Pitman Martha Bishop, Cibas Edmund S, Powers Celeste N, Renshaw Andrew A, Frable William J
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Cancer. 2002 Jun 25;96(3):128-34. doi: 10.1002/cncr.10618.
The diagnosis of "atypical squamous cells of undetermined significance" (ASCUS) is controversial, not only for the clinical utility of its subcategories (favor reactive vs. favor dysplasia), but for its very existence as an expression of uncertainty. In the current study, the authors investigated the impact of reducing and eliminating this category on the sensitivity and predictive values for detecting squamous intraepithelial lesions (SILs).
One hundred cervical Papanicolaou (Pap) smears originally diagnosed as ASCUS, all of which had histologic follow-up, were reviewed blindly and reclassified as either negative (within normal limits/benign cellular changes), low-grade SIL (LSIL), or high-grade SIL (HSIL) by 1 reviewer who eliminated ASCUS as a diagnostic possibility entirely. A second reviewer reinterpreted the cases but attempted to use the ASCUS diagnosis (favor reactive or favor dysplasia) sparingly. All histologic diagnoses were reviewed, and an adjudicated final diagnosis was established. Reviewed smear interpretations were correlated with the histologic diagnosis (original, reviewed, and adjudicated). Statistical analysis was performed using the Fisher exact test.
Thirty-eight women had histologically confirmed SIL (21 LSIL cases and 17 HSIL cases [including 1 case of endocervical adenocarcinoma]); 31 of these 38 cases originally were classified as ASCUS, not otherwise specified, 1 case was classified as ASCUS favor reactive, and 6 cases were classified as ASCUS favor dysplasia. The reviewer who used the ASCUS diagnosis sparingly reclassified the smears as negative (62 cases); ASCUS, favor reactive (3 cases); ASCUS, favor dysplasia (13 cases); LSIL (19 cases); and HSIL (3 cases). The reviewer who eliminated the ASCUS category reclassified the smears as negative (59 cases), LSIL (29 cases), and HSIL (12 cases). The rate of SIL/HSIL in those cases interpreted as abnormal was 38%/17% originally, 42%/24% with a reduced ASCUS interpretation, and 37%/17% when the ASCUS category was eliminated. In those ASCUS smears that were reclassified as negative, the SIL/HSIL rate was 35%/13% with the reduced ASCUS interpretation and 39%/17% when the ASCUS category was eliminated. The sensitivity for detecting a SIL/HSIL was reduced from 100%/100% for the original ASCUS interpretation to 42%/53% for the reduced ASCUS interpretation to 39%/41% with the elimination of the ASCUS interpretation.
Although in the current study utilization of the ASCUS diagnosis was found to result in a 62% negative or reactive outcome on biopsy, a significant number of patients with SIL were detected (38% in the current series, 17% with HSIL). Despite the improved correlation with negative biopsies, reducing or eliminating the ASCUS diagnosis appears to decrease the sensitivity of the Pap smear significantly and appears to be no better than chance at predicting a diagnosis of SIL on biopsy, including HSIL.
“意义不明确的非典型鳞状细胞”（ASCUS）的诊断存在争议，这不仅体现在其亚分类（倾向反应性改变与倾向发育异常）的临床实用性上，还体现在它作为不确定性表达的存在本身。在本研究中，作者调查了减少和消除这一类别对检测鳞状上皮内病变（SIL）的敏感性和预测价值的影响。
对100例最初诊断为ASCUS的宫颈巴氏涂片进行盲法复查，所有病例均有组织学随访结果。由1名审阅者将这些涂片重新分类为阴性（在正常范围内/良性细胞改变）、低级别SIL（LSIL）或高级别SIL（HSIL），该审阅者完全排除了ASCUS作为诊断可能性。第二名审阅者重新解读这些病例，但尽量少用ASCUS诊断（倾向反应性或倾向发育异常）。对所有组织学诊断进行复查，并确定最终的裁定诊断。将复查后的涂片解读结果与组织学诊断（原始、复查和裁定）进行关联分析。使用Fisher精确检验进行统计分析。
38名女性经组织学证实存在SIL（21例LSIL和17例HSIL[包括1例宫颈管腺癌]）；这38例中，31例最初被分类为未另行指定的ASCUS，1例被分类为倾向反应性的ASCUS，6例被分类为倾向发育异常的ASCUS。尽量少用ASCUS诊断的审阅者将涂片重新分类为阴性（62例）、倾向反应性的ASCUS（3例）、倾向发育异常的ASCUS（13例）、LSIL（19例）和HSIL（3例）。排除ASCUS类别的审阅者将涂片重新分类为阴性（59例）、LSIL（29例）和HSIL（12例）。最初被解读为异常的病例中，SIL/HSIL的比例分别为38%/17%，减少ASCUS解读时为42%/24%，排除ASCUS类别时为37%/17%。在重新分类为阴性的ASCUS涂片中，减少ASCUS解读时SIL/HSIL的比例为35%/13%，排除ASCUS类别时为39%/17%。检测SIL/HSIL的敏感性从最初ASCUS解读时的100%/100%降至减少ASCUS解读时的42%/53%，排除ASCUS解读时降至39%/41%。
尽管在本研究中发现使用ASCUS诊断导致活检结果为阴性或反应性的比例为62%，但仍检测出了相当数量的SIL患者（本系列中为38%，HSIL为17%）。尽管与阴性活检结果的相关性有所改善，但减少或排除ASCUS诊断似乎会显著降低巴氏涂片的敏感性，并且在预测活检时SIL（包括HSIL）的诊断方面似乎并不比随机猜测更好。
