Gastrointestinal neuroendocrine tumors (NETs) are tumors derived from the diffuse neuroendocrine system of the GI tract; that system is composed of amine- and acid-producing cells with different hormonal profiles, depending on the site of origin. The tumors historically are divided into carcinoid tumors and pancreatic endocrine tumors (PETs), although recent pathologic classifications have proposed that they all be classified as gastrointestinal NETs. In this chapter the term carcinoid tumor is retained because it is widely used. These tumors originally were classified as APUDomas (for amine precursor uptake and decarboxylation), as were pheochromocytomas, melanomas, and medullary thyroid carcinomas, because they share certain cytochemical features as well as various pathologic, biologic, and molecular features (Table 350-1). It was originally proposed that APUDomas had a similar embryonic origin from neural crest cells, but it is now known the peptide-secreting cells are not of neuroectodermal origin. Nevertheless, the concept of APUDomas is useful because the tumors from the cells have important similarities as well as some differences (Table 350-1). In this section, the areas of similarity between PETs and carcinoids will be discussed together and areas in which there are important differences will be discussed separately.
Table 350-1 General Characteristics of Gastrointestinal Neuroendocrine Tumors [Carcinoids, Pancreatic Endocrine Tumors (PETs)] |Favorite Table|Download (.pdf)
Table 350-1 General Characteristics of Gastrointestinal Neuroendocrine Tumors [Carcinoids, Pancreatic Endocrine Tumors (PETs)]
A. Share general neuroendocrine cell markers (identification used for diagnosis)
1. Chromogranins (A, B, C) are acidic monomeric soluble proteins found in the large secretory granules. Chromogranin A is the most widely used.
2. Neuron-specific enolase (NSE) is the γ-γ dimer of the enzyme enolase and is a cytosolic marker of neuroendocrine differentiation.
3. Synaptophysin is an integral membrane glycoprotein of 38,000 molecular weight found in small vesicles of neurons and neuroendocrine tumors.
B. Pathologic similarities
1. All are APUDomas showing amine precursor uptake and decarboxylation.
2. Ultrastructurally they have dense-core secretory granules (>80 nm).
3. Histologically, generally appear similar with few mitoses and uniform nuclei.
4. Frequently synthesize multiple peptides/amines, which can be detected immunocytochemically but may not be secreted.
5. Presence or absence of clinical syndrome or type cannot be predicted by immunocytochemical studies.
6. Histologic classifications increasingly predictive of biologic behavior. Only invasion or metastases establish malignancy
C. Similarities of biologic behavior
1. Generally slow growing, but a proportion are aggressive.
2. Secrete biologically active peptides/amines, which can cause clinical symptoms.
3. Generally have high densities of somatostatin receptors, which are used for both localization and treatment.
D. Similarities/differences in molecular abnormalities
a. Uncommon—alterations in common oncogenes (ras, jun, fos, etc).
b. Uncommon—alterations in common tumor-suppressor genes (p53, retinoblastoma).
c. Alterations at MEN 1 locus (11q13) and p16INK4a (9p21) occur in a proportion (10–45%).
d. Methylation of various genes occurs in 40–87% (ras-associated domain family I, p14, p16, O6 methyl guanosine methyltransferases, retinoic ...