Cardiac xenografts show reduced survival in the absence of transgenic human thrombomodulin expression in donor pigs.

A combination of genetic manipulations of donor organs and target-specific immunosuppression is instrumental in achieving long-term cardiac xenograft survival. Recently, results from our preclinical pig-to-baboon heterotopic cardiac xenotransplantation model suggest that a three-pronged approach is successful in extending xenograft survival: (a) α-1,3-galactosyl transferase (Gal) gene knockout in donor pigs (GTKO) to prevent Gal-specific antibody-mediated rejection; (b) transgenic expression of human complement regulatory proteins (hCRP; hCD46) and human thromboregulatory protein thrombomodulin (hTBM) to avoid complement activation and coagulation dysregulation; and (c) effective induction and maintenance of immunomodulation, particularly through co-stimulation blockade of CD40-CD40L pathways with anti-CD40 (2C10R4) monoclonal antibody (mAb). Using this combination of manipulations, we reported significant improvement in cardiac xenograft survival. In this study, we are reporting the survival of cardiac xenotransplantation recipients (n = 3) receiving xenografts from pigs without the expression of hTBM (GTKO.CD46). We observed that all grafts underwent rejection at an early time point (median 70 days) despite utilization of our previously reported successful immunosuppression regimen and effective control of non-Gal antibody response. These results support our hypothesis that transgenic expression of human thrombomodulin in donor pigs confers an independent protective effect for xenograft survival in the setting of a co-stimulation blockade-based immunomodulatory regimen.

Cytologic features of metastatic epithelioid uterine leiomyosarcoma to the pancreas.

Although uterine leiomyosarcoma (ULMS) is a rare disease, it accounts for a significant proportion uterine cancer-related deaths due to frequent metastasis and chemoresistance. The WHO currently recognizes the conventional (spindle), myxoid, and epithelioid variants of ULMS, the latter of which is the rarest, least understood, and cited as clinically more aggressive than the other variants. Descriptions of the histologic features of epithelioid ULMS are extremely limited, and are absent from the cytology literature which has only published descriptions of conventional ULMS or epithelioid variants of other LMS primaries. Therefore, we present a unique case of metastatic epithelioid ULMS to an unusual location, the pancreas, along with its cytologic features on endoscopic ultrasound-guided fine needle aspiration not previously described including pseudoglandular arrangements, scant cytoplasm, and frequent molding.

Metastatic mesonephric-like endometrial adenocarcinoma diagnosed on transbronchial needle aspirate cytology.

Mesonephric-like adenocarcinoma is a relatively rare neoplasm with morphology similar to mesonephric adenocarcinoma but unassociated with mesonephric remnants. Its relatively recent description and rarity make it difficult to diagnose, but it has a high rate of distant metastasis, making distinction from endometrioid carcinoma important. Descriptions of its cytologic features are particularly limited. We describe a case of mesonephric-like adenocarcinoma diagnosed on transbronchial needle aspiration of the lung, that had been misdiagnosed as endometrioid endometrial adenocarcinoma on a prior hysterectomy. We discuss the characteristic cyto and histomorphology, immunoprofile, molecular alterations, and clinical significance of this uncommon tumor.

Pathology Trainees Gain Clinical Pathology Experience as Lab Consultants Through Auditing Myeloid Mutation Panel Send-Out Tests: Hitting Two Birds With One Stone?

CONTEXT.­: Inappropriate laboratory testing and the threat it poses to patient care and rising health care costs has become an important focus in the medical literature. Pathology residents, as physicians with an intimate knowledge of laboratory testing, may be uniquely equipped with the tools to intervene in situations of inappropriate testing and also benefit from lab use experience as part of their clinical pathology training. OBJECTIVE.­: To employ a resident-driven initiative aimed at incorporating pathology residents as consultants for appropriate ordering of high-volume, send-out myeloid mutation panel testing. DESIGN.­: During a 6-month study period, all myeloid mutation panel send-out tests were screened by senior pathology residents on their clinical chemistry rotation prior to approval at an academic medical center. A retrospective review of myeloid mutation panels from the prior 6 months was conducted with the same criteria to determine effectiveness of the intervention. RESULTS.­: Of the 234 tests ordered during the study period, screening resulted in cancellation of 17% (n = 39), with proportional cost savings. The number of inappropriate orders successfully cancelled was significant compared with the preintervention period (control, 0%; intervention, 76.5%; P < .001, Fisher exact test). There was no significant difference in the proportion of inappropriate tests before and after intervention. CONCLUSIONS.­: Although test ordering patterns did not substantially change during the intervention period, pathology residents effectively reduced inappropriate myeloid mutation panel testing through prospective send-out auditing, leading to significant cost savings. Moreover, assessment of test use and appropriateness provided critical clinical pathology training within the areas of hematology, molecular genetics, and laboratory management.

Evaluation of Inappropriate COVID-19 RT-PCR Test Utilization at an Academic Medical Center.

BACKGROUND: An evolving COVID-19 testing landscape and issues with test supply allocation, especially in the current pandemic, has made it challenging for ordering providers. We audited orders of the Xpert® Xpress SARS-CoV-2 PCR with reverse transcription (RT-PCR) platform-the fastest of several other testing modalities available-to illuminate these challenges utilizing a multidisciplinary laboratory professional team consisting of a pathology resident and microbiology laboratory director. METHODS: Retrospective review of the first 5 hundred Xpert Xpress SARS-CoV-2 RT-PCR test orders from a 2-week period to determine test appropriateness based on the following indications: emergency surgery, emergent obstetric procedures, initial behavioral health admission, and later including discharge to skilled care facilities and pediatric admissions. Our hypothesis was that a significant proportion of orders for this testing platform were inappropriate. RESULTS: On review, a significant proportion of orders were incorrect, with 69.8% (n = 349, P < 0.0001) not meeting indications for rapid testing. Of all orders, 249 designated as emergency surgery were inappropriate, with 49.0% of those orders never proceeding with any surgical intervention; most of these were trauma related (64.6% were orders associated with a trauma unit). CONCLUSIONS: Significant, pervasive inappropriate ordering practices were identified at this center. A laboratory professional team can be key to identifying problems in testing and play a significant role in combating inappropriate test utilization.