Case Reports
RENAL ADENOCARCINOMA WITH SOLITARY METASTASIS TO THE CONTRALATERAL ADRENAL GLAND: REPORT OF 2 CASES AND REVIEW OF THE LITERATURE
MICHAEL LEMMERS, KEVIN WARD, THOMAS HATCH AND PETER STENZEL From the Division of Urology and Department of Pathology, Oregon Health Sciences University, Portland, Oregon
ABSTRACT
We report 2 rare cases of renal adenocarcinoma with solitary metastasis to the contralateral adrenal gland, 1 recognized synchronously with the primary neoplasm and 1 found 15 years after nephrectomy. The latter case represents the longest reported interval between nephrectomy and treatment of a solitary contralateral adrenal metastasis of renal adenocarcinoma. Distinction of these metastatic tumors from primary adrenocortical carcinoma was facilitated by immunohisto- chemical markers. Twelve other reported cases of renal adenocarcinoma with solitary contralateral adrenal metastasis support aggressive surgical management of this lesion. (J. Urol., 141: 1177-1180, 1989)
Refined radiological techniques have improved the antemor- tem detection of solitary contralateral adrenal metastasis from renal adenocarcinoma. Consequently, some urologists have had the opportunity to manage this unusual lesion and generally have selected the aggressive surgical approach for solitary me- tastases of renal adenocarcinoma.1 We present 2 cases illus- trating several difficulties that confront urologists treating renal adenocarcinoma metastatic to the contralateral adrenal gland, including diagnosis and localization of the metastasis, surgical approach to the lesion and identification of the correct tissue of origin.
CASE REPORTS
Case 1. A 67-year-old man with persistent microscopic he- maturia had a left renal mass on excretory urography (IVP). Computerized tomography (CT) suggested a renal tumor (fig. 1) and a right adrenal mass. A 24-hour urine collection was negative for vanillylmandelic acid and metanephrines. Radioi- sotope bone scan and correlative spine radiographs revealed no
metastases. After successful completion of an inpatient alcohol detoxification program the patient underwent angiography, which demonstrated hypervascular masses in the left kidney and right adrenal gland without evidence of vena caval involve- ment. Via a right thoracoabdominal approach left radical ne- phrectomy and right adrenalectomy were performed without complication. Perioperative stress steroid doses were tapered rapidly to maintenance doses and the patient was discharged from the hospital 8 days postoperatively. He was well and without evidence of renal adenocarcinoma 5 months postoper- atively.
Pathological diagnosis was left renal adenocarcinoma with- out intravascular tumor, capsular invasion or local nodal in- volvement. The left adrenal gland was normal but there was a metastatic focus of adenocarcinoma in the right adrenal gland. The adrenal tumor was immunoreactive with antibodies to cytokeratin and to epithelial membrane antigen but not with anti-vimentin antibodies.
Case 2. A 68-year-old man underwent uncomplicated right nephrectomy for a lower pole renal adenocarcinoma 15 years before presentation with fatigue, early satiety, 30-pound weight
Accepted for publication November 15, 1988.
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loss and anemia. The right adrenal gland had not been removed. Initial evaluation of the recent symptoms revealed an epigastric mass, suggestive of a pancreatic tumor. CT revealed a mass 12 cm. in diameter adjacent to the tail of the pancreas, splenic hilus and upper pole of the left kidney (fig. 2). An IVP dem- onstrated prompt function in the left kidney, which was dis- placed inferiorly by the mass. Selective arteriography showed a large hypervascular mass in the left adrenal gland (fig. 3). The left kidney and renal vessels were uninvolved. At hospi- talization the serum creatinine was 1.2 mg./dl. (normal 0.8 to 1.3) and the hematocrit was 30 per cent with hypochromic, microcytic erythrocyte indexes. Radioisotope bone scan, chest radiographs and lung tomograms revealed no evidence of me-
tastases. No other abnormalities were found on the remainder of the physical examination or laboratory evaluation.
Complete resection of the mass required left adrenalectomy, splenectomy and distal pancreatectomy through a left thora- coabdominal incision. The left kidney was uninvolved. A month postoperatively poor appetite and a transient hemolytic anemia necessitated rehospitalization. The patient responded well to nutritional supplementation and the hemolytic process resolved spontaneously without an identified etiology. He was well and gaining weight 1 year postoperatively, with no evidence of renal adenocarcinoma.
The 610 gm., 16 x 10 x 9 cm. tumor was grossly encapsulated. Microscopically, malignant neoplasm consistent with met- astatic renal adenocarcinoma of the clear cell type was identi- fied, which did not invade adjacent structures. The tumor was similar histologically to the primary right renal adenocarci- noma resected 15 years previously. Electron microscopic ex- amination of formalin-fixed tissue revealed epithelial cells con- taining cytoplasmic lipid but details of cell membranes and mitochondria were not preserved sufficiently for ultrastructural distinction of renal or adrenal origin.2 Immunohistochemistry revealed the presence of cytokeratin and epithelial membrane antigen but failed to demonstrate vimentin in the tumor.
DISCUSSION
Owing to the clinically silent nature of many primary renal adenocarcinomas, distant metastatic disease occurs in approx- imately a third of the patients by the initial diagnosis and has been documented in about half of the autopsy cases.3 Most frequently, metastases involve lung, lymph nodes, liver and bone. Less often, adrenal glands harbor metastases (about 5 per cent antemortem4 and up to 19 per cent postmortem5), almost always ipsilateral to the primary tumor. Occasionally, contralateral adrenal metastasis occurs, rarely achieving clini- cal significance in its usual setting of multiple diffuse metas- tases with an attendant grave prognosis. Sometimes, however, renal adenocarcinoma involves the contralateral adrenal gland as a solitary metastasis, creating a therapeutic challenge.
Since 1939, when Barney and Churchill reported the first resection of a solitary metastasis of renal adenocarcinoma and subsequent long-term patient survival,6 surgeons often have resected such metastatic lesions, providing survival rates simi- lar to those of patients without detectable metastatic disease at nephrectomy.1,7, 8 In the 1967 review by Middleton of the 33- year experience with renal adenocarcinoma at New York Hos- pital-Cornell Medical Center solitary metastases were identi- fied in only 8 of 503 patients (1.6 per cent), none of which was reported in the adrenal glands.1 Of these 8 metastatic lesions half were recognized after nephrectomy. Despite surgical treat- ment most of the 8 patients died of diffuse metastatic disease within 4 years of nephrectomy. However, 1 patient survived at
| Reference | Pt. Age-Sex | Side of Primary | Detection of Adrenal Metastasis | Diagnostic Procedures |
|---|---|---|---|---|
| Foucar and Dehner12 | 58-M | Rt. | Before primary | Exploration |
| 80-F | Lt. | Before primary | Ultrasound, CT and IVP | |
| Previte and associates13 | 54-F | Rt. | Synchronous | CT, angiography, and venacavography |
| 55-F | Lt. | Synchronous | CT, angiography | |
| Neal and associates14 | 54-M | Lt. | Synchronous | Angiography |
| 57-F | Rt. | Synchronous | Angiography | |
| Campbell and associates5 | 56 --- F | Lt. | Synchronous | IVP and angiography |
| Masuda and associates15 | 60-M | Lt. | Synchronous | CT |
| Katsuoka and associates16 | 77-M | Rt. | Within 1 yr. of | CT |
| nephrectomy | ||||
| Kondoh and associates17 | 55-M | Lt. | Synchronous | CT, angiography |
| Hasegawa and associates18 | 57-M | Lt. | 6 mos. after | CT, angiography |
| nephrectomy | ||||
| 46-F | Rt. | 1 yr. after nephrectomy | CT | |
| Current report | 67-M | Lt. | Synchronous | IVP, CT and angiogra- phy |
| 68-M | Rt. | 15 yrs. after nephrectomy | CT, IVP and angiogra- phy |
Although frequently cited, a case reported by Deodhar and associates involved a patient whose right primary renal adenocarcinoma (with right adrenal extension) had metastasized to the left adrenal gland and left kidney.19
least 17 years after excision of a solitary temporal lobe metas- tasis that appeared 14 years after initial nephrectomy. The remote occurrence of metastatic renal adenocarcinoma has received ample documentation, with lesions recognized as long as 31 years after nephrectomy.9 Such long latency illustrates the capacity of this tumor for remarkably slow growth. Reports of therapeutic success with solitary metastases of renal adenocarcinoma? justify an aggressive surgical approach. Timely intervention in these cases has been facilitated by significant advances in diagnostic radiology, including selective arteriography,1º CT and percutaneous needle biopsy.11
Although exceptionally rare, the antemortem detection and treatment of a solitary contralateral adrenal metastasis of renal adenocarcinoma have been reported by several investigators (see table).5,12-19 Of the 12 patients other than our own half were reported without evidence of disease at least 20 to 36 months after nephrectomy, 3 had died of distant metastatic disease between 12 and 22 months postoperatively, and the followup status of the remaining 3 is uncertain. These cases demonstrate either synchronous identification of primary and metastatic tumor, or metachronous detection within 1 year of diagnosis of primary renal adenocarcinoma. Our case 1 repre- sents the more typical presentation-evaluation of urinary tract signs or symptoms leading to discovery of solitary adrenal metastasis from a contralateral primary renal neoplasm. In contrast, case 2 demonstrates the appearance of metastatic disease of the contralateral adrenal gland many years after treatment of the primary tumor. To the best of our knowledge this latter case also represents the longest reported interval between nephrectomy and resection of a solitary contralateral adrenal metastasis. Despite its location in the contralateral adrenal gland, the metastatic lesion in case 2 failed to induce preoperative or postoperative adrenal insufficiency owing to retention of the ipsilateral adrenal gland. In general, metastatic adrenal disease of any type rarely destroys enough tissue to cause adrenocorticoid insufficiency.20 Conversely, of 8 cases found in 1 retrospective study of Addison’s disease due to adrenal metastases21 2 resulted from contralateral adrenal me- tastases after right radical nephrectomy. Obviously, radical nephrectomy and contralateral adrenalectomy, as in case 1, necessitate life-long steroid replacement. The handling of the ipsilateral adrenal glands in our cases demonstrates a potential benefit of adrenal-sparing nephrectomy.4
Proving the renal origin of a clear cell carcinoma in the adrenal gland is difficult or impossible by conventional histo- logical techniques, 12,22 and is particularly problematic when the
adrenal tumor is found long after resection of the primary renal tumor, as in case 2. Electron microscopy may be helpful if suitably preserved tissue is available2 but it is insufficient for the distinction of renal or adrenal origin with suboptimally fixed tissue (also illustrated by case 2). The application of immunocytochemistry to the differential diagnosis of adreno- cortical and renal cell neoplasms has established markers for their distinction.23 Cytokeratin and epithelial membrane anti- gen immunoreactivity in the absence of vimentin immunoreac- tivity offered strong evidence in favor of the diagnosis of metastatic renal adenocarcinoma in both of our cases.
ADDENDUM
The patient described in case 1 died 14 months postopera- tively with radiological evidence suggesting metastatic pulmo- nary disease.
Dr. John Barry reviewed the manuscript and suggested im- provements.
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