Comparisons of magnetic resonance imaging, histopathological and Ki-67 labeling index findings in a single myxofibrosarcoma: a case report.

BACKGROUND: Myxofibrosarcoma is a myxoid soft tissue sarcoma showing T2 high intensity on magnetic resonance imaging. However, myxofibrosarcoma is a heterogeneous sarcoma with both myxoid and cellular portions. Magnetic resonance imaging findings were obtained MRI findings for comparison with histological and Ki-67 immunohistochemical features, in different portions of one myxofibrosarcoma. CASE PRESENTATION: Magnetic resonance imaging observations were compared with gross pathological and microscopic findings of a myxofibrosarcoma from a 50-year-old Japanese female. The Ki-67 labeling indices of different portions of the tumor, that is, the myxoid, cellular, and histologically confirmed infiltrative margin portions (pathological tail sign), were compared. The T2 low intensity area was more cellular than the T2 high intensity area, while the cellular portion had a significantly higher Ki-67 index than the myxoid portion (p = 0.0313). The portions with the pathological tail sign had a significantly higher Ki-67 labeling index than those without this sign (p = 0.0313). CONCLUSIONS: More cellular portions of a myxofibrosarcoma correspond to more areas of the tumor showing aggressive features. Furthermore, our data also support the hypothesis of high aggressiveness being associated with the pathological tail sign in myxofibrosarcoma. To our knowledge, this is the first case report to describe comparisons among the imaging findings, histological features, and Ki-67 immunohistochemistry results for different portions of one myxofibrosarcoma.

Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries.

AIMS: Though the number of patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) is increasing, few histopathological studies of PAD, particularly that involving below-the-knee arteries, has been reported. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) specimens obtained from patients who underwent lower extremity amputation due to CLIMethods: Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 histological sections. This protocol was approved by the Ethics Review Board of Nihon University Itabashi Hospital (RK-190910-01) and Kyorin University Hospital (R02-179). RESULTS: The calcified area distribution was significantly larger in PTAs than in ATAs on soft X-ray radiographic images (ATAs, 48.3% ±19.2 versus PTAs, 61.6% ±23.9; p＜0.001). Eccentric plaque with necrotic core and macrophage infiltration were more prominent in ATAs than in PTAs (eccentric plaque: ATAs, 63.7% versus PTAs, 49.1%; p＜0.0001, macrophage: ATAs, 0.29% [0.095 - 1.1%] versus PTAs, 0.12% [0.029 - 0.36%]; p＜0.001), histopathologically. Thromboembolic lesions were more frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p＜0.05). Moreover, post-balloon injury pathology differed between ATAs and PTAs. CONCLUSIONS: Histological features differed strikingly between ATAs and PTAs obtained from CLI patients. Clarifying the pathological features of CLI would contribute to establishing therapeutic strategies for PAD, particularly disease involving below-the knee-arteries.

Acute decompensated heart failure in a patient with primary aldosteronism successfully treated with an adrenalectomy: A case report.

Primary aldosteronism is often associated with heart failure (HF), and is reportedly difficult to treat in some cases. We report a case of severe HF associated with primary aldosteronism. A patient with HF, who was suspected of having primary aldosteronism, was referred to and examined at our hospital. After detailed examination, the patient was diagnosed with exacerbation of HF, and was treated at our department. Catheterization after admission revealed Forrester class IV HF. The patient was treated with catecholamine infusion in combination with medical treatment including mineralocorticoid receptor antagonists. The patient was diagnosed with hypertension due to primary aldosteronism and intractable secondary HF with increased peripheral vascular resistance. An open adrenalectomy was successfully performed under intra-aortic balloon pumping. Right heart catheterization, performed soon thereafter, demonstrated improvement in the patient's blood pressure and hemodynamics. We speculate that the improved cardiac function resulted from a reduction in the vascular resistance, as a consequence of the adrenalectomy. .

Prominent atrial fibrosis and its correlation with atrial tachyarrhythmia and dilated atrium long after classic Fontan surgery.

BACKGROUND: The progression of atrial fibrosis long after Fontan surgery is unclear. This study aimed to evaluate the degree of atrial fibrosis long after the classic Fontan procedure and to investigate the factors associated with atrial fibrosis. METHODS: We obtained atrial free wall specimens resected at Fontan conversion from 43 patients (Fontan group) and studied the degree of atrial fibrosis, along with its association with atrial tachycardia/fibrillation (AT/AF) and other clinical parameters, compared with those of the control group without heart disease (n=6). RESULTS: The time after the initial Fontan procedure was 19.9 (15.9-25.3) years. Atrial fibrosis (%) was more common in the Fontan group than in the control group [24.3 (20.9-35.0)% vs. 6.2 (5.6-7.5)%, p<0.001]. The severity of atrial fibrosis was mild in 16% (n=7), moderate in 54% (n=23), and severe in 30% (n=13) of cases. Atrial fibrosis (%) was more common in the persistent/permanent AT/AF group than in the no AT/AF (p<0.001) and paroxysmal AT/AF (p<0.001) groups. The maximum atrial diameter on computed tomography (CT) (mm) significantly correlated with atrial fibrosis (%) (r=0.52, p<0.001). The maximum diameter of the right atrium (≥75 mm) on CT was a significant risk factor for severe atrial fibrosis on multivariate logistic analysis (hazard ratio=10.22, 95% confidence interval=1.04-254.8, p=0.04). CONCLUSIONS: Atrial fibrosis was prominent long after classic Fontan surgery, especially in patients with non-paroxysmal AT/AF and dilated right atrium.

Inhibition of extracellular matrix integrity attenuates the early phase of aortic medial calcification in a rodent model.

BACKGROUND AND AIMS: The mechanism of vascular calcification (VC) resembles that of bone metabolism, and a correlation has frequently been reported between calcification and vascular extracellular matrix (ECM) regulating its integrity; however, the detailed mechanisms remain unclear. In this study, we examined how the vascular ECM, especially collagen metabolism, is involved in the process of VC. METHODS: VC was modeled using 5-week-old male Sprague-Dawley rats fed a diet containing warfarin and vitamin K1 (WVK). Additionally, ß-aminopropionitrile (BAPN) was administered to inhibit lysyl oxidase (LOX), which is an enzyme that mediates collagen cross-linking. Harvested aortic samples were analyzed by staining with alizarin red (AR), immunohistochemistry (IHC), transmission electron microscopy (TEM), and ex vivo microcomputed tomography (µCT). RESULTS: Rats fed WVK developed increasing numbers of aortic medial calcifications (AMCs) over time. TEM images indicated punctate calcification within collagen fibers in the early phase of AMC. AR staining of translucent samples revealed the distribution and severity of calcification, and these lesions were significantly decreased in the BAPN group. Three-dimensional reconstructed µCT images that allowed the quantification of calcified volumes revealed that BAPN significantly reduced the bulk of calcification. Moreover, IHC showed that both LOX and collagen I were present around the sites of AMC, and thus the IHC-positive area was reduced in the BAPN group compared to the WVK group. CONCLUSIONS: The results indicated that inhibition of LOX by BAPN attenuated AMC, and that collagen metabolism plays a significant role in the early pathogenesis of VC.

Pleural changes in patients with pneumothoraces and Marfan syndrome.

BACKGROUND: Patients with Marfan syndrome (MFS) often develop pneumothorax, but the features of pneumothorax in the context of MFS have not been well described in the literature. We clarified the clinical and histopathological characteristics of this condition in these patients. METHODS: Patients with MFS were selected from among all patients who underwent surgery for pneumothorax, between December 1991 and January 2015, in our hospital. We studied the histopathological characteristics of the resected lungs as well as the clinical features of the selected patients, including surgical findings and postoperative recurrence status. RESULTS: There were 966 operations underwent pneumothorax-related surgeries in our hospital. A total of 16 operations (1.66%) were performed on patients with MFS in 11 cases. In this study, 9 patients (6 men, 3 women) were included. Clinically, 7 patients (77.8%) had bilateral pneumothoraces and 4 (44.4%) exhibited postoperative recurrent pneumothoraces. Pathologically, the resected pulmonary bullae exhibited blood vessel cystic medial degeneration (55.6% of cases), calcification (55.6% of cases), and demonstrated elastic fiber fragmentation and degeneration (all cases). CONCLUSIONS: As in few previous reports, many patients with MFS develop bilateral or postoperative recurrent pneumothoraces. In many patients, characteristic changes in the pulmonary bullae, possibly caused by degenerated elastic fibers, were observed.

Histological features of endomyocardial biopsies in patients undergoing hemodialysis: Comparison with dilated cardiomyopathy and hypertensive heart disease.

BACKGROUND: Heart failure is a frequently occurring complication in patients on maintenance hemodialysis (HD). However, the histological features of right ventricular endomyocardial biopsy (RVEMB) samples remain unclear. METHODS: The clinical characteristics and histological findings of consecutive patients undergoing HD with available RVEMB samples (HD group; n=28) were retrospectively compared with those of patients with dilated cardiomyopathy (n=56) and hypertensive heart disease (n=15). RESULTS: The mean myocyte diameter was significantly larger in the HD group than in the other groups (P<.001), whereas the mean percent area of fibrosis did not differ among the three groups. Immunohistochemical analysis revealed that the capillary density was significantly lower in the HD group compared with the other groups (P<.001), and it was positively associated with left ventricular ejection fraction (P=.014). The number of CD68-positive macrophages, which was significantly higher in the HD group compared with the other two groups (P<.001), was associated with cardiovascular mortality (P=.020; log-rank test). CONCLUSIONS: Myocyte hypertrophy, macrophage infiltration, and reduced capillary density were characteristic histological features of the RVEMB samples in patients undergoing HD, which may be related to the pathogenesis of cardiac dysfunction.

Recurrent pericardial effusion with pericardial amyloid deposition: a case report and literature review.

Pericardial amyloidosis is a rare cause of pericardial effusion. Here, we report a case of recurrent pericardial effusion because of pericardial amyloid deposition. The patient was a man in his 40s admitted for pulmonary embolism. During hospitalization, arterial fibrillation and cardiac tamponade were observed, and an initial pericardial puncture was performed. Thereafter, pericardial puncture was repeated nine times over the next two years. Cytological examination of the pericardial effusion suggested malignant mesothelioma. Afterward, pericardial fenestration and partial resection were performed. Intraoperatively, a thickened pericardium and hemorrhagic pericardial effusion were noted. Histologically, the surface of the pericardium was covered by an eosinophilic amorphous material. Congo red and DYLON stains, electron microscopy, and immunohistochemical findings revealed localized amyloidosis composed of an immunoglobulin lambda light chain. Although the patient did not receive further treatment for 5 years postoperatively, his renal and cardiac functions remained within normal limits. Based on these findings, the patient was diagnosed with localized amyloidosis. So far, hemorrhagic pericardial effusion has been reported in few cases with systemic amyloidosis. Because localized immunoglobulin light-chain-derived (AL) amyloidosis may progress to systemic disease (although it is a very rare occurrence), long-term follow-up is necessary to detect recurrence or progression to a systemic form.

A case of desmoplakin mutation and delayed arrhythmogenic right ventricular cardiomyopathy/dysplasia after atrial septal defect closure.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a slow-developing cardiomyopathy characterized by ventricular arrhythmias and fibrofatty replacement of the right ventricular (RV) myocardium. Its clinical diagnosis is challenging because of its variable clinical presentation and low genetic penetrance. We describe the case of a 67-year-old man who was diagnosed as having ARVC/D with a desmoplakin mutation that appeared after occlusion of an atrial septal defect (ASD). He underwent patch closure surgery for ASD at the age of 54 years. Four years later, he underwent catheter ablation for multifocal atrial tachycardias. Because of pre-syncope and inducible sustained monomorphic ventricular tachycardia, an implantable cardioverter defibrillator was implanted. When he was admitted for worsening heart failure at the age of 61 years, the desmoplakin mutation was detected with progressive left ventricular (LV) dysfunction. Subsequently, he was diagnosed as having ARVC/D with RV dysfunction. At cardiac autopsy, characteristics of ARVC/D, including dilatation, fibrofatty changes in the right ventricle, and diffuse fibrosis in the left ventricle were detected. Along with the effect of RV dysfunction caused by ASD, the progression of LV dysfunction after ASD closure was also possibly caused by the disease progression of ARVC/D. Physicians should carefully assess the various states of ARVC/D. .

Successfully treated eosinophilic granulomatosis with polyangiitis relapse presenting as myocarditis and followed by multimodality imaging.

A 60-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA), which was diagnosed 12 years earlier and managed with prednisolone, was admitted to our hospital because of dyspnea and paresthesias in both hands. Laboratory test revealed peripheral eosinophilia along with elevated troponin T and brain natriuretic peptide (BNP). The patient's clinical picture was consistent with myocarditis and relapse of EGPA. Endomyocardial biopsy showed marked infiltration of eosinophils in myocardium, which confirmed relapse of EGPA with myocarditis. Thallium-201 and iodine-123-beta-methyl iodophenyl pentadecanoic acid dual single-photon emission computed tomography (TL-BMIPP SPECT), as well as cardiac magnetic resonance imaging (CMR), also confirmed cardiac involvement. The patient was treated with methylprednisolone and improved dramatically. CMR and TL-BMIPP SPECT performed after discharge showed improvement of abnormal lesions, while anomalies detected by these modalities remained. This is a case of EGPA relapse presenting as myocarditis despite treatment with prednisolone. .

Identification of MYLK3 mutations in familial dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a primary cause of heart failure, life-threatening arrhythmias, and cardiac death. Pathogenic mutations have been identified at the loci of more than 50 genes in approximately 50% of DCM cases, while the etiologies of the remainder have yet to be determined. In this study, we applied whole exome sequencing in combination with segregation analysis to one pedigree with familial DCM, and identified a read-through mutation (c.2459 A > C; p.*820Sext*19) in the myosin light chain kinase 3 gene (MYLK3). We then conducted MYLK3 gene screening of 15 DCM patients (7 familial and 8 sporadic) who were negative for mutation screening of the previously-reported cardiomyopathy-causing genes, and identified another case with a MYLK3 frameshift mutation (c.1879_1885del; p.L627fs*41). In vitro experiments and immunohistochemistry suggested that the MYLK3 mutations identified in this study result in markedly reduced levels of protein expression and myosin light chain 2 phosphorylation. This is the first report that MYLK3 mutations can cause DCM in humans. The clinical phenotypes of DCM patients were consistent with MYLK3 loss-of-function mouse and zebrafish models in which cardiac enlargement and heart failure are observed. Our findings highlight an essential role for cardiac myosin light chain kinase in the human heart.

Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients.

BACKGROUND: Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients. METHODS AND RESULTS: We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (<14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. P. acnes-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CM-group samples. CONCLUSIONS: Frequent identification of P. acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of P. acnes in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.

Cardiac Sarcoidosis Masked by Malignant Lymphoma.

There is an association between sarcoidosis and lymphoma, termed "sarcoidosis-lymphoma syndrome." Sarcoidosis is generally detected before lymphoma, but it could present after or even concurrently with the diagnosis of lymphoma. We describe a patient presenting with ventricular tachycardia and lymphadenopathy. A diagnosis of Hodgkin lymphoma was made histologically. The patient responded to treatment, but had persistent (18)F-fluoro-deoxyglucose uptake in the lymph nodes and heart on follow-up positron emission tomography. Second biopsies of lymph node and endomyocardial both confirmed sarcoidosis. This finding suggests that we should maintain a high degree of suspicion for cardiac sarcoidosis in lymphoma patients.