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Mixed endometrial carcinomas are defined as a combination of 2 or more distinct histologic subtypes, one of which must be a type II tumor comprising at least 5% of the tumor volume. The oncogenesis of these tumors remains unclear, particularly in light of the increasingly appreciated morphologic overlap among subtypes, as well as evolving molecular data. We evaluated 8 cases of mixed endometrial carcinoma, including 4 endometrioid (EC)/serous (SC), 1 SC/clear cell (CC), and 3 EC/CC cases, to study the underlying molecular features and oncogenic mechanisms at play. Each component was analyzed by a targeted next-generation sequencing assay. All tumors shared mutations in both components. In 6 cases, one component showed additional mutations. Two EC/SC cases showed shared mutations and mutations unique to each component. When present, unique mutations were typically seen in the SC component, including variants in POLE and TP53, as well as potentially targetable genes DDR2, MAP2K1, and CCNE1. In EC/SC tumors, ERBB2 abnormalities were seen in 2 cases. EC/CC cases showed FGFR2 activating mutations in the EC component only. No fusion drivers were identified. Our data suggest that the majority of these tumors begin as a single clone and diverge along 2 pathways: (1) tumor progression, with one component showing additional mutations, and (2) tumor divergence, in which tumor components have both shared mutations and mutations unique to each component. In addition, the findings suggest a component of morphologic mimicry in these tumors. Our findings are clinically relevant since targetable mutations may be present in only one component of mixed tumors.

RadioGraphics continues to publish radiologic-pathologic case material selected from the American Institute for Radiologic Pathology (AIRP) "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology Correlation Course, which is offered five times per year. On the penultimate day of the course, the best case presentation is held at the American Film Institute Silver Theater and Cultural Center in Silver Spring, Md. The AIRP faculty identifies the best cases, from each organ system, brought by the resident attendees. One or more of the best cases from each of the five courses are then solicited for publication in RadioGraphics. These cases emphasize the importance of radiologic-pathologic correlation in the imaging evaluation and diagnosis of diseases encountered at the institute and its predecessor, the Armed Forces Institute of Pathology (AFIP).

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Low-grade, low-stage endometrioid carcinomas (LGLS EC) demonstrate 5-yr survival rates up to 95%. However, a small subset of these tumors recur, and little is known about prognostic markers or established mutation profiles associated with recurrence. The goal of the current study was to identify the molecular profiles of the primary carcinomas and the genomic differences between primary tumors and subsequent recurrences. Four cases of LGLS EC with recurrence and 8 cases without recurrence were evaluated via whole-exome sequencing. Three of the 4 recurrent tumors were evaluated via Oncomine Comprehensive Assay. The resulting molecular profiles of the primary and recurrent tumors were compared. Two of the 3 recurrent cases showed additional mutations in the recurrence. One recurrent tumor included an additional TP53 mutation and the other recurrent tumor showed POLE and DDR2 kinase gene mutation. The POLE mutation occurred outside the exonuclease domain. PIK3CA mutations were detected in 4 of 4 primary LGLS EC with recurrence and in 3 of 8 disease-free cases. LGLS EC with recurrence showed higher MSIsensor scores compared with LGLS without recurrence. The level of copy number gains in LGLS EC with recurrence was larger than LGLS EC without recurrence. This pilot study showed 1 of 3 recurrent cases gained a mutation associated with genetic instability (TP53) and 1 of them also acquired a mutation in the DDR2 kinase, a potential therapeutic target. We also noted a higher level of copy number gains, MSIsensor scores and PIK3CA mutations in the primary tumors that later recurred.

e14602 Background: The number one challenge in clinical biomarker testing for non-small cell lung cancer (NSCLC) has been the sample adequacy, given that the majority of patients are diagnosed based on minimally invasive sampling of tumor tissue. The increasingly evolving integration of high-throughput next-generation sequencing (NGS) has redefined molecular diagnostic lab practice allowing for time- and cost-efficient parallel testing of multiple biomarkers with limited specimen. Two NGS companion diagnostic (CDx) tests have been approved by FDA, FoundationOne CDx (F1CDx) and Oncomine Dx Target Test (Oncomine Dx), but with different sample acceptance criteria. The minimum tumor content requirement for F1CDx is 20% while it is 10% for Oncomine Dx. The surface area requirement for F1CDx is 25mm2 while there is no required minimum surface area for Oncomine Dx. The difference in sample acceptance criteria may have a major impact on the number of advanced NSCLC patient samples that can be accepted and tested successfully, affecting biomarker-directed therapy. Methods: The analysis of 153 NSCLC patient samples tested by Oncomine Dx at Cancer Genetics, Inc. CLIA-certified and CAP-accredited lab from October 2017 to September 2018 evaluated the sample acceptance rate, biomarker results, and testing turn-around time (TAT). Results: Based on the data, a significant portion of the samples submitted for routine clinical testing consists of extremely small specimen, including FNA cytology, with 42% less than 1mm2. 83% of samples are acceptable by Oncomine Dx criteria, compared to 14% by F1CDx. Of the 82 samples that would not be acceptable by F1CDx but generated results by Oncomine Dx, 5 were positive for EGFR exon 19 deletions and L858R, 1 for BRAF V600E, 1 for a ROS1 fusion, and the remaining 35 were positive for other actionable alterations. Average TAT was 9.2 days, consistent with recommendation by IASLC/AMP/CAP guideline of within 10 days. Conclusions: The real-world routine clinical testing of NSCLC patient samples demonstrated that a higher number of specimens with limited tumor tissue could be tested with the FDA-approved NGS CDx Oncomine Dx providing rapid TATs, actionable insights, and impacting the patient treatment outcomes.