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Pancreatic Neoplasms: HELP
Articles by Fausto Sessa
Based on 15 articles published since 2010
(Why 15 articles?)
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Between 2010 and 2020, Fausto Sessa wrote the following 15 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Calcitonin-Producing Neuroendocrine Neoplasms of the Pancreas: Clinicopathological Study of 25 Cases and Review of the Literature. 2017

Uccella, Silvia / Blank, Annika / Maragliano, Roberta / Sessa, Fausto / Perren, Aurel / La Rosa, Stefano. ·Department of Medicine and Surgery, Unit of Pathology, University of Insubria, 21100, Varese, Italy. silvia.uccella@uninsubria.it. · Institute of Pathology, University of Bern, Bern, Switzerland. · Department of Medicine and Surgery, Unit of Pathology, University of Insubria, 21100, Varese, Italy. · Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland. ·Endocr Pathol · Pubmed #29063495.

ABSTRACT: Increased levels of circulating calcitonin are a clue in the diagnosis of medullary thyroid carcinoma. However, hypercalcitoninemia can also be related to other pathological conditions, including pancreatic neuroendocrine neoplasms (PanNENs). Ectopic hormonal production is not unusual in both functioning and non-functioning PanNENs; however, little is known about the frequency of calcitonin expression in these neoplasms. The aims of this study were to assess the frequency of calcitonin immunoreactivity in PanNENs, independently from serum calcitonin levels, and to evaluate the clinicopathological and prognostic features of calcitonin-immunoreactive (Cal-IR) PanNENs, including a comparison with cases already reported in the literature. We screened 229 PanNENs for the immunohistochemical expression of calcitonin, including both functioning and non-functioning neoplasms, as well as both well-differentiated and poorly differentiated PanNENs. Both the clinicopathological data and the follow-up information were available and were compared with the immunohistochemical results. In addition, we reviewed the features of the calcitonin-producing PanNENs previously reported in the literature. Calcitonin was expressed in 25 of our 229 PanNENs (10.9%). Examples of well- and poorly differentiated, as well as both functioning and non-functioning PanNENs, were found to be calcitonin immunoreactive. Cal-IR PanNENs did not show any significant difference with the whole series of neoplasms included in the study, when the clinicopathological parameters were considered, except for a younger age at diagnosis and for a larger size of the tumor in non-functioning Cal-IR PanNENs. Taken together, our results show that calcitonin immunoreactivity is not an exceptional event in PanNENs. Furthermore, calcitonin expression does not identify a separate clinical entity, in contrast to other PanNENs with ectopic hormone production, such as adrenocorticotropic hormone (ACTH)-producing PanNENs, which show a distinctively more aggressive behavior.

2 Review Diagnostic Approach to Neuroendocrine Neoplasms of the Gastrointestinal Tract and Pancreas. 2015

Uccella, Silvia / Sessa, Fausto / La Rosa, Stefano. ·Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy. ·Turk Patoloji Derg · Pubmed #26177322.

ABSTRACT: The gastroenteropancreatic (GEP) system is the site of origin of about two thirds of all neuroendocrine neoplasms (NENs) of the human body. GEP-NENs encompass a wide spectrum of entities, from very indolent tumors to highly aggressive carcinomas. They represent a challenge for the oncologist and a correct diagnostic approach is crucial for the management of patients. The nomenclature and classification of these tumors have been a matter of debate for more than a century, since their first description by Siegfried Oberdorfer. The last WHO classification provided a robust and easy-to-use tool to prognostically stratify GEP-NENs, based on morphological aspects and on proliferation rate. This review examines current approaches to the diagnosis and prognostic classification of GEP-NENs, focusing on the critical use of morphological parameters and immunohistochemical stainings, including diagnostic, site-specific and prognostic markers. The key issues of the current classification are addressed, including the emerging topics about cases with discordant morphology and proliferative index. Finally, we attempted to highlight the diagnostic pitfalls and the caveats in the use of immunohistochemical stains.

3 Review ACTH-secreting pancreatic neoplasms associated with Cushing syndrome: clinicopathologic study of 11 cases and review of the literature. 2015

Maragliano, Roberta / Vanoli, Alessandro / Albarello, Luca / Milione, Massimo / Basturk, Olca / Klimstra, David S / Wachtel, Antonio / Uccella, Silvia / Vicari, Emanuela / Milesi, Marina / Davì, Maria Vittoria / Scarpa, Aldo / Sessa, Fausto / Capella, Carlo / La Rosa, Stefano. ·*Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy ‡‡Department of Pathology, Ospedale di Circolo, Varese, Italy †Department of Molecular Medicine, University of Pavia, Pavia, Italy ‡Department of Pathology, San Raffaele Hospital, Milan, Italy §Department of Pathology, National Institute of Cancer, Milan, Italy #Department of Pathology, Multimedica, Milan, Italy **Department of Medicine, "G.B. Rossi" University Hospital, Verona, Italy ††ARC-NET Research Center and Department of Pathology and Diagnostics, University of Verona, Verona, Italy ∥Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY ¶Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru. ·Am J Surg Pathol · Pubmed #25353285.

ABSTRACT: Adrenocorticotropic hormone (ACTH)-secreting pancreatic neuroendocrine tumors (PanNETs), although rare, are responsible for about 15% of ectopic Cushing syndrome (CS). They represent a challenging entity because their preoperatory diagnosis is frequently difficult, and clear-cut morphologic criteria useful to differentiate them from other types of PanNETs have not been defined. Ectopic ACTH secretion associated with CS can also be rarely due to pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma, rare tumor types with morphologic features sometimes overlapping those of PanNETs and, for this reason, representing a diagnostic challenge for pathologists. We herein describe the clinicopathologic and immunohistochemical features of 10 PanNETs and 1 ACC secreting ACTH and associated with CS together with an extensive review of the literature to give the reader a comprehensive overview on ACTH-producing pancreatic neoplasms. ACTH-secreting PanNETs are aggressive neoplasms with an immunohistochemical profile that partially overlaps that of pituitary corticotroph adenomas. They are generally large and well-differentiated neoplasms without distinctive histologic features but with signs of aggressiveness including vascular and perineural invasion. They are more frequent in female individuals with a mean age of 42 years. At 5 and 10 years after diagnosis, 35% and 16.2% of patients, respectively, were alive. ACTH-secreting ACCs and pancreatoblastomas are very aggressive pediatric tumors with a poor prognosis. Using an appropriate immunohistochemical panel including ACTH, β-endorphin, trypsin, and BCL10 it is possible to recognize ACTH-secreting PanNETs and to distinguish them from the very aggressive ACTH-secreting ACCs.

4 Review High-grade poorly differentiated neuroendocrine carcinomas of the gastroenteropancreatic system: from morphology to proliferation and back. 2014

La Rosa, Stefano / Sessa, Fausto. ·Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100, Varese, VA, Italy, stefano.larosa@ospedale.varese.it. ·Endocr Pathol · Pubmed #24715269.

ABSTRACT: Poorly differentiated neuroendocrine carcinomas (PDNECs) of the gastroenteropancreatic system (GEP) are a heterogeneous group of aggressive malignancies with a high propensity for distant metastases and an ominous prognosis. They have traditionally been divided into small and large cell subtypes on morphological grounds. However, histological diagnosis needs to be supported by immunohistochemistry to avoid possible misdiagnoses either with the more frequent poorly differentiated adenocarcinomas and squamous cell carcinomas or with lymphomas and mesenchymal neoplasms. Although it is well known that GEP PDNECs are associated with a poor prognosis, data from some published studies seem to suggest that there is a fraction of patients with PDNECs who have better survival than expected. GEP PDNECs are currently classified according to the criteria proposed in the 2010 WHO classification. They are simply called neuroendocrine carcinomas (NECs) and are defined by mitotic count >20 × 10 HPF and/or Ki-67 labeling index >20 %. However, a few recent papers have indicated that some NECs, as defined by the 2010 WHO scheme, do not show a poorly differentiated morphology as expected. This category seems to show a better prognosis and, especially, does not respond to cisplatin-based chemotherapy, which represents the goal standard therapeutic approach to high-grade PDNECs. In the present review, the main morphological, immunohistochemical, and prognostic features will be discussed as well as the opportunity to introduce a new category characterized by well to moderately differentiated morphology associated with high proliferation (mitotic count >20 × 10 HPF and/or Ki-67 index >20 %).

5 Review Ectopic duodenal insulinoma: a very rare and challenging tumor type. Description of a case and review of the literature. 2013

La Rosa, Stefano / Pariani, Dario / Calandra, Calogera / Marando, Alessandro / Sessa, Fausto / Cortese, Ferdinando / Capella, Carlo. ·Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100, Varese, Italy, stefano.larosa@ospedale.varese.it. ·Endocr Pathol · Pubmed #24006218.

ABSTRACT: Although most insulinomas are located in the pancreas, very rare ectopic cases have been described in the spleen, perisplenic tissue, duodenohepatic ligament, and adjacent to the ligament of Treitz. Moreover, three cases located in the duodenum have also been reported in the English literature. Ectopic insulinomas represent challenging neoplasms with clinical implications mainly due to the difficulties in their pre-operatory diagnosis and localization. In the present paper, we describe the fourth ectopic duodenal insulinoma so far reported. A 75-year-old woman presented at clinical observation due to neuroglycopenic symptoms that disappeared after glucose intake. Tumor was localized in the second portion of the duodenum in front of the papilla of Vater and was surgically enucleated. Microscopically, it was composed of monomorphic cells with eosinophilic cytoplasm arranged in trabecular and lobular patterns and diffusely positive for insulin, proinsulin, amylin, and PDX1. About 30 % of tumor cells also showed immunoreactivity for somatostatin, while no positivity for glucagon, pancreatic polypeptide, gastrin, serotonin, and somatostatin receptor subtype 2A was found. The Ki67 proliferative index was 1 %. We have also reviewed the literature on this topic to give the reader a comprehensive overview of this very rare tumor type.

6 Article Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. 2018

Rindi, Guido / Klersy, Catherine / Albarello, Luca / Baudin, Eric / Bianchi, Antonio / Buchler, Markus W / Caplin, Martyn / Couvelard, Anne / Cros, Jérôme / de Herder, Wouter W / Delle Fave, Gianfranco / Doglioni, Claudio / Federspiel, Birgitte / Fischer, Lars / Fusai, Giuseppe / Gavazzi, Francesca / Hansen, Carsten P / Inzani, Frediano / Jann, Henning / Komminoth, Paul / Knigge, Ulrich P / Landoni, Luca / La Rosa, Stefano / Lawlor, Rita T / Luong, Tu V / Marinoni, Ilaria / Panzuto, F / Pape, Ulrich-Frank / Partelli, Stefano / Perren, Aurel / Rinzivillo, Maria / Rubini, Corrado / Ruszniewski, Philippe / Scarpa, Aldo / Schmitt, Anja / Schinzari, Giovanni / Scoazec, Jean-Yves / Sessa, Fausto / Solcia, Enrico / Spaggiari, Paola / Toumpanakis, Christos / Vanoli, Alessandro / Wiedenmann, Bertram / Zamboni, Giuseppe / Zandee, Wouter T / Zerbi, Alessandro / Falconi, Massimo. ·Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italyguido.rindi@unicatt.it. · Service of Biometry and Clinical Epidemiology, Research Department, and IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Oncology, Cancer Campus, Villejuif, France. · Department of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Surgery, University Hospital Heidelberg, Neu Heidelberg, Germany. · Neuroendocrine Tumour Unit, Centre for Gastroenterology, London, United Kingdom. · Department of Pathology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Section Endocrinology, Department of Internal Medicine, Erasmus University Medical Center and and Erasmus MC Cancer Institute Rotterdam, Rotterdam ENETS Center of Excellence, Rotterdam, The Netherlands. · Digestive and Liver Disease Unit, Sant'Andrea University Hospital, Roma ENETS Center of Excellence, Rome, Italy. · Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Department of Surgery, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Pancreatic Surgery, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Hepatology and Gastroenterology, Charité, Campus Virchow Klinikum and Charite Mitte, University Medicine Berlin, Berlin ENETS Center of Excellence, Berlin, Germany. · Institute of Pathology, Stadtspital Triemli, Zurich, Switzerland. · Department of Surgery and Oncology, General and Pancreatic Surgery, The Pancreas Institute, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, Ospedale di Circolo, Università dell'Insubria, Varese, Italy. · Section of Pathology and ARC-Net Research Centre, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Institute of Pathology, University of Bern, Bern, Switzerland. · Pancreatic Surgery Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, Marche Polytechnic University, Ancona, Italy. · Department of Gastroenterology and Pancreatology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Medical Biology and Pathology, Cancer Campus, Villejuif, France. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Pathology Department, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·Neuroendocrinology · Pubmed #30300897.

ABSTRACT: BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

7 Article c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers. 2018

La Rosa, Stefano / Bernasconi, Barbara / Vanoli, Alessandro / Sciarra, Amedeo / Notohara, Kenji / Albarello, Luca / Casnedi, Selenia / Billo, Paola / Zhang, Lizhi / Tibiletti, Maria Grazia / Sessa, Fausto. ·Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, 25 rue du Bugnon, 1011, Lausanne, Switzerland. stefano.larosa@chuv.ch. · Department of Medicine and Surgery, University of Insubria, Varese, Italy. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, 25 rue du Bugnon, 1011, Lausanne, Switzerland. · Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Centre de Pathologie, Strasbourg, France. · Unit of Pathology, Ospedale Civile, Legnano, Italy. · Department of Pathology, Mayo Clinic, Rochester, MN, USA. · Department of Pathology, ASST-Sette Laghi, Varese, Italy. ·Virchows Arch · Pubmed #29721608.

ABSTRACT: The molecular alterations of pancreatic acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MANECs) are not completely understood, and the possible role of c-MYC amplification in tumor development, progression, and prognosis is not known. We have investigated c-MYC gene amplification in a series of 35 ACCs and 4 MANECs to evaluate its frequency and a possible prognostic role. Gene amplification was investigated using interphasic fluorescence in situ hybridization analysis simultaneously hybridizing c-MYC and the centromere of chromosome 8 probes. Protein expression was immunohistochemically investigated using a specific monoclonal anti-c-myc antibody. Twenty cases had clones with different polysomies of chromosome 8 in absence of c-MYC amplification, and 5 cases had one amplified clone and other clones with chromosome 8 polysomy, while the remaining 14 cases were diploid for chromosome 8 and lacked c-MYC amplification. All MANECs showed c-MYC amplification and/or polysomy which were observed in 54% pure ACCs. Six cases (15.3%) showed nuclear immunoreactivity for c-myc, but only 4/39 cases showed simultaneous c-MYC amplification/polysomy and nuclear protein expression. c-myc immunoreactivity as well as c-MYC amplification and/or chromosome 8 polysomy was not statistically associated with prognosis. Our study demonstrates that a subset of ACCs shows c-MYC alterations including gene amplification and chromosome 8 polysomy. Although they are not associated with a different prognostic signature, the fact that these alterations are present in all MANECs suggests a role in the acinar-neuroendocrine differentiation possibly involved in the pathogenesis of MANECs.

8 Article The number of positive nodes accurately predicts recurrence after pancreaticoduodenectomy for nonfunctioning neuroendocrine neoplasms. 2018

Partelli, Stefano / Javed, Ammar A / Andreasi, Valentina / He, Jin / Muffatti, Francesca / Weiss, Matthew J / Sessa, Fausto / La Rosa, Stefano / Doglioni, Claudio / Zamboni, Giuseppe / Wolfgang, Christopher L / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Medicine and Surgery, University of Insubria, Varese, Italy. · Service of Clinical Pathology, Lausanne University Hospital, Institute of Pathology, Lausanne, Switzerland. · Department of Pathology, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Pathology, Ospedale "Sacro Cuore-Don Calabria", Negrar, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #29610023.

ABSTRACT: BACKGROUND: The most appropriate nodal staging for pancreatic neuroendocrine neoplasms (PanNENs) is unclear. Aim of the study was to evaluate the effect of the number of positive lymph nodes on prognosis after pancreaticoduodenectomy for PanNENs. METHODS: A retrospective analysis of pancreaticoduodenectomies for nonfunctioning PanNENs was performed. PanNENs with nodal metastases (N+) were classified into N1 (1 to 3 positive lymph nodes) and N2 (4 or more positive lymph nodes). Univariate and multivariate analyses of disease-free survival were performed. RESULTS: 157 patients were included. 99 patients (63%) had N0 PanNENs whereas 58 patients (37%) had nodal involvement (N+). Patients with N0 PanNENs had a 3-year disease-free survival rate of 89% compared with 83% and 75% in patients with N1 and N2 PanNENs, respectively (P < 0.0001). Independent predictors of disease-free survival were the presence of necrosis, lymph node ratio and nodal status. Factors positively correlated with the number of positive lymph nodes were the Ki67 value, the T stage and the number of examined lymph nodes. Similar percentage of N0 and N+ PanNENs was demonstrated for a cut-off of 13 examined lymph nodes. CONCLUSIONS: The number of positive lymph nodes is accurate in predicting recurrence for PanNENs. Thirteen examined lymph nodes seems to be the minimum number of lymph nodes to be resected/examined in patients who undergo pancreaticoduodenectomy for PanNENs.

9 Article The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: Morphological Differentiation and Proliferation Identify Different Prognostic Categories. 2017

Milione, Massimo / Maisonneuve, Patrick / Spada, Francesca / Pellegrinelli, Alessio / Spaggiari, Paola / Albarello, Luca / Pisa, Eleonora / Barberis, Massimo / Vanoli, Alessandro / Buzzoni, Roberto / Pusceddu, Sara / Concas, Laura / Sessa, Fausto / Solcia, Enrico / Capella, Carlo / Fazio, Nicola / La Rosa, Stefano. ·Anatomic Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy. ·Neuroendocrinology · Pubmed #26943788.

ABSTRACT: BACKGROUND/AIMS: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with a Ki-67 index >20% according to the 2010 WHO classification. Some reports suggest that this category is heterogeneous. We retrospectively studied a series of 136 patients affected by grade 3 GEP-NECs with the aim to clarify the prognostic role of tumor morphological differentiation, proliferation, defect in mismatch repair proteins (MMRd), CD117 expression, and site of origin. The primary endpoint was the correlation between these parameters and the overall survival (OS). METHODS: Univariate and multivariable Cox proportional hazards regression analyses were used to assess the prognostic significance of various clinical and histopathologic features. RESULTS: With a median follow-up of 81 months, the median OS was 12.9 months. At multivariate analysis, morphological differentiation, Ki-67 index, MMRd, stage, and CD117 expression were independent prognostic markers in NECs. Three different prognostic categories of NECs were identified according to the degree of morphologic differentiation (well vs. poorly differentiated) and Ki-67 index (<55% vs. ≥55%). On this basis, median OS was 43.6 months in well-differentiated neoplasms with a Ki-67 index 20-55% (named type A), 24.5 months in poorly differentiated neoplasms with a Ki-67 index 20-55% (type B), and 5.3 months (p < 0.0001) in poorly differentiated neoplasms with a Ki-67 index ≥55% (type C). CONCLUSIONS: The present study suggests that GEP-NECs represent a heterogeneous group of neoplasms which can be better classified in different prognostic categories using both tumor morphology and Ki-67 index.

10 Article TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer. 2016

La Rosa, Stefano / Bernasconi, Barbara / Frattini, Milo / Tibiletti, Maria Grazia / Molinari, Francesca / Furlan, Daniela / Sahnane, Nora / Vanoli, Alessandro / Albarello, Luca / Zhang, Lizhi / Notohara, Kenji / Casnedi, Selenia / Chenard, Marie-Pierre / Adsay, Volkan / Asioli, Sofia / Capella, Carlo / Sessa, Fausto. ·Department of Pathology, Ospedale di Circolo, viale Borri 57, 21100, Varese, Italy. stefano.larosa@ospedale.varese.it. · Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy. · Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland. · Department of Pathology, Ospedale di Circolo, viale Borri 57, 21100, Varese, Italy. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. · Department of Pathology, Kurashiki Central Hospital, Kurashiki, Japan. · Centre de Pathologie, Strasbourg, France. · Department of Pathology, Hospital De Hautepierre, Strasbourg, France. · Department of Pathology, Emory University, Atlanta, GA, USA. · Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. ·Virchows Arch · Pubmed #26586531.

ABSTRACT: The molecular alterations of pancreatic acinar cell carcinomas (ACCs) are poorly understood and have been reported as being different from those in ductal adenocarcinomas. Loss of TP53 gene function in the pathogenesis of ACCs is controversial since contradictory findings have been published. A comprehensive analysis of the different possible genetic and epigenetic mechanisms leading to TP53 alteration in ACC has never been reported and hence the role of TP53 in the pathogenesis and/or progression of ACC remains unclear. We investigated TP53 alterations in 54 tumor samples from 44 patients, including primary and metastatic ACC, using sequencing analysis, methylation-specific multiplex ligation probe amplification, fluorescence in situ hybridization, and immunohistochemistry. TP53 mutations were found in 13 % of primary ACCs and in 31 % of metastases. Primary ACCs and metastases showed the same mutational profile, with the exception of one case, characterized by a wild-type sequence in the primary carcinoma and a mutation in the corresponding metastasis. FISH analysis revealed deletion of the TP53 region in 53 % of primary ACCs and in 50 % of metastases. Promoter hypermethylation was found in one case. The molecular alterations correlated well with the immunohistochemical findings. A statistically significant association was found between the combination of mutation of one allele and loss of the other allele of TP53 and worse survival.

11 Article Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the clinical, morphological, immunohistochemical, and molecular characteristics of an unusual pancreatic carcinoma. 2015

Vanoli, Alessandro / Argenti, Francesca / Vinci, Alessio / La Rosa, Stefano / Viglio, Alessandra / Riboni, Roberta / Necchi, Vittorio / Pugliese, Luigi / Sessa, Fausto / Pietrabissa, Andrea / Paulli, Marco. ·Department of Pathology, Fondazione IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Pavia, Italy, ale.vanol@virgilio.it. ·Virchows Arch · Pubmed #25989715.

ABSTRACT: We report a case of tumour in the head of the pancreas observed in a 57-year-old man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP) serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the tumour was predominantly composed of solid sheets of large eosinophilic cells with a prominent lymphoid infiltration without association neither with DNA microsatellite instability nor Epstein-Barr virus infection. The tumour was diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic staining for AFP was focally observed. Moreover, tumour cells showed countless cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A primary hepatocellular carcinoma of the liver was ruled out by careful clinical analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here, we describe the first case of such variant associated with lymphoid stroma. The characteristic histologic features and the immunophenotypic profile help in distinguishing this carcinoma from other pancreatic tumours, notably from medullary carcinoma.

12 Article Prognostic relevance of aberrant DNA methylation in g1 and g2 pancreatic neuroendocrine tumors. 2014

Stefanoli, Michele / La Rosa, Stefano / Sahnane, Nora / Romualdi, Chiara / Pastorino, Roberta / Marando, Alessandro / Capella, Carlo / Sessa, Fausto / Furlan, Daniela. ·Section of Anatomic Pathology, Department of Surgical and Morphological Sciences, University of Insubria and Ospedale di Circolo, Varese, Italy. ·Neuroendocrinology · Pubmed #25011998.

ABSTRACT: BACKGROUND/AIMS: The occurrence and clinical relevance of DNA hypermethylation and global hypomethylation in pancreatic neuroendocrine tumours (PanNETs) are still unknown. We evaluated the frequency of both epigenetic alterations in PanNETs to assess the relationship between methylation profiles and chromosomal instability, tumour phenotypes and prognosis. METHODS: In a well-characterized series of 56 sporadic G1 and G2 PanNETs, methylation-sensitive multiple ligation-dependent probe amplification was performed to assess hypermethylayion of 33 genes and copy number alterations (CNAs) of 53 chromosomal regions. Long interspersed nucleotide element-1 (LINE-1) hypomethylation was quantified by pyrosequencing. RESULTS: Unsupervised hierarchical clustering allowed to identify a subset of 22 PanNETs (39%) exhibiting high frequency of gene-specific methylation and low CNA percentages. This tumour cluster was significantly associated with stage IV (p = 0.04) and with poor prognosis in univariable analysis (p = 0.004). LINE-1 methylation levels in PanNETs were significantly lower than in normal samples (p < 0.01) and were approximately normally distributed. 12 tumours (21%) were highly hypomethylated, showing variable levels of CNA. Interestingly, only 5 PanNETs (9%) were observed to show simultaneously LINE-1 hypomethylation and high frequency of gene-specific methylation. LINE-1 hypomethylation was strongly correlated with advanced stage (p = 0.002) and with poor prognosis (p < 0.0001). In the multivariable analysis, low LINE-1 methylation status and methylation clusters were the only independent significant predictors of outcome (p = 0.034 and p = 0.029, respectively). CONCLUSION: The combination of global DNA hypomethylation and gene hypermethylation analyses may be useful to define distinct subsets of PanNETs. Both alterations are common in PanNETs and could be directly correlated with tumour progression.

13 Article APC alterations are frequently involved in the pathogenesis of acinar cell carcinoma of the pancreas, mainly through gene loss and promoter hypermethylation. 2014

Furlan, Daniela / Sahnane, Nora / Bernasconi, Barbara / Frattini, Milo / Tibiletti, Maria Grazia / Molinari, Francesca / Marando, Alessandro / Zhang, Lizhi / Vanoli, Alessandro / Casnedi, Selenia / Adsay, Volkan / Notohara, Kenji / Albarello, Luca / Asioli, Sofia / Sessa, Fausto / Capella, Carlo / La Rosa, Stefano. ·Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy. ·Virchows Arch · Pubmed #24590585.

ABSTRACT: Genetic and epigenetic alterations involved in the pathogenesis of pancreatic acinar cell carcinomas (ACCs) are poorly characterized, including the frequency and role of gene-specific hypermethylation, chromosome aberrations, and copy number alterations (CNAs). A subset of ACCs is known to show alterations in the APC/β-catenin pathway which includes mutations of APC gene. However, it is not known whether, in addition to mutation, loss of APC gene function can occur through alternative genetic and epigenetic mechanisms such as gene loss or promoter methylation. We investigated the global methylation profile of 34 tumor suppressor genes, CNAs of 52 chromosomal regions, and APC gene alterations (mutation, methylation, and loss) together with APC mRNA level in 45 ACCs and related peritumoral pancreatic tissues using methylation-specific multiplex ligation probe amplification (MS-MLPA), fluorescence in situ hybridization (FISH), mutation analysis, and reverse transcription-droplet digital PCR. ACCs did not show an extensive global gene hypermethylation profile. RASSF1 and APC were the only two genes frequently methylated. APC mutations were found in only 7 % of cases, while APC loss and methylation were more frequently observed (48 and 56 % of ACCs, respectively). APC mRNA low levels were found in 58 % of cases and correlated with CNAs. In conclusion, ACCs do not show extensive global gene hypermethylation. APC alterations are frequently involved in the pathogenesis of ACCs mainly through gene loss and promoter hypermethylation, along with reduction of APC mRNA levels.

14 Article Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: insights into the morphology and immunophenotype and search for prognostic markers. 2012

La Rosa, Stefano / Adsay, Volkan / Albarello, Luca / Asioli, Sofia / Casnedi, Selenia / Franzi, Francesca / Marando, Alessandro / Notohara, Kenji / Sessa, Fausto / Vanoli, Alessandro / Zhang, Lizhi / Capella, Carlo. ·Department of Pathology, Ospedale di Circolo, 21100 Varese, Italy. stefano.larosa@ospedale.varese.it ·Am J Surg Pathol · Pubmed #23026929.

ABSTRACT: Acinar cell carcinoma (ACC) of the pancreas is a very rare tumor that has various morphologic features, which may give rise to diagnostic difficulties. Because of its rarity, many clinicopathologic characteristics remain to be further elucidated, and prognostic factors are yet to be well established. With the aim of better characterizing this carcinoma and searching for prognostic indicators, we collected 62 ACCs and investigated the following parameters: site, size, local infiltration, node and distant metastases, architectural pattern, nuclear atypia, presence of necrosis, lymphovascular and perineural invasion, proliferation, BCL10, trypsin, carboxyl ester lipase, amylase, lipase, PDX1, cytokeratin 19 (CK19), CK7, p53, and β-catenin expression. Twelve cases showing >30% of endocrine cells were reclassified as mixed acinar-neuroendocrine carcinomas, whereas 1 tumor was reclassified as a mixed ductal-acinar carcinoma and was excluded from the statistical prognostic evaluations. BCL10 and trypsin were the most reliable immunohistochemical markers, whereas amylase and lipase were not. Surgery was statistically correlated with a better prognosis (P=0.0008). Among resected tumors there was no difference in survival between ACCs and mixed acinar-neuroendocrine carcinomas, and factors that significantly correlated with poor prognosis were size >6.5 cm (P=0.004), lymph node (P=0.0039) and distant (P=0.008) metastases, and UICC stage (P=0.009). Stage was the only independent prognostic factor at multivariable analysis, and the best prognostic discrimination was observed on grouping together stages I and II and grouping together stages III and IV, suggesting a simplification of the UICC staging for such cancers. In addition, vascular and perineural invasion and CK19 and p53 expression showed a trend for poor prognosis, not reaching statistical significance.

15 Article Pancreatic PEComa: a case report with ultrastructural localization of HMB-45 within melanosomes. 2012

Finzi, Giovanna / Micello, Donata / Wizemann, Giorgio / Sessa, Fausto / Capella, Carlo. ·Department of Pathology, Ospedale di Circolo, Varese, Italy. giovanna.finzi@ospedale.varese.it ·Ultrastruct Pathol · Pubmed #22471435.

ABSTRACT: PEComas (perivascular epithelioid cell tumors) represent a group of mesenchymal neoplasms showing characteristic morphologic, immunohistochemical, ultrastructural, and genetic features. These neoplasms are usually considered benign, being often well circumscribed by a thin capsule and showing scarce atypia. However, in some cases, they show local invasion and multiple metastases and cause the patient's death. PEComas have been found in many locations, but only 7 cases have been described in the pancreas to date. Here, the authors report an additional case of this rare neoplasm and demonstrate the HMB-45 immunoreactivity of melanosomes or premelanosomes at the ultrastructural level.