甲胎蛋白阴性的肝细胞肝癌5例临床病理观察

[目的]探讨甲胎蛋白(AFP)阴性的肝细胞肝癌(hepatocellular carcinoma,HCC)的病理形态特点及鉴别诊断。[方法]观察和分析5例HCC的临床和病理组织学特点及免疫组和染色结果。[结果]5例中女2例,男3例,年龄50~69(中位年龄58.8)岁。临床表现病毒性肝炎、肝硬化及肝部占位并血清AFP检测值阴性。光镜下癌细胞密度增加,肝板细胞层数增多,排列呈条索状、小梁状、实性巢团状,小梁周围为扩张不规则的肝窦,癌细胞大小不一,异型性明显,细胞胞浆嗜酸核分裂像易见。免疫组化:5例AFP、CD10、CK7、CK20、GCDFP15、ER、PR、CK19、CDX-2、CEA均为阴性,CD34、VIllin均为阳性,Hep pax1 3例阳性、1例阴性、1例点灶阳性。[结论]APF阴性的HCC是少见病理类型,结合其临床症状、部位、组织病理特点和免疫组化标记可确定诊断。     

胃癌表皮生长因子与表皮生长因子受体与增殖细胞核抗原表达的意义

目的观察胃癌细胞表皮生长因子（Epidermalgrowthfactor，EGF），表皮生长因子受体（Epidermalgrowthfactorreceptor，EGFR）与增殖细胞核抗原（Proliferatingcellnuclearantigen，PCNA）表达的关系．方法23例胃癌切除标本用免疫组织化学染色法检测EGF、EGFR与PCNA．组织学分型，乳头状腺癌3例，管状腺癌6例，低分化腺癌14例．对EGFR阳性胃癌以镜面切片染色法，计算出EGFR阳性癌细胞以及EGFR阴性癌细胞PCNA数．资料以studentt测验进行统计学处理．结果EGF阳性胃癌14例（60．9％），EGFR阳性胃癌5例（21．7％），EGF与EGFR同为阳性胃癌3例（13％）．EGFR阳性胃癌细胞PCNA阳性率为49．95％±20．30％，EGFR阴性胃癌18例细胞PCNA阳性率为28．48％±18．18％，EGF与EGFR同为阴性7例，PCNA阳性率为18．82％±14．24％，差异性有显著意义（P＜0．05）．5例EGFR阳性胃癌镜面切片免疫组织化学染色结果，EGFR阳性癌细胞与EGFR阴性癌细胞PCNA阳性率分别为49．95％±20．30％与39．68％±17．88％．5例EGFR阳性胃癌和3例EGFR与EGF同为阳性胃癌中，全部为低分化型腺癌，且均有静脉浸润．结论EGFR阳性胃癌细胞PCNA高表达表明，EGFR与EGF配体结合可促进癌细胞异常分裂增殖．EGFR与EGF表达与肿瘤高浸润性低分化性相关，     

胃肝样腺癌9例并文献复习

目的探讨胃肝样腺癌的病理形态和临床特点。方法回顾性分析2005年1月至2012年1月崇阳县人民医院收治的9例胃肝样腺癌患者的临床资料。结果 9例患者临床表现以上腹部疼痛、腹胀、黑便等消化道症状为主;血清甲胎蛋白(AFP)含量异常持续增高(92.34～1 984.03 ng/ml),阳性率为77.78%(7/9);B超或CT检出伴有肝转移者为33.33%(3/9):该病以胃窦部多发,占66.67%(6/9),病理类型多为溃疡型(77.78%,7/9);胃癌组织内出现肝细胞癌样分化区是其特有的病理形态,9例患者平均存活19个月。结论胃肝样腺癌具有独特的病理形态和临床特点,血清AFP阳性,发病年龄高,易转移,治疗及预后较其他胃腺癌差,应引起临床医师足够重视。     

胃肝样腺癌6例临床资料分析

[目的]探讨胃肝样腺癌患者的临床表现、治疗以及预后。[方法]回顾性分析6例手术病理证实为胃肝样腺癌患者的临床、病理资料。[结果]6例胃肝样腺癌占医院同期入院胃癌患者的0.4%(6/1 494);1例表现为癌肉瘤,血清甲胎蛋白(AFP)阳性5例,均明显高于正常值上线;3例行根治性手术及化疗,1例行全胃+脾+胰切除及化疗,1例行单纯化疗,1例保守治疗。临床及术后病理提示,6例均有淋巴结转移,其中有2例伴远处转移,术后AFP无明显下降。随访全组患者存活时间2~10个月。[结论]胃肝样腺癌临床表现无明显特异性,病理诊断是其金标准,AFP可用于胃肝样腺癌早期诊断及疗效的判断,部分胃肝样腺癌可以合并肉瘤成分。胃肝样腺癌预后极差,治疗效果欠佳。     

60例胃黏液腺癌患者淋巴结CK表达及意义

60例胃黏液腺癌根治性切除标本,选取常规HE染色有淋巴结转移患者的阴性淋巴结168枚（A组）和无淋巴结转移者的淋巴结351枚（B组）,采用免疫组织化学染色检测细胞角蛋白（CK）表达。结果CK阳性39例,淋巴结总转移率65．0％,其中A组CK阳性58枚（33．4％）,B组CK阳性59枚（16．8％）。认为对胃黏液腺癌根治性切除术标本HE检查阴性的淋巴结应行常规CK免疫组化检查,以确定是否存在微转移。     

AFP阳性或阴性的肠道肝样腺癌的病理及临床特征

目的探讨甲胎蛋白(?-fetoprotein,AFP)阳性或阴性的肠道肝样腺癌(hepatoid adenocarcinoma,HAC)的病理特征、诊断治疗及预后.方法收集2010-01/2016-07就诊于西京医院并经病理科确诊为肠道HAC的病例3例,观察记录患者临床相关症状,用电化学发光方法检测血清内肿瘤标志物,影像科检查肝及肺转移情况,手术后标本行常规病理及免疫组织化学验查染色,观察分析病理特征,随访预后并进行回顾性分析.结果术前患者血清学AFP检查,1例呈高浓度阳性,并发生肝转移,1例为阴性,1例未查.3例患者均行肠癌根治术,病理学特征为可见到肝细胞样和腺样两种分化,肝细胞样分化区瘤胞浆内可见嗜酸性玻璃样小体,免疫表型为AFP和/或Hepatocyte阳性.术后临床病理分期为3期2例、4期1例,淋巴结转移2例,均可见或经免疫组织化学染色提示脉管、神经侵犯.患者术后随访时间为2-16 mo,1例死亡,2例生存.结论HAC患者临床症状无特异性,具有特征性的病理学特征和免疫表型,需与肝细胞癌及卵黄囊瘤相鉴别.依靠血清学诊断肠道HAC不可行,但其可能预测肿瘤的生物学行为及转移、复发情况,AFP阴性的患者预后可能要比阳性的好.     

胃肝样与非肝样腺癌的临床对比研究

目的探讨胃肝样与非肝样腺癌的临床病理差异．方法以胃肝样腺癌（２４例）为研究对象，以胃非肝样腺癌（１１２８例）为对照组，由２名以上作者对全部病例的临床病理资料进行回顾性分析．采用放射免疫双抗法和ＡＢＣ免疫组化法检测９５６例（含部分门诊病例）胃癌患者血清ＡＦＰ和４５例石蜡包埋胃癌组织中的ＡＦＰ及ＣＥＡ．对１４０例胃癌患者术后进行了随访．结果对比行卡方检验．结果脉管浸润率、术前肝及其它脏器转移率和术后１年死亡率胃肝样腺癌组和非肝样腺癌组分别为７５００％，２０８３％，８３３％，５０００％及５３３２％，１６０％，０８０％，２８４５％．前组明显高于后组（Ｐ＜００５，Ｐ＜００１）．而发病年龄、性别分布、好发部位及大体类型两组相似．淋巴结转移率无显著性差异（Ｐ＞００５）．结论胃肝样腺癌比一般类型胃癌在生物学行为上更易浸润腺管，肝转移率高，预后差．     

CD34和VEGF在肝癌组织中的表达及与肿瘤血管生成的相关性

目的探讨CD34和血管内皮生长因子（VEGF）在肝细胞肝癌（HCC）组织中的表达及微血管密度（MVD）的临床病理意义。方法应用链霉素扰生物素蛋白-过氧化物酶法（S—P法）对50例HCC患者进行肿瘤血管生成免疫组织化学检测。对CD34阳性血管进行MVD计数．对VEGF进行半定量计数，并分析与HCC的临床病理特征的关系及意义。结果CD34在HCC组织中呈广泛、窦隙状表达，MVD值在有汇管区癌栓和肝内转移者高于无汇管区癌栓和无肝内转移者（P〈0．05），VEGF表达的阳性率在有汇管区癌栓和肝内转移者明显高于元汇管区癌栓及无肝内转移者（P〈0．05）。MVD值在VEGF阳性组和阴性组之间差异有显著性（P〈0．05）。结论HCC中MVD值和VEGF阳性表达率明显增高，由自分泌和旁分泌产生的VEGF通过促进HCC肿瘤血管生成而促进HCC的生长和转移。     

产甲胎蛋白胃癌

产甲胎蛋白胃癌（AFPGC），被认为是一种特殊类型甲癌，组织学上含髓样癌和乳头状或管状腺癌两种成分，前者的癌细胞含甲胎蛋白（AFP），临床上伴血清AFP增高，其异质体的研究表明，系胃肠道特异性AFP，与普通胃癌相比，其肝转移率高，预后差。     

胃腺癌组织P53,P63和P73蛋白表达的意义

目的:探讨P53,P63和P73蛋白表达与胃腺癌临床病理特征之间的关系．方法:用免疫组织化学技术,检测72例胃腺癌及其癌旁正常组织中P53,P63和P73蛋白表达情况．所有研究对象均为湖北地区汉族人．其中,癌肿位于胃远端(胃窦、胃角)51例,胃近端(胃底、胃体)21例;肠型GAC 44例、弥漫型28例;高分化腺癌20例、中分化腺癌29例、低分化和未分化腺癌23例;TNM分期:Ⅰ和Ⅱ期13例,Ⅲ和Ⅳ期59例．结果:胃腺癌组织中P53,P63和P73蛋白阳性表达率均明显高于正常组织(X2=4．72,P<0．05; X2=5．51,P<0．05;X2=9．75,P<0．01);胃窦／胃角腺癌与胃底／胃体腺癌组织P53蛋白表达率无显著差异(P>0．05);在弥漫型胃腺癌中的表达率明显高于肠型胃腺癌(X2=4．68,P<0．05);在低分化腺癌与高中分化腺癌之间以及Ⅲ,Ⅳ期腺癌与Ⅰ,Ⅱ期胃腺癌之间的表达率的差异均有显著性(X2=7．06,P<0．05;X2=3．95, P<0．05)．P63蛋白在低分化腺癌组织中表达率明显高于高中分化腺癌(X2=7．36,P<0．05);在胃窦／胃角腺癌与胃底／胃体腺癌之间、在弥漫型与肠型胃腺癌之间、在Ⅰ,Ⅱ期胃腺癌与Ⅲ,Ⅳ期腺癌之间均无显著差异．P73蛋白在Ⅰ,Ⅱ期胃腺癌组织中的阳性表达率明显低于Ⅲ,Ⅳ期腺癌(X2=4．14,P<0．05),在胃窦／胃角腺癌与胃底／胃体腺癌之间、在弥漫型与肠型胃腺癌之间、在高、中及低分化胃腺癌之间均无显著差异．在P53蛋白阳性与阴性表达的胃腺癌之间,P63和P73蛋白阳性表达率的差异无显著性．结论:P53,P63和P73过度表达与胃腺癌的发生相关联,但并无交互作用．     

Preliminary study on the clinical and pathological relevance of gastric hepatoid adenocarcinoma

OBJECTIVE: To appraise the histological characteristics and clinical features of gastric hepatoid adenocarcinoma (GHAC) and their relevance with prognosis. METHODS: From January 2001 to December 2003, six patients were diagnosed and confirmed pathologically in Ruijin Hospital as having a gastric hepatoid carcinoma. All these six patients, together with 30 randomly selected patients with gastric poorly differentiated adenocarcinoma (GPDA) and 30 with a primary hepatocellular carcinoma (HCC) who served as controls, were studied and analyzed clinically, histologically and immunohistologically. RESULTS: The average age of the six patients with GHAC was 66.8 years, and their serum alpha fetoprotein (AFP) level was 84–2230 ng/mL. Of these six patients, two had a recurrence of cancer and two had liver metastasis. Their average survival period was 17 months. Morphologically, the histological appearance was similar to that of HCC, with glycogen granules and hyaline globules arranged in a solid or trabecular pattern and an abundance of blood vessels and sinusoids, while blood vessel or lymphatic invasion were more often seen. Immunohistological staining showed that the tumor cells were positive for AFP and negative for Hepatocyte paraffin 1 (HepPar1), and the tumor cells were separated by CD34‐positive blood vessels into a small trabecular pattern. The GPDA had a solid nest or diffuse distribution pattern and was negative for both AFP and HepPar1. In the HCC, the histological feature was manifested as solid, small and large trabecular patterns with abundance of blood vessels and sinusoids; immunohistochemical staining showed the tumor cells were positive for HepPar1. CONCLUSION: Serum AFP‐positive GHAC occurred more frequently in older patients with higher rates of recurrence and liver metastasis and a poor prognosis. Histologically, GHAC was similar to HCC. The tumor cells that were positive for AFP but negative for HerPar1 could be used to differentiate with GPDA (both AFP and HerPar1 negative) and primary HCC (most AFP and HerPar1 positive).     

Solitary AFP- and PIVKA-II-producing hepatoid gastric cancer with giant lymph node metastasis

A 61-year-old man was admitted to our hospital because of abdominal pain and an abdominal mass. The patient had anemia and elevated serum alpha-fetoprotein (AFP) (9630ng/mL) and PIVKA-II (91mAU/mL) levels. Roentgenographic examination revealed an extra-gastric tumor in the upper abdomen, and gastroscopy revealed Bormann type 2 gastric cancer in the lower portion of the stomach. The preoperative diagnosis was synchronous gastric cancer and hepatocellular carcinoma (HCC), and surgery was performed. The extra-gastric tumor appeared to be an extra-hepatically growing HCC because the tumor was fed by vessels ramifying from the umbilical portion of the liver. Distal gastrectomy with resection of the extra-gastric tumor was performed, and histological examination of the resected specimen revealed that the gastric cancer was an AFP-producing hepatoid gastric adenocarcinoma and that the extra-gastric tumor was a lymph node metastasis. AFP-producing hepatoid gastric adenocarcinoma tends to metastasize to the regional lymph nodes and form a giant tumor. A giant tumor in the upper abdomen associated with gastric cancer may therefore be a clinical manifestation of AFP-producing hepatoid gastric adenocarcinoma.     

Hepatoid adenocarcinoma of the gallbladder

We describe here a rare case of hepatoid adenocarcinoma (HAC) of the gallbladder without the production of alpha‐fetoprotein (AFP). A 77‐year‐old man was referred to our division with complaints of general fatigue, loss of appetite, and loss of body weight. A preoperative diagnosis of advanced gallbladder cancer was made, and cholecystectomy with combined resection of two liver subsegments (S4a + S5) and lymph node dissection were performed. Microscopically, the tumor was mainly composed of characteristic cells featuring eosinophilic cytoplasm, enlarged nuclei, and prominent nucleoi, arranged in nests or proliferated in a trabecular pattern. These features were highly suggestive of HAC of the gallbladder, and the tumor cells were negative for AFP immunohistochemical staining. The patient is doing well and has survived for 15 months postoperatively without any recurrence.     

Protein induced by vitamin K absence or antagonist II-producing gastric cancer

Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a putative specific marker of hepatocellular carcinoma (HCC), but it may also be produced by a small number of gastric cancers. To date, 16 cases of PIVKA-II-producing gastric cancer have been reported, 2 of which were reported by us and all of which were identified in Japan. There are no symptoms specific to PIVKA-II-producing gastric cancer, and the representative clinical symptoms are general fatigue, appetite loss, and upper abdominal pain. Serum alpha-fetoprotein (AFP) levels are also increased in almost all cases. Liver metastasis is observed in approximately 80% of cases and portal vein tumor thrombus is observed in approximately 20% of cases. Differential diagnosis between metastatic liver tumor and HCC is often difficult. Grossly, almost all cases appear as advanced gastric cancer. Histologically, a hepatoid pattern is observed in many cases, in addition to a moderately to poorly differentiated adenocarcinoma component. The production of PIVKA-II and AFP is usually confirmed using immunohistochemical staining. Treatment and prognosis largely depends on the existence of liver metastasis, and the prognosis of patients with liver metastasis is very poor. PIVKA-II may be produced during the hepatocellularmetaplasia of the tumor cells.     

原发性肝癌患者外周血中甲胎蛋白mRNA的意义

目的由于ＰＣＲ技术的应用,血循环中癌细胞的检测近有很大进展．本文用ＲＴＰＣＲ检测肝癌（ＨＣＣ）和其他慢性肝病患者外周血中ＡＦＰｍＲＮＡ,藉以反映ＨＣＣ细胞的存在,并与其他血清标记物比较．方法ＨＣＣ患者２２例,肝硬变和慢性乙型肝炎患者各１０例,健康成人受试者（对照）５例．取患者和对照的外周血,分离单核细胞,提取总ＲＮＡ并作电泳鉴定,用合成的两对引物进行巢式ＲＴＰＣＲ扩增ＡＦＰｍＲＮＡ,同时分析血清ＡＦＰ和乙肝标记物．结果ＡＦＰｍＲＮＡ在１３例ＨＣＣ（５９１％）,２例肝硬变（２００％）患者外周血中测到,其余标本均为阴性．ＡＦＰｍＲＮＡ阳性的１３例患者肿瘤均大于５ｃｍ,为晚期患者．在该１３例患者中仅有６例（４６１％）在血清中测到ＡＦＰ,但有１２例（９２３％）ＨＢｓＡｇ,抗ＨＢｅ,抗ＨＢｃ全阳性,而ＡＦＰｍＲＮＡ阴性的５例该３标记物全阴性．结论ＲＴＰＣＲ扩增ＡＦＰｍＲＮＡ是检测ＨＣＣ和肝硬变患者循环肝癌细胞的敏感方法．患者外周血中的ＡＦＰｍＲＮＡ有可能作为肿瘤转移和复发的标记对ＨＣＣ诊断、随访观察和疗效评定有较大临床意义．     

α-Fetoprotein-producing adenocarcinoma of the pancreas presenting focal hepatoid differentiation

Summary We report a rare case of pancreatic carcinoma producing α-fetoprotein (AFP), showing focal hepatoid differentiation in metastatic lymph nodes. A 65-yr-old female was admitted because of abdominal pain. The serum AFP was measured at 16,170 ng/mL. Radiological examinations revealed a mass measuring 6 cm in diameter in the body and tail of the pancreas. A right supraclavicular lymphadenopathy was found and biopsied. Light microscopy showed a tumor consisting of a portion of a hepatoid area and well-differentiated adenocarcinoma, which was suggestive of a hepatoid adenocarcinoma. Immunohistochemical analysis showed that the tumor cells expressed AFP, α₁-antitrypsin (AT) and albumin. Although the pathological diagnosis of the primary pancreatic tumor was not obtained, this appears to be the first case of hepatoid adenocarcinoma of the pancreas.     

Cerebral metastasis from hepatoid adenocarcinoma of the stomach

We first report a rare case of metastasis from gastric hepatoid adenocarcinoma （HAC） to cerebral parenchyma, in a 50-year-old Chinese patient. He complained of a one-month history of a paroxysm of headache in the left temple and pars parietalis accompanied with binocular caligation caligo, insensible feeling of limbs and transient anepia. Magnetic resonance （MR） imaging revealed a spherical occupying lesion in the left posterior-temple lobe which was clinically diagnosed as a metastatic tumor. Three years ago, the patient accepted total gastrectomy as he was pathologically diagnosed at gastroscopy having an adenocarcinoma. Eight months after gastrectomy, the occupying lesion in liver was detected by ultrasound and CT, and he accepted transcatheter arterial embolization. Before operation of the brain metastasis, no obvious abnormality was found in liver by ultrasound. Histopathological characteristics of the brain tumor were identical to those of stomach tumor. The growth pattern of both tumors showed solid cell nests. The tumor cells were polygonal, and had abundant eosinophilic cytoplasm and round nuclei with obvious nucleoli. Sinusoid-like blood spaces were located between nodular tumor cells. Immunohistochemistrystained tumor cells were positive for AFP and negative for Hep-Par-1. According to these histopathological findings, both tumors were diagnosed as HAC and metastatic HAC. The patient remained alive 16 mo after tumorectomy of the cerebral metastasis. The differential diagnosis of brain metastasis from metastatic tumors should use a panel of antibodies to avoid confusing with the brain metastasis of hepatocellular carcinoma （HCC）. This paper describes this rare case of metastasis from gastric hepatoid adenocarcinoma to cerebral parenchyma, and provides a review of the literature concerning its histopathological and immunohistochemical characteristics.     

alpha-Fetoprotein-producing adenocarcinoma of the pancreas presenting focal hepatoid differentiation.

We report a rare case of pancreatic carcinoma producing alpha-fetoprotein (AFP), showing focal hepatoid differentiation in metastatic lymph nodes. A 65-yr-old female was admitted because of abdominal pain. The serum AFP was measured at 16,170 ng/mL. Radiological examinations revealed a mass measuring 6 cm in diameter in the body and tail of the pancreas. A right supraclavicular lymphadenopathy was found and biopsied. Light microscopy showed a tumor consisting of a portion of a hepatoid area and well-differentiated adenocarcinoma, which was suggestive of a hepatoid adenocarcinoma. Immunohistochemical analysis showed that the tumor cells expressed AFP, alpha 1-antitrypsin (AT) and albumin. Although the pathological diagnosis of the primary pancreatic tumor was not obtained, this appears to be the first case of hepatoid adenocarcinoma of the pancreas.     

Human chorionic gonadotropin and alpha-fetoprotein in cholangiocarcinoma in relation to the expression of ras p21: an immunohistochemical study

The immunohistochemical localization of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) was studied in 44 cases with cholangiocarcinoma (CC) to determine the correlation to the expression of ras oncogene product p21 on tumor cells. HCG-immunoreactivity was found in 10 of 44 cases (23%) and AFP in only one (2.3%), whereas the expression of ras p21 was demonstrated in 39 (88.6%). The incidence of HCG-positive cells within the tumor was less than 1% in 8 of 10. The incidence of AFP-positive cells was less than 0.01%. All were histologically classified as adenocarcinoma and none of them had histologic features of trophoblastic tumors, yolk sac tumor or hepatocellular carcinoma. Nine of 10 HCG-positive and one AFP-positive CC expressed ras p21 on their tumor cells. However, one HCG-positive CC was negative for ras p21, though the incidence of HCG-positive cells within the tumor was 25%. HCG- and AFP-immunoreactivity was more frequently observed in poorly or undifferentiated tumor cells than in moderately or well-differentiated areas, whereas the expression of ras p21 was more diffuse in well-differentiated tumor and stronger in moderately differentiated areas, but rarely found in poorly and undifferentiated tumor. These results suggest that HCG production by CC of the usual adenocarcinoma variety is not rare, when compared to AFP production, and is preferentially localized in a small number of poorly differentiated and undifferentiated carcinoma cells, and there is no correlation between the production of HCG or AFP and the expression of ras p21 in CCs.