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Cytologic Features of Urothelial Carcinoma in Catheterized Urine with Cellular Fragments

萬芳醫院 陳嘉偉

Mohamed El-Fakharany, M.D. et al.ACTA CYTOLOGICA May-June 2006

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Objective To identify architectural and cytomorp

hologic differences that might help distinguish urothelial neoplasms from instrument

ation artifact

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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.

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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).

Introduction (2)

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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)

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Introduction (4)

Study to identify the cytomorphologic differences between cellular fragments

shed by bladder tumors and those shed by

mechanical instrumentation trauma.

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Study DesignExamined 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.

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Materials and Methods (1)15,000 urine cytology smears - 1998

and 2004. Identified 73 smears of catheterized urine specimens

diagnosis (artifact vs. neoplasm), and each had at

least 1 follow-up urinary bladder biopsy for definitive diagnosis.

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Reviewed features: a thin rim of cytoplasm (collar) around cell fragments (present vs. absent)

Fragment border (regular vs. irregular)Nuclear diameterNuclear chromatin (fine vs. coarse)Nucleoli (prominent, present or not

seen)Background inflammation (present vs.

absent).

Materials and Methods (2)

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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

Materials and Methods (3)

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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.

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ResultsFragment border (cytoplasmic collar) Benign cases 74% (29 of 39) Malignant cases 15% (5 of 34)

(p < 0.0001) (Figure 1)

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

A B

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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)

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

A B

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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)

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

A B

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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)

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

A B

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ResultsParameter Artifact Neoplasm

Collar around cell fragments Present Absent

Fragment border Regular Irregular

Nuclear chromatin Fine Coarse

Nuclear diameter >16 μm 12 μm

Nucleoli PresentPresent or not present

Background inflammation Present Absent

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Discussion (1) Low grade bladder malignancy vs.

catheterized urine specimens ( 0-73%)

Lack of distinguish between cellular fragments due to true bladder neoplasms,

mechanical traumaRife CC, et al , Urol Clin North Am 1979 6. Koss LG, Dietch D, et al,Acta Cytol 1985 Shenoy UA, et al, Cancer 1985

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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

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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

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ConclusionCertain architectural and

nuclear features can help differentiate urothelial

neoplasms from instrumentation artifact in

urine cytologic smears.

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Thanks for your attention