Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges.

PURPOSE: Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs). METHODS: Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4%) and FFPE samples (22.4%), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83%). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6%); the remaining samples were evaluated by array-comparative genomic hybridization (CGH). RESULTS: A successful result was obtained in 7,396 of 8,118 (91.1%), with 92.4% of fresh tissue samples and 86.4% of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7% of specimens (3,975 of 7,396), 94% of which were considered causative. CONCLUSION: Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.Genet Med 19 1, 83-89.

Incidental power morcellation of malignancy: a retrospective cohort study.

OBJECTIVE: Uterine fibroids often require hysterectomy via a laparotomy or utilizing minimally invasive surgical (MIS) approach. Morcellation is a fragmentation of the uterus into smaller pieces. The objective of this study is to determine the incidence of malignancies found in morcellated specimens at our institution. METHODS: Women who had a minimally invasive hysterectomy, for presumptive benign uterine conditions were identified, included and reviewed. Patients were divided into two groups being either benign disease or malignancies. The continuous variables uterine weight and patient age were tested for normalcy with the Shapiro-Wilk test. The exposure of subspecialist vs general gynecology was interrogated via a Chi-Squared analysis. RESULTS: 10 cases of malignancies were identified including endometrioid endometrial carcinomas (3), uterine serous carcinoma (1), endometrial stromal sarcomas (ESS) (3), and leiomyosarcomas (LMS) (3). An overall risk of occult cancer on a morcellated specimen was .73%; leiomyosarcoma was 0.22%, endometrial stromal sarcoma 0.22%, and endometrial cancer 0.29%. The median uterine weight for the 10 morcellated malignancies was 293.5g whereas the median weight for the benign uteri was only 117.5g giving a theta of -106 (95% CI -261,20). There was no difference in patient age or surgeon type between the groups (See Table 1). CONCLUSIONS: Morcellation was associated with substantially higher risk of abdominopelvic recurrence and lower disease-free survival. Morcellated uterine malignancies were significantly heavier than benign uteri. Further research on uterine morcellation should focus on decision and cost-benefit analyses to determine the ideal candidate in whom uterine morcellation during minimally invasive hysterectomy would facilitate more good than harm.

Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC).

OBJECTIVES: Lymphadenectomy as a part of the staging for EC patients is controversial. Sentinel lymph node detection has been introduced to determine which patients would benefit from adjuvant therapy and to limit morbidities associated with a full pelvic nodal dissection. The purpose of this study is to evaluate diagnostic accuracy and detection rate of robotic sentinel lymph node detection (RSLND) as a part of the surgical staging for EC. METHODS: A retrospective database of all patients who underwent intraoperative lymphatic mapping using cervical injection methylene blue followed by RSLND as a part of their procedure was reviewed. Sentinel lymph node (SLN) was initially examined by routine Hematoxylin and Eosin (H&E) and ultrastaging by immunohistochemistry (IHC). RESULTS: Between 4/2011 and 6/2013, 120 patients with endometrial cancer underwent RSLND. The median age was 62years (25-87); median BMI was 32 (18-76). Out of 120 patients, only one patient underwent RSLND with fertility preservation; and 119 patients underwent robotic hysterectomy and surgical staging with RSLND. None of the cases was converted to an open procedure. At least 1 SLN was detected in 86% (103/120) of the patients. Bilateral SLNs were detected in 52% (62/120). Positive nodes were identified in 8% (10/120) of the patients. Of those with SLN (+), 50% (5/10) were by ultrastaging (IHC) alone. No patients had positive regional nodes without SLN (+). CONCLUSIONS: RSLND using methylene blue cervical injection can identify SLN in most patients with EC. IHC ultrastaging improves the detection of node positive disease when compared to traditional pathological evaluation.