Interventional Radiology Case Conference Massachusetts General Hospital

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1 Interventional Radiology Case Conference Massachusetts General Hospital Adrenal Biopsy in a Patient with Lung Cancer: Imaging Algorithm and Biopsy Indications, Technique, and Complications C ase History A 51-year-old man with a 31 pack-year smoking history was referred to the Massachusetts General Hospital for evaluation of a 5-cm right upper lobe mass that was detected on a chest radiograph. Sputum cytology revealed adenocarcinoma, and the patient was referred for staging CT. An unenhanced CT scan of the chest and a contrast-enhanced CT scan of the abdomen were obtained; both revealed a 2-cm left adrenal mass (Figs. 1A and 1B). An attempt to characterize the lesion on CT initially proved indeterminate because attenuation measurements of the adrenal lesion revealed 20 H on unenhanced CT and 78 H on contrastenhanced CT (Fig. 1B). Furthermore, a 10-min delayed contrast-enhanced CT study through the adrenal glands also proved indeterminate, revealing a lesion attenuation measurement of 34 H (Fig. 1C). Therefore, the division of abdominal imaging and intervention was consulted for biopsy of the left adrenal gland. Dr. Mueller. Given this patient s clinical history and imaging findings, what is the likelihood that the left adrenal mass represents metastatic disease? Dr. Boland. In patients without a history of malignancy, any incidentally detected adrenal mass (usually on CT) is almost always benign [1 3]. However, in patients with a history of a known malignancy, as in this patient, the likelihood that the incidentally detected left adrenal mass is metastatic increases dramatically. Up to 35% of patients with a history of malignancy (particularly small cell carcinoma of the lung) have adrenal metastases, either microscopic or macroscopic [4 7]. Therefore, the incidentally detected adrenal mass in this group of patients must be further characterized, by imaging or by biopsy, to allow appropriate staging and therapeutic planning. Dr. Boland. What imaging features help to characterize adrenal masses? Dr. Arellano. Lesions greater than 5 cm are almost always malignant and usually represent either primary (adrenocortical carcinoma) or metastatic disease. The exception to this rule is the rare myelolipoma, which can easily be recognized by its visible macroscopic fat on CT [1, 2]. Smaller lesions can be either benign or malignant, and size criterion alone is insufficient for lesion characterization. Similarly, lesions with irregular morphology often suggest a malignant process, but not always. Occasionally, larger lesions may show internal heterogeneity, particularly if IV contrast material has been administered. However, many benign lesions can also enhance in an inhomogeneous fashion after IV contrast material has been administered. Ronald S. Arellano 1, Giles W. L. Boland, Peter R. Mueller Dr. Mueller. The left adrenal mass in this patient measured approximately 2 cm. How does this help you to characterize the lesion? Dr. Boland. As mentioned earlier, size criterion alone is usually insufficient to adequately characterize an adrenal mass. Most incidentally detected adrenal lesions, whether benign or malignant, are in fact small (<3 cm), relatively smooth in shape, and homogenous on unenhanced CT [8 10]. It is therefore difficult to characterize these lesions by morphologic criteria alone. The 2-cm adrenal lesion in this patient with a known lung malignancy is therefore indeterminate and further characterization is necessary. It should be kept in mind that one of the initial steps in characterizing a lesion is to review any available previous studies. If an older CT scan or MR image is available and the lesion in question has not changed in size in more than 6 months, then the lesion is most likely benign [1, 2]. However, any new lesion or a recent increase in size in a preexisting lesion without features of hemorrhage is almost certainly malignant, and no further workup is necessary. Dr. Arellano. Besides lesion size and morphology, what other imaging characteristics aid in lesion characterization? Received March 14, 2000; accepted after revision May 16, All authors: Division of Abdominal Imaging and Interventional Radiology, Ellison 234, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., Boston, MA, Address correspondence to G. W. L. Boland. AJR 2000;175: X/00/ American Roentgen Ray Society AJR:175, December

2 Arellano et al. Dr. Boland. Most imaging algorithms for adrenal lesions have been designed to help differentiate benign from malignant diseases on the basis of the presence or absence of adrenal intracytoplasmic fat. Benign adrenal adenomas often contain abundant intracytoplasmic fat (mainly cholesterol, fatty acids, and neutral fat) [11] within the adrenal cortex. Malignant lesions, on the other hand, are usually lipid-poor or lipid-deplete. Imaging techniques that can depict intracytoplasmic fat should therefore allow lesion characterization. Indeed, Korobkin et al. [11] were able to show an inverse linear relationship between the intracytoplasmic fat content of an adrenal adenoma and the CT density value. Unfortunately however, up to 40% of adrenal adenomas are also lipid-poor, and as a result, the test is not highly sensitive for the detection of an adrenal adenoma. A C Fat-sensitive imaging techniques serve to further differentiate benign lesions (containing intracytoplasmic fat) and indeterminate lesions (both lipid-poor benign lesions and malignant lesions). These latter indeterminate lesions would obviously require further imaging or percutaneous biopsy for definitive characterization. Despite this limitation, lipid-sensitive imaging techniques have proved highly useful over the last decade and have substantially reduced the need for percutaneous biopsy. After unenhanced CT has been performed, a region of interest (ROI) is placed over the adrenal lesion. Attenuation density values of 10 H or less indicate the presence of enough intracytoplasmic fat for the lesion to be considered benign [2], and no further workup is required. Increasing the density threshold above 10 H decreases the specificity for the test because some malignant lesions have D B Fig year-old man with 31 pack-year smoking history who was referred for evaluation of 5-cm right upper lobe mass that was detected on chest radiography. Sputum cytology revealed adenocarcinoma. A, Unenhanced CT scan through region of adrenal glands in this patient reveals 2-cm left adrenal mass (arrow). Attenuation measurement was 20 H, which is consistent with indeterminate lesion. B, Dynamic contrast-enhanced CT scan reveals that attenuation measurement of left adrenal gland (arrow) is 78 H. Lesion remains indeterminate according to CT density criteria. C, Delayed contrast-enhanced CT scan reveals attenuation measurement of 34 H. Calculation of percentage washout from dynamic to delayed scan is 56%, which is consistent with adenoma (arrow). D, CT scan obtained during CTguided biopsy of left adrenal gland (straight arrow); patient is prone. Nineteen-gauge coaxial needle (curved arrow) was placed adjacent to adrenal capsule before 22-gauge aspirate needle was introduced into lesion. density values of between 10 and 20 H. Therefore, 10 H is generally considered an appropriate threshold by which to separate benign from indeterminate lesions. If the density value is greater than 10 H, then the lesion is indeterminate, and further workup is indicated. Dr. Boland. Most patients with malignant disease undergo contrast-enhanced CT. How does this affect the imaging workup of adrenal masses? Dr. Arellano. Unfortunately, no distinguishing enhancement patterns are present on dynamic contrast-enhanced CT alone that permit adrenal lesion characterization. Both benign and malignant lesions enhance to similar density values on the dynamic scan (generally in the H range), rendering density measurement useless because no differentiating threshold between benign and 1614 AJR:175, December 2000

3 Adrenal Biopsy in a Patient with Lung Cancer malignant disease can be made [12]. However, adenomas tend to enhance to a much greater degree than metastases when compared with their unenhanced values. Because unenhanced CT is rarely performed, most investigators will not have the benefit of an unenhanced comparison CT. Several authors have attempted to characterize adrenal lesions using delayed contrast-enhanced CT [12 15]. The premise is that by waiting a variable time period after dynamic scanning, enough contrast material will washout of the adrenal gland so that density values can be used again in a manner analogous to unenhanced CT. It has been shown that the delay can be as early as 5 10 min after the dynamic scan has been obtained [12, 13, 15 17]. Although the density values will not have dropped to their unenhanced values, it has been shown that a cutoff threshold of between 25 and 30 H with a 10- to 15-min delayed scan is highly accurate for separating benign from malignant disease [12, 13, 15 17]. However, some benign lesions will still remain indeterminate because they do not contain sufficient intracytoplasmic fat to permit a decrease in their attenuation measurements to less than 30 H. It has been shown, however, that even lesions that do not contain sufficient intracytoplasmic fat can be characterized by measuring the percentage decrease of the adrenal density value from the dynamic contrast-enhanced scan to the 10- to 15-min delayed scan [17, 18]. Benign adrenal lesions tend to washout significantly faster than malignant lesions. If the adrenal gland density washout from the dynamic to delayed study is greater than 50%, then these lesions are almost always benign [17 19]. The washout characteristics apply to both adrenal adenomas that are abundant in intracytoplasmic fat and those that are not (which would usually be classified as indeterminate). The physiologic mechanism for this phenomenon remains unexplained, and further studies are needed to confirm these findings. However, we have found this method to be extremely accurate, and we now routinely use this algorithm at our institution. It should be emphasized that when attempting to characterize adrenal lesions using CT criteria, one must ensure that the density measurements obtained have been measured appropriately. Frequently, ROIs on the lesion have been placed inappropriately, leading to sampling errors. Too large of an ROI often lowers measurements because of inclusion of adjacent macroscopic fat from the surrounding retroperitoneum. Too small of an ROI leads to pixel sampling errors and may not represent the true density value of the whole lesion. ROIs should be from one half to two thirds the size of the adrenal gland and should be placed on a slice above and below that on which the adrenal tissue also exists to avoid introducing partial volume averaging from adjacent retroperitoneal fat. Dr. Mueller. Does MR imaging have any role? Dr. Arellano. The usefulness of MR imaging, similar to CT, depends on lipid-sensitive techniques. Chemical shift techniques have been developed over the last 10 years that enable MR imaging to depict intracytoplasmic fat content within adrenal adenomas [20, 21]. Although fat and water protons precess at different frequencies, the signal from conventional MR images usually detects both water and fat protons from different organs and summates their signal. Chemical shift techniques exploit the different precessing frequencies of fat and water protons so that any detected fat signal can be subtracted from the water signal. If sufficient intracytoplasmic fat is present, the signal from the adrenal gland will drop off and appear dark [21]. However, as with CT, there may not be enough fat within an adenoma for this phenomenon to occur and these lesions will remain indeterminate. Ultimately, because of the indeterminate nature of these lesions by both CT and MR imaging, one is left with little resort but to biopsy the mass for definitive characterization. There is therefore little advantage in using chemical shift MR imaging techniques over unenhanced CT. Indeed, MR imaging can now be considered less useful than CT because most, if not all, adrenal lesions can be characterized by the percentage washout criteria. Dr. Boland. On the basis of the imaging characteristics of the lesion in the patient described, should biopsy have been pursued? Dr. Arellano. With the use of the size criterion alone, the adrenal lesion in this patient (2-cm lesion) is indeterminate. Therefore, further characterization is required before determining the appropriateness of biopsy. Unenhanced, dynamic contrast-enhanced, and 10-min delayed CT proved indeterminate (20 H, 78 H, and 34 H, respectively). The percentage washout from the dynamic to the delayed scan, however, was 56%, which is consistent with an adenoma. The formula for calculating the washout is as follows: 1 (attenuation measurement on delayed scan / attenuation measurement on dynamic scan) 100%. Therefore, this lesion was confidently thought to be benign, and no further imaging or biopsy was deemed necessary. However, because this method for calculating benignity is new, the referring physician believed strongly that definitive proof was necessary before considering the patient to be a candidate for curative chest surgery. Therefore, the patient was scheduled for CT-guided percutaneous biopsy of his left adrenal gland (Fig. 1D). Dr. Boland. When is an adrenal biopsy indicated? Dr. Mueller. With the new imaging algorithms [13, 15 17, 21], there is a decreasing tendency to perform percutaneous biopsy for definitive characterization. However, there are still occasions when percutaneous biopsy is recommended. Imaging algorithms need to be highly specific for the detection of benign disease so triage of patients is not performed inappropriately. Patients in whom an adrenal adenoma is diagnosed might be placed on aggressive surgical, radiation, and chemotherapeutic regimes, in an attempt to cure the primary disease, rather than on palliative treatment. Consequently, biopsy is still performed in patients with lesions that appear equivocal on CT and MR imaging and in those for whom pathologic proof is necessary to initiate a specific treatment. Equivocal lesions can be classified as lesions with washout percentage values close to the 50% mark or as a lesion that may have increased in size despite benign CT density criteria. From time to time, as in this patient, the referring physician may require definitive pathologic proof despite adequate characterization by CT density methods. Dr. Arellano. What imaging modalities do you use to perform adrenal biopsies? Dr. Boland. Most adrenal biopsies are performed with CT guidance. Occasionally, biopsy of large adrenal masses can be carried out under sonographic guidance [8, 22]. Although CT-guided biopsy is more time-consuming, it provides better anatomic resolution and more accurate evaluation of the relationship between the adrenal gland and the adjacent structures [23]. Dr. Arellano. When performing biopsies, how should patients be positioned on the CT table? Dr. Mueller. Depending on the patient body habitus, adrenal size, and the relationship of the adrenal gland to the surrounding structures, several positioning options are available for performing CT-guided adrenal biopsy. The lateral decubitus approach is safe and well tolerated by patients and can be used for both left- and right-sided lesions AJR:175, December

4 Arellano et al. [24]. The patient is placed downside for whichever adrenal gland that is being biopsied. This position elevates the diaphragm on the lesion side and decreases the volume of the lung, thereby reducing the risk of the needle traversing the lung en route to the adrenal gland. Adrenal biopsies can also be performed via a posterior approach with the patient in the prone position, but this approach has the potential disadvantage that nondependent air tends to expand the lung in the posterior costophrenic recess, thus increasing the likelihood that the lung and pleura will be traversed during the biopsy [25]. This potential risk can be reduced or minimized by CT gantry angulation [26, 27]. This method uses the tilt capabilities of most CT scanners and usually involves caudal angulation of the gantry to avoid the posterior costophrenic sulcus. An anterior approach has been described for left-sided lesions in which the stomach, pancreas, or both are traversed by the biopsy needle en route to the adrenal gland [28]. However, this approach carries the potential risk of pancreatitis and should be considered only when other safer approaches cannot be used. Right-sided lesions, in addition to the prone and lateral decubitus approaches, can also be reached via a transhepatic trajectory [29]. Dr. Boland. What needle sizes do you use for adrenal biopsies? Dr. Mueller. A variety of needle sizes are available for percutaneous biopsy of the adrenal gland [30 32]. Most adrenal biopsies performed at our institution are performed using the coaxial technique. This technique limits the number of passes required over what is typically a longer needle path than that of other biopsies. Typically, an outer 19- or 17- gauge needle is positioned just within the lesion. This allows use of both a small-gauge (22- or 23-gauge) needle for aspirations and a 18- to 20-gauge core biopsy needle. Dr. Arellano. What are the contraindications of adrenal biopsy? Dr. Mueller. As with most other organs within the abdomen and pelvis, percutaneous adrenal gland biopsy is a relatively safe procedure and contraindications are relative. Uncorrectable bleeding disorders, an uncooperative or unwilling patient, or lesion inaccessibility are situations that preclude adrenal biopsy. Coagulopathies can be treated with fresh frozen plasma and platelets. Transfusion of fresh frozen plasma, platelets, or both is considered at our institution when the prothrombin time is greater than 14 sec and the platelet count is less than 50,000 per cubic millimeter. Dr. Boland. What are the risks of adrenal biopsy? Dr. Arellano. Bleeding, infection, organ injury, pneumothorax, and allergic reactions to IV conscious sedation are all potential risks of percutaneous biopsy. The risk of bleeding will depend on the chosen biopsy path, the number of passes, and the patient s coagulation status. Meticulous attention to sterile technique limits the risk of infection. The liver is usually not prone to hemorrhage in otherwise healthy patients particularly because any inadvertent hepatic hemorrhage is likely to be tamponaded by nontraumatized liver. Because of the anatomic proximity of the adrenal gland to the diaphragm, patients undergoing adrenal biopsy should be closely monitored for the potential risk of pneumothorax. Patients with one lung or severe chronic obstructive pulmonary disease should be carefully monitored, particularly for complications of a pneumothorax. Any patient with a symptomatic pneumothorax will need to be treated with a chest tube. A small pneumothorax is usually well tolerated by patients who do not have underlying lung disease without the need for percutaneous chest tube placement. One should always be mindful that the lesion in question might be a pheochromocytoma and that severe hypertensive crises have been reported during biopsy of these lesions [33]. Biochemical markers usually reveal abnormal findings in these patients. Finally, adrenal biopsies performed at our institution are carried out with IV conscious sedation. This requires the presence of a nurse specially trained in the delivery of conscious sedation and in the monitoring of patients. The sedative and analgesics effects of IV conscious sedation allow percutaneous biopsy of the adrenal to be performed safely and with minimal discomfort to the patient. Dr. Mueller. What is the expected biopsy yield? Dr. Arellano. If both the cytopathologist and the interventional radiologist have adequate experience, one should expect sufficient biopsy material for diagnosis in 80 95% of patients [23, 34, 35]. The overall accuracy of adrenal biopsy increases with increasing needle size, but this must be balanced with an increase in the risk complications. Decreased diagnostic yields are usually associated with hemorrhagic sampling or biopsies performed with smaller 22-gauge needles. Dr. Mueller. What does a biopsy with negative findings mean? Dr. Arellano. The negative predictive value for abdominal biopsy in general is related to several factors, including lesion size, morphology, biopsy needle size, and the oncologic history of the patient. Phillips et al. [36] evaluated the predictive value of imaging-guided adrenal biopsies in both oncology and nononcology patients. In patients without a known oncology history, obtaining a negative biopsy result had a negative predictive value of 91%, and even in patients with a history of lung cancer, a benign biopsy result was highly predictive of benignity, with a negative predictive value of 92% [36]. When nondiagnostic samples are obtained, one must consider the options of repeating the biopsy or, rarely, performing a surgical biopsy. Based on the negative biopsy results for this patient, the referring clinician was confident that the patient was free of metastasis and his operative course was planned accordingly. One year has passed since curative surgery for the primary lung lesion, and the left adrenal adenoma has, as expected, remained unchanged in size. References 1. Boland GWL. The incidental detected adrenal mass: an integrated approach to lesion characterization. Appl Radiol 1999;28: Korobkin M, Francis IR, Kloos RT, Dunnick NR. Advances in uroradiology. Radiol Clin North Am 1996;34: Dunnick NR, Korobkin M, Francis I. Adrenal radiology: distinguishing benign from malignant adrenal masses. AJR 1996;167: Pagani JJ. Normal adrenal glands in small cell lung carcinoma: CT-guided biopsy. AJR 1983; 140: Oliver TW, Bernardino ME, Miller JL, et al. 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