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Mixed endometrioid and clear cell carcinoma of the endometrium refers to a scenario in which the tumor exhibits histologic features of both endometrioid and clear cell carcinoma. We observed a tendency for these tumors to occur in a mismatch repair (MMR) protein-deficient molecular background in a prior study that examined a small cohort of mixed-type endometrial carcinomas. The aim of this study was to determine the rate of MMR protein deficiency in a larger series of endometrial mixed endometrioid and clear cell carcinomas, through a retrospective survey of MLH1, PMS2, MSH2, and MSH6 expression in such tumors at 5 tertiary centers. A total of 41 cases were identified and 27 (66%) tumors demonstrated MMR protein deficiency with a comparable frequency across the contributing centers (ranging from 56% to 83%). Among the MMR protein-deficient cases, 59% showed concurrent MLH1 and PMS2 loss, 33% showed concurrent MSH2 and MSH6 loss, and 4% showed isolated PMS2 or MSH6 loss. Compared with a previously published series of 15 pure endometrial clear cell carcinomas, mixed endometrioid and clear cell carcinomas are associated with significantly better disease-specific survival (P=0.02). In summary, endometrial carcinomas with mixed endometrioid and clear cell histology are frequently MMR protein deficient. This finding has implications both for our understanding of its tumor biology and for the identification of patients with potential Lynch syndrome.

Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It has histologic features that overlap with other endometrial carcinomas and is frequently misclassified. Accurate classification is crucial, however, to improve treatment options. The objectives of this study were (1) to assess diagnostic interobserver variability among 5 gynecologic pathologists for tumors originally diagnosed as CC or with a component of CC (n=44); (2) to determine the utility of immunohistochemical markers estrogen receptor and HNF-1β; and (3) to detect mutations in select genes. Clinical data and morphologic features were also recorded. Agreement among reviewers was only moderate: only 46% of the original CC remained classified as such. After reclassification, estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC), and 47% of serous carcinomas (SC). Sensitivities of HNF-1β in CC, SC, and EC were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41% of 37 cases that had adequate material for study. At least 1 mutation was identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had poor outcomes: 72% of the patients with follow-up information had died of disease. In summary, this study suggests that the current pool of CC is a heterogeneous group of tumors from the morphologic, immunophenotypic, and molecular point of views and that only a percentage of them represent true CC.

Many ovarian tumors, including high-grade serous carcinoma (HGSC), show clear cell change. Accurate diagnosis is important, however, as ovarian clear cell carcinoma (OCCC) is known to be less responsive to traditional types of ovarian cancer chemotherapies. In a previous study, the clinical, morphologic, and immunohistochemical features of 32 ovarian carcinomas, which had been previously diagnosed as pure OCCC (n=11), pure HGSC (n=11), and mixed serous and clear cell (MSC) (n=10), were analyzed. The immunoreactivities of WT1, ER, and p53, as well as the mitotic indices and stages of presentation of the MSC, were similar to those of HGSC. It was consequently concluded that MSC represented HGSC with clear cell change. Hepatocyte nuclear factor-1β (HNF-1β) is a relatively new immunohistochemical marker that has been shown to be rather sensitive and specific for OCCC. We thus sought to evaluate this marker in this specific group of tumors. One block each of pure HGSC and pure OCCC were stained with HNF-1β. In the cases of MSC, 2 blocks were stained when the serous and clear cell components were not present on the same slide. None (0/11) of the pure HGSC showed immunoreactivity for HNF-1β, whereas all (11/11) of the pure OCCC were positive. In the cases of MSC, both the serous and clear cell components were negative for HNF-1β. HNF-1β seems to be a sensitive and specific marker for OCCC and is not expressed in HGSC with clear cell change. The pattern of immunoreactivity of HNF-1β in tumors with both serous and clear cell change supports the conclusion that MSC are HGSC with clear cells.

Robotic surgery is increasingly being performed for endometrial cancer. Robotic hysterectomies (RH), like traditional laparoscopic hysterectomies (LH), involve a significant amount of uterine manipulation. The use of a manipulator is thought to possibly increase the incidence of artifactual tumor displacement beyond the endometrium, including the fallopian tube. The objective of this study was to determine whether there is an association between RH and tumor present in the fallopian tube lumina. All RH and LH cases performed for endometrial cancer from May 2007 to August 2009 were reviewed. Of the cases not converted to laparotomy, 137 RH and 184 LH were identified. Age, body mass index, operative and hysterectomy time, type and grade of tumor, stage, pelvic wash results, and the presence of detached tumor fragments (contaminants) in the lumina of the fallopian tubes were recorded. Appropriate statistical tests were applied. Of the 184 LH, 4 (2.2%) were reported to have detached fragments of tumor in the lumina of the fallopian tubes compared with 16 of the 137 (11.7%) RH cases (P<0.001). The majority of the patients with RH and tumor present in the tubes had Stage I disease (9/16, 56.2%) and Grade 1 tumors (9/16, 56.2%). Four (4/16, 25%) patients had Stage IIIa disease detected by a pelvic wash. Patients with contaminants had a higher body mass index, but the difference was not statistically significant and was possibly due to small numbers. In conclusion, our data demonstrate an association between RH and tubal contamination. The clinical significance of this phenomenon remains to be determined.

Primary percutaneous coronary intervention (PCI) of culprit lesions (CLs) is the standard of care in patients presenting with ST elevation myocardial infarction (STEMI). However, optimal revascularization strategy for significant nonculprit lesions (non-CLs) in the setting of STEMI remains controversial. The importance of defining of such a strategy lies in the fact that approximately 50% of patients with STEMI have multivessel disease (MVD). The aim of this study was to describe characteristics, therapeutic strategies, and 1-year outcomes in a cohort of patients with STEMI and MVD. We retrospectively analyzed a cohort of 63 patients with STEMI and MVD obtained from a 5-year catheterization database. MVD was defined as ≥70% stenosis of ≥2 epicardial coronary arteries. This cohort was followed for a period of 1 year for major adverse cardiac events (MACE was defined as acute coronary syndrome, new onset heart failure, or death) and all-cause mortality. PCI with stent placement was the major therapeutic procedure (87.5%) performed for CLs. Non-CLs did not undergo interventions in a majority of individuals (47.6%), while the remaining patients underwent PCI (29%) and coronary artery bypass graft surgery (22%) for non-CLs. At 1-year follow-up, prevalence of MACE events and death in the entire cohort were 30% and 15%, respectively. A trend for better outcomes (1-year cumulative MACE events but not mortality) was observed in CL-only intervention cohort compared with non-CL intervention. The PCI and Coronary artery bypass graft surgery cohorts did not show any significant difference in clinical outcomes. In this retrospective cohort of patients with MVD who presented with STEMI, no intervention of noncritical lesions was the prevalent approach, reflecting guideline recommendations. CL-only intervention strategy showed a better clinical outcome than non-CL intervention. Intervention of noncritical lesions therefore did not seem to improve MACEs or all-cause mortality at 1-year of follow-up and might in fact have had a detrimental effect on outcomes.