Pancreatic Neuroendocrine Neoplasms: Practical Approach to Diagnosis, Classification, and Therapy

195 Pages·2015·13.932 MB·English

by  Stefano La Rosa, Fausto Sessa

Pancreatic
Neuroendocrine
Neoplasms
Practical Approach to
Diagnosis, Classifi cation,
and Therapy
Stefano La Rosa
Fausto Sessa
Editors
123
Pancreatic Neuroendocrine Neoplasms

Stefano La Rosa (cid:129) Fausto Sessa
Editors
Pancreatic
Neuroendocrine
Neoplasms
Practical Approach to Diagnosis,
Classifi cation, and Therapy
Editors
Stefano La Rosa Fausto Sessa
Department of Pathology Department of Surgical
Ospedale di Circolo and Morphological Sciences
Varese , Italy University of Insubria
Varese , Italy
ISBN 978-3-319-17234-7 ISBN 978-3-319-17235-4 (eBook)
DOI 10.1007/978-3-319-17235-4
Library of Congress Control Number: 2015940328
Springer Cham Heidelberg New York Dordrecht London
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Pref ace
Since the early 2000s, the advances in imaging technologies and the wide
diffusion of endoscopic ultrasound-guided fi ne needle aspiration have led to
an increased detection of pancreatic neuroendocrine neoplasms compelling
radiologists, pathologists, and nuclear medicine physicians to manage these
diseases at an earlier stage. The increased surgical expertise together with
new pharmacological options has also changed the therapeutic approach. At
the same time, the refi ned WHO classifi cation of 2010, increased experience
of pathologists in this fi eld, better knowledge of the clinicopathological fea-
tures, and the availability of new molecular technologies have all increased
our understanding of the pathogenesis and progression of such neoplasms.
For all these reasons, the fi eld of pancreatic neuroendocrine neoplasms has
rapidly grown in the last 10 years and the aim of this book is to capture these
dynamic changes providing a broad overview of this topic.
After a historical and epidemiological overview, four chapters attempt to
capture the technical advances in diagnostic procedures providing insights
for a critical evaluation of the new diagnostic options. The chapters on the
immunohistochemical approach to diagnosis and on the criteria now used to
classify pancreatic neuroendocrine neoplasm in different prognostic catego-
ries represent the bridge between the diagnostic step and the full characteriza-
tion of the different entities. These are treated in 11 chapters which cover the
epidemiology, diagnosis, morphology, and prognosis of each tumor type.
A specifi c chapter is also dedicated to hyperplastic and microadenomatous
neuroendocrine lesions, which may represent a diagnostic challenge for
pathologists and clinicians.
Careful consideration is given to the molecular features of various tumors
and a specifi c chapter gives a critical overview of the most important knowl-
edge which has contributed to our understanding of the pathogenesis of such
neoplasms and may have potential implications for new therapeutic path-
ways. The fi nal chapters consider the surgical and medical approaches to
therapy, providing a practical and analytical overview of the available
options.
The book is written by a multidisciplinary team of worldwide-recognized
experts and is addressed to radiologists, nuclear medicine physicians,
v
vi Preface
endocrinologists, pathologists, surgeons, and oncologists interested in endo-
crine tumors of the pancreas.
The editors wish to thank the contributing authors and hope the readers
will fi nd all the information they need for their daily practice.
Varese, Italy Stefano La Rosa
Varese, Italy Fausto Sessa
Contents
1 Historical Background and Epidemiology . . . . . . . . . . . . . . . . . 1
Fausto Sessa and Roberta Maragliano
2 Radiological Diagnosis of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Carlo Fugazzola, Maria Gloria Angeretti, Natalie Lucchina,
Ejona Duka, Valeria Molinelli, and Fausto Sessa
3 The Role of Nuclear Medicine in the Diagnosis of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Vittoria Rufi ni, Paola Castaldi, and Valerio Lanni
4 Endocrinological Approach to the Diagnosis of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Wouter W. de Herder
5 Cytological Diagnosis of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Massimo Bongiovanni, Christine Sempoux, and Antoine Nobile
6 Classifi cation and Staging of Pancreatic Neuroendocrine
Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Frediano Inzani, Gianluigi Petrone, and Guido Rindi
7 Immunohistochemical Approach to the Diagnosis
and Prognostic Evaluation of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Ricardo V. Lloyd, Jason N. Rosenbaum, and Lori A. Erickson
8 Insulinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Jean-Yves Scoazec
9 Glucagonoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Anne Couvelard and Olivia Hentic
10 Somatostatin-Producing Tumor . . . . . . . . . . . . . . . . . . . . . . . . . 89
Paul Komminoth
11 VIPoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Carlo Capella and Stefano La Rosa
vii
viii Contents
12 Gastrinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Anja M. Schmitt, Annika Blank, and Aurel Perren
13 ACTH-Producing Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Silvia Uccella, Roberta Maragliano, and Francesca Magnoli
14 Serotonin-Producing Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Stefano La Rosa, Nora Sahnane, and Laura Cimetti
15 Pancreatic Neuroendocrine Tumors Producing GHRH, GH,
Ghrelin, PTH, or PTHrP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Kai Duan, Shereen Ezzat, Sylvia L. Asa, and Ozgur Mete
16 Nonfunctioning Pancreatic Neuroendocrine
Neoplasms (Including PP-Producing
and Calcitonin-Producing Tumors) . . . . . . . . . . . . . . . . . . . . . . . 141
Alessandro Vanoli and Enrico Solcia
17 Poorly Differentiated Neuroendocrine Carcinoma
of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Olca Basturk and David S. Klimstra
18 Mixed Adenoneuroendocrine Carcinoma of the Pancreas . . . . 155
Michelle D. Reid, Gizem Akkas, Olca Basturk,
and Volkan Adsay
19 Hyperplastic and Microadenomatous Pancreatic
Neuroendocrine Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Günter Klöppel, Martin Anlauf, Aurel Perren, and Bence Sipos
20 Molecular Pathology of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Daniela Furlan
21 Surgical Therapy of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Angela Maurizi, Stefano Partelli, Francesca Muffatti,
Sara Nobile, and Massimo Falconi
22 Medical Therapy of Pancreatic
Neuroendocrine Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Nicola Fazio
1
Historical Background
and Epidemiology
Fausto Sessa and Roberta Maragliano
1.1 Historical Background the bile duct and suggested that the pancreatic
juice could act by diluting and softening the bile.
The pancreas is a deeply located organ, which Thomas Wharton observed the similarity between
had been neglected for centuries until 1543 when the structure of the pancreas and that of the sub-
the anatomist Andries van Wesel, better known maxillary gland from which Samuel Thomas v on
as Andreas Vesalius (1514–1564), gave his Sömmerring (1755–1830) employed the term
description in the fi fth book of “De Humani “Bauchspeicheldrüse” or “abdominal salivary
Corporis Fabrica Libri Septem.” However, Rufus gland.” This terminology was used until the
of Ephesus (circa 100 A.D.) fi rst gave the name beginning of the last century [1 – 4 ].
pancreas to the organ, which had previously been In February 1869, Paul Langerhans (1847–
described by Herophilus of Chalcedon (circa 300 1888) fi rst described the pancreatic islets, which
B.C.). For several centuries, this organ was for- make up the 1–2 % of the mass of the pancreas
gotten probably because the canons of ancient (average weight 70–100 g) (Fig. 1 .1a ). At the end
medicine had not linked the theories of body fl u- of his medical studies, he presented a thesis enti-
ids to any pancreatic diseases. tled “Contributions to the microscopic anatomy
In 1642, Johann Georg Wirsung (1589–1643) of the pancreas,” in which he refers to i slands of
described the main pancreatic duct when he was clear cells throughout the gland, staining differ-
a prosector in Padua, Italy, where he performed ently than the surrounding tissue (Fig. 1 .1b ) [5 ].
autopsies under the guidance of his mentor, In 1893, E. Laguesse named these clusters of
Ioannes Veslingius (Johann Vesling, 1598–1649). clear cells “Islands of Langerhans” and suggested
In 1720, the German anatomist Abraham Vater that they were the pancreatic units involved in
described the site of conjunction between the bile diabetes mellitus [6 ]. In 1902, he described in
duct and the pancreatic duct, now known as the detail the histological characteristics of the islets
ampulla of Vater. The physiologist Albrecht Von in dogs after ligation of the duct. After that,
Haller (1708–1777) noted that the pancreatic E. Lindsay Opie (1873–1971) described the hya-
duct entered the small bowel in conjunction with line changes of pancreatic islets in diabetic
patients. At the beginning of the last century,
F.G. Banting and C.H. Best, working at the
F. Sessa (*) (cid:129) R . Maragliano University of Toronto under the supervision of
Department of Surgical and Morphological Sciences ,
the physiologist J.J. R. Macleod, obtained “isle-
University of Insubria , Via O. Rossi 9 ,
tin” from Ringer’s solution containing pancreatic
21100 Varese , Italy
e-mail: [email protected] juice from dogs (Fig. 1 .2 ). Insulin was not
S. La Rosa, F. Sessa (eds.), Pancreatic Neuroendocrine Neoplasms: Practical Approach to Diagnosis, 1
Classifi cation, and Therapy, DOI 10.1007/978-3-319-17235-4_1,
© Springer International Publishing Switzerland 2015