Abstract：
OBJECTIVE: Areas of gland crowding that do not fulfil diagnostic criteria of endometrioid intra-epithelial neoplasia (EIN) are often encountered in endometrial biopsies. In this study, we document the prevalence of neoplastic outcome in patients with these subdiagnostic lesions (SL) and assess the utility of morphological features and a three-marker immunohistochemistry panel (PAX2, PTEN, beta-catenin) to predict outcome.
RESULTS: Of 430 women with SL on endometrial sampling at Brigham and Women\'s Hospital between 2001 and 2021 with available follow-up biopsy, 72 (17%) had a neoplastic outcome (EIN or endometrioid carcinoma). Multilayered epithelium and mitoses in SL were statistically associated with a neoplastic outcome. Abnormal three-marker staining was observed in 93% (53 of 57) of SL with neoplastic outcome and 60% (37 of 62) of a control group with benign outcome. Among the 72 patients with neoplastic outcome, EIN/carcinoma tissue was available in 33; of these, 30 (91%) showed abnormal staining for one or more markers. Remarkably, in 84% of these cases the EIN/carcinoma had the aberrant expression seen in the preceding SL. Based on a prevalence of 17%, the positive and negative predictive values of abnormal staining in one or more markers were 24 and 97%, respectively.
CONCLUSIONS: The presence of SL warrants clinical surveillance and repeat sampling because it is followed by endometrioid neoplasia in a significant subset of patients. Normal three-marker staining identifies women with a very low risk of neoplastic outcome. Conversely, abnormal staining is frequent in SL with benign outcome leading to poor specificity and positive predictive value.
RESULTS: Of 430 women with SL on endometrial sampling at Brigham and Women\'s Hospital between 2001 and 2021 with available follow-up biopsy, 72 (17%) had a neoplastic outcome (EIN or endometrioid carcinoma). Multilayered epithelium and mitoses in SL were statistically associated with a neoplastic outcome. Abnormal three-marker staining was observed in 93% (53 of 57) of SL with neoplastic outcome and 60% (37 of 62) of a control group with benign outcome. Among the 72 patients with neoplastic outcome, EIN/carcinoma tissue was available in 33; of these, 30 (91%) showed abnormal staining for one or more markers. Remarkably, in 84% of these cases the EIN/carcinoma had the aberrant expression seen in the preceding SL. Based on a prevalence of 17%, the positive and negative predictive values of abnormal staining in one or more markers were 24 and 97%, respectively.
CONCLUSIONS: The presence of SL warrants clinical surveillance and repeat sampling because it is followed by endometrioid neoplasia in a significant subset of patients. Normal three-marker staining identifies women with a very low risk of neoplastic outcome. Conversely, abnormal staining is frequent in SL with benign outcome leading to poor specificity and positive predictive value.
摘要：
目的：在子宫内膜活检中经常遇到不符合子宫内膜样上皮内瘤变（EIN）诊断标准的腺体拥挤区域。在这项研究中,我们记录了这些亚诊断性病变（SL）患者中肿瘤结局的患病率，并评估了形态学特征和三标记免疫组织化学组（PAX2，PTEN，β-连环蛋白)来预测结果。
结果：在2001年至2021年期间在布莱根妇女医院进行子宫内膜采样的430名患有SL的妇女中，并进行了随访活检，72（17％）有肿瘤结果（EIN或子宫内膜样癌）。SL中的多层上皮和有丝分裂与肿瘤结局具有统计学相关性。在93％（57个中的53个）的具有肿瘤结果的SL和60％（62个中的37个）的具有良性结果的对照组中观察到异常的三标记染色。在72例有肿瘤结局的患者中，EIN/癌组织在33个中可用；其中，30(91%)显示一种或多种标记物的异常染色。值得注意的是,在84％的这些病例中，EIN/癌具有在先前SL中可见的异常表达。基于17%的患病率，一种或多种标志物异常染色的阳性和阴性预测值分别为24％和97％，分别。
结论：SL的存在需要进行临床监测和重复采样，因为在相当一部分患者中，子宫内膜样瘤形成紧随其后。正常的三标记染色表明女性患肿瘤的风险非常低。相反，SL中经常发生异常染色，良性结局导致特异性差和阳性预测值。
结果：在2001年至2021年期间在布莱根妇女医院进行子宫内膜采样的430名患有SL的妇女中，并进行了随访活检，72（17％）有肿瘤结果（EIN或子宫内膜样癌）。SL中的多层上皮和有丝分裂与肿瘤结局具有统计学相关性。在93％（57个中的53个）的具有肿瘤结果的SL和60％（62个中的37个）的具有良性结果的对照组中观察到异常的三标记染色。在72例有肿瘤结局的患者中，EIN/癌组织在33个中可用；其中，30(91%)显示一种或多种标记物的异常染色。值得注意的是,在84％的这些病例中，EIN/癌具有在先前SL中可见的异常表达。基于17%的患病率，一种或多种标志物异常染色的阳性和阴性预测值分别为24％和97％，分别。
结论：SL的存在需要进行临床监测和重复采样，因为在相当一部分患者中，子宫内膜样瘤形成紧随其后。正常的三标记染色表明女性患肿瘤的风险非常低。相反，SL中经常发生异常染色，良性结局导致特异性差和阳性预测值。
