Nature of APUD cells
The pathogenesis is based on damage to cells that make up 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 understand that such tumors share a common origin with the epithelial cells of the organ in which they develop.
Classification by malignancy
In clinical practice, tumors are divided according to their aggressiveness:
- Benign: represented by carcinoids.
- Malignant: include atypical carcinoid, as well as high- and low-grade neuroendocrine carcinomas.
Hormonal activity
Tumors are often classified by the type of hormone they produce. This determines the clinical presentation of the disease. Examples of such conditions include:
- Insulinomas (insulin production).
- Gastrinomas (gastrin production).
Carcinoids are most commonly found in the appendix, stomach, and lungs.
Briefly: answers to topical questions
What biologically active substances do APUD cells normally secrete?
APUD 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 are involved in local neuroendocrine regulation.
What types of apudomas are distinguished depending on the type of hormone produced?
Depending on the type of hormone produced, various types of hormonally active apudomas are distinguished. These include:
- Gastrinoma — a gastrin-producing carcinoid.
- Insulinoma — a tumor producing insulin.
- VIPoma (Werner–Morrison tumor) — a tumor synthesizing vasoactive intestinal peptide.
- Corticotropinoma — a tumor with ectopic secretion of glucocorticoids.
- Parathyrenoma — a tumor with ectopic secretion of parathyroid hormone.
- Somatostatinoma — a δ-cell tumor secreting somatostatin.
- PPoma — a PP-cell tumor 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 hormonally active apudomas?
Hormonally active apudomas cause specific clinical syndromes depending on the secreted substance:
- Carcinoid syndrome — occurs due to serotonin secretion, manifests as flushing.
- Zollinger–Ellison syndrome — develops in gastrinoma, characterized by high acid production and symptomatic ulcers.
- Pancreatic cholera syndrome — occurs in VIPoma, manifests as severe watery diarrhea and water-electrolyte disturbances.
- Cushing's syndrome — develops in corticotropinoma due to ectopic hypercorticism.
Hypercalcemia (in parathyrenoma) and mild diabetes mellitus (in somatostatinoma) may also be observed.
APUD = Amine Precursor Uptake and Decarboxylation. Remember that they are "ubiquitous" (like the system itself), so look for them in any organ.
Class and exam questions
What are apudomas?
This is a common collective term for all neuroendocrine tumors originating from APUD system cells.
Where are carcinoids most commonly found?
The most typical localization sites are the appendix, stomach, and lungs.
Are all neuroendocrine tumors malignant?
No, they range from benign carcinoids to high- and low-grade neuroendocrine carcinomas.
What else to study on this topic
- Detailed analysis of the mechanisms of hormonal secretion in various types of apudomas.
- Histological criteria for the differentiation of neuroendocrine carcinomas.
- Comparative characteristics of clinical manifestations at different localizations.
- The role of the APUD system in the physiological regulation of homeostasis.
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