A case of heterotopic pancreas in lymph node

Summary A case of pancreatic heterotopia in a lymph node is described. Small pieces of pancreatic tissue were found incidentally in four lymph nodes located around the common hepatic artery in a 65-year-old man. Both exo- and endocrine elements of the pancreas, together with ductal structures were found to constitute the heterotopic tissue. No authentic case of heterotopic pancreas in lymph node has been previously reported in the literature.     

Hyperplastic and neoplastic endocrine cells of the pancreas in aspiration biopsy

Aspiration biopsy of four primary endocrine tumors of the pancreas showed single and large sheets of tumor cells. Tumor cells were polygonal in shape with ill-defined, filmy or granular cytoplasm and regular round nuclei containing a finely granular chromatin pattern and inconspicuous or prominent nucleoli. Focal gland-like arrangement was seen in several sheets of tumor cells. Aspirate from liver metastases of an endocrine tumor of the pancreas showed single and clustered oval cells with granular cytoplasm and eccentrically located round and hyperchromatic nuclei. Smears prepared from aspirates of three fibrotic pancreata containing nodules of hyperplastic endocrine cells showed smaller fragments of endocrine-cell epithelium with focal gland-like arrangement. Individual hyperplastic endocrine cells displayed granular, filmy, and ill-defined cytoplasm and round to oval hyperchromatic nuclei showing a finely granular chromatin pattern. Nuclear pleomorphism was noted in some cell groups.     

The endocrine pancreas in chronic pancreatitis

Summary The endocrine pancreatic tissue from patients with severe primary chronic pancreatitis (n=6), secondary chronic pancreatitis due to duct obstruction by carcinoma (n=6) and non-diabetic, non-pancreatitic controls (n=4) was studied qualitatively and quantitatively using specific immunocytochemistry and electron microscopy. Grouping of variously sized islets in the sclerotic tissue (sclerosis islets), islet neoformation by ductuloinsular proliferation, and intrainsular fibrosis were the main qualitative findings. Immunocytochemical quantitation of the distribution of insulin (B), glucagon (A), somatostatin (D) and pancreatic polypeptide (PP) producing cells revealed a significant relative increase in the number of A cells and a decrease in the number of B cells of the sclerosis islets in primary chronic pancreatitis (B-44.1±9.3%:A-38.3±2.4%:D-8.6±5.1%:PP-4.6±4.1%) as well as in secondary chronic pancreatitis (B-38.0±14.3%:A-38.4±19.0%:D-9.1±5.8%:PP-14.5±23.4%) compared with controls (B-71.1±8.1%:A-24.3±5.5%:D-8.0±2.8%:PP-0.5±0.4%). The number of PP cells was significantly increased in primary chronic pancreatitis only. It is suggested that scarring of the exocrine pancreas affects islet composition, probably by impairment of the local circulation and of glucose diffusion, thus leading to reduction of the number and glucose sensitivity of B cells. The hyperplasia of A and PP cells appears to be a secondary phenomenon due to the loss of B cells.     

A novel subtyping of intestinal metaplasia of the stomach,with special reference to the histochemical characterizations of endocrine cells

Summary Intestinal metaplasia of the stomach was grouped into 3 subtypes (A, B and C) according to the degree of pyloric gland involution which was judged from patterns of paradoxical Concanavalin A staining after Katsuyama and Spicer. The appearance of endocrine cells was investigated with immunohistochemical and silver methods. Type A metaplasia with slightly to moderately atrophic pyloric glands corresponded to the incomplete type in the previous classification, while Type C showing complete disappearance of pyloric glands corresponded to the complete type. Type B with severely atrophic pyloric glands was an intermediate. This subtyping reflects the cell kinetics in the intestinalized mucosa well. Regarding the endocrine cells, their total number varied in the order Type A > Type B > Type C. The selective populations of the endocrine cells including glicentin-containing cells, Grimelius-positive argyrophil cells without argentaffinity and intestinal-type enterochromaffin cells frequently formed hyperplastic foci in the intestinalized areas, where the other gut-type and proper gastric-type endocrine cells were scarcely noted. Immunoreactivity of glucagon or bovine pancreatic polypeptide were occasionally identified in a subpopulation of the glicentin-containing cells.     

Ontogeny, differentiation and growth of the endocrine pancreas

The pancreas develops from the primitive foregut endoderm, which differentiates into ductal, acinar and endocrine cells. This complex process is probably replicated in the adult pancreas when endocrine cell renewal is required, as may be the case in diabetes mellitus. This review describes what is known about the morphogenesis of the endocrine pancreas during ontogeny and the mechanisms regulating its differentiation and growth. Received: 23 December 1999 / Accepted: 15 February 2000     

Dysregulation of the cell cycle and chromosomal imbalances in juxtaglomerular cell tumors - a comparative study with endocrine tumors of the pancreas

Two juxtaglomerular cell tumors (JGCTs) were investigated in comparison with 14 endocrine tumors of the pancreas (ETPs), focusing on the cell cycle, apoptosis, and cytogenetic changes. JGCTs revealed nuclear accumulation of Cyclin D₁, together with the cyclin-dependent kinase inhibitors p21^Cip1/Waf1 and p27^Kip1. In contrast, no accumulation of Cyclin D₃, p53, p16^INK4a, or Mdm-2 was seen. Bcl-2 protein was intensively, but Rb only moderately, expressed. This immunoreactive profile was not found in the ETPs, which were negative for Bcl-2, p27^Kip1, p21^Cip1/Waf1, and - with one exception - for Cyclin D₁ (1/14) but expressed Cyclin D₃ in 7/14 cases. JGCTs displayed characteristic genetic alterations with combined losses of chromosomes 9, 11, 15, and 21 and gains of chromosome 18. In contrast, no characteristic pattern of genetic alterations was found in ETPs. In both, the amount of chromosomal aberrations correlated with tumor size. In small ETPs and JGCTs, genetic losses dominated over gains of chromosomes, whereas in large/malignant ETPs, gains and losses were equally affected. Thus, JGCTs represent a special type of renal endocrine neoplasm characterized by deregulation of cell cycle components and a typical profile of chromosomal aberrations. Since only two JCTs were investigated, further studies for validation of these results are, however, necessary.     

Development of the adult endocrine pancreas during metamorphosis in the sea lamprey,Petromyzon marinus L. II. Electron microscopy and immunocytochemistry

The development of the adult endocrine pancreas was followed throughout metamorphosis in the sea lamprey using electron microscopy and immunocytochemistry. It was discovered that the caudal pancreas develops from the larval extrahepatic common bile duct through the process of transdifferentiation (dedifferentiation/redifferentiation). Early in metamorphosis the bile duct epithelial cells possess large vacuoles, resembling autophagic vacuoles, containing recognizable cell material. There is a loss of the large bundles of intermediate filaments characteristic of the larval bile duct epithelium. These same cells are then seen to contain granules immunoreactive for insulin. Pancreatic islets develop within the base of the bile duct epithelium from these transdifferentiated cells and migrate into the surrounding connective tissue to form the caudal pancreas. The cranial pancreas was found to develop from the epithelia lining the developing adult diverticulum and anterior intestine in a similar fashion as those in the larva. The second cell type to appear in either portion of the developing pancreas is similar to the third cell type of the adult: cells immunoreactive for somatostatin do not appear until late in metamorphosis in either region. © 1993 Wiley-Liss Inc.     

赤链蛇达氏腺内分泌细胞免疫细胞化学

目的：研究赤链蛇达氏腺内分泌细胞类型、分布特点。方法：用免疫细胞化学ABC法。结果：发现赤链蛇达氏腺内有8种物质均免疫反应阳性细胞,分别为5-羟色胺、生长抑素、P物质、胰高血糖素、胃泌素、表皮生长因子受体、上皮膜抗原及睾酮,以5-HT数量最多,GAS细胞最少,各细胞分布部位也有所不同。结论：赤链蛇达氏腺的各种内分泌细胞功能与蛇类取食习惯及其他蛇类特有生理活动相适应。     

Morphology and staining patterns of endocrine cell tumours in the gut, pancreas and bronchus and their possible significance

We have studied 109 endocrine cell tumours of the gastrointestinal tract, pancreas and bronchus in terms of histological pattern and histochemical staining with immunocytochemical studies on seven tumours. As a result we believe that previous histological classifications need modification. 5-Hydroxytryptamine secreting tumours have a carcinoid (A1) pattern with, in some cases, an additional tubuloacinar element (A1A2) and definable histochemical reactions; well differentiated gastrinomas, insulinomas and glucagonomas are associated commonly, but not exclusively, with particular histological patterns and argyrophilia, but no such association exists for less differentiated tumours. This may be related to the synthesis of precursor hormones by less differentiated tumours. Mixed patterns are common, particularly in tumours of foregut derivation. Prospective studies planned to correlate histology, histochemistry, immunocytochemistry and ultrastructure are needed on all endocrine cell tumours.     

Immunohistochemical study of endocrine cells in ductal adenocarcinoma of the pancreas

To clarify whether scattered endocrine cells in pancreatic ductal adenocarcinoma are neoplastic or not, we immunohistochemically studied 29 cases of invasive pancreatic ductal adenocarcinomas, 17 with metastases, for chromogranin A, insulin, glucagon, pancreatic polypeptide, serotonin, gastrin, laminin, and Ki-67. Endocrine cells were found in primary sites in 24 cases (82.3%), where endocrine cells showed at least a visibly close location to adjacent islet cells. Although endocrine cells in neoplastic glands were within the neoplastic basement membrane, endocrine cells were not seen in invasive sites beyond the pancreas where islets were not present. Endocrine cells in neoplastic glands were reactive for two or three of the islet hormones in all cases, and different types of hormonal reactivity was recognized in the same neoplastic gland or the same cluster of neoplastic glands in 22 (91.7%) cases, thus suggesting a close relation with islets. Ki-67 did not stain any endocrine cells in ten of the adenocarcinomas studied. In three (10.3%) cases, endocrine cells were found in the intraductal extensions. They may have pre-existed in non-neoplastic ducts. In 17 cases with metastatic sites, all but one had no endocrine cells in the metastases. Serotonin-positive cells were found in one metastatic lymph node in one case. We concluded that most endocrine cells seen in ductal adenocarcinomas of the pancreas are non-neoplastic and are derived from the surrounding islets. Some neoplastic endocrine cells may exist, though their frequency is low.     

异位胰腺32例临床诊治分析

目的总结探讨异位胰腺的临床特点及诊治方式。方法 回顾分析北京协和医院1992～2010年经病理证实的32例异位胰腺患者的临床特点及诊治情况。结果 32例异位胰腺分布于胃(15例)、十二指肠(4例)、空肠(9例)和回肠(4例),其中26例为近4年检出。除8例术前获确诊外,6例误诊为胃肠间质瘤,5例误诊为平滑肌瘤,1例误诊为胃溃疡恶变;其余12例为其他腹部手术中发现。1例行胃镜活检证实,31例行手术切除后经术后病理确诊;所有患者无明显并发症发生。结论 胃肠道黏膜下隆起病变应考虑异位胰腺可能,确诊后可选择内镜摘除或手术切除。     

Mucosal colonization of gastric endocrine tumors mimicking mixed neoplasms

Two cases of gastric tumors showing mixed composition of endocrine cell clusters and exocrine glands and originally diagnosed as mixed neoplasms are described. In both cases, the exocrine glandular component was restricted to the upper third of the neoplasms being consistently absent in areas of muscular wall invasion and, in case 2, in nodal metastases. These glands were in close anatomical contiguity with the glands of the overlying gastric mucosa or, in case 1, apparently derived from deep pouch-like invaginations of the mucosa. They showed either lack of dysplasia (case 1) or mild dysplasia (case 2) with a Ki67 proliferation index consistently lower than that of the intramucosal glands. The intratumoral glands presented intestinal metaplastic features confirmed by intense Cdx2 immunostaining that, conversely, was absent in the endocrine component of the tumors. The latter showed intense vesicular monoamine transporter 2 immunoreactivity consistent with its origin from the enterochromaffin-like cells of the gastric oxyntic mucosa. On the basis of these findings, it is proposed that the exocrine glands do not represent a true neoplastic component of the tumors. Although mucosal entrapment by the tumor cannot be ruled out, they more likely reflect a hitherto unrecognized mechanism of mucosal colonization of gastric endocrine tumors.     

EphB3 marks delaminating endocrine progenitor cells in the developing pancreas

Background: Understanding the process by which pancreatic beta‐cells acquire their “fate” is critical to the development of in vitro directed differentiation protocols for cell replacement therapies for diabetics. To date, these efforts are hampered by a paucity of markers that distinguish pancreatic endocrine cells at different stages of differentiation. Results: Here, we identify EphB3 as a novel pro‐endocrine marker and use its expression to track delaminating islet lineages. First, we provide a detailed developmental expression profile for EphB3 and other EphB family members in the embryonic pancreas. We demonstrate that EphB3 transiently marks endocrine cells as they delaminate from the pancreatic epithelium, prior to their differentiation. Using a Tet‐inducible EphB3^rtTA‐lacZ reporter line, we show that short‐term pulse‐labeled EphB3⁺ cells co‐express Pdx1, Nkx6.1, Ngn3, and Synaptophysin, but not insulin, glucagon, or other endocrine hormones. Prolonged labeling tracks EphB3⁺ cells from their exit from the epithelium to their differentiation. Conclusions: These studies demonstrate that pro‐endocrine cell differentiation during late gestation, from delamination to maturation, takes approximately 2 days. Together, these data introduce EphB3 as a new biomarker to identify beta‐cells at a critical step during their step‐wise differentiation and define the timeframe of endocrine differentiation. Developmental Dynamics 241:1008–1019, 2012. © 2012 Wiley Periodicals, Inc.     

Islet cell tumor arising from a heterotopic pancreas in the duodenal wall with ulceration

A rare case of symptomatic islet cell tumor arising from heterotopic pancreas in the duodenum with ulceration is described. Gastrointestinal bleeding was the only sign observed in this patient. Tagged red blood cell scan, upper endoscopy, and computed tomography scan showed active bleeding ulcer from a periampullary mass. Removal of the submucosal tumor was done to prevent future re-bleeding. Histologic and immunohistochemical characterization of the tumor showed an endocrine tumor that expressed a variety of endocrine peptides.     

Oncocytic non-functioning endocrine tumor of the pancreas

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.     

Coexistence of gastric- and intestinal-type endocrine cells in gastric and intestinal mixed intestinal metaplasia of the human stomach

Intestinal metaplasia (IM) in the human stomach has previously been classified into a gastric and intestinal mixed (GI-IM) and a solely intestinal phenotype (I-IM). The phenotypes of mucous and endocrine cells were evaluated in 3034 glandular ducts associated with chronic gastritis. In the pyloric region, the relative expression of gastric endocrine cell markers, such as gastrin and somatostatin, decreased gradually from glandular ducts with only gastric mucous cell phenotype (G type) to GI-IM toward I-IM, while that of the intestinal endocrine cell markers, glicentin, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) was inversely correlated. In the fundic region, gastrin-positive cells emerged in the pseudo-pyloric and GI-IM glands, whereas I-IM glands did not possess any gastrin-positive cells, suggesting the presence of a distinct pathway of intestinalization. Double staining revealed coexistence of gastrin- and GLP-1-positive cells in the same gland and occasionally in the same cell in GI-IM glands. These results suggest that the phenotypes of endocrine cells are in line with those for mucous counterparts and support the concept that all of the different types of mucous and endocrine cells in normal and IM glands might be derived from a single progenitor cell in each gland.     

Glicentin-containing cells in intestinal metaplasia,adenoma and carcinoma of the stomach

Summary Glicentin-containing cells (Glic. cells) in intestinal metaplasia, adenoma and carcinoma of the stomach were examined using immunohistochemical techniques. Glic. cells first occurred in the gastric mucosa of the transitional area between metaplastic and intact gastric glands. They frequently showed hyperplasia or micronoduli in the budding area of the deeper metaplastic glands, but in completely intestinalized mucosa these endocrine cells decreased remarkably. Gastric adenomas with mild dysplasia had a good number of glicentin-immunoreactive cells which were located in the deeper adenoma glands. Gastrin- and somatostatin-positive cells were also detected in the adenomas. The incidence of glicentin-positive tumor cells was significantly higher in well differentiated adenocarcinoma than in poorly differentiated adenocarcinoma. Among the seven cases of scirrhous argyrophil cell carcinoma, three showed glicentin- and glucagon-immunoreactivity in the same area of the tumor. These findings suggest that the selective increase of Glic. cells in intestinal metaplasia may be closely related to the development of gastric adenoma. Glicentin positive tumor cells in gastric carcinomas can be regarded to be an expression of intestinal or fetal markers.     

Immune aspects of intestinal metaplasia of the stomach: An immunohistochemical study

Summary Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.     

Fine-needle aspiration cytology in pancreatic endocrine tumors

Pancreatic endocrine tumors (PETs) are relatively uncommon neoplasms. Although their histologic patterns have been widely studied, their cytologic features as they appear in fine-needle aspiration (FNA) specimens have rarely been reported. In this study, aspirates of seven PETs, four primary and three metastatic lesions (two to liver and one to bone), are described. The tumors occurred in seven men ranging in age from 37 to 72 yr. Six tumors presented as nonfunctioning masses and one produced Zollinger-Ellison syndrome. Three were located in the head of the pancreas and four in the body and tail. The pancreatic and liver aspirations were performed under computed tomographic guidance and the bone lesion, under fluoroscopy. The aspiration specimens were hypercellular. The tumor cells occurred singly and in small clusters. In three cases, there was a tendency toward acinar formations. In two cases, there were prominent, thin-walled, branching blood vessels with tumor cells attached to the vascular walls. The cells were round or polygonal with a moderate amount of finely granular, well-defined cytoplasm. The nuclei were eccentrically located and round-to-oval--with one or two small nucleoli and finely granular, evenly-dispersed chromatin. The diagnosis was confirmed by immunocytochemistry (two cases) and electron microscopy (four cases) of the aspirated material and histology sections of the resected tumors (two cases). The results of this study demonstrate that FNA is a useful method to establish the diagnosis of PETs.