DOI: 10.1148/rg.276075001
RadioGraphics 2007;27:1667-1679
© RSNA, 2007
Neuroendocrine Neoplasms of the Gastrointestinal Tract: Classification, Pathologic Basis, and Imaging Features1
Samuel Chang, MD,
Dongil Choi, MD,
Soon Jin Lee, MD,
Won Jae Lee, MD,
Mi-hyun Park, MD,
Sang Won Kim, MD,
Da Keun Lee, MD, and
Kee-Taek Jang, MD
From the Department of Radiology and Center for Imaging Science (S.C., D.C., S.J.L., W.J.L., M.P., S.W.K.) and the Department of Diagnostic Pathology (D.K.L., K.-T.J.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710, South Korea. Presented as an education exhibit at the 2005 RSNA Annual Meeting. Received January 4, 2007; revision requested February 5 and received March 15; accepted March 16. All authors have no financial relationships to disclose.
Address correspondence to D.C. (e-mail: dichoi{at}smc.samsung.co.kr).
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Abstract
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Many radiologists are unfamiliar with the recently developed World Health Organization classification scheme for neuroendocrine tumors. According to this classification scheme, neuroendocrine tumors are divided into well-differentiated endocrine tumors (carcinoids), well-differentiated endocrine carcinomas (malignant carcinoids), and poorly differentiated endocrine carcinomas on the basis of their location, histologic features, and biologic behavior. Most neuroendocrine tumors have nonspecific imaging characteristics. However, they sometimes have peculiar clinical manifestations and radiologic features, on the basis of which radiologists may infer the specific diagnosis. Neuroendocrine tumors of the gastrointestinal tract originate from the cells derived from the embryonic neural crest, neuroectoderm, and endoderm. They usually produce bioactive substances and show immunoreactivity to neuroendocrine markers. Although neuroendocrine tumors are uncommon, they should be considered in developing the differential diagnosis for gastrointestinal tumors in patients with a typical syndrome or when the tumors have characteristic imaging features.
© RSNA, 2007
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LEARNING OBJECTIVES FOR TEST 3
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After reading this article and taking the test, the reader will be able to:
- Discuss the classification scheme for neuroendocrine neoplasms of the gastrointestinal tract and its histopathologic and immunohistochemical bases.
- Describe the imaging features of various neuroendocrine neoplasms of the gastrointestinal tract.
- List the organs of the gastrointestinal tract that are most often affected by neuroendocrine neoplasms and the relative frequencies with which they are affected.
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Introduction
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Most of the neoplasms involving the gastrointestinal tract are adenocarcinomas or squamous cell carcinomas, both of which have an endodermal epithelial origin. However, there are many different types of endocrine cells in the gastrointestinal tract that are derived from the neural crest, neuroectoderm, and endoderm. These cells can give rise to various neuroendocrine tumors that differ considerably from the more commonly seen tumors (1). The neuroendocrine system includes neuroendocrine cells of the adrenal medulla, pancreatic islets, and paraganglia; parathyroid, pituitary, and thyroid C cells; and neuroendocrine cells that are widely dispersed throughout the body, with locations including the gastrointestinal tract, biliary tract, liver, lung, urethra, and skin (2). Thus, neuroendocrine tumors may involve many different organs and sites containing these cells, although the majority of these tumors occur within the gastroenteropancreatic (GEP) axis. Because these cells share a number of antigens with nerve elements (neuroendocrine markers), the term neuroendocrine has been widely used to describe such cell types and derived tumors (3). The classification of neuroendocrine tumors has evolved rapidly over the past decade, keeping pace with the development of techniques of immunohistochemical analysis but perhaps confusing radiologists in the process.
Neuroendocrine tumors account for 1.2%–1.5% of all gastrointestinal neoplasms, with an incidence of 1.6–2.0 new cases per 100,000 persons per year (4). In the past decade, pathologically proved neuroendocrine tumors of the gastrointestinal tract from the hypopharynx to the rectum were diagnosed in 187 patients at our institution. According to our data, the rectum was the most common location (51.9% of cases), followed by the stomach (21.9%), duodenum (11.2%), colon (5.9%), appendix (3.2%), esophagus (3.2%), and other portions of the small intestine (2.1%). The majority of neuroendocrine tumors occur sporadically; that is, they are nonfamilial. However, they sometimes occur as part of complex familial endocrine cancer syndromes such as type 1 multiple endocrine neoplasia (MEN 1) (Fig 1) and neurofibromatosis type 1 (5,6). In this article, we briefly discuss gastrointestinal tumor markers. We also review the bases for the classification of gastrointestinal neuroendocrine tumors and discuss and illustrate the pathologic and radiologic manifestations of these tumors.
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Figure 1a. MEN 1 in a 33-year-old woman. (a) Transverse contrast material–enhanced computed tomographic (CT) scan shows a 1.3-cm enhancing tumor (arrow) in the greater curvature of the gastric midbody. The tumor was confirmed to be a carcinoid after subtotal gastrectomy. Pathologic analysis revealed eight more carcinoids, all of which were 0.7 cm or less in diameter and could not be visualized at CT. (b) Transverse CT scan shows another well-enhanced tumor 1.5 cm in diameter with a few small foci of low attenuation in the pancreatic tail (arrow). The tumor was confirmed to be an islet cell tumor after distal pancreatectomy. Pathologic analysis demonstrated two more islet cell tumors measuring 0.3 cm and 0.1 cm, respectively, neither of which was depicted at CT.
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Figure 1b. MEN 1 in a 33-year-old woman. (a) Transverse contrast material–enhanced computed tomographic (CT) scan shows a 1.3-cm enhancing tumor (arrow) in the greater curvature of the gastric midbody. The tumor was confirmed to be a carcinoid after subtotal gastrectomy. Pathologic analysis revealed eight more carcinoids, all of which were 0.7 cm or less in diameter and could not be visualized at CT. (b) Transverse CT scan shows another well-enhanced tumor 1.5 cm in diameter with a few small foci of low attenuation in the pancreatic tail (arrow). The tumor was confirmed to be an islet cell tumor after distal pancreatectomy. Pathologic analysis demonstrated two more islet cell tumors measuring 0.3 cm and 0.1 cm, respectively, neither of which was depicted at CT.
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Neuroendocrine Tumor Markers
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Immunohistochemical staining has played an important role in the diagnosis of neuroendocrine tumors. The neuroendocrine cells of the diffuse neuroendocrine system are characterized by (a) the presence of dense core granules ultra-structurally; and (b) the expression of certain marker proteins (ie, general neuroendocrine markers) such as chromogranin, synaptophysin, and neuron-specific enolase (NSE), as well as cell type–specific hormonal products such as peptide hormones and amines.
The chromogranin-secretogranin family is composed of acidic proteins that are present in the core of secretory granules of neuroendocrine cells. Chromogranin A has been detected in most neuroendocrine cells and neoplasms (Fig 2a). Tumors with few secretory granules may not show immunoreactivity with antibodies to chromogranin (7). Apart from these exceptions, chromogranin A is considered to be the single most important marker of neuroendocrine differentiation in general use (8). Synaptophysin is a trans-membrane glycoprotein that is present in the membranes of presynaptic vesicles (9). These vesicles differ from the secretory granules of chromogranin; thus, the staining profile of synaptophysin differs from that of chromogranin. Synaptophysin is also widely distributed in neuroendocrine cells and neoplasms and is a good general marker (Fig 2b). However, it is not specific for neuroendocrine cells and tumors because normal cells, adenomas, and carcinomas of the adrenal cortex may show immunoreactivity to synaptophysin (10). NSE is localized to neurons and neuroendocrine cells (Fig 2c) but is of limited usefulness because of its relative lack of specificity. Immunohistochemical antibodies are directed against the 
homodimer subunit of an NSE, which is specific to neurons and neuroendocrine cells. However, there is cross-reactivity with the 
heterodimeric form present in nonendocrine cells, including smooth muscle cells, myoepithelial cells, and lymphocytes (11).
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Figure 2a. General markers of neuroendocrine tumors. Photomicrographs (original magnification, x 100) obtained in a patient with well-differentiated endocrine carcinoma of the esophagus show reactivity with antibodies to chromogranin A (a), synaptophysin (b), and NSE (c).
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Figure 2b. General markers of neuroendocrine tumors. Photomicrographs (original magnification, x 100) obtained in a patient with well-differentiated endocrine carcinoma of the esophagus show reactivity with antibodies to chromogranin A (a), synaptophysin (b), and NSE (c).
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Figure 2c. General markers of neuroendocrine tumors. Photomicrographs (original magnification, x 100) obtained in a patient with well-differentiated endocrine carcinoma of the esophagus show reactivity with antibodies to chromogranin A (a), synaptophysin (b), and NSE (c).
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The hormones that are present in the GEP axis are specific markers of the normal and neoplastic neuroendocrine cells (Fig 3). Fifteen types of cells that produce hormonal peptides or biogenic amines are present in the pancreas and in the mucosa of the gastrointestinal tract (12).
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Figure 3a. Specific markers of neuroendocrine tumors. Photomicrographs (original magnification, x100) obtained in a patient with well-differentiated endocrine carcinoma of the rectum show reactivity with antibodies to serotonin (a) and glucagon (b).
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Figure 3b. Specific markers of neuroendocrine tumors. Photomicrographs (original magnification, x100) obtained in a patient with well-differentiated endocrine carcinoma of the rectum show reactivity with antibodies to serotonin (a) and glucagon (b).
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Classification of Neuroendocrine Tumors
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A variety of nomenclature has been used for neuroendocrine tumors, which may be confusing to radiologists. Traditionally, neuroendocrine tumors have been classified into three groups on the basis of whether they originated in the foregut, the midgut, or the hindgut (13). This classification scheme was designed to emphasize clinical-pathologic differences between the tumor groups. However, it was never generally accepted in routine practice because it was too imprecise to distinguish between the different biologically relevant GEP–neuroendocrine tumor entities (14).
In the first World Health Organization (WHO) classification scheme for neuroendocrine tumors, published in 1980, the term carcinoid was applied to most of the tumors. Carcinoids were divided into enterochromaffin cell carcinoids, gastrin cell carcinoids, and other (unspecified) carcinoids. However, these categories have often led to misunderstandings between pathologists and clinicians, with pathologists applying the term carcinoid to all tumors with neuroendocrine features and clinicians understanding the term to refer to a serotonin-producing tumor with carcinoid syndrome. The classic carcinoid syndrome develops in less than 10% of patients with gastrointestinal carcinoids and includes cutaneous flushing and gut hypermotility with diarrhea (1). Carcinoids have various clinical manifestations depending on the combination of bioactive substances (ie, serotonin, histamine, tachykinins) present. The WHO classification scheme of 1980 did not take into account the heterogeneity of these tumors. For example, a carcinoid of the stomach is not the same as a carcinoid of the ileum or rectum (15). For these reasons, the terms neuroendocrine tumor and carcinoma were adopted in the WHO classification scheme of 2000 (16).
In this newer classification scheme, (neuro)endocrine tumors are divided into well-differentiated endocrine tumors, well-differentiated endocrine carcinomas, and poorly differentiated endocrine carcinomas (Fig 4). Well-differentiated endocrine tumors demonstrate benign behavior or uncertain malignant potential, well-differentiated endocrine carcinomas are characterized by low-grade malignancy, and poorly differentiated endocrine carcinomas show high-grade malignancy. Most poorly differentiated endocrine carcinomas are small cell carcinomas. For gastroenteric neuroendocrine tumors, the term carcinoid has been retained and is used synonymously with the term well-differentiated endocrine tumor. The term malignant carcinoid is used synonymously with the term well-differentiated endocrine carcinoma.
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Figure 4a. WHO classification of endocrine tumors. Photomicrographs (original magnification, x 200; hematoxylineosin [H–E] stain) show a well-differentiated endocrine tumor manifesting with round cells with scanty cytoplasm arranged in a glandular pattern (a), a well-differentiated endocrine carcinoma with the characteristic rosettes (b), and a poorly differentiated endocrine carcinoma manifesting with densely packed small cells with scanty cytoplasm and finely granular nuclear chromatin (c).
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Figure 4b. WHO classification of endocrine tumors. Photomicrographs (original magnification, x 200; hematoxylineosin [H–E] stain) show a well-differentiated endocrine tumor manifesting with round cells with scanty cytoplasm arranged in a glandular pattern (a), a well-differentiated endocrine carcinoma with the characteristic rosettes (b), and a poorly differentiated endocrine carcinoma manifesting with densely packed small cells with scanty cytoplasm and finely granular nuclear chromatin (c).
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Figure 4c. WHO classification of endocrine tumors. Photomicrographs (original magnification, x 200; hematoxylineosin [H–E] stain) show a well-differentiated endocrine tumor manifesting with round cells with scanty cytoplasm arranged in a glandular pattern (a), a well-differentiated endocrine carcinoma with the characteristic rosettes (b), and a poorly differentiated endocrine carcinoma manifesting with densely packed small cells with scanty cytoplasm and finely granular nuclear chromatin (c).
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The classification schemes for neuroendocrine tumors also contain subdivisions based on the location and biologic behavior of the tumors. Tumor locations include the stomach, duodenum and proximal jejunum, distal jejunum and ileum, appendix, colorectum, and pancreas. Morphologicbiologic criteria include tumor size, vascular invasion, and mitotic activity as well as histologic differentiation, presence of metastases, and invasion of adjacent organs. Hormonal activity and association with certain clinical syndromes are also included. If neuroendocrine tumors are functionally active due to uncontrolled secretion of insulin, gastrin, vasoactive intestinal polypeptide, glucagon, or some rare hormone, they can induce characteristic syndromes (hypoglycemia syndrome, Zollinger-Ellison syndrome [ZES], Verner-Morrison syndrome, glucagonoma syndrome) (15). These tumors have been referred to as insulinomas, gastrinomas, vipomas, and glucagonomas depending on the dominant hormone.
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Gastrointestinal Neuroendocrine Tumors
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Hypopharynx
Our Internet search showed no reports of neuroendocrine tumor of the hypopharynx, although such tumors could theoretically exist. Indeed, we saw one case of neuroendocrine tumor of the hypopharynx among the 187 patients with gastrointestinal neuroendocrine tumors at our institution (Fig 5).
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Figure 5a. Poorly differentiated neuroendocrine carcinoma of the hypopharynx in a 79-year-old man. (a) Transverse early arterial phase CT scan obtained at the level of the cricoid cartilage shows a relatively large mass with faint enhancement (arrows). The mass is circumscribed by the wall of the hypopharynx. Arrowheads indicate the very narrow hypopharyngeal lumen. (b) Transverse late arterial phase CT scan shows progressive enhancement of the mass (arrows). (c) Photomicrograph (original magnification, x200; H-E stain) shows that the majority of the tumor consists of poorly differentiated neuroendocrine carcinoma. The tumor contained a focal area of sarcomatoid differentiation. (d) Photomicrograph (original magnification, x100) reveals that the tumor is positive for synaptophysin.
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Figure 5b. Poorly differentiated neuroendocrine carcinoma of the hypopharynx in a 79-year-old man. (a) Transverse early arterial phase CT scan obtained at the level of the cricoid cartilage shows a relatively large mass with faint enhancement (arrows). The mass is circumscribed by the wall of the hypopharynx. Arrowheads indicate the very narrow hypopharyngeal lumen. (b) Transverse late arterial phase CT scan shows progressive enhancement of the mass (arrows). (c) Photomicrograph (original magnification, x200; H-E stain) shows that the majority of the tumor consists of poorly differentiated neuroendocrine carcinoma. The tumor contained a focal area of sarcomatoid differentiation. (d) Photomicrograph (original magnification, x100) reveals that the tumor is positive for synaptophysin.
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Figure 5c. Poorly differentiated neuroendocrine carcinoma of the hypopharynx in a 79-year-old man. (a) Transverse early arterial phase CT scan obtained at the level of the cricoid cartilage shows a relatively large mass with faint enhancement (arrows). The mass is circumscribed by the wall of the hypopharynx. Arrowheads indicate the very narrow hypopharyngeal lumen. (b) Transverse late arterial phase CT scan shows progressive enhancement of the mass (arrows). (c) Photomicrograph (original magnification, x200; H-E stain) shows that the majority of the tumor consists of poorly differentiated neuroendocrine carcinoma. The tumor contained a focal area of sarcomatoid differentiation. (d) Photomicrograph (original magnification, x100) reveals that the tumor is positive for synaptophysin.
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Figure 5d. Poorly differentiated neuroendocrine carcinoma of the hypopharynx in a 79-year-old man. (a) Transverse early arterial phase CT scan obtained at the level of the cricoid cartilage shows a relatively large mass with faint enhancement (arrows). The mass is circumscribed by the wall of the hypopharynx. Arrowheads indicate the very narrow hypopharyngeal lumen. (b) Transverse late arterial phase CT scan shows progressive enhancement of the mass (arrows). (c) Photomicrograph (original magnification, x200; H-E stain) shows that the majority of the tumor consists of poorly differentiated neuroendocrine carcinoma. The tumor contained a focal area of sarcomatoid differentiation. (d) Photomicrograph (original magnification, x100) reveals that the tumor is positive for synaptophysin.
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Esophagus
Neuroendocrine tumors of the esophagus are extremely rare but were seen in six of 187 patients. These tumors are usually located in the distal portion of the esophagus (Fig 6) and manifest as a small polypoid or ulcerative tumor (Table). Metastases are sometimes found in the regional lymph nodes or the liver (17).
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Figure 6a. Composite well-differentiated endocrine carcinoma and squamous cell carcinoma of the distal esophagus in a 69-year-old man. (a) Transverse CT scan shows diffuse circumferential wall thickening and dilatation of the distal esophagus (arrows). (b) Transverse CT scan obtained at the level of the upper gastric body shows multiple enlarged lymph nodes (arrows), findings that imply the presence of metastases. (c) Photomicrograph (original magnification, x 1.25; H–E stain) shows invasive squamous cell carcinoma (S) in the esophageal surface and neuroendocrine carcinoma (N) in the muscularis submucosa and muscularis propria.
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Figure 6b. Composite well-differentiated endocrine carcinoma and squamous cell carcinoma of the distal esophagus in a 69-year-old man. (a) Transverse CT scan shows diffuse circumferential wall thickening and dilatation of the distal esophagus (arrows). (b) Transverse CT scan obtained at the level of the upper gastric body shows multiple enlarged lymph nodes (arrows), findings that imply the presence of metastases. (c) Photomicrograph (original magnification, x 1.25; H–E stain) shows invasive squamous cell carcinoma (S) in the esophageal surface and neuroendocrine carcinoma (N) in the muscularis submucosa and muscularis propria.
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Figure 6c. Composite well-differentiated endocrine carcinoma and squamous cell carcinoma of the distal esophagus in a 69-year-old man. (a) Transverse CT scan shows diffuse circumferential wall thickening and dilatation of the distal esophagus (arrows). (b) Transverse CT scan obtained at the level of the upper gastric body shows multiple enlarged lymph nodes (arrows), findings that imply the presence of metastases. (c) Photomicrograph (original magnification, x 1.25; H–E stain) shows invasive squamous cell carcinoma (S) in the esophageal surface and neuroendocrine carcinoma (N) in the muscularis submucosa and muscularis propria.
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Stomach
From a clinical point of view, there are three types of carcinoids of the stomach. Type 1 gastric carcinoids are associated with chronic atrophic corpus gastritis and grow from the fundus and body. They are the most common type of gastric neuroendocrine tumor (70%–80% of cases) (18) and usually manifest as small (< 2-cm), often multiple tumors. A small gastric carcinoid resembles other more common submucosal tumors at endoscopy and radiology. Type 2 carcinoids are frequently associated with ZES and MEN 1. ZES–MEN 1 patients have a 29%–34% risk of developing type 2 gastric carcinoid. In contrast, no more than 1% of patients with sporadic ZES (not associated with MEN 1) develop gastric carcinoid (19). Type 2 carcinoids are also small (< 2 cm) and often multiple, with metastases being reported in 10%–30% of cases (20). Type 3 carcinoids occur in the absence of underlying gastric disease or hypergastrinemia (sporadic tumors). They are usually large (> 2-cm) single neoplasms located in the body and fundus and typically show vascular invasion at the time of diagnosis. Type 3 carcinoids often manifest with metastases, which are found in 50%–70% of gastric well-differentiated neuroendocrine carcinomas and in up to 100% of gastric poorly differentiated endocrine carcinomas (20).
According to a study of a large patient population by Modlin et al (21), gastric carcinoids account for 8.7% of all gastrointestinal neuroendocrine tumors. Among the 187 patients at our institution, 41 (21.9%) had neuroendocrine tumors of the stomach. The discrepancy between our data and those of Modlin et al had several causes, including ethnic and regional differences (eg, patients with mild symptoms and even healthy individuals underwent gastroscopy much more frequently in our country [South Korea] than in the United States). According to our data, well-differentiated endocrine carcinomas accounted for the largest proportion of gastric neuroendocrine tumors (19 of 41 cases [46%]) (Fig 7), followed by poorly differentiated endocrine carcinoma (10 of 41 [24%]) (Fig 8), endocrine-exocrine carcinoma (seven of 41 [17%]), and well-differentiated endocrine carcinoma (five of 41 [12%]) (Fig 9). At barium examination and CT, gastric neuroendocrine carcinomas, especially ulcerofungating or ulceroinfiltrative tumors, appear similar to advanced gastric cancer. Regional metastatic lymphadenopathy is frequently seen.
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Figure 7a. Well-differentiated endocrine tumor (carcinoid) of the stomach in a 63-year-old woman. (a) Transverse CT scan shows a large, enhancing polypoid mass with a cleft in the anterior wall of the gastric midbody (arrows). (b, c) Photomicrographs (original magnification, x100; H–E stain) show a carcinoid with the typical organoid or nesting pattern (b) and with strong reactivity to chromogranin A (c).
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Figure 7b. Well-differentiated endocrine tumor (carcinoid) of the stomach in a 63-year-old woman. (a) Transverse CT scan shows a large, enhancing polypoid mass with a cleft in the anterior wall of the gastric midbody (arrows). (b, c) Photomicrographs (original magnification, x100; H–E stain) show a carcinoid with the typical organoid or nesting pattern (b) and with strong reactivity to chromogranin A (c).
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Figure 7c. Well-differentiated endocrine tumor (carcinoid) of the stomach in a 63-year-old woman. (a) Transverse CT scan shows a large, enhancing polypoid mass with a cleft in the anterior wall of the gastric midbody (arrows). (b, c) Photomicrographs (original magnification, x100; H–E stain) show a carcinoid with the typical organoid or nesting pattern (b) and with strong reactivity to chromogranin A (c).
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Figure 8a. Poorly differentiated endocrine carcinoma (small cell carcinoma) of the stomach in a 64-year-old woman. (a) Transverse CT scan shows a 3-cm ulcerofungating mass with moderate enhancement around the gastric angle (arrows). (b) Virtual gastroscopic image shows an ulcerofungating tumor.
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Figure 8b. Poorly differentiated endocrine carcinoma (small cell carcinoma) of the stomach in a 64-year-old woman. (a) Transverse CT scan shows a 3-cm ulcerofungating mass with moderate enhancement around the gastric angle (arrows). (b) Virtual gastroscopic image shows an ulcerofungating tumor.
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Figure 9a. Well-differentiated endocrine carcinoma (malignant carcinoid) of the stomach in a 61-year-old man. (a) Transverse CT scan shows a large mass in the lower gastric body and proximal antrum (arrows). (b) Three-dimensional volume-rendered image shows a large indentation caused by an ulceroinfiltrative lesion in the lower gastric body and proximal antrum.
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Figure 9b. Well-differentiated endocrine carcinoma (malignant carcinoid) of the stomach in a 61-year-old man. (a) Transverse CT scan shows a large mass in the lower gastric body and proximal antrum (arrows). (b) Three-dimensional volume-rendered image shows a large indentation caused by an ulceroinfiltrative lesion in the lower gastric body and proximal antrum.
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Small Intestine
The small intestine is derived from both the foregut and the midgut. Neuroendocrine tumors of the duodenum and proximal jejunum are different from those of the distal jejunum and ileum. Duodenal carcinoids account for approximately 2% of all carcinoids involving the gastrointestinal tract (22) and were seen in 21 of 187 patients at our institution. There are five types of duodenal neuroendocrine tumors (15). Duodenal gastrinomas make up approximately two-thirds of all duodenal neuroendocrine tumors, followed by duodenal somatostatinomas; nonfunctioning serotonin-, gastrin-, or calcitonin-producing tumors; poorly differentiated ampullary neuroendocrine carcinomas; and duodenal gangliocytic paragangliomas.
Duodenal gastrinomas are either sporadic or associated with MEN 1 and ZES (23). They are usually smaller than 1 cm and are located predominantly in the upper portion of the duodenum (Fig 10). At immunohistochemical analysis, duodenal gastrinomas are clearly positive for gastrin. Unlike sporadic gastrinomas, gastrinomas associated with MEN 1 are usually multiple. Metastases are often found in the regional lymph nodes at the time of diagnosis, despite their small size and their confinement to the duodenal mucosa and submucosa. Metastasis to the regional lymph nodes occurs at an early stage, whereas liver metastases usually occur late.
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Figure 10a. Well-differentiated endocrine tumor (carcinoid) in the duodenal bulb in a 49-year-old man. (a) Transverse CT scan show a small, well-enhanced intraluminal polypoid lesion in the duodenal bulb (arrow). (b) Image from a double-contrast barium examination of the upper gastrointestinal tract also shows the lesion (arrows).
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Figure 10b. Well-differentiated endocrine tumor (carcinoid) in the duodenal bulb in a 49-year-old man. (a) Transverse CT scan show a small, well-enhanced intraluminal polypoid lesion in the duodenal bulb (arrow). (b) Image from a double-contrast barium examination of the upper gastrointestinal tract also shows the lesion (arrows).
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Carcinoids of the ampulla of Vater are extremely rare. We saw only one case at our institution (Fig 11). The most common clinical signs and symptoms are obstructive jaundice (Fig 11b) and abdominal pain. Multidetector thin-section CT can also demonstrate small ampullary tumors quite well (Fig 11a).
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Figure 11a. Well-differentiated endocrine carcinoma of the ampulla of Vater in a 39-year-old man. (a) Transverse arterial phase CT scan shows mild enlargement of the major duodenal papilla (arrow). (b) Transverse CT scan shows dilatation of the extrahepatic bile duct (arrowheads), along with multiple metastatic tumors in the liver (arrows). (c, d) Photomicrographs (original magnification, x200; H–E stain) show a tumor with a solid growth pattern. The tumor cells are variable in size, with occasional prominent nucleoli (c) that are reactive for synaptophysin (d).
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Figure 11b. Well-differentiated endocrine carcinoma of the ampulla of Vater in a 39-year-old man. (a) Transverse arterial phase CT scan shows mild enlargement of the major duodenal papilla (arrow). (b) Transverse CT scan shows dilatation of the extrahepatic bile duct (arrowheads), along with multiple metastatic tumors in the liver (arrows). (c, d) Photomicrographs (original magnification, x200; H–E stain) show a tumor with a solid growth pattern. The tumor cells are variable in size, with occasional prominent nucleoli (c) that are reactive for synaptophysin (d).
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Figure 11c. Well-differentiated endocrine carcinoma of the ampulla of Vater in a 39-year-old man. (a) Transverse arterial phase CT scan shows mild enlargement of the major duodenal papilla (arrow). (b) Transverse CT scan shows dilatation of the extrahepatic bile duct (arrowheads), along with multiple metastatic tumors in the liver (arrows). (c, d) Photomicrographs (original magnification, x200; H–E stain) show a tumor with a solid growth pattern. The tumor cells are variable in size, with occasional prominent nucleoli (c) that are reactive for synaptophysin (d).
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Figure 11d. Well-differentiated endocrine carcinoma of the ampulla of Vater in a 39-year-old man. (a) Transverse arterial phase CT scan shows mild enlargement of the major duodenal papilla (arrow). (b) Transverse CT scan shows dilatation of the extrahepatic bile duct (arrowheads), along with multiple metastatic tumors in the liver (arrows). (c, d) Photomicrographs (original magnification, x200; H–E stain) show a tumor with a solid growth pattern. The tumor cells are variable in size, with occasional prominent nucleoli (c) that are reactive for synaptophysin (d).
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Gastrointestinal carcinoids most frequently involve the small intestine, particularly the ileum (Fig 12), and represent almost 30% of all gastrointestinal neuroendocrine tumors (22). At the time of diagnosis, they are usually larger than 2 cm and have invaded the muscularis propria, which means that they have already metastasized to the regional lymph nodes. These neuroendocrine tumors may be multiple in up to 40% of cases. Approximately 20% of patients with ileal neuroendocrine tumors have hepatic metastasis (Fig 12b) (22). The most common clinical signs and symptoms of small bowel carcinoids are intermittent intestinal obstruction and vague abdominal pain. Desmoplastic reaction may kink the bowel and cause obstruction, or it may obstruct vascular supply, causing ischemia or infarction of the involved segment. CT performed with negative oral contrast material earlier than usual (ie, prior to the portal venous phase) may be helpful in detecting small enhancing neuroendocrine tumors in the small intestine. In addition, CT protocols with similar modifications can help depict small enhancing neuroendocrine tumors in the stomach and rectum.
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Figure 12a. Poorly differentiated endocrine carcinomas in the ileum in a 53-year-old man. (a) Transverse CT scan obtained at the level of the pelvis shows a large necrotic tumor in the distal ileum (arrows). Peritumoral infiltration and regional metastatic lymphadenopathy are also seen. (b) Transverse CT scan shows multiple metastatic tumors in the liver (arrows).
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Figure 12b. Poorly differentiated endocrine carcinomas in the ileum in a 53-year-old man. (a) Transverse CT scan obtained at the level of the pelvis shows a large necrotic tumor in the distal ileum (arrows). Peritumoral infiltration and regional metastatic lymphadenopathy are also seen. (b) Transverse CT scan shows multiple metastatic tumors in the liver (arrows).
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Appendix
Although neuroendocrine tumor of the appendix is one of the most common gastrointestinal neuroendocrine tumors (20% of cases) (22), it was found in only six of 187 patients. Appendiceal carcinoids are diagnosed at an earlier patient age than are other carcinoids and occur twice as often in women as in men (Fig 13) (24). They occur primarily in the tip of the appendix and almost always invade the muscularis mucosa and the adjacent fat tissue of the mesoappendix. Most of them are smaller than 1 cm, and metastasis to regional lymph nodes is rare. Appendiceal carcinoids have the most favorable prognosis of all gastrointestinal neuroendocrine tumors, probably because they have a tendency to cause symptoms early due to appendiceal luminal obstruction followed by acute appendicitis.
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Figure 13a. Carcinoid in the appendix in a 42-year-old woman who presented with pain in the right lower abdomen. (a) Transverse CT scan shows a small enhancing tumor in the midportion of the appendix (arrows). (b) Transverse CT scan shows an inflamed appendix (arrow), a finding that, along with a small carcinoid, was observed at both CT and pathologic analysis.
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Figure 13b. Carcinoid in the appendix in a 42-year-old woman who presented with pain in the right lower abdomen. (a) Transverse CT scan shows a small enhancing tumor in the midportion of the appendix (arrows). (b) Transverse CT scan shows an inflamed appendix (arrow), a finding that, along with a small carcinoid, was observed at both CT and pathologic analysis.
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Colon and Rectum
Neuroendocrine tumors of the colon are very rare. During the 10 years that we collected data, we saw colonic neuroendocrine tumors in only 11 patients. These tumors occur more commonly in the right colon (Fig 14) and tend to produce larger lesions (mean, ~5 cm) (25). At histologic analysis, they are poorly differentiated endocrine carcinomas, almost all of which have already metastasized at the time of diagnosis and, therefore, have a poor prognosis (26). Right colonic carcinoids are closely related to typical serotonin-producing carcinoids of the small bowel, since they are derived from the midgut.
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Figure 14. Mixed poorly differentiated neuroendocrine carcinoma and adenocarcinoma in the proximal ascending colon in a 57-year-old man. Transverse CT scan shows a large tumor (arrows) with associated extensive peritumoral infiltration.
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Rectal neuroendocrine tumors are much more common than colonic neuroendocrine tumors, representing about 11% of all gastrointestinal neuroendocrine tumors (22). Most of them (85%) are still localized at the time of diagnosis; thus, their prognosis is much better than that of colonic neuroendocrine tumors (22). Typically, rectal neuroendocrine tumors occur singly, are smaller than 1 cm, and manifest as movable submucosal tumors (Fig 15). Metastases occur in tumors larger than 2 cm (Fig 16), and tumors are often positive for serotonin (45% of cases) and pancreatic polypeptide (46%). However, glucagon, gastrin, and somatostatin are less often expressed (27). Transrectal ultrasonography (US) is useful for determining the depth of tumor invasion preoperatively (Fig 15c).
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Figure 15a. Well-differentiated endocrine tumor (carcinoid) in the distal rectum in a 64-year-old man. (a) Transverse CT scan shows a tiny enhancing tumor in the posterior wall of the distal rectum (arrow). (b) Virtual colonoscopic image shows a small dimple in the posterior wall of the distal rectum (arrow). (c) Transrectal US image shows a small hypoechoic tumor in the submucosal layer of the distal rectum (arrow).
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Figure 15b. Well-differentiated endocrine tumor (carcinoid) in the distal rectum in a 64-year-old man. (a) Transverse CT scan shows a tiny enhancing tumor in the posterior wall of the distal rectum (arrow). (b) Virtual colonoscopic image shows a small dimple in the posterior wall of the distal rectum (arrow). (c) Transrectal US image shows a small hypoechoic tumor in the submucosal layer of the distal rectum (arrow).
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Figure 15c. Well-differentiated endocrine tumor (carcinoid) in the distal rectum in a 64-year-old man. (a) Transverse CT scan shows a tiny enhancing tumor in the posterior wall of the distal rectum (arrow). (b) Virtual colonoscopic image shows a small dimple in the posterior wall of the distal rectum (arrow). (c) Transrectal US image shows a small hypoechoic tumor in the submucosal layer of the distal rectum (arrow).
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Figure 16. Well-differentiated endocrine carcinoma (malignant carcinoid) of the proximal rectum in a 62-year-old man. Transverse CT scan obtained at the level of the lower pelvis shows extensive wall thickening of the proximal rectum (arrows) with prominent enhancement. The patient had multiple metastatic tumors in the liver at the time of diagnosis.
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Conclusions
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Neuroendocrine tumors include many different types of tumors, and various terms are used for these tumors depending on tumor location, histologic features, and biologic behavior. Most neuroendocrine tumors have nonspecific imaging characteristics. However, they sometimes have peculiar clinical manifestations and radiologic features, on the basis of which radiologists may infer the specific diagnosis. Neuroendocrine tumors of the gastrointestinal tract are not common but should be considered in developing the differential diagnosis for gastrointestinal tract tumors in patients with a typical syndrome or when the tumors have characteristic imaging features.
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Footnotes
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Abbreviations: GEP = gastroenteropancreatic, H-E = hematoxylineosin, MEN = multiple endocrine neoplasia, NSE = neuron-specific enolase, WHO = World Health Organization, ZES = Zollinger-Ellison syndrome
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References
|
|---|
- Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology 2005;128:1717–1751.[CrossRef][Medline]
- Erickson LA, Lloyd RV. Practical markers used in the diagnosis of endocrine tumors. Adv Anat Pathol 2004;11:175–189.[CrossRef][Medline]
- Rindi G, Bordi C. Highlights of the biology of endocrine tumors of the gut and pancreas. Endocr Relat Cancer 2003;10:427–436.[Abstract]
- Thomas RM, Sobin LH. Gastrointestinal cancer. Cancer 1995;75:154–170.[CrossRef][Medline]
- Oberg K. Carcinoid tumors: current concepts in diagnosis and treatment. Oncologist 1998;3:339–345.[Abstract/Free Full Text]
- Griffiths DF, Williams GT, Williams ED. Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: islet cell tumour, phaeochromocytoma and the von Hippel-Lindau complex—two distinctive neuroendocrine syndromes. Q J Med 1987;64:769–782.[Medline]
- Wilson BS, Lloyd RV. Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 1984;115:458–468.[Abstract]
- Tischler AS. Granin for the many, epinephrine for the few [editorial]. Endocr Pathol 2003;14:1.
- Wiedermann B, Juttner W. Synaptophysin and chromogranin/secretogranins: widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Arch B Cell Pathol 1989;58:95–121.[Medline]
- Lloyd RV. Practical markers used in the diagnosis of neuroendocrine tumors. Endocr Pathol 2003; 14:293–302.[CrossRef][Medline]
- Lloyd RV. Overview of neuroendocrine cells and tumors. Endocr Pathol 1996;7:323–328.[Medline]
- Solcia E, Capella C, Fiocca R, Sessa F, LaRosa S, Rindi G. Disorders of the endocrine system. In: Ming SC, Goldman H, eds. Pathology of the gastrointestinal tract. Philadelphia, Pa: Williams & Wilkins, 1998; 295–322.
- Williams ED, Sandler M. The classification of carcinoid tumours. Lancet 1963;1:238–239.[Medline]
- Klöppel G, Heitz PU, Capella C, et al. The spectrum and classification of gastric and duodenal neuroendocrine tumours. Curr Diagn Pathol 1995;2:10–14.[CrossRef]
- Klöppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci 2004;1014:13–27.[CrossRef][Medline]
- Solcia EG, Klöppel G, Sobin LH, et al. Histological typing of endocrine tumours. WHO international histological classification of tumours. 2nd ed. Berlin, Germany: Springer, 2000.
- Lindberg GM, Molberg KH, Vuitch MF, et al. Atypical carcinoid of the esophagus: a case report and review of the literature. Cancer 1997;79: 1476–1481.[CrossRef][Medline]
- Bordi C. Gastric carcinoids. Ital J Gastroenterol Hepatol 1999;31(suppl 2):S94–S97.[Medline]
- Lehy T, Cadiot G, Mignon M, Ruszniewski P, Bonfils S. Influence of multiple endocrine neoplasia type I on gastric endocrine cells in patients with the Zollinger-Ellison syndrome. Gut 1992;33: 1275–1279.[Abstract/Free Full Text]
- Rindi G, Azzoni C, La Rosa S, et al. ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis. Gastroenterology 1999;116: 532–542.[CrossRef][Medline]
- Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97: 934–959.[CrossRef][Medline]
- Modlin IM, Sandor A. An analysis of 8,305 cases of carcinoid tumors. Cancer 1997;79:813–829.[CrossRef][Medline]
- Pipeleers-Marichal M, Somers G, Willems G, et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med 1990; 322:723–727.[Abstract]
- Sandor A, Modlin IM. A retrospective analysis of 1,570 appendiceal carcinoids. Am J Gastroenterol 1998;93:422–428.[CrossRef][Medline]
- Berardi RS. Carcinoid tumors of the colon (exclusive of the rectum): review of the literature. Dis Colon Rectum 1972;15:383–391.[CrossRef][Medline]
- Grabowski P, Schönfelder J, Ahnert-Hilger G, et al. Expression of neuroendocrine markers: a signature of human undifferentiated carcinoma of the colon and rectum. Virchows Arch 2002;441:256–263.[CrossRef][Medline]
- Federspiel BH, Burke AP, Sobin LH, et al. Rectal and colonic carcinoids: a clinicopathologic study of 84 cases. Cancer 1990;65:135–140.[CrossRef][Medline]
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