False-Negative Urine Human Chorionic Gonadotropin Testing in the Clinical Laboratory.

BACKGROUND: Human chorionic gonadotropin (hCG) assays are used to detect pregnancy, and urine point-of-care tests are frequently used to triage patients. Under certain conditions, urine tests can fail to detect pregnancy, which can have serious consequences for patient management. OBJECTIVES: To understand the prevalence of different factors contributing to false-negative urinary hCG testing results at our institution. METHODS: Clinical data for patients with negative urine hCG results and subsequent positive or equivocal serum hCG results within a 1-year period were reviewed. RESULTS: Out of 9447 negative urine hCG results, 11 potential missed diagnoses were identified, with early gestational age as the most common factor, followed by ß-core hook effects. CONCLUSIONS: Although false-negative urine hCG test results are rare, understanding the commonly encountered reasons for inaccurate testing results can help clinical centers develop strategies to minimize risk for patients.

Discordant loss of mismatch repair proteins in advanced endometrial endometrioid carcinoma compared to paired primary uterine tumors.

OBJECTIVE: A subset of endometrial cancer is characterized by deficiencies in the mismatch repair (MMR) pathway. MMR testing is a well-established tool to screen for Lynch syndrome, but has also become a companion diagnostic test for immunotherapy. We compared the MMR status of primary and paired metastatic endometrial cancer to determine whether MMR deficiency can occur specifically in advanced endometrial cancer compared to primary tumor. METHODS: Matched primary uterine and metastatic endometrioid adenocarcinoma from 2009 to 2018 at our institution were identified. PMS2 and MSH6 protein expression in metastatic and matched primary tumor was assessed using clinically validated immunohistochemistry methods for Lynch syndrome screening. MLH1 promoter hypermethylation and microsatellite instability (MSI) were performed in discordant cases. RESULTS: 29 patients were identified with paired primary endometrial endometrioid adenocarcinoma and metastasis or recurrence after the original hysterectomy. Fourteen of 29 cases (48.2%, 14/29) were found to be MMR deficient at the metastatic or recurrent site. Two patients (6.9%, 2/29) showed discordant MMR status with PMS2 protein loss at the metastatic sites and intact expression in the primary uterine tumors. Both discordant cases exhibited abnormal subclonal loss at primary site and MLH1 promoter hypermethylation. High levels of microsatellite instability (MSI-H) was confirmed in one discordant metastatic site. CONCLUSION: Advanced endometrial cancer can rarely (~7%) show somatic loss of MMR protein expression in recurrent or metastatic sites compared to matched paired primary tumor. MMR testing of recurrent or metastasis should be considered for guiding immunotherapy if primary uterine tumor exhibits abnormal subclonal MMR loss.

A novel MRI-compatible brain ventricle phantom for validation of segmentation and volumetry methods.

PURPOSE: To create a standardized, MRI-compatible, life-sized phantom of the brain ventricles to evaluate ventricle segmentation methods using T(1) -weighted MRI. An objective phantom is needed to test the many different segmentation programs currently used to measure ventricle volumes in patients with Alzheimer's disease. MATERIALS AND METHODS: A ventricle model was constructed from polycarbonate using a digital mesh of the ventricles created from the 3 Tesla (T) MRI of a subject with Alzheimer's disease. The ventricle was placed in a brain mold and surrounded with material composed of 2% agar in water, 0.01% NaCl and 0.0375 mM gadopentetate dimeglumine to match the signal intensity properties of brain tissue in 3T T(1) -weighted MRI. The 3T T(1) -weighted images of the phantom were acquired and ventricle segmentation software was used to measure ventricle volume. RESULTS: The images acquired of the phantom successfully replicated in vivo signal intensity differences between the ventricle and surrounding tissue in T(1) -weighted images and were robust to segmentation. The ventricle volume was quantified to 99% accuracy at 1-mm voxel size. CONCLUSION: The phantom represents a simple, realistic and objective method to test the accuracy of lateral ventricle segmentation methods and we project it can be extended to other anatomical structures.