Aldosterone-Producing Adrenocortical Carcinoma Metastases Found Seven Years After Adrenalectomy
Naoki Sakai,1* Tetsuo Yamada,1 Takeshi Asao,2 and Tetsuo Murayama1
Departments of 1Urology and 2Pathology, Sagamihara National Hospital, Sagamihara, Japan
We report a case of metastatic adrenocortical carcinoma detected 7 years after adrenalectomy. A 52- year-old woman, who had undergone adrenalectomy for an aldosterone-producing adrenocortical carcinoma at age 45, was found on examination by computerized tomography to have enlarged para- aortic lymph nodes. These nodes were surgically resected, and the histological diagnosis from the resected tissue was metastatic adrenocortical carcinoma. The patient has now survived for more than 9 years following the original adrenalectomy. Evidence suggests that this was a slow-growing tumor, because the primary tumor was sharply demarcated and the metastases were found 7 years after the original operation. We believe that aggressive surgical resection of metastatic lesions could lead to prolonged survival in patients with adrenocortical carcinomas of this type.
Int J Urol 1997;4:79-82
Key words: adrenocortical carcinoma, aldosterone-producing, lymph node metastases, surgical treatment, prolonged survival
INTRODUCTION
Aldosterone-producing adrenocortical carcinoma is extremely rare. Approximately 30 cases have been reported in the literature,1 one of which was described in 1988 by some of the present authors.2 In our cur- rent report we focus on this patient’s unusual subse- quent clinical course, featuring the discovery of lymph node metastases 7 years after adrenalectomy and sur- vival for a total of more than 9 years following the initial surgery. Certain other patients with adreno- cortical carcinomas have likewise been reported to survive for more than 10 years despite local recur- rence and/or metastasis.3-6 These cases indicate that some such tumors grow slowly, and that aggressive surgical excision of the metastatic lesion may allow prolonged survival of patients with slow-growing tumors.
CASE REPORT
A 45-year-old woman presented in August 1986 with pain in the left upper quadrant of her abdomen and a 2-year history of hypertension. Physical examination revealed a large mass in the left hypochondrium, which was demonstrated on computerized tomo- graphy (CT) to be an enhancing adrenal mass. The
levels of potassium, aldosterone, cortisol, and renin activity were 2.7mEq/L (normal range, 3.0-5.0), 850 pg/mL (35.7-240), 20.5mg/dL (3.7-13.0), and 0.5 (0.3-2.9), respectively. The excretion of urinary 17-ketosteroids was 5.2mg/day (1.5-6.5).
The patient underwent adrenalectomy in Septem- ber 1986. Macroscopically, the specimen was a well- encapsulated, multinodular mass, measuring 14 × 14 × 8 cm and weighing 470g (Fig. 1). Several histologi- cal structures were seen, including large areas where small polygonal tumor cells were arranged in a papil- lary trabecular pattern (Fig. 2A) and/or in solid nests (Fig. 2B). In a few areas, cellular pleomorphism with large nuclei was detected (Fig. 2C) and clear cells were also seen (Fig. 2D). In most areas, at least 1 mitotic figure was seen in each high power field. These observations led to a histological diagnosis of adrenocortical carcinoma. Postoperatively, hyperten- sion disappeared and the aldosterone level was re- duced to 57 pg/mL.
In June 1993, routine CT revealed enlarged para- aortic lymph nodes. At this time the patient was normotensive and the aldosterone level was normal. The enlarged nodes, extending from the left supra- renal region up to the iliac bifurcation in the para-aortic region, were surgically resected. Micro- scopically, they were almost entirely occupied by the same type of carcinoma cells as had been seen in the primary tumor (Fig. 3). Postoperatively, the patient received adjuvant chemotherapy with cisplatin, fluorouracil, and adriamycin. She has now been free of disease for more than 2 years following the second operation.
Received Mar. 21, 1996; accepted for publication in revised form Sep. 9, 1996. * Correspondence and requests for reprints to: Depart- ment of Urology, Sagamihara National Hospital, 18-1 Sakuradai, Sagamihara-shi, Kanagawa 228, Japan.
(A)
(B)
(C)
(D)
DISCUSSION
Aldosterone-producing adrenal tumors are usually adenomas; carcinomas of this type are rare.1 Bodie et al. examined 40 patients with hormonally functional adrenal carcinomas and reported that only 1 pre- sented with hyperaldosteronism.7 Furthermore, adre- nal carcinomas excreting only mineralocorticoid are even rarer. Greathouse et al. reviewed 30 cases of aldosterone-producing adrenal carcinomas and found that there were only 2 cases in which the tumor pro- duced solely aldosterone.1 In the other cases, secre- tion of adrenal glucocorticoids and/or sex steroids was also increased.1 In our case, in addition to the elevated aldosterone level, the cortisol level was also slightly increased.
Adrenocortical carcinoma, especially in the pres- ence of metastasis, is a highly lethal cancer. Bodie et al. analyzed 82 patients with this disease, and found that the 5-year survival rates were 43.9% when the cancer was localized, 12.5% when it had spread regionally, and 5.5% when metastasis had occurred.7 They noted that there was no significant difference in the survival rate between hormonally functional tumors and those that were nonfunctional. The out- comes reported by Sullivan et al. were even more dismal: only 11% survival when the cancer had spread to the lymph nodes or invaded locally, and no patient remaining alive at 2 years after distant metastasis had been found.8
However, some patients have survived much longer following a late local recurrence,3,4 while others have been reported to survive for a long time despite re- peated metastasis.5,6 Tikkanen et al. described a pa- tient who had multiple recurrent cancers surgically removed, yet survived for 25 years after the original adrenalectomy. These authors insisted that their pa- tient proved the existence of a relatively benign variant of metastatic adrenocortical carcinoma.5 Sakamoto et
al. also reported on a patient who was treated by repeated surgical resection, but who survived for more than 18 years.6 These cases indicate that some adrenocortical carcinomas grow slowly, and that ag- gressive removal of the metastatic lesions could result in long-term survival.
Weiss et al. reported that mitotic rate showed a strong correlation with survival.9 These authors pro- posed that adrenocortical carcinomas with more than 20 mitoses per 50 high power fields be designated as high grade, while others should be described as low grade. According to their study, high-grade tumors were usually associated with a poor prognosis. This classification places our case among the high grade tumors, since at least 1 mitosis was seen in almost every high power field. However, the patient has now survived for more than 9 years after the original adrenalectomy.
In our case, lymph nodes metastases were found 7 years after the primary surgery. This indicates that tumor cells had already metastasized to the lymph nodes at the time of primary surgery. (Left para-aortic lymph nodes should have been, but were not, dis- sected as part of the adrenalectomy procedure.) The long intervening period before the metastases became clinically apparent, however, indicates that they grew very slowly. The surgical observation that the primary tumor was well encapsulated also implies a slow growth rate.
We therefore speculate that some adrenocortical carcinomas are characterized by slow growth. Al- though mitotane, (o,p’-DDD), is effective for some adrenocortical carcinomas, surgical removal remains the treatment of choice not only for the primary tumor but for metastatic lesions. In some patients with these tumors, aggressive resection of the metastatic lesions could lead to prolonged survival.
REFERENCES
1. Greathouse DJ, McDermott MT, Kidd GS, Hofeldt FD. Pure primary hyperaldosteronism due to adrenal cortical carcinoma. Am J Med 1984;76:1132-1136.
2. Murayama T, Yamada T, Taguchi H, Tsuboi K. A case of aldosterone-producing carcinoma of adrenal cortex. Iryo 1988;42:637-639 (in Japanese).
3. Ishida T, Tokunaga S, Ohkawa M, Hisazumi H, Sasano H. Local recurrence of non-functioning adrenocortical carcinoma 14 years following surgical treatment: a case report. Acta Urol Jpn 1993;39:549-551 (in Japanese).
4. Donckier JE, Michel LA, Berbinschi A, De Coster PM, De Plaen JF, Ketelslegers JM, Buysschaert M. Late re- currence of operated adrenocortical carcinoma: atrial natriuretic factor before and after treatment with mitotane. Surgery 1989;105:690-692.
5. Tikkanen MJ, Sivula A, Kahri A, Pelkonen R. Recurrent adrenal cortical carcinoma with Cushing’s syndrome: twenty-five-year follow-up of a patient. J Endocrinol Invest 1980;4:425-427.
Int J Urol 1997;4:79-82
6. Sakamoto K, Ariyoshi A, Okazaki M. Metastatic adrenocortical carcinoma treated by repeated resection: a case report of long-term survival over 18 years. Int J Urol 1995;2:50-52.
7. Bodie B, Novic AC, Pontes JE, Straffon RA, Montie JE, Babiak T, Sheeler L, Schumacher P. The Cleveland Clinic experience with adrenal cortical carcinoma. J Urol
1989;141:257-260.
8. Sullivan M, Boileau M, Hodges CV. Adrenal cortical carcinoma. J Urol 1978;120:660-665.
9. Weiss LM, Medeiros LJ, Vickery AL. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989;13:202-206.