myxomas, cutaneous myxomas, testicular tumors, and other endocrine neoplasms. Beckwith-Wiedemann Syndrome. Beckwith-Wiedemann syndrome is a con-.
G e n i t o u r i n a r y I m a g i n g • R ev i ew Bharwani et al. CT and MRI of Adrenocortical Carcinoma
FOCUS ON:
Genitourinary Imaging Review
Nishat Bharwani1 Andrea G. Rockall1 Anju Sahdev1 Maria Gueorguiev 2 William Drake 2 Ashley B. Grossman2 Rodney H. Reznek1 Bharwani N, Rockall AG, Sahdev A, et al.
Adrenocortical Carcinoma: The Range of Appearances on CT and MRI OBJECTIVE. Adrenocortical carcinoma (ACC) is a rare, aggressive tumor arising from the adrenal cortex that typically presents late with a large mass. The increased use of crosssectional imaging for unrelated reasons has led to a greater number of ACCs being detected incidentally at an earlier stage. Recognition of the typical clinical, biochemical, and imaging findings is imperative for rapid diagnosis, prompt intervention, and early use of the appropriate therapy. CONCLUSION. Cross-sectional imaging with CT and MRI is essential for determining the extent of local and distant tumor spread. Complete surgical resection is currently the only potentially curative treatment of ACC, and the information attained from CT and MRI is important to guide surgery and further patient management.
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Keywords: adrenal gland, adrenal neoplasms, adrenocortical carcinoma, CT, MRI DOI:10.2214/AJR.10.5540 Received August 11, 2010; accepted after revision November 2, 2010. 1 Imaging Department, St. Bartholomew’s Hospital, King George V Wing, Ground Fl, Room 3 West Smithfield, London EC1A 7BE, United Kingdom. Address correspondence to N. Bharwani. 2
Department of Endocrinology, Barts & The London NHS Trust, London, United Kingdom. CME This article is available for CME credit. See www.arrs.org for more information. WEB This is a Web exclusive article. AJR 2011; 196:W706–W714 0361–803X/11/1966–W706 © American Roentgen Ray Society
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drenocortical carcinoma (ACC) is a rare, aggressive tumor arising from the adrenal cortex that typically presents late with a large mass. The increased use of cross-sectional imaging for unrelated reasons has led to a greater number of ACCs being detected incidentally at an earlier stage. Recognition of the typical clinical, biochemical, and imaging findings is imperative for rapid diagnosis, prompt intervention, and early use of the appropriate therapy. Cross-sectional imaging with CT and MRI is essential for determining the extent of local and distant tumor spread. Complete surgical resection is currently the only potentially curative treatment of ACC, and the information attained from CT and MRI is important to guide surgery and further patient treatment. Epidemiology ACCs account for only 0.05–0.2% of all cancers [1, 2] or 1–2 patients per 1 million population per year [3]. The age distribution of the affected population is bimodal, with an increased incidence in infants and children younger than 5 years old and in individuals in their fourth and fifth decades of life [4, 5]. A female preponderance has been noted [2, 3], and women are more likely than men to present with more well-differentiated tumors that tend to be functional [6].
Cause Most ACCs are sporadic; however, they also can be associated with several complex genetic syndromes. Li-Fraumeni Cancer Syndrome Li-Fraumeni cancer syndrome results in a familial susceptibility to a variety of cancers including adrenocortical tumors (carcinomas, adenomas), sarcomas, leukemias, breast, brain, lung, and laryngeal cancers because of a germline TP53 mutation. Carney Complex Carney complex consists of primary pigmented nodular adrenal dysplasia, cardiac myxomas, cutaneous myxomas, testicular tumors, and other endocrine neoplasms. Beckwith-Wiedemann Syndrome Beckwith-Wiedemann syndrome is a congenital disorder characterized by pre- and postnatal overgrowth, macroglossia, and anterior abdominal wall defects (most commonly exomphalos). Familial Adenomatous Polyposis Coli Familial adenomatous polyposis coli causes multiple adenomatous polyps and cancer of the colon and rectum, thyroid tumors, hepatoblastoma, and adrenocortical tumors (carcinomas, adenomas).
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CT and MRI of Adrenocortical Carcinoma Multiple Endocrine Neoplasia, Type 1 Multiple endocrine neoplasia, type 1, causes pituitary, parathyroid, and pancreatic tumors; adrenocortical adenomas or hyperplasia; and, very rarely, adrenocortical carcinomas. Clinical and Biochemical Features ACCs are functional in approximately 60% of cases [4, 5, 7, 8], more commonly in children (? 85%) than in adults (15–30%) [4, 7]. Unlike adrenal adenomas that predominantly secrete cortisol, ACCs secrete a variety of hormones including androgens, cortisol, estrogens, and aldosterone [1]. In adult patients with functioning tumors, 30% present with Cushing syndrome, 20% with virilization, and 10–20% with a combination of the two [1, 8]. Feminization and hyperaldosteronism are much rarer, each accounting for approximately 2% of ACC cases [8]. The rapid onset of Cushing syndrome, often with virilizing features, is characteristic of ACC in adults [9]. Although benign adrenocortical tumors tend to secrete a single class of steroid, ACC can secrete various types; cosecretion of cortisol with androgens is a frequent combination and is highly suggestive of malignancy [3, 10–12]. In children, ACCs can present with virilization, Cushing syndrome, feminization, or Conn syndrome [1]. Approximately 65–85% of ACCs in adults are nonfunctioning, and patients present with a large mass and symptoms related to mass effect (e.g., abdominal or flank pain in 55%) [7] or with a palpable mass (40–50%) [1, 7]. Some ACCs are discovered incidentally (0–25%) when they tend to be smaller [2, 13]. Due to the late presentation of nonfunctioning tumors, a significant proportion (~ 30% of ACC cases) presents with metastatic disease to the regional and paraaortic lymph nodes, lung, liver, and bone [7, 12]. Pathologic Features Separating benign from malignant adrenal cortical neoplasms is not always possible on the basis of histologic findings alone, particularly from biopsy specimens [2, 14]; however, there are macroscopic and microscopic criteria that favor malignancy [14–17]. Macroscopic Criteria The macroscopic criteria that favor malignancy are tumor wet weight of greater than 500 g; a tumor with a grossly lobulated cut surface; and the presence of necrotic areas, calcification, or hemorrhage in the tumor.
Microscopic Criteria The microscopic criteria that favor malignancy are architectural disarray, mitotic rate, marked nuclear pleomorphism, nuclear atypia, hyperchromasia, capsular invasion, and venous or sinusoidal invasion. The mitotic rate is also important for predicting tumor aggressiveness. Staging The most widely used staging system for ACC was proposed by the American Joint Committee on Cancer and the International Union Against Cancer (UICC) and uses the TNM principle [18, 19] (Tables 1 and 2). This system is based largely on earlier classification systems proposed by MacFarlane [20] and modified by Sullivan and colleagues [21]. In recent evaluations, authors have suggested that there are significant limitations in the prognostic accuracy of the UICC system [22, 23], and a new system, the European Network for the Study of Adrenal Tumors (ENSAT) classification, has been proposed [22]. According to the ENSAT system, stage III disease is defined as the presence of positive lymph nodes, infiltration of the surrounding tissues, or venous tumor thrombus, and stage IV disease is restricted to patients with distant metastases. Imaging Appearances The presence of metastatic disease is definitive of malignancy [24]. However, several imaging features should increase the suspicion of
ACC within an adrenal mass [1, 25–27]: tumor size greater than 4 cm, irregular tumor margins, central intratumoral necrosis or hemorrhage, heterogeneous enhancement, invasion into adjacent structures, venous extension (renal vein or inferior vena cava [IVC]), and calcification. Using a logistic regression model, Hussain et al. [25] found tumor size of greater than 4 cm and heterogeneous enhancement to be the most important discriminators of malignancy. ACCs are usually large at presentation, ranging from 2 to 25 cm (average size, approximately 9 cm). Approximately 70% of ACCs are larger than 6 cm [24] (Figs. 1–3). They are bilateral in 2–10% of cases [2] and are slightly more common on the left than on the right [4]. Tumors are frequently hemorrhagic (Fig. 1) and necrotic [24, 28] (Fig. 2) and may contain small areas of intracytoplasmic lipid or fatty regions [29, 30] (Fig. 3). The existence of intracytoplasmic fat in ACCs has been attributed to the presence of cortisol and related fatty precursors in hormonally active tumors [30]. On occasion, pockets of fat may be seen within the mass, indicating coexistent myelolipomatous tissue. IVC invasion has been reported in 9–19% of ACC cases at presentation [5] (Figs. 4 and 5). CT The typical appearance of ACC on unenhanced CT is of a large, inhomogeneous but well-defined suprarenal mass that displaces adjacent structures as it grows [24]. Regions
TABLE 1: TNM Staging of Adrenocortical Carcinoma [18–21] TNM Stage
Description
Primary tumor (T) Tx
Primary tumor cannot be assessed
T0
No evidence of primary tumor
T1
≤ 5 cm in greatest dimension, extraadrenal invasion absent
T2
> 5 cm in greatest dimension, extraadrenal invasion absent
T3
Tumor of any size with local invasion, but not invading adjacent organsa
T4
Tumor of any size with invasion of adjacent organsa
Regional lymph nodesb (N) Nx
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Positive regional lymph nodes
Distant metastases (M) M0
No distant metastases
M1
Distant metastases present
a Adjacent organs include kidney, diaphragm, great vessels, pancreas, and liver.
bThe regional lymph nodes are hilar, abdominal paraaortic, and paracaval nodes.
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Bharwani et al. TABLE 2: Surgical Staging of Adrenocortical Carcinoma [8, 18, 20, 21, 73] Surgical Stage I
Percentage at Presentation
5-year Survival (%)
Tumor ≤ 5 cm without local invasion, nodal or distant metastases
Imaging Feature
2.2–6.3
65
II
Tumor > 5 cm without local invasion, nodal or distant metastases
21.7–49.8
65
III
Tumor with local invasion or positive lymph nodes
17.9–22.5
40
IV
Tumor with local invasion and positive lymph nodes or distant metastases
21.3–34.7a
10
aPresence of metastases.
Fig. 1—32-year-old woman with cortisol-secreting right adrenocortical carcinoma resulting in Cushing syndrome. (Reprinted with permission from [27]) A, Unenhanced CT scan shows large low-attenuation suprarenal mass (arrowheads), with internal areas of high attenuation (arrows) consistent with hemorrhage. B, Axial T1-weighted MR image shows high signal intensity (arrows) within right adrenal mass (arrowheads) consistent with hemorrhage.
the vein [38]. The presence and cephalad extent of tumor thrombus can be identified on contrast-enhanced CT or MRI (Fig. 4 and 5). CT is also of value in showing the local and distant spread of an ACC. Preservation of fat planes around the tumor indicates that there is no local invasion. Where there is a paucity of retroperitoneal fat, it may be impossible to determine whether tumor has invaded adjacent organs. Metastases are frequently found at presentation: Regional and paraaortic lymph nodes (25–46%), lungs (45–97%), liver (48–96%), and bone (11–33%) are the common sites [1, 5, 28]. Hepatic metastases tend to be hypervascular and are best seen on arterial phase imaging after IV contrast administration.
ally centrally located [24, 32] (Fig. 3). Calcification is rare in adenomas, although it is present in approximately 10% of pheochromocytomas [37]. Tumor thrombus extending into the IVC at presentation is not rare [28] and is more frequently seen in right-sided tumors. A tumor thrombus within a vein is usually well encapsulated and can often be withdrawn intact from
MRI ACC is typically heterogeneous in signal intensity on MRI because of the presence of hemorrhage and/or necrosis [30]. On T1weighted imaging, ACC is typically isointense or slightly hypointense to normal liver parenchyma. However, high T1 signal intensity is often seen because of the presence of hemorrhage (Fig. 1). On T2-weighted imag-
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of low attenuation correspond to necrosis pathologically (Fig. 2); in one reported series, necrosis was invariably present when tumors reached 6 cm in size [24]. However, smaller lesions may be homogeneous on unenhanced CT [31]. After the administration of IV contrast material, there is inhomogeneous enhancement of the tumor, typically with greater enhancement seen peripherally and relatively little enhancement seen centrally, because of central necrosis [24, 32]. Measurement of the attenuation of adrenal lesions on unenhanced CT is of great value in distinguishing between benign and malignant masses. Cumulative data obtained for the identification of adrenal adenomas indicate that ACCs rarely have an attenuation value of less than 10 HU. The specificity of this threshold for the identification of benign adenomas is approximately 98% [33]. Equally, ACCs retain IV contrast material and have absolute and relative percentage washout of less than 60% and less than 40%, respectively, at 15 minutes after contrast administration [26, 34] or less than 50% and less than 40%, respectively, at 10 minutes [34–36] (Fig. 6). Calcification, either microcalcification or coarse calcification, is seen on CT in approximately 30% of patients with ACC and is usu-
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Fig. 2—35-year-old woman with adrenocortical carcinoma. A, Portal venous phase CT scan shows large heterogeneously enhancing left suprarenal mass that displaces left kidney inferiorly. Regions of nonenhancing tissue (arrows) are consistent with necrosis. B, Axial T2-weighted MR image shows high signal intensity (arrows) consistent with necrosis.
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Fig. 3—20-year-old woman with adrenocortical carcinoma. A and B, Axial (A) and sagittal (B) contrast-enhanced images show large right suprarenal mass that is displacing inferior vena cava medially and right kidney inferiorly. Tumor contains flecks of coarse calcification (black arrows, B) and macroscopic fat (–20 HU) (white arrows) centrally.
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er than 0.38 (92% sensitivity and 90% specificity). ACCs and pheochromocytomas could be differentiated from adenomas and metastases using a 4.0–4.3 ppm/creatine ratio greater than 1.50 (87% sensitivity and 98% specificity). By combining these two spectral analyses, they were able to divide adrenal mass lesions into one of four distinct groups: adenoma, pheochromocytoma, ACC, or metastasis [42]. Although some criticisms of this study have been raised, the technique appears to offer potential in helping to distinguish among adrenal mass lesions [43].
Enhancement after the administration of IV contrast material is generally avid with slow washout [3]. MRI has been shown to be superior to CT in the delineation of the presence and extent of IVC invasion [40, 41] (Fig. 5). The results of early studies suggested that proton MR spectroscopy may be useful in differentiating adrenal adenomas and pheochromocytomas from adrenal metastases and ACC [42]. Faria et al. [42] looked at the spectral traces obtained from 60 patients with adrenal masses. Adenomas and pheochromocytomas could be differentiated from ACCs and metastases using choline-creatine ratios of greater than 1.20 (92% sensitivity and 96% specificity) and choline-lipid ratios of great-
Functional Imaging FDG PET can identify some malignant adrenal masses by virtue of their increased metabolic activity; however, when FDG uptake is only modest, the likelihood of benign versus malignant is about equal [44]. FDG PET combined with contrast-enhanced CT has a sensitivity of 100% and specificity of 87–97% for identifying malignant adrenal masses. The lower specificity is because a small number of adenomas and other benign lesions mimic malignancy [45, 46]. The novel PET tracer 11C metomidate, a marker of 11β-hydroxylase, is used as tracer for adrenocortical tissue and is taken up by adenomas and ACCs. This marker differentiates adrenal cortical lesions from pheochromocytomas and metastases, which are uptake-negative [47]. However, the most valuable aspect of PET is its ability to detect distant metastases (Fig. 8); it is important to remember that one third of pa-
A Fig. 5—60-year-old woman with adrenocortical carcinoma (ACC). A and B, Axial T2-weighted (A) and coronal MR venography (B) images show large heterogeneous left-sided ACC (asterisk) with tumor thrombus extending into adrenal vein (arrow, B) and inferior vena cava (arrow, A).
ing, ACC is usually hyperintense to liver parenchyma and has a heterogeneous texture because of the presence of intratumoral cystic regions and hemorrhage [39] (Fig. 2). A functioning ACC can contain small regions of intracytoplasmic lipid resulting in small nonuniform areas of loss of signal on chemical shift imaging (< 30% of the lesion) [26, 29, 30] (Fig. 7). Although similar small nonuniform loss can occur in lipid-poor adenomas, the significant uniform signal loss seen in lipid-rich adenomas does not occur. Schlund et al. [30] described the presence of peripheral mural-based enhancing nodules in seven of eight ACCs reviewed. This feature has not been described elsewhere in the medical literature.
Fig. 4—52-year-old man with metastatic adrenocortical carcinoma. Portal venous phase CT scan shows large, irregular right suprarenal mass (black arrow) with enhancing tumor thrombus (arrowheads) extending into right renal vein and inferior vena cava resulting in luminal filling defect. At least two metastatic deposits (white arrows) are shown within adjacent liver.
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Fig. 6—50-year-old woman with right-sided adrenocortical carcinoma (ACC). Dedicated adrenal CT with washout studies shows 2.5-cm right suprarenal mass. A, Unenhanced CT image shows that lesion (arrow) has attenuation of 29 HU and therefore requires further characterization. B and C, CT images obtained 60 seconds (B) and 15 minutes (C) after administration of IV contrast material show lesion (arrow) has attenuation values of 54 and 43 HU, respectively. These attenuation values result in absolute percentage washout of 43% at 15 minutes, making lesion indeterminate by CT washout criteria. Mass was confirmed to be ACC on histology.
tients with ACC will have metastatic disease at presentation [7, 12, 48]. Differential Diagnosis and Distinguishing Features Adenoma Adenomas may be diagnosed with a sensitivity of 75–98% and specificity of 92–100% using CT washout characteristics [49] and chemical shift imaging [50]. However, in some cases, it can be difficult to distinguish benign from malignant lesions. If they measure 3–4 cm in diameter, the pathologic label of “indeterminate malignant potential” is often applied, and if they are larger than 4 cm, they are generally managed as malignant lesions.
Fig. 7—38-year-old man with right-sided adrenocortical carcinoma (ACC). A and B, Chemical shift imaging shows large irregular right-sided lesion (arrow) that does not show signal loss between in-phase (A) and out-of-phase (B) images. Tumor was confirmed to be ACC on histology.
Pheochromocytoma Pheochromocytomas may be benign or malignant. Small pheochromocytomas are usually homogeneous in appearance with a density of 40–50 HU on unenhanced CT [26], whereas larger pheochromocytomas can be inhomogeneous with areas of hemorrhage and necrosis [51] (Fig. 9A). There is no correlation between tumor size and malignancy [52]. On MRI, pheochromocytomas are typically described as isointense or hyperintense to liver on T1 and hyperintense to fat on T2 [51]. However, appearances can be variable. For example, Jacques et al. [52] reported in 2008 that only 11% of pheochromocytomas showed “typical” T2 hyperintensity and that pheochromocytomas that were only mildly hyperintense to the spleen (34%) or that were heterogeneous on T2 (39%) were more common. Increasing heterogeneity was
seen to correlate with increasing amounts of hemorrhage, necrosis, and fibrosis. After IV contrast administration, pheochromocytomas enhance avidly and have a prolonged washout phase, although exceptions do exist [53]. Ninety-one percent of pheochromocytomas are functioning and biochemical markers are important in establishing the diagnosis [54]. Nonfunctioning pheochromocytomas (9%) pose more of a diagnostic dilemma; although many will be differentiated from ACC using 123I-metaiodobenzylguanidine (MIBG) scintigraphy, some nonfunctioning pheochromocytomas will not be MIBG-avid [54]. Dominantly inherited succinate dehydrogenase (SDH) gene mutations account for most familial paraganglioma syndromes in which patients have an increased incidence of adrenal and extraadrenal paragangliomas. In patients with SDH-B gene mutations,
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there is an increased risk of malignancy, which is reported as between 34% and 97%, and paragangliomas usually show intense uptake on FDG PET [55, 56]. Lymphoma The primary pathologic type that involves the adrenal glands is non-Hodgkin diffuse large Bcell lymphoma [57, 58]. Disease is usually bilateral with enlarged adrenal glands [57, 58] that maintain their normal “adeniform” shape. Metastases Adrenal metastases are found in up to 27% of patients with malignant epithelial tumors at autopsy [59]. This diagnosis should be considered when bilateral adrenal lesions are present and there is a known primary malignancy elsewhere or there is evidence of other metastases. The most common primary site is the lung.
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B Fig. 8—52-year-old man with metastatic adrenocortical carcinoma (ACC). A–C, Axial diagnostic contrast-enhanced CT image (A) and axial (B) and coronal (C) fused PET/CT images show large right adrenal mass (arrow) with avid FDG uptake and multiple metabolically active hepatic metastases (arrowheads).
enhancement after IV contrast administration (Fig. 9C). On MRI they are typically hypointense on T1 and heterogeneously hyperintense on T2 depending on the content of their myxoid stroma [61, 62]. Infection The imaging appearances of infection within the adrenal gland are generally nonspecific and can be seen as soft-tissue masses and cystic changes with or without calcification. Tuberculosis and histoplasmosis tend to be bilateral but can be asymmetric and give the appearance of unilateral disease [63].
C Composite or Collision Tumors Composite or collision tumors are rare tumors that consist of two contiguous but histologically different tissues within a single mass [60]. A collision tumor is composed of independently coexisting neoplasms without significant tissue admixture, whereas a composite tumor contains coexisting neoplasms with considerable admixture of the two different cell types such as a ganglioneuroma and pheochromocytoma (Fig. 9B) or myelolipoma and Cushing adenoma. Ganglioneuroma Ganglioneuromas are benign neoplasms arising from the sympathetic ganglia. Generally, they are large solid lesions on CT with homogeneous to mildly heterogeneous
All the diagnoses discussed can present a diagnostic challenge in trying to differentiate them from an ACC. In practice, however, it is most frequently adenomas that can present the greatest difficulty, partly because of the frequency with which they occur. Indeed, on occasion, pathologists also find it difficult to make this distinction [2, 14, 15]. Thus, although most benign cortical adenomas can now be confidently diagnosed on the basis of the criteria mentioned, some lesions remain indeterminate. When biochemical testing shows these lesions to be functioning, most endocrinologists would advocate removal of the mass. Surgery may also be indicated if doubt exists about the true nature of a nonfunctioning lesion. A detailed clinical history and biochemical testing can often distinguish between a pheochromocytoma and an ACC without the need for diagnostic imaging tests, although imaging is still often required for surgical planning. The distinction between large nonfunctioning pheochromocytomas and ACCs can be problematic, particularly when the lesion is not 123I-MIBG-avid. Once again, surgery is sometimes required to resolve the diagnostic dilemma.
Neuroblastoma Neuroblastomas occur most frequently in children and are rare in the adult population. Calcification is a hallmark of neuroblastoma in children but is rarely seen in adults. Adults with neuroblastoma tend to show a higher rate of metastatic disease at presentation than children do [64, 65].
Treatment Planning Role of Biopsy There is controversy concerning the role of biopsy in indeterminate adrenal lesions. On one hand, percutaneous biopsies of suspected ACC may not be justified in light of the risks of inducing tumor capsule breakdown and tumor spread along the needle track [68]. The difficulty arises with suspected adrenocortical lesions that are borderline in size (3–4 cm) in patients at high surgical risk. In some of these cases, biopsy may be justified, but decisions need to be made for each patient individually.
Adrenal Hemangioma Adrenal hemangiomas are well-defined soft-tissue masses with inhomogeneous enhancement after contrast administration. They are often calcified because of either intratumoral phleboliths or previous hemorrhage. On MRI, adrenal hemangiomas are typically hypointense to liver on T1 and may exhibit central hyperintensity due to hemorrhage. On T2, lesions are hyperintense. Foci of low signal intensity on T1 and T2 are caused by calcification. Characteristically, they show persistent peripheral enhancement on delayed imaging [66, 67].
Surgery The definitive treatment of all stages of ACC is en bloc resection of the tumor with or without adjacent invaded organs. If en bloc resection is not possible because of local extension into adjacent structures, maximal tumor debulking surgery is indicated. This surgery decreases the amount of hormone-secreting tissue present and also reduces complications due to mass effect. IVC invasion is not rare, and surgery is performed even when tumor extends the entire length of the IVC and into the right atrium; cardiac bypass techniques may be used
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Fig. 9—Examples of some differential diagnoses. A, 36-year-old man who presented with hypertension and flushing. Arterial phase CT image shows large heterogeneous enhancing left suprarenal mass, which also showed intense metaiodobenzylguanidine uptake (not shown). Mass was confirmed to be pheochromocytoma after surgery. B, 27-year-old woman who presented with left flank pain and palpitations. Portal venous phase CT image shows large left suprarenal mass with regions of necrosis (arrows) seen centrally. Mass was confirmed to be collision or composite tumor on pathologic examination and contained both pheochromocytoma and ganglioneuroma tissue. C, 42-year-old man who presented with refractory hypertension. Portal venous phase image through upper abdomen shows lobulated infiltrative left suprarenal mass. Mass was confirmed to be benign ganglioneuroma on pathologic examination.
in these cases. Delineation of IV tumor is paramount in surgical planning because venous control must be established distal to the tumor thrombus and may require bypass procedures for venotomy or tumor thrombectomy. Surgery can be open or laparoscopic for small tumors without local invasion or tumor thrombus depending on the tumor extent and the expertise of the local surgical team [69]. However, open adrenalectomy is currently the preferred option because of the high rate of recurrence and peritoneal carcinomatosis associated with laparoscopic procedures [70, 71]. There are no published guidelines regarding postsurgical imaging follow-up of patients with ACC. At our institution, the interval and modality are decided on an individual patient basis and include CT, MRI, and PET/CT. More recently, less invasive techniques have been introduced whereby both adrenocortical tumors and adrenal metastases have been treated successfully by radiofrequency ablation [72].
Radiotherapy Radiotherapy is indicated in patients with a high risk for local recurrence including those with advanced locoregional disease and incomplete or indeterminate resection; radiotherapy may be helpful in treating the symptoms from bone metastases [73].
Chemotherapy Treatment with the adrenolytic drug mitotane may improve survival or at least control symptoms [3, 7, 12] and is used in both primary and adjuvant therapy. It also plays a role in metastatic and recurrent disease. There is currently no agreement about the possible role of other forms of cytotoxic chemotherapy, but large-scale trials are under way to assess different chemotherapeutic regimens.
Conclusions The imaging appearances of ACC are diverse because of the variable presence of necrosis, hemorrhage, calcification, and intracellular lipid content. As illustrated, other diseases can simulate ACC, and familiarity with both typical and atypical appearances on cross-sectional imaging taken in conjunction with clinical information helps to suggest the accurate diagnosis and appropriate treatment.
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Prognosis Patients with unresectable stage IV ACC have a median survival of 3 months [20]. When treated aggressively with surgery, patients with stage I and II tumors have an approximately 65% 5-year survival, whereas patients with stage III and IV disease have 40% and 10% 5-year survival, respectively [74]. The overall 5-year survival rate for all patients with ACC is 38% [8, 75]. Recurrence (Fig. 10) and metastatic disease (Figs. 4 and 8) are common in patients with ACC. Of the patients undergoing apparent complete resection, 35–85% will develop recurrent or metastatic disease [5, 76].
Fig. 10—45-year-old man with recurrent disease in right adrenalectomy bed. Surgical clips (arrows) are engulfed by abnormal enhancing soft tissue in right adrenalectomy bed. Infiltrative recurrent tumor (arrowheads) invades liver and inferior vena cava.
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