STANDARDIZED MANAGEMENT RECOMMENDATIONS FOR ADRENAL NODULES: EVIDENCE-BASED CONSENSUS POWERSCRIBE MACROS FROM AN ACADEMIC/PRIVATE PRACTICE

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1 STANDARDIZED MANAGEMENT RECOMMENDATIONS FOR ADRENAL NODULES: EVIDENCE-BASED CONSENSUS POWERSCRIBE MACROS FROM AN ACADEMIC/PRIVATE PRACTICE COLLABORATIVE

2 Pamela Johnson 1, Darcy Wolfman 2, Upma Rawal 3, Farzad Sedaghat 1, Jay Bronner 3 1 Johns Hopkins Department of Radiology, Baltimore, MD 2 Johns Hopkins Department of Radiology, Washington, DC 3 Radiology Partners Research Institute, El Segundo, CA THE AUTHORS HAVE NOTHING TO DISCLOSE

3 PURPOSE & METHODS Incidental adrenal nodules are identified in 7% of patients on imaging. Evidence based management guidelines incorporate medical history (cancer, endocrine syndrome) and imaging features (nodule size, attenuation, enhancement pattern and heterogeneity) into decision-making. The purpose of this initiative was to create a set of standardized report recommendations to manage adrenal nodules, for broad adoption across radiology practices. An academic department and large private practice group collaborated to establish a set of evidence-based consensus macros in Powerscribe for incidental adrenal nodules. The process for guideline development included literature review and consultation with endocrine specialists. Criteria for pheochromocytoma were included, as they comprise 7-19% of incidental nodules. These criteria were based on published data pertaining to contrast enhancement patterns Five variants were created with relevant clinical and imaging variables in each algorithm.

4 PEARLS & PITFALLS FROM PUBLISHED DATA Incidental adrenal nodules < 3 cm usually benign > 4 cm require surgical consultation Adrenal adenoma (lipid rich or lipid poor) Pheocrhomocytoma: enhancing to 217 HU Often homogeneous Increase in enhancement from arterial to venous phase Typically enhances <100 HU on arterial phase & <130 HU on venous phase Usually exceeds APW & RPW thresholds on 15 minute delayed imaging Pheochromocytoma Metastatic leiomyosarcoma: peripherally enhancing Often heterogeneous Can be hypovascular or hypervascular; may enhance >100 HU arterial & >130 HU venous Can exceed APW & RPW thresholds on 15 minute delayed imaging Metastatic disease Do not typically exceed APW (absolute percentage washout) & RPW (relative percentage washout) thresholds on 15 minute delayed imaging Peripheral enhancement should raise concern for metastasis in setting of primary malignancy Hypervascular metastases (RCC, HCC) Can exceed APW & RPW thresholds on 15 minute delayed imaging Metastatic RCC enhances to 153 HU arterial phase and washes out on the delayed phase

5 INTERPRETATIVE VARIANTS CT Classification Cancer history Prior imaging Variant 1 No follow up imaging necessary Yes or no Yes or no Variant 2 Indeterminate adrenal nodule No No Variant 3 Indeterminate adrenal nodule Yes or No Yes Variant 4 Isolated indeterminate adrenal nodule Yes No Variant 5 Adrenal washout CT interpretation Yes or no Pheochromocytoma (pheo) Hypervascular* vs hypovascular primary cancer No *Hypervascular cancers include renal cell carinoma (RCC) and hepatocellular carcinoma (HCC)

6 VARIANT 1 UNSUSPECTED ADRENAL NODULE ON CT REGARDLESS OF CANCER HISTORY OR PRIOR IMAGING NO FOLLOW UP IMAGING NECESSARY. Adenoma < 10 HU on noncontrast CT Meets absolute and/or relative percentage washout criteria on 4 phase renal scan Myelolipoma macroscopic fat can be heterogeneous owing to myelogenous components often contain calcification any size with caveat that bleeding risk increases > 4 cm Pseudocyst Homogeneous fluid density Thin, uniform wall that may contain calcification

7 VARIANT 2 NO CANCER HISTORY INDETERMINATE NODULE NO PRIOR IMAGING Protocol variables noncontrast CT venous phase CT arterial & venous phase CT Size variables Up to 2 cm 2-4 cm > 4 cm Imaging feature variables Hounsfield units homogeneous heterogeneous VARIANT 2A NO CANCER HISTORY INDETERMINATE NODULE NO PRIOR IMAGING NONCONTRAST CT CT Findings Diagnosis Recommendation Up to 2 cm >10 HU homogeneous or heterogeneous 2-4 cm >10 HU homogeneous 2-4 cm >10 HU heterogeneous Probable adenoma, possible pheo Probable adenoma Probable adenoma, possible pheo Clinical assessment for signs or symptoms of pheo. Pursue labs if necessary. Otherwise, <1 cm: no follow-up; 1-2 cm: 1 year follow up CT. If stable at 1 year, no follow up necessary Adrenal washout CT or chemical shift MRI Clinical assessment for signs or symptoms of pheo. Pursue labs if necessary. If no clinical suspicion or labs normal, adrenal washout CT or chemical shift MRI > 4 cm Possible malignancy Surgical consultation

8 VARIANT 2B NO CANCER HISTORY INDETERMINATE NODULE NO PRIOR IMAGING VENOUS PHASE CT CT Findings Diagnosis Recommendation <1 cm & >130 HU Up to 2 cm <130 HU & homogeneous 2-4 cm, <130 HU & homogeneous 1-4 cm >130 HU OR heterogeneous Possible pheo Probable adenoma Probable adenoma Possible pheo Clinical and laboratory assessment for pheo. If negative, 1 year follow up CT. If stable at 1 year, no follow up necessary. <1 cm: no follow up; 1-2 cm:1 year follow up CT. If stable at 1 year, no follow up necessary. Adrenal washout CT or chemical shift MRI. Clinical assessment for signs or symptoms of pheo. Pursue labs if necessary. If no clinical suspicion or labs normal, adrenal washout CT or chemical shift MRI. > 4 cm Possible malignancy Surgical consultation VARIANT 2C NO CANCER HISTORY INDETERMINATE NODULE NO PRIOR IMAGING ARTERIAL AND VENOUS PHASE CT CT Findings Diagnosis Recommendation Any size >100 HU arterial >130 HU venous arterial HU > venous HU Up to 2 cm <100 HU arterial <130 HU venous venous > arterial 2-4 cm <100 HU arterial <130 HU venous venous>arterial Possible pheo Probable adenoma Probable adenoma Clinical and laboratory assessment for pheochromocytoma. If negative, no follow up for <1cm, 1 year follow up CT for 1-2 cm and adrenal washout for 2-4 cm. <1 cm: no follow up 1-2 cm: 1 year follow up CT. If stable at 1 year, no follow up necessary Adrenal washout CT or chemical shift MRI > 4 cm Possible malignancy Surgical consultation

9 VARIANT 3 INDETERMINATE NODULE PRIOR IMAGING Clinical variables Cancer history No cancer history Size variables Up to 2 cm 2-4 cm > 4 cm Interval change variables Stable <20% increase >20% increase VARIANT 4 HISTORY OF CANCER ISOLATED INDETERMINATE NODULE NO PRIOR IMAGING Clinical variables Hypervascular cancer (RCC or HCC) Other cancer Size variables Up to 2 cm 2-4 cm > 4 cm Enhancement variables Arterial < or > 100 HU Venous < or > 130 HU Arterial > venous

10 VARIANT 3A NO CANCER HISTORY INDETERMINATE NODULE PRIOR IMAGING VARIANT 3B CANCER HISTORY INDETERMINATE NODULE PRIOR IMAGING CT Findings Diagnosis Recommendation CT Findings Diagnosis Recommendation Any size < 130 HU stable > 1 year Any size >130 HU stable > 1 year Benign Possible pheo No follow up necessary Laboratory investigation for pheochromocytoma. If negative, no follow up needed Any size Stable > 1 year < 4 cm Enlarging <20% in 1 year Benign Adenoma vs hypovascular* metastasis No follow up necessary Adrenal washout CT, chemical shift MRI or PET/CT < 4 cm Enlarging <20% in year < 4 cm New or enlarging >20% Probably adenoma Concern for malignancy or pheo > 4 cm Possible malignancy If clinical or imaging concern for pheo: laboratory assessment If no concern for pheo: adrenal washout CT or chemical shift MRI If clinical or imaging concern for pheo: laboratory assessment No concern for pheo: oncology & surgical consults and biopsy Surgical consultation >4 cm Enlarging <20% in 1 year Any size New or enlarging >20% Adrenal neoplasm vs metastasis Probably metastasis Surgical consultation PET/CT or biopsy *Hypervascular metastases (RCC, HCC) can exceed APW and RPW thresholds on adrenal washout CT, which is not a reliable for discriminating these from adrenal adenoma.

11 VARIANT 4A CANCER HISTORY. ISOLATED INDETERMINATE NODULE. NO PRIOR IMAGING. VENOUS PHASE CT VARIANT 4B CANCER HISTORY. ISOLATED INDETERMINATE NODULE. NO PRIOR IMAGING. ARTERIAL & VENOUS PHASE CT CT Findings Diagnosis Recommendation Any cancer < 4 cm, <130 HU Hypovascular cancer (not RCC or HCC) up to 4 cm >130 HU RCC or HCC < 4 cm >130 HU Adenoma vs metastasis Possible pheo Metastasis > adenoma, possible pheo > 4 cm Concern for malignancy Adrenal washout CT or chemical shift MRI If clinical concern for pheo: lab correlation Otherwise chemical shift MRI, PET/CT or adrenal washout If clinical concern for pheo: lab correlation Otherwise chemical shift MRI, PET/CT or biopsy; adrenal washout CT is not reliable in this setting Surgical consultation CT Findings Diagnosis Recommendation Any cancer < 4 cm <100 HU arterial <130 HU venous venous > arterial Hypervascular cancer < 4 cm >100 HU arterial >130 HU venous Arterial > venous Hypovasular cancer < 4 cm >100 HU arterial >130 HU venous Arterial > venous Any cancer > 4 cm Adenoma vs metastasis Metastasis > adenoma, possible pheo Possible pheo Concern for malignancy Adrenal washout CT or chemical shift MRI If clinical concern for pheo: lab correlation Otherwise chemical shift MRI, PET/CT or biopsy; adrenal washout CT is not accurate in this setting If clinical concern for pheo: lab correlation Otherwise chemical shift MRI or PET/CT; adrenal washout CT is not accurate in this setting Surgical consultation

12 VARIANT 5 ADRENAL WASHOUT CT INTERPRETATION Clinical variables No history of cancer Hypovascular cancer Hypervascular cancer (RCC or HCC) Concern for pheochromocytoma Washout variables APW < or > 60 RPW < or > 40 Enhancement variables Venous HU < or > 130 HU Formula for APW: > 60% ~ adenoma 100 x (Venous HU Delayed HU) Venous HU-Precontrast HU Formula for RPW: > 40% ~ adenoma 100 x (Venous HU Delayed HU) Venous HU

13 VARIANT 5A ADRENAL WASHOUT CT INTERPRETATION NO CANCER HISTORY VARIANT 5B ADRENAL WASHOUT CT INTERPRETATION HYPOVASCULAR CANCER ISOLATED ADRENAL NODULE CT findings Diagnosis Recommendation CT findings Diagnosis Recommendation Meets washout criteria* Venous < 130 HU Adenoma No follow up necessary Meets washout criteria* Venous < 130 HU Adenoma No follow up necessary Meets washout criteria* Venous > 130 HU Pheo > adenoma Laboratory evaluation for pheochromocytoma Meets washout criteria* Venous > 130 HU Pheo > adenoma Laboratory evaluation for pheo Doesn t meet washout criteria* Venous < 130 HU Possible primary adrenal neoplasm Endocrine consultation advised for further management. Doesn t meet washout criteria* Venous < 130 HU Concern for metastasis PET/CT or biopsy Meets washout criteria* Venous > 130 HU Pheo vs primary adrenal neoplasm Laboratory evaluation for pheochromocytoma. If negative for pheochromocytoma, endocrine consultation advised for further management. Doesn t meet washout criteria* Venous > 130 HU Metastasis vs pheo Laboratory evaluation for pheo If negative, PET/CT or biopsy *APW > 60 or RPW > 40

14 CONCLUSIONS A growing body of evidence in the literature can be used to improve interpretative performance and management recommendations for adrenal nodules. In addition to well established size criteria and washout characteristics, enhancement patterns across phases can assist in distinguishing different pathologies. Understanding of the pitfalls associated with hypervascular pheochromocytoma, RCC and HCC is important to avoid misdiagnoses. Radiologists can increase the value of care delivered by incorporating standardized evidence-base best-practice recommendations based on these variants and variables into the report impression. Consensus across practice settings and specialties is critical for broad adoption and adherence.

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