Nephrogenic adenoma of bladder in immunosuppressed renal transplantation

Nephrogenic adenoma of bladder in immunosuppressed renal transplantation

NEPHROGENIC ADENOMA IN IMMUNOSUPPRESSED OF BLADDER RENAL TRANSPLANTATION HARVEY L. GORDON, STEVEN G. KERR, M.D. M.D. From the Roy and Lillie C...

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NEPHROGENIC

ADENOMA

IN IMMUNOSUPPRESSED

OF BLADDER RENAL

TRANSPLANTATION HARVEY L. GORDON, STEVEN

G. KERR,

M.D.

M.D.

From the Roy and Lillie Cullen Department of Urologic Research, J. Sayles Leach Laboratory, Division of Urology, Baylor College of Medicine, and the Urology Service, The Methodist Hospital, Houston, Texas

ABSTRACT -A case of nephrogenic adenoma is reported in an immunosuppressed renal transplant recipient. The nature of the lesion is discussed, and a possible relationship between benign tumors and impaired immunologic surveillance is considered.

sterile. Urine protein excretion was 110 mg. per twenty-four hours; blood urea nitrogen was 18 mg. and serum creatinine 1.1 mg. per 100 ml., and the endogenous creatinine clearance was 75 cc. per minute per 1.73 square meters. An infusion nephrotomogram demonstrated the graft and its collecting system to be normal in appearante . At cystoscopy a 5-mm. papillary lesion was excised transurethrally from the right posterolatera1 wall. The patient had no subsequent recurrence of hematuria, and another cystoscopy in January, 1973, showed no abnormalities. Microscopically the specimen was glandular in character (Fig. 1). There were papillary projections covered with cuboidal and low columnar epithelium. Within the stroma were small glandlike spaces similarly lined. A few chronic inflammatory cells were present, as well as an occasional small focus of calcific material. The cells were uniform in size and appearance, showing no mitotic activity. Pathologic diagnosis was benign nephrogenic adenoma.

It is well established that there is a greater chance of malignant tumor developing in patients who have undergone immunosuppression in conjunction with renal transplantation. 1 No change in the incidence of benign tumors in these patients has been noted. Therefore, we found the occurrence of a rare type of benign bladder tumor in an immunosuppressed renal transplant recipient to be a coincidence sufficiently striking to warrant this report. Case Report A thirty-six-year-old white man was admitted to The Methodist Hospital in September, 1972, for evaluation of gross, painless, terminal hematuria. In May, 1966, the patient had received a cadaver kidney transplant for treatment of renal failure secondary to chronic pyelonephritis. For most of the ensuing six and one-half years the graft functioned well, with only two mild episodes of rejection in 1967. At the time of admission, immunosuppressive medications consisted of azathioprine, 125 mg. daily, and methylprednisolone, 4 mg. three times a day, three days a week. This regimen had been satisfactory for prevention of rejection since shortly after transplantation. Urinalysis showed 2 to 5 red blood cells per high-power field. The culture was

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Comment adenoma (nephrogenic Since nephrogenic metaplasia, adenomatoid tumor) of the bladder was first described by Davis,* there have been

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FIGURE 1. (A) Low mugni$cation: papillary projections covered with cuboidal and low columnar epithelium; within stroma are small gland-like spaces similarly lined. (B) High magni.cation: cells rather uniform in size and appearance without mitotic activity.

sporadic case reports. 3-5 Friedman and Kuhlenbeck4 recognized the essential feature of the lesion to be epithelial tubules lined with cuboidal or columnar cells, giving them the appearance of loops of Henle, distal convoluted tubules, or collecting tubules. He, therefore, coined the term “nephrogenic adenoma.” The lesion has been well characterized in a recent article by Goldman.3 It is his opinion that the lesion represents a metaplastic change arising in bladder epithelium of mesodermal origin, as would be found in the region of the trigone, or as local mesothelial islands in entodermally derived areas of the bladder. Ultrastructural and histochemical studies support the notion of mesodermal origin. Goldman considers a choristomatous origin unlikely because there have been no reports of such tubular structures in the fetal and neonatal bladder. In our case, were this a choris-

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toma, it should have been noted during one of the numerous cystoscopic examinations or open bladder procedures made during the patient’s long urologic illness. Goldman noted a frequent coincidence of the lesion with chronic cystitis and considers this the likely stimulus to metaplasia. Although our patient had chronic cystitis for many years, he was free of infection for the seven years preceding the discovery of this lesion. A review of the literature reveals other cases in which the cause of the lesion is not determined. It must be admitted that the case for metaplastic, rather than neoplastic, origin of this lesion is unproved. If one were to postulate a neoplastic origin, this must raise the question in our patient of possible relationship to the immunosuppressed state. Azathioprine has been shown to produce chromosomal abnormalities in man, a potential

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teratogenic risk.6 It has been amply documented that there is a marked increase in the incidence of malignant tumors, particularly lymphomas, but epithelial and brain cancers as well, in patients who have received kidney transplants. l,‘+ The ability to reject an allograft is ubiquitous among higher forms of animal life and indeed cell-mediated immunity can be found quite low on the phylogenetic tree.” No creature in the natural state is at risk to organ transplantation. The widespread prevalence of allograft rejection in nature, therefore, may be only an arcane aspect of a far more basic biologic response. This was suggested in 1959 by Lewis Thomas.” He proposed that a multicellular organism with cellular immunity capability would enjoy an evolutionary advantage in survival if it could recognize mutant cells as foreign and destroy them before a neoplastic clone could develop into an established tumor. His suggestion was that neoplastic disease ensued when this immunologic disposal system failed or was overwhelmed, and that its efficient function kept most animals free of tumors most of the time. The term “immunologic surveillance” has been coined by Burnet,12 who has further extended Thomas’ original proposal. Lawrence” cites three areas of evidence which support this proposal: (1) there is a higher incidence of tumors in children with congenital T-cell immunodeficiency diseases; (2) there is a gradual increase in the incidence of tumors associated with aging, a biologic change associated with waning T-cell function; and (3) there is a higher incidence of lymphomas and certain carcinomas in thymectomized animals, animals treated with antilymphocyte serum, and more pertinently, in human transplant recipients undergoing immunosuppressive therapy. It is not known if immunologic surveillance plays a role in suppressing benign tumors. Investigation has been directed toward malignant neoplasms with their much greater clinical importance. Moreover, a malignant tumor, by its nature, will become clinically manifest. A benign

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tumor may remain occult and, although present, never come to diagnosis. It has not been determined which benign neoplasms contain tumor-specific antigens, and a nephrogenic adenoma in our immunosuppressed patient may be only coincidental. Nonetheless, the appearance of a rare lesion in a rare clinical setting warrants the consideration of an etiologic relationship. Division of Urology Baylor College of Medicine Houston, Texas 77025 (DR. KERR) References 1. STARZL, T. E., et al.:

Iatrogenic alterations of im-

munologic surveillance in man and their influence on malignancy, Transplant Rev. 7: 112 (1971). 2. DAVIS, T. M.: Hamartoma of the urinary bladder, Northwest Med. 43: 182 (1949). 3. GOLDMAN, R. L.: Nephrogenic metaplasia (nephrogenic adenoma, adenomatoid tumor) of the bladder, J. Urol. 108: 565 (1972). 4. HASEN, H. B.: Nephrogenic adenoma of the bladder, ibid. 88: 629 (1962). 5. FRIEDMAN, N. B., and KUHLENBECK, H.: Adenomatoid tumors of the bladder reproducing renal structures (nephrogenic adenoma), ibid. 64: 657 (1950). Chromosome studies in patients 6. JENSEN, M. X.: treated with azathioprine and amethopterin, Acta Med. Stand. 182: 445 (1967’). 7. SCHNECK, S. A., and PENN, I. : De-novo brain tumors in renal transplant recipients, Lancet 1: 983 (1971). of immuno8. ALLISON, A. C.: The complications suppression-tumor development following immunosuppression, Proc. Roy. Sot. Med. 63: 1077 (1970). 9. BEZZAR, F. 0.) et al. : Malignancy and immunosuppression. Renal homotransplantation in patients with primary renal neoplasms, Transplantation 13: 164 (1972). 10. SMITH, R. T., MIESCHER, P. A., and GOOD, R. A.: Phylogeny of Immunity, Gainesville, Univ. of Florida Press, 1966, p. 95. New 11. LAWRENCE, H. S.: Clinical Immunobiology, York, Academic Press, 1972, p. 52. sur12. BURNET, F. M.: The concept of immunological veillance, Prog. Exp. Tumor Res. 13: 1 (1970).

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