Aspiration Cytology of Simultaneous Bilateral Adrenal Metastases From Renal Cell Carcinoma. A Case Report and Review of the Literature

0022-534 7/85/1342-0315$02.00/0 Vol. 134, August

THE JOURNAL OF UROLOGY

Copyright © 1985 by The Williams & Wilkins Co.

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Case Reports ASPIRATION CYTOLOGY OF SIMULTANEOUS BILATERAL ADRENAL METASTASES FROM RENAL CELL CARCINOMA. A CASE REPORT AND REVIEW OF THE LITERATURE LUCIO LUCIANI,* PIERANTONIO SCAPPINI, TERESA PUSIOL

AND

FRANCESCO PISCIOLI

From the Division of Urology and Institute of Anatomic Pathology, S. Chiara Hospital, Trento, Italy

ABSTRACT

We report the computerized tomography and ultrasound-guided aspiration cytology results in the first case of renal cell carcinoma with bilateral adrenal involvement. The adrenal metastases were evident clinically 6 years after radical nephrectomy and were treated successfully by an operation. Aspiration cytology under computerized tomographic and sonographic guidance is an excellent procedure to evaluate enlarged adrenal glands in patients with renal cell carcinoma or other malignant neoplasms. Contralateral adrenal involvement is an extremely rare complication of renal cell carcinoma and the diagnosis is inaccurate in 25 per cent of the cases reported. 1- 6 The remarkable advances in imaging procedures made in recent years, particularly in computerized tomography (CT) and ultrasonography, allowed a cytological study of retroperitoneal organs inaccessible by physical examination. In fact, the chances of obtaining adequate tissue from the adrenal gland have improved significantly with the advent of these new imaging methods, which facilitate accurate needle placement. We report the CT-guided aspiration cytology diagnosis in the first case of simultaneous bilateral adrenal involvement with renal cell carcinoma. Emphasis is placed on the value and role of aspiration cytology studies in the diagnosis of adrenal tumors. CASE REPORT

A 60-year-old man with renal cell carcinoma of the lower pole of the kidney involving the renal vein and vena cava (stage 3) underwent left nephrectomy with removal of an intracaval tumor thrombus in April 1978. The patient was healthy until August 1983, when he was rehospitalized because of abdominal pain and nausea. Excretory urography revealed a suprarenal growth approximately 7 cm. in diameter with inferior displacement of a normal right kidney. Abdominal aortography and right renal arteriography showed the presence of bilateral adrenal masses (fig. 1). Abdominal ultrasound revealed 8 and 6 cm. growths in the right and left adrenal glands, respectively. The findings were confirmed by phlebography and CT scanning, which also demonstrated infiltration of the posterior wall of the inferior vena cava. A chest x-ray and bone scan were negative. A percutaneous fine needle aspiration cytology study was performed under sonographic and CT guidance with the patient under local anesthesia (fig. 2). While the patient suspended respiration, a long beveled modified 22 gauge Chiba needle with side holes was inserted from a posterior approach. Microscopic Accepted for publication March 12, 1985. Supported in part by grants from Lega per la Lotta contro i TumoriTrento, Italy. * Requests for reprints: Division of Urology, S. Chiara Hospital, 138100, Trento, Italy. 315

examination of the aspirate revealed the metastatic nature of the masses (fig. 3). Staged right and left adrenalectomies were done. No macroscopic involvement of the regional lymph nodes was observed at operation. Histopathological examination of the surgical specimens demonstrated bilateral metastatic involvement from renal cell carcinoma (fig. 4). The patient remained asymptomatic during the following 10 months. Gross tumor and histological findings. The right adrenal mass measured 9 x 8 x 5 cm. and was of a bright yellow color. The lesion was hemorrhagic, with focal areas of necrosis. At the periphery of the tumor the adrenal parenchyma was com pressed, forming a pseudocapsule. The left adrenal mass measured 4 x 5 x 3 cm., with a gross appearance similar to the contralateral lesion. Histological examination revealed neoplastic cells similar to those of renal cell carcinoma (fig. 4). The adrenal parenchyma was evident at the periphery of the malignant tissue. Cytological results. The aspirate from the adrenal lesions was highly cellular and showed malignant cells clumping in dense large sheets or small clusters. Sometimes, the cells showed a papillary arrangement with a remarkable tendency to overlap (fig. 3, A). Atypical cells arranged singly were inconstant in occurrence as a consequence of the cohesiveness of the neoplastic tissue. The background showed granular proteinaceous precipitate, many erythrocytes and hemosiderin pigment. Neoplastic cells were round or oval in shape, varied considerably in size and generally were well preserved. The typical clear cytoplasm showed a faintly eosinophilic staining pattern, with large, irregular vacuoles displacing the nucleus to the edge of the cell border, and was studded occasionally with tiny vacuoles giving it the appearance of lace. The main diagnostic feature of malignancy in these neoplastic cells was the typically large, round, single, eosinophilic nucleolus, which often was placed centrally in the nucleus and was surrounded by a clear halo (fig. 3, B). The nucleolus was round and sometimes polymorphous with a thick irregular nuclear outline. The chromatin was granular and the more degenerated the cells were the greater the tendency for the granularity of the chromatin to progress from fine to coarse. In the well preserved nuclei the chromatin tended to collect at the nuclear margins and, when

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cells appeared in large clusters, differences in the chromatin pattern and hyperchromatism of the individual cells could be recognized. Since the neoplastic cells showed morphological features similar to those of the removed neoplasm, the diagnosis was bilateral adrenal metastases from renal cell carcinoma. DISCUSSION

Aspiration cytology has been used extensively in the diagnosis of many human neoplasms but it has not gained widespread acceptance in the diagnosis of adrenal tumors. The adrenal growths may be reached safely by the fine needle with the aid of CT or ultrasound and are optimal sites for aspiration biopsy. In the United States and Europe there have been few aspiration cytology studies of primary and metastatic adrenal tumors, while a dramatic increase has occurred in the reports on fine needle aspiration cytology studies of other deep-seated retroperitoneal tissues and organs (see table). 1 - 21 Even in texts of fine needle aspiration the adrenal neoplasms are not discussed extensively. In the diagnosis of adrenal lesions the combination of ultrasound, CT and aspiration cytology may provide definitive and conclusive diagnosis in most of the cases. CT is the single best

FIG. 1. Midstream aortogram shows high neovascularity in right and left suprarenal masses. Larger right adrenal mass displaces kidney inferiorly and laterally.

imaging method for adrenal tumors, since it can delineate accurately any lesion larger than 1 cm. and provides information about the precise relationship of the tumor to adjacent organs. Ultrasonography has been reported to be useful, especially with adrenal masses larger than 2 to 3 cm. The size of the mass perhaps is the most helpful determinant of the nature of an adrenal lesion. Adrenocortical tumors larger than 5 cm. in diameter generally behave like carcinomas even if malignancy is not evident microscopically. Malignancy is statistically unlikely in small nonfunctioning tumors less than 5 to 6 cm. in diameter detected by CT. Since histological confirmation of whether an adrenocortical lesion is benign or malignant may be difficult, aspiration cytology alone also cannot be helpful in such differentiation. The bland cytological finding from adrenal masses smaller than 5 cm. indicates the benign nature of the lesion. Aspiration cytology is useful in distinguishing metastatic from primary malignant adrenal neoplasms. In patients with known malignant disease a concomitant lesion located in the adrenal gland should be biopsied to establish whether the mass is a metastasis or a nonfunctioning adenoma. The finding of

FIG. 2. Transcutaneous fine needle biopsy of solid left adrenal tumor. Long beveled modified 22 gauge needle with side holes passes through space between spleen and spine. Correct placement of tip within mass is verified by CT scan (arrow).

FIG. 3. A, cluster of adenocarcinoma cells with great variability in nuclear size and large vacuoles in cytoplasm displacing nuclei to periphery of cells. H & E, reduced from X250. B, neoplastic cells with single round nucleolus surrounded by clear halo and cytoplasmic vacuoles. H & E, reduced from Xl,000.

ASPIRATION CYTOLOGY OF BILATERAL ADRENAL METASTASES FROM RENAL CELL CARCINOMA

metastasis often is significant in clinical staging. Therefore, an operation in these cases will be mainly for diagnostic purposes. The positive cytology aspiration indicating adrenal metastatic involvement may spare patients the higher risk of an exploratory operation and/or may obviate extensive local therapy when systemic therapy may be more appropriate.

317

In patients with renal cell carcinoma the correct preoperative identification of contralateral adrenal involvement is difficult. The preoperative diagnosis was inaccurate in 25 per cent of the cases reported. In our case extraction of the tumor thrombus through a venacavotomy prolonged the operating time and the left adrenal gland (macroscopically normal) was not removed so as not to increase the morbidity of the operation. The neovascularity seen in the midstream aortogram was highly suspicious of bilateral adrenal involvement from renal cell carcinoma, especially when the history was considered. Since radiology was not conclusive of the nature of the adrenal masses, aspiration biopsy seemed useful. Cytology confirmed the true nature of the lesions. The aspirate demonstrated malignant cells that were similar to those of renal cell carcinoma. It also is noteworthy that in patients with malignancy a normal-sized adrenal gland may contain metastases. In conclusion, aspiration cytology under CT or ultrasound guidance may be considered the procedure of choice in the diagnostic evaluation of the status of normal-sized or enlarged adrenal glands in patients with renal cell carcinoma or other malignancy. ADDENDUM

FIG. 4. Histological section of adrenocortical metastasis from renal cell carcinoma.

Since this paped was submitted for publication an excellent article by Berkman and associates has been published. 22 These authors studied 18 adrenal masses in 16 patients with CTguided aspiration biopsy using an 18 to 20 gauge modified Chiba needle. Adrenal adenomas, cysts, metastases, melanoma and adrenal hemorrhage were diagnosed. In our experience with aspiration cytology in the staging of

Summary of reported adrenal aspiration cytology results Cytology Findings Reference

No. Pts.

Needle (gauge)

Guidance No. Pos.

Not specified

Fluoroscopy

Scheible and associates7

3

Pereiras and associates8 Haaga• Ferrucci and associates 10

2

Chiba

Fluoroscopy

3

Menghini (14) Chiba (22)

CT CT, ultrasound and fluoroscopy Fluoroscopy Ultrasound

Levin 11

Buonocore and Skipper12 Zornoza and associates 13 Heaston and associates 14

-(22)

1 1

Turner (20)

21

Spinal type (18-22)

14

Spinal or screw type

Dubious, Inadequate, Neg.

Final Diagnosis

Complications

3

2 adrenal cysts, 1 bloody aspirate

None

2

(hemorrhage and hematoma at operation) Not specified

None

3

Not specified

5*

1 pneumothorax

1 1

Fluoroscopy, CT

12

CT

13

4 false and 5

true neg. 1 inadequate

(20-22)

Adrenocortical Ca Not specified

None

9 adenoca., 3 adrenocortical Ca, 3 neuroblastomas, 1 melanoma, 4 cysts, 1 myelolipoma 2 nonfunctioning adrenal adenomas, 2 primary adrenocortical Ca, 8 metastatic adrenal Ca, 1

None None

blastomycosis Nosher and associates 15 Halvorsen and associates 16 Liiningand associates17 Pagani 18

4

-

(20-22)

Ultrasound

1 cyst, 2 adrenal metastases, 1

None

primary adrenal Ca Adrenal blastomycosis

None

1

Chiba

CT

1

6

Chiba

CT

6

24

-(22)

CT

4

12 true neg., 8 inade-

Chiba T (19-

CT

7

1 inadequate

CT

14

5 adenomas, 1 metastatic adenoca. from breast 3 rt. and 1 bilat. adrenal metastatic small cell lung Ca

None 2 pneumothorax

quate Price and associates 19

Pagani20

Katz and associates21

8

20)

14 32 22

-(22)

-

(18-22)

* Do not distinguish perirenal from adrenal lesions.

Fluoroscopy

4 18

2 failed and

2 false neg.

Adrenal hyperplasia, adrenal hemorrhage, nonfunctioning adenoma, metastatic oat cell Ca, metastatic adenoca., metastatic melanoma 13 lung Ca metastases, 1 primary adrenal tumor 4 lung Ca metastases 3 nodular hyperplasia adenomas, 5 cysts, 1 myelolipoma, 4 ad-

renocortical Ca, 2 neuroblastomas, 7 metastatic tumors

None

1 retroperito-

neal hematoma 4 pneumothorax 1 pneumothorax

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LUCIANI AND ASSOCIATES

urological neoplasms we recently identified an additional case of bilateral adrenal metastases from prostatic carcinoma and an example of monolateral adrenal involvement from bladder carcinoma, both verified by aspiration biopsy. These data emphasize the feasibility and diagnostic value of aspiration cytology in detecting these still unusual metastases from urological cancer. 28 REFERENCES 1. Zornoza, J., Bracken, R. and Wallace, S.: Radiologic features of adrenal metastases. Urology, 8: 295, 1976. 2. Deodhar, S. D., Mehendale, V. G. and Bhave, G. G.: Renal cell carcinoma with unusual metastases. J. Postgrad. Med., 24: 55, 1978. 3. Foucar, E. and Dehner, L. P.: Renal cell carcinoma occurring with contralateral adrenal metastasis: a clinical and pathological trap. Arch. Surg., 114: 959, 1979. 4. Previte, S. R., Willscher, M. K. and Burke, C. R.: Renal cell carcinoma with solitary contralateral adrenal metastasis: experience with 2 cases. J. Urol., 128: 132, 1982. 5. Neal, P. M., Leach, G. E., Kaswick, J. A. and Lieber, M. M.: Renal cell carcinoma: recognition and treatment of synchronous solitary contralateral adrenal metastasis. J. Urol., 128: 135, 1982. 6. Campbell, C. M., Middleton, R. G. and Rigby, 0. F.: Adrenal metastasis in renal cell carcinoma. Urology, 21: 403, 1983. 7. Scheible, W., Coe!, M., Siemers, P. T. and Siegel, H.: Percutaneous aspiration of adrenal cysts. Amer. J. Roentgen., 128: 1013, 1977. 8. Pereiras, R. V., Meiers, W., Kunhardt, B., Troner, M., Huston, D., Barkin, J. S. and Viamonte, M.: Fluoroscopically guided thin needle aspiration biopsy of the abdomen and retroperitoneum. Amer. J. Roentgen., 131: 197, 1978. 9. Haaga, J. R.: New techniques for CT-guided biopsies. Amer. J. Roentgen., 133: 633, 1979. 10. Ferrucci, J. T., Jr., Wittenberg, J., Mueller, P. R., Simeone, J. F., Harbin, W. P., Kirkpatrick, R.H. and Taft, P. D.: Diagnosis of abdominal malignancy by radiologic fine-needle aspiration biopsy. Amer. J. Roentgen., 134: 323, 1980. 11. Levin, N. P.: Fine needle aspiration and histology of adrenal cortical carcinoma: a case report. Acta Cytol., 25: 421, 1981. 12. Buonocore, E. and Skipper, G. J.: Steerable real-time sonographically guided needle biopsy. Amer. J. Roentgen., 136: 387, 1981. 13. Zornoza, J., Ordonez, N., Bernardino, M. E. and Cohen, M. A.: Percutaneous biopsy of adrenal tumors. Urology, 18: 412, 1981. 14. Heaston, D. K., Handel, D. B., Ashton, P. R. and Korobkin, M.: Narrow gauge needle aspiration of solid adrenal masses. Amer. J. Roentgen., 138: 1143, 1982.

15. Nosher, J. L., Amorosa, J. K., Leiman, S. and Plafker, J.: Fine needle aspiration of the kidney and adrenal gland. J. Urol., 128: 895, 1982. 16. Halvorsen, R. A., Jr., Heaston, D. K., Johnston, W. W., Ashton, P. R. and Burton, G. M.: Case report. CT guided thin needle aspiration of adrenal blastomycosis. J. Comput. Assist. Tomogr., 6: 389, 1982. 17. Liining, M., Neuser, D., Kursawe, R. and Piitschke, B.: CT guided percutaneous fine needle biopsy in the diagnosis of small adrenal tumours. Eur. J. Rad., 3: 358, 1983. 18. Pagani, J. J.: Normal adrenal glands in small cell lung carcinoma: CT-guided biopsy. Amer. J. Roentgen., 140: 949, 1983. 19. Price, R. B., Bernardino, M. E., Berkman, W. A., Sones, P. J., Jr. and Torres, W. E.: Biopsy of the right adrenal gland by the transhepatic approach. Radiology, 148: 566, 1983. 20. Pagani, J. J.: Non-small cell lung carcinoma adrenal metastases: computed tomography and percutaneous needle biopsy in their diagnosis. Cancer, 53: 1058, 1984. 21. Katz, R. L., Patel, S., Mackay, B. and Zornoza, J.: Fine needle aspiration cytology of the adrenal gland. Acta Cytol., 28: 269, 1984. 22. Berkman, W. A., Bernardino, M. E., Sewell, C. W., Price, R. B. and Sones, P. J., Jr.: The computed tomography-guided adrenal biopsy: an alternative to surgery in adrenal mass diagnosis. Cancer, 53: 2098, 1984. 23. Zornoza J.: Aspiration biopsy of adrenal masses. In: 1st International Congress on Aspiration Cytology in the Staging of Urological Neoplasms (Abstracts). Edited by L. Luciani and F. Piscioli, Trento, Italy, p. 47, 1985. EDITORIAL COMMENT This article indicates the feasibility of aspiration cytology of adrenal lesions. Several points can be mentioned. In general, with gross invasion of tumor in the left renal vein, it is not too surprising that there was an ipsilateral adrenal recurrence. Contralateral adrenal metastases are much rarer. We have had experience with several cases of contralateral adrenal metastases. One patient suffered nausea, cramps and leg weakness several months after resection of the metastasis and required mineralocorticoid (fludrocortisone acetate) supplementation, even though he had been maintained on cortisone acetate. The symptoms subsided immediately. Adrenal insufficiency can result from tumor replacement of the adrenal gland or, obviously, surgical removal. Mineralocorticoid deficiency may be insidious and the surgeon must be aware of this potential eventuality. Fray F. Marshall Department of Urology The Johns Hopkins Hospital Baltimore, Maryland