Accepted for publication 10 August 1992 Abstract Ten patients in whom cystic dystrophy developed in a heterotopic pancreas of the duodenal (nine patients) or gastric (one patient) wall are reported. All were young or middle aged white men, only two of whom were alcoholic. The symptoms were caused by intestinal or biliary stenosis, or both, secondary to the inflammation and fibrosis. Only endosonography provided strong evidence for the diagnosis in three patients. All patients underwent surgery:

Aims: To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour.Methods and results: In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over-expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E-cadherin was expressed in the squamous cells and absent in the spindle cells.Conclusions: The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E-cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.

Introduction In acute pancreatitis, nonesterified fatty acids (NEFA) might be released by lipase and cause tissue necrosis by their detergent properties, but this has not been established in vivo. Aims To measure the release of NEFA in the blood stream, pancreatic tissue, and peritoneal cavity during taurocholate-induced acute necrotizing pancreatitis in rats. Methodology Ascites and blood were repeatedly sampled; after 24 hours, pancreatic lesions were scored, and NEFA were measured in the pancreas. The effects of a specific lipase inhibitor (Tetrahydrolipstatin [THL]) were also studied. Results A slight transient increase (22%) of NEFA concentration was observed in systemic circulation but did not parallel the time course of lipase activity, arguing against an intravascular production of NEFA by circulating lipase. Pancreatic NEFA did not differ between rats with pancreatitis and control rats. NEFA in ascites increased to threefold the basal value immediately after taurocholate and decreased rapidly thereafter, whereas lipase increased later in ascites and remained elevated during the 24-hour duration of the experiment. Lipase inhibition by THL neither modified the early increase of NEFA in ascites, nor altered the macroscopic, enzymatic, and histologic evolution of pancreatitis. Conclusion This in vivo study does not confirm the hypothetical role of NEFA produced by pancreatic lipase in the necrotic process and its systemic complications, up to now mainly suggested on the basis of ex vivo experiments.

Aims: Multiple familial gastrointestinal stromal tumours are rare. We report the third family with two cases of multiple gastrointestinal stromal tumours showing skeinoid fibres. Associated abnormalities of the myenteric plexus layer are described and new hypotheses for the histogenesis of gastrointestinal stromal tumours are formulated.Methods and results: Multiple gastrointestinal stromal tumours developed in the duodenum and proximal jejunum were removed from mother and son. No history of a specific syndrome or of mastocytosis was known. Light microscopy revealed typical gastrointestinal stromal tumours with skeinoid fibres. An unusual abnormality of the myenteric plexus layer, showing a diffuse spindle cell hyperplasia. was noted in the macroscopically normal digestive wall. No abnormalities of the ganglion cells were associated. Tumours and the spindle cell hyperplasia showed similar morphological and immunohistochemical features with expression of CD34 and CD117 antigens. Follow-up revealed recurrences in the mother.Conclusion: The morphological characteristics of these two cases of familial gastrointestinal stromal tumours and of the associated abnormalities of the myenteric plexus layer, help to better explain the histogenesis of multiple familial gastrointestinal stromal tumours. The hyperplasia of the myenteric plexus could be considered a risk factor for recurrent tumours.

Aims and methods-Digestive stromal tumors are the most frequent undifferentiated mesenchymal tumors. The prognosis of these tumors is difficult to predict and the histogenesis is still subject to controversy. However, the frequent and specific expression of CD 117 (c-kit) by these tumors could suggest an origin from interstitial cells of Cajal. The aim of this study was to analyse the histological and immunohistochemical characteristics of 46 digestive stromal tumors surgically resected with comparaison of CD34 and CD 117 expression in these tumors. Sixteen tumors were analyzed on electron microscopy.Results-Sixty three and 74% of the stromal tumors were positive for CD 117 and CD34 respectively. While CD 117 expression was similar in all locations, on the contrary, there was a decreasing gradient of CD34 expression between gastric (87%) and jejunal (33%) tumors. All tumors with skeinoid fibers expressed CD 117. Focal expression of smooth muscle actin was noted in 43% of the cases. The ultrastructural study showed no correlation with the immunohistochemical results.Conclusion-Digestive stromal tumors show an immunophenotypic and ultrastructural heterogeneity. CD 117 expression is frequent, but not constant.

Intraductal papillary mucinous tumors (IPMTs) of the pancreas are rare tumors characterized by a malignant potential. Because of the progress of imaging procedures, smaller cystic pancreatic lesions are now detected and some of them correspond to IPMTs that involve ectatic pancreatic branch ducts but spare the main pancreatic duct. To investigate differences in morphology and clinical behavior of branch and main duct types of IPMT, a surgical series of 43 cases was studied. All pathologic specimens of IPMT, surgically resected in our institution between October 1987 and July 1998, were analyzed. In all cases, the entire pancreatic specimen was systematically examined. IPMT of the branch type was found in 13 (30%) patients, whereas IPMT of main pancreatic duct type that involved the main pancreatic duct and branch ducts was observed in 30 (70%) patients. Patients with IPMT of the branch type were younger (median age, 55 yrs vs 64 yrs), and all but one of the lesions were located in the head and neck of the pancreas (vs 17 of 30 patients with the main duct type). The size of the cysts ranged from 4 to 55 mm, and the major duct showed a mild dilation in most cases. in contrast to the main pancreatic duct type, which showed invasive carcinoma and in situ carcinoma in 11 (37%) of 30 patients and 6 (20%) of 30 patients, respectively, IPMT of the branch type showed significantly less aggressive histologic lesions with five (39%) patients with simple hyperplasia, six (46%) patients with atypical hyperplasia, and two (15%) patients with in situ carcinoma. No invasive carcinoma was observed in this group, IPMT of the branch type occurs in younger patients and is associated with less aggressive histologic features than is the main pancreatic duct type. Our findings raise the difficult issue of clinical management of IPMT of the branch type as a distinctive group.

Granular cell tumor of the esophagus is an unusual tumor. It presents usually as a small and well limited lesion, localized in the mucosa or the submucosa. We report two cases of granular cell tumor of the esophagus, remarkable for their infiltrative growth. The tumor invaded the esophageal muscularis propria in one case and went through the adventitia in the other. There was no recurrence 1 year and 7 years after surgery, despite an incomplete resection in the second case. Thirteen cases of infiltrative granular cell tumors of the esophagus have been published. They are usually responsible for dysphagia. They can invade the muscularis propria and the adventitia as well as the periesophageal organs. There is no recurrence, even after an incomplete resection. The infiltrative feature of the granular cell tumors of the esophagus, by itself, cannot be considered as a malignant feature. The diagnosis of malignant granular cell tumor of the esophagus lies on the discover of metastases.

The ciliated hepatic foregut cyst is an unusual solitary cystic lesion of the liver. In a series of 7 cases of hepatic ciliated cysts, we performed a histological, histochemical, and immunohistochemical study to better define the histogenesis of this rare entity. The patients were 4 women and 3 men, aged 39 to 75 years. Four patients presented with abdominal pain. In 3 cases the cyst was discovered incidentally on ultrasonography. The cysts measured from 1 to 4 cm in diameter. Microscopically, the lining of the columnar epithelium was composed of ciliated cells and mucin secreting goblet cells. The wall was composed of bands of smooth-muscle fibers surrounded by an outer fibrous capsule. The goblet cells stained with PAS, alcian blue, and high-iron diamine. The immunohistochemical study showed that endocrine cells were present within the cyst epithelium, positive for chromogranin, synaptophysin, bombesin, and calcitonin, and negative for serotonin, somatostatin, glucagon, insulin, gastrin, and pancreatic polypeptide. In all the cases, immunoreactivity of some cells for CC10 strongly suggested the presence of Clara cells. Our study shows that the epithelium lining ciliated hepatic foregut cysts has histological, histochemical, and immunohistochemical features similar to those observed in the bronchiolar epithelium. This lesion is a developmental ventral foregut abnormality that could arise from a bronchiolar bud of the tracheobronchial diverticulum.

Granular cell tumor of the esophagus is an unusual tumor. It presents usually as a small and well limited lesion, localized in the mucosa or the submucosa. We report two cases of granular cell tumor of the esophagus, remarkable for their infiltrative growth. The tumor invaded the esophageal muscularis propria in one case and went through the adventitia in the other. There was no recurrence 1 year and 7 years after surgery, despite an incomplete resection in the second case. Thirteen cases of infiltrative granular cell tumors of the esophagus have been published. They are usually responsible for dysphagia. They can invade the muscularis propria and the adventitia as well as the periesophageal organs. There is no recurrence, even after an incomplete resection. The infiltrative feature of the granular cell tumors of the esophagus, by itself, cannot be considered as a malignant feature. The diagnosis of malignant granular cell tumor of the esophagus lies on the discover of metastases.

To report 20 years of natural history data for a facial paraganglioma and provide a comprehensive review of the existing literature.81-year-old female with a remote history of cardiac arrest while under anesthesia who elected to observe her facial paraganglioma for 20 years.Observation, clinical documentation, radiographic surveillance.Tumor progression, patient symptomatology, and review of management options.The initial presentation of the facial paraganglioma was facial spasm. Over the course of observation, symptoms progressed to include complete facial nerve paralysis, pulsatile tinnitus, and otalgia on the affected side. Radiologic surveillance demonstrated incremental growth and erosion of surrounding structures, including the posterior external auditory canal, stylomastoid foramen, and lateral semicircular canal with near-dehiscence. Twenty-four cases of facial paraganglioma were identified in the extended literature search and are summarized herein.This unique case contributes to the scarce literature surrounding facial paragangliomas by reporting the extended natural history of this disease.

Malignant vascular neoplasms of the liver are uncommon. We report the case of a young woman who developed an epithelioid hemangioendothelioma of the liver associated with multiple focal nodular hyperplasias and hepatic cavernous hemangiomas. Such an unusual association is probably not fortuitous and could support the theory that focal nodular hyperplasia is a reaction to an abnormal vascular supply rather than a true neoplasm.

AIM To assess the feasibility and diagnostic accuracy of endoscopic ultrasound guided fine needle biopsy (EUS-FNAB) in patients with solid pancreatic masses. METHODS Ninety nine consecutive patients with pancreatic masses were studied. Histological findings obtained by EUS-FNAB were compared with the final diagnosis assessed by surgery, biopsy of other tumour site or at postmortem examination, or by using a combination of clinical course, imaging features, and tumour markers. RESULTS EUS-FNAB was feasible in 90 patients (adenocarcinomas, n = 59; neuroendocrine tumours, n = 15; various neoplasms, n = 6; pancreatitis, n = 10), and analysable material was obtained in 73. Tumour size (⩾ or < 25 mm in diameter) did not influence the ability to obtain informative biopsy samples. Diagnostic accuracy was 74.4% (adenocarcinomas, 81.4%; neuroendocrine tumours, 46.7%; other lesions, 75%; p<0.02). Overall, the diagnostic yield in all 99 patients was 68%. Successful biopsies were performed in six patients with portal hypertension. Minor complications (moderate bleeding or pain) occurred in 5% of cases. CONCLUSIONS EUS-FNAB is a useful and safe method for the investigation of pancreatic masses, with a high feasibility rate even when lesions are small. Overall diagnostic accuracy of EUS-FNAB seems to depend on the tumour type.

Calcitonin release has rarely been reported in patients (pts) with neuroendocrine pancreatic tumors (NPT). The aim of this study was to describe the characteristics of calcitonin-secreting tumors (CST) of the pancreas. Serum calcitonin determination was part of the prospective evaluation of 66 pts with NPT referred to our institution over a 3-year period. Six pts (9%) had elevated calcitonin levels [at least twice the limit of the normal value (N)]. Abdominal ultrasonography, computed tomography scan, and endoscopic ultrasound were performed to identify the primary tumor(s) and metastases. Immunostaining using anticalcitonin and other antibodies was performed on the surgical resection specimen (four pts) or biopsy of liver metastases (two pts). Three of the six pts (four males, two females; median age, 51.5 years) had diarrhea. Serum calcitonin levels (median, range) were 17.5 N (6N-40N). Slight elevations in serum somatostatin (1.2N-2.3N) were associated in three pts. Pancreatic tumors were single in five of six pts and evenly distributed in the head and in the tail. Five pts had metastases, mainly in the liver. Multiple endocrine neoplasia type I was present in one pt. Immunostaining using calcitonin and somatostatin antibodies was positive in four pts each, respectively, and areas that were positive for one peptide were negative for the other. Diarrhea disappeared in the two pts who responded to treatment of the tumor(s). Three of the four pts with liver metastases died from tumor progression after 2, 10, and 24 months, respectively. CST of the pancreas are often malignant and can be considered as functional in half of the cases, irrespective of the serum calcitonin levels. Somatostatin secretion is often associated. Although rare, calcitonin secretion should be investigated in NPT pts presenting with diarrhea that cannot be explained by an increase in other hormone levels or in patients with nonfunctioning NPT.

Mucinous cystic tumors of the pancreas must be distinguished from other cystic lesions because of their potential malignancy. Our purpose was to assess the reliability of gastric MI mucin analysis in the fluid of cystic lesions of the pancreas in comparison or association with carcinoembryonic antigen. MI mucin and carcinoembryonic antigen were measured in cyst fluid obtained preoperatively by fine-needle aspiration. The lesions consisted of 12 serous cystadenomas, 9 mucinous cystadenomas, 8 cystadenocarcinomas and 6 intraductal mucinous hypersecreting neoplasms. Thirty pancreatic pseudocysts complicating well-documented chronic pancreatitis were also examined, in addition, MI mucins were localized by immunoperoxidase staining in fetal and normal adult pancreas and in mucinous and serous tumors. Carcinoembryonic values of >20 ng/ml and MI mucin values of >50 U MI/ml represented 82 and 78% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from serous cystadenomas; the sensitivity for this purpose was 100% using these criteria in combination. Carcinoembryonic antigen values of >300 ng/ml and MI mucin values of > 1,200 U MI/ml represented 56 and 30% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from pseudocysts; the sensitivity for this purpose was 60% using these criteria in combination. By immunohistology, MI mucins were detected in the wall of mucinous lesions but not in fetal and normal adult pancreas and in serous cystadenomas. Measurement of MI mucin antigen in cyst fluid could thus improve the diagnosis of mucinous cystic lesions of the pancreas. (C) 1997 Wiley-Liss, Inc.

Background: We report the clinical and histologic features of a distinctive form of chronic esophagitis for which we propose the term chronic esophagitis dissecans.Methods: The study group included five patients diagnosed at Hopital Beaujon, Clichy, from 1988 to 1994. Clinical and endoscopic examinations were performed. Samples of esophageal biopsy specimens were analysed by histologic and ultrastructural examinations and by immunohistochemistry with antibodies directed against cell adhesion molecules.Results: All patients were elderly (mean age, 66 years). They presented the following combination of clinical and endoscopic features: (1) long-standing history of chronic dysphagia, without symptoms of reflux, (2) shedding of mucosal fragments, occurring spontaneously or after mechanical trauma, (3) existence of localized esophageal strictures, (4) lack of concurrent chronic cutaneomucous lesions. Two patients presented with thymoma. Histologic examination showed evidence of mucosal blistering; in the absence of significant inflammatory lesions. Altered cell-cell adhesion was suggested by the reduced number of desmosomes on ultrastructural examination and the decreased expression of immunoreactive intercellular adhesion molecule E-cadherin.Conclusion: Chronic esophagitis dissecans likely represents a hitherto unrecognized clinicopathologic entity and must be added to the causes of chronic dysphagia.

Lipid peroxidation, which may be involved in the pathogenesis of acute pancreatitis, is usually assessed in vitro or indirectly using antioxidants or free radical scavengers. We assessed lipid peroxidation in an in vivo model by measuring ethane exhalation in two models of acute pancreatitis. Edematous acute pancreatitis was induced by a supramaximal intraperitoneal injection of cerulein. Necrotizing acute pancreatitis was induced by retrograde infusion of sodium taurocholate into the pancreaticobiliary duct. Rats were placed in closed chambers and ethane exhalation was measured in aliquots. Ethane exhalation was significantly increased (p < 0.002) in cerulein (n = 12)- but not in taurocholate (n = 6)-induced pancreatitis compared to controls (n = 12 and 6, respectively). Our results suggest that free radicals may play a role in the pathogenesis of edematous pancreatitis but do not play an important role in the progression to necrotizing pancreatitis.

We report the case of an adult patient affected by acute syncytial giant cell hepatitis which had a subfulminant course leading to liver transplantation. Syncytial giant cell hepatitis recurred after transplantation and was efficiently treated with ribavirin, In this patient, the recurrence of the disease, the presence of filamentous strands on electron microscopy during both bouts of hepatitis and the efficacy of ribavirin on post-transplantation hepatitis suggest that the disease was caused by an original virus. This observation also suggests that early administration of ribavirin in patients affected by acute syncytial giant cell hepatitis of unknown origin could avoid liver transplantation.

In contrast with the well-recognized membranous obstruction of the inferior vena cava, short-length hepatic vein stenoses are not well-recognized causes of hepatic venous outflow block. The aim of this study was to ascertain the prevalence, causes, manifestations, and outcome of short-length hepatic vein stenoses. We performed a retrospective study of patients with short-length hepatic vein stenosis among 86 patients with hepatic venous outflow block who were seen between 1970 and 1992. There were 25 patients with short-length hepatic vein stenosis. A thrombogenic condition was identified in 14 patients (56%). The lesions of the accompanying hepatic veins in these patients were variable (short-length stenoses, thromboses, or nonspecific changes) and similar to that seen in patients without short-length hepatic vein stenosis. In 3 necropsied cases, the venous lesions were suggestive of fibrous sequela of prior thromboses. In patients with short-length hepatic vein stenosis, splenomegaly (28% vs. 55%, P < .05) and hypersplenism were significantly less common; serum transaminase (P < .001) and creatinine levels (P < .02) were lower, prothrombin was higher (P < .001), and 5-year survival was significantly better (Kaplan-Meier estimates: 80% vs. 50%, P < .05). In patients with hepatic venous outflow block, short-length hepatic vein stenosis is a common lesion that appears to be the sequela of localized thrombosis. Long-term anticoagulation and percutaneous angioplasty (with or without stenting) are potentially applicable in these lesions. The long-term results of these treatments merit further evaluation.