The NET Alliance™ and Novartis Oncology continue their commitment to improving knowledge and management of neuroendocrine tumors, and empowering patients to be more informed advocates.

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Characterizing a challenging cancer

Neuroendocrine neoplasms can be characterized by their1,4,10:

  • Anatomic site of origin
  • Histology
  • Grade
  • Stage (extent of disease)
  • Hormone secretion (functional or nonfunctional)

Anatomic site of origin

Many characteristics of NET are site specific,11 and most NET arise in these locations4,8:

Chart showing the classification of neuroendocrine tumors (NET)

Despite these varied tissues of origin, all NET:

  • Have similar pathologic features
  • Can secrete bioactive products (most commonly serotonin or peptides such as insulin, gastrin, and glucagons)
  • Express neuroendocrine markers including chromogranin A (CgA)5,10

It is important to note that primary tumors are often small,3,12 which may contribute to diagnosis being delayed until after the tumor has metastasized.4,13

Even small NET (<2 cm) have the potential to metastasize.14,15


The World Health Organization (WHO) guidelines divide neuroendocrine neoplasms into 2 clinically distinct pathologic classes: well and poorly differentiated.

  • Well-differentiated NET can be classified as either grade 1 or grade 2
  • Poorly differentiated neuroendocrine carcinomas are classified as grade 31,16


Some of the biological behavior exhibited by neuroendocrine neoplasms is highly correlated with neoplasm grade.10,17 Generally:

  • Grade 1 NET are relatively slow growing, but still potentially malignant17
  • Grade 2 NET have a less predictable, moderately aggressive course10
  • Grade 3 neuroendocrine carcinomas can be highly aggressive17

Grading systems are similar across NET anatomic locations, although different nomenclature may be used for lung NET and the presence of necrosis is considered for these tumors17,18:

Current grading system for neuroendocrine tumors (NET)

Learn more about NET nomenclature

Stage, or extent of disease

The Surveillance, Epidemiology, and End Results (SEER) program database uses a “localized,” “regional,” and “distant” system to stage disease. NET are also staged using this system.17

Additionally, the Worldwide Health Organization (WHO), the Union for International Cancer Control (UICC), and the American Joint Committee on Cancer (AJCC) classification systems reflect the widespread recognition that NET should be staged using tumor-node-metastasis (TNM) staging criteria. In TNM guidelines, the fundamental staging landmarks for NET parallel those used for carcinomas of the corresponding organs.1,17

Secretory potential (functional or nonfunctional)

Finally, NET can be classified by whether or not they are capable of producing hormonal substances. This is sometimes referred to as functional status.7,13,19

  • Functional NET cause symptoms that can be attributed to the secretion of specific hormones or peptides (eg, diarrhea, hypoglycemia, flushing)
  • Nonfunctional NET also can release hormones, but do not cause symptoms related to hormonal hypersecretion. Symptoms are associated with increasing tumor mass (eg, pain, obstruction, bleeding)2

Most NET are nonfunctional, and some NET remain asymptomatic indefinitely. Many of the symptoms and syndromes that NET can cause do not occur until the tumor has metastasized.3,12 In fact, about 50% of patients with reported disease stage have either regional or distant metastases at diagnosis.4

Learn more about different symptoms caused by NET

Resource for Nurses: Take the NET Nurse Quiz! 

The NET Nurse Quiz is an interactive quiz to test your knowledge on neuroendocrine tumors and how the disease affects your patients.

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