The distinction between well-differentiated intrahepatic cholangiocarcinoma (iCCA) from its morphological mimics such as bile duct adenoma (BDA) and hamartoma (BDH) can be challenging, particularly in small biopsies. Although a few cases of BDA and BDH have been reported to undergo malignant transformation into iCCA, their neoplastic versus benign nature remains debated. DNA flow cytometry was performed on 47 formalin-fixed paraffin-embedded samples of iCCA, 14 BDA, and 18 BDH. Aneuploidy was detected in 22 iCCA (47%) but in none of the 32 BDA and BDH samples. Among the 34 iCCA patients who underwent complete resection and were followed up to tumor recurrence, tumor-related death, or at least for 1 year, the overall recurrence or death rates (regardless of flow cytometric results) were 18, 56, and 71% within 1, 3, and 5 years, respectively. The 1-, 3-, and 5-year recurrence or death rates in 18 iCCA patients with aneuploidy were 28, 66, and 66%, respectively, whereas 16 iCCA patients in the setting of normal DNA content had 1-, 3-, and 5-year rates of 6, 44, and 72%, respectively. Although aneuploid tumors were associated with worse outcomes during the first 3 years, this difference was not statistically significant (hazard ratio = 1.4, p = 0.473) in the present sample size. In conclusion, the frequency of aneuploidy was significantly higher in iCCA (47%) than in its benign morphological mimics (0%), suggesting that it may potentially serve as a diagnostic marker of malignancy in challenging situations. Our findings also suggest that most BDAs and BDHs, if not all, are benign entities and may not represent precursor lesions to iCCAs that often harbor aneuploidy. Although a larger cohort will be necessary to further determine the prognostic significance of aneuploidy in iCCA patients after resection, the patients with aneuploid tumors may have a higher risk for tumor progression, especially during the first 3 years.

中文翻译：

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DNA流式细胞术在区分恶性和良性肝内胆管病变中的实用性。

高分化肝内胆管癌（iCCA）与其形态模拟物（例如胆管腺瘤（BDA）和错构瘤（BDH））之间的区别可能具有挑战性，特别是在小活检中。尽管据报道有几例BDA和BDH发生恶性转化为iCCA，但其肿瘤性与良性性仍有争议。对47个福尔马林固定的石蜡包埋的iCCA，14 BDA和18 BDH样品进行了DNA流式细胞术。在22个iCCA中检测到非整倍性（47％），但在32个BDA和BDH样品中均未检测到。在34例行完全切除术并随访至肿瘤复发，与肿瘤相关的死亡或至少1年的iCCA患者中，总复发率或死亡率（与流式细胞术结果无关）分别为18％，56％和71％在1年，3年和5年内。1，18例非整倍性iCCA患者的3年和5年复发率或死亡率分别为28％，66％和66％，而16名处于正常DNA含量的iCCA患者的1年，3年和5年复发率或死亡率分别为6、44和72％。尽管在前三年中，非整倍体肿瘤的预后较差，但在当前样本量中，这种差异在统计学上并不显着（危险比= 1.4，p = 0.473）。总之，iCCA中的非整倍性频率（47％）显着高于其良性形态模拟物（0％），这表明它可能在挑战性环境中作为恶性肿瘤的诊断标志。我们的发现还表明，即使不是全部，大多数BDA和BDH都是良性实体，可能并不代表通常带有非整倍性的iCCA的前体病变。