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Clinical Radiology
journal homepage: www.clinicalradiologyonline.net
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clinical ŘADÍOLOGY
Commentary
CT of the adrenal: Not just distinguishing non-adenoma versus adenoma
I. Vlahos*
Radiology Department, St George’s Hospital, London, UK
ARTICLE INFORMATION
Article history: Received 31 May 2011 Accepted 3 June 2011
The progressive evolution of multidetector computed tomography (CT) technology in parallel with the increased clinical utilization of CT has compelled the definition of imaging strategies for incidentally detected asymptomatic adrenal lesions. These small (<3 cm) “incidentalomas” are common, present in approximately 5-10% of abdominal examinations, and the vast majority are, of course, benign. Recent CT adrenal imaging research has largely revolved around algorithms for the discrimination of these lesions as benign adrenal adenomas or non-adenomas. Rather less emphasis has been placed on differentiating the aetiologies of non-adenomatous adrenal lesions. It is for this reason that the article by Zhang et al.1 in this issue of the Journal addressing the morphological and enhancement CT char- acteristics of adrenocortical carcinomas, one rarer subset of non-adenomatous lesions, is particularly welcome.
Adrenocortical carcinomas are a rare entity with an incidence of only 0.5-2 per million. Large case series are generally historical registry studies reflecting the manage- ment and outcome of these patients. The authors’ collection of 41 adrenocortical carcinomas is one of the largest radiological series to date focussing on their morphological features at CT. The imaging findings reported are in general harmony with earlier descriptions in smaller groups. As per
earlier reports, the vast majority of these lesions presented at over 6 cm in size and were heterogeneous in their attenuation and enhancement.2 All lesions demonstrated central areas of low attenuation and over a third exhibited punctuate calcification. Adding to the existing knowledge base is confirmation of the suspicion gleaned from anec- dotal case reports of the occasional incidence of mature fat within approximately 10% of lesions. In two cases there was histological confirmation that this was not due to a “colli- sion” lesion. This is important as the presence of intrinsic macroscopic “bulk” fat within a larger adrenal lesion has often been considered pathognomonic of the more indolent myelolipoma.
Where does this leave abdominal imagers with respect to determining the aetiology of a larger adrenal lesion? The differential for this type of lesion would usually include commoner lesions, such as atypical benign adenomas, or metastases, but also the rarer adrenal paragangliomas and adrenocortical carcinomas. The ubiquitous presence of central low attenuation in adrenocortical carcinomas can also occur in larger paragangliomas. Venous invasion is also reported in these two entities albeit more rarely in para- gangliomas. Disseminated metastatic adenocarcinoma may be difficult to differentiate from metastases from another source.
We are aware from several seminal studies that the extent of adrenal gland enhancement washout may assist in differentiating fat-poor benign adenomas from non- adenomas.3,4 Benign adenomas, irrespective of fat content,
DOI of original article: 10.1016/j.crad.2011.03.023.
* Guarantor and correspondent: I. Vlahos, St George’s Hospital London, Radiology Department, St. James’ Wing, Blackshaw Road, London SW17 OQT, UK. Tel .: +44 208 725 1160; fax: +44 208 725 2936.
E-mail address: ioannis.vlahos@stgeorges.nhs.uk
washout more rapidly. This adrenal lesion washout can either be expressed as an absolute washout (where the pre-contrast density is known) or a relative washout (where only a portal venous phase baseline is available). Adenomas are typically associated with >60% absolute washout and >40% relative washout.
Could enhancement be used as a discriminator between non-adenomatous lesions? Unfortunately the landmark studies comparing washout in adenomatous versus non- adenomatous lesions contained only token numbers of adrenocortical carcinomas. One subsequent study specifi- cally evaluating the reduced washout of adrenocortical carcinoma evaluated only seven patients.5 Szolar and colleagues6 evaluated 11 patients with adrenocortical carcinomas against a comparable collection of adrenal paragangliomas corroborating they had overlapping washout characteristics with metastases. Zhang et al. offer the largest series to date of washout evaluation in 17 patients. The mean absolute and relative washout values (50%, 27%) are slightly higher than previously recorded but do not significantly vary from prior reported values for other causes of non-adenomas. The authors rightly conclude that in general adrenocortical carcinoma washout values help differentiate these lesions from non-adenomas. However, it is noteworthy that five of the 17 lesions had absolute enhancement values, and three of the 17 had relative enhancement values, in the adenoma range. Contrary to prior studies the high-washout lesions were not the small minority of lesions <6 cm. These results should come as no surprise. A recent large study by Sangwaiya et al.7 indeed suggests that the accuracy of washout studies as a whole for discriminating adenomas may be lower than initially suspected. In the future it will be important to determine whether differences in technique (timing, contrast volume, washout thresholds) between adrenal washout investigators has a role to play. In the interim we are reminded that no single imaging test is absolute.
It is worthwhile remembering that isolated, larger, non- metastatic adrenal lesions (>6 cm) tend to be resected anyway because the likelihood of malignancy is relatively high. Both the current and prior adrenocortical imaging studies reflect presentation appearances; at this stage the vast majority of patients are symptomatic either due to endocrine dysfunction or local symptoms. As the ever pro- gressing trend to increased CT imaging utilization demon- strates no signs of abatement, the possibility of earlier incidental detection of asymptomatic adrenocortical carci- nomas smaller than 6 cm is a significant consideration. Differentiating patients where early biopsy or resection
should be considered rather than follow-up imaging is likely to become an increasingly problematic issue. In this group, extrapolating densitometric data predominantly acquired from series evaluating lesions <3 cm is likely hazardous, due to the expected atypia of larger benign lesions. The very limited data on washout in this subset, added to by the current study, are conflicting.
Could other functional imaging techniques help us with these or larger lesions? Limited experience with perfusion CT and dual-energy CT do not appear to-offer different evaluation parameters than unenhanced CT or washout evaluations. Positron-emission tomography (PET) imaging using [18F]-fluoro-2-deoxy-D-glucose to date is still largely limited to case series in adrenocortical carcinoma rather than differentiating adrenocortical carcinoma from other non-adenomatous lesions.8 PET-CT with other adrenocortical specific ligands based on markers for 11ß-hydroxylase is still in its infancy.9
In conclusion, it is perhaps ironic that the ever greater resolution of multidetector CT has enabled depiction of the adrenal gland with exquisite anatomic accuracy and yet larger lesions, visible with much earlier generations of CT, can still remain a diagnostic enigma.
References
1. Zhang H, Perrier ND, Grubbs EG, et al. CT features and quantification of the characteristics of adrenocortical carcinomas on unenhanced and contrast-enhanced studies. Clin Radiol, in this issue.
2. Fishman EK, Deutch BM, Hartman DS, et al. Primary adrenocortical carcinoma: CT evaluation with clinical correlation. AJR Am J Roentgenol 1987;148:531-5.
3. Korobkin M, Brodeur FJ, Francis IR, et al. CT time-attenuation washout curves of adrenal adenomas and nonadenomas. AJR Am J Roentgenol 1998;170:747-52.
4. Caoili EM, Korobkin M, Francis IR, et al. Adrenal masses: characterization with combined unenhanced and delayed enhanced CT. Radiology 2002; 222:629-33.
5. Slattery JM, Blake MA, Kalra MK, et al. Adrenocortical carcinoma: contrast washout characteristics on CT. AJR Am J Roentgenol 2006;187:W21-4.
6. Szolar DH, Korobkin M, Reittner P, et al. Adrenocortical carcinomas and adrenal pheochromocytomas: mass and enhancement loss evaluation at delayed contrast-enhanced CT. Radiology 2005;234:479-85.
7. Sangwaiya MJ, Boland GW, Cronin CG, et al. Incidental adrenal lesions: accuracy of characterization with contrast-enhanced washout multi- detector CT-10-minute delayed imaging protocol revisited in a large patient cohort. Radiology 2010;256:504-10.
8. Leboulleux S, Dromain C, Bonniaud G, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective comparison with computed tomography. J Clin Endocrinol Metab 2006;91:920-5.
9. Blake MA, Prakash P, Cronin CG. PET/CT for adrenal assessment. AJR Am J Roentgenol 2010; 195:W91-5.