Histological and genetic analysis of anaplastic pleomorphic xanthoastrocytoma suspected of malignant progression over a 12-year clinical course.

We report a case of anaplastic PXA for which histological study and molecular analysis were performed at the time of the first resection and two recurrences. A 15-year-old girl had a temporal lobe tumor that had been followed as a cystic lesion from three years of age without histopathological examination. The first and second surgical specimens exhibited typical histological features of PXA such as nuclear and cytoplasmic pleomorphism. In addition, microvascular proliferation was observed in the second surgical specimen. On the other hand, nuclear pleomorphism was unclear in the third surgical specimen and it was mainly composed of spindle cells. Palisading necrosis was observed. Mitotic figures and the Ki-67 proliferation index gradually increased. BRAF V600E and TERT promoter mutation were detected in the first, second, and third surgical specimens. In addition, PTEN mutation and CDNK2A deletion were detected in the third surgical specimen. Considering the histopathological and genetic changes over time, we concluded that our case of anaplastic PXA underwent malignant progression.

Identification of cardiac progenitors that survive in the ischemic human heart after ventricular myocyte death.

Atypically-shaped cardiomyocytes (ACMs) are beating heart cells identified in the cultures of cardiomyocyte-removed fractions obtained from adult mouse hearts. Since ACMs spontaneously develop into beating cells in the absence of hormones or chemicals, these cells are likely to be a type of cardiac progenitors rather than stem cells. "Native ACMs" are found as small interstitial cells among ventricular myocytes that co-express cellular prion protein (PrP) and cardiac troponin T (cTnT) in mouse and human heart tissues. However, the endogenous behavior of human ACMs is unclear. In the present study, we demonstrate that PrP+ cTnT+ cells are present in the human heart tissue with myocardial infarction (MI). These cells were mainly found in the border of necrotic cardiomyocytes caused by infarcts and also in the hibernating myocardium subjected to the chronic ischemia. The ratio of PrP+ cTnT+ cells to the total cells observed in the normal heart tissue section of mouse and human was estimated to range from 0.3-0.8%. Notably, living human PrP+ cTnT+ cells were identified in the cultures obtained at pathological autopsy despite exposure to lethal ischemic conditions for hours after death. These findings suggest that ACMs could survive in the ischemic human heart and develop into a sub-population of cardiac myocytes.

Prion protein- and cardiac troponin T-marked interstitial cells from the adult myocardium spontaneously develop into beating cardiomyocytes.

Atypically-shaped cardiomyocytes (ACMs) constitute a novel subpopulation of beating heart cells found in the cultures of cardiac myocyte-removed crude fraction cells obtained from adult mouse cardiac ventricles. Although ~500 beating ACMs are observed under microscope in the cell cultures obtained from the hearts of either male or female mice, the origin of these cells in cardiac tissue has yet to be elucidated due to the lack of exclusive markers. In the present study, we demonstrate the efficacy of cellular prion protein (PrP) as a surface marker of ACMs. Cells expressing PrP at the plasma membrane in the culture of the crude fraction cells were found to develop into beating ACMs by themselves or fuse with each other to become larger multinuclear beating ACMs. Combining PrP with a cardiac-specific contractile protein cardiac troponin T (cTnT) allowed us to identify native ACMs in the mouse cardiac ventricles as either clustered or solitary cells. PrP- and cTnT-marked cells were also found in the adult, even aged, human cardiac ventricles. These findings suggest that interstitial cells marked by PrP and cTnT, native ACMs, exhibit life-long survival in the cardiac ventricles of both mice and humans.