Urologia Internationalis
Urol Int 2010;84:315-318 DOI: 10.1159/000288235
Received: January 2, 2009 Accepted: June 23, 2009
Percutaneous Adrenal Biopsy for Indeterminate Adrenal Lesion: Complications and Diagnostic Accuracy
Yasser Osman Mohsen El-Mekresh Abdul-Monem Gomha Tarek Mohsen Noheir Taha Naser Hussein Ibrahim Eraky Urology Department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
Key Words
Percutaneous biopsy · Adrenal gland · Indeterminate lesion
Abstract
Purpose: To critically analyze the role, accuracy and safety of percutaneous adrenal biopsy for indeterminate adrenal le- sions. Materials and Methods: Adrenal biopsies were per- formed in 15 among 214 patients (7%) diagnosed with adre- nal masses being indeterminate on preoperative imaging. Definitive histopathology was obtained in all and overall sensitivity and negative predictive value were calculated. Safety of the procedure was reported. Results: The study included 8 male and 7 female patients with a mean age of 33.3 ± 20.3 years (range 7-65). Biopsy was carried out under computed tomography and ultrasound guidance in 12 and 3 patients, respectively. There were 2 nonrepresentative bi- opsies that were proved to be adrenocortical carcinoma and myelolipoma after adrenalectomy. Results of biopsy in the remaining 13 patients provided accurate diagnosis as proved by definitive histopathology in all but 2 in whom the final diagnosis was established as adrenocortical carcinoma while biopsy was paraganglioma in one and cortical adenoma in the other. Overall sensitivity and negative predictive value of adrenal biopsy was 73.3 and 60%, respectively. Apart from
two mild hypertensive episodes following silent pheochro- mocytoma biopsy, no complications were reported. Conclu- sions: Percutaneous biopsy is a safe procedure for the diag- nosis of pathologic conditions of the adrenal gland with a reasonable diagnostic aid.
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Introduction
Adrenal disorders represent an important portion of the urologic disease armamentarium. Incidence of adre- nal tumors is much lower than that of other tumors in humans. Nevertheless, rarity of these tumors should not belie their clinical significance because of their particular anatomical locations and potential endocrinal effects. In- cidence of adrenal tumors is apparently increasing in the last decade probably due to the frequent use of imaging studies [1]. It is always crucial to judge adrenal masses pathologically and functionally to spare unnecessary surgical interventions. Although computed tomography (CT) and magnetic resonance imaging (MRI) can be helpful in differentiating a benign from a malignant adrenal lesions, they are not specific and percutaneous adrenal biopsy might be indicated in indeterminate le- sions [2].
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| Adrenal biopsy | Definitive histopathology |
|---|---|
| Pheochromocytoma (5) | Pheochromocytoma (5) |
| Adrenocortical carcinoma (2) | Adrenocortical carcinoma (2) |
| Nonrepresentative (2) | Adrenocortical carcinoma (1) Myelolipoma (1) |
| Cortical adenoma (1) | Adrenocortical carcinoma (1) |
| Paraganglioma (1) | Adrenocortical carcinoma (1) |
| Schwannoma (1) | Schwannoma (1) |
| Myelolipoma (1) | Myelolipoma (1) |
| Cystic teratoma (1) | Cystic teratoma (1) |
| Adrenal metastasis (1) | Adrenal metastasis (1) |
Most of the literature that discussed adrenal biopsy focused on radiological technical details and examined patient populations that are believed to have metastatic disease as it plays an important role in staging and de- finitive therapy. Moreover, most of these patients were followed up clinically and radiologically without avail- able definitive histopathology of most biopsied masses [3-7]. We believe that the role of adrenal biopsy is to be more clarified in an exclusive urologic practice. We aimed to critically analyze the role, accuracy as well as safety of this procedure based on a single institution experience.
Materials and Methods
Between 1992 through 2005, 214 patients with adrenal masses were diagnosed in a tertiary care academic urologic institute with a large oncology referral base. These patients represent 2.3% among patients with urologic tumors and 0.2% among those with genitourinary disorders treated during the same period. Files of the patients were revised including history, clinical assessment, laboratory profile, hormonal essay, radiological evaluation, surgi- cal intervention as well as definitive histopathology.
Adrenal biopsies were performed in 43 patients (20.1%). Twen- ty-eight patients (13.1%) with adrenal neuroblastoma were biop- sied prior induction of preoperative chemotherapy and were not included in our study group. Adrenal biopsies were performed in 15 patients (7%) being indeterminate on preoperative imaging. Indeterminate lesions included small lesions <4 cm with irregular margins ± heterogeneous enhancement with equivocal fat con- tent on CT or MRI. Biopsy was also indicated in larger masses in patients with comorbid conditions to confirm the benign nature of the lesion prior to surveillance. These patients were the subject of our analytical study and definitive histopathology was avail- able in all. Patients lied in a prone position adopting the paraver- tebral posterior approach. In our study, biopsies were performed under ultrasound (US) (Acuson xp 128) guidance using 3.5-5 Hz probe for large well delineated lesion with good accessibility while
CT (light speed plus GE multi-detector) guided biopsy was per- formed for smaller lesions or those closely related to vital organs. Biopsies were performed utilizing 18-gauge needle with automat- ed gun system. The procedure was performed under local anes- thesia (lidocaine 2%) administered subcutaneously with or with- out intravenous sedation. Light general anesthesia was provided in children.
Sensitivity was defined as the number of true test (biopsy) re- sults divided by overall true results as determined by the gold standard (definitive histopathology) while negative predictive value was defined as the number of true negative test results di- vided by the overall test negative results. Statistical significance was considered utilizing the Pearson x2 test with p < 0.05 consid- ered significant. A complication was considered if a therapeutic intervention was offered for the patient.
Results
Fifteen patients were the subject of this investigation and surgical excision of the adrenal mass was performed following the biopsy in all. Patients included 8 male and 7 female patients with mean age of 33.3 ± 20.3 years (range 7-65 years). Mean tumor size was 7.7 + 4.6 cm (range 1-15). Of the lesions 10 were in the right adrenal while 5 were in the left. Biopsy was carried out CT and US guided in 12 and 3 patients, respectively. MRI was in- troduced in our institute in 1998. Eight adrenal biopsies were requested among 75 diagnosed cases (10.7%) prior to introduction of MRI while 7 were requested among 138 diagnosed cases (5.1%) after MRI introduction (p = 0.2). Indications of adrenalectomy were pheochromocytoma in 5, malignant pathology in 3 and nonrepresentative pa- thology in 2 patients. Five patients were subjected to ad- renalectomy despite benign biopsy results within 12 months of follow-up because of anxious patients in 2 and radiological increase in size in 3 patients.
The 2 nonrepresentative biopsies were proved to be ad- renocortical carcinoma and myelolipoma after surgical excision. The results of the biopsy in the remaining 13 patients were: 5 pheochromocytoma, 2 adrenocortical carcinoma, 1 metastatic lesions from primary bladder carcinoma, 1 cortical adenoma, 1 paraganglioma, 1 cystic teratoma, 1 schwannoma, and 1 myelolipoma. The biop- sies provided accurate diagnosis as proved by definitive histopathology after surgical excision in all but two pa- tients in whom the final diagnosis was established as ad- renocortical carcinoma while the biopsy was paragangli- oma in one and cortical adenoma in the other. Table 1 summarizes the biopsy results with its corresponding de- finitive histopathology.
Overall sensitivity of percutaneous adrenal biopsy was 73.3% while its sensitivity in diagnosing malignant adre- nal lesions was 50%. The negative predictive value was calculated to be 60%. Apart from 2 hypertensive episodes following silent pheochromocytoma biopsy that was managed conservatively without serious sequels, no com- plications were reported.
Discussion
The adrenal gland is a common site for both primary and secondary disease. Traditionally, most suspicious solid adrenal masses have been managed surgically with adrenalectomy. Nevertheless, not all these masses are malignant or hormonally active and surgery may not be always indicated. The problem has been magnified with the expanding use of cross-sectional imaging [8]. These new imaging modalities are playing a critical role not only in detection of small adrenal lesions but also in char- acterizing them as benign or malignant. Nevertheless, they are not that specific [2]. Since 1970s, the percutane- ous adrenal biopsy has become a commonly performed interventional procedure that is accepted as a safe option for diagnosis of indeterminate adrenal masses [3, 4, 9]. Most of previous studies discussing percutaneous adre- nal biopsy were focusing upon the technical details in radiological literature and examining mainly oncologic patient population with possible adrenal deposits [3-7]. The possible advantage of this contribution is that it judged the role of that procedure in an exclusive urologi- cal practice. Up to our knowledge, this approach was nev- er challenged in the urologic literature.
In this investigation, incidence of adrenal biopsy for indeterminate lesions was 7% among the study group. Fa- via et al. [10] reported an incidence of 12% among 158 patients with incidentally discovered adrenal masses none of them was known to harbor cancer. Other group of investigators reported even a lower incidence (5%) in a similar group of patients [8]. One study has shown that MRI could replace adrenal biopsy being more cost effec- tive than performing biopsies in all equivocal lesions [11]. Nevertheless, our data failed to demonstrate a statisti- cally significant impact of MRI introduction upon adre- nal biopsy rate. Similar to our observation, Favia et al. [10] demonstrated significantly inferior diagnostic abili- ty of MRI compared with adrenal biopsy.
Generally, adrenal biopsy is accepted as a standard for diagnosis of adrenal pathologic conditions [2] with a high degree of accuracy [6]. Reported sensitivity ranged be-
tween 81% up to 93% by two independent investigators [3, 6]. Favia et al. [10] recently reported up to 100% sensitiv- ity. It was suggested that larger needle 21-22 vs. 18-19 improved the sensitivity without parallel increase in complications rate [3]. On the other hand, others sug- gested a limited value of the procedure in the diagnosis of adrenal lesions [8] probably as they depend on fine as- piration technique that could not differentiate between an adrenal cortical carcinoma and adenoma [12]. No- tably, all these studies relied mainly on clinical and ra- diological follow up with only minority of masses were excised. On absence of definitive histopathology of the biopsied glands, calculation of sensitivity would be inac- curate and misleading. In this investigation, we included only glands that were subjected to adrenalectomy with available final pathology. Our results demonstrated over- all sensitivity of 73.3% while its sensitivity in diagnosing malignant adrenal lesions was only 50% with no false- positive malignant results.
Generally, it is well agreed that a positive malignant biopsy result would confirm the diagnosis while negative results is not helpful in ruling out the disease [6, 13, 14]. Conversely, Harisinghani et al. [4] evaluated the accuracy of a negative for tumor adrenal biopsy in an oncologic patient population by assessing subsequent clinical and radiological outcome and concluded that a negative or a benign pathology for CT-guided percutaneous adrenal biopsy can be regarded as true negative with no necessity to repeat the biopsy. In the previous study, pathologic post mortem examination of adrenal gland was available in only 5% of the examined patients. Two studies evalu- ated the negative predictive value and reported a rate of 80 and 91% [3, 6]. We reported even a lower negative pre- dictive value (60%) based on definitive histopathologic examination and we do suggest to continue in close fol- low-up for all indeterminate adrenal masses with nega- tive adrenal biopsy.
In this investigation, one out of two reported cases with inconclusive biopsy were proved to be malignant on adrenalectomy. This is matched with Paulsen et al. [7] who reported 2 patients with nonrepresentative pathol- ogy. Both showed progressive malignancy on follow-up. Silverman et al. [6] suggested that surgery should be in- dicated in patients with inconclusive biopsy that does not contain benign adrenal tissues or malignant cells. Al- though rebiopsy could be considered, all the patients with nonrepresentative pathology were also nonrepresentative on rebiopsy. Similarly, inconclusive biopsy in cases of small equivocal renal lesions was generally accepted to be dealt as malignant [15].
Adrenal biopsy was generally accepted as a safe proce- dure with low complications rate that ranged between 0% and up to 9% and varied from mild abdominal discom- fort and up to major complications as perinephric hema- toma, pneumothorax necessitating chest tube or malig- nant seeding [3, 5-7]. If a biopsy is planned, pheochro- mocytoma must be excluded by biochemical testing prior to the biopsy to avoid life threatening complications [16] as silent pheochromocytoma could be diagnosed in up to one quarter of asymptomatic adrenal masses [1]. Never- theless, even the most sensitive biochemical test - serum metanephrines - could not provide 100% diagnostic ac- curacy [17]. Interestingly, among five adrenal biopsies that were proved to be pheochromocytoma, only two pa- tients experienced mild hypertensive episodes following
the biopsy without serious sequels. Paulsen et al. [7] sim- ilarly reported adrenal biopsies in 3 pheochromocytoma patients without hypertensive crises.
Conclusions
Percutaneous biopsy is a safe procedure for diagnosis of pathologic conditions of the adrenal gland with rea- sonable diagnostic aid. In urologic practice, it should be spared as the last diagnostic reserve for indeterminate adrenal masses where positive malignant or inconclusive biopsy results should suggest adrenalectomy whereas pa- tients with negative biopsy would be excluded from sur- gery with close follow-up protocol.
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