Focal acinar cell dysplasia in human pancreas

A series of 108 prospectively collected human pancreata were evaluated histologically for the presence of acinar cell and ductal lesions. Foci of dysplastic acinar cells were present in 44% of the series. Some of the focal acinar cell abnormalities were similar to atypical acinar cell nodules which have been described in carcinogen-treated experimental animals. The incidence of nodules was higher among patients with a history of heavy cigarette smoking than among nonsmokers, and among patients with a history of alcohol abuse than among abstainers. The presence of dysplastic acinar cell nodules in a pancreas seemed unrelated to the presence of cancer in other sites, or diabetes. Ductal epithelial abnormalities were more frequent than focal acinar cell dysplasia.     

Kinetics of induction and growth of putative precancerous acinar cell foci in azaserine-induced rat pancreas carcinogenesis

The kinetics of induction and growth of acinar cell lesions has been investigated in rat pancreas after a single dose of the carcinogen azaserine. The time--response relationship was studied in male Wistar-related rats given a single i.p. injection of 30 mg L-azaserine/kg body weight at 18 days of age. Rats were killed between 4 and 78 weeks after treatment and ATPase-stained pancreas sections were quantitatively evaluated for the number and size of acidophilic, ATPase-positive and basophilic, ATPase-deficient foci. The number of acidophilic foci remained constant from 8 weeks onwards, while the number of basophilic foci slightly increased with time. The size of both acidophilic and basophilic foci increased throughout the experimental period. Due to two times higher number/cm3 and faster growth of the acidophilic foci, four times more acidophilic than basophilic focus tissue was present at the end of the experiment. Progression of acidophilic foci to adenomas and carcinomas was occasionally seen at later time points (greater than 34 weeks) in this rat strain. The dose--response relationship was studied in male and female Sprague--Dawley rats given a single i.p. injection of 0-45 mg azaserine/kg body weight at 19 days of age. Rats were autopsied at 17 weeks after treatment, and pancreas sections were quantitatively evaluated after ATPase histochemistry. The relationship between dose and number of foci was linear up to 30 mg/kg azaserine for both acidophilic and basophilic foci in males and females. For each individual dose, the number of foci induced was the same in males and females, and there were two to three times more acidophilic than basophilic foci. The percentage of pancreatic tissue occupied by focus tissue was 1.75 times higher in males, pointing to a higher growth-potential of acidophilic foci in males than in females. The first-order dose--response kinetics indicate that the conversion of a normal acinar cell into a focus-forming cell occurs by one specific azaserine-mediated rare event, occurring probably at the genetic level of the target cell.     

Atypical and neoplastic acinar cell lesions of the pancreas in an autopsy study of Japanese patients

A histopathologic examination of the pancreas was performed on a series of adult Japanese autopsies. In ten of 162 pancreases (6%) with adequate tissue available, two types of focal atypical acinar cell lesions, composed of acidophilic or basophilic cells, were found. Acidophilic atypical acinar cell lesions were more frequent than basophilic ones, although the one case of acinar cell adenoma and two cases of acinar cell carcinomas showed high incidences of basophilic atypical acinar cell lesions. The findings are concluded to support the possibility that atypical acinar cell lesions are precursors for acinar cell carcinomas.     

胰腺腺泡细胞癌的CT表现

背景与目的：胰腺腺泡细胞癌(acinar cell carcinoma of the pancreas,ACCP)是一种罕见的胰腺恶性肿瘤,相关的影像学报道较少。该研究旨在探讨ACCP的CT表现。方法：收集自2011年1月-2014年1月经手术病理证实为ACCP的9例患者资料,回顾性分析其CT征象。结果：在9例ACCP患者中,肿块最大径均值为52 mm,肿瘤边缘不清的6例(66.7%),外生型生长者有6例(66.7%),强化程度低于正常胰腺组织者8例(88.9%),强化不均者6例(66.7%),累及血管者7例(77.8%),淋巴结转移者5例(55.6%),无出现肝转移病例,仅1例出现胰管扩张。结论：较大体积的乏血供胰腺肿块,内部异质性明显,呈外生型生长而无显著胰管扩张时,提示ACCP的可能。     

Plasma carcinoembryonic antigen and acinar cell carcinoma of the pancreas

Seventeen patients with histologically proven pancreatic cancers were studied in order to clarify the relationship of histologic types to plasma carcinoembryonic antigen (CEA) values. Two cases with marked elevation of plasma CEA values having 6100 ng/ml and 2500 ng/ml, respectively, disclosed histologically acinar cell carcinoma and mixed acinar and ductal cell carcinoma, respectively. Despite of massive hepatic metastases, the other 15 cases with ductal cell carcinoma, including 3 cases with cystadenocarcinoma, adenoacanthoma, and undifferentiated pancreatic cancer, respectively, showed normal or very modest elevation of plasma CEA values. No correlation was obtained between plasma CEA values and several biochemical tests. Two patients with marked elevation of plasma CEA value revealed strong staining in the cancerous areas of the pancreas by using a peroxidase-antiperoxidase staining technique. These findings suggest that acinar cell carcinoma of the pancreas may contribute to increase the circulating plasma CEA value.     

Alterations in glycoproteins and lipids in azaserine-induced acinar cell carcinoma of rat pancreas

Glycoproteins and lipids of rat pancreatic acinar cell carcinomas maintained in nude mice and in cell culture, were analyzed. The tumor contained significantly elevated levels of glycoproteins when compared with their normal counterparts. SDS-PAGE of tumor glycoproteins revealed that there were increased amounts of small molecular weight glycoproteins and the tumor also contained a 51,000 dalton glycoprotein which was not detected in the pancreas, liver or the sera of the control animals. The tumor in nude mice and cancer cells in culture had decreased lecithins and triglycerides, and increased amounts of free fatty acids, and both free and esterified cholesterols. The results indicate that altered glycoprotein and lipid compositions represent some of the characteristic features of the acinar cell carcinoma.     

A case of solid and cystic acinar cell tumor of the pancreas

A 35-year-old woman with a tumor of the pancreatic head is presented. A filling defect, suggesting an extragastric mass, was found in the photofluorogram of a gastric mass survey. But she had no complaints. CT showed a cystic mass in the pancreatic head, but ERCP and celiac angiography indicated no invasive findings. The resected tumor, wrapped well with a partially calcifying fibrous capsule, measured 7 X 7 X 5 cm and was mostly necrotic. On histological examination, malignant findings, were not revealed. PAS-positive granules and zymogen-like granules were found in the cytoplasm by electronmicroscopic examination. Immunohistochemically, alpha 1-antitrypsin granules were detected.     

Altered drug metabolizing potential of acinar cell lesions induced in rat pancreas by hydroxyaminoquinoline 1-oxide

Foci of atypical acinar cells observed in male rats 1 year after a single injection of hydroxyaminoquinoline 1-oxide (HAQO) were assessed immunohistochemically for altered expression of a number of enzyme forms considered to play important roles in drug metabolism. The pancreatic lesions, classified as of either basophilic or eosinophilic type on histological appearance, demonstrated distinctive patterns of altered enzyme phenotype. On the one hand, the basophilic foci composed of enlarged cells/nuclei with very prominent nucleoli were characterized by increase in GST-P, G6PD and P450 PB1 and MC2 forms. The eosinophilic type, in contrast, comprised smaller cells demonstrating elevated P450 MC1 and PB1 but not MC2, normal G6PD and strong GST-P binding limited only to a proportion of the nuclei. Both shared decreased GGT and almost total lack of GST-B positive connective tissue and ductular elements. Apparent islet cell lesions and normal islet tissue were characterized by a distinct enzyme phenotype strongly positive for all P450 species investigated. The results indicate that HAQO-induced putative preneoplastic pancreatic lesions, like equivalent carcinogen associated with focal populations in liver, kidney and ductular pancreas, demonstrate a non-random altered expression of specific drug metabolizing enzyme species.     

Differentiation of muscarinic cholinergic receptors in acinar carcinoma of rat pancreas

Analysis of muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat by measurement of N-[methyl-3H]scopolamine binding has revealed a single homogenous population of muscarinic receptors in the tumor. The plasmalemma density (approximately 25 receptors/micron 2 of cell membrane surface) and dissociation constant (approximately 0.4 nM) of muscarinic receptors in acinar carcinoma cells are identical to the density and affinity of muscarinic receptors in normal acinar cells of rat pancreas. Muscarinic receptors in the carcinoma are functionally linked to cholinergic stimulation of cellular Ca2+ release. An equivalent number of functional muscarinic receptors is present in poorly differentiated carcinoma cells which are deficient in zymogen granules and protein secretion, as compared to well-differentiated carcinoma cells which contain granules and secrete protein in response to cholinergic stimulation. These observations indicate that muscarinic cholinergic receptors are displayed in normal fashion on tumor membranes and are fully expressed in carcinoma cells regardless of their degree of secretory development. Expression of muscarinic cholinergic receptors is thus a stable phenotypic property of pancreatic acinar carcinoma cells. This suggests that muscarinic receptor maturation is an early event in the differentiation of pancreatic exocrine cells, preceding acquisition of secretory responsiveness to cholinergic stimulation.     

Identification of human acinar cell carcinoma by monoclonal antibody and in vitro differentiation

Methylnitrosourea (MNU)-induced carcinomas in organ-cultured human pancreas when injected into nude mice produced subcutaneous carcinomas none of which were recognizable as being of acinar cell origin. Both monoclonal antibody to acinar cell surface marker produced by hybridoma, and in vitro tumor cell differentiation were used to detect tumors of acinar cell origin. Only 1 out of 14 tumors, a highly undifferentiated carcinoma, proved to be of acinar origin. This tumor was composed of cells devoid of zymogen granules but with abundant acinar cell surface marker. The acinar origin of this tumor was also confirmed by its differentiative features after 7 weeks of culture.     

Histopathologic findings of minute foci of squamous cell carcinoma in the human esophagus

To examine the histogenesis and progression of esophageal squamous cell carcinoma, 76 cases of a primary squamous cell carcinoma were reviewed retrospectively, and 16 lesions of squamous cell carcinoma of the esophagus less than 1.0 cm in diameter were studied histopathologically. None of the patients had received radiation therapy preoperatively. Among 16 foci, 13 were intraepithelial carcinomas, and three were restricted to within the mucosa. In two patients with a solitary, minute cancer, there were no associated areas of dysplasia. In 11 patients with multiple primary minute foci, seven contained 14 areas of dysplasia in the esophagus. There was no continuity between the minute foci of carcinoma and areas of dysplasia. These findings are interpreted to mean that dysplasia is a "subcancerous" lesion rather than a "precancerous" one and that various degrees of lesions such as dysplasia and carcinoma occur multicentrically in the same esophagus. The sequence of dysplasia to carcinoma must be examined using the techniques of molecular biology.