Original Article Adrenal cortical adenoma with the maximal diameter greater than 5 cm: can they be differentiated from adrenal cortical carcinoma by CT?
Li Tian*, Jun Dong*, Yun-Xian Mo, Chun-Yan Cui, Wei Fan
Imaging Diagnosis and Interventional Center, Sun Yat-Sen University Cancer Center, State Key Laboratory of On- cology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of China. * Equal contributors.
Received August 15, 2014; Accepted September 20, 2014; Epub October 15, 2014; Published October 30, 2014
Abstract: To study the computed tomographic findings of adrenal adenoma with the maximal diameter greater than 5 cm and to discuss whether such tumor can be differentiated from adrenal carcinoma by CT examination. Fourteen consecutive patients with adrenal adenoma with the maximal diameter larger than 5 cm, proven pathologically, were enrolled. All patients underwent non-enhanced and contrast-enhanced CT examination. The CT findings, in- cluding size, shape, edge, density on non-enhanced CT and schedule of reinforcement after contrast administra- tion for each lesion were retrospectively analyzed. CT data of 13 patients with adrenocortical carcinoma were also evaluated to determine whether differentiating characteristics existed. The maximal diameter of the 14 masses of adenoma ranged from 5.5 cm to 20 cm (mean, 10 cm). One mass showed lobulated, the rest 13 masses showed rounded or ovoid. Eleven and 3 masses appeared well-circumscribed and ill-circumscribed, respectively. All of 14 masses presented heterogeneous density on non-enhanced CT images with patchy low-attenuation foci or stippled calcification. All of 14 masses revealed moderately to markedly heterogeneous enhancement after contrast admin- istration. None of 14 masses developed local invasion and distant metastasis. Except for recurrence, metastasis and venous tumor emboli which only occurred in the cases of adrenal carcinoma, no definite computed tomographic features could be found that enabled the identification of adenomas with the maximal diameter greater than 5 cm with adrenal carcinomas. The characteristic CT findings of adrenal adenoma with the maximal diameter greater than 5 cm include bulky, well-circumscribed, rounded or ovoid masses, heterogeneous attenuation with low-attenuation foci on non-enhanced CT images and heterogeneous enhancement after contrast administration. The differential diagnosis between such tumor and adrenal cortical carcinoma by CT examination is relatively difficult, such findings as recurrence, metastasis and venous tumor emboli may be of some significance.
Keywords: Adrenal cortical neoplasm, adenoma, carcinoma, diameter, computed tomography, differentiation
Introduction
Most adrenal adenomas have some character- istic radiologic findings: the maximal diameter of tumors are almost always less than 5 cm, relatively homogeneous, and display rapid and relatively uniform enhancement with rapid washout of iodinated or gadolinium-based con- trast material. In addition, they often reveal computed tomography (CT) and magnetic reso- nance (MR) imaging findings associated with intracellular lipid and almost never liquefy; cal- cification is very rare.
With reference to literatures [1-7], we define those adrenal adenomas whose maximal diam-
eters are more than 5 cm as large adenomas, whereas those adenomas with the maximal diameter less than or equal to 5 cm are defined as small adenomas. Compared with small ade- nomas, large adenomas are relatively rare.
On account of gigantic tumor and heteroge- neous attenuation on CT images, large adrenal adenomas are usually diagnosed as malignant entities by many radiologists, such as adrenal cortical carcinomas, which will influence clini- cians’ therapeutic decision-making and prog- nostic prediction. Hence, the purpose of this study was to analyze the computed tomograph- ic findings of 14 patients with large adrenal cor- tical adenoma, meanwhile, the CT data of 13
Diagnosis and differential diagnosis of large adrenal cortical adenoma by CT
| Case | Sex | Age | Clinical Manifestation | Pathologic Variant |
|---|---|---|---|---|
| 1 | Female | 45 | Hypertension, Headache, Obesity | Cortisol producing adenoma |
| 2 | Male | 10 | Hypertension, Headache, Obesity | Cortisol producing adenoma |
| 3 | Male | 68 | Hypertension, Headache | Cortisol producing adenoma |
| 4 | Female | 52 | Absence of symptoms | Non-functional adenoma |
| 5 | Female | 49 | Hypertension, Headache, Purple striae | Cortisol producing adenoma |
| 6 | Male | 54 | Absence of symptoms | Non-functional adenoma |
| 7 | Female | 48 | Absence of symptoms | Non-functional adenoma |
| 8 | Female | 70 | Hypertension, Headache, Purple striae | Cortisol producing adenoma |
| 9 | Male | 42 | Hypertension, Headache | Cortisol producing adenoma |
| 10 | Male | 50 | Hypertension, Headache, Obesity | Cortisol producing adenoma |
| 11 | Female | 35 | Menstrual disorder, Blushing | Cortisol producing adenoma |
| 12 | Male | 44 | Absence of symptoms | Non-functional adenoma |
| 13 | Male | 63 | Absence of symptoms | Non-functional adenoma |
| 14 | Female | 37 | Absence of symptoms | Non-functional adenoma |
| Case | Sex | Age | Clinical Manifestation | Clinical Outcome |
|---|---|---|---|---|
| 1 | Male | 52 | Hypertension, Adynamia, Nocturia | Uneventful after surgery |
| 2 | Male | 30 | Hypertension, Adynamia, Nocturia | Uneventful after surgery |
| 3 | Male | 16 | Feminization | Uneventful after surgery |
| 4 | Male | 72 | Abdominal pain; Abdominal distention | Uneventful after surgery |
| 5 | Female | 77 | Abdominal pain; Abdominal distention | Uneventful after surgery |
| 6 | Female | 57 | Hypertension, Obesity, Purple striae | Local recurrence |
| 7 | Male | 52 | Hypertension, Obesity | Local recurrence and celiac lymph node metastasis |
| 8 | Male | 77 | Hypertension, Headache, | With tumor thrombus into inferior vena cava |
| 9 | Female | 45 | Virilization | Local recurrence and pulmonary metastasis |
| 10 | Male | 49 | Hypertension, Headache, | Uneventful after surgery |
| 11 | Male | 60 | Hypertension, Adynamia, Nocturia | Uneventful after surgery |
| 12 | Female | 3 | Virilization | Uneventful after surgery |
| 13 | Female | 40 | Menstrual disorder, Blushing | Uneventful after surgery |
patients with adrenal carcinoma were also eval- uated so as to determine whether large adeno- ma can be differentiated from adrenocortical carcinoma by CT examination.
Materials and methods
Patients
This retrospective study was approved by our institutional review board, and informed con- sent was waived. Between January 2009 and July 2013, 18 consecutive patients who were diagnosed as adrenal cortical adenoma with the maximal diameter greater than 5 cm by CT examination were recruited. Four patients were
excluded because the pathologic diagnosis for these tumors were absent. Finally, 14 patients (7 men and 7 women; mean age 48 years, range 10-70 years) with definite pathological diagnosis were included in our study. Mean- while, 13 patients (8 men and 5 women; mean age 52 years, range 3-77 years) with adrenal cortical carcinoma, pathologically proven, were enrolled in our study.
Imaging protocol
All the 27 patients underwent non-enhanced and enhanced CT examination simultaneously. CT imaging was performed using a Brilliance TM16 (Philips Medical Systems, Best, The
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Netherlands) helical scanner with the following parameters: 5 mm slice thickness reconstruc- tions, 120 kV voltage, 200 mA current, and 256×256 matrix. After non-enhanced CT imag- ing, an intravenous bolus dose of 100 ml of a nonionic iodinated contrast agent (iopromide; Ultravist; Schering) was administered at a rate of 2.5 mL/s for the patients. Enhanced CT images were obtained at 60 s after the contrast agent injection.
Image assessment
Two radiologists who were experienced in per- forming CT of the adrenal glands and unaware of the clinical, surgical, pathologic results eval-
uated the CT images separately, any disagree- ments were resolved by consensus. The obser- vations included size, shape, edge, density on non-enhanced CT and schedule of reinforce- ment after contrast administration, and inva- sion of adjacent structure and distant metasta- sis of each mass. For each mass, the maximal cross section was selected and an ovoid or rounded ROI was placed in the center of the section to include as much of the cross-sec- tional area as possible but avoiding the outer- most edge (to prevent partial volume artifact). The same measurements were performed on enhanced CT images, and the ROIs were placed in the corresponding slices. The degree of enhancement after contrast administration of
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each mass was compared with that of the mus- cles in the lateral abdominal wall.
Results
Clinical data
Large adrenal adenoma group: The clinical data of the 14 patients are summarized in Table 1. There was no sex and age predilection on the incidence of large adrenal adenoma. Eight patients who were proved as cortisol pro- ducing adenoma mainly complained of hyper- tension and headache. Six patients who were proved as non-functional adenoma felt unevent- ful, who, actually, were detected adrenal mass incidentally during abdominal CT scan for other reasons.
Adrenal carcinoma group: The clinical data of the 13 patients are summarized in Table 2. There was no sex and age predilection on the
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incidence of adrenal carcinoma. Of the 13 patients, 11 manifested endocrine dysfunction including Cushing syndrome, virilization, femini- zation, hyperaldosteronism, 2 old patients com- plained of abdominal pain and abdominal distention.
CT findings
Large adrenal adenoma group: All the 14 large adenomas were unilateral and single, a total of 14 masses, 6 of which were on the left and the other 8 masses were on the right. The maximal diameter of the 14 masses ranged from 5.5 cm to 20 cm (mean, 10 cm), of those, the maximal diameter of the cortisol producing adenoma and non-functional adenoma ranged from 5.5 cm to 10 cm (mean, 8 cm) and 8 cm to 20 cm
(mean, 12 cm), respectively. One mass showed lobulated (Figure 1), the rest 13 masses showed rounded or ovoid (Figure 2). Eleven masses appeared well-circumscribed (Figure 2) and 3 masses appeared ill-circumscribed (Figure 3). All the 14 masses presented hetero- geneous density on non-enhanced CT images, 12 of which showed patchy low attenuation foci (Figure 4), 2 of which showed stippled calcifica- tion (Figure 5). After contrast administration, all the masses revealed moderately to markedly heterogeneous enhancement (Figure 6). None of the masses developed local invasion and distant metastasis.
Adrenal carcinoma group: All the 13 adrenal carcinomas were unilateral and single, a total of 13 masses, 7 of which were on the left and
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the other 6 masses were on the right. The maxi- mal diameters of 13 masses ranged from 5.5 cm to 12 cm (mean, 8 cm). Three masses showed lobulated, the rest 10 masses showed rounded or ovoid (Figure 7). Seven masses appeared ill-circumscribed and 6 masses appeared well-circumscribed. All the 13 mass- es presented heterogeneous density on non- enhanced CT images, 12 of which showed patchy low attenuation foci (Figure 8), 3 of which showed stippled calcification. After con- trast administration, all the masses revealed heterogeneous enhancement (Figure 8). Three, two and one patient developed recurrence after surgery (Figure 9), distant metastasis and
tumor thrombus into inferior vena cava (Figure 10), respectively.
Computed tomographic features that permit- ted confident differentiation between adeno- mas and carcinomas were found in 4 cases. Recurrence after surgery, metastases and tumor thrombus were present only in patients with carcinomas.
Discussion
Adrenal adenomas with the maximal diameter greater than 5 cm are benign entities originat- ing from adrenal cortex and are considerably rare clinically. Because of gigantic mass and heterogeneous density on CT image, such tumors are more likely diagnosed as malignan- cies such as adrenal cortical carcinomas which usually confuse most surgeons due to the dif- ferent treatment and prognosis for both tumors. Therefore, it is necessary to investigate the CT findings of large adrenal adenomas and deter- mine whether differentiation of these lesions from adrenal carcinomas can be made by means of preoperative CT imaging.
With regard to the age of onset and sex of patients with large adrenal adenoma, there was no specificity in our study group, which was consistent with previous reports [1-7]. Clinically, most of 8 patients with cortisol producing ade- noma complained of hypertension and head- ache, while all the 6 patients with non-function- al adenoma didn’t feel any unwell. Due to absence of symptoms, non-functional adeno- mas usually develop larger masses than do cor-
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tisol producing adenomas when they are de- tected (mean maximal diameter of 12 cm of non-functional adenomas versus that of 8 cm of cortisol producing adenomas in our study group). On the other hand, this sign implies that large adrenal cortisol producing adenomas should be considered when the patients with adrenal masses complain of hypertension and headache without obvious motivation.
There were 14 large adrenal cortical adenomas in our study. Except one mass revealed lobu- lated, the rest 13 masses (93%, 13/14) reve- aled rounded or ovoid, and 11 masses (79%, 11/14) showed well-circumscribed, which sug- gested that the large adrenal adenoma grew relatively slowly and regularly and confirmed their non-invasive growth pattern. On the other hand, of the 13 cases of adrenal carcinoma, 10 (77%, 10/13) presented round or ovoid, and six (46%, 6/13) revealed well-circumscribed. There- fore, the shape and edge of mass are of no sig- nificant meaning for identification of both entities.
In our study series, all the 14 large adrenal ade- nomas presented heterogeneous attenuation on non-enhanced CT images, 12 (86%, 12/14) of which showed patchy low attenuation foci. After contrast administration, all the 14 mass- es showed moderately to markedly heteroge- neous enhancement. According to reports in the literature [6, 8], the low-attenuation foci may represent cystic degeneration within the lesions. Newhouse JH et al [6] reported 30 patients with large adrenal adenoma, 17 of which appeared complete or partial cystic degeneration. Masugi Y et al [8] also reported
one patient with large adrenal adenoma which appeared extensive cystic degeneration. Also, other related documents [9, 10] reported that large adrenal adenoma was more likely to develop cystic degeneration. As for this point, our results are in accordance with literature report. We speculate that large adrenal tumors easily become ischemic and anoxic, and the ischemic and anoxic regions develop cystic degeneration eventually. However, in this study, 12 (92%, 12/13) masses of cortical carcinoma also manifested patchy low attenuation foci possibly representing necrotic lesions, which made the identification of large adenoma with cortical carcinoma quite difficult.
Only 2 (14%, 2/14) masses of large adenoma and 3 (23%, 3/13) masses of cortical carcino- ma showed stippled calcification, respectively. Because of small sample size, we don’t think the occurrence of calcification is helpful for the diagnosis of both large adrenal cortical adeno- ma and cortical carcinoma.
None of the large adrenal adenomas developed local invasion and distant metastasis on CT images, while three, two and one patient with cortical carcinoma developed recurrence after surgery, distant metastasis and tumor throm- bus into inferior vena cava, respectively. These results indicated the benign and malignant bio- logic behaviour of large adenoma and cortical carcinoma, respectively, and, this finding was the only valuable identification between large adenoma and cortical carcinoma.
A potential limitation of the present study is the small sample size analyzed here, which may
Diagnosis and differential diagnosis of large adrenal cortical adenoma by CT
lead to lack of certain CT findings of large ade- noma. For example, according to some docu- mentary literature [11-14], large adrenal lesion, no matter benign or malignant, may be prone to developing internal hemorrhage, while in this study cohort, no hemorrhage was detected in both large adenoma and cortical carcinoma. Therefore, we look forward to collecting more cases in the future so as to discuss this issue.
Conclusion
To sum up, the characteristic CT findings of adrenal cortical adenoma with the maximal diameter greater than 5 cm include bulky, well- circumscribed mass with rounded or ovoid shape, heterogeneous attenuation with low- attenuation foci on non-enhanced CT images and moderately to markedly heterogeneous enhancement after contrast administration. The tumor scarcely develops local invasion and distant metastasis. Such findings as recur- rence, metastasis and venous tumor emboli are of some significance to the differential diag- nosis between large adrenal adenoma and cor- tical carcinoma, while the exact identification of both lesions depends on pathological examina- tion [15].
Disclosure of conflict of interest
None.
Address correspondence to: Dr. Wei Fan, Depar- tment of Nuclear Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guang- zhou 510060, Guangdong, People’s Republic of China. Tel: +86-20-87343049; Fax: +86-20-8734- 3049; E-mail: fanwei_9798@163.com
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