Vol. 114, August

THE JOURNAL OF UROLOGY

Copyright © 1975 by The Williams & Wilkins Co.

Printed in U.S.A.

THE VALUE OF MECHANICAL CELL HARVESTING IN DIAGNOSIS AND PROGNOSIS OF BLADDER TUMOR RECURRENCE ALVARO MORALES,* JOHN MARRIOTT

AND

,JOHN G. CONNOLLYt

From the Departments of Urology and Pathology, Queen's University, Kingston, Ontario, Canada

ABSTRACT

Specimens obtained after scraping the bladder mucosa were found to be of excellent quality because of the large cell harvest and the minimal inflammatory exudate. In addition, tumor recurrence could be predicted in a significant number of cases with this technique. Exfoliative cytology is an effective tool in the diagnosis of bladder tumors. 1 The accuracy of the technique is high in anaplastic lesions. 2 However, cytological diagnosis loses much of its value when well differentiated neoplasms are present because the exfoliated cells differ little from normal mucosa! cells. In addition, attention has been drawn to the unreliability of the technique in recurrent tumors, although a convincing explanation is not available. 3 A positive diagnosis by exfoliative cytology depends largely on an adequate cellular population and the absence of blood and cellular debris which interfere with proper identification of the urothelial cells.• We have used scrapings of the bladder mucosa with 2 specific aims: 1) to increase cell harvest and the accuracy of urinary cytodiagnosis and 2) to establish its value in predicting frank tumor recurrence in the presence of a negative cystoscopy.

Two patients were eliminated from the study because of inadequate followup. METHODS

MATERIALS

There were 35 consecutive patients with previously diagnosed transitional cell carcinoma of the bladder entered in the study. All patients had had superficial tumors (TO to Tl, International Union Against Cancer classification) eradicated endoscopically at least 3 months previously. Patients ranged in age from 43 to 72 years, with an average of 58 years. There were 23 male and 12 female subjects, with a ratio of 2 to 1. At the beginning of the study 2 voided specimens were examined for the presence of malignant cells and cystoscopy was performed in each case. All investigations were negative for tumor recurrence. After cystoscopy scraping of the bladder mucosa was performed as will be explained. Subsequently, cytology of voided specimens and J::ystoscopy were carried out at 2 to 6-month intervals for 3 years. Accepted for publication November 22, 1974. Read at annual meeting of Northeastern Section, American Urological Association, Whitefield, New Hampshire, September 29-0ctober 2, 1974. *Requests for reprints: Etherington Hall, Queen's University, Kingston, Ontario, Canada. t Current address: Women's College Hospital, Toronto, Ontario, Canada.

Scraping of the bladder mucosa ivas done immediately after the cystoscope had been removed. A 24 Stern-McCarthy resectoscope sheath was passed into the bladder. Then 100 cc Eagle's minimal essential medium was injected through the sheath and the mucosa was scraped thoroughly and gently, under direct vision with the cold loop of the resectoscope. Special care was taken to avoid significant trauma to the epithelium so that no bleeding was produced. After scraping the medium was forcefully irrigated 3 times and removed. The specimen was sent immediately to the laboratory and processed in a similar manner to the voided samples. Voided urine specimens obtained in the ward prior to cystoscopy were processed promptly. The sample was centrifuged at 2,000 revolutions per minute for 15 minutes. After the supernatant was discarded the sediment was spread on slides previously treated with egg albumin fixative to keep the cells from washing off during the staining procedure. The slide was then stained as described' and routine cytological examination was done. RESULTS

Effect of mucosa/ scrapings on the quality of the specimens. There were 102 specimens evaluated for this purpose: 69 voided samples prior to cystoscopy and 33 specimens obtained following scrape. Cellularity was compared in each case between voided and scrape specimens. The results are depicted in table 1. The samples also were compared in regard to the amount of inflammatory exudate present (table 2). An interesting finding became evident early in the study of the specimens obtained following the endoscopic procedure: the presence of bizarre cell clusters reminiscent of the phenomenon observed in the presence of well differentiated papillary bladder tumors. This abnormality was observed in 84 per cent of the samples obtained. An example of such cell clustering is shown in the figure.

220

CELL HARVESTING IN DIAGNOSIS AND PROGNOSIS OF BLADDER TUMOR RECURRENCE

221

negative for tumor, 7(20 per cent) were later found to have a recurrence. The intervals between the initial evaluation and the appearance of recurrence ranged from 12 to 144 weeks, with an average of 53 weeks. DISCUSSION

Example of _phenomenon of cell clustering frequently found m specimens obtained after instrumentation of urinary tract.

Correlation of

and cytologic findings.

Of the 33 patients with a negative cystoscopy and voided samples at the start of the study, 25 also had a negative by the scraping method. In the remaining 8 patients the well known criteria for the presence of tumor cells were present. Correlation positive endoscopy and development. In the group of 8 patients in whom the scraped specimens were considered positive for tumor but no endoscopic evidence of it was found, 4 patients had endoscopically detectable lesions between 10 and 16 weeks after the initial examination. The other 4 patients remained free of tumor during fo!lowup. These latter 4 cases were considered falsely positives. Correlation between a negative cytology and subsequent tumor development. In the group of 25 patients in whom cytology and cystoscopy were TABLE

1. Percenta{?e of specimens according to

cellularity

Good* Fairt Poor:j:

Voided(%)

Scrape(%)

36 35 29

77

14 9

* More than 100 cells per low power field.

t Between

50 and 100 cells per low power field.

One major obstacle for an accurate urinary cytoresides in unsatisfactory specimens to the sparseness of eel.ls in the Several methods have been described to obviate this voided spec7 volume concentration of different rnethods 8 • 9 and the use of soluble swabs. 10 More forceful of the bladder increase the cell mens with less exudate. 11 The method described herein has been effective in enhancing the cell harvest and has provided samples of superior quality owing to the minimal amount of cellular debris and exudate. However these advantages are partially negated th; bizarre cell clusters observed in a high percentage of the specimens obtained this method. Theresamples examined after instrumentation of the urinary tract should be considered with great caution since the presence of cell aggregation is one of the cytological characteristics of urothelial tumors. In 4 patients (50 per cent) the technique of mucosa! scraping predicted the subsequent macrotumor development in the presence of negative voided specimens and cystoscopy. In these 4 cases a recurrence became evident within 16 weeks. It is believed that in these patients tumor was present although not evident on endoscopy and the cells were too few to be detected in voided specimens. Therefore, the technique may have merit in the short range prediction of tumor development. In 7 patients (21 per cent) tumor was found at a later date although the investigations at the start of the study were all negative. However, the appearance of a recurrence in this group took a long interval; increased cell population and better quality of the sample appear to have little value in giving advanced notice of late recurrence. This technique also may have a place as an alternative to serial bladder biopsies when one encounters a restless mucosa but no definite tumor. However, the cytologist should be aware of the artificial cell clustering produced by this technique and base the criteria for malignancy on individual cellular morphology.

:j: Less than 50 cells per low power field. TABLE

2. Percenta{?e of specimens according to amount

of inflammatory exudate

Minimal

Moderate Marked

Voided(%)

Scrape (Sf)

59 29 12

89 9

2

REFERENCES

Accuracy of cytologic diagnosis of cancer of the urinary tract. Acta Cytol., 8: 186, 1964.

1. Umiker, W ..

2, MacFarlane. E. W., Ceelen, G. H. and Taylor, ,J. N .. Urine cytology after treatment of bladder tumors. Acta CvtoL. 8: 288, 196'"., :3 Connolly. ,J. G .. Promislovv, C. 2nd Marriott, J. · Intermittent exfoliation of epithelial cells i:1 carci11-

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4.

5.

6. 7.

MORALES, MARRIOTT AND CONNOLLY

oma of the urinary bladder. Canad. J. Surg., 13: Cytol., 7: 199, 1963. 144, 1970. 8. Fischer, S.: Diagnostic cytology by an extended memPapanicolaou, G. N. and Marshall, V. F.: Urine sedibrane filter technique. Acta Path. MicrobioL ment smears as a diagnostic procedure in cancers Scand., suppl. 212, p. 33, 1970. of the urinary tract. Science, 101: 519, 1945. 9. Trott, P. A., Williams, G. and Attridge, P. W.: Use Tyrkko, J.: Exfoliative cytology in the diagnosis and of soluble swabs in the diagnosis of bladder neofollow-up of urothelial neoplasms. Scand. J. Urol. plasia. J. Clin. Path., 22: 731, 1969. Nephrol., su_ppl. 19, 7: 1, 1973. 10. Trott, P. A. and Edwards, L.: Comparison of bladder Deden, C.: Cancer cells in urinary sediment. Acta washings and urine cytology in the diagnosis of Radio!., suppl. 115, p. 3, 1954. bladder cancer. J. Urol., 110: 664, 1973. Failde, M., Eckert, W. G. and Patterson,-J-. N.: A- 11-:-- Mostofi,- F.-K. :--Pathologkal- aspects and--spr.ead .of comparison of a simple centrifuge method and the carcinoma of the bladder. J.A.M.A., 206: 1764, 1968. millipore filter technic in urinary cytology. Acta

The value of mechanical cell harvesting in diagnosis and prognosis of bladder tumor recurrence.

Specimens obtained after scraping the bladder mucosa were found to be of excellent quality because of the large cell harvest and the minimal inflammat...
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