3. Less common solid tumors of pancreas

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Introduction

Pancreatic adenocarcinoma arising from the ductal cells in the pancreas remains the most common pancreatic malignancy and accounts for 85–90% of all pancreatic neoplasms. While pancreatic adenocarcinoma has a poor prognosis, nonductal solid pancreatic tumors may be associated with a considerably better prognosis and can be differentiated from the more common adenocarcinoma based on imaging and pathological characteristics. This chapter reviews these less common solid tumors, including pancreatic neuroendocrine tumors (PNETs), acinar cell carcinomas (ACCs), solid pseudopapillary tumors (SPTs), primary pancreatic lymphomas (PPLs), and isolated pancreatic metastases.

Pancreatic neuroendocrine tumors

Neuroendocrine neoplasms of the pancreas were traditionally referred to as pancreatic carcinoids or islet cell tumors, assumed to arise from the islet cells, and were thought to have an indolent course. As the heterogeneous nature of this lesion was recognized, the term “neuroendocrine tumor” was proposed in place of “carcinoid” as it conveys the potential malignant nature and histopathology of the tumor more accurately [1]. These tumors are now classified as pancreatic neuroendocrine tumors (PanNETs) and are believed to be a group of epithelial neoplasms that are derived from multipotential stem cells of endodermal origin with predominant neuroendocrine differentiation [2]. PanNETs account for approximately 3% of all pancreatic neoplasms [3]. There is vast heterogeneity among these tumors; despite sharing a common histological appearance, they differ in biologic behavior, histologic differentiation, and functionality. PanNETs can be further categorized into functional and nonfunctional tumors based on the secretion of biologically active peptides and hormones, resulting in specific clinical syndromes [4, 5]. The WHO 2010 PanNET classification was revised to include mixed adenoneuroendocrine carcinomas, previously referred to as mixed-form carcinoid adenocarcinoma or mixed exocrine– endocrine carcinoma. This type of neoplasm is comprised of both adenocarcinoma and neuroendocrine carcinoma, with at least 30% of each component [6].

Epidemiology

PanNETs are rare tumors with a reported incidence of 1–2 cases/106 population/year though a much higher rate ranging from 0.07 to 10% has been reported in surgical and autopsy series [7, 8]. This variation underscores the limitation in determining the exact incidence and prevalence of PanNETs as the majority of these tumors are small and indolent and may remain asymptomatic. Registry data from Europe, the United States, and Japan showed a rising incidence of these tumors, which probably correlates with the increased use of cross-sectional imaging and more frequent detection of incidental and asymptomatic tumors [9]. Older European studies report an incidence rate (per 100,000) of approximately 0.1 while more recent studies report an incidence rate of 0.3. A similar increase is reflected in the SEER database, with a rise in incidence from 0.17 (1970s) to 0.43 (2003–2007) [9]. A stratified sample survey in Japan reported a much higher incidence rate of 1.01/100,000, with a prevalence rate of 2.23/100,000 [10]. 24% of patients in this survey had an incidental diagnosis of their tumors.

The median age at diagnosis for PanNETs is 60 years, with a peak incidence rate occurring between the sixth and eighth decades. These tumors are slightly more common among men (53%) than women (47%) [11, 12]. Most PanNETs are nonfunctional and sporadic though they may be associated with hereditary endocrinopathies such as multiple endocrine neoplasia (MEN; Type 1), von Hippel–Lindau (VHL) disease, neurofibromatosis type 1 (NF1), and tuberous sclerosis [13]. Patients with these endocrinopathies have an increased risk of developing neuroendocrine tumors ranging from 35 to 75% of MEN 1, 20% for VHL disease, 10% for NF1, and 1% for tuberous sclerosis [5, 14]. In these patients, PanNETs tend to occur at a younger age, are multiple, and are likely to be diagnosed earlier because of surveillance in carriers of the mutations.

The incidence of functional PanNETs varies by tumor type with insulinoma being the most common (1–4 cases/106 population/year), followed by gastrinoma (0.5–2 cases/106 population/year), VIPoma (0.05–0.2 cases/106 population/year), and glucagonoma (0.01–0.1 cases/106 population/ year), respectively [12]. The true incidence of rarer types of PanNETs such as somatostatinoma, GRHoma, ACTHoma, and PTHrPoma is difficult to estimate given their rarity.

Since the majority of PanNETs are nonfunctional, most patients present at an advanced stage with mass effect or metastatic disease, and the 5-year survival has been reported between 27 and 62% [9]. The 5-year survival after surgical resection of noninsulinoma PanNETs has been reported as 65%, with a 10-year survival of 45% [15].

Classification

Functional PanNETs

Functionality of PanNETs depends on the clinical symptoms rather than the level or type of hormones secreted. Each type of functional PanNETs produces a distinct clinical hormonal hypersecretion syndrome, which will be described in detail later in this chapter.


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