PMC6716019_01
(A)
18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) findings before nivolumab administration. (B,C) Chest radiograph and 12-leads-electrocardiogram obtained on the admission day. (D,E) Cardiac magnetic resonance imaging in diastole (D) and systole (E), suggesting that global left ventricular function was not impaired. (F) The dark-blood sequence for non-enhanced T2-weighted image showed slight enhancement in the septal and lateral walls. (G) Delayed gadolinium-enhanced image showed minor enhancement in the mid-myocardial septal and inferior wall. (H) Examination and treatment of the clinical course. Electrocardiogram, echocardiogram, 18F-FDG-PET, cardiac magnetic resonance imaging, and bone marrow aspiration were performed on the indicated days in the panel.
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F1
However, 18F-fluorodeoxyglucose-positron emission tomography scan suggested multiple bone metastases (Figure 1A). Chest radiographs revealed a 49% cardio-thoracic ratio, and hilum in the left lung showed a swollen lesion (Figure 1B). The twelve-leads-electrocardiogram showed a normal sinus rhythm, normal axis deviation, and no change in the ST-T segments (Figure 1C). Cardiac magnetic resonance imaging showed normal systolic contractility (Figures 1D,E) and minimal myocardial edema and inflammation (Figures 1F,G). We continued to administer 125 mg/day of methyl-prednisolone, and we added 5 g/day of gamma-globulin for 7 days, but the patient persistently showed elevated levels of total CK and cardiac troponin-T within 1 month (Figure 1H).
(A-E) Blood clot aspirates from the left side of the pelvis (A, hematoxylin-eosin; B, INSM1; C, CD56; D, troponin-T; E, CK-MB). (F-H) Primary lesion in the ethmoid sinus (F, hematoxylin-eosin; G, troponin-T; H, CK-MB). x200. Deparaffinized slide sections were heated to retrieve the antigen (citrate, pH 6.0 for CD56, Troponin-T, and CK-MB; ethylenediaminetetraacetic acid, pH 9.0 for INSM1). They were immersed in hydrogen peroxide to block the endogenous peroxidase activity. The slide sections were incubated with the following primary monoclonal antibodies; INSM1 (0.67 mug/mL, clone A-8, Santa Cruz Biotechnology, Inc.), CD56 (0.11 mug/mL, clone 1B6, Leica Biosystems Newcastle Ltd), cardiac troponin T (0.5 mug/mL, clone 13-11, ThermoFisher Scientific), and polyclonal antibody for CK-MB (2.5 mug/mL, ThermoFisher Scientific, catalog number PA5-28920). Then, the slide sections were incubated with horseradish peroxidase-polymer secondary antibody at room temperature. They were visualized with 0.05% 3, 3'-diaminobenzidine containing hydrogen peroxide, and counterstained with hematoxylin. The slides were scanned under the Olympus BX53F microscope (Olympus, Tokyo, Japan). Negative (IgG) and positive (human heart) slides were prepared for troponin-T and CK-MB staining (data not shown).
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F2
Blood clots in the bone marrow aspirates obtained from the left side of the pelvis exhibited consistent immunohistological features of the primary lesion, which showed positive staining for INSM1 and CD56 (Figures 2A-C). These clots also showed positive staining for cardiac troponin-T (Figure 2D) and CK-MB (Figure 2E) in the cytoplasm and nucleoplasm of metastatic neoplastic cells. These molecules were also scattered in the primary lesion of the ethmoid sinus (Figures 2F-H).