Case Report Non-functional adrenocortical adenoma with extensive degeneration
Youhei Masugi,1 Kaori Kameyama,1 Motohiko Aiba,2 Makio Mukai,1 Satoshi Hara,3 Takashi Ohigashi3 and Masaru Murai3
1 Division of Diagnostic Pathology and 3 Department of Urology, Keio University School of Medicine and 2Department of Surgical Pathology, Tokyo Women’s Medical Collage, Tokyo, Japan
We report a case of non-functional adrenocortical adenoma of 5.5 x 5.5 x 3.2 cm in size that had an unusual histopatho- logical appearance in two respects. First, the tumor con- tained small adipose foci with osteogenesis and was suspected of being a myelolipoma based on its appearance on computerized tomography (CT) and magnetic resonance imaging. However, pathologically, the fat element was seen focally and was not accompanied by hematopoietic cells, and the diagnosis of myelolipoma was abandoned. Second, the tumor was suspected of being an adrenal carcinoma based on its appearance on CT scans and showed exten- sive degeneration: fibrosis, hemorrhage, loss of paren- chyma and moderate atypism of the tumor cells. However, as the architecture of the tumor cells was non-diffuse and there were no necrotic foci or mitoses, and vascular or cap- sular invasion were not present, the tumor was concluded to be an adrenocortical adenoma rather than a carcinoma. We diagnosed the tumor as a non-functional adrenocortical adenoma with extensive degeneration as the extensive areas of fibrosis were particularly remarkable. Furthermore, the extensive areas of degeneration might have been caused not only by an ischemic effect but also by low hor- mone levels.
Key words: extensive degeneration, non-functional adrenocor- tical adenoma, myelolipoma
Adrenal adenomas are relatively common in adults. They appear in autopsy series with a reported prevalence of 2-9% and are frequently encountered incidentally on computed
tomography (CT) scans.1,2 The distinction between benign and malignant adrenocortical tumors can often be difficult, and the diagnosis is usually made after consideration of a combination of clinical, gross and microscopic features.3 However, it is widely accepted that demonstration of fat within a solid adrenal mass on a CT scan strongly suggests the diagnosis of myelolipoma and can rule out adrenocortical adenoma.4 Our patient had an adrenocortical adenoma that was an incidental finding during magnetic resonance (MR) imaging. This type of tumor is uncommon, especially because this tumor contained a fat component and extensive areas of fibrosis. We describe herein a case of non-functional adrenocortical adenoma with extensive degeneration.
CLINICAL SUMMARY
A 46-year-old man was evaluated for a left adrenal mass discovered during abdominal MR imaging in April 2001 and referred to Keio University Hospital, Japan, for further examination.
His past history was unremarkable. The family history revealed that his father had pulmonary tuberculosis, hyper- tension and diabetes mellitus. Laboratory studies showed no abnormal values. The plasma cortisol level was 12.7 ug/dL (normal range: 7.6-21.4 µg/dL) with a normal diurnal rhythm. The plasma aldosterone level was 117 pg/mL (normal range: 50-200 pg/mL), plasma ACTH 53 pg/mL (normal range: below 60 pg/mL) and plasma Active Renin Concentration (ARC) of 16.2 pg/mL (normal range: 3.6-36.2 pg/mL). The plasma epinephrine and norepinephrine concentrations were 0.02 ng/ml (normal range: < 0.17 ng/ml) and 0.44 ng/mL (normal range: 0.15-0.57 ng/ml), respectively.
An abdominal CT scan revealed a 5 x 5 cm mass. Because of its large size and irregular enhancement, adrenal
Correspondence: Kaori Kameyama, MD, Division of Diagnostic Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
Email: kameyama@sc.itc.keio.ac.jp
Received 18 July 2002. Accepted for publication 6 December 2002.
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carcinoma was suspected. As spotty fat densities were observed inside the mass, myelolipoma was also suspected.
The MRI demonstrated a left adrenal mass with a capsular structure. The T1-weighted MRI showed low signals, and T2-weighted MRI showed high signals (Fig. 1). Gadolinium- enhanced MRI showed irregular enhancement in the early phase, and the mass was internally enhanced in the late phase. There was no evidence of metastasis. This MRI indi- cated benign features, and the preoperative diagnosis was myelolipoma.
In view of its size and the suspicion of adenocarcinoma, left adrenalectomy was performed in August 2001. The mass measured 5.5 x 5.5 x 3.2 cm and weighed 50.0 g. The cut surface of the tumor was yellow-white. The tumor was quite solid and homogeneous. No apparent hemorrhagic areas or normal adrenal cortex were seen in the macroimage (Fig. 2).
PATHOLOGICAL FINDINGS
Light microscopic examination revealed the mass to be an adrenocortical tumor with a thin fibrous capsule (Fig. 3a). There was little normal adrenal tissue left, and the normal tis- sue and the tumor were discontinuous. The tumor cells were arranged in trabecular or cord-like structures. No clear cells were seen. The interstitial tissue showed extensive (approx- iamtely one-third of the tumor) areas of fibrosis and small areas of hyalinization, hemorrhage and loss of parenchyma
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(Figs 3b,c), but there were no necrotic foci. There were no inflammatory cells, hemosiderin, thrombus or amyloid. Blood vessels both inside and outside the tumor were free of hyper- tensive and atherosclerotic changes. The tumor contained small adipose foci with ossification, and no myeloid elements were seen (Fig. 3d). It was composed of a high nuclear cyto- plasmic ratio cells containing eosinophilic cytoplasm and round or oval shaped nuclei (Fig. 3e). Vesicular chromatin was aggregated at the nuclear periphery. The cells also had an oncocytic appearance. There were no mitoses, and nei- ther vascular nor capsular invasion was noted. According to Weiss’s criteria,3 the tumor appeared to be a benign adreno- cortical adenoma. We diagnosed the tumor as an adrenocor- tical adenoma with extensive degeneration.
The adjacent normal adrenal cortex was not atrophic. There were no hyperplastic nodules.
DISCUSSION
According to the appearance of the CT and MR images, the suspected diagnosis was myelolipoma. Myelolipoma is an uncommon benign adrenocortical tumor comprised of mature adipose tissue and hematopoietic tissue. Adipose tis- sue within adrenal adenomas has also been reported to be present in myelolipoma.5-9 However, pathological examina- tion of our patient’s tumor revealed that the fat element was not accompanied by hematopoietic cells, and the diagnosis of myelolipoma was abandoned. The existence of adipose tissue might represent adipose metaplasia with ossification.
Adrenal adenomas are common, benign adrenocortical tumors with an incidence of 2.86%,10,11 and are frequently encountered incidentally on CT scans.12 When the tumor is very large, it is difficult to distinguish adenoma from carci-
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noma. This distinction is important because of the dismal prognosis of carcinomas, different treatments and different surgical approaches.13 Compared to adenomas, carcinomas are usually larger, can occur at any age including in children (adenomas usually occur in adults), they have multiple and bleeding surfaces on gross examination, are frequently cal-
cified, generally secrete more than one steroid hormone, are not visualized on 131I-iodocholesterol scans, and might cause more pronounced hypokalemia.14,15 Microscopic examination of adrenocortical carcinomas might show a high mitotic rate, pleomorphism, vascular and capsular invasion, tumor cell necrosis and broad fibrous bands traversing the
tumor,12,16 but large adenomas might show hemorrhage, cystic degeneration and calcification.14
In our case, the tumor weighed 50 g, was not so large, the cut surface was smooth and homogeneous, and there was no evidence of malignancy clinically. Laboratory studies showed no abnormal hormone levels. Microscopic examination of the tumor showed marked degenerative change, and the inter- stitial tissue contained extensive areas of fibrosis, small areas of hyalinization, hemorrhages and loss of parenchyma. However, because the architecture of the tumor cells was non-diffuse, and there were no necrotic foci, no mitoses, and no vascular or capsular invasion, we diagnosed it as an adrenocortical adenoma.
Larger tumors are more likely to become centrally ischemic, and ischemic regions can become fibrotic or liq- uify.12,17 However, not only an ishemic effect but also low steroid hormone levels can cause degeneration of an adrenocortical tumor. According to a study by Newhouse et al. of 30 adrenocortical adenomas with degeneration areas, only four (13%) adenomas were functional, while 26 (87%) had no endocrine dysfunction.12 Nevertheless, of adrenal tumors confirmed by surgery, 72% were functional, with a prevalence of benign tumors, and 28% were non- functional, with 35% malignant.18 That is to say, the number of functional adrenal tumors surgically excised is three times as large as that of non-functional tumors. This is partly because discovering small non-functional tumors is difficult, but these data suggest that adrenocortical adenomas with degeneration are more likely to be non-functional. The ishemic effect alone cannot explain this. To understand it, it is essential that we take hormonal effects into consideration.
Functional adenomas are less degenerative. This is prob- ably because high steroid hormone levels in the adrenal cor- tex, that is, hormones secreted by adenomas, suppress the production of a series of cytokines that stimulate interstitial cells such as fibroblasts.
Then, why do adrenocortical adenocarcinomas, though more often functional, frequently show degeneration? There are indications that an ischemic reaction is involved in the degeneration. Because carcinomas grow quickly, they have partially ischemic regions that might show degeneration, fib- sosis, liquefication, carcification and so on. Because necrotic areas have no blood vessels, steroid hormones, as well as blood, do not spread into these areas. That is, both ischemic and hormonal effects cause severe degeneration. In the case of carcinoma, severe degeneration might be triggered by an ischemic effect.
In our case, the tumor was not particularly large. An ischemic effect alone could not have caused extensive degeneration. First, this tumor was non-functional. Although the plasma cortisol level was normal, the level inside the tumor might have been lower than that in the normal adrenal cortex because the tumor was filled with tumor cells not pro-
ducing hormones. Interaction between ischemia and a low hormone effect resulted in an interstitial tissue myxoid. Next, the myxoid change of the interstitial tissue progressed, becoming more ischemic. Finally, the tumor came to contain an extensive area of fibrosis. Consequently, in our case, extensive areas of degeneration might have been triggered by the effect of low hormone concentrations.
As the technology of CT and MR imaging has advanced, more adrenal microtumors have been the discovered inciden- tally. Therefore, if degenerated non-functional tumors are very small, the differential diagnosis between carcinomas and benign tumors becomes more important. To the best of our knowledge, this is the first published case of a non- functional adrenocortical adenoma with extensive degenera- tion, and in which fibrosis was particularly remarkable.
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