James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
University of British Columbia, Vancouver, BC.
Am J Surg Pathol. 2021 Aug 1;45(8):1038-1046. doi: 10.1097/PAS.0000000000001737.
Corded and hyalinized and spindled carcinomas are rare variants of endometrioid carcinoma (EC) characterized by cords of low-grade epithelial cells (±spindle cells) within a hyalinized stroma or spindled epithelial cells, respectively, that merge with conventional low-grade EC. Due to their "biphasic" morphology, these tumors are often misdiagnosed as carcinosarcoma. The clinicopathologic features including mismatch repair protein (PMS2 and MSH6) and p53 immunohistochemical expression and POLE mutational status of 9 corded and hyalinized and spindled endometrial ECs were evaluated and classified into The Cancer Genome Atlas (TCGA) based molecular subgroups. Beta-catenin immunohistochemistry was performed as a surrogate for CTNNB1 mutational status. The mean age at diagnosis was 49 years (range: 34 to 68 y) with staging information available for 6 patients: stage IA (n=1), stage IB (n=1), stage II (n=2), stage IIIA (n=1), stage IIIC1 (n=1). A prominent corded and hyalinized component was present in 7 ECs comprising 15% to 80% of the tumor with a minor (5% to 15%) spindled morphology in 5. Two additional tumors were composed of a low-grade spindled component comprising 25% to 30% of the neoplasm. Tumors were grade 1 (n=3), grade 2 (n=5), and grade 2 to 3 (n=1) and squamous differentiation was identified in 8/9. All tumors had preserved expression of mismatch repair proteins with 8 showing a p53 wild-type phenotype including the grade 2 to 3 EC; 1 grade 2, stage IB tumor exhibited a mutant pattern of expression. All (n=7) but 1 tumor demonstrated nuclear beta-catenin expression in the glandular, squamous, and corded or spindled components. POLE exonuclease domain mutations were absent in all tumors. Based on our findings, corded and hyalinized EC and EC with spindle cells are usually low grade, low stage, and present at a younger age and exhibit squamous differentiation at an increased frequency compared to typical EC. Unlike carcinosarcomas, which frequently harbor TP53 mutations, these tumors usually exhibit wild-type p53 and nuclear beta-catenin expression, indicative of underlying CTNNB1 mutations. According to the TCGA subgroups of endometrial carcinoma, the majority of corded and hyalinized and spindled EC appear to fall into the copy number low ("no specific molecular profile") subgroup.
cords 和透明化以及梭形细胞癌是子宫内膜样癌（EC）的罕见变体，其特征为 cords 的低级别上皮细胞（±梭形细胞）在透明化基质内，或者梭形上皮细胞分别与传统的低级别 EC 融合。由于它们的“双相”形态，这些肿瘤经常被误诊为癌肉瘤。评估了 9 例 cords 和透明化以及梭形子宫内膜 EC 的临床病理特征，包括错配修复蛋白（PMS2 和 MSH6）和 p53 免疫组织化学表达以及 POLE 突变状态，并根据癌症基因组图谱（TCGA）进行了分类。进行β-连环蛋白免疫组织化学作为 CTNNB1 突变状态的替代物。诊断时的平均年龄为 49 岁（范围：34 至 68 岁），有 6 例患者有分期信息：IA 期（n=1），IB 期（n=1），II 期（n=2），IIIA 期（n=1），IIIC1 期（n=1）。7 例 EC 中有明显的 cords 和透明化成分，占肿瘤的 15%至 80%，其中 5 例有较小的（5%至 15%）梭形形态。另外 2 例肿瘤由低级别梭形成分组成，占肿瘤的 25%至 30%。肿瘤分级为 1 级（n=3），2 级（n=5），2 级至 3 级（n=1），8/9 例可见鳞状分化。所有肿瘤均保留错配修复蛋白的表达，8 例显示 p53 野生型表型，包括 2 级至 3 级 EC；1 例 2 级，IB 期肿瘤表现为突变型表达模式。所有（n=7）但 1 例肿瘤在腺性、鳞状和 cords 或梭形成分中均显示核β-连环蛋白表达。所有肿瘤均未发现 POLE 外切酶结构域突变。根据我们的发现，cords 和透明化 EC 以及具有梭形细胞的 EC 通常为低级别、低分期，并且在较年轻的年龄出现，并且与典型的 EC 相比，具有增加的鳞状分化频率。与经常含有 TP53 突变的癌肉瘤不同，这些肿瘤通常表现出野生型 p53 和核β-连环蛋白表达，表明存在 CTNNB1 突变。根据子宫内膜癌的 TCGA 亚组，大多数 cords 和透明化以及梭形 EC 似乎属于拷贝数低（“无特定分子特征”）亚组。
