Surg Today (2000) 30:294â297. Recurrence of Giant Adrenocortical Carcinoma in the Contralateral. Adrenal Gland 6 Years After Surgery: Report of a Case.
Surg Today (2000) 30:294–297
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 3 19 3 10 cm in size and 4 700 g in weight, was histopathologically 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 adrenocortical 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 diagnostic imaging techniques. Because they are generally found at an advanced stage, especially when nonfunctional, and there is no effective therapy, adrenocortical carcinomas are usually associated with a poor progno-
Reprint requests to: K. Kunieda (Received for publication on Jan. 5, 1999; accepted on Sept. 17, 1999)
sis. We describe herein the case of a giant adrenocortical carcinoma which recurred in the contralateral adrenal 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 computed axial tomography (CT) and intravenous pyelography (IVP) detected a giant mass in the right side of the abdomen, which was diagnosed as right adrenocortical cancer. He was transferred to our department for surgical treatment. Physical examination revealed a slightly emaciated man, 160 cm in height and 47.5 kg 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 abdominal 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 immunosuppressive acidic protein values. A serum endocrine assessment showed increased levels of cortisol, 11deoxycortisol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate to 23.1 µg/dl, 5.6 ng/ml, 18 ng/ ml, and 3 400 ng/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 233.1 µg/day, and 17-ketosteroid (17-KS) to 28.2 mg/day. Abdominal echography revealed an encapsulated tumor with a hypoechoic outer and hyperechoic inner pattern, occupying the right side of the abdominal cavity. The inferior vena cava was
K. Kunieda et al.: Recurrent Giant Adrenocortical Carcinoma
Fig. 1. Computed tomography (CT) scan demonstrated a huge mass (20 3 20 cm) with a low-density area in the center compressing the liver to the left side and the right kidney to the caudal side
deviated to the left side by the tumor. CT confirmed the presence of a solid heterogeneous mass, 20 3 20 cm 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 deviation to the left side due to tumor compression. These results indicated a diagnosis of adrenal cancer. A laparotomy was performed which disclosed an encapsulated 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, encapsulated, elastic soft tumor, 29 3 19 3 10 cm in size and 4 700 g in weight. Its cross section demonstrated a lobular structure with solid parts, fatty necrosis, and hematoma formation (Fig. 2). Histologically, the tumor cells showed nuclear pleomorphism, hyperchromasia, mitotic figures, and liver infiltration (Fig. 3). The lesion was diagnosed as a welldifferentiated adrenal cortical carcinoma, and the patient received adjuvant chemotherapy with mitotane (o,p9-DDD), 4 g/day for 3 months. A postoperative serum endocrine assessment revealed decreases in the values of cortisol, dehydroepiandrosterone sulfate, and ACTH to 15.9 µg/ml, 2 510 ng/ml, and 55.2 pg/ml, respectively. The urinary free cortisol and 17-KS also normalized to 58.1 µg/day and 2.6 mg/day, respectively.
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Fig. 2. The resected specimen contained a reddish brown, encapsulated, elastic soft tumor, 29 3 19 3 10 cm in size and 4 700 g in weight. Its cross section demonstrated a lobular structure with solid parts, fatty necrosis, and hematoma formation
Fig. 3. Histological findings revealed tumor cells with nuclear pleomorphism, hyperchromasia and mitotic figures (H&E stain, 3200)
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 3 7.5 3 6 cm in size and 230 g in weight, and the pelvic tumor was 19 3 14 3 10 cm in size and 1 070 g in weight. Histopathological findings were again indicative of an adrenocortical car-
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Fig. 4. A CT scan done 6 years after the initial operation demonstrated a recurrent left adrenal mass, 11 3 7 cm in size
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 problematic to diagnose since they cause various clinical symptoms 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 frequency of incidentally discovered adrenal masses, making it now possible to detect adrenal carcinomas at an early stage. According to a review by Wooten et al.,4 adrenocortical 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 frequently in children and young women, whereas nonfunctional 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
K. Kunieda et al.: Recurrent Giant Adrenocortical Carcinoma
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 symptoms to be larger than functioning tumors with symptoms. They also found a correlation between tumor size and prognosis. On the other hand, Didolkar et al.9 reported an inverse relationship between the two, stating that patients with tumors over 10 cm 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 metastases 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 peritoneal 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 administered 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 recurrence is generally poor, Kizaki et al.10 reported a patient who delivered a healthy baby after overcoming four recurrences of adrenocortical carcinoma. They confirmed the efficacy of surgery even for recurrent tumors and also speculated that a close relationship exists between 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 operation 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 characteristics, including histological differentiation, are determinants of the prognosis. References 1. Copeland PM (1983) The incidentally discovered adrenal mass. Ann Intern Med 98:940–945
K. Kunieda et al.: Recurrent Giant Adrenocortical Carcinoma 2. Greenberg PH, Marks C (1978) Adrenal cortical carcinoma: a presentation of 22 cases and a review of the literature. Am Surg 44:81–85 3. Karakousis CP, Rao U, Moore R (1985) Adrenal adenocarcinomas: histologic grading and survival. J Surg Oncol 29:105– 111 4. Wooten MD, King DK (1993) Adrenal cortical carcinoma: epidemiology and treatment with mitotane and a review of the literature. Cancer 72:3145–3155 5. Sullivan M, Michel B, Hodges CV (1978) Adrenal cortical carcinoma. J Urol 120:660–665 6. Bradley EL (1975) Primary and adjunctive therapy in carcinoma of the adrenal cortex. Surg Gynecol Obstet 141:507–511
297 7. Cohn K, Gottesman L, Brennan MF (1986) Adrenocortical carcinoma. Surgery 100:1170–1177 8. Shimazaki J, Ichikawa T, Shiseki Y, Kuramochi H (1993) Adrenal cortical carcinoma (in Japanese with English abstract). Nippon Rinshou (Jpn J Clin Med) 51:766–782 9. Didolkar MS, Bescher RA, Elias EG, Moore RH (1981) Natural history of adrenal cortical carcinoma: a clinicopathologic study of 42 patients. Cancer 47:2153–2161 10. Kizaki Y, Yamamori K, Sudoh S, Fusaoka T, Ueshima Y, Matsuo T, Inoue F, Furukawa N, Kinugasa A, Sawada S (1994) A case of adrenocortical carcinoma who delivered a healthy baby after overcoming four recurrences (in Japanese with English abstract). Nippon Shonika Gakkai Zassi (J Jpn Pediatr Soc) 98:2176–2184
