Mesonephric-like endometrial carcinoma is a rare but frequently misclassified and aggressive malignancy. KRAS mutations, limited estrogen receptor (ER) expression, and TTF-1, GATA3, and luminal CD10 expression are described in these tumors, but an immunohistochemistry-based screening approach has not been studied. We assessed 300 endometrial carcinomas/carcinosarcomas to ascertain the specificity of TTF-1/GATA3/luminal CD10 expression with or without ER staining for this diagnosis. Next-generation sequencing and morphologic review were performed on screen-positive cases. In all, 3% (9/300) were TTF-1⁺; 2 coexpressed GATA3. No cases expressed luminal CD10 or GATA3 in isolation. Two TTF-1⁺/ER⁻ cases, one of which was also GATA3⁺, were reclassified as mesonephric-like based on morphology and molecular results (KRAS mutations without mismatch repair deficiency, TP53 mutations, or PTEN mutations): these represented 0.7% of all cases (2/300). The reclassified cases were originally diagnosed as grade 1 and 2 endometrioid carcinoma, and the latter had pulmonary metastases and pelvic recurrences. Six TTF-1⁺ cases retained their original serous (3) and endometrioid (3) diagnoses; 1 was reclassified as dedifferentiated. All had negative or low ER. KRAS mutations were identified in 4 TTF-1⁺ non–mesonephric-like cases, including 1 serous and 1 grade 3 endometrioid with p53 abnormalities, 1 mismatch repair–deficient endometrioid with a complex molecular profile, and 1 endometrioid with mucinous differentiation. These findings suggest that TTF-1 and ER are good first-line screens for mesonephric-like carcinoma, but caution that a TTF-1⁺/ER⁻ immunoprofile is not specific, even in the setting of KRAS mutations. A final diagnosis of mesonephric-like carcinoma requires integration of morphologic and immunohistochemical features, with molecular support when relevant.

中肾样子宫内膜癌是一种罕见但经常被错误分类的侵袭性恶性肿瘤。这些肿瘤中描述了KRAS突变、有限的雌激素受体 (ER) 表达以及TTF-1、GATA3 和腔 CD10 表达，但尚未研究基于免疫组织化学的筛查方法。我们评估了 300 例子宫内膜癌/癌肉瘤，以确定TTF-1 /GATA3/luminal CD10 表达（带或不带 ER 染色）对于该诊断的特异性。对筛查阳性病例进行了下一代测序和形态学审查。总共 3% (9/300) 是TTF-1 ⁺；2共表达GATA3。没有病例单独表达 Luminal CD10 或 GATA3。两例TTF-1 ⁺ /ER ^-病例，其中一例也是 GATA3 ⁺，根据形态学和分子结果（无错配修复缺陷的KRAS突变、 TP53突变或PTEN突变）被重新分类为中肾样：这些占 0.7%占所有案例 (2/300)。重新分类的病例最初诊断为1级和2级子宫内膜样癌，后者有肺转移和盆腔复发。6 例TTF-1 ⁺病例保留了原来的浆液性 (3) 和子宫内膜样 (3) 诊断；1被重新分类为去分化。所有患者的 ER 均为负值或较低。在 4 例TTF-1 ⁺非中肾样病例中发现 KRAS 突变，包括 1 例浆液性子宫内膜样和 1 例 p53 异常的 3 级子宫内膜样，1 例分子谱复杂的错配修复缺陷型子宫内膜样，以及 1 例粘液分化型子宫内膜样。这些发现表明TTF-1和 ER 是中肾样癌的良好一线筛查，但请注意，TTF-1 ⁺ /ER ^-免疫谱并不具有特异性，即使在KRAS突变的情况下也是如此。中肾样癌的最终诊断需要整合形态学和免疫组织化学特征，并在相关时提供分子支持。