Sechenov School
Home › Pathology › Neuroendocrine Neoplasms

Neuroendocrine Neoplasms

*Neuroendocrine neoplasmata*

For medical students2 min readUpdated 2026-10-10

Neuroendocrine neoplasms (NENs) are a group of tumors arising from cells of the diffuse neuroendocrine system (APUD system). They can originate in almost any organ and are characterized by the ability to secrete biologically active substances.

OriginDevelop from precursor cells of the APUD system.
FunctionSynthesis of biogenic amines and polypeptide hormones.
LocalizationCan affect virtually all organs of the body.
ClassificationDivided by degree of malignancy and hormone type.

Nature of APUD Cells

The pathogenesis is based on pathology of cells belonging to the diffuse APUD system. Normally, these cells are responsible for local neuroendocrine regulation, producing a wide range of compounds: from serotonin to calcitonin and ACTH. It is important to note that these tumors share a common origin with the epithelial cells of the organ in which they develop.

Classification by Malignancy

In clinical practice, tumors are classified according to their aggressiveness:

Hormonal Activity

Tumors are frequently classified by the type of hormone they produce, which determines the clinical presentation. Examples of such conditions include:

  1. Insulinomas (insulin production).
  2. Gastrinomas (gastrin production).

Carcinoids are most commonly found in the appendix, stomach, and lungs.

Mnemonic

APUD = Amines, Peptides, Ubiquitous, Diffuse. Remember that they are ubiquitous (like the system itself), so look for them in any organ.

Frequently asked questions

What biologically active substances do APUD system cells normally secrete?

APUD system cells normally secrete more than 60 types of peptide hormones and biogenic amines. The main biologically active substances produced include:

  • Biogenic amines — serotonin.
  • Polypeptide hormones — calcitonin, adrenocorticotropic hormone (ACTH), somatostatin, cholecystokinin, motilin, substance P, enteroglucagon, secretin, pancreozymin, gastrin, vasoactive intestinal peptide (VIP).

These substances participate in local neuroendocrine regulation.

What types of apudomas are distinguished based on the type of hormone produced?

Depending on the type of hormone produced, various hormone-secreting apudomas are distinguished, including:

  • Gastrinoma — a gastrin-producing carcinoid.
  • Insulinoma — an insulin-producing tumor.
  • VIPoma (Verner–Morrison syndrome tumor) — a tumor synthesizing vasoactive intestinal peptide.
  • Corticotropinoma — a tumor with ectopic secretion of glucocorticoids.
  • Parathyroidoma — a tumor with ectopic secretion of parathyroid hormone.
  • Somatostatinoma — a tumor derived from δ-cells secreting somatostatin.
  • PPoma — a tumor derived from PP-cells producing pancreatic polypeptide.
What immunohistochemical markers are used to verify neuroendocrine tumors?

The following immunohistochemical markers are used to verify neuroendocrine tumors:

  • General markers — cytokeratins.
  • Specific markers — chromogranins, neuron-specific enolase (NSE), synaptophysin, Leu-7 (CD57), including chromogranin A.
What clinical syndromes develop in hormone-secreting apudomas?

Hormone-secreting apudomas cause specific clinical syndromes depending on the secreted substance:

  • Carcinoid syndrome — caused by serotonin secretion, manifested by flushing.
  • Zollinger–Ellison syndrome — develops in gastrinoma, characterized by high gastric acid output and symptomatic ulcers.
  • Pancreatic cholera syndrome (Verner-Morrison) — occurs in VIPoma, manifested by severe watery diarrhea and fluid-electrolyte imbalances.
  • Cushing syndrome — develops in corticotropinoma due to ectopic hypercortisolism.

Hypercalcemia (in parathyroidoma) and mild diabetes mellitus (in somatostatinoma) may also be observed.

What are apudomas?

This is a collective term for all neuroendocrine tumors originating from cells of the APUD system.

Where are carcinoids most frequently found?

The most typical localization sites are the appendix, stomach, and lungs.

Are all neuroendocrine tumors malignant?

No, they range from benign carcinoids to well-differentiated and poorly differentiated neuroendocrine carcinomas.

Go deeper

More topics in Pathology

Epithelial TumorsCalculosisArterial AneurysmsCholelithiasisBalantidiasisWaldenström MacroglobulinemiaSyphilitic Granuloma (Gumma)ThrombophlebitisBladder Tumors: Pathology and ClassificationCholecystitisHodgkin LymphomaSoft Tissue TumorsPathology →