Pancreas transplantation: an immunohistochemical analysis of pancreatic hormones and HLA-DR expression

The immunohistochemical features of pancreatic grafts in eight patients with pancreatic transplants were analyzed and compared with pancreases from five patients with chronic pancreatitis and with three pancreatic tissues without histological abnormalities. There was a significant increase in glucagon producing cells in patients with transplanted pancreases compared with those with chronic pancreatitis (P less than 0.05). A significant decline in insulin-producing cells was seen in the transplanted pancreases with rejection in comparison with normal pancreatic tissue. Immunohistochemical staining for HLA-DR (Ia) antigens revealed expression of HLA-DR by endothelial cells, mononuclear cells, and by some ductal epithelial cells, but not by the endocrine islet cells. These results suggest that significant changes in insulin and glucagon production occur in the transplanted pancreas with rejection and that HLA-DR is not expressed by islet cells during graft rejection or with chronic inflammation.     

Expression of Lewis antigens and their precursors in gastric mucosa: relationship with Helicobacter pylori infection and gastric carcinogenesis

Lewis (Le)-associated antigens are carbohydrates that are related biochemically to the ABO blood groups, and may have a role in Helicobacter pylori adherence. To evaluate their relationship to clinicopathological outcomes, gastric Le expression, including type 1 precursor, type 1 H, Le(a), Le(b), Le(x), Le(y) and sialylated Le(a) (CA19-9), was evaluated immunohistochemically in 233 gastric biopsy specimens obtained at routine gastroscopy. Expression was also investigated in gastric tissues showing chronic gastritis, intestinal metaplasia, and carcinoma from 42 patients with gastric cancer. A polymerase chain reaction was performed for H. pylori and the bacterial babA2 gene. We identified type 1 precursor expression in 34.3%, type 1 H in 55.8%, Le(a) in 44.2%, Le(b) in 82.0%, Le(x) in 44.2%, Le(y) 56.7%, and CA19-9 in 16.3% of the 233 gastric biopsy specimens. Expression of type 1 H, Le(b), and CA19-9 was significantly associated with H. pylori infection and histological features (p < 0.05), and expression of type 1 H was an independent predictive factor for H. pylori infection by multivariate logistic regression (p = 0.020). Positivity for the babA2 genotype correlated significantly with H. pylori infection and type 1 H expression in gastric biopsy specimens (p < 0.05). The babA2 genotype was more frequent in gastric mucosa from the gastric cancer patients than in gastric biopsy specimens from routine gastroscopy (p = 0.009). In the 42 gastric cancer patients, the frequency of type 1 precursor, Le(a), and Le(x) expression was significantly higher in intestinal metaplasia and carcinoma than in chronic gastritis (p < 0.05), but the frequency of type 1 H and Le(b) expression was significantly lower in intestinal metaplasia and carcinoma (p < 0.05). In conclusion, Le expression, especially that of type 1 H, was significantly associated with clinicopathological features. In gastric cancer patients, Le expression was altered in intestinal metaplasia and carcinoma in comparison with chronic gastritis.     

Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray based study.

Maspin, a member of the serpin family of serine protease inhibitors, has been shown to limit invasion and metastases in breast and prostate carcinomas. Maspin gene expression is up-regulated in pancreatic cancer, but not in normal pancreatic tissue. Maspin expression has been documented using immunohistochemical studies in pancreatic adenocarcinoma and high-grade intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic pancreatitis utilizing tissue microarray technology to determine the utility of maspin in differentiating these lesions. Immunohistochemistry was performed on tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24 cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or poorly differentiated using the WHO criteria. The primary antibody used was monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA). Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1 + to 3 + based on intensity. Cases were considered positive if one or more cores demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1 + to 2 +) staining within occasional benign ductal epithelial cells in 29% of cases (7/24). Diffuse and intense (3 +) staining was present in ducts with squamous metaplasia (3 cases). The majority of ducts showed no staining. Ductal adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally more intense staining than cases of chronic pancreatitis. Maspin may be helpful in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous metaplasia is ruled out.     

Development of intrapancreatic transplantable model of pancreatic duct adenocarcinoma in Syrian golden hamsters.

Intrapancreatic and subcutaneous (SC) inoculation of cultured pancreatic cancer cells, derived from an induced primary pancreatic cancer in a Syrian hamster, resulted in tumor take in all recipient hamsters. The intrapancreatic allografts grew rapidly, were invasive, and metastasized into the lymph nodes and liver in 2 of 9 cases. In comparison, SC tumors grew relatively slower and formed a large encapsulated mass without invasion and metastases. Histologically, tumors of both sites showed fairly well-differentiated adenocarcinomas of ductal/ductular type resembling the induced primary cancer. Similar to the primary induced pancreatic cancers, tumor cells of both allografts expressed blood-group-related antigens, including A, B, H, Le(b), Le(y), Le(x), and tumor-associated antigen TAG-72. The tumor cells did not express Le(a), CA 19-9, 17-1A, or DU-PAN-2. The expression of these antigens was retained in the metastases and presented the same patterns of reactivity as the allografts. Thus intrapancreatic transplantation provides a rapid model for production of pancreatic cancer with morphologic similarities to human pancreatic cancer.     

Expression of blood group-related antigens, ABH, Lewis(a), Lewis(b), Lewis(x), Lewis(y), CA19-9, and CSLEX1 in early cancer, intestinal metaplasia, and uninvolved mucosa of the stomach.

The expression of blood group-related antigens, A, B, H type 2, Lewis type 1 (Lewis(a) [Le(a)] and Lewis(b) [Le(b)]), Lewis type 2 (Lewis(x) [Le(x)] and Lewis(y) [Le(y)]), sialylated Le(a) (CA19-9), and sialylated Le(x) (CSLEX1), was analyzed sequentially with immunohistochemical methods in early gastric cancer, intestinal metaplasia, and uninvolved gastric mucosa obtained from 35 surgical specimens of patients who underwent gastrectomy. The high incidence of the inappropriate expression of Lewis type 1 antigens and the deletion of H and Lewis type 2 antigens was observed similarly in patients with cancer and intestinal metaplasia. The acquisition of CA19-9 and CSLEX1 and the deletion of B antigen frequently were found in intestinal-type cancer and all types of intestinal metaplasia. The simultaneous deletion of A antigen was detected only in the combination of intestinal-type cancer and incomplete-type intestinal metaplasia. Thus the present study shows that similar changes of tissue antigenicities exist in early gastric cancer and intestinal metaplasia.     

Immunohistochemical study of colorectal adenomas with monoclonal antibodies against blood group antigens (sialosyl-Le(a), Le(a), Le(b), Le(x), Le(y), A, B, and H)

We studied 40 colorectal adenomas with monoclonal antibodies against blood group antigens (sialosyl-Le(a), Le(a), Le(b), Le(x), Le(y), A, B, and H). Sialosyl-Le(a), Le(a), Le(x), and Le(y) are usually present in different compartments of the crypts of normal colorectum and can be considered markers of normal differentiation antigens (NDA). The former two antigens represent markers for differentiated colonic epithelium and the latter two, markers for "undifferentiated" crypt base epithelium. Le(b), A, B, and H are normally absent from the distal colon and rectum, but are expressed by fetal colon and carcinomas and are considered oncofetal tumor-associated antigens (OF-TAA). Individual adenomas could be characterized as to whether or not they expressed OF-TAA and NDA. Of the adenomas, 35% were OF-TAA+/NDA+, 40% were OF-TAA+/NDA-, 17.5% were OF-TAA-/NDA+, and 7.5% were OF-TAA-/NDA-. When NDA were present, they were expressed in the same compartment of the crypt as in the normal colon and rectum. In adenomas there was proliferation of the undifferentiated enterocyte marker Lex throughout the entire length of the crypt when compared with controls (p less than 0.01). Of the adenomas, 75% expressed OF-TAA, however, 35% of adenomas concomitantly expressed NDA in the same distribution as normal colon and rectum indicating that adenomas have features of both carcinoma and normal colorectum epithelium.     

Immunohistochemical study of type-1 blood antigen expressions in thyroid tumors: the significance for papillary carcinomas.

Immunohistochemical expressions of type 1 blood group antigens were studied for 95 cases of thyroid tumors, including 29 follicular adenomas, 23 follicular carcinomas, and 43 papillary carcinomas, applying monoclonal antibodies against DU-PAN-2, CA19-9, Lewis(a) (Le(a)), and Lewis(b) (Le(b)). Normal thyroid tissue invariably failed to express all four antigens. In follicular adenomas, DU-PAN-2 and CA19-9 were focally expressed in 7% and 21% of cases, and in follicular carcinomas, CA19-9 expression was limited to one case (4%); all cases were negative for DU-PAN-2. No or little expression of Le(a) or Le(b) was observed in these follicular tumors. In contrast, DU-PAN-2, CA19-9, Le(a), and Le(b) were expressed in 98%, 84%, 33%, and 49% of 43 papillary carcinomas, respectively. The positive stainings were observed mainly on the luminal surface of the tumor cells. The number of tumor cells that expressed DU-PAN-2 generally was greater than that of tumor cells that expressed CA19-9, Le(a), or Le(b). There was no significant difference in antigen expressions in female papillary carcinomas between subjects who were younger and older than 50 years old. The results suggest that DU-PAN-2 would be a useful immunohistochemical marker for distinguishing papillary carcinomas from follicular tumors. These immunohistochemical profiles imply the following: the activity of alpha2-3 sialyltransferase, a specific glycosyltransferase, would be more strongly enhanced in papillary carcinomas than in follicular tumors; the antigen expressions in papillary carcinomas may not be related to the alteration of the female sex hormone environment.     

Expression of blood group antigens by normal bronchopulmonary tissues and common forms of pulmonary carcinomas.

The expression of ABH and Lewis antigens has been studied in a series of pulmonary carcinomas, in areas of squamous metaplasia, and in normal adjacent bronchopulmonary tissues by means of a panel of lectins and monoclonal antibodies. All respiratory epithelial cells can express antigens, with the exception of glandular serous cells. The expression of AB antigens is rather homogeneous, while Lewis antigens are expressed in a more irregular pattern, alternating positively stained cells with negatively stained cells in the same microscopic field. The expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms. Metaplastic areas show a variation in the staining profile when compared with normal tissues and pulmonary carcinomas. The most significant findings are the deletion of A antigen and the strong expression of Le antigen. Pulmonary carcinomas are composed by a heterogeneous population and tend to express antigens in the more differentiated cases or areas. The most important findings are the deletion of AB antigens and the strong expression of Le(y) antigen.     

Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth

We report a rare case of minute (5 mm x 4 mm) mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. A 34-year-old Japanese man was admitted because of elevated serum pancreatic enzymes. Endoscopic retrograde pancreatography revealed an unidentified material of 18 mm within the main pancreatic duct. Stone or parasite with acute pancreatitis was suspected clinically, and the biopsy revealed malignant cells positive for CA19-9, carcinoembryonic antigen (CEA) and synaptophysin. No apparent tumor was identified in the pancreas by various imaging techniques. Resection of pancreatic body and tail was performed. Grossly, the main pancreatic duct in the pancreatic body was occluded by as much as 20 mm. The pancreas had minute carcinoma of 5 mm x 4 mm just around the occluded main pancreatic duct. The tumor cells invaded the main pancreatic duct and spread within it as long as 20 mm. Histologically, the carcinoma had biphasic pattern; one was ductal carcinoma with tubular formations and another was carcinoma with neuroendocrine features. These two elements were admixed, and the ductal element comprised 30% while the endocrine element comprised 70%. The ductal element was immunoreactive for cytokeratins, CEA and CA19-9, while the endocrine element was immunoreactive for chromogranin A and synaptophysin. No immunoreactivity for pancreatic enzymes was noted. Ultrastructural observations showed dense core granules and no zymogen granules. Our case is unique clinically in that the tumor manifested as an intraductal material and no apparent tumor was found by imaging modalities, and pathologically in that the tumor was rare mixed ductal-endocrine carcinoma and the tumor was very small and mainly grew within the main pancreatic duct.     

The expression and significance of blood group antigens (BGA) A, B, H, Le(a) and Le(b) in hepatocellular carcinoma and chronic hepatitis]

Five monoclonal antibodies which selectively recognize A, B, H, Le(a) and Le(b) BGA had been used for immunohistochemical examination of serial sections collected from 40 cases of hepatocellular carcinomas, 63 cases of chronic hepatitis, 10 cases each of fetal and normal adult liver. All of the cases had been followed-up except the autopsy cases. The results were as follows: in fetal and normal adult liver tissues, none of the liver BGA were detected in the parenchymal liver cells. Five BGA were expressed in 11 hepatitic cases (17%) and also expressed in 19 hepatocellular carcinomas (48%). Combining the expression of BGA with the follow-up results, the study we have performed indicates that the expression of BGA in chronic hepatitis predicts cancerous change or severe liver cell damage associated with poor prognosis.     

Immunohistochemical staining of pancreatic cancer with CA19-9, KM01, unabsorbed CEA, and absorbed CEA. A comparison with normal pancreas and chronic pancreatitis.

In order to test the effectiveness of CA19-9, KM01, unabsorbed CEA (carcinoembryonic antigen) and absorbed CEA by immunoperoxidase staining, we evaluated the staining distribution, intensity, and cellular localization in pancreatic cancer. The results were then compared with those of normal pancreas and chronic pancreatitis. The positive staining rate of the pancreatic cancer with any of the four tumor markers was higher than that of the normal pancreas. However, all markers except absorbed CEA showed a higher positive staining rate for chronic pancreatitis than for pancreatic cancer. There was no stromal type in normal pancreatic or chronic pancreatitis tissues with any of the four tumor markers. Our findings, therefore, indicate that absorbed CEA is useful in differentiating pancreatic cancer from normal pancreatic tissues. It is not useful in distinguishing chronic pancreatitis, however, unless a specific staining pattern is observed.     

CA 50 and CA 19-9 antigen expression in normal, hyperplastic, and neoplastic thyroid tissue

The occurrence of the tumor-associated carbohydrate antigens defined by the monoclonal antibodies (moabs) C 50 and 19-9 has been studied by immunoperoxidase staining of formalin-fixed and paraffin-embedded tissue specimens from normal, hyperplastic, adenomatous, and carcinomatous thyroid tissues. Epithelial expression of these antigens was observed neither in normal nor in hyperplastic thyroid tissue. The antigens were expressed in only 1 of 26 follicular adenomas and the staining in this case was weak and restricted to a few cells. In contrast, the expression of this antigens is marked and progressive in carcinomatous tissues. A high proportion, 48 of 52 papillary carcinomas demonstrated C 50 reactivity, whereas 25 of these tumors expressed the CA 19-9 antigen. Of 25 follicular carcinomas, 15 gave a positive staining for the CA 50 and 6 for the CA 19-9 antigen. CA 50 antigen expression was still detected in tumor cells lacking the CA 19-9 antigen and C 50 reactive material was found in all tissue specimens from medullary carcinomas tested, whereas CA 19-9 antigen staining was consistently negative. This indicates that the moab C 50 which reacts, like the moab 19-9, with the sialylated Lewisa (Lea) blood group determinant also binds to other antigens apart from the sialylated Lea in CA 19-9 antigen negative tumor cells. Although, the functional significance of CA 50 and CA 19-9 antigen expression remains to be investigated, these results suggest that the demonstration of these antigens could provide additional differential diagnostic parameters for the characterization of hyperplastic and neoplastic lesions of the thyroid gland. Further clinical studies will show whether these carbohydrate antigens are useful serum markers for the monitoring of thyroid carcinomas.     

肿瘤-睾丸抗原SSX、NY-ESO-1、MAGE-A1在胰腺癌中的表达及其生物学意义

目的 检测肿瘤-睾丸抗原(CTA)SSX、NY-ESO-1、MAGE-A1在正常胰腺组织、慢性胰腺炎以及胰腺癌中的表达情况,寻找胰腺肿瘤中高表达的CTA.方法 应用免疫组织化学SP法检测8例正常胰腺组织、15例慢性胰腺炎组织、52例胰腺癌组织中SSX、NY-ESO-1、MAGE-A1的表达.Western blotting检测52例胰腺癌组织中SSX、NY-ESO-1、MAGE-A1的表达.结果 正常胰腺组织、慢性胰腺炎中SSX、MAGE-A1和NY-ESO-1均不表达,SSX、NY-ESO-1、MAGE-A1在52例胰腺癌的阳性表达率分别为48.08%(25/52)、7.69%(4/52)、5.77%(3/52);经相关分析,SSX、NY-ESO-1和MAGE-1的阳性表达与患者的年龄、性别、病变部位、分化程度均未见明显相关关系(P＞0.05); SSX的表达与肿瘤的浸润转移呈负相关(r=-0.306,P=0.028); 52例胰腺癌病例中55.77%(29/52)有1种以上的CTA表达.结论 不同种类的CTA在胰腺癌中的表达存在显著差异,SSX的阳性表达率最高;胰腺癌中SSX的高表达与肿瘤的转移呈明显的负相关关系;CTA在胰腺癌中的表达呈现簇生现象.     

Bombesin receptors in distinct tissue compartments of human pancreatic diseases

Overexpression of receptors for regulatory peptides in various human diseases is reportedly of clinical interest. Among these peptides, bombesin and gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize bombesin receptors in the human diseased pancreas to identify potential clinical applications of bombesin analogs in this tissue. The presence of bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with chronic pancreatitis (n = 23) and ductal pancreatic carcinoma (n = 29) with in vitro receptor autoradiography on tissue sections incubated with 125I-[Tyr4]-bombesin or the universal ligand 125I-[D-Tyr6, beta-Ala11, Phe13, Nle14]-bombesin(6-14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with chronic pancreatitis. No measurable bombesin receptors were found in the tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples. Moreover, residual pancreatic islets in these tissues were shown to express the BB3 receptor subtype. These data demonstrate the presence of bombesin receptors in three distinct tissue compartments of the pancreas, namely GRP receptors in the exocrine parenchyma in chronic pancreatitis and in peritumoral vessels around ductal pancreatic carcinomas, and BB3 receptors in residual pancreatic islets. Such a selective expression of bombesin receptor subtypes in pancreatic tissues may not only be of pathophysiological significance but may represent the basis for potential diagnostic and therapeutic clinical applications of bombesin analogs, including GRP receptor scintigraphy to differentiate chronic pancreatitis from ductal pancreatic carcinoma.     

Use of lectin histochemistry in pancreatic cancer.

Lectin peroxidase histochemical analysis was carried out on pancreatic tissue from patients with pancreatic carcinoma and chronic pancreatitis and from subjects with normal pancreas to find a tumour specific pattern of lectin binding that would aid histological and cytological diagnosis. There were striking differences between the lectin binding characteristics of the different cell types in the normal pancreas. Acinar cells were uniformly positive for binding with wheat germ agglutinin and soy bean agglutinin while islet cells were usually negative for these lectins. Ulex europaeus I lectin however, was found not to be specific for endothelium, showing positivity also for acinar and ductal tissue. Griffonia simplicifolia II lectin was found to be highly specific for ductal epithelium, and because of this was tested in a hamster pancreatic cancer model where it was not specific for ductal epithelium, reflecting differing carbohydrate expression in the hamster pancreas. Pancreatic carcinomas and chronic pancreatitis bound all five lectins without any qualitative distinction from each other or from normal pancreatic tissue, but there was increased intensity of peanut agglutinin binding to secreted mucins in pancreatic carcinoma, which may be of potential use in radiolabelled lectin scanning.     

Differences in immunohistochemical expression of xenobiotic-metabolizing enzymes between normal pancreas, chronic pancreatitis and pancreatic cancer

Metabolic activation of many toxins, carcinogens, drugs, and anti-cancer agents is governed by the cytochrome P450 (CYP) drug-metabolizing enzyme system. To help elucidate the role of this enzyme system in the pathogenesis of chronic inflammatory and malignant pancreatic diseases, we compared the immunohistochemical expression pattern of 8 CYP-enzymes in 24 normal, 20 chronic pancreatitis, and 21 pancreatic cancer specimens using antibodies to CYP 1A1, 1A2, 2B6, 2C8/9/19, 2D6, 2E1, and 3A4, and the NADPH cytochrome P450 oxido-reductase (NA-OR). Compared to the normal pancreas, a higher frequency of immunopositivity for CYP 1A2, 2B6, 2C8/9/19, 2D6, and NA-OR was found in chronic pancreatitis, and of all CYPs but 1A2 in pancreatic cancer. On the other hand, CYP 1A1 and 2E1 antibody staining was less frequently observed in chronic pancreatitis. In all specimens with pancreatic polypeptide (PP)-rich regions (pancreas head), more islet cells than ductal and acinar cells were immunopositive. Moreover, the immunoreactivity of islet cells from PP-rich specimens with anti-CYP antibodies was consistently more frequent and intense than in islet cells from PP-poor areas (body and tail). Immunoreactivity for xenobiotic-metabolizing enzymes was frequently observed in the normal pancreas, chronic pancreatitis, and pancreatic cancer, and displayed differences of its frequency and intensity between the 3 groups. Considering immunohistochemical evidence of enzyme expression and pancreatic blood supply together, islet cells appear to be an important and possible early site of CYP-enzyme induction in pancreatic diseases.     

Lewis antigens and argyrophilic nucleolar organizer regions staining for assessment of potential malignancy of adenomatous polyps of the gastrointestinal tract in children

Adenomatous polyps (AP) of the gastrointestinal tract in children are very rare. Because of their potential malignancy, they are of great clinical importance. There is little experience in the management of children with AP. The immunohistochemical expression of the Lewis blood group antigens (BGA) (sialosyl-Le(a), Le(a), Leb, Le(x), and Le(y)) and the number of activated nucleoli with the silver staining method for nucleolar organizer regions (AgNORs) were studied in two children with AP. In a girl with isolated AP of the stomach and colon, it was found that antigens Le(b) and s-Le(a) were expressed extensively in the gastric adenoma, and sialosyl-Le(a) throughout the entire length of the rectal adenoma crypts, but in the AgNORs stain the number of nucleoli ranged from two to four, evidencing changes of a benign character. In the case of familial adenomatous polyposis diagnosed in a 9-year-old boy, in some colonic adenomas the number of activated nucleoli was greater than five, and the Le(b) antigen was expressed in superficial epithelial cells in one of the adenomas. Also, extensive expression of antigens Le(y) and s-Le(a) throughout the entire length of the crypt in another polyp removed was observed. We believe that immunohistochemical study of the intensity and extent of the expression of Lewis BGA in the polyp tissue simultaneously with the determination of the number of activated nucleoli by the AgNORs staining method can be helpful in better analysis of cytological risk factors of a malignant transformation.     

Blood-group-related antigen Lewis(x) and Lewis(y) in the differential diagnosis of cholangiocarcinoma and hepatocellular carcinoma

Distribution of Lewis(x) (Le(x)) and Lewis(y) (Le(y)) blood-group antigens was studied in nine formaldehyde-fixed, paraffin-embedded cholangiocarcinomas (CCs), 26 hepatocellular carcinomas (HCCs), and eight normal livers. All CCs, with one exception, expressed both Le(x) and Le(y) antigens on few or many cells. In HCCs Lex was expressed infrequently (8%), while Le(y) was detected in 31% of cases. Both markers, when present in HCCs, tended to be spotty. Fibrolamellar carcinomas and normal livers did not react with either Le(x) or Le(y) antigens; however, Le(y) antigen was observed occasionally in bile duct epithelial and ductular cells. In conclusion, inappropriate tissue distribution of Le(y) blood-group antigens was observed in CCs and, much less frequently, in HCCs. The high frequency of Le(x) antigen in CCs but not in HCCs may help in the differential diagnosis of these two tumors.     

IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis typically produces an enlarged pancreas with narrowing of the pancreatic duct, and can mimic carcinoma. Autoimmune pancreatitis usually responds to corticosteroid treatment, making it important to differentiate from pancreatic ductal adenocarcinoma. Affected patients often have an elevated serum IgG4. It has been proposed that increased numbers of IgG4-positive plasma cells in tissue might be a marker for the condition. We investigated the role of IgG4 staining in the diagnosis of autoimmune pancreatitis, first in resected pancreas specimens (29 autoimmune pancreatitis, nine chronic alcoholic pancreatitis and 25 pancreatic cancer), then in pancreatic needle biopsies. Immunohistochemical stains for IgG4 were scored as none, mild, moderate or marked, according to published criteria. Moderate to marked numbers of IgG4-positive plasma cells were seen in 21/29 autoimmune pancreatitis patients, and were distributed in and around ducts, in interlobular fibrous tissue and in peripancreatic fat. In contrast, eight of nine examples of chronic alcoholic pancreatitis and 22/25 ductal adenocarcinomas had scores of none or mild. When we subdivided autoimmune pancreatitis into the histologic subtypes lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-destructive pancreatitis, 16/17 lymphoplasmacytic sclerosing pancreatitis had moderate to marked staining, compared to five to 12 idiopathic duct-destructive pancreatitis. Needle biopsies from nine patients suspected of having autoimmune pancreatitis had increased numbers of IgG4 cells. We conclude that pancreatic tissue from patients with autoimmune pancreatitis often shows moderate or marked infiltration by IgG4-positive plasma cells (>10/HPF). This is particularly so in the subtype we have designated lymphoplasmacytic sclerosing pancreatitis. We rarely see IgG4 staining in patients with chronic alcoholic pancreatitis and pancreatic ductal adenocarcinoma. IgG4-positive plasma cells are a useful marker for the tissue diagnosis of autoimmune pancreatitis.