To the Editor: The crux of this letter is a disagreement with the term ‘high-grade endometrioid carcinoma’. First, the authors point out that the diagnosis is not easily reproduced between pathologists. Second, they state that the molecular data indicate very little difference between high-grade endometrioid and high-grade serous carcinomas.1 Third, they perceive that continued use of the term ‘high-grade endometrioid’ will create confusion that will be detrimental to patient care. Fourth, they imply that the differences in the frequencies of two parameters—tubal intraepithelial carcinoma and dominant ovarian mass—in cases of high-grade serous and endometrioid carcinomas are insufficient reason to separate them.

We agree with the first two statements and anyone who properly reads the paper by Roh et al2 should arrive at the same conclusion. Each case of high-grade muellerian carcinoma analyzed in our study was re-reviewed and re-classified into three categories in recognition of the problem of sub-classifying these tumors. It should be obvious that we performed this study to determine whether differences existed between the histological groups. In fact, the summary statement in the abstract applies the term ‘high-grade muellerian carcinoma’ to this group of tumors. Using this term in practice addresses the third argument by making it clear to the oncologist that the tumor is not a low-grade endometrioid adenocarcinoma. Because these high-grade malignancies are typically high-stage when diagnosed, patients will not be harmed by this terminology.

But women who must deal with this disease, either directly or indirectly, and the field of ovarian cancer research in general, would be ill served by premature efforts to increase reproducibility by ignoring histological variation. In our study, we found only one tubal intraepithelial carcinoma in 12 cases of high-grade endometrioid carcinoma, which does not endorse a common origin for both high-grade serous and endometrioid carcinomas.2 However, some authors imply that all serous carcinomas come from the fimbria and a recent report suggests that fimbriectomy alone will eliminate the risk of pelvic serous cancer.3, 4 Do they know for certain that this protection will extend to all of the tumors in this proposed amalgam of high-grade serous cancer? We also disagree with the notion that ovarian involvement by a high-grade serous tumor confers ‘endometrioid’ histology. Endometrioid histology can be seen at any tumor site. Parenthetically, in our experience, about 15% of carcinomas in women with BRCA1 or BRCA2 mutations are high-grade endometrioid carcinomas. Some can even be traced to the fallopian tube, yet have distinctly different p53 expression patterns relative to their serous counterparts.5 Having progressively developed this concept of tubal carcinogenesis, we would like nothing more than to see all high-grade muellerian carcinomas traced to the fimbria.6 However, the data, even from studies that carefully evaluate the fallopian tubes, leave significant gaps.3, 7, 8

The transcriptomes, immunophenotypes, stages at presentation, and responses to therapy of high-grade muellerian carcinomas underscore their similarities in an era of imperfect prevention, detection and therapy.1, 2 Going forward, the success of efforts to prevent a given malignancy could hinge on where it originates from and its differentiation pattern. Call them all high-grade muellerian carcinomas if you wish to be consistent in clinical practice, but be ever mindful of nuances in pathology. Nuances can have powerful implications, and their recognition and translation define our discipline.