Indeterminate Adrenal Masses Research Articles

Adrenal masses in oncology patients

In the general population, adrenal masses are demonstrated in 2-9% of CT scans. Eighty per cent of these are benign cortical adenomas. However, in patients with cancer, over 50% of detected adrenal masses prove to be metastases. Despite this the techniques for the evaluation of adrenal masses in patients with cancer should be similar to patients without cancer and incidentally discovered adrenal masses. Extensive published material is now available on the diagnostic performance of CT, MRI and PET in the characterization of adrenal masses. It must be borne in mind, however, that these techniques are usually evaluated for their ability to positively identify adenomas. Other adrenal pathology also occurs incidentally and it is essential that the radiologist should be familiar with the range of appearances of this pathology. Examples of this include phaeochromocytomas, cysts, myelolipomas, haemorrhage and granulomatous infections. Furthermore, although cross-sectional imaging techniques, particularly when modified specifically to evaluate indeterminate adrenal masses, can prove to have an excellent diagnostic performance (with remarkably high specificity), all have limitations. It is a consideration of the relative comparative strengths and weaknesses of each of these imaging modalities that informs the choice of technique and interpretation of the findings. This short presentation outlines the key points relating to the most widely used techniques for evaluating the adrenal mass in patients with cancer and the evidence for their role in patient management.

MDCT of Adrenal Masses: Can Dual-Phase Enhancement Patterns Be Used to Differentiate Adenoma and Pheochromocytoma?

The purpose of this study was to compare enhancement of adrenal adenomas and pheochromocytomas during dual-phase (arterial and venous phases) CT performed with currently used MDCT protocols with the goal of defining enhancement patterns predictive of pathologic findings. Pathologically proven pheochromocytomas were retrospectively compared with adrenal adenomas. Inclusion criteria for adenomas, collected by searching the radiology database, were confirmatory adrenal CT (unenhanced with or without washout) and absence of clinical indicators of pheochromocytoma. A fellowship-trained attending radiologist blinded to the pathologic diagnosis reviewed existing images from dual-phase IV contrast-enhanced CT examinations to measure enhancement of adrenal lesions and characterize the appearance (homogeneous versus heterogeneous). Student t test analysis was performed to compare arterial and venous phase enhancement levels. The findings in 39 patients with 41 adenomas were compared with those in 10 patients with 12 pheochromocytomas. Mean arterial and venous enhancement of adenomas at 37 HU (-6 to 85 HU) and 60 HU (16-133 HU) was significantly lower than that of pheochromocytomas at 104 HU (42-190 HU) and 119 HU (61-195 HU) (p < 0.001). No adenoma was more than 85-HU enhancing in the arterial phase, and 58% of pheochromocytomas were more than 110-HU enhancing. Most adenomas (85%) were more enhancing in the venous phase. No adenoma was more enhancing in the arterial phase, but 25% (3/12) of pheochromocytomas were. Most (58%) pheochromocytomas were heterogeneous in appearance, compared with 22% of adenomas. For indeterminate adrenal masses identified at dual-phase IV contrast-enhanced CT, higher enhancement during the arterial phase, arterial phase enhancement levels greater than 110 HU, and lesion heterogeneity should prompt consideration of pheochromocytoma.

Preoperative characterization of indeterminate large adrenal masses with dual tracer PET-CT using fluorine-18 fluorodeoxyglucose and gallium-68-DOTANOC: initial results

We aimed to evaluate the usefulness of dual tracer positron emission tomography-computed tomography (PET-CT) with flourine-18 fluorodeoxyglucose (18F-FDG) and gallium-68 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide (68Ga-DOTANOC) in preoperative characterization of large indeterminate adrenal masses. Ten patients (four males, six females; median age, 35 years) with indeterminate, large (≥4 cm) adrenal masses were included in this prospective study. All patients underwent both 18F-FDG PET-CT and 68Ga-DOTANOC PET-CT within one week. Images were evaluated both visually and semi-quantitatively, with standardized uptake value (SUVmax) and SUVratio (SUVmax) of tumor/SUVmax) of mediastinum). Based on differential uptake pattern on 18F-FDG and 68Ga-DOTANOC, lesions were classified as cortical (18F-FDG>68Ga-DOTANOC), medullary (68Ga-DOTANOC>18F-FDG), or indeterminate (18F-FDG=68Ga-DOTANOC). Histopathology was taken as reference standard. Receiver operating characteristic (ROC) analysis was performed to find a cut-off of SUVmax) and SUVratio to differentiate cortical and medullary lesions. On histopathology, eight lesions were adrenocortical carcinomas, one was benign pheochromocytoma, and one was malignant pheochromocytoma. Visually, 18F-FDG PET-CT was positive in all ten lesions, while 68Ga-DOTANOC PET-CT was positive in two, both of which were pheochromocytomas. On SUVmax) based analysis, nine lesions were cortical and one was medullary. On ROC analysis, a SUVmax) cut-off of > 2.3 was obtained for 18F-FDG PET-CT and 3.6 for 68Ga-DOTANOC PET-CT for differentiating adrenal cortical and medullary lesions. The cut-off for SUVratio was 4.5 on 18F-FDG PET-CT and 11.1 on 68Ga-DOTANOC PET-CT. These preliminary results demonstrate that dual tracer PET-CT using 18F-FDG and 68Ga-DOTANOC could be informative in the preoperative characterization of large indeterminate adrenal masses.

Risk factors affecting operative approach, conversion, and morbidity for adrenalectomy: a single-institution series of 402 patients

Risk factors for selecting patients for open adrenalectomy (OA) and for conversion are limited in most series. This study aimed to investigate variables that are important in selecting patients for OA, predict risk of conversion from laparoscopic adrenalectomy (LA), and impact 30-day outcomes of OA and LA. A retrospective cohort study of prospectively collected data was conducted. Patients (≥ 16 years old) who underwent adrenalectomy in the Division of General Surgery at Barnes-Jewish Hospital (1993-2010) were grouped by operative approach (LA vs. OA) and compared using nonparametric tests and regression analyses (α < 0.05). In total, 402 patients underwent 422 adrenalectomies. Compared to LA patients, those in the OA group were older (p = 0.02), had higher ASA scores (p = 0.04), larger tumor size (p < 0.01), and fewer functioning lesions (p < 0.01). OA patients more often required concurrent procedures (p < 0.01), had a longer operative time (p = 0.04), more intraoperative complications (p = 0.02), higher estimated blood loss (EBL), and larger transfusion requirement. Preoperative factors that predicted selection for OA were higher patient age (p = 0.01), higher ASA score (p = 0.03), larger tumor size (p < 0.01), nonfunctioning lesion (p < 0.01), diagnosis of adrenocortical carcinoma (p < 0.01), and the need for concomitant procedures (p < 0.01). Conversion to open or hand-assisted approach occurred in 6.2 % of LA patients. Preoperative risks for conversion included large tumor size (>8 cm) and need for concomitant procedures (p < 0.01). Multivariate analysis revealed that large indeterminate adrenal mass, adrenocortical carcinoma, tumor size (>6 cm), an open operation, conversion, concomitant procedures, operative time >180 min, and EBL >200 mL were predictors of 30-day morbidity. Adrenal tumor size and need for concurrent procedures significantly impact the selection of patients for OA, the likelihood of conversion, and perioperative morbidity. These metrics should be considered when assessing operative approach and risks for adrenalectomy.

Cross-sectional imaging work-up of adrenal masses

Advances in medical imaging with current cross-section modalities enable non-invasive characterization of adrenal lesions. Computed tomography (CT) provides characterization with its non-contrast and wash-out features. Magnetic resonance imaging (MRI) is helpful in further characterization using chemical shift imaging (CSI) and MR spectroscopy. For differentiating between benign and malignant masses, positron emission tomography (PET) imaging is useful with its qualitative analysis, as well as its ability to detect the presence of extra-adrenal metastases in cancer patients. The work-up for an indeterminate adrenal mass includes evaluation with a non-contrast CT. If a lesion is less than 10 Hounsfield Units on a non-contrast CT, it is a benign lipid-rich adenoma and no further work-up is required. For the indeterminate adrenal masses, a lipid-poor adenoma can be differentiated from a metastasis utilizing CT wash-out features. Also, MRI is beneficial with CSI and MR spectroscopy. If a mass remains indeterminate, PET imaging may be of use, in which benign lesions demonstrate low or no fluorodeoxyglucose activity. In the few cases in which adrenal lesions remain indeterminate, surgical sampling such as percutaneous biopsy can be performed.

The indeterminate adrenal mass

This paper is a review of the evidence base carried out to provide recommendations to aid the clinical management of patients with a CT/MRI-detected lipid-poor/indeterminate adrenal mass in whom phaeochromocytoma and metastatic adrenal disease are excluded. A Medline keyword search of English-language articles led to the production of a draft document and consensus statement containing levels of evidence and grading of recommendations as proposed by the Agency for Healthcare Research and Quality. Literature review clearly defines the extent and definition of what constitutes a lipid-poor adrenal mass. The ability of MRI to better distinguish adrenocortical adenoma from adrenocortical cancer is increasing, although there is little high-level evidence to confirm this. FDG PET appears promising in its ability to predict that an adrenal lesion is benign. The management of a patient with an indeterminate adrenal mass in the absence of clear clinical, biochemical, and radiological indications for adrenalectomy may be aided by further assessment using chemical-shift/contrast-enhanced MRI and (18)F-FDG PET/CT.

Role of positron emission tomography/computed tomography in adrenal and neuroendocrine tumors

Positron emission tomography (PET) has seen an increasing clinical utilization in the last decade, such that it is now a standard oncology imaging modality. Its success is based on the detection of altered fluorine-18 fluorodeoxyglucose (18F-FDG) biodistribution, reflecting glucose transport/metabolism in malignant tumor tissues. Integrated PET/computed tomography cameras combine functional and anatomical information in a synergistic manner that improves diagnostic interpretation, and newer positron-emitting radiopharmaceuticals have been developed to expand the application of non-FDG PET imaging. The increasing use of cross-sectional imaging procedures has led to a more frequent detection of incidental adrenal masses. Although conventional imaging modalities such as computed tomography and MRI can characterize the majority of these lesions, 18F-FDG PET has been reported as a useful tool to distinguish benign from malignant etiologies in indeterminate adrenal masses. Although 18F-FDG PET has enjoyed success in staging a wide range of cancers, including detection of adrenal metastases and evaluation of adrenocortical carcinoma, it has had limited impact for the evaluation of neuroendocrine tumors. Positron-emitting amine precursor and somatostatin analogs have been validated in research settings to provide accurate imaging of enterochromaffin and chromaffin neuroendocrine tumors and medullary thyroid cancer. The aim of this review article is to provide an overview of the role of 18F-FDG and newer positron-emitting radiopharmaceuticals in the evaluation of adrenal and neuroendocrine tumors.

Incidental and other indeterminate adrenal masses

Incidental and other indeterminate adrenal masses

Usefulness of Positron Emission Tomography for Characterization of the Indeterminate Adrenal Tumor

Abstract Incidental adrenal masses are common, with most representing benign, nonfunctional cortical adenomas. The diagnostic approach should consist of a biochemical evaluation for hormonal hypersecretion, as well as an assessment of the risk of malignancy (primary adrenal cancer vs metastasis from another site). The size and appearance of the adrenal tumor on imaging studies are critical to management decisions. Computed tomography (CT) or T1 weighted chemical shift magnetic resonance imaging (MRI) can usually diagnose a cortical adenoma based on characteristics related to intracellular lipid content. However, 30% of cortical adenomas are lipid-poor, and will be classified as indeterminate on CT or MRI. Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a useful method of further characterizing an indeterminate adrenal mass, particularly in an oncology patient in whom identification of an adrenal metastasis will affect disease stage and therapy. FDG-PET has been found to have a sensitivity of 93 to 100% and a specificity of 70 to 100% for the identification of an adrenal malignancy in both oncology and non-oncology patient populations. Indications for adrenalectomy include all functional adrenal tumors, known or suspected primary adrenal cancers that appear resectable, adrenal tumors &gt; 4 cm, and isolated adrenal metastases.

The Incidental Indeterminate Adrenal Mass on CT (&gt; 10 H) in Patients Without Cancer: Is Further Imaging Necessary? Follow-Up of 321 Consecutive Indeterminate Adrenal Masses

The Incidental Indeterminate Adrenal Mass on CT (&gt; 10 H) in Patients Without Cancer: Is Further Imaging Necessary? Follow-Up of 321 Consecutive Indeterminate Adrenal Masses

The Incidental Indeterminate Adrenal Mass on CT (&gt; 10 H) in Patients Without Cancer: Is Further Imaging Necessary? Follow-Up of 321 Consecutive Indeterminate Adrenal Masses

The objective of our study was to determine whether follow-up imaging evaluation is necessary for incidentally discovered indeterminate adrenal lesions (> 10 H) on CT in patients with no known malignancy. A computer search of CT reports from January 2000 to December 2003 identified patients with incidentally detected, indeterminate, but benign-appearing adrenal lesions who had no known malignancy and no clinical suspicion of hyperfunctioning adrenal mass. Patients with adrenal masses diagnostic on the initial CT or heterogeneous masses were excluded. Two hundred ninety patients with 321 lesions met the study criteria. Each lesion was determined to be benign or malignant based on histopathology, characterization with diagnostic imaging studies, or a minimum of 1 year of stability on imaging follow-up or 2 years of stability on clinical follow-up. Of the 321 lesions, 318 masses (99.1%) were confirmed to be benign and clinically insignificant. These included three (0.9%) histologically confirmed adenomas, 198 (61.7%) adenomas by imaging characterization, five (1.6%) other benign lesions, 71 (22.1%) masses stable on imaging follow-up, and 41 (12.8%) masses with clinical stability. There were three (0.9%) clinically unsuspected functioning masses: one cortisol-producing adenoma and two pheochromocytomas. There were no metastatic adrenal lesions, even among the 13 patients who subsequently developed malignancy elsewhere. All of the incidentally detected adrenal masses with a CT attenuation of > 10 H were benign in patients with no known malignancy. Follow-up imaging to characterize an incidental adrenal mass appears to have a limited role in this patient cohort.

The indeterminate adrenal mass in patients with cancer

With the increasing use of abdominal cross-sectional imaging, incidental adrenal masses are frequently detected. The commonest clinical question is whether these are benign adenomas or malignant primary or secondary masses. The nature of incidentally detected adrenal masses can be determined with a high degree of accuracy using computed tomography (CT) and magnetic resonance imaging (MRI) as benign adrenal masses such as myelolipomas, lipid-rich adenomas, adrenal cysts and adrenal haemorrhage which have pathognomonic imaging findings. However, there remains a significant overlap between the imaging features of some lipid-poor adenomas and malignant lesions. We review the recent advances in CT, MRI and positron emission tomography (PET) which can be used to distinguish between benign adenomas and malignant lesions of the adrenal gland.

Adrenocortical carcinoma

Adrenocortical carcinoma is a rare malignancy, accounting for 0.02% of all annual cancers reported. Given the generally advanced stage at diagnosis, the overall 5-year survival remains poor, varying between 20 and 45%. While older studies purported an improved outcome for functional tumors in adult patients, this has not been borne out in more recent studies. In the pediatric population, though, virilizing tumors carry a better survival than non-functional or cortisol-secreting tumors. Recent studies focusing on the tumorigenesis of adrenocortical carcinoma have focused on onco-developmental genes present in the fetal adrenal cortex, as well as local adrenal paracrine and autocrine effects of cellular peptides. Pre-operative diagnostic advances in positron emission scanning are emerging as promising modalities for confirmation of malignancy of indeterminate adrenal masses. No significant advances in the treatment of adrenocortical carcinoma have been developed. Surgery remains the mainstay for primary and recurrent disease, including select patients with isolated liver metastases. Mitotane has remained the preferred adjuvant treatment agent, showing modest effect in patients with unresectable, residual or metastatic disease. Multi-institutional registries and trials need to be established, with multidisciplinary efforts focused on the development of new therapeutic strategies.

Non-invasive evaluation of the incidentally detected indeterminate adrenal mass

Clinically silent adrenal masses are discovered incidentally during diagnostic testing or treatment for clinical conditions that are not related to suspicion of adrenal disease; thus, they are commonly referred to as 'incidentalomas'. The widespread use of high-resolution anatomic imaging techniques such as computed tomography (CT) and magnetic resonance (MR) imaging has led to the increased detection of these masses. In many patients without a known extra-adrenal primary malignancy--and even in patients with a primary neoplasm--most adrenal masses ultimately prove to be benign. However, it remains important that these adrenal masses are accurately characterized to exclude the treatable causes of adrenal disease, and also to accurately stage the oncology patient. The purpose of this chapter is to describe the findings and recent advances in non-invasive imaging methods that are now available for the accurate characterization of incidentally detected adrenal masses (i.e. the differentiation of benign from malignant masses). The imaging techniques and the algorithms that are used in our institution for the evaluation of incidentally detected adrenal mass will be described.

Predictive Value of Benign Percutaneous Adrenal Biopsies in Oncology Patients

PURPOSE: Percutaneous CT guided biopsy is accepted as a safe procedure for the diagnosis of indeterminate adrenal masses in oncologic patients. The purpose of this study was to evaluate the accuracy of a ‘negative for tumour’ adrenal biopsy in the oncologic patient population by assessing subsequent outcome including clinical course, size and imaging characteristics of the adrenal lesions on follow-up imaging studies and pathological findings at re-biopsy or following adrenal mass resection. MATERIALS AND METHODS: Retrospective analysis of 225 oncological patients (FM, 128;87; age range 33–87 years, mean age 66 years) who had undergone CT guided biopsies of an adrenal mass over a 5-year period was performed. Those patients with a report consistent with ‘negative for malignancy’ were evaluated by reviewing the medical records for patient demographics, primary malignancy, histology of adrenal tumour, subsequent surgical interventions, repeat adrenal biopsy under image guidance, by open surgery or at autopsy, subsequent abdominal imaging in which the adrenal gland was imaged, and long-term outcome including hospital admissions, or death. RESULTS: Of the 225 CT-guided adrenal biopsies performed, 41 (18%) were negative for neoplasm. The primary neoplasm in these 41 patients included lung cancer (n=32), breast (n=5), renal cell carcinoma (n=2), bladder (n=1), and prostate (n=1). The size of the adrenal lesions ranged from 2.8–5cm. Of the 41 biopsies, which were negative for tumour; 10 were identified as adenomas and the rest showed benign adrenal cortical cells or hyperplasia on cytopathology and histopathology. Repeat biopsies were obtained in 13/41 (31%) patients; whereas 2/41 (5%) had their adrenal gland analyzed on post mortem examination. None of these 15 repeat evaluations yielded tumour. CONCLUSION: In oncological patients, pathological analysis of tissue samples obtained by CT-guided percutaneous biopsy, suggesting benign aetiology, is reliable and predicts a benign course on long-term follow-up. A negative or benign pathology result for a CT guided percutaneous adrenal biopsy can be regarded as a true negative evaluation in oncological patients with no necessity to repeat the biopsy. Harisinghani M. G. et al. (2002) Clinical Radiology,57, 898–901.

Characterization of indeterminate (lipid-poor) adrenal masses: use of washout characteristics at contrast-enhanced CT.

To determine whether computed tomographic (CT) scans and attenuation measurements on contrast material-enhanced and nonenhanced CT scans could be used to characterize adrenal masses, in particular, to characterize these lesions by using adrenal washout characteristics at contrast-enhanced CT. Eighty-six patients (49 men, 37 women; age range, 29-86 years; mean age, 72 years) with 101 adrenal lesions depicted at contrast-enhanced CT underwent delayed (mean, 9 minutes) enhanced scanning. Seventy-eight patients also underwent nonenhanced CT. Mean diameter of the benign lesions was 2.1 cm (range, 1.0-4.2 cm); mean diameter of the malignant lesions was 2.3 cm (range, 1.0-4.1 cm). Region-of-interest measurements were obtained at nonenhanced, dynamic enhanced, and delayed enhanced CT and were used to calculate a relative percentage washout as follows: 1 - (Hounsfield unit measurement on delayed image / Hounsfield unit measurement on dynamic image) x 100%. Ninety-nine of 101 lesions were correctly characterized as benign or malignant with a relative percentage washout threshold of 50% on delayed scans; benign lesions demonstrated more than 50% washout; and malignant lesions, less than 50% washout. Two benign lesions demonstrating less than 50% washout were characterized as benign by using conventional CT. Calculation of relative percentage washout on dynamic and delayed enhanced CT scans may lead to a highly specific test for adrenal lesion characterization, reduce the need for, and possibly obviate, follow-up imaging or biopsy.

Indeterminate adrenal mass in patients with cancer: evaluation at PET with 2-[F-18]-fluoro-2-deoxy-D-glucose.

To evaluate the ability of positron emission tomography (PET) to characterize adrenal masses in patients with cancer. Twenty-four adrenal masses (size range, 1.5-10.0 cm [mean, 2.8 cm]) in 20 patients (13 men and seven women) with cancer (lung [n = 10], colon [n = 3], lymphoma [n = 3], miscellaneous [n = 4]) were evaluated. PET was performed in fasting patients 45 minutes after infusion of 5-10 mCi (185-370 MBq) of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG). PET images were correlated with findings at computed tomography (CT), surgery, and/or percutaneous biopsy. Fourteen adrenal masses were proved malignant at surgery (n = 4), biopsy (n = 7), or follow-up (n = 3). Ten lesions were proved benign at biopsy (n = 4) or follow-up CT (n = 6). PET helped correct differentiation of benign from malignant adrenal lesions in all patients. A statistically significant difference (P < .001) was seen between mean tumor-to-background ratios for malignant (mean, 7.4; range, 2.9-16.6; median, 6.9) versus benign (mean, 0.8; range, 0.2-1.2; median, 0.6) adrenal lesions. PET helped correct differentiation of benign from malignant adrenal lesions.