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  • Title: Primary sclerosing cholangitis with equivocal cytology: fluorescence in situ hybridization and serum CA 19-9 predict risk of malignancy.
    Author: Barr Fritcher EG, Voss JS, Jenkins SM, Lingineni RK, Clayton AC, Roberts LR, Halling KC, Talwalkar JA, Gores GJ, Kipp BR.
    Journal: Cancer Cytopathol; 2013 Dec; 121(12):708-17. PubMed ID: 23839915.
    Abstract:
    BACKGROUND: Patients diagnosed with primary sclerosing cholangitis (PSC) and dominant strictures often undergo endoscopic retrograde cholangiopancreatography with brush cytology to exclude or confirm the development of malignancy. Equivocal (atypical or suspicious) routine cytologic results may confound patient management decisions, especially in the absence of a mass on imaging. The objective of the current study was to identify independent predictors of malignancy in patients with PSC with an equivocal cytology diagnosis. METHODS: Patients with PSC underwent brush cytology for routine cytology and fluorescence in situ hybridization (FISH) during endoscopy as per standard care. FISH slides were classified as polysomy if at least 5 cells displayed a gain of ≥ 2 probes. A retrospective search identified 102 patients without a mass lesion noted on initial imaging studies, an equivocal routine cytology, and ≥ 2 years of follow-up. RESULTS: Of 102 patients, 30 (29%) with an equivocal cytology result developed cancer within 2 years. Serum carbohydrate antigen 19-9 (CA 19-9) levels ≥ 129 U/mL (hazard ratio [HR] 3.19; P = .001) and polysomy (HR 8.70; P < .001) were each found to be predictive of cancer. Of 10 patients who had elevated CA 19-9 levels and polysomy, all went on to develop cancer (9 within 2 years). Although only 10 patients were included in this subset, the combination of elevated CA 19-9 and polysomy was found to be predictive of cancer (HR 10.92; P < .001). CONCLUSIONS: Polysomy by FISH identified those patients most likely to have or develop malignancy in the challenging clinical scenario of PSC with no mass at baseline and equivocal cytology. The combination of an elevated serum CA 19-9 level with polysomy is highly suspicious for the presence of malignancy.
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