Case Report of an Hepatoid Adenocarcinoma of the Stomach Raffaele Gaeta, MD, Clara Ugolini, MD, and Maura Castagna, MD Abstract: Hepatoid adenocarcinoma (HAC) is a rare but im- portant type of extrahepatic tumor that has a morphologic similarity to hepatocellular carcinoma, with production of a- fetoprotein in high amounts and a poor prognosis. Stomach is one of the organs in which HAC has been most commonly identified. We report a case of an old man with a polypoid mass in the prepyloric region. The microscopical aspects were sug- gestive for an undifferentiated adenocarcinoma, but the positive immunohistochemical staining for a-fetoprotein, a-1-anti- trypsin, a-1-antichymotrypsin, and Hep Par1 were crucial for the final diagnosis of hepatoid adenocarcinoma of the stomach. Because of the poor prognosis for this type of tumor, correct and early-stage diagnosis of HAC is essential and long-term follow-up is required. Key Words: hepatoid adenocarcinoma, stomach, a-fetoprotein (Appl Immunohistochem Mol Morphol 2016;24:e6–e8) T he hepatoid variant of gastric carcinoma, first de- scribed in 1970 1 , is a rare form of tumor characterized by the presence of neoplastic cells similar to the hep- atocytes in the context of an adenocarcinoma. The bio- chemical characteristic of this malignant neoplasia is the production of a-fetoprotein (AFP) in high amounts, while clinically has a significant aggressiveness with frequent liver metastasis, even in early-stage neoplasia. The poor prognosis of the tumor may be attributed to extensive venous involvements by neoplastic cells and production of AFP, a-1-antitrypsin, and a-1-antichymotrypsin, which have immunosuppressive and protease-inhibitory properties that enhance invasiveness. Hepatoid adenocarcinoma (HAC) had been found in a variety of organs, such as ovary, 2 renal pelvis, 3 lung, 4 and pancreas, 5 although gastric localization continues to be the most common. 6 In fact, summarizing data from 261 HAC cases published, the percentage of HAC loca- tion is 63% in the stomach, 10% in the ovaries, 5% in the lung, 4% in the gallbladder, 4% in the pancreas, and 4% in the uterus. 7 With the exception of gallbladder HAC, there was a male predominance (M:F = 2.4:1). The rea- son for the preponderance of hepatoid adenocarcinomas in the stomach (HAS) is unknown, but it is thought that the common embryologic derivation of the liver and the stomach from the foregut may have a significant role. 8 Only a few cases of HAS have been previously re- ported, especially in Europe and North America, and most case reports are from the Far East. 9 In this article, we report a case of HAS with a particular focus on the immunohistochemical analysis. CASE PRESENTATION A 72-year-old Italian man presented with sense of post- prandial fullness and marked fatigue even after small efforts for about 2 months. Hematological investigations revealed anemia and fecal occult blood. The patient had no relevant past medical history, except for hypertension and osteomyelitis at young age. The esophagogastroduodenoscopy revealed a 3  3 cm polypoid lesion in the prepyloric region, confirmed by a subsequent computed tomography. It was macroscopically classified as type 1, according to the general rules of the Japanese Gastric Cancer Association. 10 In addition, the next “whole-body 3D PET” showed 2 omental enlarged lymph nodes. Testing the levels of AFP in the blood was not performed. The man indeed under- went subtotal gastrectomy with gastrojejunal anastomosis after gastric biopsy, which revealed poorly differentiated carcinoma. The tumor was then sampled and analyzed with hematoxylin and eosin staining. Light microscopic examination revealed the presence of large polygonal cells organized in trabecular and solid pattern with scarce eosinophilic cytoplasm, big clear nucleus, and hyperchromatic nucleoli. The mitotic counts were high (>10 mitotic figures/10 HPF). Intravascular proliferation of tumor cells or tumor thrombi were not clearly observed. There were not unequivocal hepatocyte-like aspects, hence the first diag- nosis was undifferentiated carcinoma. Hemorrhage, necrosis, and chronic inflammatory cellular reaction were abundantly seen. Three greater curvature lymph nodes were involved by metastatic carcinoma. The tumor invasion spread from mucosa to serosa without infiltration of adjacent structures, hence was designated stage IIIb (T4a, N2, M0) according to the American Joint Committee on Cancer guidelines. 11 A definite diagnosis of HAS was difficult only based on findings in hematoxylin and eosin staining. Further immuno- histochemical stains were performed for differential diagnosis. Received for publication August 27, 2015; accepted September 3, 2015. From the U.O. Anatomia Patologica III, Azienda Ospedaliero-Uni- versitaria Pisana, University of Pisa, Pisa, Italy. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study. The authors declare no conflict of interest. Reprints: Raffaele Gaeta, MD, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Via Roma 57, Pisa 56126, Italy (e-mail: gaeta-raffaele@libero.it). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. CASE REPORT e6 | www.appliedimmunohist.com Appl Immunohistochem Mol Morphol  Volume 24, Number 2, February 2016 Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.