Department of Pathology, University of California San Francisco, 505 Parnassus Avenue, M-551, San Francisco, CA 94143, USA.
Am J Surg Pathol. 2010 Feb;34(2):137-46. doi: 10.1097/PAS.0b013e3181c89c98.
Mesonephric remnants of the cervix are vestiges of the embryonic mesonephric system which typically regresses during female development. Uncommonly, hyperplasia of the mesonephric remnants may occur. The differential diagnosis of exuberant mesonephric hyperplasia includes minimal deviation adenocarcinoma of the cervix, a tumor with deceptively bland morphology for which no reliable diagnostic biomarkers currently exist. PAX2 encodes a transcription factor necessary in the development of the Wolffian duct system, and the protein is expressed in several tumors of mesonephric origin, including renal cell carcinoma, Wilm tumor, and nephrogenic adenoma. We hypothesized that PAX2 may also be expressed in mesonephric lesions of the cervix and may distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma of the cervix. We demonstrated that PAX2 was strongly and diffusely expressed in mesonephric remnants (6 of 6) and in mesonephric hyperplasia (18 of 18); however, no expression was noted in mesonephric adenocarcinoma (0 of 1). PAX2 was expressed in normal endocervical glands (including tunnel clusters and Nabothian cysts) (86 of 86), lobular endocervical glandular hyperplasia (5 of 5), tubal/tuboendometrioid metaplasia (8 of 8), and cervical endometriosis (13 of 14). In contrast, only 2 cases of endocervical adenocarcinoma were positive for PAX2 [invasive adenocarcinoma of the minimal deviation type (0 of 5), usual type (1 of 22), and endometrioid type (1 of 1)]. Adjacent adenocarcinoma in situ, as well as cases of pure adenocarcinoma in situ (0 of 6), were also PAX2 negative. PAX2 expression in the 2 positive endocervical adenocarcinomas was patchy and weak. Most (11 of 15) stage II endometrial endometrioid adenocarcinomas lacked PAX2 expression but 1 of 10 grade 1 tumors and 3 of 5 grade 2 tumors did express PAX2. These results suggest that PAX2 immunoreactivity may be useful to (1) distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma, (2) to distinguish lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma, and (3) to distinguish endocervical tubal metaplasia or cervical endometriosis from endocervical adenocarcinoma in situ. Overall, a strong, diffuse nuclear PAX2 expression pattern in a cervical glandular proliferation predicts a benign diagnosis (positive predictive value 90%, negative predictive value 98%; P<0.001); however, PAX2 should not be interpreted in isolation from the architectural and cytologic features of the lesion as it may be expressed in some stage II endometrial adenocarcinomas involving the cervix.
宫颈中肾残留是胚胎中肾系统的遗迹，通常在女性发育过程中退化。罕见情况下，中肾残留可能会增生。过度增生的中肾残留的鉴别诊断包括宫颈极小部分偏离型腺癌，这是一种形态上具有欺骗性的肿瘤，目前尚无可靠的诊断生物标志物。PAX2 编码 Wolffian 管系统发育所必需的转录因子，该蛋白在几种中肾来源的肿瘤中表达，包括肾细胞癌、Wilms 瘤和肾源性腺瘤。我们假设 PAX2 也可能在宫颈的中肾病变中表达，并可区分中肾增生与宫颈极小部分偏离型腺癌。我们证明 PAX2 在中肾残留（6/6）和中肾增生（18/18）中均呈强烈弥漫性表达；然而，在中肾腺癌（0/1）中未观察到表达。PAX2 在正常宫颈内膜腺（包括隧道簇和 Nabothian 囊肿）（86/86）、小叶宫颈内膜腺增生（5/5）、输卵管/管状内膜样化生（8/8）和宫颈子宫内膜异位症（13/14）中表达。相比之下，只有 2 例宫颈腺癌对 PAX2 呈阳性反应[微小偏离型浸润性腺癌（5/5）、普通型（22/1）和子宫内膜样型（1/1）]。邻近的原位腺癌以及单纯原位腺癌（6/6）也为 PAX2 阴性。2 例阳性宫颈腺癌的 PAX2 表达呈斑片状和弱阳性。大多数（11/15）II 期子宫内膜样腺癌缺乏 PAX2 表达，但 1 例 I 级肿瘤和 3 例 II 级肿瘤表达 PAX2。这些结果表明，PAX2 免疫反应性可能有助于（1）区分中肾增生与微小偏离型腺癌，（2）区分小叶宫颈内膜腺增生与微小偏离型腺癌，（3）区分宫颈管状化生或子宫内膜异位症与宫颈原位腺癌。总的来说，宫颈腺性增生中强烈、弥漫的核 PAX2 表达模式预示着良性诊断（阳性预测值 90%，阴性预测值 98%；P<0.001）；然而，不应孤立地根据病变的结构和细胞学特征来解释 PAX2，因为它可能在一些累及宫颈的 II 期子宫内膜腺癌中表达。
