Neuropathology最新文献

Solitary fibrous tumors (SFTs) of the central nervous system (CNS) are rare mesenchymal tumors characterized by a fusion of the NGFI-A-binding protein 2 (NAB2) gene and the signal transducer and activator of transcription 6 (STAT6) gene, immunohistochemically resulting in nuclear expression of STAT6 - an immunohistochemical hallmark essential for diagnosis, as outlined in the fifth edition of the World Health Organization Classification of Tumors. Dedifferentiation, where low-grade tumors transform into high-grade forms, has been observed in SFTs, with documented cases involving sarcomatous or rarely epithelial transformations. We report the first case of a CNS SFT exhibiting "transdedifferentiation" into epithelioid neuroendocrine differentiation. A 36-year-old woman presented with worsening frontal headaches and vision deterioration due to an 8.2-cm frontal tumor with skull erosion. Histologically, the tumor consisted of predominantly high-grade undifferentiated epithelioid round cells that expressed STAT6, along with multifocal synaptophysin and chromogranin A positivity, and occasional cytokeratin and claudin-4 reactivity, resembling large cell neuroendocrine carcinoma. A minor bland spindle cell component with STAT 6 immunoreactivity was also noted. This case highlights the rare occurrence of neuroendocrine "transdedifferentiation" in CNS SFTs. This case highlights the importance of recognizing dedifferentiation in CSF SFTs, which often correlates with aggressive tumor behavior and poor prognosis. Given the rarity of neuroendocrine "transdedifferentiation," this case adds valuable insight into the diverse dedifferentiation patterns seen in CNS SFTs, emphasizing the need for accurate diagnosis to guide appropriate treatment strategies.

Rosette-forming glioneuronal tumors (RGNTs) with FGFR1 tyrosine kinase domain internal tandem duplication (FGFR1 ITD) is exceedingly rare, with only a few cases reported in the literature. Hereby we present a case of a tumor with RGNT morphology occurring in area of septum pellucidum of 43-year-old male. The tumor showed FGFR1 ITD, no PIK3CA, PIK3R1 or NF1 alterations and inconclusive methylation profile with match for class of "low-grade glial/glioneuronal/neuroepithelial tumors". No areas characteristic of dysembryoplastic neuroepithelial tumor were identified. A brief review of literature on discrepancies between morphological diagnosis of RGNT and molecular profile of the entity is provided.

We report a patient who presented clinically with progressive supranuclear palsy (PSP) but was pathologically diagnosed as having primary lateral sclerosis (PLS) with magnetic resonance imaging (MRI) with a quantitative susceptibility mapping (QSM) protocol. A 70-year-old man was clinically diagnosed with PSP due to early falls and unresponsiveness to levodopa therapy. Postmortem pathological examination revealed mild loss of Betz cells, gliosis, and transactive response DNA binding protein of 43 kDa (TDP-43)-positive inclusions in the motor cortex, leading to the pathological diagnosis of PLS. To explore methods for differentiating PLS from PSP, ante-mortem QSM images were visually and quantitatively assessed for abnormal increases in magnetic susceptibility in the motor cortex. Prussian blue and Luxol fast blue combined with periodic acid-Schiff staining were also performed to understand the source of the susceptibility increases. QSM showed clear hyperintense signals in the motor cortex. Magnetic susceptibility in the motor cortex was higher in the PLS patient (Z = 4.7, p < 0.001) compared to normal controls and pathologically diagnosed PSP patients. Pathological examination of the region showed intracortical myelin loss, as well as iron deposition. Underlying pathological processes for the increased magnetic susceptibility include not only iron deposition but also intracortical myelin. Our case suggests that QSM is a potential tool to differentiate PLS from PSP, providing insights for accurate diagnosis and enhancing clinical decision-making.

Subependymal giant cell astrocytoma (SEGA) is a rare, low-grade glioma typically associated with tuberous sclerosis (TS) and mutations in the TSC1 or TSC2 genes. It is characterized by an intraventricular location, an expansive growth pattern, and the expression of glial and neural markers. TTF-1 expression is considered a sensitive marker of SEGA, likely reflecting its origin from progenitor cells in the caudothalamic groove. We report a case of SEGA with unusual immunohistochemical and molecular features in a 20-year-old man with no signs or family history of TS. The tumor was located in the anterior horn of the right ventricle and obstructed the foramen of Monro. Histologically, it exhibited an expansive growth pattern and was composed of cells with ovoid nuclei and abundant eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for GFAP and S-100 protein, weakly positive for SOX2, focally positive for synaptophysin, and negative for TTF-1, neurofilament protein, NeuN, EMA, chromogranin, and BCOR. Scattered OLIG2-positive neoplastic cells were also observed. Molecular analysis revealed no pathogenic mutations or copy number variations in the analyzed 174 genes, including TSC1/2, except for a variant of unknown significance in BAP1. The histopathological features and immunohistochemical profile suggested SEGA, despite the absence of TTF-1 expression and TSC1/2 mutations. The diagnosis was confirmed by DNA methylation profiling, which assigned the tumor to the methylation class "subependymal giant cell astrocytoma with TSC1/TSC2 alterations" with a calibrated score of 0.95. This case highlights the potential diagnostic pitfall of SEGA lacking TTF-1 expression and emphasizes the importance of considering this entity in the differential diagnosis of intraventricular tumors, even in the absence of TS and characteristic molecular alterations. The existence of TTF-1 negative SEGAs reveals that these tumors might also derive from TTF-1 negative cells in the subpendymal region.

Ovarian mature teratomas frequently contain central nervous system (CNS) tissue that often exhibits a variety of neuropathologic alterations. The author systematically examined the changes seen in CNS tissue from a series of 251 cases of resected ovarian mature teratomas. A total of 101 (40.2%) samples contained CNS tissue in varying amounts. The principal pathologic findings in the CNS tissue from ovarian mature teratomas were as follows: (i) CNS tissue tended to form a relatively thin, undulating, plate-like structure that comprised the walls or septa of cystic tumors; (ii) most neurons were small or medium sized, and no CD34-positive "ramifying cells" were observed; (iii) cytoplasmic processes of some astrocytes closely surrounded the walls of capillaries, suggesting formation of a blood-brain barrier; (iv) some ependymal cells exhibited a columnar shape and showed a pseudostratified arrangement, and these cells extended thick basal cytoplasmic processes into the neuropil; (v) a few choroid plexus epithelial cells showed melanin deposition, tubular transformation, or oncocytic changes; (vi) hamartoma-like hyperplasia of arachnoid cells was noted beneath skin tissue; (vii) some CNS tissue showed formation of cerebral cortical structures exhibiting "gyration" with incompletely layered structures, and disruption of the glia limitans with spillage of cortical tissue into the "subarachnoid" space was also observed; and (viii) in the well-formed cerebellar cortex, dendrites of Purkinje cells exhibited varied dysmorphic changes. These neuropathologic observations should lead to a deeper understanding of the pathogenesis of various lesions in the brain.

The aim of this paper is to analyze the pathophysiological mechanisms acting in very early classic Guillain-Barré syndrome (GBS) (≤4 days of symptomatic onset). In this inaugural period, both in GBS and its animal model, experimental autoimmune neuritis, the outstanding pathological feature is inflammatory edema predominating in proximal nerve trunks, particularly spinal nerves, and possibly in preterminal nerve segments. Nerve trunks external to the subarachnoid angle possess epi- perineurium that is relatively inelastic and of low compliance. Here such edema can increase endoneurial fluid pressure that, when sufficiently critical, may stretch the perineurium and constrict transperineurial microcirculation, compromising blood flow and producing the potential for ischemic nerve injury, whose consequence is rapid partial or complete loss of nerve excitability. These histopathological features correlate well with electrophysiological and imaging findings reported in early GBS stages. Spinal nerve edema and ischemia help to understand the pattern of Wallerian-like degeneration observed in the axonal form of GBS, predominating in motor spinal roots at their exit from the dura matter (spinal nerves) with centrifugal distribution in more distant motor nerve trunks, and centripetal extension to the distal portion of intrathecal roots. The similarity of initial pathogenic mechanisms between demyelinating and axonal forms of GBS explains why an early increase of serum biomarkers of axonal damage is detected in both forms. In conclusion, knowledge of the microscopic anatomy of the peripheral nervous system is an essential step for a reliable understanding of pathophysiological mechanisms operating in the early phase of any classic GBS subtype.

Primary intracranial sarcomas constitute a rare group of tumors, with the most common types described in the literature being chondrosarcoma and fibrosarcoma. Dedifferentiated liposarcoma (DDLS) is a high-grade sarcoma that sometimes metastasizes to the brain. However, a primary intracranial DDLS is exceedingly rare. A 45-year-old patient from the Middle East came to India for treatment. His magnetic resonance imaging (MRI) scans revealed a space-occupying lesion at the level of the lateral ventricle T2/fluid attenuated inversion recovery hyperintensity with peripheral edema. A T1 perfusion map showed high relative cerebral blood volume values in the peripheral part, suggesting a high-grade neoplasm. Gross total resection was performed, and histopathology showed a high-grade tumor composed of sheets of pleomorphic lipoblasts and epithelioid tumor cells arranged in nests and cords. Immunohistochemistry showed diffuse immunopositivity for MDM2, CDK4, and p16, while GFAP and OLIG2 were negative. Fluorescence in situ hybridization showed MDM2 amplification. Final diagnosis of DDLS was rendered. The patient had no systemic lesions elsewhere on positron emission tomography computed tomography scan.

Clinical diagnosis of progressive supranuclear palsy (PSP) is difficult due to various phenotypes. Neuropathologically, PSP is defined by neuronal loss in the basal ganglia and brainstem with widespread occurrence of neurofibrillary tangles (NFTs) and accumulation of phosphorylated tau protein in neurons and glial cells in the brain. We previously identified the point mutation p.Pro3866Ala in the Bassoon (BSN) gene in a Japanese family with PSP-like syndrome. We newly detected BSN mutations in two autopsied PSP cases carrying p.Thr2542Met and p.Glu2759Gly, respectively. The case with p.Thr2542Met mutation showed neurological symptoms including behavioral abnormalities, cognitive dysfunction, and parkinsonism. Brain magnetic resonance imaging (MRI) showed atrophy of the midbrain tegmentum and hippocampus. Pathologically, moderate to severe loss of neurons with gliosis was also found in the substantia nigra, and there was an almost complete loss of neurons with gliosis in the transitional zone of the cornu ammonis (CA) 1 region to the subiculum. NFTs were observed in the globus pallidus, subthalamic nucleus, substantia nigra, and CA1. 4R tau-dominant tauopathy was detected. The case with p.Glu2759Gly mutation showed neurological symptoms, including right-dominant motor impairment, right limping gait, postural instability, and cognitive dysfunction. Brain MRI showed mild atrophy of the midbrain tegmentum and left-dominant parietal lobe atrophy. Pathologically, NFTs were detected in the globus pallidus, subthalamic nucleus, substantia nigra, thalamus, putamen, and brainstem tegmentum. Most neurons were immunopositive for four-repeat tau, whereas only a few of them harbored three-repeat tau-positive NFTs in the hippocampus. We showed the results of a pathological study of PSP cases with BSN mutations; these were two new cases. The clinical phenotypes were similar to the first case in the point of neurological symptoms. Accumulation of four-repeat tau was dominant. Further autopsies of BSN mutation cases and further elucidation of the molecular biological mechanism are desirable.

Germ cell tumors (GCTs) are categorized as gonadal or extra-gonadal, based on the origin. Extra-gonadal GCTs predominantly manifest within the central nervous system (CNS), mediastinum, retroperitoneum, and sacrococcygeal region. These malignancies are most frequently diagnosed in the pediatric, adolescent, and young adult demographics. Incidences of GCT within the nasal cavity are notably scarce, with only six cases documented. This report details the case of a 70-year-old man who presented with a left nasal mass ultimately diagnosed as immature teratoma. A remarkable aspect of this case was the detection of SMARCA4 (BRG1) loss through immunohistochemical analysis. In addition, methylation profiling aligned this case with CNS GCTs, specifically those classified as non-germinomatous GCTs. This molecular characterization informed a tailored therapeutic strategy incorporating carboplatin and etoposide, alongside localized irradiation. This individualized treatment regimen achieved favorable outcomes, with the patient remaining recurrence free for over three years. This highlights the need for precise therapeutic approaches in the management of extragonadal GCTs, particularly those arising in atypical anatomical locations. The present case accentuates the significance of thorough diagnostic evaluations and customized treatment plans for rare GCT presentations. Further empirical and clinical investigations are warranted to enhance our understanding of and refine therapeutic protocols for such exceptional cases.

Here, we report a case of antineutrophil cytoplasmic antibody (ANCA)-associated central nervous system (CNS) vasculitis that mimicked a brain tumor. The patient presented with progressive right upper arm weakness. Brain magnetic resonance imaging (MRI) revealed large tumor-like lesions in the left frontal and parietal lobes, with patchy and irregular enhancement with gadolinium and edema. Based on the clinical course and radiological findings, a brain tumor was suspected, and stereotactic brain biopsy was performed. Brain histopathology revealed necrotic tissue and lymphocyte infiltration around small vessels and blood vessel walls. Although the patient's clinical course and pathological findings suggested primary angiitis of CNS (PACNS), double staining for myeloperoxidase (MPO) and CD31 (a neutrophil marker) revealed infiltration of MPO-positive neutrophils in the blood vessel walls. Therefore, we diagnosed the patient with ANCA-associated CNS vasculitis. Because CNS vasculitis, including PACNS, presents nonspecific clinical findings and can depict brain tumor-like MRI findings, CNS vasculitis should be carefully differentiated from brain tumors. Additionally, double staining for MPO and CD31 might be useful for evaluating the pathogenesis of CNS vasculitis.