PRESENTATION AND SYMPTOMS

The presentation of NETs ranges from no symptoms to profound symptoms. With the increased frequency and availability of imaging scans (CT and MRI) and endoscopic procedures, NETs are increasingly being diagnosed incidentally in patients without symptoms or with symptoms unrelated to the diagnosis. In patients who develop symptoms, these are often vague gastrointestinal or respiratory symptoms such as cough, wheezing, abdominal pain, diarrhea, or flushing. Patients are often misdiagnosed with other more common conditions such as irritable bowel syndrome, reflux, inflammatory bowel disease, menopause, rosacea, or asthma. Delay in diagnosis can exceed five years from the onset of symptoms in numerous cases.

Rarely do patients present with the classic symptoms described in textbooks. Patients may present with only partial symptoms. THE MAJORITY OF NETS ARE NON-FUNCTIONAL, meaning they do not secrete systemic peptide or amines, so patients may suffer mostly from mechanical complications of the tumor, including obstruction and bleeding. These occur in both the digestive and respiratory tracts. In the small bowel, intermittent sub-acute small bowel obstructions may occur resulting from a desmoplastic reaction around the tumor that causes abdominal pain and kinking of the bowel. In the lungs, airway obstruction may result in recurrent bronchitis or pneumonia. Paragangliomas may cause mass effect in the neck or torso. Therefore, persistent symptoms without a clear cause warrant further investigation. Because NETs are difficult to diagnose, a thorough workup is required before completely ruling out the disease.

Peptide and amine hormone induced symptoms are well-described and include:

CARCINOID SYNDROME

(usually small intestinal or pulmonary NETs)

  • flushing
  • night sweats
  • diarrhea
  • wheezing
  • pellagra

Note: Carcinoid heart disease occurs in 50-70% of patients diagnosed with carcinoid syndrome.

ZOLLINGER ELLISON SYNDROME/GASTRINOMA

(usually duodenal or pancreatic)

  • diarrhea
  • severe small bowel ulceration
  • heartburn
  • abdominal pain

GLUCAGONOMA

(usually pancreatic)

  • diabetes
  • cachexia (severe weight loss)
  • necrolytic migratory erythema
  • (severe migrating skin rashes)
  • deep venous thrombosis

INSULINOMA

(almost always pancreatic)

  • symptoms of hypoglycemia (neuroglycopenia, sympathetic overdrive)

VIPOMA

(usually pancreatic)

  • watery secretory diarrhea
  • electrolyte disturbances

PHEOCHROMOCYTOMA

(adrenal)

  • hypertension
  • headaches
  • sweating
  • palpitations
Image from upper endoscopy, demonstrating a large gastric NET with overlying ulceration.

Image from upper endoscopy, demonstrating a large gastric NET with overlying ulceration.

 
Specimen of surgical resection of small bowel, demonstrating multiple small NETs.

Specimen of surgical resection of small bowel, demonstrating multiple small NETs.

 
Cross section of a small bowel NET, demonstrating invasion through the deep muscle layer.

Cross section of a small bowel NET, demonstrating invasion through the deep muscle layer.

“My patients have been told by other physicians that they had irritable bowel syndrome, inflammatory bowel disease, and even psychiatric disorders, when they in fact had a neuroendocrine tumor. While I understand that these conditions are much more common than NETs, an astute clinician who thinks of a NET may be instrumental in providing an earlier diagnosis.”
— Michelle Kim, MD, Mount Sinai Medical Center