pag. 295-398 - Siapec

PATOLOGIA DELL’APPARATO DIGERENTE331cune neoplasie endocrine ed in alcuni tumori solidi pseudopapillari.Descriviamo un caso di adenocarcinoma papillare intraduttaleoncocitico con estensione all’intero organo.MaterialiSi tratta di una paziente di 71 anni con importante calo ponderaleche radiologicamente presentava un pancreas completamentesostituito da multiple formazioni cistiche confluenti,la maggiore di 18 cm, localizzata a livello del corpo, con all’internogettoni solidi parietali. Sospettando una neoplasiaintraduttale del pancreas è stato eseguito un intervento displenopancreasectomia totale.RisultatiL’esame macroscopico ha evidenziato un dotto di Wirsungprogressivamente dilatantesi dalla papilla di Vater sino alcorpo ove appariva comunicare con una voluminosa neoformazionecistica a parete sottile e con superficie interna trabecolataricoperta da materiale mucoide. Lungo il suo interodecorso il lume del dotto risultava occupato da multipleproiezioni papillari. Il parenchima pancreatico circostante eracostituito da dotti ectasici d’aspetto cistico, talora a contenutomucoide e occupati da vegetazioni papillari. Microscopicamente,il rivestimento delle strutture cistiche e le proiezionipapillari erano costituiti da cellule cilindriche a citoplasmaossifilo, formanti un epitelio pseudostratificato. Solo un estesocampionamento ha messo in evidenza microfocolai di infiltrazionestromale, mentre non era presente diffusione extrapancreatica.La paziente è viva ed in buona salute 5 mesidopo l’intervento chirurgico.ConclusioniLe neoplasie intraduttali papillari oncocitiche sono rare, presentanocaratteristiche macroscopiche sovrapponibili alleneoplasie mucinose intraduttali ed hanno tipicamente un decorsoclinico indolente. Ulteriori studi sono necessari permettere in evidenza l’eventuale presenza di caratteristichecliniche distintive.Involvement of RASSF1A tumor suppressorgene in distinct subtypes of digestiveendocrine tumorsS. Pizzi, C. Azzoni, L. Bottarelli, T. D’Adda, G. Rindi, C.BordiDep. Pathology & Laboratory Medicine, Pathologic Anatomy,University of Parma, ItalyBackgroundRASSF1A is a Ras effector homologue gene, mapping on3p21.3 and epigenetically inactivated in a wide variety of humancancers. RASSF1A induces cell cycle arrest through theRb-mediated checkpoint, inhibiting accumulation of cyclin-D1. Frequent hypermethylation of RASSF1A promoter isfound in pancreatic carcinomas, especially in endocrine tumors(PETs), and seems to be associated with malignancy.Indeed, 3p LOH is considered a frequent event at least in malignantPETs and its correlation with metastatic progressionis under debate. Aims of this study were to analyze the involvementof RASSF1A as candidate tumor suppressor geneat 3p, and to clarify its role in the whole spectrum of digestiveendocrine tumors.MethodsSixty benign and malignant gastroenteropancreatic endocrinetumors have been analyzed. Tissues were formalin-fixed,paraffin-embedded. RASSF1A promoter hypermethylationhas been investigated by chemical modification of genomicDNA with sodium bisulfite and methylation-specific PCR.LOH has been determined using two 3p21.3 microsatellitemarkers (D3S1100 and D3S1621).ResultsRASSF1A promoter hypermethylation was found in gastric(37.5%) and pancreatic (100%) tumors, including both benignand malignant cases, and was virtually absent in otherdigestive endocrine neoplasms. Similarly, 3p21.3 LOH wasfound only in gastric (56%) and pancreatic (75%) tumors, beingsignificantly more frequent in malignant (70%) than inbenign (33%) cases.ConclusionsRASSF1A tumor suppressor gene plays a role in the progressionof gastric and pancreatic endocrine neoplasms, but notin other digestive endocrine tumors, supporting distinct molecularmechanisms in the development of digestive endocrinetumors with different site of origin.Loss of heterozigosity on chromosomesegments Xq25 and Xq26 in malignantgastroenteropancreatic endocrinecarcinomasC. Azzoni, L. Bottarelli, S. Pizzi, T. D’Adda and C. BordiDepartment of Pathology and Laboratory Medicine, Universityof ParmaIntroductionThe X chromosome is involved in the carcinogenesis andmalignant progression of different types of human tumorsand an increasing number of genes potentially involved hasbeen identified. The aims of this study were: first, to compareX chromosome loss of heterozigosity (LOH) in low and highgrade gastroenteropancreatic (GEP) endocrine carcinomas;second, to investigate common regions of deletion harboringputative tumor suppressor genes potentially involved in thesetypes of tumors.MethodsA comparative analysis of LOH on X chromosome was performedon 12 low grade well differentiated (WDECs) and 5high grade poorly differentiated (PDECs) GEP endocrinecarcinomas. In attempt to identify common regions of deletionthe allelotyping analysis was carried out using 24 polymorphicmarkers covering the whole X chromosome at regularintervals.ResultsOverall, the frequency of LOH on X chromosome in all informativeloci investigated was 59%, with a significantlyhigher rate in PDECs (69%) than in WDECs (52%),(p