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Abstract 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.

BackgroundWe herein detail our experience with a unique patient with a primary central nervous system (PCNS) B-cell lymphoma concomitant with anti-N-methyl-d-aspartate receptor (NMDAR) antibodies that satisfied the criteria of “probable anti-NMDAR encephalitis (ProNMDARE)” based on the Graus criteria 2016.Case presentationA 73-year-old Japanese woman presented with acute pyrexia, agitation, and disturbance of consciousness. She gradually developed a reduction in speech frequency and truncal dystonia causing abnormal posture. Brain magnetic resonance imaging (MRI) demonstrated high-intensity lesions in the bilateral frontal lobes, and her cerebrospinal fluid revealed mild pleocytosis. She was diagnosed with acute encephalitis and treated with acyclovir and intravenous dexamethasone; however, no improvement was observed. She was transferred to our hospital 6 weeks after the onset of her symptoms, and anti-NMDAR antibodies were identified in her cerebrospinal fluid through indirect immunolabeling with rat brain frozen sections and cell-based assays with NR1/NR2 transfected HEK cells. Follow-up MRI showed enlargement of the lesions in the right frontal lobe with gadolinium enhancement, suggesting a brain tumor. Stereotactic surgery was implemented, with subsequent pathological examination revealing that the tumor was consistent with diffuse large B-cell lymphoma (DLBCL) without evidence of systemic satellite lesions. Stereotactic irradiative therapies were then added to her treatment regimen, which partly improved her neurological symptoms with only mild cognitive dysfunction still remaining. A decrease in anti-NMDAR antibody titer was also confirmed after immunotherapy and tumor removal.ConclusionsWe herein report our experience with a novel case of PCNS-DLBCL masquerading as anti-NMDAR encephalitis that satisfied the diagnostic criteria of “proNMDARE.” Treatment, including tumor removal, ameliorated disease severity and antibody titers of the patient. Our findings suggest that anti-NMDAR antibody-associated autoimmunity can be triggered by PCNS B-cell tumors, although primary brain tumors need to be excluded before establishing a diagnosis of autoimmune encephalitis.

Abstract Pathological changes after third-generation drug-eluting stent implantation remain unclear. We compared the tissue responses of coronary arteries after the implantation of third-generation abluminal biodegradable-polymer everolimus-eluting stent (3rd EES) and second-generation durable-polymer EES (2nd EES) using autopsy specimens and an atherosclerotic porcine model. We compared the histology of stented coronary arteries obtained by autopsy performed 1–10 months after 3rd EES (n (number of cases) = 4, stent-implanted period of 3–7 months) and 2nd EES (n (number of cases) = 9, stent-implanted period of 1–10 months) implantations. The ratio of covered stent struts was higher with 3rd EESs than with 2nd EESs (3rd; 0.824 ± 0.032 vs. 2nd; 0.736 ± 0.022, p = 0.035). Low-density lipoprotein receptor knockout minipigs were stented with 3rd or 2nd EES in the coronary arteries and the stented regions were investigated. The fibrin deposition around the 2nd EES was more prominent. Additionally, higher density of smooth muscle cells was confirmed after the 3rd EES implantation. Pathological examination after the 3rd EES demonstrated a combination of less fibrin deposition and more rapid acquisition of well-developed neointima as compared to the 2nd EES at autopsy and the atherosclerotic porcine model.

Abstract 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.

We report an autopsy case of a 69-year-old female with cervical cancer. She was given bevacizumab-containing chemotherapy for 4 months. After two years of chemotherapy, she developed congestive heart failure (CHF) with left ventricular dysfunction. Cardiac magnetic resonance (CMR) imaging revealed late gadolinium enhancement (LGE) of linear mid-wall delayed enhancement located in the basal to the mid-septal wall, suggesting bevacizumab-related cardiotoxicity. Although she was treated with cardioprotective medications and discharged, she eventually died from worsening CHF a year later, and we conducted an autopsy. Histopathological examination revealed diffuse fibrosis in the myocardium, and the area where LGE was present on CMR showed thinning and wavy changes in cardiomyocytes with diffuse interstitial fibrosis and edema.

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

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

Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.

Moraxella lacunata (M. lacunata) is a Gramnegative bacterium, which rarely causes serious infection. This is a rare case report of acute glomerulonephritis diagnosed by pathological findings in a child accompanied by M. lacunata infection. The patient showed hematuria, proteinuria and hyperkalemia requiring emergency hemodialysis. After hospitalization, M. lacunata bacteremia 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 of M. lacunata infection 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 of M. lacunata infection. 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 with M. lacunata infection. Although there are various causes for acute glomerulonephritis, infection-related glomerulonephritis (IRGN) is an important concept. M. lacunata infection might have a potential risk for IRGN with dysregulation of complement activity leading to serious and invasive clinical conditions than previously considered. [ABSTRACT FROM AUTHOR]

Aims This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology. Methods and results A total of 902 pathological cross-sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross-sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well-delineated heterogeneous signal-poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high-backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses <893 µm as cut points for the prediction of measurable calcification (72% sensitivity and 91% specificity, area under the curve = 0.893, P < 0.001). Conclusion Our study demonstrated the potential capability of OFDI to characterize various types of coronary calcifications, which may contribute to the understanding of the pathogenesis of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by intravascular thrombus formation in the pulmonary arteries. Recently, it has been shown that a myofibroblast cell phenotype was predominant within endarterectomized tissues from CTEPH patients. Indeed, our recent study demonstrated the existence of not only myofibroblast-like cells (MFLCs), but also endothelial-like cells (ELCs). Under in vitro conditions, a few transitional cells (co-expressing both endothelial- and SM-cell markers) were observed in the ELC population. We hypothesized that MFLCs in the microenvironment created by the unresolved clot may promote the endothelial-mesenchymal transition and/or induce endothelial cell (EC) dysfunction. Methods: We isolated cells from these tissues and identified them as MFLCs and ELCs. In order to test whether the MFLCs provide the microenvironment which causes EC alterations, ECs were incubated in serum-free medium conditioned by MFLCs, or were grown in co-culture with the MFLCs. Results: Our experiments demonstrated that MFLCs promoted the commercially available ECs to transit to other mesenchymal phenotypes and/or induced EC dysfunction through inactivation of autophagy, disruption of the mitochondrial reticulum, alteration of the SOD-2 localization, and decreased ROS production. Indeed, ELCs included a few transitional cells, lost the ability to form autophagosomes, and had defective mitochondrial structure/ function. Moreover, rapamycin reversed the phenotypic alterations and the gene expression changes in ECs cocultured with MFLCs, thus suggesting that this agent had beneficial therapeutic effects on ECs in CTEPH tissues. Conclusions: It is possible that the microenvironment created by the stabilized clot stimulates MFLCs to induce EC alterations. [ABSTRACT FROM AUTHOR]