Presentation: Adult with possible adrenocortical carcinoma

A 45-year-old woman is referred to the endocrine clinic after a right-sided 5.5cm adrenal mass is discovered on a CT scan performed to investigate abdominal pain. The adrenal mass is radiologically characterised as indeterminate (unenhanced Hounsfield units of 21) and biochemical testing demonstrates evidence of autonomous cortisol secretion, which is adrenocorticotropic hormone-independent. After discussion at a cancer multidisciplinary team meeting, the patient is referred for a right-sided adrenalectomy, and histology confirms an adrenocortical carcinoma (ACC). There is a family history of breast cancer in two first-degree relatives, both of whom were diagnosed at under 45 years old.

• All patients diagnosed with ACC should be offered genomic testing for Li-Fraumeni syndrome.
• All patients under the age of 50 who are diagnosed with ACC should be offered genomic testing for Lynch syndrome.
• All patients diagnosed with ACC over the age of 50 should be offered genomic testing for Lynch syndrome if one of the following criteria is met:
  • there is a personal or family history of colorectal cancers reaching Modified Amsterdam Criteria (three or more relatives with Lynch-related cancers over two or more generations, with one or more case(s) diagnosed under the age of 50);
  • the patient has any Lynch-related cancer diagnosis under the age of 50 (excluding isolated pancreas, prostate or gastric cancers);
  • the patient has two Lynch-related cancers (at any age) where one is colorectal or endometrial;
  • the patient has Lynch-related cancer and one or more first-degree relative(s) with Lynch-related cancer (both having occurred at or before the age of 60, where one is colorectal or endometrial);
  • the patient has Lynch-related cancer and two or more first-, second- or third-degree relatives with Lynch-related cancer (all occurring at or below the age of 75, where one is colorectal or endometrial); or
  • the patient has Lynch-related cancer and three or more first-, second- or third-degree relatives with Lynch-related cancer (occurring at any age, where one is colorectal or endometrial).

Lynch-related cancers comprise colorectal cancer, endometrial cancer, epithelial ovarian cancer, ureteric cancer, transitional cell cancer of the renal pelvis, cholangiocarcinoma, small bowel cancer, glioblastoma, endocervical cancer and multiple sebaceous tumours.

• Genomic testing for multiple endocrine neoplasia type 1 (MEN1) should be considered for patients presenting with adrenocortical carcinoma if one of the following criteria is met:
  • parathyroid multi-glandular disease (hyperplasia or adenoma) (diagnosed before the age of 35);
  • any pituitary adenoma or insulinoma (diagnosed before the age of 20);
  • pituitary macroadenoma (diagnosed before the age of 30);
  • two or more MEN1-related endocrine anomalies (diagnosed at any age);
  • one or more MEN1-related endocrine anomaly(ies) and one or more MEN1-related non-endocrine tumour(s) (diagnosed at any age); or
  • one or more MEN1-related endocrine anomaly(ies) and a first-degree relative with one or more MEN1-related endocrine anomaly(ies).
• Tumour sequencing (somatic testing) can be considered for all patients diagnosed with ACC if a molecular diagnosis would alter management or aid diagnosis (this is especially relevant for patients under consideration for neurotrophic tyrosine receptor kinase inhibitors). M14 Adrenal cortical carcinoma should be requested if a suitable tissue sample is available.

For more information about endocrine anomalies, see Endocrine neoplasia.

• Consult the National Genomic Test Directory. From here, you can access the rare and inherited disease eligibility criteria, which contains information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Select the appropriate test panel for your patient, depending on their presentation. Some of the panels to consider are listed below.
  • R216 Li-Fraumeni syndrome. This involves small gene panel sequencing (including TP53 and POT1) and multiplex ligation-dependent probe amplification (MLPA) or equivalent.
  • R210 Inherited MMR deficiency (Lynch syndrome). This involves small gene panel sequencing (including EPCAM, MLH1, MSH2, MSH6 and PMS2) and MLPA or equivalent, plus MLH1 promoter methylation testing if required.
  • R217 Multiple endocrine neoplasia. This involves small gene panel sequencing (including AIP, CDC73, CDKN1B, MEN1, PRKAR1A, RET and VHL) and MLPA or equivalent.
  • M14 Adrenal cortical carcinoma. This includes TP53, NTRK1, NTRK2 and NTRK3.
• None of the tests outlined above include whole genome sequencing, so you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• Most tests are DNA based, and an EDTA sample (purple-topped tube) is required. The sample is best stored at four degrees Celsius until it can be posted to the genomic laboratory.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory

For patients

• ACC Support UK
• Association for Multiple Endocrine Neoplasia (AMEND)