DNA image analysis combined with routine cytology improves diagnostic sensitivity of common bile duct brushing

BACKGROUND. Cytologic evaluation of common bile duct brushings has a low sensitivity for diagnosing malignancy because of scant cellularity, poor cellular preservation, or sampling errors occur. The aim of this study was to evaluate whether cytology combined with image analysis improves the diagnostic accuracy of bile duct brushing in comparison with cytology alone. METHODS. Forty-nine specimens of bile duct brushings obtained from 45 patients during endoscopic retrograde cholangiopancreatography were evaluated using cytology and image analysis. Specimens were classified as negative, atypical, suspicious, or malignant by using cytologic evaluation. DNA histograms were classified as diploid (D), broad diploid (BD), aneuploid (A), or tetraploid (T). Degree of hyperploidy (DH), representing cells with a DNA content > 5C was evaluated using a cutoff value of greater than or equal to 1%. Final diagnosis of cancer was based on tissue specimens that were obtained by fine-needle aspiration or surgical biopsy and clinical follow-up. RESULTS. Thirty-four patients ultimately proved to have a malignancy. Cytology revealed 19 negative cases, 15 atypical cases, 9 suspicious cases, and 6 malignant cases. Together, suspicious and malignant cytology cases yielded a sensitivity of 44% and a specificity of 100% for a cytologic diagnosis of cancer. The DNA histogram pattern was D in 24 cases, ED in 9 cases, and A in 16 cases. ED and A patterns were significantly associated with malignancy (P < 0.001). A DH > 1% was noted in 22 cases. DH alone had a sensitivity of 62% and a specificity of 91% and was significantly associated with malignancy (P < 0.004). Atypical cytology alone had a false-negative rate of 29%, but in combination with a DH <greater than or equal to> 1%, the false-negative rate decreased to 7%. Additionally, when the authors combined atypical, suspicious, and malignant cytology with a DH > 1%, the diagnostic sensitivity increased to 88%, but the specificity decreased to 73%. CONCLUSIONS. Combined cytology and image analysis of bile duct brushing increased diagnostic sensitivity compared with cytology alone. The findings suggest that image analysis may help select patients having atypical cytology who should undergo a more rigorous evaluation for malignancy. A larger prospective study of the usefulness of combined cytology and image analysis of bile duct brushing is warranted. Cancer (Cancer Cytopathol) 2001;93:229-235. (C) 2001 American Cancer Society.