AFP levels were measured on postsurgical days 9 and 30 at 116.7 and 17.3 ng/ml, respectively. Subsequently, chemotherapy was performed 3 weeks after the after surgery. The chemptherapy regimen, was 130 mg oxaliplatin on day 1 plus 2 mg capecitabine, twice daily, on days 1–14, for two cycles. The patient survived during 7 months of follow-up, at which point the AFP levels were 10.4 ng/ml.

Discussion

For patients with HAS, the initial symptoms are usually upper abdominal pain (9); more rarely, individuals may also exhibit melena. On pathological evaluation, elevated AFP is commonly noted in these patients. In such cases, the AFP is typically significantly reduced compared with the baseline levels following surgery and chemotherapy.

The diagnosis of HAS is largely dependent upon hematoxylin and eosin (H&E) staining and immunohistochemical staining. When stained with H&E, HAS typically exhibits similar features to hepatocellular carcinoma. In addition, proliferation of polygonal tumor cells is observed in trabecular and intestinal-like structures. For the differential diagnosis, immunohistochemical staining is required. In the current case, AFP expression was confirmed using immunohistochemical staining, as shown in Fig. 2E.

All articles cited in the Medline/PubMed database between January 2001 and December 2013 were searched using the terms ‘hepatoid adenocarcinomas of stomach’, ‘AFP-producing tumor’ and ‘AFP-producing gastric cancer’. Simultaneously, a manual search of all relevant articles was performed. The search was limited to English language articles. A total of 6 patients (including the current case) were included in the literature review (Table I) (68).

To date, no consensus has been reached regarding the treatment of HAS, as little data are available in the literature (10,11). Usually, the disease is treated using similar strategies as those used to treat gastric adenocarcinoma. Radical surgery is considered to be the optimal treatment option and, at the same time, adjuvant chemotherapy and radiotherapy should be performed according to the indications of the gastric cancer (12). In the literature review, 4 patients (66.7%) received gastrectomy and chemotherapy, while 2 patients (33.3%) received only chemotherapy. For patients with metastasis, including metastasis to the liver, simultaneous resections are necessary (2). In the present case, the patient received oxaliplatin (130 mg; day 1) and capecitabine (2 mg, twice daily; days 1–14), and radical surgery was performed to remove the lesions.

The literature review indicates that men are more prone to developing HAS compared with women. In addition, the mean age of the patients was 64.3 years, demonstrating that individuals of advanced age are more prone to developing the disease. The rate of positive AFP expression was 100.0%. Following surgery, AFP expression was also used as a marker for the subsequent treatment. In the present study, AFP expression levels were significantly reduced on postoperative day 30 compared with that on day 9. In addition, AFP expression levels were stable during the 7-month follow-up.

In summary, HAS is a rare type of carcinoma with poor prognosis. The current study presented a case of HAS occurring in a 70-year-old male, and summarized the treatment outcomes of the chemotherapy and/or gastrectomy in previous studies of this disease. The present results indicated surgery and chemotherapy may positively affect the outcome of similar patients. As the number of cases is still limited, further randomized controlled trials are necessary to confirm the efficacy of this treatment for HAS.

References

1 

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2 

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4 

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7 

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12 

Xie Y, Zhao Z, Li P, Wang Y, Guo C, Wang X, Tang W, Liu Q, Lu N, Xue L and Zhao D: Hepatoid adenocarcinoma of the stomach is a special and easily misdiagnosed or missed diagnosed subtype of gastric cancer with poor prognosis but curative for patients of pN0/1: The experience of a single center. Int J Clin Exp Med. 8:6762–6772. 2015.PubMed/NCBI

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Spandidos Publications style
Shen Z, Liu X, Lu B and Ye M: Hepatoid adenocarcinoma of the stomach: A case report of a rare type of gastric cancer. Oncol Lett 11: 1077-1080, 2016
APA
Shen, Z., Liu, X., Lu, B., & Ye, M. (2016). Hepatoid adenocarcinoma of the stomach: A case report of a rare type of gastric cancer. Oncology Letters, 11, 1077-1080. https://doi.org/10.3892/ol.2015.4023
MLA
Shen, Z., Liu, X., Lu, B., Ye, M."Hepatoid adenocarcinoma of the stomach: A case report of a rare type of gastric cancer". Oncology Letters 11.2 (2016): 1077-1080.
Chicago
Shen, Z., Liu, X., Lu, B., Ye, M."Hepatoid adenocarcinoma of the stomach: A case report of a rare type of gastric cancer". Oncology Letters 11, no. 2 (2016): 1077-1080. https://doi.org/10.3892/ol.2015.4023