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Cytologic Features of Urothelial Carcinoma in Catheterized Urine with Cellular Fragments

Cytologic Features of Urothelial Carcinoma in Catheterized Urine with Cellular Fragments. Mohamed El-Fakharany, M.D. et al. ACTA CYTOLOGICA May-June 2006. 萬芳醫院 陳嘉偉. Objective. To identify architectural and cytomorphologic differences that might help distinguish

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Cytologic Features of Urothelial Carcinoma in Catheterized Urine with Cellular Fragments

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  1. Cytologic Features of Urothelial Carcinoma in Catheterized Urine with Cellular Fragments Mohamed El-Fakharany, M.D. et al. ACTA CYTOLOGICA May-June 2006 萬芳醫院 陳嘉偉

  2. Objective • To identify architectural and cytomorphologic differences that might help distinguish urothelial neoplasms from instrumentation artifact

  3. Introduction (1) • Powerful tools for screening bladder tumors is the urine cytology smear • Several findings that can help the cytopathologist diagnose bladder neoplasms on these smears. • Presence of cellular fragments in voided urine specimens, especially in patients with no history of renal stones, strongly raises the suspicion of a tissue-shedding bladder neoplasm.

  4. Introduction (2) • catheterized urine specimens, these tissue fragments usually present a challenge to the cytopathologist • mechanical trauma (also known as instrumentation artifact) or due to a true bladder neoplasm (particularly low grade neoplasms).

  5. Introduction (3) • This instrumentation artifact can cause a rate of false positive diagnosis of urothelial neoplasms (e.g., urothelial carcinoma) as high as 11% ( Rife CC, et al,Urol Clin North Am 1979;6:599–612)

  6. Introduction (4) • Study to identify the cytomorphologic differences between cellular fragments shed by bladder tumors and those shed by mechanical instrumentation trauma.

  7. Study Design • Examined 73 cytologic smears of catheterized urine containing urothelial cell clusters - 1998 and 2004. • All patients had at least 1 follow-up biopsy. Smears were reviewed for several morphologic features blindly, without knowledge of the follow-up diagnosis.

  8. Materials and Methods (1) • 15,000 urine cytology smears - 1998 and 2004. Identified 73 smears of catheterized urine specimens • diagnosis (artifactvs. neoplasm), and each had at least 1 follow-up urinary bladder biopsy for definitive diagnosis.

  9. Materials and Methods (2) • Reviewed features: a thin rim of cytoplasm (collar) around cell fragments (present vs. absent) • Fragment border (regular vs. irregular) • Nuclear diameter • Nuclear chromatin (fine vs. coarse) • Nucleoli (prominent, present or not seen) • Background inflammation (present vs. absent).

  10. Materials and Methods (3) • The nuclear and fragment diameters were measured along the long axis using a calibrated eyepiece. • Results were then analyzed (χ2 test) against the follow-up diagnosis to determine which parameters were significant in distinguishing benign cell clusters from urothelial carcinoma

  11. Results • 73 smears- 39 benign diagnosis 34 urothelial carcinoma on biopsy • Review results: significant differences between benign and malignant cases with respect to 4 features: cytoplasmic collar, fragment border, nuclear chromatin and nuclear diameter.

  12. Results • Fragment border (cytoplasmic collar) Benign cases 74% (29 of 39) Malignant cases 15% (5 of 34) (p < 0.0001) (Figure 1)

  13. Figure 1 Cytoplasmic collar.(A) Instrumentation artifact. (B)Urothelial carcinoma. A B

  14. Results • Regular and rounded fragment borders Benign cases, 80% (31 of 39) malignant cases, 24% (8 of 34) • Irregular and/or ragged fragment edges 76% ( 26 of 34) (p < 0.0001) (Figure 2)

  15. Figure 2 Fragment border.(A) Instrumentation artifact. (B)Urothelial carcinoma. A B

  16. Results • Nuclear chromatin -fine and evenly dispersed Benign cases-64% (25 of 39) Malignant cases 18% (6 of 34); • Nuclear chromatin -coarse and clumped Malignant cases 82% (p < 0.0001) (Figure 3)

  17. Figure 3 Nuclear chromatin.(A) Instrumentation artifact. (B)Urothelial carcinoma. A B

  18. Results • Nuclear size Benign cases –12 μm Malignant cases – 16 μm Maximum nuclear diameter of 20 - 7 cases; proven malignant on follow-up biopsy (p < 0.0001) (Figure 4)

  19. Figure 4 Nuclear diameter.(A) Instrumentation artifact. (B)Urothelial carcinoma. A B

  20. Results

  21. Discussion (1) • Low grade bladder malignancy vs. catheterized urine specimens ( 0-73%) • Lack of distinguish between cellular fragments due to true bladder neoplasms, mechanical trauma Rife CC, et al , Urol Clin North Am 1979 6. Koss LG, Dietch D, et al,Acta Cytol 1985 Shenoy UA, et al, Cancer 1985

  22. Discussion (2) • Irregular,ragged border, absent cytoplasmic collar and coarse nuclear chromatin were combined, the sensitivity for diagnosing true malignant cellular fragments was 100% and the specificity, 94%. • Nuclear diameter of ≥ 20 μm was 100% specific for malignancy

  23. Discussion (3) • The concurrent presence of the above features is a powerful tool that should be used by the cytopathologist to screen out urothelial carcinoma in catheter urine cytology • Avoid unnecessary follow-up procedures and help provide more efficient health care

  24. Conclusion • Certain architectural and nuclear features can help differentiate urothelial neoplasms from instrumentation artifact in urine cytologic smears.

  25. Thanks for your attention

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