CT imaging characteristics of oncocytic adrenalneoplasms (OANs): comparison withadrenocortical 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, USA2Oakland University William Beaumont School of Medicine, 2200 Squirrel Road, Rochester, MI 48309, USA3University of Michigan Health System, 1301 Catherine Blvd., Ann Arbor, MI 48109, USA

Abstract

Objective: Oncocytic adrenal neoplasms (OANs) arerare, but are an important subtype of adrenal tumorsthat is being diagnosed with increasing frequency.Unfortunately, the imaging characteristics of this tumorhave not been well described. Our purpose was toidentify CT features to differentiate OANs from adre-nocortical carcinomas (ACC).Materials and methods: From 1991 to 2012, 18 patientswith OANs were identified from our institution’s pathol-ogy database. Twelve had CT examinations available forreview. CT characteristics of five benign and sevenmalignant OANs were reviewed by two abdominalradiologists, and compared to ACC (n = 10). Morpho-logic characteristics and density measurements wererecorded for each imaging phase. Absolute contrastwashout was calculated and compared.Results: Benign OANs were smaller [mean size 3.7 cm(range 2.6–5.3)] and more homogeneous than malignantOANs and demonstrated greater washout [mean wash-out percentage 72.3% (range 61–88)]. Malignant OANsdemonstrated features similar to ACCs, including size[mean 9.4 cm (range 5.2–9.8)] and internal necrosis(n = 6). Mean enhancement washout percentage formalignant OANs was 12% (range -8 to 32).Conclusion: Benign OANs (oncocytomas) may be distin-guished from lipid-rich adenomas on non-contrast CTbut may be indistinguishable from lipid-poor adenomas.Malignant oncocytic neoplasms can demonstrate fea-

tures similar to ACCs, including larger size, internalnecrosis, and lower percentage enhancement washout.

Key words: Adrenal gland—Adrenal corticalcarcinoma—CT

Adrenal masses are commonly found on abdominal CTexaminations [1–3]. While most are benign adenomas,additional testing is sometimes required to exclude le-sions that require treatment. Oncocytic neoplasms havebeen described in many organs, including the kidney,salivary gland, thyroid gland, and parathyroid gland [4].Oncocytic neoplasms of the adrenal gland are rare, withfewer than 100 cases documented in the literature [5–8].Histologically, oncocytic adrenal neoplasms (OANs)demonstrate >75% oncocytes—epithelial cells withabundant granular eosinophilic cytoplasm [9]. OANsmay be benign (oncocytomas) or malignant and thedistinction is made histologically using the modifiedWeiss criteria [10]. Unlike adrenal adenomas, adrenaloncocytomas rarely produce unregulated amounts ofhormone [11]. Furthermore, malignant OANs have amore favorable prognosis than adrenocortical carcino-mas (ACCs) [9] and thus are important to identify.

The largest published study of the imaging features ofOANs includes nine patients who underwent CT of theabdomen of which only one underwent both an unen-hanced and enhanced CT imaging [5]. However, nostudy, to our knowledge, has compared the imagingfeatures of OANs with ACCs. The purpose of our studywas to assess the CT imaging characteristics of OANsand to determine whether they could be differentiatednoninvasively.Correspondence to: Elaine M. Caoili; email: caoili@umich.edu

ª Springer Science+Business Media New York 2013

Published online: 24 November 2013AbdominalImaging

Abdom Imaging (2014) 39:86–91

DOI: 10.1007/s00261-013-0047-z

Materials and methods

Subjects

Prior to the initiation of this investigation, InstitutionalReview Board approval was obtained and the study wascarried out in compliance with the Health InsurancePortability and Accountability Act (HIPAA, USA). Pa-tient informed written consent was waived based on theretrospective nature of the study.

Over a 21-year period from 1991 through 2012, theEndocrine Tumor Board pathology database was sear-ched, yielding 18 patients with OANs (Table 1) based onpathology results. There were 6 males and 12 femaleswith a mean age at diagnosis of 49.6 years (range 3–74).Of these patients, 12 had retrievable digital CT imagesavailable. In all but one patient, a single adrenal masswas identified. In the patient with two adrenal masses,only the dominant mass was included. All neoplasmsincluded in our study were surgically excised. OANs werehistologically characterized by the predominance (‡75%

of the lesion) of oncocytes: epithelial cells containing asignificant amount of granular eosinophilic cytoplasmusually arranged in a sheet-like pattern [9]. Malignancywas determined by application of the modified Weisscriteria for adrenal cortical neoplasms [10]. Among all 18patients with OANs, 5 were benign and 13 were malig-nant. Of the patients with retrievable CT images, 4 werebenign and 8 were malignant.

Patients with adrenocortical carcinomas (ACCs) wereidentified for comparison. Through a search of ourinstitution’s imaging archives and the Endocrine TumorBoard pathology database, ten patients with pre-adre-nalectomy abdominal CT examinations and histologi-cally confirmed ACC were selected during the same timeperiod. The patient population with ACCs consisted of 5men and 5 women with a mean age at diagnosis of47.1 years (range 24–68).

We reviewed the electronic medical records of thesepatients 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 CTexamination underwent a triphasic adrenal protocol CTconsisting of (1) non-contrast (unenhanced), (2) postcontrast at a 50–80-s delay (enhanced), and (3) 15-mindelay (delayed contrast-enhanced) images. Studies per-formed at our institution used the following scanparameters: 120–140 kVp, variable mA, 1:1 pitch,2.5 mm contiguous slices, and 4-, 8-, 16-, or 64-slicemulti-detector CT [lightspeed QXI, lightspeed ultra,lightspeed 16, lightspeed VCT, HD 750 (all scanners: T

able

1.Characteristics

oftheim

aged

adrenalneoplasm

s

Typeofadrenal

lesion(N

o.of

patients)

Sex

Meanage

(years)

Side

Mean

size

(cm)

Heterogenous

Calcifications

Internal

hem

orrhage

Internal

necrosis

Presence

ofcapsule

Venous

invasion

Regional

enlarged

lymph

nodes

Perilesional

fatstranding

BenignOAN

(4)

0M,4F

39.3

1R,3L

3.7

2(50%)

00

2(50%)

2(50%)

00

0MalignantOAN

(8)

3M,5F

47.6

6R,2L

9.4

6(75%)

2(25%)

1(13%)

6(75%)

5(63%)

01(13%)

1(13%)

Adrenocorticalcarcinoma(10)

5M,5F

47.1

6R,4L

11.1

9(90%)

6(60%)

07(70%)

6(60%)

4(40

%)

4(40%)

2(20%)

OAN,oncocyticadrenalneoplasm

;R,right;L,left

M. Khan et al.: CT imaging characteristics of OANs 87

G.E. Healthcare, Waukesha, WI, USA)]. An intravenousbolus injection (100–150 mL) of low-osmolality contrastmaterial (iopamidol 300, iohexol 300, or iopromide 300)was administered at a rate of 2–3 mL/s following theunenhanced scan, and post-contrast imaging was ob-tained at 1 and 15 min. Outside hospital studies wereperformed using a variety of protocols and scanner typesusing the following parameters: 100–140 kVp, variablemA, 1:1 pitch, and 2–5 mm contiguous slices. Contrastmaterial type and dose information was not available forthe outside studies.

Of the patients with OANs, 12 patients with CTimaging had abdominal contrast-enhanced CT imagesavailable within our imaging archives, and these wereused for image analysis. Seven had undergone the dedi-cated adrenal protocol CT described. Four patients hadundergone portal venous phase contrast-enhanced CTimaging, and one patient had undergone only delayedcontrast-enhanced CT imaging. Of the ten patients withACCs, two had undergone a dedicated adrenal protocolCT. One patient underwent portal venous phase anddelayed contrast-enhanced CT. Two patients underwentunenhanced and portal venous phase imaging and fivehad undergone just portal venous phase imaging.

Imaging assessment

Two experienced genitourinary radiologists (EC, NRD)who were blinded to the radiology and pathology reportsreviewed the images. The maximal diameter and locationof each adrenal mass was recorded. The presence or ab-sence of heterogeneity, calcifications, internal hemor-rhage, internal necrosis (defined as areas of internal fluidattenuation), (pseudo)capsule formation, macroscopicvenous invasion (renal vein and/or IVC), enlarged re-gional lymph nodes (>1 cm, short axis diameter), andperilesional fat stranding were assessed and documented.CT attenuation values were measured on images obtainedduring all available imaging phases with a circular regionof interest, each of which covered one-half to two-thirds ofthe mass while avoiding partial volume effects. At leasttwo measurements were obtained for each mass duringeach phase of imaging and themean attenuation value wasrecorded. Calcifications were avoided. When the fulladrenal protocol was available, absolute enhancementwashout percentages were calculated using the followingequation: percentage enhancement washout =[(enhancement attenuation value - delayed contrast en-hanced attenuation value)/(enhancement attenuationvalue - unenhanced attenuation value)] 9 100. Thethreshold for benignity was ‡60% as established by pre-vious studies [12–14]. In the cases that included only portalvenous and delayed phase CT imaging, relative washoutpercentages were calculated using the following equation:percentage relative washout = [(enhancement attenua-tion value - delayed contrast enhanced attenuation

value)/enhancement attenuation value] 9 100. Thethreshold 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 exacttest was used to determine whether the presence of spe-cific imaging features was associated with the histologicdiagnosis. For all analyses, p £ 0.05 was considered toindicate statistical significance. The mean attenuationvalues and the absolute percentage enhancement wash-outs for all masses were compared using the unpairedStudent’s t test.

Results

Demographics (n = 18)

All five patients with benign adrenal oncocytomas werefemale, and the mean age at presentation was 45.6 years.Of the five patients with benign disease, two (40%)demonstrated unregulated hormone secretion, both withcortisol-secreting tumors (Fig. 1). In both patients,symptoms resolved after surgical resection of the tumors.None of the patients with benign histology had evidenceof metastatic disease.

Of the 13 patients with malignant OANs, 6 were maleand 7 were female and the mean age at presentation was51.1 years. One (7.7%) of these patients had a hormone

Fig. 1. 25-year-old female with a clinical diagnosis ofCushing’s syndrome and a pathologically proven benignoncocytic adrenal neoplasm. Contrast-enhanced CT shows ahomogenously enhancing, well-circumscribed 2.6 cm masswithin the left adrenal gland (white arrow).

88 M. Khan et al.: CT imaging characteristics of OANs

secreting tumor. This was a 3-year-old female with viri-lizing symptoms and elevated DHEA and testosteronelevels, which improved after resection of the mass. Of the13 patients with malignant disease, 3 (23%) had evidenceof 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]. Themalignant 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 10ACCs showed this feature. Necrosis was a commonfeature in benign OANs (n = 2/4), malignant OANs(n = 6/8), and ACCs (n = 7/10) (Fig. 2). Calcificationswere present in both malignant OANs (n = 2/8) andACCs (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-lesionalstranding and infiltrative margins were seen with bothmalignant OANs (n = 1/8) and ACCs (n = 2/10) but

not benign OANs. Venous invasion was evident onlywith ACCs (n = 4/10).

The mean unenhanced attenuation of the benignOANs (40 HU) was not significantly different than themalignant OANs (39 HU, p = 0.91) nor the ACCs (38HU, p = 0.74). The mean contrast-enhanced attenua-tion of the benign OANs (98 HU) was significantlyhigher than both the malignant OANs (62 HU,p = 0.003) and ACCs (62 HU, p = 0.006). The meandelayed contrast-enhanced attenuation of the benignOANs (56 HU) was not significantly different than themalignant OANs (47 HU, p = 0.36) nor the ACCs (52HU, p = 0.75).

A comparison of absolute washout for each type ofadrenal mass is shown in Table 2. The percentage

Table 2. Mean attenuation values of imaged adrenal masses

Type of adrenallesion

Unenhanced Portalvenous

Delayed Averageabsoluteenhancementwashoutpercent (%)

Benign OAN 39.8 97.5 56.3 72Malignant OAN 39 62 46.8 12Adrenocortical carcinoma 37.8 62.2 52.33 -2

OAN, oncocytic adrenal neoplasm

Fig. 2. 52-year-old female with a malignant OAN. Contrast-enhanced CT shows a heterogeneous 6.9 cm right adrenalgland mass with internal low attenuation (16 HU) consistentwith necrosis (asterisk).

Fig. 3. 56-year-old male with a malignant OAN. Contrast-enhanced CT shows a 19.8 cm heterogeneous left adrenalmass with internal necrosis (asterisk) and areas of calcifica-tion (white arrow).

M. Khan et al.: CT imaging characteristics of OANs 89

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). Thepercentage enhancement washout of malignant OANswas not significantly different from ACCs (p = 0.23). Asingle 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 groupwere found predominantly in women (67%) with themean age of discovery in the fourth and fifth decades.Two patients with benign oncocytomas and one patientwith a malignant OAN showed evidence of hormonalhypersecretion which is higher than reported previously[11]. However, our patient population included only re-sected masses, conferring a bias toward symptomaticlesions.

Twenty-three percent of the malignant OANs in ourstudy had metastatic disease at the time of presentation.This contrasts with a study by Tirkes et al. [5] in whichthe four malignant OANs in their dataset demonstratedno instances of metastatic disease. However, the inci-dence of metastases from malignant OANs in our studygroup is lower than the 39% incidence reported for ACCsby Ng and Libertano [15], suggesting that malignantOANs tend to have a more favorable prognosis thanconventional ACCs as others have proposed [9].

Size is a feature often used to distinguish benign frommalignant adrenal neoplasms. A diameter <5 cm suggestsa benign lesion [2]. The size of theOANs in our study groupsupported this theory. The mean diameter of the oncocy-tomas was 3.7 cm (range 2.6–5.3) whereas the malignantOANs measured greater than 5 cm in diameter. Thisfinding is unlike the results reportedbyTirkes [5], where themean diameter of their oncocytomas was 7.6 cm.

In our study group, benign oncocytomas were oftenhomogeneous and lacked calcification or hemorrhage.Oncocytomas were not associated with venous invasion,enlarged regional lymph nodes, or perilesional fatstranding. Our benign OANs measured >10 HU on un-enhanced CT which is consistent with histologic findingsthat lipid content is not a distinguishing characteristic ofan OAN. However, our oncocytomas demonstrated per-centage washout characteristics similar to benign adeno-mas. In this respect, the benign OANs in our datasetresembled lipid-poor adenomas [12, 13]. Therefore, it doesnot appear possible to distinguish lipid-poor adenomasfrom benign OANs using accepted washout criteria. For-tunately, both masses are benign, and therefore thisoverlap may not affect clinical management.

Malignant OANs and ACCs had overlapping CTimaging 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%, andregional lymph node enlargement. It would be difficult, ifnot impossible, to distinguish ACC from amalignant OANonCT imaging except for the fact thatnoneof themalignantOANs 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 studyingsuch a rare entity. Similar to other small studies, thislimits the generalizability of our findings and we havealready noted several clinical differences in our studygroup in comparison to others. Another limitation is thatour analysis was retrospective and some of the imagingexaminations we analyzed were performed at institutionsother than our own allowing for a variety of protocols tobe used. Another limitation is that given our findings, itis possible that there may have been oncocytomas thatnever were surgically excised and were treated as pre-sumed lipid-poor adenomas.

In conclusion, both benign and malignant OANs arerare tumors that may be hormonally active. MalignantOANs can be more aggressive than their benign coun-terparts, demonstrating metastases. On CT, benignadrenal OANs can mimic lipid-poor adenomas. Malig-nant OANs may be distinguished from benign OANsand adenomas based on their larger size, heterogeneity,and lower percentage enhancement washout. However, alarger number of cases are needed to confirm theseconclusions and to better understand these adrenal tu-mors. Differentiation of malignant OANs vs. ACCs isdifficult using CT imaging.

References

1. Dunnick NR (1990) Adrenal imaging: current status. AJR 154:927–936

2. Dunnick NR, Korobkin M (2002) Imaging of adrenal inciden-talomas: current status. AJR 179:559–568

3. Boland GW, Blake MA, Hahn PF, et al. (2008) Incidental adrenallesions: principles, techniques, and algorithms for imaging charac-terization. Radiology 249:756–775

4. Baloch Z, LiVolsi VA (1999) Oncocytic lesions of the neuroendo-crine system. Semin Diagn Pathol 16:190–199

5. Tirkes T, Gokaslan T, McCrea J, et al. (2011) Oncocytic neoplasmsof the adrenal gland. AJR 196:592–596

6. Gandras EJ, Schwartz LH, Panicek DM, et al. (1996) Case report:adrenocortical oncocytoma—CT and MRI findings. J ComputAssist Tomogr 20:407–409

7. Poretti D, Mazzarol G, Bonomo G, et al. (2003) Adrenocorticaloncocytoma: case report. Clin Imaging 27:426–430

8. Shah RK, Oto A, Ozkan OS, et al. (2004) Adrenal oncocytoma: USand CT findings. JBR-BTR 87:180–182

9. Wong DD, Spagnolo DV, Bisceglia M, et al. (2011) Oncocyticadrenocortical neoplasms—a clinicopathologic study of 13 newcases emphasizing the importance of their recognition. Hum Pathol42:489–499

10. Bisceglia M, Ludovico O, Di Mattia A, et al. (2004) Adrenocorticaloncocytic tumors: report of 10 cases and review of the literature. IntJ Surg Pathol 12:231–243

11. Hoang MP, Ayala AG, Albores-Saavedra J (2002) Oncocyticadrenocortical carcinoma: a morphologic, immunohistochemicaland ultrastructural study of four cases. Mod Pathol 15:973–978

90 M. Khan et al.: CT imaging characteristics of OANs

12. Caoili EM, Korobkin M, Francis IR, et al. (2002) Adrenal masses:characterization with combined unenhanced and delayed enhancedCT. Radiology 222:629–633

13. Korobkin M, Brodeur FJ, Yutzy GG, et al. (1996) Differential ofadrenal adenomas from nonadenomas using CT attenuation values.AJR 166:531–536

14. Blake MA, Kalra MK, Sweeney AT, et al. (2006) Distin-guishing benign from malignant adrenal masses: multi-detectorrow CT protocol with 10-min delay. Radiology 238:578–585

15. Ng L, Libertino JM (2003) Adrenocortical carcinoma: diagnosis,evaluation and treatment. J Urol 169:5–11

M. Khan et al.: CT imaging characteristics of OANs 91