Fulminant Myocarditis with Combination Immune Checkpoint Blockade.

Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).

Indwelling ports for prophylactic RBC exchanges in sickle cell patients: Comparison of bard and vortex ports.

INTRODUCTION: Red blood cell exchange (RCE) procedures are commonly used for stroke prevention in sickle cell disease (SCD) patients. We compared two different dual lumen ports used for RCE because differences between the port and catheter design may lead to functional variance. METHODS: We reviewed the RCE parameters of SCD patients following implantable port placement encountered at a single institution. Five Vortex and four Bard ports were used and compared. Patients were followed for 1-24 exchange procedures over 3-26 months performed between 2013 and 2015. RESULTS: Nine patients underwent 124 RCE procedures with no failures. A total of 74 exchanges used Vortex ports with a mean flow rate of 45.2 mL/min while 50 exchanges used Bard ports with a mean flow rate of 42.1 mL/min which was a significant difference (P = .002). A total of 85 exchanges with tPA administration preprocedure had a mean flow rate of 43.8 mL/min while 39 exchanges without had a mean flow rate of 45.4 mL/min which was not a significant difference (P = .19). CONCLUSION: Both the Bard and Vortex ports functioned well during our study period with no treatment failures, no significant complications requiring removal or replacement, and adequate mean flow rates. While the difference in mean flow rates was statistically significant between Vortex and Bard ports, there may not be a practical difference in performance. There also does not appear to be a significant benefit in flow rates with preprocedure tPA. We conclude that both ports may be a satisfactory choice for vascular access in SCD patients expected to undergo regularly scheduled RCE.

A Collision Tumor in the Breast Consisting of Invasive Ductal Carcinoma and Malignant Melanoma.

Collision tumors are rare neoplasms that consist of at least two different cell lineages at the same site. Given the many possible combinations that can occur, collision tumors, while rare, have been reported in multiple locations such as the stomach, bladder, and thyroid. Collision tumors are rarely found in breast tissue, with only a few cases reported in the literature. We herein report a unique case of a 79-year-old woman with a history of melanoma who presented with a left breast mass that was subsequently found to have invasive ductal carcinoma (IDC) and metastatic melanoma in the breast tissue. This is one of the first reported combinations of these two malignancies.

Mortality and morbidity rounds (MMR) in pathology: relative contribution of cognitive bias vs. systems failures to diagnostic error.

Background Heuristics and cognitive biases are thought to play an important role in diagnostic medical error. How to systematically determine and capture these kinds of errors remains unclear. Morbidity and mortality rounds (MMRs) are generally focused on reducing medical error by identifying and correcting systems failures. However, they may also provide an educational platform for recognizing and raising awareness on cognitive errors. Methods A total of 49 MMR cases spanning the period 2008-2015 in our pathology department were examined for the presence of cognitive errors and/or systems failures by eight study participant raters who were trained on a subset of 16 of these MMR cases (excluded from the main study analysis) to identify such errors. The Delphi method was used to obtain group consensus on error classification on the remaining 33 study cases. Cases with <75% inter-rater agreement were subjected to subsequent rounds of Delphi analysis. Inter-rater agreement at each round was determined by Fleiss' kappa values. Results Thirty-six percent of the cases presented at our pathology MMRs over an 8-year period were found to contain errors likely due to cognitive bias. Conclusions These data suggest that the errors identified in our pathology MMRs represent not only systems failures but may also be composed of a significant proportion of cognitive errors. Teaching trainees and health professionals to correctly identify different types of cognitive errors may present an opportunity for quality improvement interventions in the interests of patient safety.

Comparative analysis of Rb1, P16 and ER as diagnostic, prognostic and potential targets for therapeutic agents in ovarian epithelial tumors: an immunohistochemical study of 130 ovarian carcinomas.

BACKGROUND: Deregulation of CDK4/6, cyclin D/P16 and retinoblastoma (Rb) are known aberrations in certain malignancies. There has been a recent interest in exploring the combination of letrozole and CDK4/6 inhibitors in recurrent ER+ ovarian cancers. METHODS: This study aimed to determine the frequency of expression of Rb1, P16 and ER in ovarian epithelial tumors by immunohistochemistry. RESULTS: Co-expression of all 3 markers studied was seen in 10% of high grade serous carcinoma (HGSC) and low grade serous carcinoma (LGSC). Coordinate expression of Rb1+ and ER+ in HGSC and LGSC was seen in 67% of grade 1/2 vs. 44 % of grade three tumors (p < 0.05). The reverse was true with positive P16 staining in 73% of grade three vs. 32% of grade 1/2 tumors (p < 0.001). CONCLUSIONS: Coordinate pattern of Rb1+ and ER+ in HGSC and LGSC is 19 and 50%, respectively. Rb1 and P16 show inverse expression pattern according to tumor grade with more frequent Rb1 in low grade vs. more frequent P16 in grade 3 tumors. These data provide a rational basis for clinical trials that aim to target these proteins.