Adriana Handra-Luca

Adenomyoma and Adenomyomatous Hyperplasia of the Vaterian System: Clinical, Pathological, and New Immunohistochemical Features of 13 Cases

Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are consistently benign lesions. Clinically, adenomyoma mimics frequently ampullary adenoma or carcinoma, and biopsy analysis is often difficult. The histogenesis of ampullary adenomyoma and adenomyomatous hyperplasia is still subject to debate. We present a retrospective study of clinicopathological features of 13 cases of surgically resected ampullary adenomyoma. The age of our patients was between 38 and 78 years (mean: 63 y). The preoperative diagnosis was ampullary tumor or tumor of the head of the pancreas. On macroscopy, a white, firm lesion of the ampullary wall was observed; its size ranged between 10 and 30 mm. Histologically the lesion consisted of multiple glandular structures surrounded by a fibroblastic/myofibroblastic proliferation, resulting in a “pseudo-hypertrophy” of the Vaterian system. The immunophenotype of the epithelial component was cytokeratin 7+/cytokeratin 20−, similar to that of the normal biliary and pancreatic duct system. The epithelial cells exhibited low proliferative activity. The hyperplastic myofibroblastic cells expressed smooth muscle actin. A complete pancreatic heterotopy contiguous with the adenomyoma was noted in three cases. Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are benign lesions frequently treated by extensive surgery because of long-term biliary obstruction. The clinicopathological characteristics suggest either a reactive and/or a malformative, nonneoplastic nature for this lesion, which could, in some cases, develop from heterotopic pancreas. The immunophenotype of epithelial cells may be a useful tool for differentiating it from ampullary adenoma on biopsy specimens.

Human pancreatic mucinous cystadenoma is characterized by distinct mucin, cytokeratin and CD10 expression compared with intraductal papillary-mucinous adenoma

Aims :u2002To examine cytokeratin, epithelial glycoprotein (mucin) and glycoprotein CD10 expression in benign mucinous cystdenomas (MCAs) in comparison with intraductal papillary mucinous adenomas (IPMAs).

Familial multiple gastrointestinal stromal tumours with associated abnormalities of the myenteric plexus layer and skeinoid fibres

Familial multiple gastrointestinal stromal tumours with associated abnormalities of the myenteric plexus layer and skeinoid fibres

Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin.

Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin

Multiple mixed adenoma-focal nodular hyperplasia of the liver associated with spontaneous intrahepatic porto-systemic shunt: a new type of vascular malformation associated with the multiple focal nodular hyperplasia syndrome?

Ireland). It was performed on a viable tumour specimen frozen at the time of macroscopic examination. Very high amounts of amylase (1800 U ⁄ mg pancreatic protein) were detected in the cytosol of the tumour cells. On the basis of the histopathological findings and the biological features, the diagnosis of acinar cell carcinoma was established. Acinar cell carcinoma is a rare malignant exocrine pancreatic tumour affecting adults and rarely occurs in young patients. The main difficulty is to rule out the diagnosis of a pancreatoblastoma which is one of the most frequently encountered tumours in infants. However, on the basis of biological and pathological features, although these two tumours share many similarities, they can be distinguished by the presence of squamoid corpuscules in pancreatoblastoma but not in acinar cell carcinoma. Microscopically, acinar cell carcinoma is a cellular epithelial tumour displaying acinar differentiation, variably associated with a glandular and a minor endocrine component. However, staining for somatostatin has not been previously reported. Even in the most comprehensive study to date of acinar cell carcinoma of the pancreas, no positivity was found for this islet cell hormone in adult or in childhood tumours. In the present case, clusters of cells positive for somatostatin were detected with a polyclonal antibody specific for human somatostatin, that showed no cross-reactivity with other antigens. Somatostatin, normally produced by the D cells of pancreatic islets, is variably expressed in islet cell tumours of the pancreas that are generally nonfunctioning, with a low grade of malignancy. Since somatostatin is known to inhibit cell proliferation and counteracts growth factors in cancer cells, its detection in tumour cells could reflect reduced tumour aggressiveness.

Correlation between patterns of DNA mismatch repair hmlh1 and hmsh2 protein expression and progression of dysplasia in intraductal papillary mucinous neoplasms of the pancreas

Defective DNA mismatch repair results from genetic or epigenetic alterations that most frequently inactivate the genes hMLH1 and hMSH2. This is thought to promote tumourigenesis by accumulation of mutations in oncogenes and tumour suppressor genes. This pathway, first reported in colon cancer, has been recently demonstrated in a subgroup of sporadic pancreatic adenocarcinomas. Intraductal papillary-mucinous neoplasms of the pancreas are a special type of pancreatic tumours, characterised by a spectrum of morphological changes from mild to moderate and to non-invasive, and they may associate with adenocarcinoma. An immunohistochemical study of hmlh1 and hmsh2 protein expression was performed on 26 intraductal papillary-mucinous neoplasms. All tumours showed nuclear expression of hmlh1 and hmsh2 proteins. There were two distinctive patterns of protein expression on the basis of the location of cells expressing these markers: the “normal” pattern, observed mainly in adenoma and rarely in intraductal papillary-mucinous neoplasms with moderate dysplasia and the “dysplastic” pattern, frequently encountered in moderate dysplasia neoplasms, non-invasive and invasive carcinomas. These findings suggest that defective DNA mismatch repair, due to inactivation of hMLH1 and hMSH2, does not play a significant role in the pathogenesis of intraductal papillary-mucinous neoplasms of the pancreas. Two patterns of protein expression were observed and were correlated with the progression of dysplasia in intraductal papillary mucinous neoplasms.

Mucinous cystadenoma with mesenchymal over-growth: a new variant among pancreatic mucinous cystadenomas?

We report an unusual type of mucinous cystadenoma of the pancreas, characterised by a predominantly solid gross appearance due to the presence of an abundant ovarian-type stroma. The tumour, located in the body of the pancreas, was discovered after episodes of acute pancreatitis. It was composed of several mucus-secreting benign cysts placed within a highly cellular ovarian-type stroma, composed of undifferentiated spindle cells with mild atypia but without any increase of mitotic activity and with a low proliferative index. These cells expressed oestrogen and progesterone receptors, but they did not express CD34, CD117, p53 protein or bcl-2. Recognition of this peculiar mainly solid mucinous cystadenoma containing an abundant ovarian-type stroma is difficult. It is conceivable that the mesenchymal component described in our case could represent an early stage in the development of sarcoma in mucinous cystadenoma of the pancreas.

CO.59 L’expression de mTOR activé est corrélée à la prolifération cellulaire, à l’expression de PTEN et à la survenue de récidive dans les adénocarcinomes pancréatiques

Introduction mTOR est un des substrats de la voie de signalisation PI3K/AKT intervenant dans la proliferation cellulaire tumorale. Il existe sous forme de 2 complexes : mTORC1, sensible a la rapamycine, et mTORC2 interferant avec l’activite AKT. La signification biologique de mTOR dans les adenocarcinomes canalaires pancreatiques (ACP) est peu connue. Le but du travail a ete d’etudier la relation entre l’expression de la forme activee, phosphorylee de mTOR (p-mTOR), d’autres proteines de la voie PI3K/AKT et les caracteristiques clinico-pathologiques dans les ACP. Patients et Methodes Les donnees de 99 patients ayant eu la resection chirurgicale d’un ACP sans traitement neoadjuvant (1999-2004) ont ete analysees. Une etude immunohistochimique sur des puces tissulaires a ete effectuee avec des anticorps anti-proteines Ki67,AKT2,AKT phosphorylee (p-AKT), p-mTOR, PTEN. Pour Ki67, le pourcentage de noyaux tumoraux positifs a ete note. L’expression de PTEN a ete identifiee comme presente/non-detectee. Un score integrant le pourcentage et l’intensite du marquage a ete etabli pour les autres proteines ; sa valeur mediane utilisee comme seuil pour classer les tumeurs a expression proteique faible ou elevee. Le test de Fisher et une etude de survie type Kaplan-Meier ont ete utilises pour l’analyse ; 0,05 etant le seuil de significativite. Resultats Parmi les 99 patients (age median, 62 ans), 47 etaient des femmes. 26 tumeurs etaient classees T1, 32 T2 et 41 T3. Il existait une necrose tumorale chez 58 patients. 80 patients presentaient des metastases ganglionnaires et 2 une dissemination a distance. 59 patients ont eu un traitement post-operatoire radio-et/ou chimiotherapique. 53 patients ont developpe une recidive et 56 patients sont decedes (survie mediane 2,7 ans). Une survie diminuee etait correlee a la presence de plus de 3 metastases ganglionnaires (pxa0=xa00,04), d’une necrose tumorale (pxa0=xa00,01) et a un T eleve (pxa0=xa00,03). L’expression de p-mTOR et AKT2 etait cytoplasmique, detectee dans 70 et 71 ACP. L’expression de p-AKT et PTEN etait nucleaire, observee dans 93 et 42 tumeurs. L’index Ki67 median etait de 40 % (limites, 0-75). L’expression elevee de p-mTOR etait correlee a un index Ki-67 eleve (pxa0 Conclusion Les resultats de cette etude montrent que les formes activees de mTOR et AKT sont frequemment exprimees dans les ACP et qu’une expression elevee de p-mTOR est correlee a une proliferation cellulaire elevee, a l’expression de PTEN et a la survenue d’une recidive. Ces resultats suggerent que les ACP pourraient etre cibles par des agents therapeutiques agissant sur la voie PI3K/AKT. Remerciements, financements, autres Ce travail est realise grâce aux fonds a la recherche de la SNFGE.