3.1 Specialist diagnostic work-up

3.1 Specialist diagnostic work-up

The treatment team, after taking a thorough medical history and making a thorough medical examination of the patient, should undertake the following investigations under the guidance of a specialist.

  • Biochemical markers – measurement of serum chromogranin A may be appropriate. Specific hormonal assessment will be depend on symptomology of the primary NET.
  • Anatomical (e.g. CT, MRI) and functional imaging (68Ga-DOTATATE PET/CT, 18F-FDG PET) as indicated.
  • Biopsy – histopathological diagnosis (grade and differentiation). Biopsies should be reviewed by a pathologist with experience in NETs.

All diagnostic investigations should be completed within two weeks of the initial specialist appointment.

Hereditary susceptibility should be considered in any patient with a NET. The risk of a heritable cause is particularly high for people with medullary thyroid cancer, phaeochromocytoma and paraganglioma, for whom genetic counselling and testing should be routinely performed.

MEN-1 should be considered in those with a gastrinoma or multifocal gastroenteropancreatic neuroendocrine cancer (GEP-NET) at any age; patients with a GEP-NET before age 40 years; and patients with a bronchial or thymic NET at any age.

In MEN, approximately 10–15 per cent of all pNETs are associated with MEN-1, and up to 80 per cent of patients with MEN-1 will develop pNETs (O’Shea & Druce 2017).

For the exact tumours related to each MEN subtype, refer to section 1.3.

Other potential genetic causes include mutations in VHL, SDHA/B/C/D, fumarate hydratase and TMEM127 – refer to section 1.3 for more information.

Other rare genetic causes of phaeochromocytoma and paraganglioma include KIF1B, MDH2, GOT2, DLST and SLC25A11.

Anyone diagnosed with cancer should have a detailed personal and family cancer history taken. Consult relevant guidelines to determine if referral to a familial cancer service is appropriate.

A familial cancer service assessment can determine if genetic testing is appropriate. Genetic testing is likely to be offered when there is at least a 10 per cent chance of finding a causative ‘gene error’ (pathogenic gene variant; previously called a mutation). Usually testing begins with a variant search in a person who has had cancer (a diagnostic genetic test). If a pathogenic gene variant is identified, variant-specific testing is available to relatives to see if they have or have not inherited the familial gene variant (predictive genetic testing).

Medicare funds some genetic tests via a Medicare Benefits Schedule (MBS) item number but most are not. Depending on the personal and family history, the relevant state health system may fund public sector genetic testing.

Pre-test counselling and informed consent is required before any genetic testing. In some states the treating team can offer ‘mainstream’ diagnostic genetic testing, after which referral is made to a familial cancer service if a pathogenic gene variant is identified. The familial cancer service can provide risk management advice, facilitate family risk notification and arrange predictive genetic testing for the family.

Visit the Centre for Genetics Education website for basic information about cancer in a family.

For detailed information and referral guidelines for NETs risk assessment and consideration of genetic testing, see When should genetic testing be performed in patients with neuroendocrine tumours.

Find more information on MEN-1 genetic testing, risk management and lifetime risk.

For more information on MEN-2, visit the eviQ website.

The succinate dehydrogenase (SDH) complex genes are a family of genes (SDHA, SDHB, SDHC, SDHD and SDHAF2). For more information visit the eviQ website.

Pharmacogenetics describes how individual genetic differences can lead to differences in the way certain medicines interact with the body. These interactions can affect the effectiveness of medications and any side effects. Applying pharmacogenetics to treatment planning may help patients to be prescribed the most appropriate treatment at the optimal dose from the beginning
of treatment (NHMRC 2013).