Special Considerations in Classification and Workup of Endometrial Carcinomas.

CONTEXT.­: A variety of uncommon malignant endometrial tumors can be challenging to diagnose because of overlapping morphology with more common entities. In some cases, immunohistochemical stains and/or molecular testing allow for more definitive diagnosis or prognostication. OBJECTIVE.­: To review classic morphologic features of uncommon endometrial tumors, pathologic features of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in the diagnosis of these tumors. DATA SOURCES.­: University of Michigan (Ann Arbor) cases and review of pertinent literature about each entity. CONCLUSIONS.­: Although each of these uncommon endometrial tumors has morphologic mimics, key histologic features, immunohistochemical stains, and molecular testing allow for accurate classification.

KRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence.

Oncogenic activation of the mitogen-activated protein kinase (MAPK) pathway due to KRAS or BRAF gain-of-function mutation is frequently found in ovarian serous borderline tumor (SBT) and their extraovarian implants. We investigated mutational status of KRAS and BRAF of the primary ovarian SBTs that had a high stage presentation in correlation with clinical outcome. Among 39 consecutive primary SBTs with either invasive implants (20 cases) or non-invasive implants (19 cases), KRAS and BRAF mutational analysis was informative in 34 cases. Sixteen cases (47%) harbored a KRAS mutation, while 5 cases (15%) had a BRAF V600E mutation. High-stage disease (IIIC) was seen in 31% (5/16) of patients with a KRAS mutation and 39% (7/18) of patients without a KRAS mutation (p = 0.64). KRAS mutations were present in 9/16 (56%) tumors with invasive implants/LGSC versus 7/18 (39%) tumors with non-invasive implants (p = 0.31). BRAF mutation was seen in 5 cases with non-invasive implants. Tumor recurrence was seen in 31% (5/16) of patients with a KRAS mutation, compared to 6% (1/18) of patients without a KRAS mutation (p = 0.04). A KRAS mutation predicted an adverse disease-free survival (31% survival at 160 months) compared to those with wild-type KRAS (94% at 160 months; log-rank test, p = 0.037; HR 4.47). In conclusion, KRAS mutation in primary ovarian SBTs is significantly associated with a worse disease-free survival, independent of the high tumor stage or histological subtypes of extraovarian implant. KRAS mutation testing of primary ovarian SBT may servce as a useful biomarker for tumor recurrence.