Inflammatory progressive multifocal leukoencephalopathy with human T-cell lymphotropic virus-1 coinfection.

A middle-aged man with progressive multifocal leukoencephalopathy (PML) in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier on haemodialysis presented with mild dysarthria and ataxia. Brain MRI revealed asymmetric T2-hyperintense lesions in the cerebral white matter, cerebellum and brainstem. A small amount of JC virus (JCV) genome in cerebrospinal fluid was detected by PCR and cerebellar biopsy demonstrated JCV-DNA presence. Pathological findings showed demyelinating lesions and glial cells with mildly enlarged nuclei, accompanied by T-lymphocytes, neutrophils and plasma cell infiltration. The CD4+/CD8+ratio was 0.83. High-dose corticosteroid therapy was effective for inflammatory PML lesions, and the administration of mefloquine combined with mirtazapine led to favourable outcome. The encephalitis in this case is considered to have occurred secondarily to JCV infection in the presence of HTLV-1 infection. Therefore, it is crucial to investigate the presence of HTLV-1 in order to understand the aetiology of this brain inflammation.

Fabrication of Artificial Nerve Conduits Used in a Long Nerve Gap: Current Reviews and Future Studies.

There are many commercially available artificial nerve conduits, used mostly to repair short gaps in sensory nerves. The stages of nerve regeneration in a nerve conduit are fibrin matrix formation between the nerve stumps joined to the conduit, capillary extension and Schwann cell migration from both nerve stumps, and, finally, axon extension from the proximal nerve stump. Artificial nerves connecting transected nerve stumps with a long interstump gap should be biodegradable, soft and pliable; have the ability to maintain an intrachamber fibrin matrix structure that allows capillary invasion of the tubular lumen, inhibition of scar tissue invasion and leakage of intratubular neurochemical factors from the chamber; and be able to accommodate cells that produce neurochemical factors that promote nerve regeneration. Here, we describe current progress in the development of artificial nerve conduits and the future studies needed to create nerve conduits, the nerve regeneration of which is compatible with that of an autologous nerve graft transplanted over a long nerve gap.

Two Cases of Atypical Teratoid/Rhabdoid Tumor in the Spinal Cord: Loss of SMARCB1 in a Child and Loss of SMARCA4 in an Adult.

We compare two cases of primary spinal atypical teratoid/rhabdoid tumor (AT/RT), which rarely occurs in adults marked by SMARCA4 inactivation, and SMARCB1 inactivation for pediatric cases. AT/RT represents a highly malignant neoplasm comprising poorly differentiated constituents and rhabdoid cells, with SMARCB1(INI1) or infrequently SMARCA4 (BRG1) inactivation. These tumors are predominantly found in children but are rare in adults. While AT/RT can arise anywhere in the central nervous system, spinal cord localization is comparatively scarce. Despite mutation or loss of SMARCB1 at the 22q11.2 locus serving as the genetic hallmark of AT/RTs, infrequent cases of SMARCA4 inactivation with intact SMARCB1 protein expression are significant. We present each case of primary spinal tumors in a child and an adult, showing loss of the SMARCB1 and SMARCA4 proteins, respectively. Both tumors met the AT/RT diagnostic criteria. The histopathology demonstrated the presence of rhabdoid cells in both cases. Diagnosing primary spinal AT/RT with SMARCB1 protein loss remains a challenge. Nevertheless, the presence of SMARCB1 positivity alone must be noted to be insufficient to exclude the possibility of AT/RT diagnosis. In cases in which the diagnosis of AT/RT is highly suspected clinically, additional testing is warranted, including SMARCA4 analysis.

Pathology for severe inflammatory PML with PD1/PD-L1 expression of favorable prognosis: What's a prognostic factor for PML-IRIS?

A 72-year-old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1-hypointense area. Multiple T2/FLAIR-hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of "suspicious of malignant lymphoma." Owing to emergent clinical conditions, high-dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR-hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4+ and CD8+ T cells, and the CD4+ /CD8+ ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20+ B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti-viral response. Variable inflammatory cells were observed, including CD4+ and CD8+ T cells, plasma cells, and a small amount of perivascular CD20+ B cells. PD-1 and PD-L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8+ T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD-1/PD-L1 immune-checkpoint regulation.

Analysis of False-negative Findings of the Incomparable Accuracy and Swiftness of Flow Cytometric Diagnosis of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL), a relatively rare brain tumor, bears a dire prognosis. On occasion, the rapid progression of the tumor makes immediate diagnosis and initiation of therapy imperative. To achieve swift diagnosis, we adopt flow cytometry (FCM) in addition to conventional histopathology. This study aimed to reveal the utility of FCM diagnosis for PCNSL and the cause of false-negative results of FCM diagnosis. We investigated 33 patients with suspected PCNSL on neuroradiological findings and received both FCM and histological diagnosis. The patients' electronic medical records were investigated, and histological findings, results of FCM, and other clinical data were evaluated. Overall, 27 patients (14 males and 13 females) were diagnosed with PCNSL by histological confirmation. The median age at diagnosis was 68 years. FCM analysis showed lymphoma pattern in 24 cases; however, FCM results did not show lymphoma pattern (sensitivity: 88.9%, specificity: 100%) in the other three lymphoma cases (FCM discordant: FCM-D) and six nonlymphomatous tumor cases. Analysis of FCM-D cases showed the infiltration of T lymphocytes or astrocytes into the tumor tissue, indicating tumor microenvironmental reaction; it is assumed that these reactions deceived FCM diagnosis. The survival of FCM-D patients was superior to FCM concordant counterpart, although the difference was not significant (p = 0.459). The diagnosis of PCNSL by FCM is rapid and highly reliable. Some FCM-D cases are PCNSLs with strong tumor microenvironmental reactions.

Progressive Multifocal Leukoencephalopathy Initially Suspected As Brain Relapse From Classical Hodgkin's Lymphoma.

HIV-negative progressive multifocal leukoencephalopathy (PML) has a poor prognosis due to a lack of standard treatment. Herein, we report a patient with HIV-negative PML which occurred after the treatment for classical Hodgkin's lymphoma (CHL). A 71-year-old male patient was admitted to our hospital due to various neurological symptoms, including memory disturbance, dysgraphia, ataxia, and ideomotor apraxia, at 16 months after high-dose salvage chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for primary treatment-refractory CHL. The patient's blood and serological examination results were mainly normal, including CD4-positive T lymphocyte count and serum immunoglobulin levels. T2-weighted fluid-attenuated inversion recovery MRI showed high-intensity lesions from the left occipital lobe to the corpus callosum. Moreover, the rapid intraoperative pathological assessment of biopsy specimens obtained from abnormal brain lesions suggested brain relapse of CHL. The patient's symptoms progressed rapidly; therefore, treatment with high-dose methotrexate was started, which significantly improved the patient's symptoms and MRI findings within a week. However, further examinations of the biopsy specimens with in situ hybridization and immunohistochemical examinations showed reactivation of the John Cunningham virus (JCV) in the astrocytes. Further, cells initially believed to be Hodgkin cells based on the rapid intraoperative pathological assessment were found to be destructive astrocytes, thereby confirming the diagnosis of PML. The patient was then successfully treated with combined mefloquine and mirtazapine and did not have any fatal outcomes. Based on this case, a differential diagnosis of PML from CNS involvement of CHL is important even in cases without evident biomarkers for immunodeficiency. Moreover, methotrexate was likely to be effective in improving neurological symptoms by decreasing brain parenchyma inflammation in the acute phase in this particular patient.

Genetic Alteration May Proceed with a Histological Change in Glioblastoma: A Report from Initially Diagnosed as Nontumor Lesion Cases.

Despite recent signs of progress in diagnostic radiology, it is quite rare that a glioblastoma (GBM) is detected asymptomatically. We describe two patients with asymptomatic nonenhancing GBMs that were not diagnosed with neoplasia at first. The patients had brain scans as medical checkups, and incidentally lesions were detected. In both cases, surgical specimens histopathologically showed no evidence of neoplasia, whereas molecular genetic findings were isocitrate dehydrogenase (IDH)-wildtype, O6-methylguanine-DNA methyltransferase promoter (pMGMT) unmethylated, and telomerase reverse transcriptase (TERT) promoter mutated, which matched to GBM. One patient was observed without adjuvant therapy and the tumor recurred 7 months later. Reoperation was performed, and histopathologically GBM was confirmed with the same molecular diagnosis as the first surgical specimen. Another patient was carefully observed, and chemoradiotherapy was begun 6 months after the operation following the extension of the lesion. Eventually, because of disease progression, both patients deceased. We postulate that in each case, the tumor was not lower-grade glioma but corresponded to the early growth phase of GBM cells. Thus far, cases of malignant transformation from lower-grade glioma or asymptomatic GBM with typical histologic features are reported. Nevertheless, to the best of our knowledge, no such case of nonenhancing, nonhistologically confirmed GBM was reported. We conjecture these cases shed light on the yet unknown natural history of GBM. GBM can take the form of radiological nonenhancing and histological nonneoplastic fashion before typical morphology. Molecular genetic analysis can diagnose atypical preceding GBM, and we recommend early surgical removal and adjuvant treatment.

Prevention of New Metastatic Lesions by Eribulin Monotherapy Is Associated with Better Prognosis in Patients with Metastatic Breast Cancer.

BACKGROUND: Eribulin therapy has been reported to prolong overall survival (OS) but not progression-free survival, probably because it prevents the development of metastatic lesions; however, this effect has not yet been confirmed. METHODS: We reviewed the medical charts of 50 patients with metastatic breast cancer who underwent eribulin monotherapy at our hospital between 2014 and 2019. Patients were divided into two groups, namely, those who discontinued eribulin because of disease progression due to development of new lesions (NL group) and those who discontinued eribulin for other reasons, such as lesion growth and unacceptable side effects (non-NL group). Survival times were estimated for both groups and we investigated if eribulin-mediated suppression of new metastasis increased OS. RESULTS: Median OS for all patients, from eribulin initiation, was 14.4 months (range 1.2-60.1), whereas it was 4.6 months (range 1.7-24.7) in the NL group and 16.8 months (range 1.2-60.1) in the non-NL group. OS was significantly poorer in the NL group than in the non-NL group (p < 0.05). CONCLUSION: Eribulin monotherapy-mediated suppression of new metastatic lesions results in a better prognosis in patients with metastatic breast cancer.

An autopsy case of COVID-19 with a sudden death: Clinico-pathological comparison.

Autopsy was performed on a COVID-19 patient, who suddenly died despite the extensive anti-viral and anti-inflammatory therapies. Although moderate subpleural fibrosis was seen, pathology of DAD, a well-known cause for pulmonary failure, was minimum. Instead, severe hemorrhage was observed. Therapeutic effects were indicated; however, why severe hemorrhage occurred was unclear.

No evidence of bovine leukemia virus proviral DNA and antibodies in human specimens from Japan.

BACKGROUND: The potential risk and association of bovine leukemia virus (BLV) with human remains controversial as it has been reported to be both positive and negative in human breast cancer and blood samples. Therefore, establishing the presence of BLV in comprehensive human clinical samples in different geographical locations is essential. RESULT: In this study, we examined the presence of BLV proviral DNA in human blood and breast cancer tissue specimens from Japan. PCR analysis of BLV provirus in 97 Japanese human blood samples and 23 breast cancer tissues showed negative result for all samples tested using long-fragment PCR and highly-sensitive short-fragment PCR amplification. No IgG and IgM antibodies were detected in any of the 97 human serum samples using BLV gp51 and p24 indirect ELISA test. Western blot analysis also showed negative result for IgG and IgM antibodies in all tested human serum samples. CONCLUSION: Our results indicate that Japanese human specimens including 97 human blood, 23 breast cancer tissues, and 97 serum samples were negative for BLV.

Non-Destructive Measurement of Acetic Acid and Its Distribution in a Photovoltaic Module during Damp Heat Testing Using pH-Sensitive Fluorescent Dye Sensors.

An optical pH sensor that enables the non-destructive measurement of acetic acid and its distribution in a photovoltaic module during damp heat (DH) testing is reported. The sensor was fabricated by impregnating a solution of a pH-sensitive fluorescent dye into a fluororesin membrane filter, which was then dried. While conducting the DH test, fluorescence spectra from 20 pH sensors were periodically recorded and converted into pH values using a predetermined calibration curve. As a result, we succeeded in measuring changes in pH with a DH test time of up to 2000 h, and it was possible to obtain information on the pH distribution in the module. We also confirmed no change in pH in a module with a silicone encapsulant free from acetic acid, and revealed that the sensor that we developed does not respond to moisture and heat, but only to acetic acid.

A tumefactive anti-MOG antibody associated disorder heralding central nervous system B-cell lymphoma: Case report on diagnostic challenge.

We present the case of a 52-year-old woman with right hemiparesis due to a mass lesion in the left parietal white matter and corpus callosum. The lesion was hyperintense on diffusion weighted image and homogenously enhanced with gadolinium on magnetic resonance imaging, and was radiologically indistinguishable with lymphoma. Following progressive aggravation of symptoms, craniotomy for biopsy of the lesion was performed, and it was revealed that the patient had anti-myelin oligodendrocyte glycoprotein-associated disease by histopathological and serological diagnosis. Initial treatment with steroid dramatically improved the symptoms, but they exacerbated again. Then, through cerebrospinal fluid examination, it was revealed that the patient had B-cell lymphoma.

Survival With Surgery Is Superior to Survival Without Surgery in Breast Cancer Patients Aged 85 years or Older: A Retrospective Study.

BACKGROUND: Surgical treatment of breast cancer patients aged 85 years or older is still controversial. METHODS: A series of surgically treated breast cancer patients aged 85 years or older was evaluated. The clinicopathological features and outcomes of these patients were compared with the features and outcomes of breast cancer patients in the same age group who were managed without surgery. RESULTS: A total of 45 patients (75%) received surgical treatment, and 15 patients (25%) were managed without surgery. Significantly more patients treated by surgery underwent systemic treatment than patients managed without surgery (P = .003). The 5-year disease-free survival rate of patients treated by surgery was 80.7% (95% confidence interval: 66.2-98.5%), which was significantly higher than that of the patients managed without surgery (P = .001). CONCLUSIONS: The surgical treatment of breast cancer patients aged 85 years or older is warranted. This outcome was achieved with the use of hormonal therapy.

Radiologic-pathologic association of tumor-like lesions with inflammation in cerebral white matter: Comparison of two cases with distinct clinical outcomes.

Here, we report two cases showing tumor-like white matter lesions; one case was diagnosed as having inflammatory disease, and the other was diagnosed as having astrocytoma. Their outcomes were completely distinct despite similar pathology. Prior to biopsy, perfusion computed tomography (CT) and magnetic resonance imaging (MRI) were conducted. The two mass-forming lesions were distinct in edema level and vascularity patterns on CT and MRI. However, pathological examination of brain biopsy specimens revealed commonalities, including (1) proliferation of glial cells, (2) perivascular lymphocytic infiltration, and (3) appearance of numerous macrophages. Although atypical astrocytes proliferated in both cases, nuclear atypia was more distinct in case 2 than in case 1. The immunohistochemical results were the same for both cases: isocitrate dehydrogenase 1 (IDH1) R132H mutation was negative, and alpha thalassaemia mental retardation X-linked (ATRX) was retained. Faint immunoreactivity for p53 was observed in a few glial cells, and Ki-67 immunoreactive cells were markedly reduced in numbers (< 1%). Inflammatory reactions were evident in both cases: T cells dominantly infiltrated over B cells in the perivascular area in case 1, whereas both T and B cells infiltrated in case 2. Molecular analysis revealed wild-type IDH1 and IDH2 in both cases. However, a telomerase reverse transcriptase (TERT) sequence mutation was detected in case 2 but not in case 1. Eventually, case 1 was diagnosed as having inflammatory lesions, whereas case 2 was diagnosed as having diffuse astrocytoma associated with inflammatory reactions. The prognosis was favorable for case 1, whereas case 2 died 10 months following biopsy. These data indicated the diagnostic value of molecular analysis, for example, a TERT mutation, in association with the radiological findings. Although in case 2, histopathological evidence did not suggest high-grade glioma, the case met the new diagnostic criteria: "diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma, World Health Organization (WHO) grade IV," according to cIMPACT-NOW, update 3. Thus, interdisciplinary approaches are essential for accurate diagnosis of newly categorized white matter diseases.

Laser astrophysics experiment on the amplification of magnetic fields by shock-induced interfacial instabilities.

Laser experiments are becoming established as tools for astronomical research that complement observations and theoretical modeling. Localized strong magnetic fields have been observed at a shock front of supernova explosions. Experimental confirmation and identification of the physical mechanism for this observation are of great importance in understanding the evolution of the interstellar medium. However, it has been challenging to treat the interaction between hydrodynamic instabilities and an ambient magnetic field in the laboratory. Here, we developed an experimental platform to examine magnetized Richtmyer-Meshkov instability (RMI). The measured growth velocity was consistent with the linear theory, and the magnetic-field amplification was correlated with RMI growth. Our experiment validated the turbulent amplification of magnetic fields associated with the shock-induced interfacial instability in astrophysical conditions. Experimental elucidation of fundamental processes in magnetized plasmas is generally essential in various situations such as fusion plasmas and planetary sciences.

Magnetic Resonance Imaging of Orbital Solitary Fibrous Tumors: Radiological-Pathological Correlation Analysis.

BACKGROUND: Solitary fibrous tumors (SFTs) are rare and can be misdiagnosed because of their various radiological appearances. PURPOSE: To clarify the characteristic MRI findings of SFTs by analyzing their radiological-pathological correlation. MATERIAL AND METHODS: Nine consecutive patients with SFT who underwent magnetic resonance imaging (MRI) prior to surgery were analyzed. Eight patients underwent contrast-enhanced MRI, and three underwent dynamic MRI. Radiological-pathological correlation analysis, co-occurrence matrix, run-length matrix, and histogram analysis were performed to assess the relationship between pathological findings T1- and T2-weighted images (T1-WI and T2-WI). RESULTS: All nine lesions ranged in size from 20 to 36 mm. Seven lesions were located in the superior portion of the retrobulbar space found outside of the muscle cone, and two lesions in the inferior portion were located within it. No significant correlation was observed between the amount of collagenous tissue and the qualitative evaluation of the signal on T1-WI and T2-WI. Kurtosis on T2-WI was significantly correlated with the amount of collagenous tissue (ρ = -0.97, p < 0.0001) and endothelial cells (ρ = -0.49, p = 0.0479). CONCLUSION: Kurtosis in the histogram analysis on T2WI showed a strong correlation with the amount of collagenous tissue.

Relationship between MRI findings and invasive breast cancer with podoplanin-positive cancer-associated fibroblasts.

OBJECTIVE: Purpose of our study is to assess the relationship between MRI findings and invasive breast cancer (IBC) with cancer-associated fibroblasts (CAFs) that are positive for podoplanin. METHODS: We retrospectively analyzed the consecutive 109 IBCs. The IBCs were dichotomized as with (+) or without (-) podoplanin-positive CAFs. In MRI analyses, the dichotomized IBCs were compared the lesion to muscle ratio (L/M ratio) in STIR images, the ADC value, the distribution of kinetic parameters, and morphological findings. RESULTS: Of the 109 IBCs, 28 (26%) IBCs had podoplanin(+) CAFs. Compared to the podoplanin(-) group, the podoplanin(+) group tended to have a more malignant pathological status. In the STIR images, the podoplanin(+) group had significantly higher L/M ratio (7.59 vs. 6.55, p = 0.040). In a dynamic study, the podoplanin(+) group had a significantly higher percentage of the washout pattern (42.21% vs. 29.43%, p = 0.045). There were 23 mass lesions and 5 non-mass enhancement (NME) lesions in the podoplanin(+) group, and 69 mass lesions and 12 NME lesions in the podoplanin(-) group. The mass lesions of the podoplanin(-) group had a significantly higher likelihood of showing an irregular shape (n = 47 vs. 8, p = 0.035). The podoplanin(+) group's lesions had a significantly higher likelihood of showing a circumscribed margin (n = 14 vs. 6, p < 0.001) and a rim enhancement (n = 10 vs. 13, p = 0.047). In multivariate analyses, only high nuclear grade was significant predictive value of podoplanin(+) CAFs. CONCLUSION: Although not significant in multivariate analyses, MRI findings may be used to determine the podoplanin-positive CAF status of invasive breast cancer.

Early Pathological JC Virus Lesions in a Patient without Any MRI-based Indications.

A 70-year-old woman with a human T-cell leukemia virus type 1 infection without any focal neurological symptoms showed age-related atherosclerotic changes in the white matter without any suspicious signal changes suggestive of progressive multifocal leukoencephalopathy (PML) based on the findings of MRI. Viral polymerase chain reaction (PCR) revealed 6,700 copies/mL of the JC virus genome in the cerebrospinal fluid (CSF). An immuno-pathological examination of the autopsied brain revealed JC virus capsid proteins, and in situ hybridization confirmed a JC virus infection, indicating that an active infection begins at the radiologically indistinguishable phase of PML. An early JC virus infection is probably associated with small, scattered demyelinating lesions around the cortico-medullary area of the cortex.