AFP-producing hepatoid adenocarcinoma in association with Barrett's esophagus with multiple liver metastasis responding to paclitaxel/CDDP: a case report

A case of alpha-fetoprotein (AFP)-producing hepatoid adenocarcinoma in association with Barrett's esophagus with multiple liver metastases, responding to chemotherapy, is reported. A 47-year-old man was admitted to our hospital with abdominal pain after subtotal esophagectomy for an esophageal adenocarcinoma in association with Barrett's esophagus, and was diagnosed as having multiple liver tumors. Most tumor markers were normal, but the serum AFP level was markedly elevated. Dynamic computed tomography and ferumoxide enhanced magnetic resonance imaging did not provide evidence of any primary hepatocellular carcinoma. Since microscopic examination of the resected tumor showed a poorly-differentiated adenocarcinoma with hepatoid features displaying AFP-immunoreactivity, the liver tumors were thus considered to be metastatic deposits. Surgery was not feasible so chemotherapeutic agents were tried, and the combination of paclitaxel (TXL) and cisplatin (CDDP) gave a partial response and good control for a period. This is the first report, to our knowledge, of effective chemotherapy for liver metastases from an AFP-producing hepatoid adenocarcinoma of the esophagus.     

胃的肝样腺癌的临床病理分析

目的 研究胃的肝样腺癌（ｈｅｐａｔｏｉｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ ｏｆ ｔｈｅ ｓｔｏｍａｃｈ，ＨＡＳ）和病理形态和临床特点。方法 采用常规ＨＥ染色和免疫组织化学方法对３例胃的肝样腺癌进行研究。结果 ３例ＨＡＳ细胞胞质内均有甲胎蛋白（ＡＦＰ），α－抗胰糜蛋白酶（ＡＣＴ）和α－抗胰蛋白酶（ＡＡＴ）表达。肿瘤的发病部位以胃窦部多见，３例均有局部胃壁脉管浸润和局部淋巴结转移，其中２例有肝转移，分别     

A case of hepatoid adenocarcinoma of the stomach

A patient, male, 57 years old, with hepatoid adenocarcinoma of the stomach is reported. Chief complaint was right upper abdominal mass and anorexia for 11 months. The patient's serum AFP level was found to be elevated (652.8 ng/ml) and a mass was observed in left hepatic lobe by isotope scan. It was diagnosed as primary hepatic carcinoma. A large ulcerative tumor (14 x 13 x 0.8 cm) in gastric pylorus-antrum and liver metastasis were found by autopsy. Histologically, the tumor, diagnosed as hepatoid adenocarcinoma of the stomach by pathology, was composed of two but closely related to well differentiated tubular papillary adenocarcinoma and differentiated hepatoid adenocarcinoma. Histogenesis, production of AFP and its significance, and clinicopathologic characteristics of this tumor are discussed with review of literature.     

Hepatoid carcinoma of the pancreas

BACKGROUND: The majority of primary extrahepatic neoplasms exhibiting features of hepatocellular carcinoma in terms of morphology, immunohistochemistry, and behavior have been described in the stomach. To the authors' knowledge only a few cases have involved other organ sites. They frequently are associated with other histologic type tumors such as adenocarcinoma, and portend an aggressive behavior. METHODS: Two examples of hepatoid carcinoma arising from the pancreas are reported in the current study. RESULTS: One case was a malignant islet cell tumor with a full-blown clinical syndrome of glucagon overproduction, histologic evidence of hepatocytic differentiation, bile production, and alpha-fetoprotein (AFP) positivity. The second tumor was a ductal carcinoma showing periodic acid-Schiff positive and diastase-resistant hyaline globules, AFP production, and ultrastructural resemblance to hepatocytic cells. CONCLUSIONS: The rare observation of cellular phenotypic transformation that corresponds with the process of hepatocytic transdifferentiation of pancreatic cells demonstrated in animal models and the common embryologic foregut derivation of the pancreas and liver also may explain the phenomenon of pancreatic hepatoid carcinoma.     

Different characteristics of hepatoid and non-hepatoid α-fetoprotein-producing gastric carcinomas: An experimental study using xenografted tumors

The characteristics, including metastatic potential, of 5 xenografts of α-fetoprotein (AFP)-producing gastric carcinomas in nude mice, designated TSG1, TSG3, TSG11, TSG17 and TSG20, were examined. Of these xenografts, TSG1, TSG11 and TSG20 were regarded as hepatoid adenocarcinomas based on their morphological resemblance to hepatocellular carcinoma, frequent immunoreactivity for liver-cell markers, and excessive production of AFP with a high concanavalin A (Con-A)-binding property of hepatic type. On the other hand, TSG3 and TSG17 tumors showed the features of poorly differentiated medullary adenocarcinoma with scattered AFP-positive cells consistent with low AFP levels in mouse sera, and negative immunoreactivity for other liver-cell markers. Ultrastructurally, these tumors were composed of undifferentiated cells with a little adenocarcinomatous differentiation. Moreover, the AFP produced by TSG3 and TSG17 tumors had an extremely high Con-A non-bound fraction (80% to 90%), which was different from that of the hepatic or yolk-sac types. Therefore, both TSG3 and TSG17 tumors were regarded as non-hepatoid, poorly differentiated adenocarcinomas which could be differentiated from any types of AFP-producing gastric carcinoma. Furthermore, cells from hepatoid adenocarcinoma strains (TSG1, TSG11 and TSG20) injected into the spleens of nude mice produced liver metastases in all the mice examined, whereas cells from non-hepatoid carcinoma strains (TSG3 and TSG17) produced few or no liver metastases. Our data show that some non-hepatoid AFP-producing gastric carcinomas have lower liver-metastasizing potential than hepatoid AFP-producing gastric carcinomas.     

An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report

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.     

胃肝样腺癌伴肝转移治疗成功1例报告

我们报告一例成功治疗胃肝样腺癌(hepatoid adenocarcinoma of stomach,HAS)伴肝转移的病例,并复习了相关文献。患者男性,60岁,诊断为HAS伴肝转移,血AFP 780ng/ml,行根治性胃大部切除和肝切除术。术后经肝动脉行灌注化疗后,血AFP降至正常。胃的肝样腺癌(HAS)是具有肝细胞样分化和腺癌分化的胃癌,通常可以产生甲胎蛋白(AFP),易早期发生肝脏转移,预后不良,平均生存期<1年。此例病人随访8年,无肿瘤复发迹象。提示对HAS伴肝转移的病人仍有积极治疗的价值。     

Hepatoid carcinoma of the stomach: is it still an unusual anatomo-clinical entity? Six cases-report

Hepatoid carcinoma of the stomach is a rare neoplasm (especially in western countries) characterized by high levels of serum alpha-fetoprotein (AFP), the presence of "hepatoid foci" inside the gastric tumor and poor prognosis, due to the earlier onset of liver metastases. We treated six patients for hepatoid carcinoma of the stomach between 1990 and 1997. The female to male ratio was 1:1, the average age was 71 (54-81) and the average AFP-level was 1160 ng/ml (603-1531). We performed 2 total gastrectomies, 2 subtotal gastrectomies and 2 gastro-jejunostomies (due to presence of liver metastases): in one case, the patient underwent a splenectomy as well. All the tumors showed the presence of "hepatoid foci" (the morphological feature is close to the hepatocellular carcinoma) and a positive immunoreactivity to AFP. The mean survival was 3 months: only one patient is still alive and disease-free (with a 52 months follow-up). After radical surgery, she underwent a chemotherapic treatment with cisplatin, epirubicin, 5-fluorouracil and l-leucovorin. We conclude that our series (the widest in Italy and one of most impressive in Europe) confirm the poor prognosis of this neoplasm, but we also want to underline that this tumor is not so "unusual" any more and it requires new types of treatment, like postoperative chemotherapy, besides surgery, to be fighted properly.     

AFP-producing Xp11 translocation renal cell carcinoma: Case report and review of the literature

Alpha-fetoprotein (AFP) is a useful tumor marker for hepatocellular carcinomas and yolk sac tumors. Rare extrahepatic visceral malignancies may be associated with AFP production and those exhibiting a hepatoid differentiation by morphology and immunohistochemical are classified as hepatoid adenocarcinoma. Renal cell carcinoma (RCC) producing AFP is a rare entity. To date, only one case of AFP-producing Xp11 translocation RCC has been reported. We reported another case of Xp11 translocation RCC, in which the tumor cells displayed strong immunostaining for AFP, HepPar1, and GPC-3. Additionally, the other published cases are reviewed.     

胃肝样腺癌11例分析

目的探讨胃肝样腺癌(HAS)的临床和病理特点及其诊断和治疗。方法回顾我院11例胃肝样腺癌的临床病理特点及其诊断和治疗。结果 11例肝样腺癌平均59.27岁,其中男性9例;治疗前血清AFP均升高(5/5);病变均为溃疡或溃疡型肿物、低分化或中低分化腺癌伴部分肝样腺癌,位于胃窦部2例,胃体部3例,贲门部6例;同时有肝转移者5例(5/11);手术切除者7例,其中3例行根治性手术;7例患者均有淋巴结转移;临床病理分期Ⅲ期2例、Ⅳ期9例;5例手术患者、3例未手术患者行不同疗程的全身化疗±介入化疗;患者总体预后差,死亡4例,其生存期为1～10个月。结论胃肝样腺癌是一类特殊的胃癌,容易发生淋巴结、肝脏转移,临床疗效差,应予以重视。     

胃肝样腺癌诊疗现状及进展

本文主要介绍胃癌当中一种很少见的特殊亚型,胃肝样腺癌,这种腺癌在发病机制、病理、治疗与预后方面与传统胃癌有较大区别。因其兼有胃癌及肝细胞癌的特征,很容易在临床上造成漏诊与误诊,因此我们有必要把胃肝样腺癌与胃癌区分开来,进一步提高胃肝样腺癌的诊出率,并降低其死亡率,延长生存期。     

胃肝样腺癌的免疫病理特点分析-附1例病例报告

目的:报道1例伴有神经内分泌特征的胃肝样腺癌,分析其病理组织形态学特点及临床表现。方法:组织形态学结合免疫组织化学研究。结果:本例胃肝样腺癌患者血清AFP水平显著升高;组织学检查显示该肿瘤由类似肝细胞肝癌和腺癌两种病变组成;免疫组织化学染色显示,病变组织表达AFP、PLAP和HCG。结论:伴PLAP和HCG表达的胃肝样腺癌属于未分化癌,未分化癌其组织学特点与胃肝样腺癌相似;胃肝样腺癌伴有PLAP和HCG表达的机制及其生物学行为有待深入研究。     

Alpha-fetoprotein (AFP)-producing gastric carcinoma. Is it hepatoid differentiation?

Biochemical and immunohistochemical analyses were done on five cases of gastric carcinoma with excessive production of alpha-fetoprotein (AFP). Histologic and ultrastructural examination of these cases showed conventional poorly differentiated adenocarcinoma of cuboidal or polygonal tumor cells in the medullary area with scattered AFP-positive cancer cells. Comparative studies on serum AFP between these cases and in hepatocellular carcinoma (HCC) or in testicular yolk sac tumor cases using concanavalin A (ConA)-affinity and lens culinalis agglutinin A (LCA)-affinity sepharose columns revealed that the AFP derived from four cases had a high ConA nonadsorping rate and high LCA-reactive fraction similar to that of yolk sac tumor. The AFP from one case had a small LCA-reactive fraction similar to that of HCC. Further immunohistochemical study using several markers for liver cells or germ cell tumor did not show additional evidence of these tumor cells to differentiate into liver cells or yolk sac tumor cells. Thus, this study indicates that AFP-producing gastric carcinomas are not always derived from hepatoid differentiation of the foregut. These gastric carcinomas might be categorized into medullary tumor with gastrointestinal tract-specific AFP.     

PIVKA-II-producing advanced gastric cancer

We describe the case of a 68-year-old man with primary advanced adenocarcinoma of the stomach, who displayed extremely high plasma levels of protein induced by vitamin K antagonist (PIVKA)-II (15600mAU/ml) and normal levels of alphafetoprotein (AFP) (4ng/ml). Ultrasonography and dynamic computed tomography ruled out hepatocellular carcinoma (HCC) or liver metastasis. After preoperative chemotherapy, pancreatico-spleno total gastrectomy with D2 lymphadenectomy was performed. Postoperatively, plasma levels of PIVKA-II returned to within the normal range (29mAU/ml). Microscopic examination revealed stomach adenocarcinoma showing various histological types, such as moderately to poorly differentiated mucinous adenocarcinoma, but hepatoid differentiation of gastric adenocarcinoma was not detected. Localization of PIVKA-II and AFP within tumor cells was demonstrated by immunohistochemical staining using monoclonal antibodies. These results indicate that tumor cells from gastric cancer may produce PIVKA-II. Some cases of PIVKA-II- and AFP-producing advanced gastric cancer with liver metastasis have been reported, but this is the first report of gastric cancer without liver metastasis producing PIVKA-II alone.     

胃肝样腺癌的研究进展

原始多潜能干细胞在癌肿瘤发生发展过程中,由于分化的失常,某些胃癌可能向肝细胞、胎儿胃肠方向分化,从而发生肝样癌或肝样腺癌(HAS).HAS的预后非常差.到目前为止还没有看到大规模或长期的临床报道.研究发现预后相关因素为肝转移和淋巴转移.HAS在胃癌基础上对肝癌的完美"模拟"以及嗜血管牛长特性为其易发生肝转移的主要原因.     

Hepatoid adenocarcinomas of the stomach. An analysis of seven cases

Hepatoid adenocarcinomas of the stomach are gastric carcinomas with both adenocarcinomatous and hepatocellular differentiations. They usually produce large amounts of alpha-fetoprotein (AFP) with a Concanavalin A-binding property of hepatic type. In this study, these carcinomas occurred in older persons, with the antrum being a common site. Observed grossly, growth of the tumors was nodular and massive. Prognosis was poor because of frequent liver metastases. In the cytoplasms of tumor cells, various serum proteins were identified, including AFP, alpha-1 antitrypsin (AAT), alpha-1 antichymotrypsin (ACT), albumin, and prealbumin. Localizations of ferritin, prothrombin, and transferrin were demonstrated with less frequency. Adenocarcinomatous foci were composed of well-differentiated, intestinal-type epithelial cells and often contained carcinoembryonic antigen. These adenocarcinomatous and hepatoid areas were often intermingled with each other. There were extensive venous involvements by tumor cells. The poor prognosis of the tumors may be attributed to these involvements as well as to production of AFP and presence of AAT/ACT, which have immunosuppressive and protease-inhibitory properties, respectively.     

Tumor pulmonar productor de alfafetoproteína

The secretion of alfafetoprotein (AFP) by lung carcinoma is rare and few cases have been described. Morphologically, these tumors present a characteristic hepatoid differentiation, thus the term hepatoid adenocarcinoma has been suggested for them. We report two cases of lung carcinoma with secretion of AFP and hepatoid differentiation.     

An autopsy case of AFP-producing gastric carcinoma resembling hepatocellular carcinoma on light microscopy

We experienced an autopsy case of alpha-fetoprotein(AFP)-producing advanced gastric carcinoma with liver metastasis. Microscopically, the tumor was compose by medullary nests of poorly differentiated adenocarcinoma cells. The cells had an exclusively hepatoid pattern characterized by discrete masses, nests, and broad bands, consisting of large eosinophilic epithelial cells and separated by fibrous stroma. Immunohistochemical studies of hepatoid cells yielded a positive reaction for AFP, but negative for CEA. Electron microscopically, tumor cells possess a ductal lumina with abundant microvilli having a central core filaments, and secretory granules in cytoplasma. These findings suggest that the tumor cells differentiated into intestinal direction, irrespective of the appearance of their hepatoid features characterized by light microscopy.     

AFP阳性结肠癌和直肠癌的临床病理分析

报道４例罕见的ＡＦＰ阳性结肠和直肠癌，此癌多见于中、老年男性患者，具有独特的病理形态与临床生物学行为，血清ＡＦＰ明显增高。病理组织形态特点是：除１例为单纯性腺癌外，另３例均见两种不同而又密切相关的腺癌区和肝样分化区。免疫组织化学染色，显示在肝样区的癌细胞浆内含有ＡＦＰ、ＡＡＴ和ＡＣＴ成份，而在腺癌区的癌细胞浆内则以ＣＥＡ成份为主。此癌高度恶性，由于ＡＦＰ的免疫抑制作用，常发生肝转移（３／４），所以预后不良。本组４例均死亡，术后平均生存１６．２５个月。综合文献与本组结果，作者认为此癌应列为结肠与直肠癌的一个特殊亚型。     

Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment.

A right renal pelvic mass in a 72-year-old man was resected. The histologic appearance of the tumor was a mixture of tubular adenocarcinoma cells and hepatoid neoplastic cells, and there was a resemblance to hepatoid adenocarcinoma. The intraoperative level of serum alpha-fetoprotein (AFP) was calculated to be 2246 ng/ml, and the postoperative level ranges from 183.6 to 285.6 ng/ml. Lectin binding assays showed that the serum AFP was the hepatic carcinoma type. In a hepatoid portion, an iron-negative, brown to green pigment was positive for bile. Alpha-fetoprotein was immunohistochemically evident in the neoplastic cells. In addition to the hepatic differentiation, the tumor had differentiated into intestinal absorptive or pancreatobiliary tract cells, as deduced from the frequent presence of spicular bodies, a unique light microscopic feature equivalent to microvilli with an actin core. The hepatoid adenocarcinoma is a distinct type of AFP-producing carcinoma present in the organs with epithelium of endodermal origin. Hepatoid adenocarcinoma in the renal pelvis may arise from a metaplasia of neoplastic mesonephric cells into endodermal cells.