Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Biol Blood Marrow Transplant. 2017 Aug;23(8):1367-1373. doi: 10.1016/j.bbmt.2017.04.022. Epub 2017 Apr 24.
Hematopoietic stem cell transplant (HSCT) recipients have a higher risk of cervical cancer. Papanicolaou (Pap) smear is the standard tool for screening cervical cancer, but there is limited research about the cervical cytology in HSCT recipients. Here, we retrospectively included adult female patients who underwent allogeneic or autologous HSCT at National Taiwan University Hospital during 2009 to 2015 and reviewed their Pap smears before and after HSCT. There were 248 allogeneic and 131 autologous HSCT recipients in our study. In allogeneic HSCT recipients, 38.7% (96 of 248) had pre-HSCT Pap smears and 17.1% (44 of 248) had post-HSCT Pap smears. In the autologous HSCT recipients, 35.1% (46 of 131) had pre-HSCT Pap smears and 13.7% (18 of 131) had post-HSCT Pap smears. Compared with allogeneic HSCT recipients without post-HSCT Pap smears, more recipients with post-HSCT Pap smears received bone marrow-derived stem cells (18.2% versus 4.9% respectively; P = .0077) and had longer overall survival (median overall survival, not reached versus 22.1 months; P < .0001). The abnormal rates of post-HSCT Pap smear were 13% (6 of 44) and 11% (2 of 18) in allogeneic and autologous recipients respectively, higher than in the general Taiwanese population (1.22%). Infections were rare in post-HSCT Pap smears. Of note, 11% (5 of 44) of post-HSCT Pap smears from allogeneic recipients showed therapy-related atypia, manifesting as enlarged hyperchromatic nuclei, vacuolated cytoplasm, and occasional tadpole-like cells. These atypical cytological features mimic precancerous lesions, but cervical biopsies and human papilloma virus tests were negative. The atypical cytological features resolved spontaneously in the subsequent follow-up Pap smears. On average, Pap smears with therapy-related atypia were sampled at day +77, significantly earlier than those without therapy-related atypia (P = .016). Therapy-related atypia was more frequent in post-HSCT Pap smears sampled within 100 days after HSCT (before day +100, 4 of 5, 80%, versus after day +100, 1 of 39, 2.56%; P = .0002). The strong temporal relationship suggests these atypical cytological changes resulted from conditioning regimen, most likely busulfan-containing chemotherapy. No therapy-related atypia were observed after total body irradiation or nonbusulfan-containing chemotherapy. In conclusion, therapy-related atypia was common in post-HSCT Pap smears sampled within 100 days after HSCT. Clinical information is critical for correct cytological diagnosis.
造血干细胞移植（HSCT）受者宫颈癌风险较高。巴氏涂片是筛查宫颈癌的标准工具，但关于 HSCT 受者的宫颈细胞学研究有限。在这里，我们回顾性纳入了 2009 年至 2015 年在国立台湾大学医院接受异基因或自体 HSCT 的成年女性患者，并回顾了她们 HSCT 前后的巴氏涂片检查结果。本研究共纳入 248 例异基因 HSCT 受者和 131 例自体 HSCT 受者。在异基因 HSCT 受者中，38.7%（248 例中的 96 例）有 HSCT 前巴氏涂片，17.1%（248 例中的 44 例）有 HSCT 后巴氏涂片。在自体 HSCT 受者中，35.1%（131 例中的 46 例）有 HSCT 前巴氏涂片，13.7%（131 例中的 18 例）有 HSCT 后巴氏涂片。与没有接受 HSCT 后巴氏涂片的异基因 HSCT 受者相比，更多接受 HSCT 后巴氏涂片的受者接受了骨髓源性干细胞（分别为 18.2%和 4.9%；P=0.0077），并且具有更长的总生存期（中位总生存期，未达到与 22.1 个月；P<0.0001）。异基因和自体 HSCT 受者的 HSCT 后巴氏涂片异常率分别为 13%（6/44）和 11%（2/18），高于台湾一般人群（1.22%）。HSCT 后巴氏涂片中感染很少见。值得注意的是，11%（5/44）的异基因 HSCT 后巴氏涂片显示治疗相关的非典型性，表现为核增大、深染、空泡化和偶尔出现蝌蚪样细胞。这些非典型细胞学特征类似于癌前病变，但宫颈活检和人乳头瘤病毒检测均为阴性。随后的巴氏涂片随访中，这些非典型细胞学特征自发消退。平均而言，具有治疗相关非典型性的巴氏涂片在 HSCT 后 77 天左右（+77 天）采样，明显早于无治疗相关非典型性的巴氏涂片（P=0.016）。在 HSCT 后 100 天内（+100 天前，5 例中有 4 例，80%，与+100 天后，39 例中有 1 例，2.56%；P=0.0002）采样的 HSCT 后巴氏涂片中，治疗相关非典型性更常见。强烈的时间关系表明，这些非典型细胞学变化是由预处理方案引起的，很可能是含有白消安的化疗。全身照射或不含白消安的化疗后未观察到治疗相关的非典型性。总之，HSCT 后 100 天内采样的巴氏涂片检查中常可见治疗相关的非典型性。临床信息对于正确的细胞学诊断至关重要。
