Department of Pathology.
Morristown Medical Center, Morristown, NJ.
Am J Surg Pathol. 2020 Nov;44(11):1573-1579. doi: 10.1097/PAS.0000000000001561.
Uterine carcinosarcomas (UCSs) are aggressive neoplasms composed of high-grade malignant epithelial and mesenchymal elements with most (∼90%) showing TP53 abnormalities. A subset, however, shows mismatch repair deficiency (MMR-D). We sought to describe their clinical, morphologic, and molecular features. Clinicopathologic data of MMR-D UCSs were recorded including age, stage, follow-up, mismatch repair and p53 immunohistochemistry (IHC), MLH1 promoter methylation status, and germline alterations, TP53 mutation status, microsatellite instability and mutational burden by massively parallel sequencing. Seventeen (6.2%) MMR-D were identified among 276 UCSs. Of MMR-D UCSs, the median age was 60 years. mismatch repair IHC loss is as follows: MLH1/PMS2 65%, MSH2/MSH6 18%, MSH6 12%, and PMS2 6%. MLH1 promoter methylation and Lynch syndrome was identified in 47% and 12% of cases, respectively. Cases with p53 IHC showed the following patterns: wild-type 70%, aberrant 20%, and equivocal 10%. Of cases with sequencing, 88% were hypermutated and microsatellite instability high. High-grade endometrioid, undifferentiated, and clear cell carcinoma was present in 53%, 41%, and 6% of cases, respectively and 47% also showed a low-grade endometrioid component. Most patients presented at an early stage (67%) and upon follow-up, 18% died of disease, 65% showed no evidence of disease, while 18% are alive with disease. Patients with MMR-D UCS are younger than the reported median age (70 y) for traditional UCS and most do not show p53 abnormalities. Low-grade endometrioid and undifferentiated carcinoma were seen in approximately half of all cases. Although UCSs have a high tendency for early extrauterine spread, most patients in our cohort presented at an early stage and at follow-up were no evidence of disease. MMR-D UCSs display distinct clinical, morphologic, and molecular features compared with traditional UCSs.
子宫癌肉瘤（UCS）是由高级别恶性上皮和间叶成分组成的侵袭性肿瘤，大多数（约 90%）存在 TP53 异常。然而，有一部分表现为错配修复缺陷（MMR-D）。我们旨在描述其临床、形态学和分子特征。记录了 MMR-D UCS 的临床病理数据，包括年龄、分期、随访、错配修复和 p53 免疫组化（IHC）、MLH1 启动子甲基化状态、种系改变、TP53 突变状态、微卫星不稳定性和突变负担的大规模平行测序。在 276 例 UCS 中发现了 17 例（6.2%）MMR-D。在 MMR-D UCS 中，中位年龄为 60 岁。MMR 免疫组化缺失如下：MLH1/PMS2 65%，MSH2/MSH6 18%，MSH6 12%，PMS2 6%。分别在 47%和 12%的病例中发现 MLH1 启动子甲基化和林奇综合征。有 p53 IHC 的病例表现为以下模式：野生型 70%，异常 20%，可疑 10%。在有测序的病例中，88%为高突变和微卫星不稳定高。高级别子宫内膜样癌、未分化癌和透明细胞癌分别占 53%、41%和 6%，47%还表现为低级别子宫内膜样癌成分。大多数患者在早期阶段（67%）就诊，随访时，18%死于疾病，65%无疾病证据，18%仍有疾病。与传统 UCS 报道的中位年龄（70 岁）相比，MMR-D UCS 的患者年龄更年轻，大多数患者没有 p53 异常。大约一半的病例中可见低级别子宫内膜样癌和未分化癌。尽管 UCS 有早期子宫外扩散的高倾向，但我们队列中的大多数患者在早期就诊，随访时无疾病证据。与传统 UCS 相比，MMR-D UCS 具有明显的临床、形态学和分子特征。
