ACC is very rare, with an incidence of 1-2 per 1 billion people per year. It demonstrates a bimodal incidence at <5 years and 50 years with the adult ACC more aggressive than the pediatric entity. The female to male ratio is 2:1 and there is a 10x increased incidence of ACC in southern Brazil. The majority of ACC cases are sporadic, however it may be associated with several syndromes, including Li-Fraumeni, Beckwith-Wiedemann and MEN1 syndromes. Molecularly, ACC is thought to be monoclonal in origin. The p53 gene on chromosome 17p13 has been implicated in 50-80% of cases of ACC in children.
ACC in adults typically presents with (i) a hormone excess (60%) - including Cushings alone (45%), Cushings and virilization (25%), and virilization alone (<10%); (ii) pain (20%); (iii) incidentally discovered on CT scan (20-30%). An “incidentaloma” is an accidentally discovered mass detected on a radiology exam performed for an unrelated reason. With an increased volume and resolution of imaging, incidental findings are becoming more common, however most incidental findings are benign. Dr. Mayo-Smith notes that the approach to incidental findings is highly variable by radiologist and institution.
The prevalence of adrenal masses is ~5-7% of the population in both pathology and imaging literature. The main risk factor is patient age, as 0.2% of adrenal masses are found in people 20-29 years of age, whereas 7-10% are found in people >70 years of age. The prevalence of incidentalomas in the US is estimated at 12 million, of which the overwhelming majority are hyperplastic nodules or benign non-functioning adenomas. The concern, however, is for (i) the occult hyperfunctioning neoplasm such as an adenoma secreting cortisol or aldosterone, as well as pheochromocytoma, and (ii) a malignant neoplasm, either an ACC or a metastatic lesion. A study from 2008 of which Dr. Mayo-Smith was the senior author provocatively outlined the basis of adrenal pathology on abdominal CT exams . On review of 65,231 abdominal CT exams from 2000-2003, adrenal masses were seen in 3,344 (5%) of cases of which 1,099 patients without cancer had the mass characterized. Of these, 85% were adenomas, 6% myelolipomas, 4% hematomas, 4% calcification, 1% cyst. Although there were three pheochromocytomas and one cortisol secreting adenoma, there were no instances of ACC.
The stage of presentation of ACC is as follows:
- Stage I: 14% (<5 cm)
- Stage II: 45% (>5 cm)
- Stage III: 27% (local invasion)
- Stage IV: 24% (metastatic disease)
Dr. Mayo-Smith notes 7 imaging phenotypes to differentiate benign and pathologic adrenal masses:
- Prior exams – if there is stability it is more than likely benign
- Lesion size and shape – larger masses and those with necrosis are associated with increased concern for cancer
- Imaging features may be diagnostic – particularly for myelolipomas, hemorrhage, cysts
- Density on CT scan - ≤10 HU is associated with an adenoma
- CT contrast washout – increasing washout is associated with an adenoma
- MRI – a signal drop-off is associated with an adenoma
- PET – increased activity is associated with a concern for cancer
- Benign imaging features myelolipoma, no enhancement, benign calcium deposits, ≤10 HU or decreased signal on MRI: no follow-up
- Indeterminate imaging features ≥4 cm: if there is no history of cancer then resection; if a history of cancer then biopsy or PET-CT scan
- Indeterminate imaging features 1-4 cm: if prior imaging and stable more than 1 year then likely benign and no follow-up; if prior imaging and enlarging mass, then suspicious for malignancy – if no history of cancer then follow-up or resection; if no prior imaging and no cancer history and >2 cm < 4 cm then obtain an adrenal CT scan; if no prior imaging and no cancer history and 1-2 cm in size then probably benign and consider follow-up in 1 year
Presented by: William W. Mayo-Smith, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, @zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
1. Song JH, Chaudhry FS, Mayo-Smith WW. The incidental adrenal mass on CT: prevalence of adrenal disease in 1,049 consecutive adrenal masses in patients with no known malignancy. AJR Am J Roentgenol 2008;190(5):1163-1168.