ORIGINAL ARTICLE
Procedural and clinical outcomes of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy
Danae A. Delivanis*, Dana Erickson*, Thomas D. Atwellt, Neena Natt*, Spyridoula Maraka*, Schmit D. Grantt, Patrick W. Eikent, Mark A. Nathant, William F. Young Jr* and Irina Bancos*
*Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, and tDepartment of Radiology, Mayo Clinic, Rochester, MN, USA
Summary
Objective The role of percutaneous adrenal biopsy in a high- risk population for adrenal malignancy has not been fully inves- tigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy.
Design Single-centre, retrospective cohort study.
Patients and Measurements Medical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a prede- fined reference standard.
Results Biopsy was performed in 418 patients [62% men, med- ian age 69 years (range, 15-91)] on 419 adrenal lesions, median size 3.1 cm (range, 0-6-24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra-adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy-related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity ≤10 HU (42/ 137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88-5%, speci- ficity of 91.5%, positive predictive value of 93-4% and negative predictive value of 85-5%.
Conclusion When used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemi- cal testing for pheochromocytoma prior to adrenal biopsy are needed.
(Received 11 April 2016; returned for revision 30 April 2016; finally revised 12 May 2016; accepted 30 May 2016)
Introduction
Adrenal masses are reported in up to 4% of patients who undergo cross-sectional abdominal imaging1 and prevalence increases with patient age.2,3 Although the majority of adrenal masses are benign adrenocortical adenomas,4 clinicians need to exclude other pathologies such as metastatic carcinoma,5 pheochromocytoma2 and adrenocortical carcinoma (ACC).6,7 The risk of a metastatic malignant adrenal mass has been reported to be as high as 50-75%, particularly in patients with either a history of or current active extra-adrenal malignancy.8,9 In such cases, confirmation of the underlying aetiology of the adrenal mass guides further management as well as carries prog- nostic implications.
While computed tomography (CT) and magnetic resonance imaging (MRI) have shown good capability to characterize adre- nal masses as benign, the specificity of CT and MRI for diagnos- ing malignancy in the adrenal gland is suboptimal.10,11 Larger adrenal mass size is associated with increased likelihood of malignancy, but it also has poor specificity.12
The role for and value of adrenal biopsy in patients with adre- nal masses have not been fully established. Most published reports include small and heterogeneous samples of patients that lack stratified diagnostic performance information and provide insufficient information on complication rate and nondiagnostic samples. Moreover, reference standard used to evaluate the diag- nostic performance of adrenal biopsy is surprisingly poor. While several authors fail to provide any information on reference standard,13,14 others use only clinical follow-up15,16 and a minority of studies use adrenalectomy or imaging follow-up as a reference standard.17,18
To address this knowledge gap, we have analysed the results of adrenal biopsies performed at our institution over a 20-year period. Our objectives were to analyse the:
· demographics, clinical context, indications and computed imaging characteristics of patients undergoing adrenal biopsies,
Correspondence: Irina Bancos, Division of Endocrinology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel .: 507 284 2511; Fax: 507 284 5745; E-mail: bancos.irina@mayo.edu
· diagnostic performance of adrenal biopsy in diagnosing malignancy,
· rate of nondiagnostic adrenal biopsies and complications related to the procedure.
Subjects and methods
We reviewed a retrospective cohort of patients undergoing adrenal biopsy at Mayo Clinic in Rochester, Minnesota, between 1994 and 2014. The study protocol was approved by the Mayo Clinic Institu- tional Review Board. Given the retrospective nature of this project, records for consent waiver were reviewed and only patients who did not waive their consent were included. Medical records were reviewed for clinical information pertinent to the presentation and management of the adrenal mass. Imaging was reviewed by radiolo- gists with expertise in adrenal imaging, and imaging characteristics were recorded. Information related to the adrenal biopsy procedure, technical approach and complications was included. All pathology reports were reviewed for information regarding the histological diagnosis. In addition, all follow-up clinical, imaging and surgical information was collected for each patient.
Adrenal biopsy procedure
Adrenal biopsies were performed as an outpatient procedure in one of two hospitals within our institution. Most adrenal biop- sies were performed using CT guidance; rarely, ultrasound (US) guidance was used to biopsy right adrenal masses via a transhep- atic approach based on operator preference. Biopsies were per- formed under sterile conditions and with local anaesthetic. When necessary, conscious sedation was administered under the direction of the radiologist performing the biopsy. Core biopsy using either 18- or 20-gauge needles was performed in all patients, with touch-prep cytology specimens obtained using the core tissue sample. All tissue samples were thus reviewed by pathologists with experience in adrenal tumours for both cytol- ogy and histology. Following the biopsy, patients were observed in the radiology recovery room until discharge criteria were met, typically for 1-2 h.
Reference standard
In order to investigate the diagnostic accuracy of the adrenal biopsy to diagnose malignancy in our study, a subgroup analysis of 167 patients from the entire cohort who met the optimal ref- erence standard was performed. The reference standard for malignant adrenal masses was defined as: (i) malignant histology obtained from subsequent adrenalectomy, or (ii) increase in adrenal mass size of more than 20% on a subsequent imaging study in less than 12 months or (iii) decrease in adrenal mass size after chemotherapy or radiation. For benign adrenal masses, our reference standard was defined as: (i) benign histology obtained from subsequent adrenalectomy or (ii) stable adrenal mass size on subsequent imaging study completed more than 6 months following biopsy.
Statistics
Descriptive statistics were used to determine mean and standard deviation (SD) or median and ranges depending on data distri- bution, while categorical data are shown as a number (%). Asso- ciations between variables were assessed using the Student’s t-test and ANOVA for continuous variables and the chi-square test for categorical variables. P values less than five were considered significant. Data were analysed using JMP software, version 10 (SAS, Cary, NC, USA).
Results
Patients
Four hundred and nineteen adrenal biopsies were performed in 418 patients between 1994 and 2014. Median age of patients was 69 years (range, 15-91), and 259 (62%) were men. Median adre- nal mass size was 3.1 cm (range, 0-6-24). More adrenal biopsies were performed for left adrenal masses (257/419, 61%) than right adrenal masses (162/419, 39%; P < 0.002). Unilateral adre- nal biopsy in the setting of bilateral adrenal masses was under- taken in 82 (19%) patients.
Patients had one or more indications for adrenal biopsy which included: (i) suspected adrenal metastasis from an extra-adrenal primary source (349/419, 83%); (ii) suspected adrenocortical carcinoma (28/419, 7%); (iii) suspected infectious process (18/ 419, 4%); (iv) suspected lymphoma (26/419, 6%); and (v) other (15/419, 3%). A minority of patients were referred for adrenal biopsy by endocrinologists (44/419, 10%), while most were referred by medical oncologists (134/419, 32%), pulmonologists (107/419, 25%), internal medicine physicians (37/419, 9%) and other specialties (97/419, 23%). Prebiopsy case detection testing for pheochromocytoma was completed in 116 of 419 (28%) of the cases. Screening for pheochromocytoma (42/44, 95%) was more often requested by Endocrinologists compared to other specialties (74/375, 20%).
Adrenal biopsy technique and complications
Three hundred and ninety (93%) of the biopsies were per- formed under CT guidance, and 29 (7%) were performed under US guidance. The needle size was 18 gauge in 216 of 419 (51%) of the cases, 20 gauge in 188 of 419 (45%) and an alternate size in 15 of 419 (4%) cases. In the majority of adrenal biopsies, three passes were performed. A transhepatic approach using CT or US guidance was followed in 50 of 419 (12%) cases. The rate of nondiagnostic adrenal biopsies was 20 of 419 (5%). There was no difference in median times of needle passes or needle size between diagnostic and nondiagnostic samples. The inci- dence of a nondiagnostic adrenal biopsy was independent of the site of the adrenal mass (right vs left 5% vs 6%), P = 0.26, and independent of the size of the mass, P = 0.56.
Seventeen patients (4%) developed biopsy-related complica- tions, including a small asymptomatic self-resolving pneumotho- rax in four patients, and periadrenal gland haemorrhage in 11
patients; three of whom required overnight observation in the hospital and one patient requiring hospitalization for pain man- agement. Finally, one patient with unsuspected pheochromocy- toma developed self-limiting tremors without hypertensive urgency.
Histology
The majority of biopsied adrenal masses represented metastases (231/419, 55%), most originating from a primary lung malig- nancy: nonsmall (n = 115) and small cell origins (n = 7) (Table 1). Histology consistent with benign adrenal tissue was obtained in a third of the adrenal biopsies (137/419, 33%). Seven patients were diagnosed with pheochromocytoma based on the biopsy, none of whom had undergone biochemical screening prior to the procedure. Other pathologies included eight cases of ACC, six cases of infiltrative infectious processes and 10 patients with other aetiologies (Table 1).
Patients with adrenocortical carcinoma
Adrenal biopsy histology was suggestive of ACC in eight of 419 (2%) patients (Table 2); five of these patients underwent adrenal surgery and ACC was confirmed in four, and a benign adrenal adenoma in one. The three other patients with presumed ACC had extensive metastatic disease, and palliative care was pursued without further intervention. In addition, one adrenal mass [2.8 cm, precontrast radiodensity = 32 Hounsfield units (HU)], where adrenal biopsy indicated a benign adrenal adenoma, was ultimately proven to be ACC after being surgically resected due
| Diagnosis based on adrenal biopsy histology | n (%) | |
|---|---|---|
| Benign adrenal cortical tissue/adrenal adenoma | 137 (33) | |
| Adrenocortical carcinoma | 8 (2) | |
| Metastasis (n = 231) | Lung | 122 (29) |
| Kidney | 26 (6) | |
| Gastrointestinal | 21 (5) | |
| Lymphoma | 15 (3) | |
| Melanoma | 8 (2) | |
| Genitourinary | 7 (2) | |
| Sarcoma | 6 (1) | |
| Breast | 4 (<1) | |
| Thyroid | 3 (<1) | |
| Prostate | 2 (<1) | |
| Unknown primary | 17 (4) | |
| Other lesions (n = 23) | Infectious process | 6 (1) |
| Pheochromocytoma | 7 (2) | |
| Myelolipoma | 3 (<1) | |
| Haematoma | 3 (<1) | |
| Ganglioneuroma | 2 (<1) | |
| Neuroblastoma | 1 (<1) | |
| Neuroendocrine tumour | 1 (<1) | |
| Non diagnostic | 20 (5) | |
| Total | 419 | |
| Concordant (n = 42) | Discordant (n = 8) (adrenal biopsy # adrenalectomy) | ||
|---|---|---|---|
| (adrenal biopsy = adrenalectomy) | |||
| Adenoma | 5 | Adrenal biopsy | Adrenalectomy |
| ACC | 4 | 1 ACC | 1 Adenoma |
| Metastasis | 21* | 1 Adenomas | 1 ACC |
| Pheochromocytoma | 7 | 3 Adenomas | 2 Renal cell cancer 1 hepatic cancer |
| Neuroblastoma | 1 | 2 Renal cell cancer | 2 Adenoma |
| Ganglioneuroma | 1 | 1 Ganglioneuroma | 1 Adenoma |
| Myelolipoma | 1 | ||
| Haematoma | 2 | ||
ACC, adrenocortical carcinoma
*11 renal cell carcinoma, 5 non-small-lung carcinoma, 1 uterine carci- noma, 1 thyroid, 1 liposarcoma, 1 leiomyosarcoma, 1 unknown primary carcinoma.
to increasing size on follow-up imaging (Table 3). Sensitivity and positive predictive value (PPV) of adrenal biopsy to diag- nose ACC was 87.5% (Table 4).
Patients with metastases
Adrenal metastasis was diagnosed in 231 of 419 (55%) patients (Table 1). Most patients (202/231, 87%) had a history of extra- adrenal malignancy at the time of adrenal mass discovery, and in 18 of 231 (8%), the adrenal mass was the only presentation of malignancy. Median size of adrenal metastases was 3-4 cm (range, 0-2-12-7 cm), and median radiodensity on unenhanced CT was 36 HU (range, 12-78). The diagnostic performance of adrenal biopsy to detect adrenal metastatic disease was 88.8% sensitivity, 93-6% specificity, 88% negative predictive value (NPV) and 94% PPV (Table 4).
Patients with adrenocortical adenomas
Histology was suggestive of benign adrenal cortical tissue or adrenal adenoma in 137 of 419 (33%) adrenal biopsies, and a history of known or suspected extra-adrenal malignancy was present in 98 of 137 (71-5%) of these patients. Median size of these benign adrenal lesions was 2.1 cm (range, 0-8-8), and median radiodensity on unenhanced CT imaging was 21 HU (range, -20 to 63). All adrenal masses (42/137, 31%) with unen- hanced radiodensity ≤10 HU (median size 2.7 cm; range, 1.3- 6-3 cm) proved to be benign adrenal adenomas. In 37 of 42 of these cases, the adrenal biopsy was consistent with benign adre- nal adenoma. In five of 42 of these cases, the biopsy was nondi- agnostic; three patients underwent adrenalectomy and pathology was consistent with a benign adrenal adenoma, and two patients were followed radiologically and subsequently demonstrated no
| Patient | Age, years | Sex | Tumour size, cm | Radiodensity precontrast administration, HU | Histology from adrenal biopsy | Histology from adrenalectomy |
|---|---|---|---|---|---|---|
| 1 | 50 | F | 15 | 45 | ACC | ACC |
| 2 | 72 | M | 17 | Not available | ACC | ACC |
| 3 | 57 | M | 2.7 | 35 | ACC | Adenoma |
| 4 | 80 | F | 4.7 | 42 | ACC | Not done due to metastatic disease |
| 5 | 50 | F | 4.1 | Not available | ACC | Not done due to metastatic disease |
| 6 | 71 | F | 8 | 35 | ACC | Not done due to metastatic disease |
| 7 | 72 | M | 7.8 | 34 | ACC | ACC |
| 8 | 35 | F | 24-4 | 20 | ACC | ACC |
| 9 | 76 | F | 2.8 | 32 | Adenoma | ACC |
| Sensitivity, % | Specificity, % | NPV, % | PPV, % | |
|---|---|---|---|---|
| Any malignancy | 88.5 | 91.5 | 85-5 | 93-4 |
| Metastasis | 88-8 | 93-6 | 88 | 94 |
| Adrenocortical carcinoma | 87.5 | 99-4 | 99-4 | 87.5 |
| Adrenocortical adenoma | 87.5 | 90 | 93-4 | 81-7 |
NPV, negative predictive value; PPV, positive predictive value.
growth of the adrenal masses. As illustrated in Table 2, four dis- cordant cases of adrenal adenomas, between adrenal biopsy and adrenalectomy, were identified. Three patients were ultimately found to have metastatic extra-adrenal malignancy after adrenalectomy and one patient an ACC.
Patients with bilateral adrenal masses
Twenty per cent of patients in our cohort (82/419) had radio- graphic evidence of bilateral adrenal masses. Median size of the largest lesion was 3-2 cm (range, 0-5-12-7). A malignant adrenal mass was diagnosed in 50 of 82 (61%) patients and included metastases from lung carcinoma (n = 27), lymphoma (n = 12), renal cell carcinoma (n = 3), melanoma (n = 2), breast carci- noma (n = 1), oesophageal carcinoma (n = 1), hepatocellular carcinoma (n = 1), prostate carcinoma (n = 1), neuroendocrine tumour (n = 1) and poorly differentiated carcinoma (n = 1). The remaining bilateral adrenal lesions included benign adrenal adenomas (n = 20), infectious processes (five cases of histoplas- mosis and one case of cryptococcal infection) and nondiagnostic biopsy (n = 7, with three of seven cases later concluded to be due to metastatic lung carcinoma). The rate of metastatic lesions was similar in patients with bilateral adrenal masses (50/82, 61%) when compared to patients with unilateral masses (181/ 337, 53.7%) (P = 0.2). Primary adrenal insufficiency was docu- mented in five of 82 (6%) patients with bilateral masses (three infectious processes, one non-small-cell lung carcinoma and one lymphoma). These patients presented with symptoms of adrenal
insufficiency, and a biochemical diagnosis of adrenal insuffi- ciency was established by low levels of morning serum cortisol concentration and elevated serum adrenocortical hormone (ACTH) concentration.
Discordance between adrenal biopsy and final surgical pathology results following adrenalectomy
In eight cases, the histological diagnosis derived from the adre- nal biopsy was discordant with the adrenalectomy (Table 2). In four cases, adrenal biopsy suggested benign adrenal adenomas; however, malignant lesions were diagnosed after adrenalectomy (two renal cell carcinoma, one hepatic carcinoma and one ACC). In three cases, adrenal biopsy diagnosis indicated malig- nant lesions (one ACC and two renal cell carcinoma metastases); however, all three were proven to be benign adrenal adenomas on adrenalectomy. Finally, a ganglioneuroma diagnosed as a result of adrenal biopsy turned out to be adrenal adenoma when surgical tissue was examined.
Follow-up/prognosis/outcomes
Follow-up information was available in 286 of 419 (68%) patients observed for a median of 5-2 months (range, 1 month-15 years) after the adrenal biopsy. Adrenalectomy was performed in 50 of 419 patients within a median of 40 days after the biopsy. The remaining 236 patients had either imaging follow-up (75%) or clinical follow-up (25%). Seventy-eight per cent of patients (181/ 231) with biopsy-proven metastatic adrenal masses died within 7 months (range, 4 weeks-13 years) of the adrenal biopsy.
Diagnostic performance of adrenal biopsy
To determine the diagnostic accuracy of the adrenal biopsy, we performed a subpopulation analysis of 167 patients meeting pre- defined criteria for an optimal reference standard. Adrenal biopsy diagnosed malignancy with a sensitivity of 88-5%, speci- ficity of 91.5%, PPV of 93-4% and NPV of 85-5% (Table 4). Recognizing a selection bias in which the biopsy diagnosis may be in question, the diagnostic performance of adrenal biopsy
was assessed separately for the 50 patients who underwent adrenalectomy following biopsy (Table 2). In this population, the diagnostic performance of adrenal biopsy to detect malig- nancy slightly decreased to a sensitivity of 86-6%, specificity of 90%, PPV of 92-8% and NPV of 81-8%, and accuracy of 88%. In addition, when pheochromocytomas were excluded from the adrenalectomy cohort, performance of adrenal biopsy decreased further to a specificity of 84-6% and NPV of 73.3%.
Discussion
Adrenal biopsy is a valuable diagnostic tool in patients with an adrenal mass with indeterminate imaging characteristics and where the likelihood for an adrenal infiltrative process, such as metastasis, lymphoma and infection is high, and where histology results will guide further management. Herein, we present our experience with adrenal biopsy in a large cohort of patients with an adrenal mass. Our patient cohort clearly represented a high- risk population, as most had suspected or confirmed extra-adre- nal malignancy and most presented with adrenal masses demon- strating indeterminate image characteristics.
As expected in a high-risk population, 57% of adrenal lesions were malignant on biopsy, mainly represented by metastases (55%). A comparable prevalence of metastases was described in other smaller studies reporting an overall experience with adrenal biopsy.19-21 In studies reporting almost exclusively on oncologic patients, a higher prevalence of metastases of up to 78-81% has been described.22,23 Interestingly, even in patients with ‘benign’ imaging characteristics (i.e. unenhanced radioden- sity ≤10 HU), physicians chose to proceed with adrenal biopsy due to underlying concern for malignancy. However, even in this high-risk population, all such patients (42/137, 31%) were ultimately proven to have a benign adrenal adenoma.
A majority of patients (72%) did not undergo screening for catecholamine-producing tumours before the biopsy, leading to inadvertent biopsy of seven patients with pheochromocytoma, one of whom developed periadrenal haemorrhage and another developed mild tremors following the biopsy. Despite the minor complications seen in our cohort, other studies23-25 have shown that lack of biochemical testing for pheochromocytoma can lead to severe consequences. Thus, biochemical testing for pheochro- mocytoma should be considered in most patients before pro- ceeding to adrenal biopsy.
Overall, the rate of adrenal biopsy complications in our study was relatively low at 4%. Several authors have reported a similar rate of complications,15,18,25,26 but with others reporting a com- plication rate as high as 13%.27,28 The reasons for this discrep- ancy may be related to adrenal biopsy technique, characteristics of adrenal lesions (such as vascularity), practices in regard to preprocedural biochemical testing for pheochromocytoma, and interventional radiologist’s experience, as well as heterogeneity in regard to the practice of recording of complications.
The rate of nondiagnostic biopsy in our cohort was 5%. We have not found any relationship to utilized technique, size, site or histological diagnosis of the adrenal mass. The rates of nondi- agnostic biopsy vary between 0% and 28% in other
studies.17,20,26 It is likely that radiologist experience and tech- nique do play a significant role, as higher nondiagnostic rates were reported in smaller cohorts of patients.27 However, even in conditions of optimal sampling and zero nondiagnostic rates, as occurred in the ex vivo study of Sager et al., accuracy of core biopsy to diagnose malignancy did not reach 100%. This sug- gests that other factors, possibly related to histology sampling, need for entire tissue architecture and pathologist’s experience, play a significant role as well.29
When assessed for the 167 patients with an optimal reference standard, the diagnostic accuracy of adrenal biopsy for diagnosis of malignancy was 85-3%. Our results are comparable to other studies.15-18 When adrenal biopsy performance was assessed only for the 50 patients who underwent adrenalectomy, the overall accuracy to detect malignancy was similar (88%). This finding contrasted to our expectation of a suboptimal performance of the adrenal biopsy compared to adrenalectomy given the poten- tial technical procedural limitations, potential for location sam- pling error and inadequate biopsy specimen for proper pathology interpretation. However, this can be explained by the fact that the adrenalectomy group represented a large proportion of pheochromocytomas as well as metastases - two aetiologies that performed the best in adrenal biopsies, with the least num- ber of false-positive results.29
The diagnostic performance of adrenal biopsy for ACC was found to be higher than expected (88-5% sensitivity and 87.5% PPV), rec- ognizing that ACC was seen in only eight patients. In the absence of other diagnostic tools, certain situations may warrant biopsy of meta- static ACC (where tissue diagnosis helps guide therapy) or hormon- ally inactive ACC.30 However, due to limited diagnostic accuracy,13 difficulties in histopathologic differentiation between a degenerated adenoma and an ACC31 and theoretical risk of tumour recurrence along the needle track,32,33 adrenal biopsy should be avoided in patients with high suspicion of ACC.34,35
No difference in the incidence of adrenal malignancy was identified between patients with bilateral compared to unilateral adrenal masses. The two most commonly identified malignancies in patients with bilateral adrenal masses were non-small-cell lung carcinoma and lymphomas. Only 1% of all biopsies revealed infectious process, and all of them were found in patients with bilateral adrenal masses. As others have reported,36,37 6% of our patients with bilateral adrenal masses had primary adrenal insufficiency.
It is reassuring that even in a high-risk population, all adrenal lesions with ≤10 HU proved to be benign adrenal adenomas. Sev- eral authors9,38 have reported certain metastatic lesions and even ACC to have an unenhanced radiodensity of less than 10 HU pos- sibly due to heterogeneity of the lesions. However, this seems to be a very rare occurrence and not confirmed in our study.
Strengths and limitations
We have reviewed a large number of patients undergoing adre- nal biopsy. Unlike most other studies published on this topic, we applied a predefined stringent reference standard for the cal- culation of diagnostic accuracy. As a part of standard practice,
both immediate and delayed complications were uniformly doc- umented in all patients. In addition, as most imaging studies were available for our review, we were able to provide certain recommendations on when to avoid adrenal biopsy. Histology was interpreted by a team of pathologists with adrenal expertise, thus decreasing subjectivity and heterogeneity in reporting. Finally, this is the first study which reviews preprocedural screening practices for pheochromocytoma in an unselected cohort of patients undergoing adrenal biopsy.
This is a retrospective study with its inherent bias and limitations. Given referral bias, some of our findings might overestimate inci- dence of disease and performance of the adrenal biopsy in the broader community. However, adrenal biopsy should be performed in highly selected patients in centres with necessary expertise, and thus, the design chosen for this study is appropriate. Finally due to the nature of our practice, many patients elect to pursue routine care closer to home, creating limitations in obtaining long-term follow- up. Despite this limitation, we were still able to obtain follow-up information in more than two-thirds of our patients.
Conclusion
In summary, when used in the appropriate clinical setting, adre- nal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malig- nancy. We have found that there were no malignant adrenal tumours (primary or metastatic) if the unenhanced CT radio- density was ≤10 HU. Thus, even in a high-risk population, biopsy of such lesions is not needed. We recommend against adrenal biopsy in potentially completely resectable and non- metastatic ACC. Only a quarter of patients referred for biopsy had biochemical testing for pheochromocytoma, indicating the need for efforts to increase awareness among referring special- ties. Finally, despite a good diagnostic performance of adrenal biopsy in detecting malignancy, the clinician should assess the value of the adrenal biopsy in relation to how it changes man- agement and overall prognosis.
Conflict of interest
Nothing to declare.
References
1 Bovio, S., Cataldi, A., Reimondo, G. et al. (2006) Prevalence of adrenal incidentaloma in a contemporary computerized tomogra- phy series. Journal of Endocrinological Investigation, 29, 298-302.
2 Young, W.F., Jr. (2000) Management approaches to adrenal inci- dentalomas. A view from Rochester, Minnesota. Endocrinology and Metabolism Clinics of North America, 29, 159-185, x.
3 Kloos, R.T., Gross, M.D., Francis, I.R. et al. (1995) Incidentally discovered adrenal masses. Endocrine Reviews, 16, 460-484.
4 Herrera, M.F., Grant, C.S., van Heerden, J.A. et al. (1991) Inci- dentally discovered adrenal tumors: an institutional perspective. Surgery, 110, 1014-1021.
5 Kasperlik-Zeluska, A.A., Roslonowska, E., Slowinska-Srzednicka, J. et al. (1997) Incidentally discovered adrenal mass
(incidentaloma): investigation and management of 208 patients. Clinical Endocrinology, 46, 29-37.
6 Icard, P., Goudet, P., Charpenay, C. et al. (2001) Adrenocortical carcinomas: surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons study group. World Journal of Surgery, 25, 891-897.
7 Latronico, A.C. & Chrousos, G.P. (1997) Extensive personal experience: adrenocortical tumors. The Journal of Clinical Endocrinology and Metabolism, 82, 1317-1324.
8 Lenert, J.T., Barnett, C.C. Jr, Kudelka, A.P. et al. (2001) Evaluation and surgical resection of adrenal masses in patients with a history of extra-adrenal malignancy. Surgery, 130, 1060-1067.
9 Frilling, A., Tecklenborg, K., Weber, F. et al. (2004) Importance of adrenal incidentaloma in patients with a history of malig- nancy. Surgery, 136, 1289-1296.
10 Cawood, T.J., Hunt, P.J., O’Shea, D. et al. (2009) Recommended evaluation of adrenal incidentalomas is costly, has high false- positive rates and confers a risk of fatal cancer that is similar to the risk of the adrenal lesion becoming malignant; time for a rethink? European Journal of Endocrinology/European Federation of Endocrine Societies, 161, 513-527.
11 Reinig, J.W., Doppman, J.L., Dwyer, A.J. et al. (1986) MRI of indeterminate adrenal masses. AJR. American Journal of Roentgenology, 147, 493-496.
12 Mantero, F., Terzolo, M., Arnaldi, G. et al. (2000) A survey on adrenal incidentaloma in Italy. Study group on adrenal tumors of the Italian society of endocrinology. The Journal of Clinical Endocrinology and Metabolism, 85, 637-644.
13 Mazzaglia, P.J. & Monchik, J.M. (2009) Limited value of adrenal biopsy in the evaluation of adrenal neoplasm: a decade of experi- ence. Archives of Surgery, 144, 465-470.
14 Kocijancic, K., Kocijancic, I. & Guna, F. (2004) Role of sono- graphically guided fine-needle aspiration biopsy of adrenal masses in patients with lung cancer. Journal of Clinical Ultra- sound: JCU, 32, 12-16.
15 Welch, T.J., Sheedy, P.F. 2nd, Stephens, D.H. et al. (1994) Per- cutaneous adrenal biopsy: review of a 10-year experience. Radiol- ogy, 193, 341-344.
16 Bodtger, U., Vilmann, P., Clementsen, P. et al. (2009) Clinical impact of endoscopic ultrasound-fine needle aspiration of left adrenal masses in established or suspected lung cancer. Journal of Thoracic Oncology, 4, 1485-1489.
17 Tirabassi, G., Kola, B., Ferretti, M. et al. (2012) Fine-needle aspi- ration cytology of adrenal masses: a re-assessment with histologi- cal confirmation. Journal of Endocrinological Investigation, 35, 590-594.
18 Lumachi, F., Borsato, S., Tregnaghi, A. et al. (2007) High risk of malignancy in patients with incidentally discovered adrenal masses: accuracy of adrenal imaging and image-guided fine-nee- dle aspiration cytology. Tumori, 93, 269-274.
19 Silverman, S.G., Mueller, P.R., Pinkney, L.P. et al. (1993) Predic- tive value of image-guided adrenal biopsy: analysis of results of 101 biopsies. Radiology, 187, 715-718.
20 de Agustin, P., Lopez-Rios, F., Alberti, N. et al. (1999) Fine-nee- dle aspiration biopsy of the adrenal glands: a ten-year experience. Diagnostic Cytopathology, 21, 92-97.
21 Villelli, N.W., Jayanti, M.K. & Zynger, D.L. (2012) Use and use- fulness of adrenal core biopsies without FNA or on-site evalua- tion of adequacy: a study of 204 cases for a 12-year period. American Journal of Clinical Pathology, 137, 124-131.
22 Harisinghani, M.G., Maher, M.M., Hahn, P.F. et al. (2002) Pre- dictive value of benign percutaneous adrenal biopsies in oncol- ogy patients. Clinical Radiology, 57, 898-901.
23 Paulsen, S.D., Nghiem, H.V., Korobkin, M. et al. (2004) Chang- ing role of imaging-guided percutaneous biopsy of adrenal masses: evaluation of 50 adrenal biopsies. AJR. American Journal of Roentgenology, 182, 1033-1037.
24 Vanderveen, K.A., Thompson, S.M., Callstrom, M.R. et al. (2009) Biopsy of pheochromocytomas and paragangliomas: potential for disaster. Surgery, 146, 1158-1166.
25 Lumachi, F., Borsato, S., Brandes, A.A. et al. (2001) Fine-needle aspiration cytology of adrenal masses in noncancer patients: clin- icoradiologic and histologic correlations in functioning and non- functioning tumors. Cancer, 93, 323-329.
26 Lumachi, F., Borsato, S., Tregnaghi, A. et al. (2003) CT-scan, MRI and image-guided FNA cytology of incidental adrenal masses. European Journal of Surgical Oncology, 29, 689-692.
27 Quayle, F.J., Spitler, J.A., Pierce, R.A. et al. (2007) Needle biopsy of incidentally discovered adrenal masses is rarely informative and potentially hazardous. Surgery, 142, 497-502; discussion 502-494.
28 Osman, Y., El-Mekresh, M., Gomha, A.M. et al. (2010) Percuta- neous adrenal biopsy for indeterminate adrenal lesion: complica- tions and diagnostic accuracy. Urologia Internationalis, 84, 315- 318.
29 Saeger, W., Fassnacht, M., Chita, R. et al. (2003) High diagnostic accuracy of adrenal core biopsy: results of the German and Aus- trian adrenal network multicenter trial in 220 consecutive patients. Human Pathology, 34, 180-186.
30 Ren, R., Guo, M., Sneige, N. et al. (2006) Fine-needle aspiration of adrenal cortical carcinoma: cytologic spectrum and diagnostic challenges. American Journal of Clinical Pathology, 126, 389-398.
31 Korobkin, M., Francis, I.R., Kloos, R.T. et al. (1996) The inci- dental adrenal mass. Radiologic Clinics of North America, 34, 1037-1054.
32 Habscheid, W., Pfeiffer, M., Demmrich, J. et al. (1990) Puncture track metastasis after ultrasound-guided fine-needle puncture biopsy. A rare complication? Deutsche Medizinische Wochen- schrift, 115, 212-215.
33 Mody, M.K., Kazerooni, E.A. & Korobkin, M. (1995) Percuta- neous CT-guided biopsy of adrenal masses: immediate and delayed complications. Journal of Computer Assisted Tomography, 19, 434-439.
34 Else, T., Kim, A.C., Sabolch, A. et al. (2014) Adrenocortical car- cinoma. Endocrine Reviews, 35, 282-326.
35 Fassnacht, M. & Allolio, B. (2009) Clinical management of adrenocortical carcinoma. Best Practice and Research. Clinical Endocrinology and Metabolism, 23, 273-289.
36 Donckier, J.E., Lacrosse, M. & Michel, L. (2007) Bilateral adrenal lymphoma with Addison’s disease: a surgical pitfall. Acta Chirur- gica Belgica, 107, 219-221.
37 Mohammad, K. & Sadikot, R.T. (2009) Adrenal insufficiency as a presenting manifestation of nonsmall cell lung cancer. Southern Medical Journal, 102, 665-667.
38 Porte, H.L., Ernst, O.J., Delebecq, T. et al. (1999) Is computed tomography guided biopsy still necessary for the diagnosis of adre- nal masses in patients with resectable non-small-cell lung cancer? European Journal of Cardio-Thoracic Surgery, 15, 597-601.