We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.
We describe the case of a patient with neuroendocrine ethmoid sinus carcinoma, who exhibited markedly elevated levels of serum cardiac troponin-T and creatine kinase (CK)-MB isoenzyme without any symptom after the administration of nivolumab, immune checkpoint inhibitor. The repeated 12-leads-electrocardiogram did not show any changes in the ST-T segments or arrhythmias. The echocardiogram showed normal ranges of left ventricular contraction in the clinical course. Cardiac magnetic resonance imaging showed minimal myocardial edema and inflammation. Blood clots in the metastatic lesion of bone marrow aspirates exhibited positive staining for cardiac troponin-T and CK-MB in the cytoplasm and nucleoplasm of neoplastic cells. Although we did not perform a second cardiac magnetic resonance imaging and autopsy, we postulate that the attack of the neoplastic cells by the immune checkpoint inhibitor or the secretion from neoplastic cell-derived extracellular vesicles may have exacerbated the increase in concentrations of these molecules in the blood. Our case should warrant consideration a false-positive value of cardiac troponin-T and CK-MB can be obtained in cases with malignancy.
We report a case of amelanotic malignant melanoma (AMM) in a 66-year-old female. AMM of the lingual base was diagnosed based on a biopsy of late metastasis to the bone marrow of the L4 lumbar vertebra. The patient was initially treated with chemoradiotherapy after being misdiagnosed with poorly differentiated human papillomavirus- (HPV-) related squamous cell carcinoma of the oropharyngeal anterior wall. p16 immunostaining is used to diagnose HPV-related oropharyngeal cancer. However, while p16 expression is used as a surrogate marker of HPV infection, it is important to be aware that p16 protein overexpression can also be caused by other factors. Malignant melanoma is known to express the p16 protein. Morphologically differentiating between AMM and poorly differentiated squamous cell carcinoma based on hematoxylin-eosin staining is difficult. Therefore, in cases that are pathologically diagnosed as p16-positive poorly differentiated oropharyngeal squamous cell carcinoma, it is important to rule out AMM.
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