Neuropathology最新文献

Herein, we report an autopsy case of sporadic amyotrophic lateral sclerosis (ALS) with a p. L127S (L126S) SOD1 variant, SMN2 deletion and one hybrid SMN. A 43-year-old Japanese man noticed muscle weakness in his left lower extremity. At the age of 51, his muscle strength was moderately diminished in the upper extremities and severely in the lower extremities with hyporeflexia. At the age of 55, he started noninvasive intermittent ventilation (NIV) during nighttime. At the age of 57, he developed dysphagia and died of pneumonia. The total clinical course was 14 years and 8 months (13 years 9 months until NIV). Pathologically we found severe loss of lower motor neurons, moderate neuronal loss in Clarke's nuclei and mild grumose degeneration of the dentate nucleus. The primary motor cortex was well preserved and the pyramidal tracts showed vague myelin pallor in the lumbar cord. There were a few conglomerate hyaline inclusions (CHIs) that were negative for Bodian staining. Immunohistochemically, CHIs were positive for phosphorylated neurofilament (pNF) and were stained with Uq and SOD1 to varying degrees. Some CHIs contained granular-like components positive for p62. A post-mortem genetic test revealed that the patient had 2 copies of SMN1, 0 copies of SMN2, and one hybrid gene with exon 1 to 7 of SMN2 and SMN1 exon 8. Additional gene research elucidated a heterozygous SOD1 p. Leu127Ser (L126S) mutation. Compared to previous reports of ALS with the same mutation, the distribution of degenerative lesions was similar. It has been suggested that SMN2 deletion may not be directly implicated in lower motor neuron pathology, but further research is needed to confirm this. Further accumulation of cases is necessary to determine the effect of SMN2 on SOD1-ALS.

We performed a systematic review of the literature to better define the scope of MYB alterations in angiocentric glioma and their associated clinical characteristics, as well as to include a novel MYB mutation in an angiocentric glioma case. We also review MYB alterations in the context of oncologic disease. Following PRISMA guidelines, we searched PubMed and Web of Science for relevant literature from 2010 to October 2024. Included articles reported original data on human subjects with angiocentric glioma and a detected MYB mutation. We include one additional angiocentric glioma case showcasing a novel MYB mutation. A total of 14 studies met the inclusion criteria, with a total of 114 patients with individual data for pooled analysis. The mean age was 10.3 years (SD ±9.7 years); 60% of patients were male. MYB::QKI was the most common fusion in 68% of patients. Other MYB mutations included MYB rearrangements, MYB::ESR1, MYB::PCDHGA1, MYB::LOC105378099, and MYB::MMP16. The most common anatomical location was in the cerebral cortex in 68% of patients. MYB fusions in other relevant neuro-oncologic diseases highlight the importance of MYB fusions in adenoid cystic carcinomas, which frequently occur at the skull base, head and neck, and breast. In conclusion, we characterize the breadth of angiocentric glioma patterns in terms of demographics, anatomic location, and MYB fusion patterns. The updated molecular diagnosis of angiocentric glioma as of 2021 warrants continued exploration of the scope of MYB oncogene fusions as drivers of prognosis and targets for future therapies.

Embryonal tumors with multilayered rosettes (ETMRs) are rare and highly aggressive embryonal central nervous system tumors that predominantly affect infants younger than 3 years old. These tumors typically have a C19MC alteration (ETMR, C19MC-altered) or, more rarely, a DICER1 mutation (ETMR, DICER1-mutated). Post-chemotherapeutic or post-chemoradiotherapeutic histological changes of C19MC-altered ETMRs, such as maturation or loss of histological characteristics of ETMR have been described in several reports. However, histological changes of recurrent DICER1-mutated ETMRs have not been reported to date. Herein, we report a case of DICER1-mutated ETMR with unique post-treatment morphological changes, including both maturation and loss of histological characteristics. Although pathological examination of tissue from the first resection revealed typical ETMR histology, the recurrent tumor after chemoradiotherapy was composed predominantly of a primitive embryonal component without multilayered rosettes or neuropil-like areas. Furthermore, the recurrent tumor contained a component composed of unique tumor cells with oval eccentric nuclei and eosinophilic cytoplasm demonstrating a neuronal immunohistohemical phenotype. No mitotic figures were found in the component. Molecular analysis identified a mutation in the DICER1 RNase IIIb domain in the primary tumor and the primitive embryonal component of the recurrent tumor, but not in the unique neuronal area.

Here, we report an autopsy case of concurrent spinal and bulbar muscular atrophy (SBMA) and multiple system atrophy (MSA). A 55-year-old man presented with weakness, atrophy, and fasciculation of the tongue and the proximal parts of all limbs. The patient gradually developed severe orthostatic hypotension, urinary retention, and cerebellar ataxia; however, no parkinsonism was observed. The patient succumbed to sudden death during sleep. The autopsy revealed widespread and abundant α-synuclein-positive glial cytoplasmic inclusions in the central nervous system, indicative of MSA. Neuronal loss was also observed in the substantia nigra and locus coeruleus. Consequently, the patient was diagnosed with MSA. Additionally, immunostaining for the monoclonal 1C2 antibody revealed positive neurons in the medulla oblongata and spinal cord, supporting the additional diagnosis of SBMA. Genetic analysis revealed an expansion of 41 CAG repeats in the androgen receptor (AR) gene (normal range: 12-38), confirming the diagnosis of SBMA. Altogether, concurrent SBMA and MSA were diagnosed based on the autopsy findings, making this the first reported case of such coexistence in the Japanese and English literature.

This study aimed to evaluate the performance of ChatGPT-4.0 as a diagnostic support tool for pathologists in identifying different types of gliomas based on histopathological data and to compare its performance with that of another artificial intelligence tool (Gemini 2.5 Pro). A retrospective analysis was performed on 25 cases with histopathological descriptions. The dataset, anonymized for patient confidentiality, included clinical details such as age, sex, and site, along with two histological images for each case, obtained from the archive files of the Anatomic Pathology section, Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia" University of Catania, Italy. ChatGPT-4.0 was tasked with generating diagnoses, which were classified as correct, similar, or different when compared to the pathologists' conclusions and the diagnoses provided by Gemini. ChatGPT-4.0 achieved a diagnostic accuracy of 88%, correctly identifying 22 out of 25 cases. No significant differences in diagnostic performance were observed between male and female patients. The AI performed exceptionally well in diagnosing glioblastomas, with a 100% accuracy rate, while two oligodendrogliomas and one astrocytoma IDH-mutant G3 were misdiagnosed. A comparative evaluation with Gemini 2.5 Pro was also conducted, although its contribution was limited to a qualitative comparison based on the same dataset. ChatGPT-4.0 demonstrated moderate accuracy in the histopathological diagnosis of gliomas, with little variability depending on glioma subtype. While its performance highlights potential for future integration into clinical workflows, significant improvements are required to ensure its reliability and effectiveness in diagnostic applications. Trial Registration: ce 165/2015/PO.

Postmortem research participation remains underrepresented in research ethics discussions. Herein, we examined the associated perspectives of individuals preregistered with the Brain Bank for Aging Research at the Tokyo Metropolitan Institute of Gerontology. We conducted a postal survey targeting 88 preregistrants, yielding 52 responses (response rate: 59.1%, average respondent age: 79.5 years, range: 49-97). The questionnaire gathered information on the reasons for agreeing to participate, helpful information provided during the explanation, and expectations regarding future information. The stated reasons for participating included a desire to contribute to science, gratitude for medical care received, memories of relatives' past donations, and inspiration from staff enthusiasm and materials. Beneficial information was given in brochures, coordinator explanations, and lectures; however, guidance for family members regarding postmortem procedures and updates on recent activities and research outcomes were highlighted as areas requiring future improvement. Willingness to participate in brain banks was influenced by altruistic factors, personal medical experiences, and the influence of statements from close contacts. Registrants maintained their interest after registration and prepare for future arrangements. Family cooperation was identified as a critical factor influencing the fulfillment of participant intentions, emphasizing the need for accessible and low-burden family guidance. Registrants generally seek information to help family members and associates avoid difficulties related to their participation. Brain banks should continue conducting such surveys for registrants and reflect the findings in their information dissemination and educational programs. This approach will help improve the understanding and support for brain bank participation, ultimately contributing to the advancement of medical research and ethics in postmortem studies.

A long-surviving older sister and her younger brother, both with a juvenile type of DRPLA, were autopsied. They had 69 and 77 CAG repeats in the atrophin-1 gene (ATN1), respectively. The older sister developed intellectual disability at the age of 10 years, followed by epilepsy, and survived for 40 years supported by tube feeding and tracheostomy with laryngeal closure without signs of anoxia and malnutrition. As the disease progressed, brain CT revealed a progressive skull thickening alongside brain atrophy. The younger brother, who had developmental delay at the age of 3 years, died of status epilepticus aged 24 years. Their father developed cerebellar ataxia at 56 years old when his daughter was 27 years old, and the expanded allele had 63 CAG repeats in ATN1. His clinical course was characterized by the sudden onset of severe psychiatric symptoms and choreatic movement. He died of aspiration pneumonia and suffered from malignant lymphoma aged 72 years. Neuropathological examination of this older sister with extended survival of DRPLA revealed a thickened skull, atrophic brainstem and cerebellum, and a thin spinal cord. We found neuronal loss and gliosis across a wide range of brain regions in addition to severe degeneration of the dentatorubral and pallidoluysian systems along with regions previously reported to exhibit polyglutamine pathology. In contrast, some regions previously reported to exhibit polyglutamine pathology remained preserved. The cerebellar cortex showed three-layer degeneration, and changes in the cerebral white matter appeared to correspond to lesions in the cerebral cortex.

Monocarboxylate transporters (MCTs) are crucially implicated in cancer cell metabolism by transporting lactate/H+ ions and thus regulating the pH of the microenvironment. We assessed MCT1 and MCT4 expression in 98 cases of adult-type hemispheric Glioblastomas (GBMs) (IDH wild-type), along with 51 cases of IDH-mutant astrocytic and oligodendroglial tumors (grade 2-4) for comparison. U87MG and LN229 cell lines were used for in vitro analysis. Both MCT-1 and MCT-4 showed significantly higher expression in GBMs on immunohistochemistry than in IDH-mutated gliomas, which mostly showed weak or negative immunoreactivity. The mRNA expression was also in a similar line. Interestingly, in all areas of the pathological endothelial proliferation of grade 4 tumors, there was MCT-1 loss of expression, unlike the nonproliferating endothelium. High MCT1/4 expression was associated with shorter overall survival in all gliomas together but not in GBM separately. Syrosingopine, a dual MCT1/4 inhibitor, showed significant antitumor effects in both the glioma cell lines, including dose-dependent cytotoxicity, increased apoptosis, and decreased migration/invasion. The results indicated the role of MCT1/4 in the pathobiology of GBM and the diagnostic utility at the immunohistochemical level. Syrosingopine, an antihypertensive agent with good CNS penetration and previously used in different malignancies, may be an essential therapeutic adjunct in GBM.

This study described a case of plurihormonal tumor associated with papillary thyroid carcinoma (PTC) and summarized the treatment approaches for similar cases, while also exploring the underlying pathogenesis. The patient exhibited symptoms indicative of acromegaly, central hyperthyroidism, and hyperprolactinemia. A glucose loading test demonstrated persistently elevated growth hormone (GH) levels, while thyroid function tests revealed inappropriate thyroid stimulating hormone (TSH) secretion. Imaging of the pituitary gland revealed a 26 × 19 mm lesion compressing the optic chiasm. Thyroid ultrasound reveals bilateral Thyroid Imaging Reporting and Data System 4B nodules, with the largest on the right measuring 27 × 20 mm. Fine-needle aspiration cytology (FNAC) revealed the presence of PTC. Three weeks later, the patient underwent pituitary adenomectomy. Immunohistochemistry revealed a plurihormonal tumor positive for TSH, GH, luteinizing hormone (LH), prolactin (PRL), pituitary-specific transcription factor 1 (Pit1), and steroidogenic factor 1 (SF1). A total thyroidectomy followed 10 weeks post-adenomectomy. Immunohistochemical evaluation showed higher nuclear positivity for the high-mobility group AT-hook 1 (HMGA1) and the high-mobility group AT-hook 2 (HMGA2) proteins in neoplastic cells compared to normal tissues. In our search results, only three similar cases were identified, and we summarized the relevant literature search results which raise the possibility that the HMGA2-the Retinoblastoma Protein (pRB)/E2F Transcription Factor 1 (E2F1)-HMGA1 signaling pathway may represent a common pathogenic pathway for PTC and plurihormonal tumor. If a patient simultaneously suffers from PTC and plurihormonal tumor, the determination of the surgical sequence is crucial. In cases of postoperative recurrence, where patients are reluctant to undergo additional surgeries, targeting HMGA is likely to offer a promising approach to prevent the progression of both the pituitary tumors and PTC.