Ureteral fibroepithelial polyp with positive urinary cytology

Ureteral fibroepithelial polyp with positive urinary cytology

UROPATHOLOGY URETERAL FIBROEPITHELIAL POLYP WITH POSITIVE URINARY CYTOLOGY KOSTANTINOS E. PSIHRAMIS, M.D., C.M., F.R.C.S. (C) WARREN HARTWICK, M.D. ...

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UROPATHOLOGY

URETERAL FIBROEPITHELIAL POLYP WITH POSITIVE URINARY CYTOLOGY KOSTANTINOS E. PSIHRAMIS, M.D., C.M., F.R.C.S. (C) WARREN HARTWICK, M.D.

From the Departments of Surgery (Urology) and Pathology, Mount Sinai Hospital, and University of Toronto, Toronto, Ontario, Canada ABSTRACTWe report on a patient with two fibroepithelial polyps of the upper ureter in whom the correct diagnosis was confused by finding voided urine as well as ureteral wash, and brush biopsy cytologies positive for malignancy. Fibroepithelial polyps and causes of falsely positive urinary cytology are reviewed.

Primary ureteral neoplasms are rare, representing 1 per 3,690 urologic hospital admissions.’ Benign tumors account for approximately 20 percent of all ureteral neoplasms and include both epithelial and nonepithelial lesions.2 Nonepithelial neoplasms originate from mesoderma1 elements within the ureteral wall and the most common is the fibroepithelial polyp, with over 112 cases reported to date.3 Prior reports have repeatedly emphasized the difficulty of differentiating this benign lesion from transitional cell carcinoma (TCC). Consequently, in 41 of 112 (37%) cases of fibroepithelial polyps reviewed by Debruyne and associates,3 unnecessary nephroureterectomy was performed because of an uncertain preoperative diagnosis. The recent introduction of ureteroscopy has helped tremendously in making the proper diagnosis preoperatively and, therefore, avoiding needless radical surgery.2t4 The correct diagnosis of a ureteral filling defect, however, usually requires a number of diagnostic modalities, one of the most important being urinary cytology. We report on a patient in whom the diagnosis of fibroepithelial polyp was confused by finding voided urine to be positive for malignancy as well as ureteral wash and brush biopsy cytologic examinations. To our knowledge, this is the first such case reported to date. Case Report A twenty-six-year-old white man presented in December 1987 with left renal colic, dysuria,

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and a single episode of gross total hematuria. His excretory urogram (IVP) was interpreted as normal, and he was discharged with a provisional diagnosis of a “probable passed calculus.” He remained well until September 1988, when he returned with colicky left flank pain radiating to the left lower quadrant, dysuria, and total gross hematuria. IVP now showed left hydronephrosis and two linear, smooth, filling defects in the proximal left ureter beginning just below the left ureteropelvic junction and extending approximately 3 cm distally (Fig. 1). He had no prior medical history and was not prescribed any medications. The family history and functional inquiry were entirely negative. Physical examination revealed a healthy painfree man who was afebrile and normotensive. Findings on general examination were unremarkable, and specifically, there was no costovertebral angle or flank tenderness and no palpable masses or organomegaly. Review of the IVP from December 1987 and comparison with the current films showed the same filling defects which had been missed in 1987 and which appeared to be unchanged. Complete blood count and biochemical data were within normal limits. Urinalysis showed only microscopic hematuria, and urine culture was negative. Cystoscopic examination showed the urethra, prostate, and bladder to be normal. Left retrograde film confirmed the presence of a filling defect in the upper ureter. Ureteroscopy with the 8.5F rigid Wolfe 387

FIGURE1. (A) Fifteen minute IVP film showing left hydronephrosis and left upper ureteral filling defect (arrow). (B) Closer view of left upper ureter shows two smooth elongated intraluminal filling defects (arrows).

ureteroscope could only be carried to the level of the iliac vessels, and the lesion was, therefore, not visualized. The flexible ureteroscope was not available. A ureteral catheter was passed to the left renal pelvis and a wash was collected for cytologic examination. A brush biopsy of the area of the lesion was performed under fluoroscopic guidance. Cytopathologic examination of one voided urine specimen and the renal pelvis wash were both reported as positive for papillary TCC. Brush biopsy cytology was reported as suspicious but not diagnostic of papillary TCC. Microscopically, the brush biopsy was reported as normal except for one region where the cells are atypical. Despite the abnormal cytologic findings, the clinical and radiographic features were thought to be those of a fibroepithelial polyp, and ureteral exploration rather than nephroureterectomy with bladder cuff was performed. Surgical inspection showed the ureter was normal with no evidence of tumor involvement of its wall or the retroperitoneum. Ureteral palpation revealed a mass that corresponded to the filling defect that was seen radiologically. A longitudinal ureterotomy was made, and 2 vermi-

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form, smooth, grayish-white polyps on a narrow stalk protruded from the lumen. Local excision of both including their base was accomplished. Frozen section diagnosis was fibroepithelial polyp. The final pathologic diagnosis was fibroepithelial polyp with no evidence of dysplasia or neoplasia. His convalescence was uneventful, and he remains asymptomatic to date. Repeat ( x4) voided and bladder wash cytologic examinations have been negative. Repeat IVP findings in August 1989 were normal. Material and Methods Cytology slides from voided urine, ureteral washing, and ureteral brushing were prepared by centrifugation at 3,000 rpm for ten minutes followed by Cytospin centrifugation at 1,200 rpm for three minutes. Slides were then fixed in 95% ethanol and stained by the modified Papanicolaou technique, using regressive nuclear staining with Harris hematoxylin, HCl 0.5% and lithium carbonate 1 .O % , followed by cytoplasmic staining with OG-6 and EA-50 (both Ortho Co.). The brush biopsy tissue was fixed in 10% phosphate-buffered formalin prior to

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FIGURE 2. (A) Papillary fragments of urothelium from ureteral brushing, and (B) malignant-appearing cell with (arrow) enlarged nuclei and multiple prominent nucleoli (Papanicolaou stains, original magnifications x 125 and x 315, respectioely).

FIGURE 3. (A) Fibroepithelial polyp, and (B) higher magnification showing benign urothelial lining (hematorylin original and eosin, x 12.5 magnifications and x 125, respectively).

routine processing through to paraffinembedded block. Five-micrometer-thick sections were cut and stained by a regressive nuclear staining technique using Harris hematoxylin, acid alcohol 1 .O % , and Scott’s tap water, followed by cytoplasmic counterstaining with eosin. Results Preoperatively one voided urine, one ureteral washing, and one ureteral brushing were received. Cytologic examination revealed transitional epithelial cells arranged in papillary clusters or singly (Fig. 2A). Some cells had a malignant appearance with increased nuclear to cytoplasmic ratio and with nuclei characterized by increased size, hyperchromatism, prominent nucleoli, and nuclear molding (Fig. 2B). The voided urine and ureteral wash cytologic findings were reviewed by several pathologists and were finally interpreted as “positive for TCC.” The ureteral brushing cytologic and pathologic findings were interpreted as “suspicious for malignancy” and “atypia,” respectively. Two polypoid pieces of tan-red colored tissue measuring 2.0 by 0.1 by 0.1 cm and 3.5 by 0.2 by 0.1 cm were received from the operation and

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were labelled “ureteral tumor.” The microscopic appearances of these tissues were similar. It showed a polyp composed of an edematous fibrovascular core which was covered by benign transitional epithelium that was partially to totally denuded focally (Fig. 3). The histologic appearance was that of a benign fibroepithelial polyp. There was no evidence of malignancy. Comment The diagnosis of ureteral fibroepithelial polyp should be considered in a patient below the age of forty who gives a history of intermittent colicky flank pain and hematuria, and whose IVP shows a smooth, elongated ureteral filling defect with or without hydronephrosis. Grossly, they are grayish-white in color and appear as multiple finger-like projections attached to a single base, usually in the region of the ureteropelvic junction or the proximal ureter. Microscopically, they arise from the submucosa and are composed of a loose connective tissue core which is covered with a layer of normal transitional epithelium. Ideally the diagnosis of fibroepithelial polyp should be made preoperatively so that needless more extensive surgery can be avoided. Urinary

cytology plays a pivotal role in the differential diagnosis of upper urinary tract radiolucent filling defects and in the definitive diagnosis of j urothelial carcinoma. Even though the detec-’ tion of exfoliated bladder cancer cells in urine’ was reported as early as 1865,5 it is Papanicolaou and Marshall6 who are generally credited with initiating the modern era of cytologic examination of urine. A review of the literature to 1964 by Umiker’ revealed cytology sensitivity ranging from 26.1 to 100 percent and averaging 71.6 percent. The false-positive rate ranged from 1.3 to 11.9 percent, averaging 2.3 percent.’ A sampling of subsequent reports shows sensitivities ranging from 0 to 100 percent.8-12 Sensitivity increases with examination of more than one sample and with increasing tumor grade. Sensitivities of 86 to 98 percent for poorly differentiated (grade III to IV/IV) papillary TCC or TCC in situ, and 0 to 79 percent for well or moderately differentiated (grade I or II/IV) papillary TCC have been reported.s-12 False positivity, expressed as a percentage of total suspicious or positive cytologic diagnoses, ranged from 0 to 23 percent, averaging 6 percent.*-l2 In some series, however, subsequent cystoscopic recognition of TCC resulted in a marked reduction in the degree of false positivity.” Specificity ranged from 95.4 to 100 percent.*-l2 Besides lack of clinical history and inexperience on the part of the cytologist, a number of non-neoplastic conditions of the genitourinary system have been associated with suspicious or positive voided urine and ureter or bladder wash cytology. These conditions include: urethral caruncle, benign prostatic hyperplasia, prostatic infarction, calculi of the upper or lower urinary tract, chronic cystitis or other urinary tract infections, viral infection, eosinophilic cystitis, squamous metaplasia of the urinary bladder, bladder outlet obstruction, bladder diverticulum, extensive bladder urothelial denudation, renal cyst, renal papillary necrosis, inverted papilloma of the renal pelvis, systemic cyclophosphamide chemotherapy, intravesical cytotoxic chemotherapy or immunotherapy, radiotherapy and bladder or ureteral instrumentation, including catheterization.‘-” Such suspicious or positive cytologic findings with negative cystoscopic findings, however, may not actually represent “false” positivity. Cystoscopically unrecognized dysplasia or TCC in situ, subsequent cystoscopic recognition of

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papillary TCC, or concurrent neoplasm of kidney, prostate, vagina, cervix, or endometrium have all been associated with positive cytology. ~OJ~J~-~*For example, Allegra and associates’* reported 7 patients with positive cytologic findings and negative cystoscopic findings who were all subsequently found to have TCC of the bladder within an interval of ten days to thirty months. Rife, Farrow, and Utes” reported that in patients with negative findings on cystoscopy, 190 of 203 with positive and 158 of 279 with atypical urine cytology, genitourinary carcinomas were subsequently diagnosed. Murphy14 also reported that 7 of 9 patients with positive findings on urine cytology which were not immediately confirmed, had clinical or pathologic conditions related to urologic cancer. Careful follow-up of such patients was recommended. Finally, Heney and associates17 also recommend that falsely positive urinary cytology be followed by critical review of all cytologic and histologic material plus careful follow-up. Positive cytology has not been described in any of the previously reported cases of fibroepithelial polyp. Coexisting TCC at the tip of the polyp has been found in only 1 case and in this no cytology was obtained.lg The abnormal cytologic findings in our case may be attributed to the instrumentation, traumatic irritation of the adjacent urothelium by the polyp, and/or by the urothelial denudation noted on the surface of the polyp. We propose that fibroepithelial polyp of the ureter be added to the list of genitourologic conditions which may be associated with false-positive urinary cytology, To our knowledge, this is the first reported example of such a case. Furthermore, we are in agreement with previous reports that urinary cytology has an important role to play in the investigation and management of the patient with urologic conditions, including TCC. The interpretation of such cytology should, however, be carried out in the context of appropriate clinical information and with the recognition of the sensitivity and specificity which one may expect from one’s own experience and that reported in the literature. Follow-up of patients who manifest atypical, suspicious or positive cytology and clinical, radiographic, endoscopic, or histologic features which do not support a diagnosis of TCC is important in view of the potential of socalled “false” positive cytology to become “true” positive cytology with time.

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University Avenue Toronto, Ontario Canada MG5 1X5 (DR. PSIHRAMIS)

References 1. Abeshouse DS: Primary benign malignant tumors of the ureter, Am J Surg 91: 237 (1956). 2. Franc0 I, et al: Fibroepithelial polyp associated with congenital ureteral diverticulum: report of 2 cases, I Urol 140: 598 (1988) . 3. Debruyne FMJ, Moonen WA, Daenekindt AA, and Delaere KPI: Fibroenithelial PO~VP of ureter, Urolow 16: 355 (1980). 4. Bahnson RR, Blum~ MD, and Carte; RF: Fibroepithelial polyps of the ureter, J Urol 132: 343 (1984). 5. Sanders WR: Cancer of the bladder. Fragments forming urethral plugs discharged in the urine. Concentric colloid bodies, Edinb Med J 10: 273 (1865). 6. Papanicolaou GN, and Marshall VF: Urine sediment smears as a diagnostic procedure in cancers of the urinary tract, Science 101: 519 (1945). 7. Umiker W: Accuracy of cytologic diagnosis of cancer of the urinary tract, Acta Cytol 8: 186 (1964). 8. Esposti PL, Moberger G, and Zajicek J: The cytologic diagnosis of transitional cell tumors of the urinary bladder and its histologic bases. A study of 567 cases of urinary tract disorders

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including 170 untreated and 182 irradiated bladder tumors, Acta Cytol 14: 145 (1970). 9. Sarnacki CT, et al: Urinary cytology and the clinical diagnosis of urinary tract malignancy: a clinico-pathologic study of 1,496 patients, J Urol 106: 761 (1971). 10. Beyer-Boom ME, et al: The efficacy of urinary cytology in the detection of urothelial tumors. Sensitivity and specificity of urinary cytology, Urol Res 6: 3 (1978). 11. Rife CC, Farrow GM, and Utz DC: Urine cytology of transitional ceil neoplasms, Urol Clin North Am 6: 599 (1979). 12. Schuldheisz KD: Urinary cytology: a twelve-year review, Wis Med J 83: 27 (1984). 13. Taylor FM III, and Arroyo JG: Inverted papilloma of the renal pevis. Cytologic features of ureteral washings, Acta Cytol 30: 166 (1986). 14. Murphy WM: Falsely positive cytology: pathologists’ error or preclinical cancer, J Urol 118: 811 (1977). 15. Husserl FE, Fuselier HA Jr, and Carrera GM: False-positive urinary cytology, South Med J 72: 1466 (1979). 16. Gamarra MC, and Zein T: Cytologic spectrum of bladder cancer, Urology (Suppl) 23: 23 (1984). cytology in patients 17. Heney NM, et al: Positive urinary without evident tumor, J Urol 117: 223 (1977). 18. Allegra SR, Fanning JR Streker JF, and Corvese NM: Cytologic diagnosis of occult and “in situ” carcinoma of the urinary system, Acta Cytol 10: 340 (1966). 19. Davides KC, and King LM: Fibrous polyps of the ureter, J Urol 115: 651 (1976).

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