Mirkovic Jelena, Olkhov-Mitsel Ekaterina, Amemiya Yutaka, Al-Hussaini Maysa, Nofech-Mozes Sharon, Djordjevic Bojana, Kupets Rachel, Seth Arun, McCluggage W Glenn
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Histopathology. 2023 Jun;82(7):978-990. doi: 10.1111/his.14892. Epub 2023 Mar 31.
To report novel observations in five mesonephric-like adenocarcinomas (MLAs) of the female genital tract.
We report two endometrial MLAs in association with endometrioid carcinoma and atypical hyperplasia and three (one endometrial, two ovarian) cases with a sarcomatoid component (mesonephric-like carcinosarcoma). Pathogenic KRAS mutations, which are characteristic of MLA, were identified in all cases although interestingly, in one of the mixed carcinomas, this was confined to the endometrioid component. The concurrent MLA, endometrioid carcinoma and atypical hyperplasia components in one case harboured identical EGFR, PTEN and CCNE1 mutations, suggesting that the atypical hyperplasia gave rise to a Müllerian carcinoma with both endometrioid and mesonephric-like components. The carcinosarcomas all contained a component of MLA and a sarcomatous component with chondroid elements. In the ovarian carcinosarcomas, the coexisting epithelial and sarcomatous components shared some mutations including KRAS and CREBBP, suggesting that they are clonally related. Furthermore, in one case CREBBP and KRAS mutations detected in the MLA and sarcomatous components were also detected in an associated undifferentiated carcinoma component, suggesting that it was clonally related to the MLA and sarcomatous components.
Our observations provide additional evidence that MLAs have a Müllerian origin and characterise mesonephric-like carcinosarcomas in which chondroid elements appear to be characteristic. In reporting these findings, we provide recommendations for distinction between a mesonephric-like carcinosarcoma and a MLA with a spindle cell component.
报告女性生殖道5例中肾样腺癌（MLA）的新观察结果。
我们报告了2例与子宫内膜样癌和非典型增生相关的子宫内膜MLA，以及3例（1例子宫内膜、2例卵巢）具有肉瘤样成分（中肾样癌肉瘤）的病例。在所有病例中均鉴定出具有MLA特征的致病性KRAS突变，有趣的是，在其中1例混合癌中，该突变仅限于子宫内膜样成分。1例病例中同时存在的MLA、子宫内膜样癌和非典型增生成分具有相同的EGFR、PTEN和CCNE1突变，提示非典型增生产生了具有子宫内膜样和中肾样成分的米勒管癌。所有癌肉瘤均包含MLA成分和具有软骨样成分的肉瘤样成分。在卵巢癌肉瘤中，共存的上皮和肉瘤样成分共享一些突变，包括KRAS和CREBBP，提示它们是克隆相关的。此外，在1例病例中，在MLA和肉瘤样成分中检测到的CREBBP和KRAS突变也在相关的未分化癌成分中检测到，提示其与MLA和肉瘤样成分是克隆相关的。
我们的观察结果提供了额外证据，表明MLA起源于米勒管，并对中肾样癌肉瘤进行了特征描述，其中软骨样成分似乎具有特征性。在报告这些发现时，我们提供了区分中肾样癌肉瘤和具有梭形细胞成分的MLA的建议。
