What are the characteristics of a neuroendocrine tumor (NET) of the bowel?

From the Guidelines

Bowel neuroendocrine tumors (NETs) are characterized by their origin from neuroendocrine cells in the intestinal tract, with the majority being well-differentiated and slow-growing, and are typically classified based on their location, grade, and stage. The characteristics of bowel NETs can be understood by examining their histological diagnosis, which is mandatory and can be carried out on resection specimens or core biopsies in advanced disease 1. The diagnosis of a NET is suspected on hematoxylin eosin (HE)-stained tissue by histomorphological growth pattern and cytology, and the neuroendocrine phenotype is proven by the immunohistochemical detection of the neuroendocrine markers synaptophysin and/or chromogranin A (CgA) 1.

Key Characteristics

• Bowel NETs can occur throughout the gastrointestinal tract but are most common in the small intestine, especially the ileum 1
• They are typically well-differentiated and slow-growing, but can vary in their biology and clinical presentation based on their anatomical site of origin 1
• The primary tumor site has an impact on the prognosis in advanced disease, with patients with small intestinal NETs having a more favorable prognosis than those with pancreatic or colorectal NETs 1
• Carcinoid syndrome, characterized by flushing, diarrhea, and wheezing, may occur if the tumor secretes hormones, particularly with liver metastases, and is managed with somatostatin analogs 1

Diagnosis and Staging

• Histological diagnosis is mandatory and can be carried out on resection specimens or core biopsies in advanced disease 1
• Imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are used for staging and restaging 1
• The sensitivity and specificity of these imaging techniques vary, with PET-CT having a high sensitivity and specificity for detecting NET lesions 1

Prognosis

• Prognosis varies widely based on stage and grade, with well-differentiated, localized tumors having a much better outlook than poorly differentiated or metastatic disease 1
• The primary tumor site and the presence of carcinoid syndrome also impact prognosis 1

From the Research

Characteristics of Neuroendocrine Tumors (NETs) of the Bowel

• Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation and the ability to synthesize and secrete variable hormones and monoamines 2
• They are relatively rare, accounting for 2% of all malignancy cases in the United States 2
• The most common system affected by NETs is the gastrointestinal tract, with the small bowel being a common site 3, 2, 4
• Clinical presentation depends on the organ being involved and the hormone being secreted, and can range from asymptomatic incidental findings on imaging to intestinal obstruction, or carcinoid syndrome (CS) 3, 2, 5

Biological Characteristics

• NETs contain chromogranin A, synaptophysin, and neuron-specific enolase, which are necessary for making a diagnosis of neuroendocrine tumor 4
• Ki-67 index and mitotic index correlate with cellular proliferation 4
• Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment, and is raised in both functioning and non-functioning neuroendocrine tumors 4

Clinical Presentation and Diagnosis

• Clinical presentation is variable, ranging from incidental lesions detected on cross-sectional imaging, small bowel obstruction, carcinoid syndrome, or other syndromic presentations 3
• Diagnosis relies on biochemical markers, computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin-receptor based functional imaging 3, 2
• Several biochemical testings are developed to help with the diagnosis of NETs, including 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) 2

Treatment Options

• Surgical removal is the mainstay of treatment for locoregional tumors 2, 5, 6
• Several medical managements are available for non-resectable NETs, which include somatostatin analogues, peptide receptor radionuclide therapy (PRRT), and platinum-based chemotherapy agents 3, 2, 5
• Liver-directed therapies and sometimes chemotherapy are also used in the treatment of NETs 3, 5