ESUR 2018, Sept. 13 th.-16 th., 2018 Barcelona, Spain

ESUR 2018, Sept. 13 th.-16 th., 2018 Barcelona, Spain OUR APPROACH Incidental adrenal nodule/mass Isaac R Francis, M.B;B.S University of Michigan, Ann Arbor, Michigan

Disclosures None (in memory) M Korobkin, Richard Baron Acknowledgements: H Hussain, M Davenport, E Caoili, RH Cohan Abdominal Imaging Group

Incidental Adrenal Mass Overview Imaging features and morphology characterization Review of European Society of Clinical Endocrinology & European Network for Study of Adrenal Tumors Practice Guidelines and American College of Radiology Incidental Findings Project Guidelines CT washout and CSI MRI, technique, pitfalls and comparison Our approach to adrenal nodules/masses

Overview Occurs in approx. between 3-7% of subjects undergoing CT- more common in older subjects (approx. 10% in pts. = > 70) - majority are between 1-4 cm in size Majority are benign lesions, with most common incidental adrenal mass being a non functioning adenoma Even in cancer pts. most incidental isolated adrenal masses are benign But can be common site for metastases in some cancer(up to 20%, in some studies) Incidental Adrenal Mass Young WF Jr. NEJM 2007; Grumbach MM et al. Ann Int Med 2003 Frequency of functioning or malignant adrenal lesions in non oncological patients 1049 masses studied ( 96% of masses < 4 cm) 788 adenomas (75%) 68 myelolipomas, 47 hematomas, 13 cysts 3 pheochromocytomas and 1 cortisolproducing adenoma In 973 pts. with incidental adrenal mass and no history of cancer, there were no malignant lesions Majority were adenomas (75%) In the non-oncological pt. most incidental adrenal masses are benign Song JH AJR 2008

Definition: Incidental Adrenal Mass Incidentaloma Adrenal mass > 1 cm in size, detected on imaging not performed for suspected adrenal disease Imaging done for evaluation of symptoms not related to adrenal dysfunction Excludes imaging done as screening for hereditary syndromes Strictly also excludes imaging done as part of staging studies in patients with extra-adrenal malignancies Mayo-Smith WW, Song JH, Boland GL, Francis IR et al. JACR 2017

Specific features History of cancer Incidental Adrenal Mass Key Issues Biochemical adrenal dysfunction

Specific features Fat (Myelolipoma)-other causes: degenerated adenoma, rarely ACC Simple fluid (Cyst) Incidental Adrenal Mass High density unenhanced image (Hemorrhage) 73 Low density (<10 HU) or loss of SI on CSI- Lipid-rich adenoma

Incidental Adrenal Mass Using size vs. presence of intracellular lipid to predict malignancy What is more predictive of malignancy: Size or presence of intracellular lipid (< 10 HU or no loss of signal on CSIMRI) 113 adrenal resections- only 20/112 (18%) - small no: of resected masses malignant Imaging features (presence of lipid etc.) are more predictive of benignity than size alone If size criteria alone used (= or > 4 cm), 9/20 (45%) malignancies including 1 ACC would have not undergone surgery or biopsy Yoo JY et al. Ann Surg Oncol 2015

Masses > 4 cm Benign Masses < 4 cm Malignant - 54 HU 5.7 cm 4.6 cm Myelolipoma Lipid-Rich Adenoma 3.1 2.9 cm Adrenal Cancer

Incidental Adrenal Mass Can morphology predict malignancy? Can morphological features differentiate benign from malignant adrenal masses Gd-T1 211 masses (1-4 cm) Masses with thick enhancing rim or irregular margins are more likely to malignant but there is significant overlap with benign lesions Low sensitivity Song JH et al AJR 2013 Degenerated Pheochromocytoma Adenoma

European Society of Clinical Endocrinology & European Network for Study of Adrenal Tumors Practice Guidelines Incidental Adrenal Mass American College of Radiology Incidental Findings Management Project Recommendations and Guidelines have very LOW evidence of support Lack of sufficient data from large prospective studies Fassnacht M et al. Eur J Endocrinology 2016.online. 175:2: G1-G34 Mayo-Smith WW, Song JH, Boland GL, Francis IR et al. JACR 2017

European Society of Clinical Endocrinology & European Network for Study of Adrenal Tumors Practice Guidelines Risk of malignancy assessment: Imaging study to determine if adrenal nodule/mass is homogeneous and lipid-rich : Non contrast CT If non contrast CT is consistent with a benign lesions i.e. < 4 cm in size and homogeneous and < 10 HU No additional imaging workup is needed Incidental Adrenal Mass American College of Radiology Incidental Findings Management Project Masses with benign imaging features Masses with features of a myelolipoma, cyst, hemorrhage, require no follow up imaging Masses with features of lipid rich adenoma - < 10 HU on non contrast CT or loss of signal intensity as compared to spleen on out-of-phases (opposed phase) images on MRI Need no further follow up imaging Fassnacht M et al. Eur J Endocrinology 2016.online. 175:2: G1-G34 Mayo-Smith WW, Song JH, Boland GL, Francis IR et al. JACR 2017

Masses that do not need follow up imaging 7 HU Lipid-rich adenoma Adrenal Myelolipoma Adrenal Cyst

European Society of Clinical Endocrinology & European Network for Study of Adrenal Tumors: Practice Guidelines If the adrenal mass is indeterminate Hormonal workup needed Incidental Adrenal Mass American College of Radiology Incidental Findings Management Project For indeterminate adrenal nodule/mass > 1 cm to < 4 cm (non contrast CT), dedicated adrenal mass CT protocol (using washout ratio calculations) Fassnacht M et al. Eur J Endocrinology 2016.online. 175:2: G1-G34 Mayo-Smith WW, Song JH, Boland GL, Francis IR et al. JACR 2017

Incidental Adrenal Mass European Society of Clinical Endocrinology & European Network for Study of Adrenal Tumors: Practice Guidelines And American College of Radiology Guidelines Functioning cortisol producing adenoma 3.2 cm 33HU ESCE & ENSAT- Hormonal eval. ACR- Washout < 60% and then? hormonal eval.

Incidental Adrenal Mass European Society of Clinical Endocrinology & European Network for Study of Adrenal Tumors: Practice Guidelines Indeterminate adrenal mass with negative hormonal workup Biopsy NOT recommended Three options: - Imaging with another modality/technique - Follow up (CT or MRI) - Surgery American College of Radiology Incidental Findings Management Project CT Washout- adenoma (lipid rich and lipid poor)- stop If washout indeterminate DO NOT BIOPSY? Hormonal evaluation Repeat CT or MRI in 12 months for small > 1 to < 2 cm masses and 6 months for masses 2-4 cm Fassnacht M et al. Eur J Endocrinology 2016.online. 175:2: G1-G34 Mayo-Smith WW, Song JH, Boland GL, Francis IR et al. JACR 2017

Follow up for patients not undergoing surgery after initial assessment- ESCE &ENSA Surgical resection if lesion grows more than 20% (> 5 mm/0.5-1 yr.). If less repeat follow up imaging at same time interval In pts. with autonomous cortisol secretion without overt Cushing s, reassess for cortisol excess Incidental Adrenal Mass ACR- Masses without diagnostic ( indeterminate ) features - Size > 1 cm and < 4 cm Masses that are unchanged over 1 yr. period - likely benign Depending on rate of growth considersurgery if rapid growth rate (> 5mm/0.5-1yr.) [exc. ACC] and if growth rate slow consider biochemical evaluation Fassnacht M et al. Eur J Endocrinology 2016.online. 175:2: G1-G34 Mayo-Smith WW, Song JH, Boland GL, Francis IR et al. JACR 2017

Enlarging Adrenal Nodule in cancer pt. Sept. 2016 May 2017 Bx. Met. Urothelial malignancy

Adrenal mass showing in non cancer pt. - Interval growth 2009 2012 Nogueira TM et al Horm Canc 2015 Courtesy: T Else, MD Surgery Adrenal cortical cancer

Incidental Adrenal Mass American College of Radiology Management of Incidental Findings Project Masses without diagnostic ( indeterminate ) features Size > 4cm Isolated adrenal mass with no h/o cancer Surgery Isolated adrenal mass with h/o cancer PET/CT or biopsy Mayo-Smith WW, Song JH, Boland GL, Francis IR et al. JACR 2017

History Adrenal mass Pt. with h/o colon malignancy Colon cancer diagnosed in 2004 Treated with LAR Developed lung met in 2015 Now presents with new R adrenal mass Metastases from colon cancer

Adenomas vs. Non Adenomas Quantitative CT Densitometry With Unenhanced and Washout Features Unenhanced = < 10 H Sensitivity of 71% and specificity of 98% (lipid rich adenoma) Percentage enhancement washout: (E-D) x 100 E-D x 100 (E-U) Threshold for adenoma (lipid rich and poor) diagnosis: Absolute washout = or > 60% Relative washout = or > 40% Specificity nearly 95% * E= 60 secs. enhanced, D= Delayed 15 min. U=unenhanced Korobkin M et al. AJR 1998; Caioli EM et al. Radiology 2002 E

Pitfalls ROI- include about 2/3 rds. of lesion without extending to include adjacent fat Ensure the image is artifact free Necrotic masses- Leads to false + ve diagnosis of adenoma No data for inhomogeneous adrenal nodules Adenoma vs. Nonadenoma CT Densitometry * Johnson PT et al. Radiographics 2009 *Choi YA et al Radiology 2013

Lipid Poor Adenoma 22 HU 85 HU 42HU UNENHANCED PORTAL VENOUS PHASE 15 MINS. DELAYED Adrenal Washout = 68% 60% APW = Benign adenoma Unenhanced HU = > 10 HU

Adrenal Metastasis from Renal Cell Carcinoma 37 99 70 UNENHANCED PORTAL VENOUS PHASE 15 MINS. DELAYED Washout = 47% (<60%) Diagnosis? Not a typical adenoma Pt. with h/o renal cell carcinoma- Adrenal Bx

CT Densitometry Pitfalls Adrenal cysts may show absolute washout of less than 60%- mimic washout of non-adenomas Some of the lipid-containing vascular metastases- clear cell RCC, well-differentiated HCC

Metastatic Clear Cell Renal Cancer 32 HU 139 HU 62 HU Washout = 72% > 60% = benign? Has h/o partial nephrectomy for clear cell RCC Lipid-containing vascular metastases can show washout similar to benign adenomas

Incidental Adrenal Mass Dual energy CT In small series virtual unenhanced images show equal sensitivity to true unenhanced images for adenoma diagnosis Virtual unenhanced derived from early (portal venous phase) DECT images, show attenuation numbers of adrenal nodules which are always higher than those obtained on true unenhanced images Less overlap on delayed DECT images Some lipid rich adenomas are not diagnosed due to problems with technical failure (incomplete iodine removal) from the early portal venous phase dual energy CT images Kim YK et al. Radiology 2013; Helck A et al Eur Radiol 2014

Adenoma: Intracellular Lipid on MRI Signal loss on OP Qualitative Quantitative Dual-echo sequence Signal Intensity Index (SII) OP SII = IP OP X 100 IP Adenoma >16.5% (or 20%) IP Fujiyoshi F, et al. AJR 2003; Haider MA, et al. Radiology 2004; Schindera ST Radiology 2008

Pitfall: CSI MRI Lipid containing metastasis from clear cell renal cell carcinoma (RCC) Prior right nephrectomy for RCC New left adrenal nodule SII = 35% Mimics of lipid-containing adenomas: Metastatic (clear cell) renal cell carcinoma Metastases from HCC can also contain lipid However usually have higher T2 signal and are heterogeneous Schieda N et al AJR 2017 OP IP

Incidental Adrenal Mass CT Densitometry (Washout) vs. CS-MRI for adenoma diagnosis 37 lipid poor adenomas and 15 non adenomas studied with washout CT and CSI MR CS-MRI equivalent to CT for adenomas measuring up to 20 HU ; washout CT superior to CS-MRI for masses measuring > 20 HU Other groups also have shown greater sensitivity and specificity for differentiating between lipid poor adenomas and non adenomas especially for masses measuring > 20-30 HU on washout CT as compared to CS- MRI Seo JM et al AJR 2014: Koo HJ et al. Eur Radiol 2014: Warda MHA et al. Clin Imaging 2016

CT Densitometry Washout vs. CS-MRI for lipid poor adenoma diagnosis Seo JM et al AJR 2014 Koo HJ et al. Eur Radiol 2014

OUR APPROACH Adrenal nodule > 1 cm detected on enhanced abdominal CT cancer and non cancer pts. Compare with prior CT or MR if available If no change - assume benign - no additional workup New mass in cancer pt. likely met- in non cancer pt.? Malignancy-confirm with PET/CT or biopsy/resection If no prior imaging and characterization needed- adrenal protocol CT (portal venous and 15 min. delayed images) If less than 10 HU (non contrast CT)- stop- if more than 10 HU, perform washout CT

OUR APPROACH If CT benign washout characteristic- stop. If indeterminate additional workup in cancer pts- PET/CT/ biopsy Eval. for functioning lesion in non cancer pts.- Hormonal assessment Also based on size and appearance of adrenal lesion- additional workup in non cancer pts. - Small nodules (1-2 cm) with no h/o cancer Follow up in 12 monthsassess for growth - Larger nodules > 2- < 4 cm, short term follow up (6 months) or PET/CT/surgery based on suspicion for cancer and discussion with pt. > 4 cm- non cancer pt.- surgery; h/o cancer- PET/CT/biopsy

Incidental Adrenal Mass Overview Imaging features and morphology characterization Review of European Society of Clinical Endocrinology & European Network for Study of Adrenal Tumors Practice Guidelines and American College of Radiology Incidental Findings Project Guidelines CT washout and CSI MRI, technique, pitfalls and comparison Our approach to adrenal nodules/masses

MOLTES GRACIES BONA NIT MUCHAS GRACIAS BUENAS TARDES THANK YOU Have a good evening

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