Case Report
Long-term survival after bilateral adrenalectomy for metachronous adrenocortical cancer
ISAO HARA,1 YUICHI SAKAMOTO,2 NAOKI KANOMATA,3 MOTOTSUGU MURAMAKI,1 YUJI YAMADA,1 GAKU KAWABATA1 AND SADAO KAMIDONO1
1Division of Urology, Kobe University Graduate School of Medicine, 2Department of Urology, Shakaihoken Kobe Central Hospital and 3 Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
Abstract
We report the case of a female patient with bilateral metachronous adrenocortical cancer who survived long-term after adrenalectomy. In 1991, the patient underwent left adrenalectomy to remove a huge adrenal mass (10 x 9 cm) displaying no hormonal abnormality. Histological diagnosis was adrenocortical cancer. A right adrenal mass (7x 6 cm) was found 4 years after left adrenalectomy. Right adrenalectomy was performed, and histological diagnosis was again adrenocortical cancer. The patient remains alive with no evidence of disease 8 years after last surgery.
Key words adrenalectomy, bilateral adrenal cancer.
Introduction
Adrenocortical cancer is one of the rarest tumors.1 Gen- erally, the prognosis for non-functioning tumors is worse than that for functioning tumor, since a function- ing tumor may cause various symptoms that can provide an early warning. The prognosis in cases of bilateral tumors is particularly bad. We encountered an extremely rare case of bilateral metachronous adrenocortical can- cer in which the patient has survived long-term after bilateral adrenalectomy.
Case report
In 1991, a 40-year-old woman presented to her local urologist with symptoms of left flank pain and fever. A left adrenal tumor (Fig. 1a) with no hormonal abnor- mality was diagnosed on examination. The tumor was so large (10 x 9 cm) that open left adrenalectomy was
Correspondence: Isao Hara MD, Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki- cho, Chuo-ku, Kobe 650-0017, Japan.
Email: hara@med.kobe-u.ac.jp
Received 17 December 2003; accepted 25 May 2004.
performed and a pathological diagnosis of adrenocorti- cal cancer was made. During follow-up 4 years later, the patient reported right flank pain, fever and gen- eral fatigue. Abdominal computed tomography (CT) revealed a right adrenal mass measuring 7x6 cm (Fig. 1b) and the patient was referred to Kobe Univer- sity Hospital in July 1995. T2-weighted magnetic reso- nance imaging (MRI) revealed signal hyperintensity in the center of the tumor, suggesting central necrosis (Fig. 2a). Coronal section MRI indicated that the tumor was located just above the kidney, extending toward the liver (Fig. 2b). The patient was 159.5 cm tall, weighed 50.5 kg and displayed blood pressure of 104/64 mmHg. No clinical hormonal signs were apparent. Laboratory evaluations revealed a hemoglobin level of 11.9 g/dL, blood-urea-nitrogen 10 mg/dL, creatinine 0.5 mg/dL and liver enzymes within normal ranges. Hormonal evaluation revealed an aldosterone level of 145 µg/mL (normal, 56.9-150.3 µg/mL), serum basal cortisol 12.4 µg/dL (normal, 5.9-17.0 µg/dL), adrenocortico- tropic hormone (ACTH) 27 pg/mL (normal, 4.4-48 pg/ mL), urinary vanillylmandeic acid 3.0 mg/24 h (nor- mal, 1.5-7.5 mg/24 h), urinary 17-ketosteroids (17-KS) 5.0 mg/24 h (normal, 2.4-11.3 mg/24 h) and urinary 17-hydroxycorticosterone 4.3 mg/24 h (normal, 1.6- 8.8 mg/24 h). These findings led to a suspicion of right adrenal cancer without hormonal activity. Chest CT
a
a
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and skeletal scintigraphy demonstrated no apparent metastasis.
Right thoracoabdominal adrenalectomy was per- formed. Although the adhesion of the tumor to adjacent organs was not severe, the tumor was carefully dissected. No nodal or vascular involvement was found. The patient was administered 300 mg/day cortisol sodium phosphate for 3 days. From day 4, she received 30 mg/ day hydrocortisone. Macroscpically, the tumor consisted of white-yellowish nodular lesions. Hemorrhage and necrosis were also found. Microscopically, the tumor had several necrotic foci. The cells were arranged pre- dominantly in a trabecular pattern and approximately 20% of the tumor cells were arranged in a diffuse pat-
Fig. 2 (a) T2-weighted magnetic resonance imaging (MRI) revealed signal hyperintensity in the center of the tumor, suggesting central necrosis. (b) Coronal section MRI indicated that the tumor was located just above the kidney, extending toward the liver.
tern. The tumor cells were polygonal with occasional bizarre nuclei; Fuhrman grade 4. Over 90% of the cells had eosinophilic cytoplasm and the remaining cells had clear cytoplasm (Fig. 3). The mitotic count was 14/ 50 hpf with abnormal mitosis. The tumor did not show capsular or venous invasion. The modified Weiss score was 6 and a malignant diagnosis was rendered.1 Histo- logical characteristics were the same as the contralateral adrenal cancer previously resected. No adjuvant therapy was initiated and as of 96 months postoperatively, there has been no evidence of recurrence.
Comment
Adrenal carcinoma is one of the rarest tumors in humans, accounting for only 0.2% of all tumors2 and is classified as either functioning or non-functioning. Although the prognosis of a functioning tumor was thought to be worse than that of a non-functioning tumor, mainly because functioning tumors are discov- ered at an earlier stage, no evidence has been estab- lished. Furthermore, the ratio of finding non-functioning tumors at earlier stage has been increasing as the use of diagnostic tools, such as CT and ultrasound imaging, has become more prevalent. Bilateral adrenal neoplastic disease, except in the relatively more frequent cases of metastases, pheochromocytoma and myelolipoma, rep- resents another rare condition. The first case of bilateral metachronous adrenal carcinoma was reported by Vieta et al.3 and Lucon et al. reported two cases of synchro- nous bilateral carcinoma of the adrenal gland in 1993.4 Approximately 5-10% of adrenal carcinoma patients reportedly display bilateral tumors. However, few reports in the literature have examined this subject and details regarding diagnosis or management are lacking. In Japan, a total of 11 cases of bilateral adrenal carci- noma have been reported.5,6
The prognosis of bilateral adrenal carcinoma is gen- erally extremely poor. All 11 Japanese patients reported with bilateral adrenal carcinoma died of the disease. The
present case represents the first to have survived more than 5 years after surgical resection. Since no adjuvant therapies, such as 1,1 dichloro-2 (O-chlorophenyl)-2 (P- chlorophenyl) ethane (OPDDD), were undertaken, no specific reason for this long-term survival is apparent.
Although it remains controversial as to whether con- tralateral tumors are caused by metastasis, many reports have assumed that bilateral adrenal masses represent metastatic disease of the adrenal gland. This notion is supported by the fact that the prognosis for bilateral adrenal carcinoma is extremely poor. In the present case, the contralateral tumor appeared 4 years after the resection of the original tumor, with no other findings of metastasis, and resection of the tumor has lead to long-term survival. Given this situation, the contralat- eral tumor in the present case may have developed inde- pendently of the original tumor.
In conclusion, we encountered a patient who has survived long-term after bilateral adrenalectomy for metachronous adrenocortical cancer. Since effective chemotherapeutic protocols have not yet been estab- lished for adrenal carcinoma, surgical resection should be attempted for resectable lesions.
References
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