Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD.

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Background:Oxidative stress plays pivotal roles in the progression of lung adenocarcinoma (LUAD) through cell signaling related closely to cancer growth. We previously reported that peroxiredoxin 4 (PRDX4), a secretory-type antioxidant enzyme, can protect against the development of various diseases, including potential malignancies. Since many patients with early-stage LUAD develop recurrence, even after curative complete resection, we investigated the association of the PRDX4 expression with the clinicopathological features and recurrence/prognosis using post-surgical samples of stage I-LUAD.Methods: The expression of PRDX4 and MIB-1, a widely accepted Ki67 protein, was immunohistochemically analysed in 206 paraffin-embedded tumour specimens of patients with stage I-LUAD. The PRDX4 expression was considered to be weak when less than 25% of the adenocarcinoma cells showed positive staining.Results: A weak PRDX4+ expression demonstrated a significantly close relationship with pathologically poor differentiation, highly invasive characteristics and recurrence. The decrease in PRDX4-positivity potentially induced cell growth in LUAD, which was correlated significantly with a very high MIB-1 labelling index (≥17.3%). Univariate/multivariate analyses revealed that the subjects with both weak PRDX4+ expression and a very high MIB-1 index had significantly worse disease-free survival rates than other subjects.Conclusions: The combination of weak PRDX4 expression and a very high MIB-1 index can predict high proliferating activity and recurrence with a potential poor prognosis, especially in post-operative stage I-LUAD patients.

Multicellular structures, such as tumor buddings and poorly differentiated clusters (PDC), exist at the invasive front of colorectal cancers (CRC). Although it has been reported that CRC with PDC showed frequent lymph node metastases with a worse prognosis, the molecular markers of PDC that are responsible for prognosis have not been identified. We here noticed for the first time that Ezrin, a regulator of the actin cytoskeleton, is expressed in the corner cells of PDC. We then aimed to verify whether heterogeneous Ezrin expression in PDC predicts the prognosis of CRC patients. We immunohistochemically analyzed Ezrin expression in PDC of 184 patients with completely resected stages I‐III CRC. We established the Ezrin corner score (ECS), which quantifies the tendency of Ezrin‐positive cells to accumulate at the corners of PDC. On the basis of ECS values, 2 indices, the mean ECS and the number of PDC with high ECS, were obtained. Both indices were significantly higher in CRC with lymphatic invasion, higher PDC grade, and presence of micropapillary (MP) PDC. The mean ECS‐high group showed shorter recurrence‐free survival than the mean ECS‐low group but without significance. The other index, the number of ECS‐high PDC, was significantly associated with recurrence‐free survival. These results suggest that Ezrin is involved in PDC progression and lymphatic invasion, and that ECS may be a marker for aggressive PDC.

Background:Tumor-associated tissue eosinophilia is defined as an inflammatory response with the marked infiltration of eosinophils within tumor tissues. Tumor-associated tissue eosinophilia has been reported in various organs; however, no studies have examined the detailed cytopathological findings of tumor-associated tissue eosinophilia.Case Presentation:A 49-year-old woman presented with lower abdominal and back pain that had started 1 month earlier. A cervical biopsy revealed a diagnosis of non-keratinizing squamous cell carcinoma. A mildly increased number of eosinophils was observed in both cervical cytology and a biopsy. On pelvic computed tomography, a tumor mass measuring up to 5.5 cm in the largest diameter was seen in the uterine cervix. After 1 month, endometrial cytology was performed, and non-keratinizing squamous cell carcinoma together with normal endometrial glands was obtained in a background of marked eosinophil numbers. Tumor cells in an irregular-shaped solid nest had variable-sized hyperchromatic nuclei and light-green-stained cytoplasm. The number of eosinophils was obviously increased. Considering the possibility of tumor-associated tissue eosinophilia, we evaluated a peripheral blood sample and confirmed an increased number of eosinophils. Radical hysterectomy was performed, and the final pathological diagnosis was adenosquamous carcinoma. Although the number of eosinophils decreased after surgery, it increased again at the time of recurrence 1 year later. Chemo-irradiation was performed, but the patient died 1 year and 8 months after the operation.Conclusion:Cytopathologists should consider the presence of tumor-associated tissue eosinophilia by focusing on not only tumor cells but also the markedly eosinophilic background. The eosinophil count might be a useful marker of the disease activity.