Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Am J Surg Pathol. 2019 Jan;43(1):12-25. doi: 10.1097/PAS.0000000000000991.
Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract mainly occurring in the uterine cervix. To date, only a few cases of MNAC arising from of the uterine body (UB-MNAC) have been reported. The clinicopathologic and molecular characteristics of UB-MNAC remain unknown. In this study, we investigated the clinical, histopathologic, immunohistochemical, and genetic features of UB-MNAC. In total, 11 cases were included. Six patients developed metastatic disease, most commonly in lungs (5/6). Histopathologically, UB-MNAC was characterized by an admixture of tubular, glandular, papillary, retiform, glomeruloid, sex cord-like, and comedonecrosis-like architectural patterns. Three adverse pathologic characteristics, including advanced International Federation of Gynecology and Obstetrics stage, high mitotic activity, and presence of lymphovascular the invasion, were independent factors predicting the development of metastasis. All cases were positive for GATA-binding protein 3 and paired box 2 expression and showed wild-type p53, patchy p16, and preserved PTEN expression, as indicated by immunohistochemistry. Next-generation sequencing using 12 samples (11 primary tumors and 1 metastatic tumor) revealed 42 single nucleotide variations in 16 genes, mostly in KRAS (10/12) and ARID1A (9/12). Copy number variation was found in 16 genomic regions, and consisted of 57 gains and 10 losses, with 1q gain (11/12) being the most prevalent. In conclusion, UB-MNAC displays an aggressive biological behavior, with a tendency to metastasize to the lungs. Adverse pathologic characteristics reflect the aggressive nature of UB-MNAC. Distinct molecular features of UB-MNAC include frequent somatic mutations of KRAS and ARID1A and gain of 1q.
中肾腺癌（MNAC）是一种罕见的女性生殖道肿瘤，主要发生在子宫颈。迄今为止，仅报道了少数几例源自子宫体的 MNAC（UB-MNAC）病例。UB-MNAC 的临床病理和分子特征尚不清楚。在本研究中，我们研究了 UB-MNAC 的临床、组织病理学、免疫组织化学和遗传学特征。共纳入 11 例病例。6 例患者发生转移，最常见于肺部（5/6）。组织病理学上，UB-MNAC 的特征是管状、腺体、乳头状、网状、肾小球样、性索样和comedonecrosis 样结构模式的混合。3 个不良病理特征，包括国际妇产科联合会（FIGO）分期较晚、有丝分裂活性高和存在脉管侵犯，是预测转移发生的独立因素。所有病例 GATA 结合蛋白 3 和配对盒 2 表达均为阳性，免疫组织化学显示 p53 野生型、p16 斑驳表达和 PTEN 保留。使用 12 个样本（11 个原发性肿瘤和 1 个转移性肿瘤）进行下一代测序，在 16 个基因中发现了 42 个单核苷酸变异，主要在 KRAS（10/12）和 ARID1A（9/12）中。在 16 个基因组区域发现了拷贝数变异，包括 57 个增益和 10 个丢失，其中 1q 增益（11/12）最为常见。总之，UB-MNAC 表现出侵袭性的生物学行为，倾向于转移到肺部。不良的病理特征反映了 UB-MNAC 的侵袭性。UB-MNAC 的独特分子特征包括 KRAS 和 ARID1A 的体细胞突变频繁和 1q 的增益。
