Case Report
A case of adrenal rest tumor of the liver: Radiological imaging and immunohistochemical study of steroidogenic enzymes
Yoshifumi Baba,1 Toru Beppu,1 Katsunori Imai,1 Toshiro Masuda,1 Ken-ichi Iyama,2 Hironobu Sasano3 and Hideo Baba1
1Department of Gastroenterological Surgery, Kumamoto University, 2Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto, and 3Department of Surgical Pathology, Tohoku University School of Medicine, Sendai, Japan
A case of adrenal rest tumor in the liver of a 67-year-old female was reported. The tumor appeared on diagnostic imaging as a hypervascular and fat-containing mass at the periphery of right hepatic lobe and required differential diag- nosis from hepatocellular carcinoma (HCC). Pathological diag- nosis of the intraoperative frozen section taken under laparoscopic liver biopsy could not exclude fat-containing HCC. Therefore, she underwent partial resection of the right hepatic lobe. A yellowish-brown mass, 17 x 14 x 11 mm in a diameter, was located in the subcapsular portion. Histologi- cally, the mass presented features similar to those of the
adrenal cortex and was composed of pale cells. Immunohis- tochemically, the mass expressed the adrenal 4-binding protein and several enzymes involved in the synthesis of adrenocortical steroids. Based on these findings, the hepatic mass was finally diagnosed as an adrenal rest tumor of the liver.
Key words: adrenal rest tumor of the liver, radiological imaging, steroidogenic enzymes
INTRODUCTION
T HE ADRENAL REST tumors are collections of aberrantly-located adrenocortical cells. They are usually detected in the celiac axis, testis, and broad liga- ments, which are related to the embryogenic develop- ment of the adrenal gland, but uncommon even in those sites.1 Adrenal rest tumors arising in the liver are very rare.2-6
An accurate preoperative radiological diagnosis is very difficult. The adrenal rest tumors in the liver have been reported to appear as a fat-containing and hypervascular mass on imagings.6 Radiological differential diagnosis includes fat-containing hepatocellular carcinoma (HCC) or angiomyolipoma.
Correspondence: Professor Hideo Baba, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan.
Email: hdobaba@kumamoto-u.ac.jp
Received 29 January 2008; revision 19 February 2008; accepted 21 February 2008.
As it is occasionally difficult to pathologically distin- guish the adrenal rest tumor from hepatocellular adenoma or HCC due to morphological similarity,2-4 a reliable diagnosis is required to prove steroid hormone production or excretion.7 However, most tumors are clinically non-functioning. Even in such cases, immuno- histochemical examinations with protein antigens related to adrenocortical steroidogenesis are useful to prove the steroidogenic capability of these tumors.8,9
Here we report a case of adrenal rest tumor with radio- logical imaging findings and the immunohistochemical examination results of steroidogenic enzymes.
CASE REPORT
A 67-YEAR-OLD female visited a local medical doctor for a regular medical checkup on May 2005; a hepatic mass was detected with ultrasound sonogra- phy (US) and computed tomography (CT). She had no family history of malignancy or significant past history. She was referred to our hospital for detailed examina- tion and treatment. The laboratory investigations,
Figure 1 Computed tomography (CT) images. (a) Tumor (arrow) is revealed to be hypodense (CT number: 3HU) on plain CT. (b,c) Tumor (arrow) is revealed to be hyperdense (38HU) in the early phase (b) and hypodense (13HU) in the delayed phase (c) on dynamic CT.
CT images
a
b
c
including hepatitis viral markers, found no abnormali- ties except for a slight elevation of alanine aminotrans- ferase and aspartate aminotransferase. Tumor markers (carcinoembryonic antigen, protein-induced vitamin K absence or antagonist II, and a-fetoprotein) were all within normal range. There were no abnormal physical findings except for mild obesity (body mass index = 27.4).
The US revealed a 1.5 cm solid mass showing hetero- geneous echogenicity at the periphery of the posterosu- perior subsegment of the right hepatic lobe, and fatty deposition was observed in the surrounding liver. Plain CT images showed a hypodense mass (CT number: 3HU). On multiphase dynamic CT images, the mass was enhanced heterogeneously and appeared to be hyper- dense in the early phase (38HU) and hypodense in the delayed phase (13HU) (Fig. 1). The lesion appeared to be isointense on T1-weighted, hypointense on T2-weighted, and hyperintense on superparamagnetic iron oxide-enhanced magnetic resonance imaging. Chemical shift images showed less signal intensity in the tumor than precontrast images. Hepatic arteriogra- phy revealed no enhanced lesion, but single-slice CT arteriography showed the mass, which enhanced hetero- geneously from the periphery to the center and then washed out, particularly in the central part of the mass. CT arterial portography revealed a portal perfusion defect at the lesion.
Based on above findings, HCC with fatty metamor- phosis or liver tumors with fatty contents, such as angiomyolipoma, were suspected. We performed a laparoscopic biopsy. The pathological diagnosis of the intraoperative frozen section could not exclude fat-containing HCC or metastatic renal cell carcinoma. Thus we underwent partial resection of the right hepatic
lobe. During the operation, a right adrenal gland was recognized apart from the liver tissue.
The macroscopic findings revealed that the tumor was yellowish-brown, 17 x 14 × 11 mm in a diameter, and well circumscribed (Fig. 2). Light microscopic studies showed that the tumor was composed of pale cells, and tumor cells were aligned in alveolar or fascicular arrangements in a similar manner with the features of the adrenocortical tissue (Fig. 3). Adrenal medulla was
not found. In normal hepatic parenchyma, fatty depo- sition was histologically observed in approximately 70% of normal hepatic cells.
Immunohistochemical examinations were performed with the antibodies to adrenal 4-binding protein and several steroidogenic enzymes (Table 1). The positivity for Ad4BP was detected in the nuclei of the tumor cells (Fig. 4a), and positive staining for the steroidogenic enzymes, such as P450 C21, P450 C17 (Fig. 4b), and 3-hydroxysteroid dehydrogenase (3ß-HSD) were detected in the tumor cells. Therefore, the cells were considered to possess the steroidogenic capability. This hepatic mass was finally diagnosed as an adrenal rest tumor arising in the liver.
Because there were no symptoms of hormonal abnor- mality, preoperative blood and urinary hormone levels were not measured. The postoperative hormone levels were all within normal range. The postoperative course was uneventful, and the patient was subsequently discharged.
| Antigen | Antibody | Source |
|---|---|---|
| P450scc (cholesterol side chain cleavage) | Rabbit polyAb | Sasano |
| 3ß-Hydroxysteroid dehydrogenase | Rabbit polyAb | Sasano |
| P450 C21 (21-hydroxylase) | Rabbit polyAb | Sasano |
| P450 C17 (17a-hydroxylase) | Rabbit polyAb | Sasano |
| P450 C11 (11ß-hydroxylase) | mAb | Sasano |
| Dehydroepiandrosterone | Rabbit polyAb | Sasano |
| Adrenal 4-binding protein) | Rabbit polyAb | Sasano |
PolyAb, polyclonal antibody; mAb, monoclonal antibody.
Tumor area
Normal parenchyma
a
Tumor area
Normal parenchyma
b
DISCUSSION
T HE ADRENAL REST tumors are considered to arise from adrenal tissues which occasionally occur outside of the adrenal gland. The aberrant adrenal tissues are divided into the heterotopia and the acces-
sory adrenal gland; the former is derived from adrenal primordium that has migrated at an embryonic stage from neighboring organs, such as kidneys or the liver, whereas the latter is the ectopia of fragmented adrenal tissues into the celiac axis, retroperitoneal cavity, uterus broad ligament, or testis. They usually consist only of adrenal cortical cells, rarely containing adrenal medul- lary cells.1 The adrenal rest tumors have been detected most commonly in the celiac axis, testis, and broad ligament, but the frequency is low. In the liver tissue, the adrenal tissues are seldom detected, and the adrenal rest tumors are completely rare.2-5
Macroscopically, the adrenal rest tumors of the liver are well-circumscribed, yellowish, nodular lesions which occur mostly beneath the capsule of the right hepatic lobe. Histologically, they are composed of cord-like arrangements of round to polygonal, pale, lipid-rich cells separated by vascular channels or bands of collagen.7,9 Pathological differential diagnoses include hepatocellular adenoma, HCC, metastatic renal cell carcinoma, and metastatic adrenocortical carci- noma. In this case, it was very difficult to distinguish the adrenal rest tumor from fat-containing HCC or meta- static renal cell carcinoma by an intraoperative frozen diagnosis of the liver biopsy tissue.
For the reliable diagnosis, it is necessary to demon- strate the steroidogenic capability of the tumor. However, most cases are clinically non-functioning. To our knowledge, only five cases of clinically-functioning adrenal rest tumors have been reported.4 Recently, the immunohistochemistry of several proteins involved in adrenocortical steroidogenesis constitute the most effec- tive method in the differential diagnosis.8,9 In this case, the immunohistochemical examination revealed that tumor cells were positive (Ad4BP, which is a transcrip- tion factor that regulates the expression of steroidogenic enzymes,10 and the three types of steroidogenic enzymes (P450 C21, P450 C17, and 3ß-HSD).8,9,11 P450 C17 is involved in the synthesis of glucocorticoid and sex hor- mones, and is distributed only in the adrenal cortex and gonads.12 P450 C21 is expressed in the adrenal cortex, but not in the gonads. Although P450scc P450 C11 dehydro- epiandrosterone, were not stained, these immuno- histochemical examinations showed that this tumor dif- ferentiated functionally into the adrenal cortex. Our case was clinically non-functioning, although it might possess the capacity to produce adrenocortical steroids.
The malignant transformation of hepatic adrenal rest tumors is quite rare. There has been only one case report, a 17-month-old boy with adrenocortical hyper- function accompanied by a malignant tumor of the
liver.3 In our case, no foci of atypical mitosis, necrosis, and capsular and venous invasion were detected, and the Ki-67 labeling index was very low. As a result, this tumor was considered to be benign.
We clinically seldom experience an adrenal rest tumor in the liver, therefore preoperative radiological diagnosis is very difficult.6 One specific radiological diagnostic character of an adrenal rest tumor in the liver is the presence of fat components.6,13 This will reflect intracytoplasmic lipid droplets of the tumor cells. The differential diagnoses of hepatic tumors con- taining fat components are as follows: HCC with fatty metamorphosis, focal nodular hyperplasia, hepatocel- lular adenoma, angiomyolipoma, lipoma, and liposa- rcoma.12 The other radiological diagnostic character is hypervascularity. The tumor is mainly supplied by the hepatic artery. Therefore, HCC with fatty metamor- phosis and angiomyolipoma could be considered as a differential diagnosis. In cases of hypervascular or fat-containing hepatic tumors, adrenal rest tumors of the liver should be added to the lists of radiological differential diagnoses.
In conclusion, we have reported a rare case of adrenal rest tumor arising in the liver with the radiological appearance and the immunohistochemical study of steroidogenic enzymes.
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