Yasu-aki Tsuchida

Anaplastic thyroid carcinoma accompanied by uncontrollable eosinophilia.

Anaplastic thyroid carcinoma is a rare disease, and cases associated with eosinophilia are even rarer. We herein report a case of anaplastic thyroid carcinoma accompanied by remarkable and uncontrollable eosinophilia. A 71-year-old man was diagnosed with end-stage anaplastic thyroid carcinoma. Throughout the aggressive clinical course of the cancer, eosinophilia dramatically progressed and became extremely refractory to steroid treatment. We measured the serum levels of hematopoietic cytokines potentially involved in eosinophilia, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5. Although the GM-CSF level was moderately elevated, both the IL-3 and IL-5 levels were within the normal ranges. In this case, the patients eosinophilia may have been related to his severe dyspnea and was likely responsible for the allergic reaction to the anticancer drug. Therefore, it is essential to elucidate the etiology of eosinophilia in patients with thyroid cancer in order to improve the treatment for patients with anaplastic thyroid carcinoma.

Neoatherosclerosis after paclitaxel-eluting stent implantation: Ex vivo intravascular image and histopathology: Pathology of neoatherosclerosis

To the Editor: In-stent neoatherosclerosis is a new problem for the late drug-eluting stent (DES) failure. Although a previous paper described that neoatherosclerosis accounts for approximately one third of late and very late stent thrombosis after first-generation DES implantation, we harbor doubts for the high prevalence of the neoatherosclerosis by our expert experiences as pathologist. We need to clarify the clinical prevalence of neoatherosclerosis after DES implantation in the real world, particularly vulnerable neoathorosclerosis which initiate the prospective clinical events. In addition, the etiology of the neoatherosclerosis remains unclear and accumulation of cases with pathological examination is of importance. Recent clinical observation demonstrated that secondgeneration DES is not more protective against neoatherosclerosis compared with the first-generation DES. Although a few histological studies of neoatherosclerosis had been described using the specimens of cadavers, the comparison between intravascular imaging and histopathology of neoatherosclerosis at the consistent section has not been sufficiently demonstrated. We could speculate that the number of patients with long-term DES implantation in their coronary artery tree will increase annually. In this viewpoint, it is of great importance to understand the intravascular image of neoatherosclerosis with histological validation. We examined postmortem ex vivo optical frequency domain imaging (OFDI) for vulnerable neoatherosclerosis after DES implantation, which may contribute to the future clinical event. Comparison between intravascular imaging and corresponding histology of neoatherosclerosis was clearly documented and illustrated in this report. A seventy-year-old female was admitted to our hospital due to cardiogenic shock and died of heart failure one day after administration. She suffered diabetic nephropathy and had hemodialysis for 12 years. Paclitaxel-eluting stent (PES; TAXUS, 3.0 32, Boston Scientific, Natick, MA) was implanted in the proximal portion of right coronary artery 5 years before. An autopsy revealed no evidence of acute myocardial necrosis and acute coronary thrombosis including stent implanted segment. Epicardial coronary arteries were removed from the heart and side branches were tied off to preserve the perfusion pressure of 80mm Hg during the following procedures. Ex vivo OFDI (Terumo Corporation, Tokyo, Japan) was examined before fixation by 20% buffered formalin. After recording the ex vivo imaging, the whole stent implanted segment was fixed and embedded in plastic in order to prepare the histological tissue section with stent struts. Five micrometer thick plastic sections with stent struts were cut by a sharp tungsten knife and stained with hematoxylin-eosin. The ex vivo OFDI clearly demonstrated low intensity signal with high-backscattering in the neointima at the mid portion of stent implanted segment (Fig. 1a). In lowintensity-signal lesions, stent struts cannot be clearly visualized by OFDI because of the high-backscattering. Histology of corresponding lesion demonstrated by OFDI showed that the PES was implanted over the eccentric fibrocalcific plaque and the lumen was narrowed down by intimal hyperplasia (Fig. 1b). Cholesterin crystals and cluster of foam cells (Fig. 1c) within the neointima were clearly identified and these histological features were consistent with neoatherosclerosis. Massive inflammation remained in the media close to the stent struts. Inflammatory cells were composed by lymphocytes and plasma cells, predominantly (Fig. 1d). Necrotic core in the neointima was covered with a thin fibrous cap. These histological features indicated vulnerable neointima formation over fibrocalcific plaque 5 years after PES implantation. On OFDI, it is widely accepted that lipid-rich necrotic core of native coronary plaque appears as low signal intensity mass. In contrast, it had been described that a high intensity signal with high backscattering reflects the presence of foamy macrophages in the intima. However, by our comparison study between ex vivo intravascular image and histopathology, lesion of dense macrophage infiltration in the intima demonstrated a low intensity signal with high backscattering by OFDI. Dense macrophage infiltration in the neointima as shown in the current case, which is more alarming lesion than scattering macrophage infiltration, presented as a low intensity signal with high backscattering. In this manner, it is reasonable that the stent struts underneath the neoatherosclerosis cannot be visualized by high-backscattering on OFDI. Stent struts behind organized fibrin thrombus can be visible because OFDI signals are not attenuated by these materials. Therefore, it is crucial to detect the neoatherosclerosis whether stent struts behind the low signal intensity area are visible or invisible by OFDI. The question arises whether the “neoatherosclerosis” is derived from penetrated native plaque or newly developed

Ulcerated plaque of coronary artery: Insights from ex vivo images of optical frequency domain imaging and histopathology

To the Editor: It is known that episodes of plaque rupture are frequent and occasionally result in acute coronary syndrome (ACS). In vivo imaging studies in patients with ACS demonstrated evidence of multiple plaque ruptures other than the culprit lesion. Furthermore, recent intravascular ultrasound study demonstrated that the natural evolution and long-term impact of plaque ruptures in untreated segments were not accompanied by clinical events. However the ulcerated coronary artery plaque is still a thorny lesion in the clinical practice. A 78-year-old male died of sepsis and an autopsy was performed. The ex vivo optical frequency domain imaging (OFDI; TerumoCorporation, Tokyo, Japan) revealed a large ulceration, which was directly connected to the true lumen at the proximal portion of right coronary artery (Fig. 1a). The false lumen, which was separated by tissue showing a homogeneous, high intensity signal from the true vessel lumen, was clearly illustrated at the distal segment of ulceration by OFDI (Fig. 1b). Pathological examination revealed the ulcer formation without a necrotic core in the intima. Large disruption of fibrous cap and connection between true and false lumen were apparent (Fig. 1c). The adjacent distal section demonstrated the true and false lumen separated by fibrous septum (Fig. 1d). Fresh mural thrombus was not identified in the false lumen, and the false cavity was completely covered with endothelial cells, which were confirmed byCD31 immunohistochemistry (Fig. 1d, inset). The remodeling index of the ulcerated plaque was 1.05. Approximately 5 mm proximal section from the ulcerated plaque showed atherosclerotic plaque with necrotic core formation. The segment demonstrated a remodeling index of 1.45. The patient’s coronary artery demonstrated severe stenosis with atherosclerotic plaque formation in the left anterior descending artery and circumflex artery. We believe that the pathogenesis of coronary ulcerated lesion is a plaque rupture followed by the washing away of the necrotic core content. Although the histological finding of these sections indicated a previous plaque rupture (healed plaque rupture), no scar was observed in the posterior wall of the left ventricle. Plaque rupture is the most common lesion underlying ACS. However, pathological study has suggested evidence of silent

Ex vivo optical frequency domain imaging and histopathology of malapposed drug eluting stent in coronary artery

To the Editor: Drug eluting stents (DESs) significantly reduce the incidence of stent restenosis and target lesion revascularization in the coronary artery tree. However, late and very late stent thrombosis have been raised as the new problem after DES implantation. Stent malapposition is observed frequently by intravascular imaging in patients who underwent DES implantation. Although some previous studies have suggested that stent malapposition is associated with stent thrombosis, others have failed to demonstrate such association. We have identified malapposed DES 65 months after stent deployment in our autopsy case, and compared the ex vivo intracoronary imaging and histopathology of corresponding lesion. A 70-year-old female was admitted to our hospital due to cardiogenic shock and died of heart failure 1 day after administration. A paclitaxel-eluting stent (Taxus, Boston Scientific, Valencia, CA, USA) was implanted to the right coronary artery 65 months previously. Dual-antiplatelet therapy (DAPT) had been continued for five years until her death. An autopsy was performed followed by an ex vivo optical frequency domain imaging (ODFI; Terumo Corporation, Tokyo, Japan) and a pathological examination. Optical frequency domain imaging revealed malapposed struts at the proximal stent edge (Fig. 1a). The serial movie of OFDI revealed that the malapposition site was covered by homogenous membranous tissue without evidence of plaque and/or thrombus prolapse into the lumen. Histopathology of the corresponding site demonstrated that part of the stent struts were not attached to the vessel wall (Fig. 1b). These struts were completely covered by connective tissue with superficial

Is optical frequency domain imaging a promising modality for diagnosis of erosion

To the Editor: The important contribution of plaque rupture and erosion to the pathogenesis of acute coronary syndrome (ACS) is widely accepted. Although the current definitions of plaque rupture and erosion have been established by pathological studies, several trials have reported that optical coherence tomography (OCT) can help to identify the plaque morphology of ACS. These trials have suggested that OCT imaging can distinguish plaque erosion from plaque rupture; on OCT imaging, plaque erosion is categorized according to the absence of fibrous cap disruption and the presence of thrombus (OCT-erosion). Conversely, from the pathological point of view, plaque erosion is defined as a fibrous cap without rupture accompanied by minimal inflammation. The present case may be categorized as plaque erosion of ACS by optical frequency domain imaging (OFDI; Terumo Corporation, Tokyo, Japan), due to the presence of thrombus formation without apparent fibrous cap disruption. However, histological observation strongly suggested the evidence of plaque rupture followed by occlusive thrombus formation. A 55-year-old woman was brought to the emergency department with a ventricular fibrillation. Although cardiopulmonary resuscitation and intensive therapy were attempted, she died 2 days after her administration. Autopsy revealed acute myocardial infarction in the lateral wall of left ventricle as the cause of death. Postmortem ex vivo OFDI, which is a second-generation form of OCT, and pathological examination of coronary arteries were carried out. The culprit lesion was the proximal portion of the circumflex artery. OFDI clearly showed a fibroatheroma with approximately 150 μm thickness of fibrous cap (Fig. 1a, arrows). Signal attenuation with diffuse border was observed from the 6 to 9 o’clock position (Fig. 1a, asterisks) and this image suggested lipid accumulation within the intima. Occlusive high-intensity mass in the vessel lumen with high backscattering was illustrated by OFDI (Fig. 1b, arrows). At the distal portion of Fig. 1b, OFDI identified non-occlusive layered mass with lowbackscattering (Fig. 1c, arrows), which suggested the white thrombus superimposed by red thrombus adhesion. OFDI could not reveal apparent plaque rupture, which was characterized by fibrous cap disruption or plaque ulceration. These OFDI findings indicated plaque erosion followed by coronary thrombosis. Corresponding histopathology for the image in Fig. 1a showed the mural fibrin adhesion on the fibroatheroma (Fig. 2a). Fibrous cap thickness was 120 μm on this section, which is representative by the OFDI image. Occlusive fibrin thrombus (Fig. 2b, asterisks) was identified at the distal segment of Fig. 2a, which is corresponding to the OFDI image in Fig. 1b. Although large eccentric plaque with necrotic core (Fig. 2b, arrows) and fibrofatty intima was apparent, plaque disruption was not observed in this section. Aggregation of platelet thrombi (Fig. 2c, arrowheads, luminal greenish area), which was piled up by superficial fibrin thrombi (Fig. 2c, arrows), was observed at approximately 2 mm distal from occluded lesion shown in Fig. 2b. This section corresponds to the OFDI image in Fig. 1c. Highmagnification view of the boxed area in Fig. 2c showed dense neutrophil infiltration at the shoulder region with an extremely thin fibrous cap (Fig. 2c, inset, arrows). Deep sectioning of Fig. 2c indicated peeling of the fibrous cap (Fig. 2d, arrow) with inflammatory cell infiltrates and thrombus adhesion (Fig. 2d, arrowheads). Such a massive neutrophil