Positron Emission Tomography-avid Adrenal Mass and Incidental Renal Mass in a 70-Year-Old Woman With Newly Diagnosed Breast Cancer
Jessica H. Hannick, Lu Wang, Güliz A. Barkan, Claudia Perez, Davide Bova, Kathy S. Albain, and Marcus L. Quek
CASE PRESENTATION
A 70-year-old African American woman was referred for an evaluation of left renal and adrenal masses. She was recently diagnosed on ultrasound-guided core biopsy with grade 2, ER/PR- positive, HER2/neu-negative, Ki67-favorable infiltrating ductal carcinoma of the right breast. As part of her staging evaluation, she underwent a contrast-enhanced computed tomography (CT) that revealed an incidental 4.5 x 3.5 cm left adrenal mass and a 1 cm enhancing left lower pole renal mass (Fig. 1).
She denied any symptoms suggestive of adrenal hyperfunction. Her medical and surgical history was notable for well-controlled hypertension, obesity, and a remote hysterectomy for menorrhagia. She denied any tobacco or chemical exposures and aside from a sister who had pancreatic cancer, there was no known family history of malignancy.
Her physical examination was unremarkable. Her laboratory assessment revealed no abnormalities in her complete blood cell count, serum chemistries, liver or renal function, or urinalysis. Plasma and 24-hour urine metanephrines, catecholamines, and cortisol were all within normal limits.
She underwent an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) scan (Fig. 2). This revealed minimally increased metabolic activity in the outer portion of the right breast (standardized uptake value, SUVmax 0.9) and markedly increased metabolic activity in the region of the left adrenal gland (SUVmax
19.8). There was no significant uptake in the renal mass. No other areas of increased metabolic uptake were iden- tified. The patient underwent a CT-guided core biopsy of the left adrenal mass which was consistent with an adrenal neoplasm (please refer to the Pathology section).
DIFFERENTIAL DIAGNOSIS
The risk of a metastasis from the patient’s clinically localized breast cancer is relatively low given its favorable histologic and molecular characteristics. The differential diagnosis of the small incidentally discovered renal mass includes renal cell carcinoma, fat-poor angiomyolipoma, oncocytoma, mixed epithelial stromal tumor, meta- nephric adenoma, and less likely, metastasis. The adrenal lesion may represent a metastasis, cortical adenoma, pheochromocytoma, or adrenocortical carcinoma.
The evaluation of an incidental adrenal mass requires a thoughtful combination of laboratory and imaging studies. In this patient, with no clinical manifestations and normal metabolic studies, it would be unlikely for the adrenal mass to be a hyperfunctioning lesion (aldosteronoma, Cushing’s syndrome, and pheochro- mocytoma). Benign nonfunctioning cortical adenomas are common, although 18F-FDG avidity is generally low in such lesions.1 Adrenocortical carcinomas may present with mixed hormonal hypersecretion or be nonfunctioning and typically demonstrate an aggressive phenotype with propensity for early local spread and metastasis. Among incidental adrenal masses with a cross-sectional size >4 cm, 10% are found to be adrenal carcinomas, and among masses >6 cm, 25% are found to be malignant.2
Several studies have demonstrated high sensitivity and specificity of PET imaging for evaluating adrenal masses.3,4,5 In patients without a previous history of cancer, 18F-FDG PET/CT was shown to distinguish benign from malignant incidentally discovered adrenal lesions with a sensitivity of 73%-100% and specificity of 70%-100%. In those with a known primary malignancy, overall sensitivity was similarly 74%-100% and specificity
From the Department of Urology, Loyola University Chicago Stritch School of Medicine, Maywood, IL; the Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, IL; the Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, IL; the Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL; and the Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, IL
Reprint requests: Jessica H. Hannick, M.D., Department of Urology, Loyola University Chicago Stritch School of Medicine, 2160 S First Avenue, Fahey Center, Room 261, Maywood, IL 60153. E-mail: jhannick@lumc.edu
Submitted: June 6, 2013, accepted (with revisions): July 5, 2013
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66%-100%. When comparing 18F-FDG uptake with the liver, adrenal SUV max to liver SUV max ratio <1.7 has been used to identify benign adrenal lesions, whereas those with greater SUV max ratios or adrenal SUV max >3.1 are more likely to be malignant. This patient’s adrenal SUVmax of 19.8 was thus highly concerning for a malignant process.
MANAGEMENT AND OUTCOME
The patient underwent an uneventful right breast lump- ectomy and axillary sentinel lymph node sampling con- firming a margin-negative 1.1 cm stage I invasive ductal carcinoma (ER/PR-positive, HER2/neu-negative). She subsequently had a robotic-assisted laparoscopic left adrenalectomy and left partial nephrectomy. She had an entirely uneventful postoperative course being dis- charged on her second postoperative day. For her breast
PATHOLOGY
The core biopsy from the adrenal gland showed a neoplasm with a trabecular growth pattern composed of large eosinophilic cells with oncocytic features, low nuclear-cytoplasmic ratio, and focal cytologic atypia depicted by nuclear enlargement, pleomorphism, and macronucleoli. No necrosis was seen, and no mitoses were identified. According to the morphology and the immu- nostaining pattern, the core biopsy showed no evidence of metastatic breast or renal cell carcinoma. Therefore, the mass was diagnosed as an adrenal cortical neoplasm, favoring an adrenal adenoma. Of note, in small biopsies, the distinction between adrenal cortical neoplasms, that is, adenoma vs carcinoma, cannot be made reliably. This is because of the fact that the features necessary to diag- nose adrenocortical carcinoma, namely mitotic rate of 6 or more per 50 high power field, atypical mitoses, and invasion of venous structures as described by Weiss et al,6 may not be seen in a small biopsy. Provided that the mass is adequately sampled, in small biopsies and fine needle aspiration specimens, if an adrenal mass lesion shows benign adrenal cortical cells, it is diagnosed as an adrenal cortical neoplasm.
The adrenalectomy specimen grossly showed a 5.0 x 3.2 × 2.8 cm mass arising from the adrenal cortex (Fig. 3). The tumor had a tan-brown to yellow, homo- geneous cut surface with a focus of hemorrhage. There was no necrosis. The tumor was well circumscribed and grossly confined to the adrenal capsule. Microscopically, the tumor had a trabecular and nested growth pattern with pushing borders. No extracapsular invasion was identified. The tumor cells had a vacuolated, granular cytoplasm and low nuclear-cytoplasmic ratio. There
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were no mitotic figures or lymphovascular invasion. With these findings, the tumor was diagnosed as an adrenal cortical adenoma.
The partial nephrectomy specimen showed a mass lesion of 2.3 × 1.8 × 1.3 cm. The cut surface was tan- yellow and variegated with multiple thin-walled cysts filled with clear fluid. Microscopically, small nests of tumor cells with clear cytoplasm, and eccentric nuclei were seen amidst thin-walled vessels. The tumor cells had prominent nucleoli. The histomorphology was different from that of the invasive ductal carcinoma and the adrenal cortical adenoma. The tumor was diagnosed as renal cell carcinoma, clear cell type, Fuhrman grade 3, and pT1aNxMx.
DISCUSSION BY MARCUS L. QUEK, M.D.
The present case highlights a stepwise, multidisciplinary approach to the evaluation and management of 3 potentially related synchronous lesions, which were ulti- mately found to be completely separate neoplasms. Although the findings of an incidental small renal cell carcinoma and an incidental adrenal mass are not uncommon with current use of cross-sectional imaging, the main diagnostic dilemma in this case was the suspi- cious uptake in the adrenal mass noted on the 18F-FDG PET scan. Several studies have examined the PET- imaging characteristics of adrenal lesions and demon- strated reasonable accuracy in distinguishing benign from malignant tumors. At their baseline, the adrenal glands have mild uptake visually below that of the liver (SUVmax 0.95-2.46). When the adrenals are noted to have unilateral or bilateral uptake greater than the liver, this is concerning either for a primary adrenal carcinoma or metastasis from a known primary.
Two previous reports of 18F-FDG PET-avid adrenal adenomas have been published. Canter et al7 presented the case of a 60-year-old woman, with a history of ductal carcinoma-in-situ of the breast, who was found to have an incidental 2.1 cm left adrenal mass. The SUVmax of the lesion was 18.83, although a 15-minute CT washout study demonstrated 70% absolute washout consistent with a lipid-poor adenoma. Metabolic studies were normal. Laparoscopic left adrenalectomy yielded a benign adenoma.
Nakajo et al8 reported the case of a 58-year-old man with an incidentally discovered, metabolically silent 3 x 2 cm lipid-poor left adrenal mass found on CT and magnetic resonance imaging. MIBG scan showed no uptake, but 18F-FDG PET scan showed a hypermeta- bolic adrenal lesion with SUVmax 8.3. Left adrenalec- tomy led to the diagnosis of a benign adrenal adenoma. There have also been case reports of PET-avid adrenal masses being ultimately diagnosed as adrenal myelolipomas.9,10
The evaluation of an adrenal mass requires a thought- ful approach incorporating laboratory and radiologic modalities. Although image-guided percutaneous biopsies can distinguish a primary adrenal tumor from a metastasis, its use in differentiating an adenoma from adrenocortical carcinoma is often limited. According to the present study, it should be kept in mind that benign nonfunc- tioning adrenal adenomas may show strong 18F-FDG- avidity.
References
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