Primary Adrenocortical Carcinoma: Sonographic Evaluation with Clinical and Pathologic Correlation in 26 Patients
Ulrike M. Hamper1 Elliot K. Fishman1 David S. Hartman2 John L. Roberts1 Roger C. Sanders1
The sonograms of 26 patients (19 adults and seven children) with pathologically proven diagnoses of primary adrenocortical carcinoma were evaluated. Clinical corrob- oration was obtained in all cases. The size of the lesions ranged from 3 to 22 cm. The five smaller lesions (3-6 cm) showed a homogeneous echo pattern, similar to renal cortical echogenicity. The 21 larger lesions varied in echo texture, having a heteroge- neous appearance with focal or scattered echopenic or echogenic zones representing areas of tumor necrosis, hemorrhage, and/or, rarely (19%), calcification. Even the largest lesions were fairly well delineated, often with a lobulated border. Few (7/26 or 27%) showed a surrounding echogenic thin capsulelike rim. All five small lesions showed clinical evidence of endocrine activity. Larger lesions were hormonally active less often (9/21 or 43%). Twelve patients (46%) showed no sign of endocrine activity and pre- sented with symptoms such as fever, weight loss, abdominal discomfort, abdominal mass, hematuria, and hypertension. In the pediatric and adolescent age group (0-16 years), all tumors were hormonally active, while only seven (37%) of tumors in the adult population (17-69 years) were hormonally active.
Unfortunately no echo pattern was characteristic enough to allow differentiation of adrenal adenoma from carcinoma. Smaller lesions are more likely to be benign, and larger lesions with areas of necrosis, hemorrhage, and calcification are more likely to be malignant.
Adrenocortical carcinoma is a rare tumor that may arise from any of the layers of the adrenal cortex. It affects all ages and sexes and has a dismal prognosis [1]. Most reports of sonographic studies in the literature have been either case reports [2-4] or small series [5-9]. The report of the largest series describes the sonographic findings in 12 patients [10]. The adrenal region, once difficult to visualize on sonography, can now be imaged effectively because of advances in scanning techniques and the development of high-resolution real-time sector scan- ners [11].
We reviewed the records of the Johns Hopkins Hospital Oncology Center and the Armed Forces Institute of Pathology to examine the sonographic features and clinical presentation (hormonal activity, constitutional symptoms) in 26 patients with proved primary adrenocortical carcinoma. To our knowledge this is the largest series reported, and it includes children as well as adults.
Received September 26, 1986; accepted after revision November 26, 1986.
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the view of the Department of Defense or the Navy.
1 Department of Radiology, Johns Hopkins Uni- versity School of Medicine, Johns Hopkins Hospital, 601 N. Broadway, Baltimore, MD 21205. Address reprint requests to U. M. Hamper.
2 Department of Radiologic Pathology, Armed Forces Institute of Pathology, Uniformed Services University of Health Sciences, Washington, DC 20306.
AJR 148:915-919, May 1987 0361-803X/87/1485-0915 American Roentgen Ray Society
Materials and Methods
The sonograms of 26 patients with pathologically proven diagnoses of primary adrenocor- tical carcinoma were evaluated. These patients were identified through a computer search of the files of the Johns Hopkins Hospital Oncology Center as well as through a review of all cases of primary adrenocortical carcinoma submitted to the Armed Forces Institute of Pathology between 1977 and 1985. In each case, the diagnosis had been confirmed pathologically on the basis of tissue obtained either by biopsy, surgery, or autopsy. All patients had a sonogram performed before tissue diagnosis or therapeutic intervention. Only sonograms of adequate quality were accepted.
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Tumor characteristics evaluated included size and location, echo characteristics, necrosis or calcification, marginal definition, and evi- dence of metastatic dissemination (if it was assessed on the original study). The sonograms were obtained by using various commercially available 3.5 or 5-MHz real-time sector scanners as well as static B- scanners. All sonograms were reviewed by four radiologists and then correlated with patterns of clinical presentation and pathologic spec- imens that were available.
Results
The carcinoma originated in the right gland in 14 patients and in the left gland in 12 patients. No cases of bilateral tumor involvement were observed. Tumor size ranged from 3 to 22 cm (largest dimension), with a mean size of 13 cm. The patients ranged from 7 months to 69 years old, with a mean age of 33 years. Eighteen patients were female and 8 male. Eighteen patients were white, seven were black, and one was Hispanic. Seven patients were younger than 16 years old, and 19 were older than 16. Of the seven patients under 16, five had tumors less than 6 cm. The smallest tumor in this group was 3 cm, and the largest was 16 cm (mean tumor size, 7.4 cm). Of the 19 patients older than 16 years, six had tumors smaller than 10 cm, and 13 had tumors larger than 10 cm. The smallest tumor in the adult group was 8 cm, the largest was 22 cm (mean tumor size, 14.5 cm).
Sonography showed round or oblong masses in the region of the adrenal glands. Most lesions were fairly well defined, even the larger ones, and often they had slightly lobulated contours. Five smaller lesions (3-6 cm) showed a fairly ho- mogeneous echo texture, while the remaining 21 tumors, especially the large ones, had a heterogeneous echo pattern. Hypoechoic zones, either centrally located or diffusely inter- spersed throughout the lesion, corresponded to necrotic tu- mor on pathology and were seen in eight of the 21 patients (Fig. 1). In two of those eight patients the central necrotic area had a cystic appearance with septations and low-level echoes. In eight patients the echo pattern, although hetero- geneous, was predominantly echogenic, corresponding to necrotic and hemorrhagic tumor on pathology (Fig. 2). In the remaining five patients the echo pattern was mixed, showing
about equal amounts of echogenic and echopenic areas (Fig. 3). Tumor calcification was seen in five of the 26 patients, consisting of either small bright echogenic foci or denser accretions of calcium with or without acoustic shadowing (Fig. 4). In one additional patient, CT showed evidence of small, faint calcifications, not appreciable on the sonogram. In seven patients a thick, echogenic, capsulelike rim, either partly or completely surrounding the lesion, was identified (Fig. 1). These capsules appeared separate from the sur- rounding organs or echogenic tumor tissue, and were seen in lesions of all sizes. In one patient, comparison with a CT scan showed enhancement of a capsulelike rim surrounding the tumor with IV contrast injection, which corresponded to the echogenic rim seen on the sonogram (Fig. 5). Two of the larger tumors showed marked compression of the ipsilateral kidney with extreme inferior and medial displacement (Fig. 6).
In one patient, sonography gave a false-positive impression of inferior vena cava involvement (Fig. 7). The examination showed a large heterogeneous lobulated tumor with calcifi- cation arising from the right adrenal gland. There was marked anterior displacement of the inferior vena cava by the mass with apparent echogenic material partially filling the lumen. At surgery no tumor was identified within the inferior vena cava.
On clinical presentation, 14 patients (54%) showed signs of hormonal activity (Table 1). The spectrum included adren- ogenital syndrome (four patients), Cushing’s syndrome (eight), precocious puberty (two), and virilizing effects (three). Twelve patients (46%) showed no sign of hormone production by the tumor, and their presentation included constitutional symptoms such as weight loss, abdominal discomfort and distension, presence of an abdominal mass, fever of unknown origin, hematuria, and new onset of hypertension. One patient presented with a metastatic neck mass.
In 17 patients, several of these clinical symptoms were present simultaneously. All five of the smaller tumors (3-6 cm) showed signs of hormonal activity, while only nine (43%) of the larger tumors (7-22 cm) were hormonally active (Table 2). In the pediatric and adolescent age group (0-16 years) all tumors, regardless of size, were hormone secreting. In the adults (17-69 years), only seven patients (37%) (Table 2) had hormone-secreting tumors.
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Fig. 2 .- Longitudinal sonogram of left adrenal gland showing adrenocortical carcinoma with heterogeneous, predominantly echogenic pat- tern, corresponding to necrotic and hemorrhagic tumor on pathology.
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Fig. 7 .- A, Longitudinal sonogram of right adrenal gland showing lobulated, large, right-sided adrenal carcinoma with calcifications (arrowheads) and marked anterior displacement of inferior vena cava by mass with apparent echogenic material filling lumen (arrows). B, Inferior vena cava showing marked anterior displacement by mass (arrowheads). C, Corresponding pathologic specimen of lobulated right adrenal carcinoma.
| Endocrine Activity | Total series (n = 26) | Adults (17-69 years) (n = 19) | Children (0-16 years) (n = 7) | |||
|---|---|---|---|---|---|---|
| Males | Females | Males | Females | Males | Females | |
| + | 4 (15) | 10 (38) | 1 (5) | 6 (32) | 3 (43) | 4 (57) |
| - | 4 (15) | 8 (31) | 4 (21) | 8 (42) | 0 (0) | 0 (0) |
Notes .- + = Endocrine-active (adrenogenital syndrome, Cushing’s syn- drome, precocious puberty, virilizing effects). - = Not endocrine-active. Num- bers in parentheses are percentages.
| Endocrine Activity | Size of Lesion | Patient age at Presentation | ||
|---|---|---|---|---|
| 3-6 cm (n = 5) | 7-22 cm (n = 21) | 0-16 years (n = 7) | 17-69 years (n = 19) | |
| + - | 5 (100) | 9 (43) | 7 (100) | 7 (37) |
| 0 (0) | 12 (57) | 0 (0) | 12 (63) | |
Note .- + = Endocrine-active (See Table 1). - = Not endocrine-active. Numbers in parentheses are percentages.
Discussion
Primary adrenocortical carcinoma is a rare malignancy with a reported incidence of about 2 per million per year. It ac- counts for only 0.2% of all deaths from cancer [1]. Childhood adrenocortical carcinoma, although extremely uncommon, is still the most common tumor occurring in the adrenal cortex [5, 7]. In experienced hands, sonography is an excellent screening method for delineating an adrenal tumor and will
yield information about the internal consistency of the lesion [8, 9, 11-14]. Sonography can usually reveal the separation between an adrenal mass and a tumor originating in the liver or the upper pole of the kidney by characteristic displacement of the retroperitoneal fat planes [15]. However, if the lesion is large, cleavage planes may not easily be appreciated.
Although some adrenal lesions such as cysts or hemor- rhage may show a characteristic sonographic pattern [2], most adrenal lesions do not exhibit a specific echo pattern [4]. Sonographically, the appearance of pheochromocytoma, metastases, adenomata, or carcinoma may be similar [11]. When small, most lesions present with a homogeneous echo pattern that usually becomes complex as the lesions grow, reflecting areas of necrosis or hemorrhage. When pheochro- mocytoma is suspected, biochemical studies will aid in the differentiation. In metastases, bilaterality as well as the knowl- edge of a primary neoplasm often are helpful features. Since more adrenal masses are being discovered incidentally in patients with no clinical or biochemical abnormality, distinction between an adrenal adenoma and a small carcinoma has become more difficult [11]. Masses larger than 3-4 cm have a greater probability of being malignant, but adenomata can exceed 5 cm in diameter, as well [6]. Even on histology, adenomata may be indistinguishable from well-differentiated adenocarcinoma [5, 6].
An obvious downward displacement of the ipsilateral kidney by large adrenal neoplasms has been reported [16], and this condition was seen in two of our patients with 18- and 20-cm lesions (Fig. 6).
Because the right adrenal gland is located behind the inferior vena cava, a right adrenal mass may indent the posterior wall [9, 12]. In one patient this marked indentation of the inferior vena cava by a 14-cm right adrenal carcinoma erroneously created the appearance of intravascular tumor extension (Fig. 7), which was not found at surgery.
In seven patients an echogenic capsulelike rim around the tumor was observed. In one case, where comparison with CT was available, this rim correlated well with an enhancing capsule surrounding the mass that was visible with IV contrast injection (Fig. 5B); Fishman et al. [17] have suggested that this rim might represent a well-vascularized portion of the tumor and might be specific for carcinoma. This suggestion deserves further evaluation.
The presence of calcification is not specific for adrenal carcinoma. It can be seen in both benign and malignant disease, and it does not aid in the differential diagnosis [18].
In our study, tumor sizes ranged from 3 to 22 cm. All smaller lesions (3-6 cm) were hormonally active, probably accounting for earlier detection, especially in females (Table 1). Functional adrenocortical neoplasms have been mani- fested as Cushing’s syndrome, the adrenogenital syndrome (virilization or feminization), precocious puberty, or, rarely, the clinical syndrome of hypertension with hypokalemic alkalosis (hyperaldosteronism) [1]. Except for the last, we observed all these clinical manifestations in our series.
In the pediatric/adolescent age group, all patients pre- sented with endocrine symptoms (Table 1): virilization in the girls and signs of precocious puberty in the boys. Three children also showed signs of Cushing’s syndrome, an en- docrine abnormality most commonly caused by adrenocortical carcinoma in childhood [1]. The mean age of presentation in this group (1.8 years) was lower than the mean reported by Daneman et al. [7]. In the adult population, only 37% of patients presented with endocrine abnormalities; this was probably related to a larger mean tumor size and a more advanced patient age at the time of presentation.
The marked improvement in scanning procedures and tech- nical developments has allowed visualization of the normal and abnormal adrenal gland to be achieved by sonography in most patients. No single criterion exists to help resolve the differential diagnosis between benign and malignant adrenal lesions. If an adrenal mass of considerable size is incidentally discovered on sonography, careful evaluation of the entire abdomen for evidence of dissemination of a malignant tumor should be performed. When an adrenal tumor is suspected on clinical grounds, sonography will allow rapid, noninvasive confirmation and localization of a lesion, serve as a guide to percutaneous needle aspiration biopsy [6], and assess meta-
static spread preoperatively. Unfortunately, no echo pattern is specific enough to allow differentiation of adrenal adenoma from a small carcinoma in the absence of metastatic spread. Smaller lesions are statistically more likely to be benign ad- enomata, and larger masses with areas of necrosis, hemor- rhage, and/or calcification will probably be malignant.
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