CT imaging characteristics of oncocytic adrenal neoplasms (OANs): comparison with adrenocortical carcinomas
Mansoor Khan,1 Elaine M. Caoili,1 Matthew S. Davenport,1 Ann Poznanski,2 Isaac R. Francis,1 Thomas Giordano,3 N. Reed Dunnick1
1Department of Radiology, University of Michigan Health System, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA 2Oakland University William Beaumont School of Medicine, 2200 Squirrel Road, Rochester, MI 48309, USA
3University of Michigan Health System, 1301 Catherine Blvd., Ann Arbor, MI 48109, USA
Abstract
Objective: Oncocytic adrenal neoplasms (OANs) are rare, but are an important subtype of adrenal tumors that is being diagnosed with increasing frequency. Unfortunately, the imaging characteristics of this tumor have not been well described. Our purpose was to identify CT features to differentiate OANs from adre- nocortical carcinomas (ACC).
Materials and methods: From 1991 to 2012, 18 patients with OANs were identified from our institution’s pathol- ogy database. Twelve had CT examinations available for review. CT characteristics of five benign and seven malignant OANs were reviewed by two abdominal radiologists, and compared to ACC (n = 10). Morpho- logic characteristics and density measurements were recorded for each imaging phase. Absolute contrast washout was calculated and compared.
Results: Benign OANs were smaller [mean size 3.7 cm (range 2.6-5.3)] and more homogeneous than malignant OANs and demonstrated greater washout [mean wash- out percentage 72.3% (range 61-88)]. Malignant OANs demonstrated features similar to ACCs, including size [mean 9.4 cm (range 5.2-9.8)] and internal necrosis (n = 6). Mean enhancement washout percentage for malignant OANs was 12% (range -8 to 32).
Conclusion: Benign OANs (oncocytomas) may be distin- guished from lipid-rich adenomas on non-contrast CT but may be indistinguishable from lipid-poor adenomas. Malignant oncocytic neoplasms can demonstrate fea-
tures similar to ACCs, including larger size, internal necrosis, and lower percentage enhancement washout.
Key words: Adrenal gland-Adrenal cortical carcinoma-CT
Adrenal masses are commonly found on abdominal CT examinations [1-3]. While most are benign adenomas, additional testing is sometimes required to exclude le- sions that require treatment. Oncocytic neoplasms have been described in many organs, including the kidney, salivary gland, thyroid gland, and parathyroid gland [4]. Oncocytic neoplasms of the adrenal gland are rare, with fewer than 100 cases documented in the literature [5-8]. Histologically, oncocytic adrenal neoplasms (OANs) demonstrate >75% oncocytes-epithelial cells with abundant granular eosinophilic cytoplasm [9]. OANs may be benign (oncocytomas) or malignant and the distinction is made histologically using the modified Weiss criteria [10]. Unlike adrenal adenomas, adrenal oncocytomas rarely produce unregulated amounts of hormone [11]. Furthermore, malignant OANs have a more favorable prognosis than adrenocortical carcino- mas (ACCs) [9] and thus are important to identify.
The largest published study of the imaging features of OANs includes nine patients who underwent CT of the abdomen of which only one underwent both an unen- hanced and enhanced CT imaging [5]. However, no study, to our knowledge, has compared the imaging features of OANs with ACCs. The purpose of our study was to assess the CT imaging characteristics of OANs and to determine whether they could be differentiated noninvasively.
Materials and methods
Subjects
Prior to the initiation of this investigation, Institutional Review Board approval was obtained and the study was carried out in compliance with the Health Insurance Portability and Accountability Act (HIPAA, USA). Pa- tient informed written consent was waived based on the retrospective nature of the study.
Over a 21-year period from 1991 through 2012, the Endocrine Tumor Board pathology database was sear- ched, yielding 18 patients with OANs (Table 1) based on pathology results. There were 6 males and 12 females with a mean age at diagnosis of 49.6 years (range 3-74). Of these patients, 12 had retrievable digital CT images available. In all but one patient, a single adrenal mass was identified. In the patient with two adrenal masses, only the dominant mass was included. All neoplasms included in our study were surgically excised. OANs were histologically characterized by the predominance (≥75% of the lesion) of oncocytes: epithelial cells containing a significant amount of granular eosinophilic cytoplasm usually arranged in a sheet-like pattern [9]. Malignancy was determined by application of the modified Weiss criteria for adrenal cortical neoplasms [10]. Among all 18 patients with OANs, 5 were benign and 13 were malig- nant. Of the patients with retrievable CT images, 4 were benign and 8 were malignant.
Patients with adrenocortical carcinomas (ACCs) were identified for comparison. Through a search of our institution’s imaging archives and the Endocrine Tumor Board pathology database, ten patients with pre-adre- nalectomy abdominal CT examinations and histologi- cally confirmed ACC were selected during the same time period. The patient population with ACCs consisted of 5 men and 5 women with a mean age at diagnosis of 47.1 years (range 24-68).
We reviewed the electronic medical records of these patients including clinical notes, radiology examinations, laboratory values, and pathology reports. Demograph- ics, including gender and age of presentation, were re- corded.
CT technique
Patients that had undergone a dedicated adrenal CT examination underwent a triphasic adrenal protocol CT consisting of (1) non-contrast (unenhanced), (2) post contrast at a 50-80-s delay (enhanced), and (3) 15-min delay (delayed contrast-enhanced) images. Studies per- formed at our institution used the following scan parameters: 120-140 kVp, variable mA, 1:1 pitch, 2.5 mm contiguous slices, and 4-, 8-, 16-, or 64-slice multi-detector CT [lightspeed QXI, lightspeed ultra, lightspeed 16, lightspeed VCT, HD 750 (all scanners:
| Type of adrenal lesion (No. of patients) | Sex | Mean age (years) | Side | Mean size (cm) | Heterogenous Calcifications | Internal hemorrhage | Internal necrosis | Presence of capsule | Venous invasion | Regional enlarged lymph nodes | Perilesional fat stranding |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Benign OAN (4) | 0M, 4F | 39.3 | 1R, 3L | 3.7 | 2 (50%) 0 | 0 | 2 (50%) | 2 (50%) | 0 | 0 | 0 |
| Malignant OAN (8) | 3M, 5F | 47.6 | 6R, 2L | 9.4 | 6 (75%) 2 (25%) | 1 (13%) | 6 (75%) | 5 (63%) | 0 | 1(13%) | 1 (13%) |
| Adrenocortical carcinoma (10) | 5M, 5F | 47.1 | 6R, 4L | 11.1 | 9 (90%) 6 (60%) | 0 | 7 (70%) | 6 (60%) | 4 (40%) | 4 (40%) | 2 (20%) |
OAN, oncocytic adrenal neoplasm; R, right; L, left
G.E. Healthcare, Waukesha, WI, USA)]. An intravenous bolus injection (100-150 mL) of low-osmolality contrast material (iopamidol 300, iohexol 300, or iopromide 300) was administered at a rate of 2-3 mL/s following the unenhanced scan, and post-contrast imaging was ob- tained at 1 and 15 min. Outside hospital studies were performed using a variety of protocols and scanner types using the following parameters: 100-140 kVp, variable mA, 1:1 pitch, and 2-5 mm contiguous slices. Contrast material type and dose information was not available for the outside studies.
Of the patients with OANs, 12 patients with CT imaging had abdominal contrast-enhanced CT images available within our imaging archives, and these were used for image analysis. Seven had undergone the dedi- cated adrenal protocol CT described. Four patients had undergone portal venous phase contrast-enhanced CT imaging, and one patient had undergone only delayed contrast-enhanced CT imaging. Of the ten patients with ACCs, two had undergone a dedicated adrenal protocol CT. One patient underwent portal venous phase and delayed contrast-enhanced CT. Two patients underwent unenhanced and portal venous phase imaging and five had undergone just portal venous phase imaging.
Imaging assessment
Two experienced genitourinary radiologists (EC, NRD) who were blinded to the radiology and pathology reports reviewed the images. The maximal diameter and location of each adrenal mass was recorded. The presence or ab- sence of heterogeneity, calcifications, internal hemor- rhage, internal necrosis (defined as areas of internal fluid attenuation), (pseudo)capsule formation, macroscopic venous invasion (renal vein and/or IVC), enlarged re- gional lymph nodes (>1 cm, short axis diameter), and perilesional fat stranding were assessed and documented. CT attenuation values were measured on images obtained during all available imaging phases with a circular region of interest, each of which covered one-half to two-thirds of the mass while avoiding partial volume effects. At least two measurements were obtained for each mass during each phase of imaging and the mean attenuation value was recorded. Calcifications were avoided. When the full adrenal protocol was available, absolute enhancement washout percentages were calculated using the following equation: percentage enhancement washout = [(enhancement attenuation value - delayed contrast en- hanced attenuation value)/(enhancement attenuation value - unenhanced attenuation value)] × 100. The threshold for benignity was ≥60% as established by pre- vious studies [12-14]. In the cases that included only portal venous and delayed phase CT imaging, relative washout percentages were calculated using the following equation: percentage relative washout = [(enhancement attenua- tion value - delayed contrast enhanced attenuation
value)/enhancement attenuation value] × 100. The threshold for benignity was ≥40% [12].
Statistical analysis
Descriptive statistics were used to summarize the data. Calculations were made using SAS software, Version 9.3 (SAS Institute Inc., Cary, NC, USA). The Fisher exact test was used to determine whether the presence of spe- cific imaging features was associated with the histologic diagnosis. For all analyses, p ≤ 0.05 was considered to indicate statistical significance. The mean attenuation values and the absolute percentage enhancement wash- outs for all masses were compared using the unpaired Student’s t test.
Results
Demographics (n = 18)
All five patients with benign adrenal oncocytomas were female, and the mean age at presentation was 45.6 years. Of the five patients with benign disease, two (40%) demonstrated unregulated hormone secretion, both with cortisol-secreting tumors (Fig. 1). In both patients, symptoms resolved after surgical resection of the tumors. None of the patients with benign histology had evidence of metastatic disease.
Of the 13 patients with malignant OANs, 6 were male and 7 were female and the mean age at presentation was 51.1 years. One (7.7%) of these patients had a hormone
secreting tumor. This was a 3-year-old female with viri- lizing symptoms and elevated DHEA and testosterone levels, which improved after resection of the mass. Of the 13 patients with malignant disease, 3 (23%) had evidence of metastases at the time of presentation.
Imaging assessment (n = 12)
Characteristics of the imaged adrenal masses are pro- vided in Table 1. Benign OANs were significantly smaller [mean 3.7 cm (range 2.6-5.3)] than malignant OANs [mean 9.4 cm (range 5.2 to 19.8), p < 0.001] and ACCs [mean 11.1 cm (range 4.8-21 cm), p < 0.001]. The malignant OANs were similar in size to ACCs (p = 0.46).
Eight of twelve (67%) OANs were heterogeneous (benign, n = 2/4; malignant, n = 6/8), whereas 90% (9/ 10) of the ACCs were heterogeneous. Seven of twelve (58%) OANs (benign, n = 2/4; malignant, n = 5/8) demonstrated a discernible pseudocapsule, while 6 of 10 ACCs showed this feature. Necrosis was a common feature in benign OANs (n = 2/4), malignant OANs (n = 6/8), and ACCs (n = 7/10) (Fig. 2). Calcifications were present in both malignant OANs (n = 2/8) and ACCs (n = 6/10), but were not seen in benign OANs (Fig. 3). Regional lymph node enlargement was associ- ated with both malignant OANs (n = 1/8) and ACCs (n = 4/10) but not benign OANs. Similarly, peri-lesional stranding and infiltrative margins were seen with both malignant OANs (n = 1/8) and ACCs (n = 2/10) but
not benign OANs. Venous invasion was evident only with ACCs (n = 4/10).
The mean unenhanced attenuation of the benign OANS (40 HU) was not significantly different than the malignant OANs (39 HU, p = 0.91) nor the ACCs (38 HU, p = 0.74). The mean contrast-enhanced attenua- tion of the benign OANs (98 HU) was significantly higher than both the malignant OANS (62 HU, p = 0.003) and ACCs (62 HU, p = 0.006). The mean delayed contrast-enhanced attenuation of the benign OANS (56 HU) was not significantly different than the malignant OANs (47 HU, p = 0.36) nor the ACCs (52 HU, p = 0.75).
A comparison of absolute washout for each type of adrenal mass is shown in Table 2. The percentage
| Type of adrenal lesion | Unenhanced | Portal venous | Delayed Average absolute enhancement washout percent (%) | |
|---|---|---|---|---|
| Benign OAN | 39.8 | 97.5 | 56.3 | 72 |
| Malignant OAN | 39 | 62 | 46.8 | 12 |
| Adrenocortical carcinoma | 37.8 | 62.2 | 52.33 | -2 |
OAN, oncocytic adrenal neoplasm
enhancement washout of benign OANs (72%) was sig- nificantly higher than that of malignant OANs (12%, p = 0.03) and ACCs (-2%, respectively; p = 0.03). The percentage enhancement washout of malignant OANs was not significantly different from ACCs (p = 0.23). A single malignant OAN demonstrated relative enhance- ment washout of -8%. A single malignant ACC dem- onstrated relative enhancement washout of -44%.
Discussion
Similar to other studies [5], the OANs in our study group were found predominantly in women (67%) with the mean age of discovery in the fourth and fifth decades. Two patients with benign oncocytomas and one patient with a malignant OAN showed evidence of hormonal hypersecretion which is higher than reported previously [11]. However, our patient population included only re- sected masses, conferring a bias toward symptomatic lesions.
Twenty-three percent of the malignant OANs in our study had metastatic disease at the time of presentation. This contrasts with a study by Tirkes et al. [5] in which the four malignant OANs in their dataset demonstrated no instances of metastatic disease. However, the inci- dence of metastases from malignant OANs in our study group is lower than the 39% incidence reported for ACCs by Ng and Libertano [15], suggesting that malignant OANs tend to have a more favorable prognosis than conventional ACCs as others have proposed [9].
Size is a feature often used to distinguish benign from malignant adrenal neoplasms. A diameter <5 cm suggests a benign lesion [2]. The size of the OANs in our study group supported this theory. The mean diameter of the oncocy- tomas was 3.7 cm (range 2.6-5.3) whereas the malignant OANs measured greater than 5 cm in diameter. This finding is unlike the results reported by Tirkes [5], where the mean diameter of their oncocytomas was 7.6 cm.
In our study group, benign oncocytomas were often homogeneous and lacked calcification or hemorrhage. Oncocytomas were not associated with venous invasion, enlarged regional lymph nodes, or perilesional fat stranding. Our benign OANs measured >10 HU on un- enhanced CT which is consistent with histologic findings that lipid content is not a distinguishing characteristic of an OAN. However, our oncocytomas demonstrated per- centage washout characteristics similar to benign adeno- mas. In this respect, the benign OANs in our dataset resembled lipid-poor adenomas [12, 13]. Therefore, it does not appear possible to distinguish lipid-poor adenomas from benign OANs using accepted washout criteria. For- tunately, both masses are benign, and therefore this overlap may not affect clinical management.
Malignant OANs and ACCs had overlapping CT imaging characteristics, including larger size, heterogeneity, and internal necrosis. Both populations in our study were
associated with a percentage enhancement washout <60% or relative percentage enhancement washout <40%, and regional lymph node enlargement. It would be difficult, if not impossible, to distinguish ACC from a malignant OAN on CT imaging except for the fact that none of the malignant OANs demonstrated venous invasion, a feature seen in 40% of ACCs in our study group.
The primary limitation of our study is its small sample size, which is a common obstacle when studying such a rare entity. Similar to other small studies, this limits the generalizability of our findings and we have already noted several clinical differences in our study group in comparison to others. Another limitation is that our analysis was retrospective and some of the imaging examinations we analyzed were performed at institutions other than our own allowing for a variety of protocols to be used. Another limitation is that given our findings, it is possible that there may have been oncocytomas that never were surgically excised and were treated as pre- sumed lipid-poor adenomas.
In conclusion, both benign and malignant OANs are rare tumors that may be hormonally active. Malignant OANs can be more aggressive than their benign coun- terparts, demonstrating metastases. On CT, benign adrenal OANs can mimic lipid-poor adenomas. Malig- nant OANs may be distinguished from benign OANs and adenomas based on their larger size, heterogeneity, and lower percentage enhancement washout. However, a larger number of cases are needed to confirm these conclusions and to better understand these adrenal tu- mors. Differentiation of malignant OANs vs. ACCs is difficult using CT imaging.
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