Neuropathology最新文献

Diffuse midline glioma, is a highly aggressive deep-seated glioma whose diagnosis must be confirmed through histopathological analysis of stereotactic biopsies. Hemorrhagic complications after intracranial biopsies may occur, potentially leading to severe neurological sequelae or significantly altering the outcome. A 55-year old male with no significant medical history presented to the local emergency department with 4 days of diplopia. A magnetic resonance imaging (MRI) confirmed the presence of tumor whose characteristics were highly suggestive of a high-grade infiltrating causing blocked hydrocephalus. As no safe resection was achievable, a third ventriculostomy followed by an endoscopic biopsy of the tumor was performed. Unfortunately, the procedure was complicated by an massive intraventricular bleeding of the tumor and, the tiny tumor specimens collected were not contributive. Fortunately, the patient survived and, his clinical state slowly improved. Follow up MRIs depicted a progressive regression of the tumor. As such a wait and see policy was preferred over a chemoradiotherapy. Ultimately, the gadolinium enhancement totally vanished. Unfortunately, 27 months after the initial presentation, he presented with a quick neurological worsening with severe hemiparesis and seizures for which cerebral imaging showed a malignant-looking deep-situated unresectable brain tumor. A second biopsy was performed without any specific complication. The histopathological examination of the tumor revealed a high-grade glial tumor characterized by hypercellularity, marked atypia, mitosis, microvascular proliferation, and areas of necrosis with positive H3 p.K28M nuclear staining in combination with the loss of nuclear H3 p.K28me3. He was referred for best supportive care and, died 29.6 months after the initial presentation. To our knowledge, this is the first report of the gadolinium enhancement of a diffuse midline glioma H3 K27-altered.

We present the case of an 81-year-old man diagnosed with probable amyotrophic lateral sclerosis (ALS) based on the Updated Awaji criteria. The patient exhibited progressive motor neuron degeneration with muscle weakness, atrophy, and fasciculations primarily in the right lower limb and later extending to the right upper limb. Three months after being referred to a home care clinic, he collapsed in front of his family members and died. An autopsy revealed phosphorylated TDP-43 pathology consistent with ALS, with involvement of the hypoglossal nucleus, facial nerve nucleus, and medulla oblongata. Interestingly, widespread a-synuclein pathology indicative of diffuse neocortical type Lewy body disease (LBD; Braak stage 6) was identified, despite the absence of clinical parkinsonism or dementia with Lewy bodies (DLB) during his lifetime. The presence of autonomic symptoms such as constipation and urinary retention shortly before death may be attributable to a-synuclein pathology affecting the autonomic nervous system. The coexistence of ALS and LBD underscores the clinical challenge of diagnosing overlapping pathologies, as motor symptoms may obscure signs of LBD. Dopamine transporter imaging or MIBG myocardial scintigraphy might aid in identifying preclinical LBD in ALS patients with atypical symptoms. The patient died of respiratory failure due to extensive organizing pneumonia, but the possibility of sudden cardiac arrest could not be excluded. This case highlights the potential for coexisting neurodegenerative pathologies in ALS, emphasizing the importance of comprehensive evaluation when autonomic symptoms or other atypical features are present.

A 79-year-old former professional football player presented with language deficits and cognitive changes. A year later, he had difficulty completing sentences, and 3 years after onset, was reduced to one-word answers. He developed severe apathy and agitation, and became more impulsive. He eventually became mute and had difficulty with walking and balance. The patient had mild repetitive head injury while playing football and three concussions. Magnetic resonance imaging revealed left > right frontotemporal atrophy. Duration of illness was 6 years. Neuropathology revealed an unexpected number and diversity of degenerative pathologies, including chronic traumatic encephalopathy (CTE, high level), high level Alzheimer's disease neuropathologic change (A3B3C3), limbic Lewy body disease, cerebral amyloid angiopathy (type 2), argyrophilic grain disease (Stage 2), and neuronal intranuclear hyaline inclusion body disease. In addition, there was selective and asymmetric involvement of the corticospinal tract with globular oligodendroglial tau pathology corresponding to globular glial tauopathy (Type II). The patchy and irregular accentuation of cortical tau pathology, particularly in the depths of sulci and accumulation around blood vessels, allows the diagnosis of CTE-neuropathologic change. This diagnosis correlated with the past medical history of multiple concussions. In addition, the patient had an unprecedented number and combination of additional degenerative pathologies, including those that are rare, and how they contributed to the clinical symptoms is difficult to interpret. Globular glial tauopathy Type II is a rare disorder that has been mostly reported in association with progressive supranuclear gaze palsy, and these observations support the notion that globular glial tauopathy Type II is an independent entity with isolated corticospinal tract involvement. These observations highlight that rare disorders can occur in the same individual and be overlooked, especially when there is more obvious pathology. It is essential for neuropathologists to consider an extensive array of neuropathological examinations when assessing patients with neurodegenerative disorders.

Mid-life high blood pressure (BP) is a risk factor for Alzheimer's disease (AD). CERAD amyloid β (Aβ) plaques, Braak tau neurofibrillary tangles, and Thal Aβ plaque location are major scoring systems for quantifying neuropathological features of AD. We examined the association of late-life systolic BP (SBP) with CERAD, Braak, and Thal in the National Alzheimer's Coordinating Center (NACC) Neuropathology Dataset. Of 1978 participants with data on CERAD, 762 had scores 0-1 (none to sparse) and 1216 had 2-3 (moderate to frequent). Of 1947 with data on Braak, 411 had stages 0-II (normal to mild) and 1536 had III-VI (moderately to very severe). Of 2132 with data on Thal, 438 had phases 0-I, 428 II-III, and 1266 IV-V. Using the mean of the last four SBP before death, SBP was categorized into <120 (references), 120-139, and ≥140 mmHg. Age-sex-adjusted ORs (95% CIs) associated with SBP ≥140 mmHg for CERAD 2-3 and Braak III-VI were 1.37 (1.03, 1.83, P = 0.03) and 1.26 (0.89, 1.78, P = 0.20), respectively. Similar association was observed for Thal II-III and IV-V. These associations essentially remained unchanged after additional adjustment for APOE and Lewy Body pathology. These findings suggest that higher late-life SBP is associated with markers of presence and severity of neuropathological features of AD. Further studies with larger sample sizes are necessary to confirm the findings.

The manifestation of glioblastoma, IDH-wildtype (GB) as intracranial hemorrhage (ICH) presents diagnostic and therapeutic challenges. Molecular characteristics, including TERT promoter mutation, EGFR amplification, and chromosome 7 gain/10 loss, were incorporated to diagnose GB in the fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System. When molecular analyses fail to detect low fractions of these genetic alterations, the integrated diagnosis of GB can be enigmatic. This case report describes a 58-year-old man presenting with ICH, masking an underlying GB. Initial histopathology of the evacuated hematoma revealed a small number of atypical glial cells, but a definitive diagnosis was deferred. Subsequent surgery and molecular analysis, including digital polymerase chain reaction (dPCR), confirmed the presence of a TERT C228T mutation in the promoter area, leading to an integrated diagnosis of GB. The patient experienced a favorable clinical outcome following surgery, radiation, temozolomide, and tumor-treating field therapy, without recurrence after 50 months. This case underscores the importance of meticulous histological examination of ICH and exemplifies the clinical utility of dPCR as a complementary diagnostic tool. The effectiveness of dPCR is particularly noteworthy, even in scenarios with minimal tumor cell content, reinforcing its value in the integrated diagnosis of GB.

We report a rare case of rhabdoid meningioma (RM) originating from the optic nerve in a 57-year-old female. The tumor exhibited rhabdoid or epithelioid histology and harbored BAP1 inactivation mutations. Optic nerve meningioma typically originates from the outer meningeal cells of the optic nerve within the optic canal and is usually benign, with most cases classified as meningothelial or transitional meningiomas. This is the first reported case of RM involving the optic nerve, presenting with World Health Organization (WHO) central nervous system (CNS) grade 1 histological features but without CDKN2A/B homozygous deletions or telomerase reverse transcriptase promoter mutations, though harboring a BAP1 deletion. Despite being classified as a low-grade tumor by current standards, the rapid recurrence and progression observed underscore the importance of reporting this case to enhance awareness among pathologists and reduce misdiagnoses.

Non-neoplastic lesions of the ependyma have been neglected to date in comparison with neoplastic lesions derived from the ependyma, that is, ependymoma. The ependyma has a simple structure: mono-layered cuboidal cells covering the surface of the cerebral ventricles and the central canal of the spinal cord. In this review, the histopathological appearances of various non-neoplastic ependymal lesions are shown based on the author's personal experience, along with a review of the relevant literature. Following the introductory remarks about the normal histology and functions of ependymal cells including tanycytes, non-neoplastic lesions are then presented including, obliteration of the spinal central canal; the "ventriculus terminalis"; shedding of ependymal cells and "granular ependymitis"; "ependymal incorporation"; ependymal cells in hydrocephalus; ependymal reactions to various noxious stimuli; ependymal changes in cerebral dysgenesis; infections involving ependymal cells; glio-ependymal cyst; and finally, various intracellular inclusions in ependymal cells. Non-neoplastic ependymal lesions are intriguing and merit further investigations, which may provide deeper understanding of various brain lesions and of ependymal neoplasms.

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, marked by abnormal protein buildup (beta-amyloid and tau) resulting in neuronal loss, especially in the medial temporal lobe and other limbic regions. The presence of transactive response DNA binding protein 43 (TDP-43) immunoreactive inclusions in medial temporal lobe regions has also been associated with neuroimaging changes in limbic regions. It has been proposed that hypometabolism in limbic regions on [¹⁸F] fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a slowly evolving amnestic syndrome may be a signature of the presence of TDP-43. In this context, we observed an 86-year-old Caucasian female with dementia characterized by a slowly evolving amnestic syndrome, along with focal medial temporal atrophy evident on MRI and hypometabolism in limbic regions on FDG-PET. The patient subsequently died and underwent an autopsy. We performed detailed neuroimaging and digital neuropathological analyses of the hippocampal subfields to better understand the relationship between clinico-imaging findings and histopathology. In addition to TDP-43, we identified three other pathological processes in the medial temporal lobe: sequestosome-1/p62, argyrophilic grain disease (AGD), and primary age-related tauopathy (PART). Hippocampal subfield volumes and rates of atrophy were no different from those of matched healthy controls, except for the atrophy rate in cornu ammonis 1 (CA1). Digital histopathology revealed the relative highest burden of pathology for p62, followed by TDP-43, AGD, and PART in CA1. Multiple pathological processes appear to have contributed to the hippocampal atrophy and hypometabolism in our patient with a slowly progressive amnestic syndrome.

ADSS1 myopathy, previously known as adenylosuccinate synthetase-like 1 (ADSSL1) myopathy, is an autosomal recessive muscle disease caused by variants in ADSS1 (adenylosuccinate synthase 1). ADSS1 myopathy is complicated by respiratory muscle weakness or cardiomyopathy as well as limb muscle weakness. We analyzed two siblings with ADSS1 myopathy, both harboring compound heterozygous pathogenic variants (c.781G>A/c.919delA) in ADSS1 and provided details of their phenotypes together with muscle imaging and autopsy findings. Although it was reported that ADSS1 myopathy usually began with lower limb muscle weakness, our cases showed early involvement of the cervical paraspinal muscle, triceps brachii muscle, flexor digitorum superficialis and profundus muscles, rectus abdominis muscle, gluteus maximus and medius muscles, and cardiomyopathy. While a previous study reported that the trunk and hip muscles were relatively spared, atrophy of paraspinal muscles, gluteus medius and maximus muscles, and adductor muscles were observed. Our two siblings allowed for long-term follow-up and will be useful reference cases. We evaluated the frequency of fibers with nemaline bodies in various autopsied muscles and found that the ratio of fibers with nemaline bodies was lower compared to other nemaline myopathies. Postmortem examination revealed, for the first time, nemaline bodies in the diaphragm and myocardium, associated with respiratory failure and cardiomyopathy.

Transthyretin (TTR) can bind to Aβ and prevent the formation of Aβ fibrils in vitro; it is thus a highly interesting molecule in the field of Alzheimer's disease (AD) research. However, the distribution of TTR and its affinity to Aβ in both healthy human brains and those of AD patients remain unclear. We therefore examined TTR in human brains using postmortem brain samples. Paraffin sections and extracted protein samples were prepared from AD and control (non-AD) brains. Immunohistochemistry was performed to detect TTR expression patterns, and immunofluorescent staining was used to reveal the relationships between the intracellular and extracellular localizations of TTR and Aβ. We also performed western blotting for TTR using brain extracts. In immunohistochemical staining of the human brain, TTR signal was detected not only in extracellular tissue but also in the cytoplasm of neurons and glia. The TTR-positive area was significantly greater in AD brains than in non-AD brains. However, expression of TTR transcripts did not differ between AD and non-AD brains in our previously obtained RNA-sequencing and microarray data. Immunofluorescent staining with multiple antibodies revealed that TTR was co-localized with Aβ in the cytoplasm of neurons. In extracellular Aβ plaques, TTR presented in the same region but was not co-localized with dense Aβ fibrils. Together, our results indicate that TTR is widely expressed in the human brain rather than being limited to the choroid plexus and that TTR is more abundant in AD brains. Our results also suggest that the affinity between TTR and Aβ changes depending on the structure of Aβ. Our data will be valuable for the future development of TTR-related AD preventative methods and medications.