2018 Volume 82 Issue 3 Pages 932-933
A 70-year-old man was hospitalized due to polymyositis and died of pneumonia 1 week after admission. Sirolimus-eluting bioresorbable polymer coated stent (Ultimaster; Terumo, Tokyo, Japan) had been implanted in the circumflex artery 2 months previously. He had been prescribed aspirin 100 mg/day and clopidogrel 75 mg/day. An autopsy was performed followed by ex vivo intravascular ultrasound (IVUS; Terumo), optical frequency domain imaging (OFDI; Terumo) and coronary angioscopy (CAS; FiberTech, Tokyo, Japan). IVUS and OFDI showed a convex-shaped mass with echo attenuation, and protruding mass with a smooth surface accompanied by high back-scattering within the stent-implanted segment, respectively (Figure 1A,B; Movie S1). CAS showed a yellowish polypoid lesion over the stent struts. Red thrombus adhesion was observed at the base of the protruding mass lesion (Figure 1C).
Post-mortem ex vivo (A) intravascular ultrasound (IVUS), (B) optical frequency domain imaging (OFDI) and (C) coronary angioscopy (CAS) of an in-stent mass after bioresorbable polymer-coated sirolimus-eluting stent implantation. (A) IVUS shows a convex-shaped mass accompanied by signal attenuation within the stent-implanted segment (arrows). (B) OFDI shows a high-backscattering protruding mass at the same region (arrows; Movie S1). (C) A yellowish polypoid lesion with red thrombus adhesion is observed on CAS (arrows). Arrowhead, nylon suture for the landmark of tissue preparation.
After perfusion fixation of the heart under the normal diastolic pressure by 10% buffered formalin for 24 h, epicardial coronary arteries were removed from the heart. The whole stent segment was embedded in plastic (Technovit 8100; Heraeus Kulzer, Wehrheim, Germany) with the stent struts. Histological sections stained by hematoxylin-eosin and Masson’s trichrome showed a convex mass lesion (Figure 2A) composed of cholesterin crystals, macrophage foam cells and necrotic debris over the stent struts (Figure 2B). Although we could not confirm the endothelial cell coverage due to the technical difficulties of immunohistochemistry using the plastic embedded sections, the luminal surface of the mass was partially covered with thin and flat cells, consistent with endothelial cells. Part of the luminal surface, however, lacked the cell coverage with fibrin thrombus adhesion (Figure 2C). We speculated that the mass lesion over the stent struts may have been derived from (1) protrusion of native necrotic core after stent implantation; or (2) a lipid-rich de novo lesion after stent implantation. On histology the mass lesion was continuous with native necrotic core (Figure 2D). On additional deep sectioning, the stent struts were seen to penetrate into the underlying native necrotic core. Luminal fibrin thrombus adhesion was apparent in these sections (Figure 2E,F). Furthermore, the size of the cholesterin clefts was similar to that of native underlying plaque. Previous studies suggest that cholesterin clefts, as one of the tissue components of neoatherosclerosis, are fragmented and smaller in size compared with those identified in the native plaque.1,2 These findings support the former hypothesis of protrusion of native necrotic core toward the lumen, followed by superficial adhesion of fibrin thrombus. We could not, however, completely exclude the latter hypothesis of de novo neoatherosclerosis formation within the stent implanted segments.
Histopathology of protruding in-stent mass 2 months after bioresorbable polymer sirolimus-eluting stent implantation. (A) Projection of necrotic core component into the lumen (arrows). (B) The polypoid mass contains cholesterin clefts (arrows), macrophages and degenerated debris (arrowheads). (C) Part of the surface of the mass lacks the endothelial cell coverage (arrowheads) with superficial fibrin thrombus adhesion (arrows). (D) Continuity of native necrotic core (asterisk) to the polypoid mass. (E,F) Additional sectioning shows penetration of stent struts into the underlying necrotic core (arrows) with luminal fibrin thrombus adhesion (arrowheads). Staining: (A,B,D–F) hematoxylin-eosin; (C) Masson’s trichrome. Scale bars: (A) 1 mm; (B–D) 100 μm; (E,F) 500 μm.
Intravascular imaging, namely optical coherence tomography and CAS, could detect the various lesions including thrombus and neoatherosclerosis after drug-eluting stent (DES) implantation.3 The advantage of these imaging devices is essential and they play an important role in the present percutaneous coronary intervention era.4 The diagnostic accuracy of these devices, however, particularly with regard to positive predictive value, is relatively low, as had been expected according to pathological validation study.5,6 Although imaging was carried out within 6 h of death before tissue fixation with formalin, we understand the limitation of reproducibility of intravascular imaging in ex vivo imaging of autopsy cases. Tissue components may dramatically change after death, particularly soluble cell components. In addition, hemodynamics affect the physiology and morphology of cardiovascular tissue. These factors may affect ex vivo imaging.
The pathology of DES-implanted coronary arteries does not elucidate the whole picture.7 We discovered that the protruding in-stent mass was composed of cholesterin clefts and necrotic debris. Such lesions may require dual anti-platelet therapy due to the high thrombogenic activity derived from the endothelial cell deficit. It is important to accumulate autopsy cases after DES deployment in order to collect pathological evidence of tissue reaction against these devices, given the millions of DES implanted in our patients.
None.
Supplementary File 1
Movie S1. Optical frequency domain imaging of in-stent mass.
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-17-0263
