Joao Ribeiro Raul C. Ribeiro Barry D. Fletcher
Imaging findings in pediatric adrenocortical carcinoma
Received: 2 April 1999 Accepted: 5 August 1999
This work was supported in part by the National Cancer Institute, Cancer Center Support (CORE) grant P30 CA21765, and by the American Lebanese Syrian Associ- ated Charities.
J. Ribeiro . R. C. Ribeiro . B. D. Fletcher International Outreach Program, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
J. Ribeiro Department of Radiology, Instituto Materno Infantil de Pernambuco, Recife, Brazil
R. C. Ribeiro Department of Hematology-Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
R. C. Ribeiro · B. D. Fletcher Department of Pediatrics, University of Tennessee-Memphis, Tennessee, USA
B. D. Fletcher ☒
X Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105, USA
B. D. Fletcher Department of Radiology, University of Tennessee-Memphis, Tennessee, USA Phone: 901-495-23 09; FAX: 901-495-3978; E-mail: barry.fletcher@stjude.org
Abstract Background. Adrenocor- tical carcinoma (ACC), a tumor that is rare among children, causes clini- cally evident hormonal disturban- ces. Imaging methods are used to stage disease and to plan surgical resection.
Objective. To describe the findings of the various imaging methods used to evaluate ACC.
Materials and methods. We reviewed the records of ten consecutive pa- tients (mean age, 8.1 years) who presented from 1987 to 1998 with ACC. All patients underwent com- puted tomography (CT) scanning; five underwent magnetic resonance (MR) imaging; four underwent ul- trasonography (US); and eight un- derwent radionuclide bone scans. Results. Seven patients presented with signs of hormonally functional tumors. Typical imaging findings consisted of a large, well-defined su- prarenal tumor, containing calcifica- tions (seven patients) with a thin capsule and central necrosis or he- morrhage (six patients). The inferior vena cava (IVC) was compressed by tumor in three patients, and ultraso- nography demonstrated invasion of the IVC wall in one of these. Three patients’ bone scans showed that the primary tumor took up radioactive tracer. Spread to lungs or liver or both was demonstrated in six patients. Conclusions. CT, US and MR ima- ging are effective methods of ima-
ging the primary tumor. Chest CT and bone scintigraphy should be performed to detect metastases. The presence of a thin tumor capsule, a stellate central zone of necrosis, and evidence of hormonal function help distinguish ACC from neuroblasto- ma.
Introduction
Adrenocortical carcinoma (ACC) is a rare tumor, espe- cially among children and adolescents [1, 2]. In these pa- tients, usually girls, the tumors are almost always functional, causing virilization, Cushing’s syndrome, or both [1]. Some reports associate the tumor with conge- nital abnormalities and other tumors [3-5]. The inci- dence of pediatric ACC appears to be higher in southern Brazil than North America [1]. Abdominal imaging is necessary for detecting ACC and is an impor- tant tool for evaluating resectability and planning surgi- cal intervention, because the ability to perform total excision is the most important positive prognostic factor [2]. Previous descriptions of ACC in children have fo- cused on findings from ultrasonography (US) and com- puted tomography (CT) [6-9]. In this report, we describe our experience with CT scanning, magnetic re- sonance (MR) imaging, ultrasound (US), and nuclear imaging of children with ACC.
Materials and methods
Ten patients with a diagnosis of ACC proved by histologic findings were treated at our institution between 1987 and 1998. The mean age of the eight girls and two boys was 8.1 years (range 1 to 17 years). Nine patients underwent initial imaging either at the re- ferring institution or in our department at the time of presentation. One patient underwent imaging at the time of recurrence at the primary tumor site. All ten patients underwent CT scanning of the abdomen and thorax, four underwent abdominal US, and five un- derwent abdominal MR imaging. Radionuclide bone scintigraphy was performed on eight patients, and the skeletal maturation of nine patients was assessed by using radiographs of the hand. All patients underwent unenhanced CT scanning of the chest for the detection of lung metastases. All images were reviewed by two radiologists (J.R., B.D.F.).
The CT scans were evaluated to characterize the following as- pects of the primary tumor: size (maximum diameter), definition
of tumor margins, calcification, relationship to midline structures, local and regional lymphadenopathy, precontrast attenuation and postcontrast enhancement, presence or absence of a capsule, and inferior vena cava (IVC) involvement. On coronal and transverse MR images, we evaluated the intensity of the tumor on spin-echo T1- and T2-weighted images and (in three patients) on short inver- sion-time inversion-recovery (STIR) sequences. Contrast-en- hancement characteristics (on T1-weighted images) and other variables were also evaluated as on CT scans. On ultrasonographic images, we evaluated IVC involvement. Planar 99m technetium methylene disphosphonate (99m Tc-MDP) bone scans were evalu- ated for bone metastases and uptake of radioactive tracer by the primary lesion. Bone age was determined for nine patients and was classified as normal or advanced.
Results
Clinical presentation
Six tumors arose in the right adrenal gland and four in the left. Seven tumors were functioning at the time of di- agnosis: six patients had signs of virilization, two had as- sociated hypertension, and one had hypertension alone. Bone age was classified as advanced for six patients and as normal for three. Six patients had secondary involve- ment of the lungs, liver or both. Our series includes one previously reported patient with ACC and a ganglio- neuroblastoma that occurred synchronously in the same gland [5]. This patient also had a germline p53 mu- tation, Turner syndrome, and congenital heart disease consisting of Shone syndrome (coarctation, parachute mitral valve, bicuspid aortic valve) and a ventricular septal defect.
| Patient | Maximum diameter (cm) | Capsule | Calcification | Central scar | Crossed midline | IVC involvement | Uptake on bone scan |
|---|---|---|---|---|---|---|---|
| 1 | 10 | Yes | Yes | No | No | Not demonstrated | Yes |
| 2 | 11 | Yes | No | Yes | No | Displaced | No |
| 3 | 16 | No | Yes | Yes | No | No | Yes |
| 4 | 16 | No | Yes | Yes | Yes | No | No |
| 5 | 6.5 | Yes | Yes | No | No | No | No |
| 6 | 4 | Yes | No | No | No | No | No |
| 7 | 2 | No | No | No | No | No | No |
| 8 | 9 | No | Yes | Yes | No | Displaced, compressed wall invasion | ND |
| 9 | 19 | Yes | Yes | Yes | Yes | No | ND |
| 10 | 15 | Yes | Yes | Yes | No | Displaced, compressed | Yes |
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Imaging findings
Computed tomography
The tumors ranged in largest diameter from 2 to 19 cm (mean 10.8 cm, Table 1). In nine of the ten patients, the tumor was well defined. In the tenth patient, one of two in whom the tumor had directly invaded the liver, the superior border of the tumor was obscured. Four tu- mors had no identifiable capsule. The other six tumors
were surrounded to some degree by a thin, well-defined enhancing rim. Two of the tumors extended across the midline into the contralateral side of the abdomen. Six tumors contained an irregular area of low attenuation that corresponded to a pathologic finding of necrosis. Calcification, varying from tiny focal deposits to exten- sive linear and amorphous deposits, was present in se- ven of the tumors (Figs. 1 a, 2 a).
Two of the four tumors imaged by precontrast CT scanning had a homogeneous appearance, and both en- hanced heterogeneously with contrast. On the postcon- trast images, nine tumors had a heterogeneous appearance. Only one (the smallest tumor studied) en- hanced homogeneously. The patient with this tumor had a second lesion arising from the same adrenal gland. Histologic examination demonstrated that this second lesion was a ganglioneuroblastoma that contained a small calcification (Fig.3a). The ACC enhanced less well than the ganglioneuroblastoma.
CT scanning also showed liver metastases in one pa- tient and direct hepatic invasion in two others (Fig.4 a).
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These findings were confirmed at surgery in two of these three patients. In all of these patients, the ACC arose from the right adrenal gland. Three patients had lung metastases, two had liver involvement alone, and one had both lung and liver metastases. One of the patients with lung metastases had a hyperattenuated nodule in the subcutaneous fat of the anterior abdominal wall, but its cause was not pathologically confirmed.
We could not identify local or regional abdominal lymph-node enlargement as distinct from the primary tumor in any of the patients. Imaging did not detect ret- rocrural or distant lymphadenopathy in any patient. The IVC was displaced anteromedially in three patients, all with tumors of the right adrenal gland. In two patients, the IVC was also compressed, and in one there was also anterior displacement and slight compression of the portal vein. In one patient, the IVC was not well de- monstrated. In the remaining seven, it was well demon- strated without signs of invasion or compression.
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Displacement and mild compression of the ipsilateral kidney occurred with the larger tumors, but in no case was there renal invasion.
Magnetic resonance imaging
Five patients underwent MR imaging of the abdomen. In four, the tumor was isointense to muscle on T1- weighted images; in one, the mass was hyperintense. On T2-weighted images, the mass was isointense to hy- perintense as compared to subcutaneous fat in two pa- tients, hyperintense in two, and isointense in one patient. STIR sequences were performed on three pa- tients, and in all three the tumor was isointense as com- pared to water. In the patient with both ACC and ganglioneuroblastoma, the ACC was slightly more in- tense than the ganglioneuroblastoma on T1-weighted images and was of similar intensity on T2-weighted ima- ges (Fig. 3b).
The mass was well defined in all five patients who un- derwent MR imaging. In the patient with liver invasion, sagittal images complemented CT in localizing the in- trahepatic portion of the tumor (Fig. 4b). In all five pa- tients, a thin hypointense tumor capsule surrounding part or all of the tumor was visible on noncontrasted T1- and T2-weighted images (Fig. 1b, c).
Intensity of all tumors except one was heterogeneous on precontrast T1-weighted images. The three tumors imaged with contrast agent showed heterogeneous enhancement. Two tumors exhibited a hypointense nonenhancing central area corresponding to the hypo- attenuated area seen on CT images (Fig. 1b). This fea- ture was similar in appearance to the “central scar” described in liver tumors [10] (Table 1); it became hyper- intense in comparison with fat on T2-weighted images (Fig. 1c) and was also hyperintese on STIR images. The
central zone of one other tumor was hyperintense on the unenhanced T1-weighted images, possibly because of hemorrhagic content, and its intensity did not change with the administration of IV contrast agent (Fig.2b).
Evaluation of lymph nodes and kidneys by MR imag- ing showed no intrinsic renal abnormalities and no lym- phadenopathy. The IVC was well shown in four patients by both MR imaging and CT scanning, but in one the MR image showed anterior compression by the tumor that was not demonstrated by CT scanning. In the two patients with IVC compression, a slight intra- luminal signal visible on T1-weighted images was inter- preted as the result of slow velocity. In one patient, the intrahepatic portion of the IVC could not be visualized by either imaging method.
Ultrasonography
For the four patients who underwent US, the examina- tion was performed primarily to evaluate the IVC. In two patients, IVC compression was demonstrated, and in one patient, involvement of the IVC wall was demon- strated by US but not by CT scanning or MR imaging (Fig.5). The IVC of one patient appeared to be normal. Patency of the IVC was well demonstrated in all cases by Doppler flow imaging. The central zones in three tu- mors demonstrated by CT scanning and MR appeared hypoechoic on ultrasonographic images.
Bone scan
The findings of bone scintigrams were negative for bone metastases in all eight patients who underwent scintigra- phy. In three, the tumor took up the radioactive tracer (Fig. 1d); all of these tumors had calcifications that
were visible on CT scans. Two calcified tumors lacked avidity for the radiotracer.
Discussion
In patients with ACC, both CT scanning and MR imag- ing readily show the primary tumor. On CT scans, ACC typically appears as a well-defined, partially calcified tu-
a
mor with a thin, enhancing peripheral capsule and an ir- regular hypoattenuated nonenhancing central area. The central area, which resembles the central scar seen in primary liver tumors [10], was found in six of the ten tu- mors in our series. On CT scans, it appears as an irregu- lar hypoattenuated area [9] and on ultrasonographic images as a hypoechoic zone [7]. In our series, it was also visible on T1-weighted MR imaging as a hypoin- tense, or in one instance hyperintense, region that did not enhance. On T2-weighted and STIR images, the central scar was hyperintense. In the case of ACC, this central area correlates with confluent necrosis, hemor- rhage, or fibrosis [6, 9, 11].
ACC spreads locally to liver, lymph nodes, the dia- phragm, and the renal vein. IVC invasion is uncommon, but can occur with tumors of either the left or the right adrenal gland [12]. Compression of the IVC by the tumor can also result in thrombosis [9]. If the tumor extends to the right atrium, cardiopulmonary bypass may be neces- sary to accomplish complete tumor excision. Because right atrial extension may be missed on CT scans [12], US and possibly MR imaging should be performed.
In our patients, metastases occurred only in the liver and lungs. One patient had both liver and lung metasta- ses. Interestingly, the tumors of all of the patients with liver involvement were located in the right adrenal gland, a finding previously reported [13]. Lymph-node involvement was not identified in this study. No bone metastases were detected in the eight patients who un- derwent 99m Tc-MDP bone scintigrams.
Most malignant tumors arising from the adrenal gland during childhood are neuroblastomas or ganglio- neuroblastomas. Other less common suprarenal masses include cysts, adenomas, pheochromocytomas myeloli- pomas, and metastases [8, 9]. In the absence of metasta-
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ses, ACC cannot be reliably differentiated from adrenal adenoma on clinical or pathological grounds [14]. Al- though large size (> 6 cm) and heterogeneity of the tu- mor at imaging suggests malignancy, one of the malignant tumors in this series that presented with me- tastases was only 2 cm in diameter. The demonstration of fat within the adrenal tumors on MR images has been reported to be a reliable indicator of adenoma, but lipid-sensitive phase-selective sequences have also demonstrated fat in adrenocortical carcinoma [15]. Agrons et al. [14] have proposed that the inclusive term “adrenocortical neoplasm” be applied to these tumors in childhood.
Neuroblastomas occur in younger patients; 75% are less than 4 years of age [16]. Although adrenal neuro- blastomas infrequently exhibit hormonal activity, they cannot usually be differentiated from ACC by imaging methods alone. At the time of diagnosis, both types of tumors tend to be large and to have areas of calcification and necrosis; the pattern of calcification is variable but frequently ringlike [16, 17]. We found primarily dense calcifications in our study, but there were some instan- ces of ringlike and mottled calcifications.
An imaging feature that may aid in distinguishing ACC from neuroblastoma is the presence of a central stellate zone. Although necrosis is common in neuroblas- toma [16], it does not usually assume the stellate appear- ance that characterized the central zone of the ACC tumors in our patients. In one of our patients, the zone was hyperintense on both T1- and T2-weighted MR ima- ging, a finding consistent with hemorrhage. A thin en- hancing rim on CT scan may also be a specific finding in ACC [11], but it was not present in any of our cases.
Uptake of the radioactive tracer by the tumor was demonstrated on three of the eight 99m Tc-MDP bone scintigrams. This phenomenon can also occur in nearly 75% of neuroblastomas [18]. Therefore, the presence or absence of primary tumor uptake cannot be used as a differential diagnostic feature. In our series, both of the tumors that took up 99m Tc-MDP were calcified. However, in neuroblastoma, no association between cal- cification and primary tumor uptake has been estab- lished [18].
In our study, three patients had metastases in the lungs, a rare event in neuroblastoma, and none of our patients had bone metastases detected by scintigraphy; such metastases are common for patients with neuro- blastoma.
In summary, CT scanning, US, and MR imaging are effective methods of imaging ACC. CT scanning of the chest is necessary for detecting pulmonary metastases, which are frequently associated with ACC. US or MR imaging should be performed to detect invasion or thrombosis of the inferior vena cava. Radionuclide bone scintigraphy is used to evaluate skeletal metastases and, as is the case with neuroblastoma, may show up- take of radioactive tracer by the primary tumor. A diag- nosis of ACC rather than neuroblastoma should be considered if the tumor contains a central stellate zone of apparent necrosis and displaces or invades major ad- jacent blood vessels such as the IVC. However, the cor- rect diagnosis of ACC is more often based on clinical and laboratory findings rather than imaging because most of these tumors are hormonally functional in the pediatric population.
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