ASCO GU 2018: Adrenal Cortical Carcinoma: Finding the Wolf in Sheep’s Clothing

San Francisco, CA (UroToday.com) Dr. Mayo-Smith from Boston’s Brigham and Women’s Hospital provided the Keynote Lecture for Adrenal Cortical Carcinoma (ACC). Dr. Mayo-Smith started by highlighting that when looking at the NCI website for ACC, it states several telling points: (i) NCI does not have evidence-based information about prevention of ACC, (ii) rare endocrine cancers have novel genetic alterations, and (iii) NCI does not have evidence-based information about screening for ACC. 

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 [1]. 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)
The pathologic diagnosis of ACC is based on the Weiss Criteria, which includes the number of mitosis/high power field, capsular invasion and necrosis. Dr. Mayo-Smith notes that benign tumors tend to grow slowly and by expansion, are homogenous, smooth marginated, and well circumscribed. Alternatively, ACC grows faster and incites a desmoplastic response, are heterogeneous, have necrosis, and ill-defined margins. Histologic considerations for adrenal masses may also help with diagnosis. Adenomas tend to have high intracellular lipid content whereas ACC and metastatic lesions to the adrenal gland tend to have low lipid content.

Dr. Mayo-Smith notes 7 imaging phenotypes to differentiate benign and pathologic adrenal masses:

  1. Prior exams – if there is stability it is more than likely benign
  2. Lesion size and shape – larger masses and those with necrosis are associated with increased concern for cancer
  3. Imaging features may be diagnostic – particularly for myelolipomas, hemorrhage, cysts
  4. Density on CT scan - ≤10 HU is associated with an adenoma
  5. CT contrast washout – increasing washout is associated with an adenoma
  6. MRI – a signal drop-off is associated with an adenoma
  7. PET – increased activity is associated with a concern for cancer
Dr. Mayo-Smith concluded with a simplified algorithm for the incidental, asymptomatic adrenal mass (≥1 cm) detected on any CT or MRI:

  • 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
Dr. Mayo-Smith provided several important take-home messages: (i) ACC is rare and has a poor prognosis, (ii) adrenal incidentalomas are common (5-7% of population) and are primarily benign, (iii) there are a number of radiology tools to differential benign from malignant lesions, and (iv) combining clinical presentation with advances in radiology techniques can help separate benign from malignant adrenal masses. 


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

References: 

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.
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