NEUROENDOCRINE

TUMORS
MEDICAL&SURGICAL PATHOLOGY 1
NEUROENDOCRINE CELLS (NEC)

 Cells with mixed properties :

o Neuronal – contain dense core granules, similar to those present in
serotoninergic neurons
o Endocrine – monoamines synthesis and secretion
a) catecholamines : adrenalin, noradrenalin
b) indolamines : serotonin
NEUROENDOCRINE CELLS
DISTRIBUTION
1. Endocrine glands : pituitary, parathyroid, adrenal medulla

2. Endocrine islet tissue embedded within glandular tissue :

 Thyroid – parafollicular cells (secrete calcitonin)
 Pancreas – Langerhans islet cells (secrete insulin, glucagon, etc.)

3. Scattered cells in the exocrine parenchyma –digestive and respiratory

tract (forming the diffuse NE system)
NEUROENDOCRINE TUMORS (NETs)
 Heterogenous group of tumours, whose most common primary sites are represented by
the digestive tract and the lungs

 According to their histology, mitotic index and clinical behaviour, there are 2 types of
NETs :
1. Low grade NETs - usually indolent, with a slow growth and good prognosis
2. High grade NETs – aggressive, with a quick growth and worse prognosis

 Historically, well differentiated NETs were described as ”carcinoids”, an obsolete and

confusing term, still used today
NETs
 Represent 0.5% of all newly diagnosed tumours
 Most NETs are sporadic but some occur in association with other similar
tumours, forming hereditary syndromes (multiple endocrine neoplasia -
MEN)
 No clear relation between NETs and risk factors such as alcohol or
tobacco smoking has been identified
 Well differentiated NETs secrete chromogranin A and contain
synaptophysin granules
NETs TYPES
 Gastroenteropancreatic NETs :
o Digestive tract (gastric, small bowel, appendicular, colorectal)
o Pancreas (insulinoma, glucagonoma, gastrinoma, VIP-oma, somatostatinoma)
 Genitourinary NETs
 Pulmonary NETs
NETs
 Can be functional or non-functional
 Functional NETs are usually diagnosed based on the clinical
suspicion confirmed by the measurement of secreted
peptides/hormones with notable clinical effects
 Non-functional NETs are usually diagnosed :
a. incidentally, with imaging or endoscopic techniques performed for other
reasons
b. based on the symptoms generated by local growth or distant metastases
CARCINOID SYNDROME
 Generated by the paroxysmal serotonin secretion. It becomes manifest when
serotonin bypass liver metabolism (NETs with liver or extraabdominal metastases)

 Manifestations :
 Flushing
 Hypotension
 Bronchospasm
 Watery diarrhoea
 Right-sided heart disease with endothelial and valvular fibrosis
Carcinoid
flushing
DIAGNOSIS
 Pulmonary NETs : Chest X-ray and CT
 Digestive NETs : endoscopy, abdominal CT
 Gastroenteropancreatic NETs usually express somatostatin receptors. Its
radioactively-labelled synthetic analogue – 123I o 111In - octreotide – binds with
high affinity to these receptors and can be used in scintigraphic studies to
diagnose primary NETs and their metastases (Octreoscan)
 Biomarkers :
 Urinary 5-HIAA (5-hydroxyindole acetic acid) – serotonin metabolite
 Chromogranin A – serum marker
TNE
CT diagnosis

Gastric NET and liver metastases of the same tumour – both lesions are hypervascular and present
contrast uptake during the arterial phase
TNE
Octreoscan diagnosis

Pancreatic NET – Radiolabelled-Octreotide uptake

GASTROINTESTINAL NETs
 Gastric :
- Associated with gastric atrophy, with gastrin-secreting tumours (gastrinomas) or
sporadic; their aggressivity varies with tumour type
 Colorectal :
- Rare, usually more aggressive than colorectal adenocarcinomas
 Appendicular :
- Most have a benign behaviour
- Found in appendectomy specimens as incidental nodules or as a cause of acute
appendicitis
Endoscopic
aspect of NETs
Intraoperative
aspect of small
bowel NET
MOST FREQUENT PANCREATIC NETs
 Insulinoma :
 Symptoms of hypoglycemia and hypokalemia

 Gastrinoma :
 Gastrin hypersecretion that stimulates gastric acid secretion and favours the development of
multiple peptic ulcers, refractory to medical treatment (Zollinger-Ellison syndrome)

 Both types can be solitary or related with other neuroendocrine symptoms

(multiple neuroendocrine neoplasia)
TREATMENT
 Surgery, chemo and radiotherapy, symptomatic treatment
 Localized NETs, with good prognosis, are cured with radical surgery
 Metastatic NETs, compared with metastatic adenocarcinomas, can benefit
from a partial, cytoreductive surgery, to shrink the tumour load to a
minimum after which chemotherapy could be given with a potential higher
efficacy
 Given their hypervascular character hepatic NETs or liver metastases of
NETs can be treated with intraarterial chemo or radiotherapy