Neuroendocrine Tumors Flashcards
Neuroendocrine Cells
- cells that receive neuronal input (neurotransmitters released by nerve cells) and, as a consequence of this input, release message molecules (hormones) to the blood
- Diffusely distributed throughout the body
• Contain the enzyme aromatic acid
decarboxylase - Collectively referred to as APUD cells
NEUROENDOCRINE TUMORS
Clinical Features:
- Originate from neuroendocrine cells
• May secrete one or more peptide hormones and/or biogenic amines
• May occur sporadically or as part of a
Multiple Endocrine Neoplasia (MEN)
syndrome
• Variable biologic behavior with regard to
malignant potential and aggressiveness
- Slow growing
• Well-differentiated: Metastases and local
invasion are the only reliable criteria of
malignancy
• Morbidity may be more closely related to
hormone effects than to tumor mass
• May contain functional hormone receptors
and retain (partial) responsiveness to
hormonal suppression
• Require long-term follow-up
- Tumors can be small yet have dramatic
clinical consequences
Methods of localizing endocrine tumors
» “Conventional” imaging: CT, MRI etc.
» Functional imaging: PET, Octreotide scan
» Physiologic localization: venous sampling
MEDULLARY THYROID
CANCER
• Derived from parafollicular C-cells
• Calcitonin is a sensitive tumor marker (but no clinical
abnormality in calcium regulation)
• Presentations:
» Sporadic (75%)
» Familial (25%): MEN 2a, MEN 2b, isolated
• Activating mutations of ret proto-oncogene common
• Survival intermediate between well-differentiated
and anaplastic thyroid cancer
• Cervical nodes common
• Distant mets: mediastinum, lung, liver, abdominal
lymph nodes,bone
» No effective therapy for distal metastases
Presentation:
• Thyroid nodule: Over 50% of patients with palpable thyroid nodules have metastases at diagnosis
• Watery diarrhea
• Flushing, pruitus
• Findings related to other elements of MEN 2a or 2b syndrome
PANCREATIC ISLET CELL TUMORS
- Gastrin
- Peptic ulcer
- Secretory diarrhea - Insulin
- Hypoglycemia - Somatostatin (has broad suppressive effects on GH, Insulin, Gastrin)
- Diabetes
- Gallstones
- Diarrhea
- Steatorrhea - Vasoactive Intestinal Polypeptide
- Watery diarrhea
- hypokalemia
- metabolic acidosis
Octreotide
- a long-acting somatostatin that has broad suppressive effects on GH, Insulin, Gastrin, etc.
- can be used as an imaging agent, where a radioactive isotope is attached; the octreotide will be attracted to areas secreting lots of GH, Insulin, Gastrin, etc.
Carcinoid Tumors
- Arise from enterochomaffin cells scattered throughout the body, commonly in the appendix and small bowel
- secrete excess Bradykinin (flush) and Serotonin (5-HT) (diarrhea)
Ileal carcinoid
» Classic carcinoid syndrome
- Serotonin is usually cleared by the liver before it reaches systemic circulation; Symptoms generally don’t occur until hepatic
metastases are present
Gastric carcinoid
» Bright red flush involving base of neck
- can be blocked by H1 and H2 receptor blockers
Bronchial carcinoid
» Flush may last for hours
- associated with lacrimation and facial edema.
- Tumors occasionally secrete ACTH
MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES (generally)
• Autosomal dominant inheritance (single gene) • Tumors frequently multifocal • May arise from hyperplastic precursor • Tumor syndromes present 1 to 2 decades earlier in age than in sporadic cases • Variable penetrance of tumors
MEN1
3P’s (but no Pheochromocytoma)
1. Pituitary: Prolactin or GH
2. Parathyroid
3 Pancreas: Insulinoma
MEN2A
2P’s
- Parathyroid
- Pheochromocytoma
- Medullary thyroid carcinoma (secretes calcitonin)
MEN2B
1P
- Pheochromocytoma
- Medullary thyroid carcinoma (secretes calcitonin)
- Oral/intestinal ganglioneuromatosis (looks like a bumpy tongue)
- commonly presents with marfanoid habitus (Marfan’s body-type)
MEN1 Gene
- Located on chromosome 11
- encodes MENIN
- Menin has properties expected of a tumor
suppressor gene - Somatic mutations to the menin gene are
found frequently in sporadic endocrine tumors
