Neuroendocrine tumors classification

Neuroendocrine tumors Microchapters
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Epidemiology and Demographics
Risk factors
Natural History, Complications and Prognosis
History and Symptoms
Laboratory Findings
CT scan
PET scan
Medical Therapy
Surgery

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Classification

Human GEP-NETs by Site of Origin and by Symptom

• Carcinoids (about two thirds of GEP-NETs)
  • With carcinoid syndrome (about 10 percent of carcinoids)
  • Without carcinoid syndrome (about 90 percent of carcinoids)
• PETs (about one third of GEP-NETs)
  • Nonfunctioning (15 to 30 percent of PETs)
  • Functioning (70 to 85 percent of PETs)
    • Gastrinoma, producing excessive gastrin and causing Zollinger-Ellison Syndrome (ZES)
    • Insulinoma, producing excessive insulin
    • Glucagonoma, producing excessive glucagon
    • Vasoactive intestinal peptideoma (VIPoma), producing excessive vasoactive intestinal peptide (VIP)
    • PPoma, producing excessive pancreatic polypeptide (often classed with nonfunctioning PETs)
    • Somatostatinoma, producing excessive somatostatin
    • Watery diarrhea, hypokalemia-achlorhydria (WDHA)
    • CRHoma, producing excessive corticotropin-releasing hormonse (CRH)
    • Calcitoninoma, producing excessive calcitonin
    • GHRHoma, producing excessive growth-hormone-releasing hormone (GHRH)
    • Neurotensinoma, producing excessive neurotensin
    • ACTHoma, producing excessive adrenocorticotropic hormone (ACTH)
    • GRFoma, producing excessive growth hormone release factor (GRF)
    • Parathyroid hormone–related peptide tumor
• Rare GEP-NETs
  • Medullary carcinoma of the thyroid
  • Merkel cell cancer (trabecular cancer)
  • Small-cell lung cancer (SCLC)
  • Large-cell neuroendocrine carcinoma (of the lung)
  • Neuroendocrine carcinoma of the cervix
  • Multiple Endocrine Neoplasia type 1 (MEN-1 or MEN1) (usually nonfunctioning) (also causing ZES)
  • Multiple Endocrine Neoplasia type 2 (MEN-2 or MEN2)
  • Neurofibromatosis type 1
  • Tuberous sclerosis
  • Von Hippel-Lindau disease (VHL)
  • Neuroblastoma
  • Pheochromocytoma (phaeochromocytoma)
  • Paraganglioma
  • Neuroendocrine tumor of the anterior pituitary
  • Carney's complex

Classification of GEP-NETs by cell characteristics

The diverse and amorphous nature of GEP-NETs has led to a confused, overlapping, and changing terminology. In general, aggressiveness (malignancy), secretion (of hormones), and anaplasia (dissimilarity between tumor cells and normal cells) tend to go together, but there are many exceptions, which have contributed to the confusion in terminology. For example, the term atypical carcinoid is sometimes used to indicate an aggressive tumor without secretions, whether anaplastic or well-differentiated.

In 2000, the World Health Organization (WHO) revised the classification of GEP-NETs, abandoning the term carcinoid in favor of neuroendocrine tumor (NET) and abandoning islet cell tumor or pancreatic endocrine tumor for neuroendocrine carcinoma (NEC). Judging from papers published into 2006, the medical community is accepting this new terminology with great sluggishness. (Perhaps one reason for the resistance is that the WHO chose to label the least aggressive subclass of neuroendocrine neoplasm with the term – neuroendocrine tumor – widely used previously either for the superclass or for the generally aggressive noncarcinoid subclass.)

Klöppel et alia have written an overview that clarifies the WHO classification and bridges the gap to the old terminology (Klöppel, Perren, and Heitz 2004). In this article we conform to the old terminology.

Summary of classification by cell characteristics (the WHO classification)

• Superclass:
  • Öberg, WHO, Klöppel et alia: Gastro-entero-pancreatic neuroendocrine tumor (GEP-NET)

• Subclass 1 (less malignant)
  • Öberg: Carcinoid
  • WHO: Neuroendocrine tumor (NET)
  • Klöppel et alia: Well-differentiated neuroendocrine tumor (NET) (carcinoid)
  • this article: Carcinoid

• Subclass 2 (more malignant)
  • Öberg: Endocrine pancreatic tumor
  • WHO: Neuroendocrine carcinoma (NEC)
  • Klöppel et alia: Well-differentiated neuroendocrine carcinoma (NEC) (malignant carcinoid)
  • this article: Pancreatic endocrine tumor (PET) or endocrine pancreatic tumor (EPT) or islet cell tumor or noncarcinoid GEP-NET

• Subclass 3 (most malignant)
  • WHO: Poorly-differentiated neuroendocrine carcinoma
  • Klöppel et alia: Poorly-differentiated neuroendocrine carcinoma (high-grade malignant carcinoid)

• Subclass 4 (mixed)
  • WHO: Mixed endocrine/exocrine tumor

• Subclass 5 (miscellaneous)
  • WHO: Rare neuroendocrine-like lesions

GEP-NETs are also sometimes called APUDomas, but that term is now considered to be misleading, since it is based on a discredited theory of the development of the tumors.