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Cardiac hemangioma is relatively rare, accounting for approximately 1-3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.

Moraxella lacunata(M. lacunata) is a Gram-negative bacterium, which rarely causes serious infection. This is a rare case report of acute glomerulonephritis diagnosed by pathological findings in a child accompanied byM. lacunatainfection. The patient showed hematuria, proteinuria and hyperkalemia requiring emergency hemodialysis. After hospitalization,M. lacunatabacteremia became apparent. Pathological findings showed an increase in glomerulus inflammatory cells and glomerular C3 deposition was observed in the renal tissue biopsy. Final diagnosis was endocapillary proliferative glomerulonephritis. Clinical reports ofM. lacunatainfection requiring emergency hemodialysis in children are rare. Previous reports have suggested that lowered immune competency with chronic kidney disease may be a risk factor associated with serious invasive cases ofM. lacunatainfection. However, detailed clinical laboratory data and pathological findings have not been identified in previous case reports. Our case directly indicated complement activity and acute glomerulonephritis withM. lacunatainfection. Although there are various causes for acute glomerulonephritis, infection-related glomerulonephritis (IRGN) is an important concept.M. lacunatainfection might have a potential risk for IRGN with dysregulation of complement activity leading to serious and invasive clinical conditions than previously considered.

A 52-year-old man, with a history of allergic rhinitis and without coronary risk factors, transferred to our hospital because of cardiac arrest. Coronary angiography revealed no significant stenosis in left coronary arteries ([Figure 1A][1]), and mild stenosis in right coronary artery ([Figure 1B

Myenteric ganglionitis is a disorder that causes intestinal motor dysfunction. It may be caused due to neoplastic, central nervous system, or systemic infectious disorders. However, some cases are considered to be idiopathic in origin. A 33-year-old man was admitted to the hospital with sudden severe abdominal pain accompanied by watery diarrhea. Computed tomography imaging revealed edema of the entire small intestinal wall without ischemic changes. Detailed examination could not be performed for identifying the cause of abdominal pain because of the patient’s worsened general condition, and he died 7 days after onset. The autopsy results confirmed the cause of the patient’s severe abdominal pain as an idiopathic myenteric ganglionitis. Some patients with idiopathic myenteric ganglionitis might die without a definitive diagnosis during their lifetime because of the rarity of this disease. When encountering severe intestinal motility abnormalities of unknown cause, physicians should consider idiopathic myenteric ganglionitis when choosing therapy.

Purpose Optical frequency domain imaging (OFDI) is widely used to characterize lipidic-atherosclerotic plaques, shown as signal-poor regions with diffuse borders, in clinical setting. Given that lipid components are common to both fibroatheroma (FA) and pathological intimal thickening (PIT), it is unclear whether OFDI can be used to accurately distinguish between FA and PIT. This study evaluated the differences in OFDI findings between FA and PIT in comparison with histopathology. Methods A total of 631 histological cross-sections from 14 autopsy hearts were analyzed for the comparison between OFDI and histological images. Of those, 190 (30%) sections were diagnosed with PIT and 120 (19%) with FA. All OFDI images were matched with histology and the OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally, and the lipid arc was measured with a protractor centered in the center of the lumen. Results There was no significant difference in the OFDI signal attenuation rate between FA and PIT (3.09 ± 1.04 versus 2.79 ± 1.20, p = 0.13). However, the lipid length was significantly longer and the maximum lipid arc was significantly larger in FA than in PIT (7.5 [4.3–10.3] mm versus 4.3 [2.7–5.8] mm, p < 0.0001, and 125 [101–174]° versus 96 [74–131]°, p < 0.0001, respectively). Conclusions OFDI may be capable of discriminating advanced lipid plaques from early stage atherosclerosis based on the longitudinal and circumferential extent of signal-poor region.

Cardiac calcified amorphous tumors are rare non-neoplastic intracavitary masses with unknown cause. A 60-year-old man presented with sustained ventricular tachycardia. Transthoracic echocardiography and contrast-enhanced angio-computed tomography demonstrated an expanding 73 × 40 mm sized calcified mass in the left ventricle. He underwent successful total removal of the mass and cryo-ablation at the normal myocardial border. Histopathological examination confirmed a diagnosis of cardiac calcified amorphous tumors. The postoperative course was uneventful, without ventricular tachycardia recurrence. To our knowledge, this is the first reported case of confirmed cardiac calcified amorphous tumors causing ventricular tachycardia and treated by surgical resection combined with cryo-ablation.

A 76-year-old female presented with cognitive impairment and multiple brain infarcts and died of massive subcortical cerebral hemorrhage. A premortem clinical diagnosis was not possible. She did not show apparent microbleeds on brain images during her lifetime. An autopsy revealed vasculitis at various stages with amyloid β deposition and granulomatous reaction in cortical and leptomeningeal arteries, although almost vasculitic processes were in the healing stage, suggestive of the inactive stage of the disease process. Affected vessels were strictly limited to the brain. The final pathological diagnosis of the autopsy was amyloid β-related angiitis. Genotype analyses of ApoE revealed ApoE ε3/ε3 genotype, low risk for Alzheimer's disease. On retrospective examination, the titer of anti-amyloid β autoantibody in cerebrospinal fluid was rather high in our case, but the exact clinical significance remains unknown. Since microbleeds on brain images are diagnostic findings in patients with cerebral amyloid angiopathy-associated conditions, it is very difficult to make an accurate diagnosis of amyloid β-related angiitis without typical microbleeds or open brain biopsy like our case. Keywords: Amyloid β-related angiitis, Cerebral amyloid angiopathy, ApoE, Subcortical cerebral hemorrhage, Primary central nervous system vasculitis

Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.

BACKGROUND How obesity and epicardial fat influence atrial fibrillation (AF) is unknown. METHODS To investigate the effect of obesity/epicardial fat on the AF substrate, we divided 20 beagle dogs of normal weight into four groups (n = 5 each): one of the four groups (Obese-rapid atrial pacing [RAP] group) served as a novel canine model of obesity and AF. The other three groups comprised dogs fed a standard diet without RAP (Control group), dogs fed a high-fat diet without RAP (Obese group), or dogs fed a standard diet with RAP (RAP group). All underwent electrophysiology study, and hearts were excised for histopathologic and fibrosis-related gene expression analyses. RESULTS Left atrial (LA) pressure was significantly higher in the Obese group than in the Control, RAP, and Obese-RAP groups (23.4 ± 6.9 vs. 11.4 ± 2.1, 11.9 ± 6.4, and 13.5 ± 2.9 mmHg; p = .005). The effective refractory period of the inferior PV was significantly shorter in the RAP and Obese-RAP groups than in the Control group (p = .043). Short-duration AF was induced at greatest frequency in the Obese-RAP and Obese groups (p

Introduction: The use of drug-coated balloons (DCB) is a promising technique to treat in-stent restenosis without adding another metal scaffold. Clinical non-inferiority of DCB for treatment of in-stent restenosis (ISR) has been demonstrated compared to drug eluting stents (DES) implantation. However, pathology of neointima treated by DCB remains unclear. Aim: Pathological study of neointima after DCB treatment for ISR has not been reported. This study aimed to examine the tissue response after DCB treatment and plain old balloon angioplasty (POBA) for ISR pathologically, by using atherosclerotic femoral artery of porcine model. Methods: Using micromini pigs fed high-cholesterol, high-fat diet for 3 months, we stented bare metal stents in femoral arteries. After one month of stenting, dilatation of in-stent region by using DCB, and non-compliance balloon (NCB) as POBA were performed. Optimal coherence tomography and angioscopy showed drug adhesion on luminal surface. One month after the balloon expansion, treated arteries were dissected and stent segments were fixed with 10% buffered formalin and embedded in plastic. Stents were segmented at 3mm intervals and histologic sections were prepared. The neointimal area and blood vessel area were morphometrically evaluated, and the ratio of neointimal area per blood vessel area was calculated. Additionally, number of cells per 1mm 2 neointimal area was counted with digital morphometry. Results: We compared the histology between DCB (n=3, 18 histological sections) and POBA (n=3, 18 histological sections) lesions. The ratio of neointimal area per blood vessel area treated by DCB was 0.17 ± 0.01, while that of POBA was 0.21 ± 0.01 (P value = 0.02) respectively. Additionally, the number of cells per 1mm 2 neointimal area was significantly less in the neointima dilated by DCB (1940.9 ± 150.9), compared to that dilated by NCB (2599.8 ± 190.3) (P value = 0.01). These results suggest that DCB treatment after ISR prevents neointimal thickening by inhibiting proliferation of smooth muscle cells. Conclusions: We examined the pathology of in-stent neointima dilated by DCB in peripheral artery of atherosclerotic porcine model. Pathological analysis showed suppressed neointimal proliferation after DCB compared to POBA.

Introduction: Third-generation drug-eluting stent (3rd DES) is widely used in percutaneous coronary intervention. Clinical superiority of 3rd DES has been demonstrated, however, pathological response after 3rd DES remains unclear. We aimed to examine the histology after 3rd DESs in low-density lipoprotein receptor knockout (LDLR -/-) minipigs’ coronary arteries. Methods: Using LDLR -/- minipigs, second-generation drug-eluting stents (2nd DESs) and 3rd DESs were deployed in coronary arteries. Two weeks (n = 2) or four weeks (n = 4) after stent implantation, coronary angiography for the follow up was performed. For evaluation of the features of neointima, optical coherence tomography (OCT) examination was performed in all stented vessels. The stent-implanted arteries were dissected immediately after OCT and investigated histologically. Results: OCT analysis for four-week models showed that the thickness of neointima over 3rd DESs was significantly thinner than that over 2nd DESs (3rd DESs; 43.29 ± 3.29 μm vs. 2nd DESs; 61.67 ± 5.51 μm, P = 0.009). In two-week models, numerous inflammatory cells were observed on the luminal side of 2nd DESs’ struts, while this response was absent in 3rd DESs. Fibrin deposition around 3rd DES’s strut was 2347.9 ± 875.6 μm 2 , while that around 2nd DES’s strut was 4738.9 ± 691.0 μm 2 (P = 0.041) in four-week models. Moreover, when defining the density of smooth muscle cells as ratio of hematoxylin-eosin stained area, it was significantly higher in the neointima above 3rd DESs than that above 2nd DESs in four-week models (3rd DESs; 0.373 ± 0.011 vs. 2nd DESs; 0.265 ± 0.030, P = 0.026). Although neointima over 3rd DES was thin, the density of smooth muscle cells that compose the neointima was higher and seemed to be well-matured. Conclusion: Our pathological analysis showed advanced healing process in 3rd DES compared to 2nd DES lesions. This result may attributed to the absence or the presence of polymer applied on the luminal side of struts, which triggers severe inflammation in the early term after stent implantation, leading to formation of fibrin deposition, unnecessary neointimal thickening, and inhibition of neointimal maturation.

Background Metabolic syndrome is a cluster of conditions including obesity, insulin resistance, hypertension, and abnormal cholesterol, which increases the cardiovascular risk. Metabolic syndrome or obesity has been reported to provide systemic inflammation and oxidative stress. Increased epicardial fat volume is a manifestation of obesity or metabolic syndrome. Those systemic and local conditions related to obesity or metabolic syndrome have been linking to the risk of atrial fibrillation (AF). The underlying mechanisms of obesity linking epicardial fat to AF progression have not been fully examined. Purpose To investigate the impact of obesity linked to epicardial fat on electrophysiologic and anatomical AF substrates. Methods Twenty dogs aged 3 years were divided into four groups (n=5 per each): normal diet for over 20 weeks (control group [median body weight: 12.0 kg]), rapid atrial pacing (RAP) for last 4–15 (median 8) weeks during a normal diet for the same period (RAP group [10.5 kg]), high-fat diet (HFD) maintained for over 20 weeks without RAP (MetS group [16.0 kg]), and RAP for last 4–12 (median 6) weeks during HFD maintained for 24 weeks (MetS-RAP group [17.0 kg]), respectively. Activation/voltage maps of the atria during sinus rhythm were created with Ensite NavX mapping system. The effective refractory period (ERP) at 5 left atrial (LA) and pulmonary vein (PV) sites (LA appendage [LAA], LA body, right and left superior PVs, and inferior PV), and AF inducibility by burst LAA pacing were determined. At study completion, hearts were excised for histopathological and gene expression analyses. Results The LA pressure was more significantly increased in MetS than the MetS-RAP, RAP, and control groups (22.5 [17–28.8] mmHg vs. 14.0 [10.5–16.3] mmHg, 10.5 [7.4–17.2] mmHg and 10.7 [9.6–13.5] mmHg, respectively, P Conclusions AF vulnerability was associated with increased LA pressures and fibrofatty infiltration from epicardial fat in the MetS group, and with fibrofatty infiltration from epicardial fat with subtle fibrosis in the MetS-RAP group. This suggested that fibrofatty infiltration and epicardial fat plays an important role in AF pathogenesis in obese patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (KAKENHI)

Background To date, there have been no data available regarding the diagnostic performance of optical frequency domain imaging (OFDI) for in vivo histological classification of atherosclerotic lesions. This study investigated whether OFDI can be used to diagnose and classify histological atherosclerotic lesions in the coronary artery by ex vivo histological examinations. Methods Three-hundred-fifteen histological cross-sections from 21 autopsy hearts were matched with the OFDI images. Histological cross-sections were classified into six categories: adaptive intimal thickening (AIT), pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), calcified nodule, and healed erosion/rupture. The five observers with different years of experience in the interpretation of OFDI provided a single diagnosis for the OFDI scans of each cross-section according to the aforementioned six histological categories. The diagnostic accuracy and interobserver variability of lesion types for each OFDI observer were determined using histology as the gold standard. Results The overall agreement rates between OFDI and histopathologic diagnosis for OFDI observers 1–5 were 81%, 70%, 68%, 61%, and 50% (κ values of 0.75, 0.61, 0.58, 0.49, and 0.36), respectively. Although the diagnostic accuracy of OFDI for detecting AIT and FC was excellent for all five observers, the sensitivity, and positive predictive values of OFDI for detecting PIT and FA were low in proportion to years of experience. Conclusion The diagnostic accuracy of atherosclerotic tissue properties from OFDI scans correlated with the observers' years of experience, especially when lesions contained lipid components.

Dipeptidyl peptidase-4 (DPP-4) inhibitors have potential as a treatment for atherosclerosis. However, it is unclear whether DPP-4 inhibitors stabilize atherosclerotic plaque or alter the composition of complex plaque. Sixteen Watanabe heritable hyperlipidemic rabbits aged 10–12 weeks with atherosclerotic plaque in the brachiocephalic artery detected by iMap™ intravascular ultrasound (IVUS) were divided into a DPP-4 inhibitor group and a control group. Linagliptin was administered to the DPP-4 inhibitor group via nasogastric tube at a dose of 10 mg/kg/day for 16 weeks, and control rabbits received the same volume of 0.5% hydroxyethylcellulose. After evaluation by IVUS at 16 weeks, the brachiocephalic arteries were harvested for pathological examination. IVUS revealed that linagliptin significantly reduced the plaque volume and vessel volume (control group vs. DPP-4 inhibitor group: ∆plaque volume, 1.02 ± 0.96 mm3 vs. − 3.59 ± 0.92 mm3, P = 0.004; ∆vessel volume, − 1.22 ± 2.36 mm3 vs. − 8.66 ± 2.33 mm3, P = 0.04; %change in plaque volume, 6.90 ± 5.62% vs. − 15.06 ± 3.29%, P = 0.005). With regard to plaque composition, linagliptin significantly reduced the volume of fibrotic, lipidic, and necrotic plaque (control group vs. DPP-4 inhibitor group: ∆fibrotic volume, 0.56 ± 1.27 mm3 vs. − 5.57 ± 1.46 mm3, P = 0.04; ∆lipidic volume, 0.24 ± 0.24 mm3 vs. − 0.42 ± 0.16 mm3 P = 0.04; ∆necrotic volume, 0.76 ± 0.54 mm3 vs. − 0.84 ± 0.25 mm3, P = 0.02). Pathological examination did not show any significant differences in the %smooth muscle cell area or %fibrotic area, but infiltration of macrophages into plaque was reduced by linagliptin treatment (%macrophage area: 12.03% ± 1.51% vs. 7.21 ± 1.65%, P

Triglyceride deposit cardiomyovasculopathy (TGCV) is a newly identified disease that was discovered in individuals who required cardiac transplantation in Japan in 2008. Defective intracellular lipolysis causes triglyceride (TG) accumulation in the myocardium and coronary artery vascular smooth muscle cells, which results in severe heart failure and coronary artery disease with poor prognosis. A known cause of TGCV is a genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in the intracellular hydrolysis of TG. TGCV is classified into primary TGCV with ATGL mutations and idiopathic TGCV without ATGL mutations. Since its discovery, the Japan TGCV Study Group has attempted to elucidate its pathophysiology, develop diagnostic procedures, and specific treatment. Myocardial scintigraphy with iodine-123-β-methyl iodophenyl-pentadecanoic acid ((123)I-BMIPP) is a unique imaging modality for evaluating myocardial lipolysis in vivo. The washout rate of (123)I-BMIPP is an essential indicator for the diagnosis of TGCV. Along with our efforts to provide awareness of and insights into this disease concept, we found that the cumulative number of clinically diagnosed patients has reached >200 and the cases are distributed throughout Japan. In addition, we successfully completed three investigator-initiated clinical trials of a potential therapeutic agent (CNT-01) for TGCV, which was assigned by the Ministry of Health, Labour, and Welfare, Japan, under the SAKIGAKE Designation System in June 2020. Here, we provide the Diagnostic Criteria 2020 for TGCV in order to further promote this “rare and intractable disease” project.

•Uterine neuroectodermal tumors (NETs) are uncommon malignant neoplasm with poor prognosis.•Ganglion-like cells with fibrillary background as major component of uterine NETs are extremely rare.•We present a patient affected by uterine NET with frequent ganglion-like cells, resembling ganglioneuroblastoma.•This case report is important to define the pathogenesis and establish better treatments for neuroectodermal tumors.

Background The clinical benefit of second-generation drug-eluting stents (2nd DES) has been established, compared to first-generation drug-eluting stents (1st DES). However, pathological response after 2nd DES implantation remains unclear, particularly in the Japanese population. Methods Using specimens obtained by autopsy, we compared the histology between 2nd DES (41 sections) and 1st DES (38 sections) lesions within 1 year after stent implantation to evaluate early tissue reaction in Japanese patients. Stent segments were fixed with 10% buffered formalin and embedded in plastic, followed by hematoxylin–eosin and Masson's trichrome staining. Ratio of covered stent struts was calculated, and the area of fibrin deposition was morphometrically evaluated. The degree of inflammation around struts was examined semi-quantitatively (score 0–3). Results The ratio of covered struts and mean fibrin area of 2nd DES were 0.69 ± 0.05 and 658.0 ± 173.4 μm 2 . Those of 1st DES were 0.44 ± 0.12 and 3107.5 ± 1405.9 μm 2 . In the 2nd DES, there was significantly less fibrin deposition and a higher covered struts ratio. The inflammation score was significantly lower in 2nd DESs compared to 1st DESs (1.02 ± 0.16 vs. 1.19 ± 0.54, p Conclusions Histopathological analysis showed advanced healing process in 2nd DES compared with 1st DES lesions. These results are consistent with clinical beneficial outcome of 2nd DES implantation.

We report the case of a 53-year-old male with a history of acute myelogenous leukemia, who suffered the rupturing of a right-sided pulmonary artery pseudoaneurysm combined with pneumonia. He underwent a right-sided lower lobectomy. The resected lung tissue demonstrated a mycotic pseudoaneurysm of a pulmonary artery branch together with a filamentous fungal infection. Pseudoaneurysms are caused by the breaching of all layers of a blood vessel wall. The extravasated blood is trapped by the surrounding extravascular tissue or clots. Cladosporium was detected during a polymerase chain reaction-based analysis followed by DNA sequencing of formalin-fixed paraffin-embedded lung tissue samples. Although previous cases of pulmonary artery pseudoaneurysms caused by fungal infections, e.g., Candida or Aspergillus sp., have been reported, to the best of our knowledge this is the first case to involve cladosporiosis.

We experienced a diagnostically challenging case of Carney complex (CNC). A 24-year-old woman had a past history of surgical removal of multiple cutaneous tumors in the childhood. She was followed as a patient of neurofibromatosis type 1 (NF1) and referred to our hospital for further treatment after she grew up to adulthood. At our hospital, several cutaneous tumors were excised, and the pathological diagnosis was myxoma arising from not deep soft tissue but cutis (so-called cutaneous myxoma). Despite previous clinical diagnosis of NF1, because of the probability of CNC, detailed systemic examination was undertaken including radiological and endocrinological tests. Imaging techniques showed multiple lumps in both breasts, a mass in left atrium and nodular lesions in adrenal glands. Serum ACTH level was markedly suppressed. Surgically resected specimens revealed breast myxomas, cardiac myxoma and primary pigmented nodular adrenocortical disease (PPNAD). These findings met the diagnostic criteria for CNC. Genetic analysis revealed known non-sense mutation of PRKAR1A c.124C>T (p.R42X) (ClinVar ID 41382). Her 50-year-old mother was also shown to have cardiac myxomas, radiological finding of breast myxomatosis and the same PRKAR1A mutation as her daughter. In the present case, the accurate diagnosis of CNC was difficult not only because CNC is a rare disease but also because skin pigmentation was not obvious. Since cardiac myxoma might result in poor or fatal outcome, early and accurate diagnosis of CNC and subsequent systemic investigation including heart are important. Although pediatric cutaneous myxomas are rare, multiple cutaneous myxomas might suggest the possibility of CNC. In such cases, systemic investigation should be done for the accurate diagnosis. Keywords: Carney complex, Cutaneous myxoma, PPNAD, PRKAR1A mutation

Glucagon-like peptide-1 (GLP-1) is thought to inhibit development of aortic atherosclerosis and plaque formation. However, whether GLP-1 stabilizes fully developed atherosclerotic plaque or alters the complicated plaque composition remains unclarified.Ten Watanabe heritable hyperlipidemic (WHHL) rabbits were divided into GLP-1 receptor agonist treatment group and control group. After confirmation of atherosclerotic plaques in brachiocephalic arteries by iMap intravascular ultrasound (iMAP-IVUS), GLP-1 receptor agonist lixisenatide was administered to WHHL rabbits at 30 nmoL/kg/day for 12 weeks by osmotic pump. An equal volume of normal saline was administered in a control group. After evaluation by iMAP-IVUS at 12 weeks, brachiocephalic arteries were harvested for pathological histological analysis.iMAP-IVUS analysis revealed larger fibrotic plaque components and smaller necrotic and calcified plaque components in the GLP-1 group than in the control group; %fibrotic area: 66.30 ± 2.06% vs. 75.14 ± 2.62%, p 0.01, %necrotic area: 23.25 ± 1.87% vs. 16.17 ± 2.27%, p = 0.02, %calcified area: 2.15 ± 0.24% vs. 1.00 ± 0.18%, p 0.01), indicating that GLP-1 receptor agonist might modify plaque composition and increase plaque stability. Histological analysis confirmed that GLP-1 receptor agonist treatment improved smooth muscle cell (SMC)-rich plaque with increased fibrotic content. Furthermore, plaque macrophage infiltration and calcification were significantly reduced by GLP-1 receptor agonist treatment; %SMC area: 6.93 ± 0.31% vs. 8.14 ± 0.48%, p = 0.02; %macrophage area: 9.11 ± 0.80% vs. 6.19 ± 0.85%, p 0.01; %fibrotic area: 54.75 ± 1.63% vs. 69.60 ± 2.12%, p = 0.02; %calcified area: 3.25 ± 0.67% vs. 0.75 ± 0.15%, p = 0.02).GLP-1 receptor agonist inhibited plaque progression and promoted plaque stabilization by inhibiting plaque growth and modifying plaque composition.

A 50-year-old woman diagnosed with vasospastic angina presented to our hospital with repeated typical chest pain. The patient experienced cardiac arrest 14 years previously because of the vasospasm ([Figure 1A][1]). Although the patient was prescribed multiple medications for more than 10 years

We report the case of a 38-year-old woman who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral annular calcification (MAC). The cardiac mass was removed, and mitral valve replacement surgery was performed. Pathological examination revealed an amorphous accumulation of degenerating material within both lesions, indicating that build-up of calcium along the mitral annulus and subsequent rupture of the fibrotic tissue may be involved in the initiation and progression of CAT.

Background Third-generation drug-eluting stent (3rd DES) is commonly used now in percutaneous coronary intervention, and it has not only thinner struts, easier delivery than second-generation drug-eluting stent (2nd DES), but also abluminal biodegradable polymer. Clinical superiority of 3rd DES has been demonstrated compared to 1st and 2nd DESs. However, pathological response after 3rd DES implantation remains unclear. Purpose Pathological study of coronary artery after 3rd DES implantation have not been reported as far as we have referred to the previous studies. This study aimed to examine the initial tissue response after 3rd DES and 2nd DES implantation within one year. Methods Using specimens obtained by autopsy, we compared the histology between 3rd DES (n=3, 8 histological sections) and 2nd DES (n=6, 41 histological sections) lesions within 1 year after stent implantation to evaluate early tissue reaction. Stent segments were fixed with 10% buffered formalin and embedded in plastic, followed by hematoxylin–eosin, Masson's trichrome and elastica van Gieson. Ratio of covered stent struts by neointima was calculated. The thickness of neointima and the area of fibrin deposition were morphometrically evaluated. The degree of inflammation around struts was examined semi-quantitatively (score 0–3). Results The ratio of covered struts and thickness of neointima of 3rd DES were 0.84±0.04 and 68.2±10.3μm, while those of 2nd DES were 0.69±0.05 and 30.4±4.8μm respectively. The inflammation score was similar between two groups (1.00±0.14 vs. 1.02±0.16). The area of fibrin deposition around the struts was larger in 3rd DES compared with 2nd DES (1276.6±490.3μm2 vs. 658.0±173.4μm2). These results suggest that the 3rd DES may obtain prompt as well as rich covering of struts in the initial term after DES implantation. Although the biological feature of the polymers in 3rd and 2nd DESs is different, the inflammatory responses after both 3rd and 2nd DESs implantation were similar, at least within one year after deployment. The degree of inflammation was mild, less than approximately 50 inflammatory cells (score 1) around the struts. Conclusions Our pathological analysis showed advanced healing process in 3rd DES compared with 2nd DES lesions in the viewpoint of strut coverage by neointima. Observation of long-term pathological response may be required to evaluate the superiority of bioabsorbable polymer in 3rd DES.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.

Intravascular angioscopy is widely used for evaluating plaque characteristics through the plaque color in the coronary artery. This study evaluated whether angioscopy is capable of identifying various plaque morphologies, including necrotic core and intraplaque hemorrhage (IPH) in the carotid artery. Nine patients underwent carotid endarterectomy for carotid artery stenosis, and these specimens were imaged ex vivo by angioscopy within 6 h. An angioscopic examination of carotid plaque evaluated its color intensity as follows: white, yellow, or red. The IPH area, necrotic core area, and fibrous cap thickness was measured on histological sections at each site. A total of 7 plaques were graded as white plaques, 10 as yellow, and 8 as red by angioscopy. The IPH area and the percent area occupied by IPH were larger in red and yellow plaques than in white plaques (10.7 ± 9.3 mm2, 9.4 ± 7.8 mm2, and 2.2 ± 1.7 mm2, respectively, P = 0.074; and 25 ± 10%, 19 ± 13%, and 7 ± 5%, respectively, P = 0.008). Furthermore, the thickness of the fibrous cap was significantly thinner in red plaques than in yellow and white plaques (128 ± 34 µm, 328 ± 136 µm, and 285 ± 102 µm, respectively, P = 0.002). The ROC analysis for predicting a presence of red plaques identified that the optimal cutoff value of fibrous cap thickness was 181 µm (area under the curve = 0.987, 100% sensitivity, 90% specificity). The prevalence of red plaques on intravascular angioscopy may represent the existence of plaques containing relatively larger necrotic core and IPH with a thin fibrous cap.

Pineal anlage tumor (PAT) is a rare subtype of pineoblastoma (PB), which shows a poor prognosis. We report a case of a 5-year-old boy with PB with a rhabdomyoblastic component. He presented at a local clinic with vomiting and was transferred to our hospital following discovery of a pineal mass. An endoscopic biopsy was performed and was diagnosed as a PB with a rhabdomyoblastic component. Histopathology of PAT is characterized by both neuroectodermal and ectomesenchymal differentiation, and only a few confirmed cases have been reported. Although the histopathological features of the reported case resembled that of PAT, the ectomesenchymal component in the presented case was only a rhabdomyoblastic one. Therefore, we have diagnosed this case as PB with a rhabdomyoblastic component. As PAT is a rare pineal tumor, clinical, histopathological and genetic evaluation of additional cases is needed to define the characteristics of PAT as one of the pineal gland tumors.

Background Optical coherence tomography (OCT) is one of the tools trying to distinguish neoatherosclerosis from other neointimal tissue but its role has to be still validated. This study evaluated the diagnostic accuracy of OCT for characterization of lipid-atherosclerotic neointima following drug-eluting stent (DES) implantation. Methods Twelve stented coronary arteries from the 7 autopsy hearts were imaged by OCT. These OCT images were compared with histology. By OCT, the morphological appearances of neointima were classified into three patterns: homogeneous pattern, heterogeneous pattern with visible strut, or heterogeneous pattern with invisible strut. Results Of 21 histological cross-sections, 6 were categorized as homogeneous patterns (29%), 11 as heterogeneous patterns with visible stent strut (52%), and 4 as heterogeneous patterns with invisible stent strut (19%). All homogeneous patterns were composed of smooth muscle cells with collagen fibers. The heterogeneous patterns with visible stent strut included proteoglycan-rich myxomatous matrix and calcium deposition. On the other hand, the heterogeneous patterns with invisible stent strut comprised atheromatous tissue, including a large amount of foam cell accumulation (25%) or large fibroatheroma/necrotic core (75%) inside the stent struts within neointima. The optical attenuation coefficient was highest in the heterogeneous pattern with invisible stent strut due to scattering of light by atheromatous tissue. Conclusion The heterogeneous patterns with invisible stent strut on OCT imaging identify the presence of lipid-atherosclerotic tissue within neointima after DES. This may suggest the potential capability of OCT based on visualization of stent struts for discriminating atheromatous formation within neointima from other neointimal tissue.

Third-generation drug-eluting stent (3rd DES) is widely used in percutaneous coronary intervention. Clinical superiority of 3rd DES has been demonstrated compared to second-generation drug-eluting stent (2nd DES). However, pathological response after 3rd DES implantation remains unclear. This study

Thoracic venous aneurysms are rare, and bleeding is possible. A 9-year-old female patient presented with a thoracic wall mass. No blood flow was observed in the mass, and a chronic expanding haematoma was suspected based on the differential diagnosis. However, the venous structure was identified in the wall of the mass on pathological examination, and the diagnosis of the venous aneurysm was thereby established. Because the venous aneurysm contains fresh blood and bleeding can be profuse when such lesions are not properly handled during a surgical procedure, making the visibility of the surgeon poor, the venous aneurysm must be included in the differential diagnosis.

Background Embolism during percutaneous coronary intervention (PCI) causes microcirculation impairment. The aim of this study was to clarify the relationship between the pathological characteristics of tissue captured by distal protection device (DPD) and amount of tissue accumulated in DPD. Methods and Results: A total of 671 consecutive lesions in PCI using DPD were examined. The amount of necrotic debris, fibrous tissue, calcified particle, platelet thrombus and organized thrombus in the DPD baskets was histologically evaluated. The DPD tissue amount was assessed semi-quantitatively, and the relationship between the captured DPD tissue characteristics and tissue amount was investigated. On pathology, 40.7% of the lesions had necrotic debris, 41.4% had fibrous tissue, and 18.0% had calcified particle. The prevalence of lesions in patients with acute coronary syndrome (ACS) was 62.1%. Tissue amount score distribution was as follows: score 1 (tissue invisible), 3.9%; score 2 (tissue clinging to the basket), 52.0%; score 3 (tissue accumulated at the bottom of the basket), 38.5%; and score 4 (tissue accumulated in more than half of the basket), 5.7%. On multivariate analysis, necrotic debris and fibrous tissue were associated with greater tissue amount as well as clinical presentation of ACS. Conclusions The presence of atherosclerotic plaque component, such as necrotic debris and fibrous tissue, might be a risk for distal embolism during PCI.

Objective— Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Approach and Results— Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2′-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2′-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1–positive area was similar to areas where iron accumulated and F4/80 were positive. Conclusions— Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression.

Objectives This study sought to assess the accuracy of optical coherence tomography (OCT), gray-scale intravascular ultrasound (IVUS), and their combination for detecting thin-cap fibroatheromas (TCFA). Background The extent to which the imaging characteristics of OCT and IVUS correlate with histologically defined TCFA is unknown. Methods IVUS and OCT examinations identified focal plaques in 165 coronary arteries from 60 autopsy hearts. A total of 685 pairs of images of OCT and IVUS were compared with histology. By OCT, a TCFA was defined as a signal-poor region with diffuse borders and cap thickness Results With histology as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for OCT-derived TCFA were 100%, 97%, 41%, 100%, and 98%, respectively. The corresponding numbers for IVUS-derived TCFA were 92%, 93%, 19%, 99%, and 93%, respectively. The histological findings underlying the false positive diagnoses of OCT for TCFA included large amounts of foam cell accumulation on the luminal surface, large amounts of microcalcifications at the surface, large amounts of hemosiderin accumulation, or organized thrombus. In contrast, histological causes of mischaracterization of TCFA by IVUS were mostly TCFA. When both OCT and IVUS criteria for TCFA were required to be met, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy were 92%, 99%, 69%, 99%, and 99%, respectively. Conclusions In the present study, neither OCT nor IVUS were optimal to detect TCFA. The combined use of OCT and IVUS may improve TCFA detection accuracy.

Objective: To evaluate the incidence of cervical angiopathy caused by radiation therapy for head and neck cancer. Methods: Segments of 57 cervical arteries were obtained during surgery for head and neck malignant tumors and divided into two groups (irradiated group and non-irradiated group) based on the treatment prior to vascular resection. In order to evaluate vascular injury after radiation therapy, we examined the degree of medial atrophy, medial fibrosis, smooth muscle cell (SMC) differentiation in the media and intima, intimal hyperplasia and endothelial cell (EC) injury. Sections of arterial segments were stained with hematoxylin-eosin, Elastica van Gieson and Masson’s trichrome, and immunohistochemistry for α-smooth muscle actin (α-SMA), smoothelin, S100A4 and CD31 in the resected vessels was conducted. Results: The median interval between the completion of radiation therapy and vascular resection was nine months. No significant differences were observed between the two groups in terms of medial atrophy, medial fibrosis and intimal hyperplasia. The ratio of the smoothelin-positive area per α-SMA-positive area in the media and the S100A4-positive proportion in the intima, indicating the degree of differentiation of the medial SMC and dedifferentiation of the intimal SMC, respectively, showed no significant differences, despite the tendency toward a lower smoothelin-positive area per α-SMA-positive area in the media of the irradiated arteries. The EC coverage revealed on CD31 immunohistochemistry was significantly decreased, with mural thrombus adhesion, in the irradiated group. Conclusions: The ECs of small arteries are damaged by irradiation. Although we did not confirm the statistical significance of medial SMC dedifferentiation, a decreased expression of smoothelin tended to be observed in the media of the irradiated arteries. Our findings provide histopathological evidence of irradiation angiopathy in head and neck cancer and may help to improve the surgical safety of microvascular anastomosis and determine the treatment strategy for head and neck tumors.

We experienced a rare case of uterine metastasis of non-small cell lung cancer in an 82-year-old Japanese woman revealed by detecting the same epidermal growth factor receptor (EGFR) gene mutation in both lung and endometrial biopsy specimens. The patient noticed abnormal genital bleeding at the first presentation. Further examination revealed huge masses in both lung and uterus. Biopsies from the lung and endometrium were performed. Although the pathological findings of both specimens showed similar adenocarcinomatous features including intracytoplasmic luminas, immunohistochemical analyses could not clarify whether these two tumors are lung metastasis of endometrial adenocarcinoma, uterine metastasis of lung adenocarcinoma or double primary adenocarcinomas of the lung and endometrium. Mutational analyses of EGFR gene using genomic DNA revealed that both lung and endometrial tumors had the same substitution mutation (L858R) at exon 21 which is often observed in lung adenocarcinomas. Since EGFR mutations are rarely detected in primary endometrial cancers and especially L858R mutation has not been reported in them, detection of the same L858R EGFR gene mutation in both lung and endometrial tumors strongly suggested that uterine tumor is the metastasis of lung adenocarcinoma. Mutational analyses might be useful to determine whether the tumor is primary or metastatic when the particular mutational types are observed in particular tumor types and/or particular organs.