Prostatic Cryptococcosis: A Case Report

Prostatic Cryptococcosis: A Case Report

Vol. 94, Aug. Printed in U.S.A. THE JOURNAL OF UROLOGY Copyright © 1965 by The Williams & Wilkins Co. PROSTATIC CRYPTOCOCCOSIS: A CASE REPORT FRANK...

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Vol. 94, Aug. Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1965 by The Williams & Wilkins Co.

PROSTATIC CRYPTOCOCCOSIS: A CASE REPORT FRANK J. O'CONNOR, J. H. SMITH FOUSHEE, JR.

AND

CLAIR E. COX

Frain the Departments of Urology ancl Pathology, Bowman Gray School of Medicine, Wake Forest College, Winston-Salem, North Carolina

Localized cryptococcal involvement of the urinary tract is rare, although widely disseminated or agonal invasion of all organ systems is not uncommon. Infestation of the urinary tract associated with generalized cryptococcosis is occasionally noted at postmortem examination; however, isolated prostatic involvement masquerading as benign prostatic hypertrophy has not previously been reported. A report by Voyles and Beck1 describes a case in which a diagnosis of carcinoma of the prostate was made both preand postoperatively. The correct diagnosis was subsequently made at autopsy 4 months later at which time disseminated cryptococcosis with associated prostatic involvement was found. 1'he case presented is unique in that the patient had the usual signs and symptoms of prostatic obstruction and following prostatectomy, a histological diagnosis of cryptococcosis was noted. There was no preoperative indication of other organ system involvement and there has been no subsequent indication of generalized cryptococcal disease. Cryptococcosis is a fungal infection produced by Cryptococcus neoformans (Torula histolytica), which has a predilection for the central nervous system in man and is most often seen clinically producing slow-developing chronic meningitis. 2 Lesions of the skin and of the lung are not unusual.3 Also lesions of the muscles, soft tissues of pelvis, tongue, and nasopharnyx have been reported.4-6 Dissemination usually occurs as a Accepted for publication December 3, 1964 . . Voyles, G. Q. and Beck, E. M.: Systemic mfection due to Torula histolytica (Cryptococcus hominis). Arch. Int. Med., 77: 504-515, 1946. 2 Jawetz, E., Melnick, J. L. and Adelberg, E. A.: A Review of Medical Microbiology. Los Altos, California: Lange Medical Publications, 1954. 3 Haugen, R. K. and Bake~, R: D.: Th~ pulmonary lesions in cryptococcos1s with special reference to subpleurai nodules. Amer. J. Clin. Path., 24: 1381-1390, 1954. 4 Alverez, R. S.: Red torula as the cause of a tongue abnormality. J.A.M.A., 87: 1358-1359, 1926. 5 Jones, E. L.: Torula infection of the nasopharnyx. Southern Med. J., 20_: 1_20-126, 1~27. 6 Gill, W. D.: Torula mycosis m man w1~h special reference to involvement of upper respiratory . 1

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terminal event and may involve a variety of organs. The kidneys are not infrequently involved when the disease is widespread and the organisms have been found in the glomeruli. CASE REPORT

E. G. P., 232619, a 66-year-old man, was admitted to the North Carolina Baptist Hospital on February 20, 1964 for treatment of urinary retention, occurring 6 weeks prior to admission and requiring an indwelling catheter. The patient had been treated for chronic lymphatic leukemia since 1956. Treatment had consisted of radiotherapy and various chemotherapeutic agents. In 1961 symptoms of prostatism were noted and progressed to acute retention by January 1964. Several attempts at catheter removal were unsuccessful, and as the leukemia was in remission, the patient was admitted for prostatectomy. Rectal palpation disclosed findings consistent with benign prostatic hypertrophy of 70 to 90 gm. in size. Hemoglobin was 11.1 gm. per cent, the white blood count was 124,000 with 62 per cent lymphocytes, 30 per cent lymphoblasts and 10 per cent neurophils and the blood urea nitrogen was 20 mg. per cent. Urinalysis revealed pyuria and growth of Escherichia coli and Aerobacter on culture. A postoperative urine culture for fungal organisms revealed Cryptococcus neoformans. * On February 24 a perineal prostatectomy was performed without incident. At surgery, the prostatic capsule was noted to be extremely thickened and a very small (20 gm.) adenoma was enucleated. Pathological diagnosis of prostatic cryptococcosis was unexpected and caused concern lest a perineal fistula would result. However, the postoperative course was uneventful and the patient was discharged 11 days postoperatively. At the time of discharge a good urinarystream was noted without evidence of perineal leakage. The patient did well until 3 weeks after distract. Trans. Amer. Laryng. Rhino!. Otol. Soc., pp. 247-262, 1934.

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FIG. 1. A, area of necrosis in prostate with granulomatous reaction. XlOO. B, cryptococcus spores in area of necrosis surrounded by epithelioid cells and lymphocytes. X400.

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charge when a small (2 to 3 mm.) perinea! fistula was noted. An indwelling catheter was placed for 10 weeks; however, the fistulous tract did not close. On May 9, the patient was readmitted and the perineal-prostatic fistula was excised. Prior to excision, amphotericin B was given intravenously for 7 days in increasing increments to 60 mg. per day. This was also given for 4 days postoperatively at 50 mg. per day. The catheter was removed 3 weeks after surgery and the fistula subsequently recurred. At present, an indwelling catheter has been replaced. PATHOLOGY REPORTS

Gross examination of the specimen revealed 20 gm. prostatic tissue. Tissue on sectioning was moderately firm and gray-white. Small yellow areas measuring up to 1 to 2 mm. were noted. Microscopic examination revealed circumscribed areas of necrosis surrounded by giant cells, lymphocytes and epithelioid cells (fig. 1, A). Numerous spores were present in areas of necrosis (fig. 1, B). The organisms stained positive with the periodic acid-Schiff fungus stain. Final diagnosis was chronic granulomatous inflammation of the prostate consistent with cryptococcosis. On urine culture a fungal growth was evident which was identified as Cryptococcus neoformans in the following manner: 1) on Sabouraud's dextrose agar, growth of mucoid colonies was good at 25C and at 37C and 2) India ink preparations from these media revealed encapsulated organisms. PATHOLOGY AND MYCOLOGY

The Cryptococcus neoformans is a yeast-like fungus which infects man, inducing lesions which involve the skin, respiratory tract, brain, lung and bone. 7 These organisms induce a non-specific inflammatory reaction which later becomes a chronic granuloma. Baker and Haugen have described the tissue reactions in cryptococcosis as being gelatinous or granulomatous. 8 The former is described as containing a large number of organisms with very little cellular reaction; the latter as being granulomatous in which there are *Tobe discussed under pathology. Conant, N. F., Smith, D. T., Baker, R. D., Calloway, J. L. and Martin, D. S.: Manual of Clinical Mycology, 2nd edit. New York: W. B. Saunders, 1957, pp. 149-168. 8 Baker, R. D. and Haugen, R. K.: Tissue changes and tissue diagnosis in cryptococcosis. Amer. J. Clin. Path., 25: 14-24, 1955. 7

giant cells, macrophages, lymphocytes, and fibrosis. In tissue the organisms vary in size from 5 to 10 microns and often budding yeast forms of the fungus are present. 9 The organisms have a, mucinous capsule which is demonstrated well with the periodic acid-Schiff stain. Prostatic involvement by this organism is very uncommon. In the 26 cases discussed by Baker and Haugen, 2 cases involved the prostate in patients with dissern.inated cryptococcosis. The case presented is the first time this organism has involved the prostate in our surgical and autopsy material. In the prostatic tissue from our patient, there was marked necrosis with chronic granulomatous inflammation. Grossly, the prostatic tissue contained yellow foci or granules. This fungus can be isolated from tissue by culturing the lesion on various media such as blood agar, beef infusion glucose and Sabouraud dextrose agar. 10 In the case under discussion, urine cultures indicated growth of the fungus was good at both 25C and 37C on Sabouraud's dextrose medium. The growth of the organism at 37C identifies this fungus as Cryptococcus neoformans and differentiates it from other non-pathogenic cryptococci. India ink preparations prepared from the Sabouraud's culture indicated the presence of a capsule. In the present case of cryptococcus of the prostate, the patient had no other lesions which could be detected clinically. Therefore, the portal of entry is not known in this patient. Many believe that the common portal of entry for the cryptococcus is the respiratory tract. However, the organism has been cultured from other sites such as the gastrointestinal tract, vagina, pharynx and skin. 7 • 9 DISCUSSION

Several features of this case deserve comment. The patient had long-standing chronic lymphatic leukemia and was therefore, as usual, given a more extensive preoperative evaluation. His leukemia was in remission and he was considered in optimum condition for surgery. One of us (C. E. C) has operated upon several individuals with lymphomas and has not encountered any unusual complications, with the exception of occasional excessive bleeding during transurethral prostatectomy; therefore, we have leaned toward 9 Littman, M. L. and Zimmerman, L. E.: Cryptococcosis. New York: Grune & Stratton, 1956, p. 116.

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open, often perineal, procedures in these patients. The possibility of co-existing cryptococcosis in leukemic patients as a source of surgical complications had not previously been considered by us. The association of cryptococcosis and malignant disease of the reticulo-endothelial system is well established. 10 ·11 A high percentage of patients with Hodgkin's disease, lymphosarcoma, leukemia and sarcoid have coincident cryptococcal disease. In a report by Zimmerman and Rappaport,10 30 per cent of their patients with cryptococcosis had associated malignant lymphomas. However, in these patients the cryptococcosis usually is clinically evident, existing as pulmonary nodules, meningeal infestation or wide dissemination. In our case, the postoperative perineal fi8tula was undoubtedly secondary to the co-existent cryptococcosis. The postoperative urine culture in this patient was positive for Cryptococcus neoformans and had this been determined preoperatively, the perineal approach would have been avoided. Other surgical routes to the prostate would probably have obviated this complication. Therefore, it is suggested that individuals with .malignant lymphomas who require prostatectomy should be screened for the presence of cryptococcal disease in the urine. If the organism is found on urine culture, the perinea.I route should probably be avoided. Enucleation of only 20 gm. prostatic tissue contradicted the preoperative estimate of 80 to 10 Zimmerman, L. E. and Rappaport, H.: Occurrence of cryptococcosis in patients with malignant disease of the reticuloendothelial system. Amer. J. Clin. Path., 24: 1050-1072, 1954. 11 Collins, V. P., Gellhorn, A. and Trimble, J. R.: The coincidence of cryptococcosis and disease of the reticulo-endothelial and lymphatic systems. Cancer, 4: 883-889, 1951.

90 gm. It is presumed that this discrepancy is explained by the operative findings of an extremely thickened capsule probably secondary to the disease process. Although other forms of granulomatous prostatitis, such as described by Thompson and Albers, 12 are often misdiagnosed as carcinoma, in this case rectal palpation was consistent with benign prostatic hypertrophy. The treatment of choice of cryptococcosis is amphoptercin B. 13 -14 This drng, although relatively toxic, is effective in meningeal and pulmonary forms of the disease and less so in the disseminated form. Ko precedent has been established for treatment of urogenital cryptococcosis In this case the perineal fistula failed to respond to conservative treatment (retention catheterization for 6 weeks) and therefore the fistula was operatively excised. Prior to and following fistula excision amphoptercin B was given mtravenously. The fistula has again recurred and further treatment will be required. SUMMARY

A unique case of cryptococcosis of the prostate is described. Operative complications in this granulomatous disease are discussed. The frequent association of malignant diseases of the reticulo-endothelial system and cryptococcosis is pertinent to the urologist when urological surgery is contemplated. 12 Thompson, G. J. and Albers, D. D.: Granulomatous pros ta ti tis: A condition which clinically may be confused with carcinoma of prostate. J. Urol., 69: 530-538, 1953. 1 a Schumacher, H. R., Ginns, D. A. and Warren, W. J.: Fungus infection complicating leukemia. Amer. J. Med. Sci., 247: 313-323, 1964. 14 Seabury, J. H. and Dascomb, H. E.: Results of the treatment of systemic mycoses. J.A.M.A.,

188: 509-513, 1964.