Immunohistochemical study of pancreatoblastoma

Three cases of pancreatoblastoma in children were examined immunohistochemically and the results were compared with those of pancreatic duct carcinoma in adults. The pancreatoblastoma demonstrated positive reactions to alpha-fetoprotein (AFP) (67%: 2/3), alpha-1-antitrypsin (AAT) (100%: 3/3), carcinoembryonic antigen (CEA) (67%: 2/3) and keratin (33%: 1/3), although CEA was only weakly positive in both cases. On the other hand, adult pancreatic duct carcinoma showed positive reactions as follows; AFP: 3% (1/29), AAT: 21% (6/29), CEA: 97% (28/29) and keratin: 93% (27/29). Also, endocrine substances including insulin, glucagon and somatostatin were all negative in the pancreatoblastomas. Two cases of pancreatoblastoma which were immunohistochemically positive for AFP also showed elevation of the serum AFP level clinically. The different expressive pattern of oncofetal antigens in pancreatoblastoma as compared with pancreatic duct carcinoma in adults may provide further supporting evidence for the embryonic nature of pancreatoblastoma, and suggests that such a pattern might be used as a tumor marker for pancreatoblastoma.     

The significance of alpha-fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours

One hundred benign and malignant primary liver tumours were screened immunocytochemically for alpha-fetoprotein (AFP), alpha 1-antitrypsin, alpha-human chorionic gonadotropin, carcinoembryonic antigen (CEA), keratin and vimentin. Alpha-fetoprotein was found in 16/63 (24%) hepatocellular carcinomas and in two hepatoblastomas. When comparing tissue positivity for AFP with tumour differentiation, grade 1 hepatocellular carcinomas were found to be negative, while 21% of grade 2, 36% of grade 3 and 16% of grade 4, respectively, stained positively. Alpha-fetoprotein positive cells were present in 9/10 hepatocellular carcinomas with serum levels exceeding 5000 ng/ml, but were absent in 17 tumours with serum AFP levels below 5000 ng/ml. All tumours other than hepatocellular carcinomas and hepatoblastomas were AFP negative. Carcinoembryonic antigen was present in 72% of cholangiocarcinomas, but was demonstrated in only one hepatocellular carcinoma. This exception was a combined hepatocellular-cholangiocarcinoma in which CEA expression was restricted to the cholangiocellular part. Alpha 1-antitrypsin was found in 4/63 hepatocellular carcinomas, in 2/2 fibrolamellar carcinomas and in 2/18 cholangiocarcinomas. Alpha-human chorionic gonadotropin was detected in one hepatocellular carcinoma and was strongly expressed in both fibrolamellar carcinomas. Weak staining for keratin was seen in most tumours with hepatocellular differentiation. All cholangiocarcinomas, in contrast, were strongly labelled with the keratin antibody. Co-expression of keratin and vimentin was observed in seven poorly differentiated hepatocellular carcinomas and three cholangiocarcinomas as well as in the two hepatoblastomas. The findings suggest that AFP is a diagnostic but rather insensitive immunocytochemical marker for hepatocellular differentiation in malignant liver tumours; CEA and keratin may help in discriminating cholangiocarcinomas from hepatocellular carcinomas.     

Pancreatoblastoma with marked elevation of serum alpha-fetoprotein

Summary The autopsy findings in a pancreatoblastoma in a 7-year-old Japanese girl is reported. The tumour was in the head and body of the pancreas, and was associated with diffuse carcinomatous peritonitis and hepatic and pulmonary metastases. There was marked elevation (more than 10000 ng/ml) of serum alpha-fetoprotein (AFP). Histopathologically the tumour was composed of solid epithelial elements with fibrous stroma, showing acinar arrangement, squamoid clusters and tubular structures. The epithelial elements contained numerous fine PAS positive granules in the cytoplasm. Immunocytochemical results suggested epithelial differentiation with positivity to alpha-1-antitrypsin (AAT), keratin, CA19-9, and AFP. No endocrine elements were recognized. Characteristic feature of this tumour are discussed and compared with prevoius reports.     

Alpha-fetoprotein production by pancreatic tumors exhibiting acinar cell differentiation: study of five cases, one arising in a mediastinal teratoma

Five cases of pancreatic neoplasms accompanied by production of alpha-fetoprotein (AFP) and serum elevation of this marker are presented, and the better-documented cases of this phenomenon from the literature are reviewed. Four of the cases originated in the orthotopic pancreas, whereas the fifth arose in the pancreatic component of a mediastinal teratoma. The patients were children or young adults. AFP production in pancreatic tumors is closely linked to acinar differentiation, most cases representing either pancreatoblastoma or acinar cell carcinoma. The distinction between these 2 tumors may be difficult because of the many morphologic and immunohistochemical features they share.     

Immunohistochemical characterization of 130 cases of primary hepatic carcinomas

Primary liver carcinoma (PLC) may express a certain number of markers. Here we communicate results of an analysis of five such markers (alpha-1-antitrypsin--AAT--, carcino-embryonic antigen --CEA--, alpha-fetoprotein --AFP--, and superficial --HBsAg-- and core --HBcAg-- antigens of hepatitis B virus) by means of PAP techniques in 130 cases of PLC, comparing the neoplastic tissue and the non-tumorous liver. Three variants of PLC are distinguished: hepatocarcinoma (HC) (108 cases); cholangiocarcinoma (CC) (19 cases); and three cases of hepatocholangiocarcinoma (HCC). AAT was positive in 29 HC, 2 HCC, and negative in all 19 CC. CEA appeared positive in 16 HC, 16 CC and only one HCC. AFP was positive in two HC, and negative in all CC and HCC. HBsAg displayed positivity in 15 HC and one HCC, being negative in all 19 CC. HBcAg was positive in 4 HC, and negative in all CC and HCC. HBsAg was also positive in two neoplastic emboli associated with HC. On the non-tumorous liver tissue the immunohistochemical results showed positivity for AAT and CEA, but not for AFP. Therefore the present results confirm that in the geographical area from which these tumors proceed, PLC is closely correlated with HBsAg positivity and with cirrhosis.     

Diagnostic and Follow-up Studies on CEA, AFP and ALP4 Isoenzyme in the Sera of Gynecological Malignancies

Simultaneous determination of CEA, AFP and ALP₄ was made in patients with various gynecological malignancies. CEA was positive in 65%, AFP was positive in 1.8% of 55 cases with cervical carcinoma stage 0—-II. ALP₄ was positive in one patient in these stages. In the group of cervical carcinoma stage III, stage IV and recurrence, CEA and AFP were positive in 100% and in 8.6% of 35 cases respectively. ALP₄ was positive in 14.3%. High levels and/or progressively increasing CEA with positive ALP₄ were found to be significant in poor prognostic patients in whom ALP₄ was not always found positive. Out of 17 cases with endometrial carcinoma, CEA was positive in 12 patients. AFP and ALP₄ were each positive in one case. Of 30 cases with ovarian carcinoma, CEA was positive in 70%, AFP in 23% and ALP₄ in 14%. Increasing CEA and/or increasing AFP appeared to be correlated with poor prognosis. In the group of 5 vulvar carcinoma, only CEA was positive in 80% of the patients. Of 19 cases of choriocarcinoma, CEA was positive in 11%, AFP was positive in 5.3% and ALP₄ was positive in 5.6%. There existed reverse-correlation between serum CEA and AFP in some cases.     

Phenotypic characterization of hepatic proliferation. Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver

Different forms of hepatocellular proliferation are seen in fetal livers, massive hepatic necrosis, and nodular transformation (nodular regenerative hyperplasia) of the liver. In an attempt to characterize the proliferating cells in these conditions, we studied the expression of several antigens by immunohistochemical methods. Alpha-fetoprotein (AFP), alpha 1-antitrypsin (AAT), a hepatocellular export protein, carcinoembryonic antigen (CEA), a marker of bile duct epithelial cells, and hepatitis B virus antigens (HBsAg, HBcAg), were localized by the peroxidase-antiperoxidase method in 11 fetal livers, 10 cases of nodular transformation, and 7 cases of massive hepatic necrosis. AFP was the most prevalent antigen in fetal hepatocytes. Many hyperplastic hepatocytes in nodular transformation contained AAT, but not oncofetal antigens, supporting the differentiated hepatocellular nature of these cells. A similar staining pattern was seen in two-cell-thick plates of hepatocytes in massive hepatic necrosis. In contrast, the ductlike structures at the periphery of necrotic lobules contained both AAT and CEA, suggesting that these cells exhibit features of hepatocytes and bile duct epithelial cells. Therefore, the appropriate term for these regenerating cells appears to be "ductular" or "biliary hepatocytes".     

胰母细胞瘤的临床及病理学观察

目的 探讨胰母细胞瘤的临床病理、免疫组化特点和组织起源。方法 对１４例胰母细胞瘤患儿（男９例,女５例,年龄１．５￣８岁）,用ＨＥ、过碘酸雪夫（ＰＡＳ）、粘液卡红染色和免疫组化ＬＳＡＢ方法进行观察。     

Immunocytochemical localization of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (HCG) in cervical neoplasia

Sixty-one cases of invasive cervical carcinoma and 40 cases of dysplasia and carcinoma in situ were studied by peroxidase-antiperoxidase method (PAP) for the presence of carcinoembryonic antigen (CEA). Forty-two cases (13 carcinomas in situ and 29 invasive carcinomas) also were tested for alpha-fetoprotein (AFP) and human chorionic gonadotropin hCG. CEA was not detected in normal cervical epithelium but was present in 90% of the neoplastic lesions. Not mere presence, but a pattern of CEA tissue distribution emerged as the main differential point between noninvasive and invasive lesions. Twenty-nine of 51 invasive squamous carcinomas (57%) contained CEA-positive cells at the stromal edge of epithelium, while this feature was not found in dysplasia and carcinoma in situ. Adenocarcinomas and adenosquamous carcinomas all were positive for CEA, while clear-cell carcinomas were negative. AFP was present only in a case of poorly differentiated adenosquamous ("glassy cell") carcinoma. hCG has not been revealed in any of the tumors.     

Adenosquamous carcinoma of the pancreas: a clinicopathologic series of 25 cases.

BACKGROUND: Adenosquamous carcinoma is a rare aggressive subtype of pancreatic adenocarcinoma. We describe the clinical, pathologic, and molecular characteristics of 25 of these lesions, the largest series to date. METHODS: Twenty-five cases of adenosquamous carcinoma of the pancreas diagnosed between 1961 and 1994 were retrieved from the files of the Endocrine Registry of the Armed Forces Institute of Pathology. Histologic features were reviewed, histochemical, immunohistochemical, and molecular (k-ras) studies were performed, and patient follow-up was obtained. RESULTS: The patients included 17 men and eight women, aged 28 to 82 years (mean, 65.4 y). The patients usually experienced weight loss (n = 17) or painless jaundice (n = 11), while also presenting with other abdominal symptoms. The tumors affected the head most frequently (n = 17), followed by the tail (n = 9) or body (n = 4). Five cases involved more than one anatomic region of the pancreas. Microscopically, all tumors demonstrated dual differentiation toward adenocarcinoma and squamous cell carcinoma. All cases tested were immunoreactive with keratin (AE1:AE3 and CK1), whereas other keratin markers were variably expressed: CK5/6 (88%), CK7 (68%), Cam5.2 (41%), and CK20(26%). CA-19-9 (84%) and CEA (74%) were positive in the majority of the cases. K-ras oncogene mutations were identified in seven of 13 cases. All patients died from their disease an average of 5.8 months after diagnosis (range, 1 to 33 months). CONCLUSIONS: Adenosquamous carcinoma of the pancreas represents a distinct clinical and pathologic entity, demonstrating the expected immunoprofile and k-ras oncogene mutation of a ductal origin, with a worse prognosis than ductal adenocarcinoma.     

Pancreatic cancer and fibrinogen storage disease

BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon disorder which may be associated with hepatocellular carcinoma. Two cases of pancreatic carcinoma were encountered in a family with fibrinogen storage disease, further raising the possibility of a predilection to malignancy in this unusual disorder. The tumour in one case was of the rare clear cell type. These two cases are the basis for this report. METHODS: Sections were cut from retrieved paraffin embedded tissue and stained for routine histology. Immunohistochemistry using the avidin-biotin technique was applied for the expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2, epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA, and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS: Hepatocellular fibrinogen storage disease is rare and has been described in association with chronic hepatitis, cirrhosis, and rarely with hepatocellular carcinoma. This represents the first report of its association with carcinoma outside of the liver.     

Clinical usefulness of alpha-1-antitrypsin in the diagnosis of hepatocellular carcinoma.

Serum levels of alpha-1-Antitrypsin(AAT) were determined in 42 patients with hepatocellular carcinoma(HCC), 5 patients with metastatic liver cancer from stomach adenocarcinoma, 10 patients with liver cirrhosis, 10 patients with chronic hepatitis, and 66 controls by rocket immunoelectrophoresis using rabbit antiserum. The mean level of serum AAT was 225.5 +/- 73.0 mg/dl in 66 controls. The serum AAT in patients with HCC was 428.7 +/- 123.3 mg/dl, which was significantly higher than those in the controls and in patients with liver cirrhosis or chronic hepatitis(p less than 0.02). The level of AAT in metastatic liver cancer was similar to that in HCC. The positive cut-off value for elevation of serum AAT in this study was determined as above 445 mg/dl, the mean plus 3 standard deviations in the controls. Elevations of serum AAT were observed in 54.8%, 60.0%, and 10.0% of patients with HCC, metastatic liver cancer, and liver cirrhosis, respectively, while none of the patients with chronic hepatitis or the controls was positive. The serum AAT levels in 42 patients with HCC were analyzed with regard to sex, age, serum albumin, HBsAg, alpha-fetoprotein(AFP), and diameter of HCC, with no significant differences being observed between these factors and the serum AAT levels except for the diameter of the HCC. The positive rate in the HCC with a diameter of 10 cm or more was 74.1%, which was a significantly higher rate compared with 20.0% in the HCC with diameters less than 10cm. The positive rate of AFP for HCC was 61.9%, when 500 ng/ml of AFP was used as the cut-off value.(ABSTRACT TRUNCATED AT 250 WORDS)     

胰腺实体-假乳头状肿瘤32例临床病理分析及TFE3表达的诊断价值

目的 探讨胰腺实性-假乳头状肿瘤(solid-pseudopapillary neoplasms,SPN)的临床病理特征及转录因子E3(transcrip-tion factor E3,TFE3)表达在诊断中的价值.方法 采用免疫组化法检测32例胰腺SPN中TFE3、β-catenin、CD10、CK、vimen-ti...     

AFP阳性胃癌的组织形态及其分型研究

目的：探讨ＡＦＰ阳性胃癌的病理组织形态及其分型。方法：应用光镜、电镜、组化和免疫组织化学方法,对８７例ＡＦＰ生胃癌中临床病理资料较完整的６３例进行病理组织形态态观察,并用２例３个月妊娠的胚胎胃肠组织以同样方法行相关的对比研究。结果：ＡＦＰ阳性胃癌的发生泫为６．２％（８７／１３９５例）。６３例中依据其病理组织形态学特点和肿瘤组织内癌细胞ＡＦＰ染色阳性表达,并对比３个月妊娠胎胃肠组织学的改变,将其组织     

Liver cell dysplasia and hepatocellular carcinoma: a histoiogical and immunohistochemical study

Liver cell dysplasia (LCD) was found in 28 (60%) of 47 patients with hepatocellular carcinoma (HCC); 22 (79%) of them had associated liver cirrhosis. LCD was more frequently observed in posthepatitic cirrhosis (82%) than in the other forms. Carcinoembryonic antigen (CEA), alpha-1-antitrypsin (AAT) and alpha-fetoprotein (AFP), as demonstrated by the peroxidase-antiperoxidase method, were similarly expressed both in normal and in dysplastic cells. Hepatitis B surface antigen was found in eight cases (17%), six of which were associated with LCD. HBsAg was rarely found in dysplastic cells and frequently displayed a peculiar perinuclear pattern. The possible preneoplastic role of LCD is stressed.     

PANCREATIC CARCINOMA IN CHILDHOOD: Report of an Autopsy Case and a Review of the Literature

Clinical and histological findings of pancreatic carcinoma in a 6-year-old boy are reported. Gradual change of histological appearance of the tumor during his course of 3 years and elevation of serum alpha-1-fetoprotein (AFP) are documented. Two biopsy specimens showed immature histological appearance compatible with pancreatoblastoma, and autopsy material showed well-differentiated adenocarcinoma with distinct ductal and acinar differentiation. Electron microscopy demonstrated zymogen-like granules in the apical portion of the neoplastic cells. Immunoperoxidase method demonstrated AFP in the neoplastic cells in addition to alpha-1-antitrypsin. Literature of pancreatic tumor in the young was reviewed, and characteristics of this case were discussed. ACTA PATHOL. JPN. 35 : 1543–1554, 1985.     

Comparison of alpha-fetoprotein with some other tumour markers in Malaysians with hepatocellular carcinoma

Although alpha-fetoprotein (AFP) is regarded as the reference marker for hepatocellular carcinoma (HCC), it sometimes produces false results. The objective of this study was to see if some of the readily available laboratory markers could complement AFP to improve the laboratory diagnosis of HCC. The markers tested and their sensitivities were: CA 125, 92%; ferritin, 71.3%; CA 19-9, 69.8%; beta-2-microglobulin (B2M), 53.3%; CA 72-4, 13.6%; and carcinoembryonic antigen (CEA), 10.6%. In comparison, AFP had a sensitivity of 58.8%. CA 72-4 and CEA (at the "tumour" cut-off level of 20 ng/ml) had specificities of 100%, and AFP, 97.4%. The specificities of the other markers were less impressive: CEA, 77.8% (at the cut-off level of 5 ng/ml); ferritin, 48.6%; CA 125, 48.5%; B2M, 39.6%; and CA 19-9, 37.3%. The efficiencies of the markers for HCC, which are based on the consideration of sensitivity and specificity together, were as follows: AFP, 77.6%; CA 125, 71.3%; ferritin, 60.5%; CA 19-9, 55.3; B2M, 46.9%; CEA, 40.8%; and CA 72-4, 34.5%. The receiver-operating characteristic plots confirmed AFP to be the most efficient marker for HCC. Nevertheless, it is proposed that CA 125 be combined with AFP for HCC screening because of their excellent sensitivity and specificity, respectively: a negative result for both, or even just CA 125 alone, would indicate that the disease is unlikely while a positive AFP (which would likely occur with a positive CA 125) would make its presence highly probable. A positive CA 125 and negative AFP would be equivocal for HCC. Other markers in combination with AFP are less useful.     

Immunocytochemical staining of fine-needle aspiration biopsies of the liver as a diagnostic tool for hepatocellular carcinoma.

Fine-needle aspiration biopsy (FNAB) under ultrasonographic or computerized tomographic guidance is a useful diagnostic procedure for hepatic neoplasms. However, cytologic criteria alone may not allow for the distinction of hepatocellular carcinomas (HCC) from cholangiocarcinomas (CC) and metastatic adenocarcinomas (MA). In an effort to refine the FNAB diagnosis of hepatic malignancies, a panel of immunocytochemical stains was applied to aspiration specimens from primary and metastatic carcinomas in the liver. Anticytokeratin antibodies with different specificities (Cam 5.2 and AE1) were used in conjunction with antibodies to carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and alpha-1-antitrypsin (AAT). All HCC, CC, and MA were immunoreactive with the antikeratin antibody Cam 5.2. However, only three (15%) HCC were positive with AE1, in contrast to 100% of CC and MA. Antibodies to CEA and AFP were also helpful diagnostic aids, especially for the three HCC that were immunoreactive with AE1. Canalicular staining for CEA was present in 47% of HCC, but in none of the CC or MA. AFP positivity occurred in 45% of HCC, but only one CC and none of the MA. AAT was not a useful marker for HCC due to low sensitivity and specificity. Immunocytochemistry is an effective adjunct to the cytodiagnosis of malignant liver tumors sampled by FNAB.     

Keratin 14 immunoreactive cells in pleomorphic adenomas and adenoid cystic carcinomas of salivary glands

Our recent study of developing myoepithelial cells (MECs) in rat salivary glands demonstrated that developing MECs begin to express α-smooth muscle actin (αSMA) first and, thereafter, keratin 14. Therefore, it is unlikely that duct basal cells expressing keratin 14 alone are immature or undifferentiated MECs. In this study we carried out immunohistochemistry of pleomorphic adenomas and adenoid cystic carcinomas including normal salivary glands using monoclonal antibodies to keratin 14, smooth muscle proteins and keratin 19. The smooth muscle proteins examined included αSMA, h-caldesmon and h1-calponin; h1-calponin was observed in keratinocytes and nerve fibers, indicating that the protein is not specific to smooth muscle, whereas αSMA and h-caldesmon turned out to be highly specific markers for smooth muscle cells in normal tissues. In normal glands, MECs were positive for both keratin 14 and smooth muscle proteins (αSMA and h-caldesmon). Non-MEC cells were essentially devoid of smooth muscle proteins. Non-MEC duct basal cells expressed keratin 14 with or without keratin 19, and luminal cells keratin 19 with or without keratin 14. This suggests that the keratin 14-positive, smooth muscle proteins-negative duct basal cells are luminal cell progenitors. Luminal cells in tubular structures of both tumors were positive for keratin 19 with or without keratin 14. Nonluminal peripheral cells of pleomorphic adenomas were mostly positive for keratin 14, and a small fraction of them expressed smooth muscle proteins. Conversely, peripheral cells of adenoid cystic carcinomas were mostly positive for smooth muscle proteins, and some of them expressed keratin 14. These results strongly suggest (1) that the luminal cell progenitors transform into major constituents of pleomorphic adenoma cells with keratin 14 but not smooth muscle proteins, and (2) that the peripheral cells of adenoid cystic carcinoma are derived from undifferentiated MECs. Solid structures of pleomorphic adenomas were formed by proliferation of the peripheral cells. MECs were observed only occasionally in the periphery. Solid and cribriform structures of adenoid cystic carcinomas were formed by proliferation of the luminal cells. MECs were observed in the periphery and around the pseudocyst. Received: 2 December 1999 / Accepted: 12 January 2000     

Pancreatic carcinoma in childhood. Report of an autopsy case and a review of the literature

Clinical and histological findings of pancreatic carcinoma in a 6-year-old boy are reported. Gradual change of histological appearance of the tumor during his course of 3 years and elevation of serum alpha-1-fetoprotein (AFP) are documented. Two biopsy specimens showed immature histological appearance compatible with pancreatoblastoma, and autopsy material showed well-differentiated adenocarcinoma with distinct ductal and acinar differentiation. Electron microscopy demonstrated zymogen-like granules in the apical portion of the neoplastic cells. Immunoperoxidase method demonstrated AFP in the neoplastic cells in addition to alpha-1-antitrypsin. Literature of pancreatic tumor in the young was reviewed, and characteristics of this case were discussed.