Neuroendocrine Tumours


Neuroendocrine tumours = Gastro-entero-pancreatic tumours = Carcinoids + pancreatic endocrine tumours

Always consider familial syndromes (MEN-1, MEN-2, NF1, VHL, Carney complex), especially if there is a family history of neuroendocrine tumour.

Carcinoids

About 2/3 of NETs are carcinoid tumours (so called because resembled carcinoma but much slower-growing), of which 10% cause carcinoid syndrome. Carcinoids are commonly surrounded by fibrous tissue, possibly due to stimulation of fibroblasts by growth factors.

Incidence 2-3 per 100 000 per year.

Types of carcinoids

Classification Where Clinical features Metastasis/prognosis
Foregut
(lung, stomach, pancreas, proximal duodenum)
Lung
  • Usually perihilar
  • Pneumonia, cough, haemoptysis, chest pain
  • May secrete ACTH, GH
  • Carcinoid syndrome <5%
  • Generally <10%
  • To LN, liver, bone, skin
Stomach
  • 75% are associated with chronic atrophic gastritis type A (CAG-A)
    • >50% also have pernicious anaemia
    • Frequently multifocal
    • Hypochlorhydria causes hypergastrinaemia, thought to provoke carcinoid development
    • Animal evidence for similar effect of PPIs but not yet in humans
  • 5-10% associated with Zollinger-Ellison syndrome in MEN-1
  • 15-20% sporadic
    • Usually solitary
    • Atypical flushing-only carcinoid syndrome thought to be mediated by histamine
Generally <10%. Sporadic gastric carcinoids may be aggressive.
Midgut
(second part of duodenum to right colon)
Small intestine
  • About a third of small bowel tumours are carcinoids
  • Often multiple small tumours - rarely seen on CT/Ba studies
  • Carcinoid syndrome in 5-7%
  • Most present with mets in LN and liver
  • Primary size is a poor guide to presence of mets
  • 5-year survival 65% if distant mets, 36% if none or regional only
Appendix Usually incidental: most are in distal appendix so do not cause obstruction Large appendiceal carcinoids can metastasize
Hindgut Transverse colon to rectum
  • Rarely secretory, symptoms usually relate to mass effect/fibrosis/torsion
  • Small (<1cm): <5%
  • Large (>2cm): majority

Clinical features of carcinoids

5-hydroxytryptamine (5-HT; serotonin) is metabolized to 5-hydroxyindoleacetic acid (5-HIAA) which is excreted into the urine. 5-HT is metabolized in the liver; thus, gut carcinoids do not usually cause carcinoid syndrome until they have metastasized.

Feature Description
Abdominal pain
  • Usually intermittent, due to fibrosis of mesentery, or intestinal obstruction
Cutaneous flushing
  • Head and neck distribution with striking colour change
  • Associated unpleasant warm feeling, itch, salivation, oedema, diarrhoea
  • May be triggered by exercise/stress/foods (tryptophan-containing, e.g. cheese, chocolate)/ethanol
  • Initially brief, after long disease duration flushing may be prolonged or cause permanent skin changes
Diarrhoea/malabsorption
  • Affects most patients, stools may be watery/frothy/steatorrhoea
Bronchoconstriction
  • Minority of patients, but not rare
Valvular heart lesions
  • Typically tricuspid valve fibrosis
  • Left side spared by lung metabolism
  • Sometimes CCF
Carcinoid crisis
  • Flushing, diarrhoea, tachycardia, hypo- or hypertension, altered mental status

Diagnosis of carcinoids

Urinary 5HIAA is not sensitive for early tumours. Octreotide scanning is an option. Chromgranin A is elevated by gastrin, therefore false +ves may be seen with PPIs. Joy Ardill showed these data at her talk:

Test Sensitivity Specificity
5HIAA >47 µmol/24hr 62 65
Chromogranin A >30u/L 89 68
Pancreastatin >50ng/L 84 95
Neurokinin A >20ng/L 80 98

Treatment of carcinoids

  • Chemotherapy - little evidence but often used.
  • Somatostatin analogues - often effective for symptoms, may inhibit growth.
  • Targeted radiotherapy - typically radio-labelled somatostatin analogues.
  • Surgical resection - the mainstay, even for metastatic disease if possible.

Pancreatic endocrine tumours

About 1/3 of NETs are pancreatic, of which 70-85% are functional.

  • gastrinoma
  • insulinoma
  • glucagonoma
  • VIPoma
  • somatostatinoma
  • rarely, CRHoma, ACTHoma (Cushing's syndrome), calcitoninoma, GHRHoma, parathyroid hormone-related-peptide-oma

A small proportion are non-GI

  • medullary carcinoma of thyroid
  • bronchial carcinoid

Carney Complex

Basically, the combination of cardiac myxomas with cutaneous lentigines; various names/syndromes were described, now grouped under "Carney complex". Autosomal dominant with variable penetrance. Cushing's syndrome due to nodular adrenocortical hyperplasia may occur, and apparently also neuroendocrine tumours.