Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas.

Since the World Health Organization 2016 classification (2016 WHO), genetic status has been incorporated into the diagnosis of Grade 2/3 gliomas (lower-grade gliomas). Therefore, immunohistochemistry (IHC) of IDH1-R132H, ATRX, and p53 have been used in place of genetic status. We report the associations between histological findings, IHC, and genetic status. We performed IHC of IDH1-R132H, ATRX, and p53 in 76 lower-grade gliomas and discussed its validity based on the 2016 WHO and the upcoming 2021 WHO classification. The sensitivity and specificity of anti-ATRX, p53, and IDH1-R132H IHC were 40.9%/98.1%, 78.6%/85.4%, and 90.5%/84.6%, respectively. Among 21 IDH1-mutant gliomas without 1p/19q codeletion, two gliomas (9.5%) mimicked the so-called classic for oligodendroglioma (CFO) in their morphology. Of the 42 gliomas with 1p/19q codeletion, four cases were difficult to diagnose as oligodendroglioma through morphological examination. Moreover, there were three confusing cases with ATRX mutations but with retained ATRX-IHC positivity. The lessons learned from this study are as follows: (1) ATRX-IHC and p53-IHC should be supplementary to morphological diagnosis, (2) rare IDH mutations other than IDH1 R132H should be considered, and (3) there is no complete alternative test to detect molecular features of glioblastoma under the 2021 WHO classification.

The first autopsy case of pandemic influenza (A/H1N1pdm) virus infection in Japan: detection of a high copy number of the virus in type II alveolar epithelial cells by pathological and virological examination.

We report the pathological and virological findings of the first autopsy case of the 2009 pandemic influenza (A/H1N1pdm) virus infection in Japan. A man aged 33 years with chronic heart failure due to dilated cardiomyopathy, mild diabetes mellitus, atopic dermatitis, bronchial asthma, and obesity died of respiratory failure and multiple organ dysfunction syndrome. Macroscopic examination showed severe pulmonary edema and microscopically the lung sections showed very early exudative-stage diffuse alveolar damage (DAD). Immunohistochemistry revealed proliferation of the influenza (A/H1N1pdm) virus in alveolar epithelial cells, some of which expressed SAalpha2-3Gal on the cell surface. Influenza (A/H1N1pdm) virus genomic RNA and mRNA were also detected in alveolar epithelial cells. Real-time PCR revealed 723 copies/cell in the left lower lung section from which the influenza (A/H1N1pdm) virus was isolated. Electron microscopic analysis revealed filamentous viral particles in the lung tissue. The concentrations of various cytokines/chemokines in the serum and the autopsied lung tissue were measured. IL-2R, IL-6, IL-8, IL-10, IFN-alpha, MCP-1, and MIG levels were elevated in both. These findings indicated a case of viral pneumonia caused by influenza (A/H1N1pdm) virus infection, showing characteristic pathological findings of the early stage of DAD.