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SURGERY TODAY C Springer-Verlag 2000
Recurrence of Giant Adrenocortical Carcinoma in the Contralateral Adrenal Gland 6 Years After Surgery: Report of a Case
KATSUYUKI KUNIEDA1, SHIGETOYO SAJI1, SHIGERU MORI1, MOTOHISA KATOH1, KIICHI MIYA1, KEIGO YASUDA2, TOMOATSU MUNE2, and KUNIYASU SHIMOKAWA3
1 Second Department of Surgery, 2 Third Department of Medicine, and 3 Department of Laboratory Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan
Abstract: We report herein the case of a patient in whom a giant adrenocortical carcinoma was found to have recurred in the contralateral adrenal gland and intrapelvic cavity 6 years after his initial operation. A 52-year-old man had consulted our hospital complaining of right upper abdominal pain and weight loss, and was subsequently diagnosed as having a giant adrenal tumor by computed tomography scans and echography. A laparotomy was performed and the tumor, located in the right retroperitoneal cavity and infiltrating the liver and right kidney, was surgically removed. The lesion, 29 x 19 x 10 cm in size and 4700 g in weight, was histopathologi- cally diagnosed as an adrenocortical carcinoma. Adjuvant chemotherapy with mitotane was given for 3 months and his postoperative course was uneventful until a recurrence in the contralateral adrenal gland and peritoneal cavity was found 6 years later. The second resection was successful, and he is currently alive with no further sign of recurrence 8 years after his first operation. We report this unusual case as it provides much useful information on the biological features of adreno- cortical carcinomas and the state of tumor dormancy.
Key Words: adrenocortical carcinoma, adrenal cancer, survival time, giant adrenocortical carcinoma, contralateral adrenal gland
Introduction
Adrenocortical carcinomas are still regarded as a rare type of malignancy, although they are being detected with increasing frequency due to improvements in diag- nostic imaging techniques. Because they are generally found at an advanced stage, especially when nonfunc- tional, and there is no effective therapy, adrenocortical carcinomas are usually associated with a poor progno-
sis. We describe herein the case of a giant adrenocorti- cal carcinoma which recurred in the contralateral adre- nal gland and peritoneal cavity 6 years after surgical removal.
Case Report
A 52-year-old man who had suffered weight loss and abdominal discomfort for 4 months presented to the Third Department of Medicine at our hospital in March, 1990, complaining of a feeling of abdominal distention and upper abdominal pain. Abdominal com- puted axial tomography (CT) and intravenous pyelog- raphy (IVP) detected a giant mass in the right side of the abdomen, which was diagnosed as right adrenocor- tical cancer. He was transferred to our department for surgical treatment.
Physical examination revealed a slightly emaciated man, 160cm in height and 47.5kg in weight, with a blood pressure of 128/78 mmHg. On admission, he had marked bulging of the right side of the abdomen, due to the giant tumor, with venous dilatation of the abdomi- nal wall. The hard tumor was not tender to touch and low in mobility, although free from the abdominal wall. Blood tests revealed slight anemia, hypoalbuminemia, and elevated C-reactive protein and immunosup- pressive acidic protein values. A serum endocrine assessment showed increased levels of cortisol, 11- deoxycortisol, dehydroepiandrosterone, and dehydro- epiandrosterone sulfate to 23.1 ug/dl, 5.6 ng/ml, 18ng/ ml, and 3400ng/ml, respectively, and a decreased level of adrenocorticotropic hormone (ACTH) to 19.1 pg/ml. A urine endocrine examination also showed an increase in free cortisol to 233.1ug/day, and 17-ketosteroid (17-KS) to 28.2mg/day. Abdominal echography re- vealed an encapsulated tumor with a hypoechoic outer and hyperechoic inner pattern, occupying the right side of the abdominal cavity. The inferior vena cava was
Reprint requests to: K. Kunieda (Received for publication on Jan. 5, 1999; accepted on Sept. 17, 1999)
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deviated to the left side by the tumor. CT confirmed the presence of a solid heterogeneous mass, 20 × 20cm in size, compressing the liver to the left side and the right kidney to the caudal side, with a low-density area in the center (Fig. 1). Dripped intravenous pyelography also showed marked deviation of the right kidney to the caudal side caused by the tumor, and celiac artery angiography demonstrated a dilated tortuous feeding artery arising from the right hepatic artery and pooling in the capillary phase. Aortography comfirmed that the right adrenal artery was also feeding the tumor. Venacavography indicated a filling defect and a devia- tion to the left side due to tumor compression. These results indicated a diagnosis of adrenal cancer.
A laparotomy was performed which disclosed an en- capsulated soft tumor in the right retroperitoneal cavity adhering to the inferior vena cava and the liver. The tumor was extripated with partial resection of the liver. The resected specimen was a reddish brown, encapsu- lated, elastic soft tumor, 29 × 19 × 10cm in size and 4700 g in weight. Its cross section demonstrated a lobu- lar structure with solid parts, fatty necrosis, and he- matoma formation (Fig. 2).
Histologically, the tumor cells showed nuclear pleo- morphism, hyperchromasia, mitotic figures, and liver infiltration (Fig. 3). The lesion was diagnosed as a well- differentiated adrenal cortical carcinoma, and the pa- tient received adjuvant chemotherapy with mitotane (o,p’-DDD), 4g/day for 3 months. A postoperative se- rum endocrine assessment revealed decreases in the values of cortisol, dehydroepiandrosterone sulfate, and ACTH to 15.9 ug/ml, 2510ng/ml, and 55.2 pg/ml, respec- tively. The urinary free cortisol and 17-KS also normal- ized to 58.1 ug/day and 2.6 mg/day, respectively.
The patient had an uneventful postoperative course and remained well for 5 years, until he began to notice bilateral leg edema and consulted our hospital again in September 1996. The findings of an abdominal CT scan led to a diagnosis of obstructive renal failure caused by a huge pelvic tumor, and a left adrenal lesion (Fig. 4). Under the clinical diagnosis of metastasis from adrenal carcinoma, he underwent extirpation of the left adrenal tumor and pelvic tumor with partial resection of the rectosigmoid colon.
The adrenal tumor was 11 × 7.5 X 6cm in size and 230g in weight, and the pelvic tumor was 19 x 14 × 10cm in size and 1070g in weight. Histopathological findings were again indicative of an adrenocortical car-
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cinoma, identical to the prevous adrenal cancer. The postoperative course was uneventful and there is still no sign of recurrence, 8 years after his initial operation.
Discussion
Adrenocortical carcinoma is a rare disease, having an estimated incidence of 0.6 to 1.7 per million.1 As a cause of tumor death, its incidence has been calculated at between 0.02% and 0.2%.2,3 The tumors are composed of two types: hormonal-functioning tumors and nonfunctioning tumors. The former are less problem- atic to diagnose since they cause various clinical symp- toms but the latter are difficult to diagnose and are therefore associated with a poorer prognosis. Recent developments in diagnostic imaging techniques, such as CT and echography, have resulted in an increased fre- quency of incidentally discovered adrenal masses, mak- ing it now possible to detect adrenal carcinomas at an early stage.
According to a review by Wooten et al.,4 adrenocorti- cal tumors are more common in women (58.6%) and the age distribution is bimodal, with peaks in the first and fifth decades. Functional tumors occur more fre- quently in children and young women, whereas non- functional tumors are more common in older patients (84.7%). According to the staging system introduced by Sullivan et al.5 and Bradley,6 patients with Stage I or II disease have a good prognosis after surgery. In fact, Sullivan et al.5 reported 5-years survival rates of 100% in patients with Stage I disease, 80% in those with stage II disease, 20% in those with stage III disease, and 0% in those with stage IV disease. Cohn et al.7 noted mean survival periods of 5.0 and 2.3 Years for patients with Stage II and Stage IV disease, respectively. The disease
in our patient was classified as Stage III due to local invasion.
Shimazaki et al.8 reviewed the cases reported in the Japanese literature. They noted a tendency for nonfunctioning or functioning tumors without symp- toms to be larger than functioning tumors with symp- toms. They also found a correlation between tumor size and prognosis. On the other hand, Didolkar et al.9 re- ported an inverse relationship between the two, stating that patients with tumors over 10cm in diameter survived longer than those with smaller lesions. They speculated that this paradox was related to the fact that biologically aggressive tumors give rise to distant me- tastases and therefore become symptomatic at an early stage. Our case also supports the belief that large tumors may be relatively benign.
According to Didolkar et al.,9 the most common sites of metastases are the lung, liver, and lymph nodes in decreasing order. Interestingly, contralateral adrenal involvement was noted in 5 of 31 autopsy cases. In our patient, metachronous metastases were found in the contralateral adrenal gland and intrapelvic cavity. The intrapelvic tumor was presumably due to perito- neal dissemination.
Surgical resection is the first choice of treatment for patients with a resectable tumor; however, mitotane is recommended for first-line chemotherapy in patients with unresectable tumors, although according to the review by Wooten et al.,4 the clinical response rate is only about 35%. In our patient, mitotane was ad- ministered as postoperative adjuvant therapy and was thought to have been effective, considering the fact that the patient has survived for 8 years since his initial operation in spite of a huge malignant tumor with liver infiltration. While the prognosis of patients with recur- rence is generally poor, Kizaki et al.10 reported a patient who delivered a healthy baby after overcoming four recurrences of adrenocortical carcinoma. They con- firmed the efficacy of surgery even for recurrent tumors and also speculated that a close relationship exists be- tween prognosis and histological differentiation, based on their findings.
In conclusion, we described the case of a patient who suffered a relapse of giant adrenocortical cancer 6 years after undergoing complete resection. A second opera- tion proved successful and he is alive without any signs of recurrence 18 months later. Our experience of this case led us to speculate that the biological charac- teristics, including histological differentiation, are determinants of the prognosis.
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