Elliot K. Fishman M.D.
Johns Hopkins Hospital

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Benign

• Adrenal Adenoma
• Adrenal Cyst
• Adrenal Myelolipoma
• Adrenal Hemorrhage
• Pheochromocytoma
• Ganglioneuroma

Malignant

• Primary adrenal carcinoma
• Adrenal metastases
• Adrenal lymphoma
• Pheochromocytoma (malignant 10%)
• Adrenal sarcoma (rare)

Adrenal mass analysis

• Size of mass
• Boundaries around the adrenal gland
• Unilateral vs bilateral
• Pattern of enhancement
• Presence of calcification
• Extra adrenal findings

“Of 4085 patients with adrenal tumors, 705 (17%) had adrenal masses measuring 4 cm or more in diameter; of these, 373 (53%) were women, with a median age of 59 years (range, 18-91 years) and median tumor size of 5.2 cm (range, 4.0-24.4 cm). Underlying diagnoses were adrenocortical adenomas (n=216 [31%]), pheochromocytomas (n=158 [22%]), other benign adrenal tumors (n=116 [16%]), adrenocortical carcinomas (n=88 [13%]), and other malignant tumors (n=127 [18%]).”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

“The prevalence of malignancy in patients with adrenal tumors of 4 cm or more in diameter was 31%. Older age, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were associated with an increased risk for malignancy. Clinical context should guide management in patients with adrenal tumors of 4 cm or more in diameter.”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

”Compared with benign tumors, malignant tumors were less frequently diagnosed incidentally (45.5% vs 86.7%), were larger (7 cm [range, 4-24.4 cm] vs 5 cm [range, 4-20 cm]), and had higher unenhanced computed tomographic (CT) attenuation (34.5 Hounsfield units [HU] [range, 14.1-75.5 HU] vs 11.5 HU [range, −110 to 71.3 HU]; P<.001). On multivariate analysis, older age at diagnosis, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were all found to be statistically significant predictors of malignancy.”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

”We found that patients with adrenal tumors of at least 4 cm in diameter represent a heterogeneous group with an overall malignancy rate of 31%. We found that older age at the time of discovery of an adrenal mass, male sex, nonincidental mode of discovery, larger tumor size, and indeterminate imaging characteristics are predictors of a malignant adrenal mass. However, there are important differences in presentation and risk factors for ACC vs other malignant tumors, most notably sex (64% vs 35% women), age at diagnosis (median of 50 vs 66 years), and the presence of bilateral adrenal tumors (0% vs 30%).”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

“Pheochromocytomas were diagnosed in 22% of our cohort patients, with approximately half being discovered incidentally (54%). Thus, it is essential to biochemically exclude PHEO, especially in an adrenal mass with indeterminate imaging characteristics. The prevalence of PHEO in patients with incidentally discovered adrenal tumors of any size was previously reported to be 4.2%.”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

“It is important to note that in a third of the patients with malignant adrenal tumors, the diagnostic evaluation and management differed on the basis of etiology. We recommend that the management of patients with large adrenal tumors should be individualized to the patient's circumstances and presentation, taking into account patient age, sex, mode of discovery, imaging phenotype including unenhanced CT tumor attenuation, rate of tumor growth and size, hormonal activity, and comorbidities. An active or previously diagnosed extraadrenal malignancy should raise the suspicion for metastases.”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

”Large adrenal tumors are most frequently diagnosed incidentally and encompass a heterogeneous group. Tumor size alone is not a reliable determinant of malignancy. The overall prevalence of malignancy in patients with adrenal tumors of at least 4 cm in diameter was 31%. Risk of malignancy was associated with age at diagnosis, male sex, nonincidental mode of discovery, larger tumor size, and indeterminate imaging characteristics. All ACCs, PHEOs, and malignant adrenal tumors other than ACC demonstrated unenhanced CT attenuation of more than 10 HU, which supports the concept that malignancy and PHEO can be excluded with certainty in patients with adrenal tumors with unenhanced CT attenuation of less than 10 HU.”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors
Nicole M. Iñiguez-Ariza et al.
Mayo Clin Proc Innov Qual Outcomes. 2018 Mar; 2(1): 30–39.

“In patients without prior malignancy, size alone was a highly sensitive indicator of adrenocortical carcinoma in one study, with 90% sensitivity but only 24% specificity in one series using a 4-cm cutoff. The likelihood of adrenocortical carcinoma increases as the size increases. Approximately 6% of all adrenal tumors that have a size range of 4–6 cm are malignant, and the probability of malignancy increases to 25% for lesions larger than 6 cm.”
Interobserver agreement in distinguishing large adrenal adenomas and adrenocortical carcinomas on computed tomography. 
Thomas AJ et al.
Abdom Radiol (NY). 2018 Nov;43(11):3101-3108. 

“Morphologic features can also be useful for characterizing these lesions. Necrosis, irregular margins, heterogeneous appearance, and the absence of fat have all been associated with malignancy. Adrenocortical carcinomas also calcify in approximately 30% of cases. Tumor morphology may more reliably indicate adrenocortical carcinoma than contrast washout, owing to the heterogeneity within a given lesion. Nonetheless, adrenocortical carcinomas usually display a washout pattern similar to that of other malignant adrenal processes.”
Interobserver agreement in distinguishing large adrenal adenomas and adrenocortical carcinomas on computed tomography. 
Thomas AJ et al.
Abdom Radiol (NY). 2018 Nov;43(11):3101-3108. 

”The most predictive characteristic was precontrast attenuation. Lesions that were classified as < 10 HU in attenuation by the readers were all benign, and the lowest precontrast attenuation for an adrenocortical carcinoma was measured at 18.6 HU. Low precontrast attenuation has been demonstrated to be specific for benign adenomas due to the fact that adrenal adenomas often display abundant intracytoplasmic lipid. The presence of fat on CT was correlated to a benign pathologic diagnosis in our study with a specificity of 93%, and there was moderate interobserver agreement regarding its presence or absence.”
Interobserver agreement in distinguishing large adrenal adenomas and adrenocortical carcinomas on computed tomography. 
Thomas AJ et al.
Abdom Radiol (NY). 2018 Nov;43(11):3101-3108. 

”In conclusion, our study identified morphologic CT characteristics that correlate with the pathologic diagnosis for large adenomas and adrenocortical carcinomas, including precontrast attenuation, shape, and the presence of fat, which can be determined by different radiologists with moderate or greater consistency. Two of these, attenuation and the presence of fat were both highly specific for benign pathology, although the sensitivity for each was low, and many lesions therefore remain indeterminate by CT. Attenuation was both more specific and had higher interobserver agreement, indicating it may be the best indicator of the underlying pathology. Further study is needed to uncover additional imaging findings that can confidently and consistently predict a benign diagnosis, potentially allowing patients to undergo conservative management and avoid the cost and potential complications of surgery.”
Interobserver agreement in distinguishing large adrenal adenomas and adrenocortical carcinomas on computed tomography. 
Thomas AJ et al.
Abdom Radiol (NY). 2018 Nov;43(11):3101-3108. 

Adrenal adenomas under 4cm are usually easy to diagnose but as they get larger they ae a clinical channel

“In contrast to adrenocortical carcinomas, adrenal adenomas are the most common adrenal tumors, and they are usually small and not hormonally active . When smaller than 4 cm, approximately 70% of adenomas contain intracytoplasmic lipids and measure less than 10 HU on noncontract CT. Thus, they can confidently be considered benign. In the lipid-poor minority, a benign washout pattern can also be diagnostic of a benign lesion. Unfortunately, atypical adenomas can be large and heterogeneous, with areas of hemorrhage, calcification, and cystic degeneration, and in these cases, there can be significant imaging overlap with adrenocortical carcinomas.”Interobserver agreement in distinguishing large adrenal adenomas and adrenocortical carcinomas on computed tomography. Thomas AJ et al.Abdom Radiol (NY). 2018 Nov;43(11):3101-3108.