Neuropathology最新文献

The mutations of the feline leukemia virus subgroup C receptor-related protein 1 (FLVCR1) cause ataxia with retinitis pigmentosa. Recent studies indicated a large variation in the phenotype of FLVCR1-associated diseases. In this report, we describe an adult male who manifested first with tremors in his third decade, followed by retinitis pigmentosa, sensory ataxia, and sensory neuropathy in his fourth decade. While retinitis pigmentosa and sensory ataxia are well-recognized features of FLVCR1-associated disease, tremor is rarely described. Whole-exome sequencing revealed novel compound heterozygous pathogenic FLVCR1 variants: c.498 G > A; p.(Trp166*) and c.369 T > G; p.(Phe123Leu). In addition, we have highlighted the ultrastructural abnormalities of the sural biopsy in this patient.

Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. Neurosyphilis results from the infection of the nervous system with Treponema pallidum, which can occur at any stage of syphilis. Neurosyphilis is often overlooked because of its rarity. Early-stage neurosyphilis with brain mass formation is rare. We present a case of early-stage neurosyphilis with prominent Epstein-Barr virus (EBV)-positive monoclonal lymphoplasmacytic proliferation in an immunocompetent patient. A 36-year-old man presented with a chief complaint of a progressively worsening headache, a newly developed skin rash, and a fever. Magnetic resonance imaging showed a mass lesion, which measured 18 mm in diameter, in the left frontal lobe of the cerebrum. The patient underwent an emergency operation to remove the abscess. A pathological investigation revealed complex findings. There was an abscess in the cerebrum. Lymphoplasmacytic meningitis was also noted. In addition, a vaguely nodular lesion, which was composed of plasmacytoid and lymphoid cells, was observed around the abscess. Immunohistochemically, an anti-Treponema pallidum antibody revealed numerous Treponemas around the abscess. In situ hybridization revealed that the plasmacytoid and lymphoid cells were Epstein-Barr encoding region (EBER)-positive; κ-positive cells were significantly more prevalent than λ-positive cells, suggesting light-chain restriction. Postoperatively, parenteral antibiotics were administered for four weeks. The patient has been free of recurrence for two years since the surgery. No association between neurosyphilis and EBV-positive lymphoplasmacytic proliferation has ever been reported. Mass formation in early-stage neurosyphilis is an exceptionally rare event. The present case indicates that in syphilis patients, lymphoproliferative disorders that lead to mass formation may be caused by concomitant EBV reactivation. Furthermore, when treating patients with mass lesions of the central nervous system, it is important to check their medical history and perform laboratory screening for infectious diseases to avoid overlooking syphilis infections.

Intravascular large B-cell lymphoma can induce central nervous system manifestations, including strokes, due to small-vessel occlusion caused by lymphoma cells. However, involvement in large-sized vessels is rare. Here, we present an unusual autopsy case of an 88-year-old man showing a rapid transition from multiple strokes due to small vessel occlusion, typical of intravascular lymphoma, to progressive embolic strokes caused by the occlusion of major cerebral arteries. Magnetic resonance angiography demonstrated the major cerebral arteries associated with those multiple progressive strokes, including the right posterior cerebral artery, left anterior cerebral artery, and right middle cerebral artery, but the detectability was poor. A random skin biopsy at the abdomen confirmed the diagnosis of intravascular large B-cell lymphoma. The patient died 106 days after hospitalization despite intensive treatment. An autopsy revealed broad liquefactive necrosis in the area governed by the major cerebral arteries and multiple small infarctions caused by intravascular lymphoma cells in the small-sized vessels. In addition, the major cerebral arteries showed multiple thromboembolism with partial organization and clusters of intravascular lymphoma cells. Notably, those cells were shown aggregated and attached along the vascular wall of the basilar artery, which might have caused focal hypercoagulation in the near vessels. This aggregation might have disseminated widely in the other major cerebral arteries. Moreover, the cluster of intravascular lymphoma cells in the basilar artery was positive for tumor necrosis factor α, and similar histopathology findings were observed in the splenic veins. However, the pathogenesis of this rare phenomenon involving these cells remains unknown. From a clinical perspective, we should consider the possibility that intravascular lymphoma cells may provoke similar progressive embolic strokes.

Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.

Most meningiomas, which are frequent central nervous system tumors, are classified as World Health Organization (WHO) grade 1 because of their slow-growing nature. However, the recurrence rate varies and is difficult to predict using conventional histopathological diagnoses. Leucine-rich α-2 glycoprotein 1 (LRG1) is involved in cell signal transduction, cell adhesion, and DNA repair and is a predictive biomarker in different malignant tumors; however, such a relationship has not been reported in meningiomas. We examined tissue microarrays of histological samples from 117 patients with grade 1 and 2 meningiomas and assessed their clinical and pathological features, including expression of LRG1 protein. LRG1-high meningiomas showed an increased number of vessels with CD3-positive cell infiltration (P = 0.0328) as well as higher CD105-positive vessels (P = 0.0084), as compared to LRG1-low cases. They also demonstrated better progression-free survival (hazard ratio [HR] 0.11, 95% confidence interval [CI] 0.016-0.841) compared to LRG1-low patients (P = 0.033). Moreover, multivariate analysis indicated that high LRG1 expression was an independent prognostic factor (HR, 0.13; 95% CI, 0.018-0.991; P = 0.049). LRG1 immunohistochemistry may be a convenient tool for estimating the prognosis of meningiomas in routine practice. Further studies are required to elucidate the key role of LRG1 in meningioma progression.

We present a comprehensive characterization of clinical, neuropathological, and multisystem features of a man with genetically confirmed McLeod neuroacanthocytosis syndrome, including video and autopsy findings. A 61-year-old man presented with a movement disorder and behavioral change. Examination showed dystonic choreiform movements in all four limbs, reduced deep-tendon reflexes, and wide-based gait. He had oromandibular dyskinesia causing severe dysphagia. Elevated serum creatinine kinase (CK) was first noted in his thirties, but investigations, including muscle biopsy at that time, were inconclusive. Brain magnetic resonance imaging showed white matter volume loss, atrophic basal ganglia, and chronic small vessel ischemia. Despite raised CK, electromyography did not show myopathic changes. Exome gene panel testing was negative, but targeted genetic analysis revealed a hemizygous pathogenic variant in the XK gene c.895C > T p.(Gln299Ter), consistent with a diagnosis of McLeod syndrome. The patient died of sepsis, and autopsy showed astrocytic gliosis and atrophy of the basal ganglia, diffuse iron deposition in the putamen, and mild Alzheimer's pathology. Muscle pathology was indicative of mild chronic neurogenic atrophy without overt myopathic features. He had non-specific cardiomyopathy and splenomegaly. McLeod syndrome is an ultra-rare neurodegenerative disorder caused by X-linked recessive mutations in the XK gene. Diagnosis has management implications since patients are at risk of severe transfusion reactions and cardiac complications. When a clinical diagnosis is suspected, candidate genes should be interrogated rather than solely relying on exome panels.

Ependymomas (EPN) are central nervous system neoplasms that exhibit an ependymal phenotype. In particular, supratentorial EPN (ST-EPN) must be differentiated from more aggressive entities such as glioblastoma, IDH-wildtype. This task is frequently addressed with the use of immunohistochemistry coupled with clinical presentation and morphological features. Here we describe the case of a young adult presenting with migraine-like symptoms and a temporoinsular-based expansile mass that was first diagnosed as a GBM, mostly based on strong and diffuse oligodendrocyte transcription factor 2 (OLIG2) expression. Molecular characterization revealed a ZFTA::RELA fusion, supporting the diagnosis of ST-EPN, ZFTA fusion-positive. OLIG2 expression is rarely reported in tumors other than GBM and oligodendrocyte-lineage committed neoplasms. The patient was treated with radiotherapy and temozolomide after surgery and was alive and well at follow-up. This report illustrates the need to assess immunostains within a broader clinical, morphological and molecular context to avoid premature exclusion of important differential diagnoses.

Compared with those involving the central nervous system, lymphomas involving the peripheral nervous system, namely neurolymphomatosis, are extremely rare. Neurolymphomatosis is classified as primary or secondary; the former is much rarer than the latter. Herein, we present an autopsied case of primary cauda equina lymphoma (PCEL), a type of primary neurolymphomatosis, with a literature review of autopsied cases of PCEL as well as primary neurolymphomatosis other than PCEL (non-PCEL primary neurolymphomatosis). A 70-year-old woman presented with difficulty walking, followed by paraplegia and then bladder and bowel disturbance. On magnetic resonance imaging, the cauda equina was diffusely enlarged and enhanced with gadolinium. The brainstem and cerebellum were also enhanced with gadolinium along their surface. The differential diagnosis of the patient included meningeal tumors (other than lymphomas), lymphomas, or sarcoidosis. The biopsy of the cauda equina was planned for a definite diagnosis, but because the patient deteriorated so rapidly, it was not performed. Eventually, she was affected by cranial nerve palsies. With the definite diagnosis being undetermined, the patient died approximately 1.5 years after the onset of disesase. At autopsy, the cauda equina was replaced by a bulky mass composed of atypical B-lymphoid cells, consistent with diffuse large B-cell lymphoma (DLBCL). The spinal cord was heavily infiltrated, as were the spinal/cranial nerves and subarachnoid space. There was metastasis in the left adrenal. The patient was finally diagnosed postmortem as PCEL with a DLBCL phenotype. To date, there have been a limited number of autopsied cases of PCEL and non-PCEL primary neurolymphomatosis (nine cases in all, including ours). The diagnosis is, without exception, B-cell lymphoma including DLBCL, and the histology features central nervous system parenchymal infiltration, nerve root involvement, and subarachnoid dissemination (lymphomatous meningitis). Metastases are not uncommon. All clinicians and pathologists should be aware of lymphomas primarily involving the peripheral nervous system.

Neuropil-like islands (NIs) are a histologic hallmark of glioneuronal tumors with neuropil-like islands (GTNIs), but GTNIs are presently not considered a homogeneous entity. The essence of GTNI is likely its glial component, and NIs are now considered aberrant neuronal differentiation or metaplasia. The case we report herein is a 41-year-old woman who was synchronously affected by two brain tumors: one was a glioblastoma (glioblastoma multiforme, GBM), of isocitrate dehydrogenase (IDH)-wild type, with NIs in the left parietal lobe, and the other was histologically a composite gangliocytoma (GC)/anaplastic ganglioglioma (GG) with NIs in the right medial temporal lobe. While both tumors were genetically wild type for IDH, histone H3, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), the former tumor, but not the latter, was mutated for telomerase reverse transcriptase promoter gene (TERT). A recent systematic study using DNA methylation profiling and next-generation sequencing showed that anaplastic GG separate into other WHO tumor types, including IDH-wild-type GBM. It suggested a diagnostic scheme where an anaplastic GG is likely an IDH-wild-type GBM if it is a BRAF wild type, IDH wild type, and TERT promoter mutant tumor. The likely scenario in this patient is that the GBM results from the progression of GC/anaplastic GG due to the superimposed TERT promoter mutation and the propagation of newly generated GBM cells in the contralateral hemisphere. A systematic analysis using DNA methylation profiling and next-generation sequencing was not available in this study, but the common presence of NIs histologically noted in the two tumors could support this scenario. Although a sufficient volume of molecular and genetic testing is sine qua non for the accurate understanding of brain tumors, the importance of histologic observation cannot be overemphasized.