Acute fatal myocarditis after a single dose of anti-PD-1 immunotherapy, autopsy findings: a case report
CARDIOVASCULAR PATHOLOGY
Authors: Hardy, Tanner; Yin, Ming; Chavez, Jesus A.; Ivanov, Iouri; Chen, Wei; Nadasdy, Tibor; Brodsky, Sergey, V
Abstract
Nivolumab (PD-1 inhibitor) and Ipilimumab (CTLA-34 inhibitor) are both commonly used immune checkpoint inhibitor therapies for various cancers. Various adverse events are associated with these therapies, including hepatitis, nephritis, dermatitis, and myocarditis. It is believed these adverse events occur in part because modified cellular receptors lead to enhanced CD4 and CD8 lymphoproliferation. These events usually occur after several months and rounds of treatment. Here we present a case of an 81-year-old male with recurrent renal cell carcinoma (RCC) who experienced myocarditis after only a single dose of combination therapy with Nivolumab and Ipilimumab. He presented with elevated troponins and a third-degree heart block; three days after admission he died. Histologic examination revealed a predominance of CD3 T cells (CD4 > CD8) and CD68 macrophages, with occasional CD20 B cells. C4d staining was negative in the interstitial capillaries, suggesting that antibody-mediated injury of endothelial cells did not play a significant role in the pathogenesis of this myocarditis. Additional studies ruled out an infectious etiology. Immune checkpoint inhibitors are increasingly more common, and it is important clinicians are aware patients can present with myocarditis early in the course of treatment. (C) 2020 Elsevier Inc. All rights reserved.
Role ofCD68immunohistochemistry in categorizing benignnonmesothelialcell population and refining "atypical" category in serous fluid cytology
DIAGNOSTIC CYTOPATHOLOGY
Authors: Savari, Omid; Jassim, Sarmad; Ferrer, Hector; Ganocy, Stephen J.; Ganesan, Santhi
Abstract
Background Body fluids are rich in histiocytes and may mimic atypical epithelial cells morphologically. Histiocytes can pose a significant challenge in serous fluid cytology as they tend to appear atypical due to prolonged accumulation in serous fluids in vivo and processing by liquid-based cytology in vitro.Not many studies have documented the utilization of histiocytic marker such as CD68 in serous fluid cytology, which can subsequently reduce the "atypical" diagnostic category. Methods One thousand one hundred and twenty-nine cases of serous fluid cytology from 2016 to 2019 were reviewed and reclassified based on proposed classification of the international system for reporting serous fluid cytology. There were 133 cases with atypical diagnoses, out of which 51 cases had cellblocks. An immunohistochemistry (IHC) panel, including two mesothelial markers, two epithelial markers, and one histiocytic marker was applied to the atypical samples. Same IHC panel was utilized to evaluate 15 cases each from negative for malignancy (NFM), suspicious for malignancy (SFM), and malignant (MAL) categories for further comparison. Results After reevaluation of the cytology material with IHC stains, 924 (82%), 133 (12%), 23 (2%), and 49 (4%) of the cases were reclassified as NFM, atypia of uncertain significance, SFM, and MAL, respectively. Twenty-five out of 51 atypical cases (49%) were downgraded to "benign" after reevaluation with CD68 IHC. Conclusion Histiocytes can mimic atypical epithelial cells in body fluids. Effective utilization of CD68 IHC will be beneficial in further refining the "atypical" diagnostic category in serous fluid cytology.