Yasuo Yoshida

Hepatoid carcinoma of the pancreas producing protein induced by vitamin K absence or antagonist II (PIVKA-II) and α-fetoprotein (AFP)

We describe a rare case of hepatoid carcinoma of the pancreas with production of protein induced by vitamin K absence or antagonist II (PIVKA-II) and α-fetoprotein (AFP). The patient was a 49-year-old woman admitted because of high serum levels of PIVKA-II (1.63u2009AU/ml) and AFP (623u2009ng/ml) and abnormal ultrasonographic findings of the pancreas, found incidentally at medical checkup. Both ultrasonography and computed tomography showed swelling of the pancreas with small areas of low density, but no hepatic lesions. The serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were not increased. A PIVKA-II and AFP-producing pancreatic cancer was strongly suspected, and total pancreatectomy was performed. Pathological examination showed that the tumor cells were arranged in trabecular and solid patterns with bile production, and were immunohistochemically positive for PIVKA-II and AFP, resembling hepatocellular carcinoma cells. The tumor was diagnosed as hepatoid carcinoma of the pancreas, and the patient has survived 48 months after initial diagnosis. It is important that hepatoid carcinoma be considered as a possible malignant tumor of the pancreas, and simultaneous measurement of the serum levels of AFP and PIVKA-II will enable earlier diagnosis. This is the first report describing hepatoid carcinoma of the pancreas producing PIVKA-II.

Primary coexistent neuroendocrine carcinoma, hepatoid adenocarcinoma, and tubular adenocarcinoma of the stomach with focal trophoblastic differentiation in metastatic lymph nodes.

ated small solitary polygonal cells were growing (Fig. 2c). Those two areas were separated from each other and intermingled with the adenocarcinoma area, but the transition phenomenon was unclear. The metastasized lymph nodes were structured with small polygonal cells, but several foci of lymph nodes had syncytiotrophoblastic giant cells, which showed choriocarcinoma-like features (Fig. 2d) Those histological patterns could not be detected in the primary cancer site. In immunohistochemical examination, all histological foci were stained by the keratin markers cytokeratin 8 and AE1/AE3. The hepatoid adenocarcinoma focus was stained by AFP (Fig. 2b, lower right), and an undifferentiated cellular focus was stained by neuroendocrine markers such as cromogranin A, which revealed neuroendocrine carcinomatous features (Fig. 2c, lower right). Human chorionic gonadotropin -subunit (hCG) was positive in the syncytiotrophoblastic giant cells of metastatic lymph nodes. The preoperative serum hCGlevel was about 226.4 mIU/ml. Pathological classification concluded that this was miscellaneous carcinoma, pT3 (SE), med, INF-α, v2, ly2, pN2 (#3, 5, 6, 8). Five months after the operation, a recurrent mass lesion in the liver was revealed, although the patient had been without symptoms. She died of liver metastasis and carcinomatosis on May 12, 2002. The serum AFP level had reached a maximum level of 4286ng/ml. Motoyama et al. described a case of coexistent choriocarcinoma and hepatoid adenocarcinoma of the stomach, and concluded that their case had derived from trophoblastic metaplasia of intestinal-type adenocarcinoma and liver cell metaplasia of poorly differentiated solid-type adenocarcinoma, respectively.2 In our case, neuroendocrine carcinoma and hepatoid adenocarcinoma areas were associated with an adenocarcinoma area and were stained by keratin markers; this would have resulted from the dedifferentiation of preexisting adenocarcinoma or independent development from normal gastric epithelial cells. Trophoblastic Primary gastric carcinoma is usually composed of adenocarcinoma. However, a few rare histological variants have been reported, including neuroendocrine carcinoma, hepatoid adenocarcinoma, and choriocarcinoma.1 Its origins are controversial. We experienced the first case of coexistence of neuroendocrine carcinoma and hepatoid adenocarcinoma in the stomach with focal trophoblastic differentiation in metastatic lymph nodes, which suggests those variants are derived from the usual type of adenocarcinoma. A 78-year-old woman was admitted to our hospital because of abdominal discomfort on November 11, 1997. Serum level of alpha fetoprotein (AFP) was 168ng/ml. Gastrointestinal endoscopy revealed a protuberant lesion at the pyloric antrum. A biopsy specimen disclosed poorly differentiated adenocarcinoma. A subtotal gastrectomy with lymphadenectomy was performed on November 18, 1997. There were no tumor lesions in the liver, ovaries, uterus, and retroperitoneal area. The Japanese classification of gastric cancer was 9 6 3cm in size, L, Post-Less-Ant, type 5, T3 (SE), H0, P0, N2 (#3, 4, 5, 6, 8), stage IIIB, surgically. A macroscopic specimen is shown in Fig. 1a. A grayish-white protuberant mass surrounded by an ulcerated lesion was found in the pyloric antrum of the stomach. By hematoxylin and eosin staining, the gastric tumor showed three histological patterns (Fig. 1b). Tubular adenocarcinoma composed of cuboidal tumor cells was found in the mucous layer around the ulcerated lesion (Fig. 2a). Incomplete intestinal metaplasia was also observed. In the ulcerated lesion, tumor cells with abundant eosinophilic cytoplasm arranged in a trabecular pattern had invaded the submucosal layers, which showed hepatoid adenocarcinomatous features (Fig. 2b). In the protuberant mass lesion, undifferenti-