Clinical Neuropathology最新文献

Posterior fossa ependymomas may be classified based on H3 p.K28Me3 (also called as H3K27Me3 or K27Me3) expression status, with group A characterized by loss of K27Me3 expression. We present a rare case of posterior fossa ependymoma with H3K27M mutation, typically associated with diffuse midline gliomas. A 5-year-old child presented with headache and vomiting. Magnetic resonance imaging (MRI) revealed a 4^th ventricular space-occupying lesion extending through the bilateral foramina of Luschka, radiologically consistent with ependymoma. Following maximal surgical resection and radiotherapy (60 Gy), the patient experienced recurrence after 1 year. Histopathological examination showed a moderately to highly cellular tumor with perivascular pseudorosettes and brisk mitotic activity. Immunohistochemistry demonstrated diffuse GFAP positivity, OLIG2 negativity, and characteristic dot-like EMA positivity. Notably, the tumor showed loss of K27Me3 expression and strong diffuse nuclear expression of H3K27M and EZH2. While H3K27M mutations are hallmark features of diffuse midline gliomas, rare cases of posterior fossa ependymomas harboring these mutations have been reported. Recent studies suggest molecular similarities between diffuse midline gliomas and posterior fossa ependymomas expressing H3K27M and EZHIP, potentially reflecting shared hindbrain developmental programs in their biological origins.

Oligodendrogliomas (ODG) account for ~ 5 - 7% of neuroepithelial tumors. Since the 2016 World Health Organization classification, ODG have been defined by IDH mutation and 1p/19q co-deletion, a genetic profile typically linked with classic oligodendroglial morphology and better survival compared with astrocytic gliomas. Although this genotype is considered a favorable prognostic marker, a subset of ODGs shows early recurrence and aggressive behavior, highlighting the need for additional prognostic indicators. Capicua (CIC), located on chromosome 19q13.2, is a transcriptional repressor downstream of receptor tyrosine kinase signaling. Loss of CIC function increases neural stem cell proliferation, promotes oligodendrocyte progenitor specification, and activates proliferative pathways. Somatic CIC alterations have been reported in up to 70% of ODGs, nearly always in the setting of 1p/19q co-deletion. In this study, we investigated the prognostic value of CIC immunohistochemical (IHC) expression in a homogeneous cohort of IDH-mutant, 1p/19q-codeleted ODGs. Our results demonstrated that complete CIC expression loss and 19q polysomy greater than 22.5%, together with mitotic counts ≥ 6 per 10 high-power fields, were significantly associated with early disease recurrence. Although the absence of molecular confirmation of CIC alterations limits interpretation, the findings suggest that CIC IHC can serve as a surrogate marker to identify patients who may benefit from additional molecular analysis. Conclusion: CIC loss, 19q polysomy, and elevated mitotic activity may function as valuable prognostic indicators in ODGs. These features could improve risk stratification and guide personalized therapeutic strategies in otherwise favorable cases.
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Lissencephaly is a migrational disorder that results in abnormal gyration and cortical lamination. Type 1 lissencephaly is characterized by absent or reduced number of gyri giving the brain a smooth appearance, while type 2 lissencephaly (cobblestone lissencephaly) is described as over-migration of neurons or neuronal precursors beyond the glia-pial limitans giving rise to a cobblestone appearance of the cerebral hemispheres. Both types of lissencephaly are typically thought of as congenital anomalies secondary to genetic defects while cases of lissencephaly due to acquired injury is rare. The few examples that do exist in the literature mainly describe changes in keeping with type 1 lissencephaly. We present here an unusual case of a fetus with brain structural changes consistent with cobblestone lissencephaly with concurrent CMV (cytomegalovirus) meningoencephalitis. Our patient is a 23-week-old stillborn fetus of a 28-year-old G1P0 mother who underwent elective termination of this pregnancy after ultrasound and fetal MRI revealed multiple brain anomalies. Post-mortem examination of the fetus revealed evidence of CMV infection involving multiple systemic organs and the brain. Evidence of malformative lesions included cobblestone appearance of the cerebral hemispheres, enlarged lateral ventricles, and focal polymicrogyria. Normal diploid complement for chromosomes 13, 18, and 21 was revealed by rapid aneuploidy testing. While single case reports of CMV with features in keeping with type 1 lissencephaly have been described in the literature, to the authors' knowledge this is the first example of cobblestone lissencephaly observed in the context of congenital CMV infection.

The aberrant GGC repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene causes neuronal intranuclear inclusion disease (NIID), a progressive neurodegenerative disorder. The clinical features of NIID are highly variable and include cognitive dysfunction, peripheral neuropathy, and episodic neurogenic symptoms. The pathogenesis of episodic symptoms in NIIDs remains unknown, and histopathological studies are limited. Here, we report an autopsy case of NIID in a 32-year-old Japanese female who developed severe episodic symptoms, including hemiplegic migraine, seizures, and impaired consciousness. Her major episodic symptoms appeared at the age of 16 years and were accompanied by alternating brain edema. She developed severe episodic symptoms with right brain edema at the age of 31. She became bedridden due to irreversible brain lesions and died 1 year later from a catheter-related bloodstream infection. Neuropathological analyses revealed numerous neuronal intranuclear inclusions and white matter lesions. In addition, bizarre astrocytes with eosinophilic cytoplasmic or intranuclear inclusions were observed. GFAP immunoreactivity in the bizarre astrocytes was diminished, AQP4 showed a disorganized distribution. The histological changes observed in this case suggest an association between non-neuronal cellular disturbances and episodic neurogenic symptoms in NIIDs.

Brain tumors, including primary gliomas and metastatic brain cancers, create a complex and dynamic tumor microenvironment (TME) that significantly influences tumor progression, therapy resistance, and patient outcomes. This review explores the intricate components of the brain tumor microenvironment, including cancer cells, stromal cells, immune cells, extracellular matrix, and signaling molecules. We highlight the unique characteristics of the brain TME, such as the blood-brain barrier's role in modulating immune cell infiltration and the impact of neuroinflammation. Key interactions within the TME that promote tumor growth and resistance to conventional therapies are examined, emphasizing the crosstalk between tumor cells and the surrounding stromal and immune components. Furthermore, we discuss emerging therapeutic strategies targeting the TME, including immunotherapies, anti-angiogenic agents, and approaches to modulate the extracellular matrix. Understanding the complexities of the brain TME is crucial for developing more effective, targeted treatments and improving clinical outcomes for patients with brain tumors.

Multiple system atrophy (MSA) is a major neurodegenerative disorder characterized by phosphorylated α-synuclein-positive oligodendroglial cytoplasmic inclusions. The presence of phosphorylated τ-positive granular glia (pTGrG) in the cerebral white matter and putamen has recently been reported, and it has been suggested that pTGrG pathology may be a common pathological feature of MSA. However, its spreading pattern and relationship with clinical features remain unclear. We examined the spreading pattern of pTGrG pathology and the clinical factors associated with it. The middle frontal, precentral, and middle temporal gyri, as well as the inferior parietal lobule and occipital lobe were histopathologically examined in 14 patients with clinicopathologically confirmed MSA. A distinct spreading pattern of pTGrG pathology was revealed, initially detected in the precentral white matter and subsequently extending to the parietal, frontotemporal, and occipital white matter. The severity of pTGrG pathology significantly correlated with disease duration and tracheostomy duration, but was not associated with any clinical MSA subtype or with dementia. The findings suggest that pTGrG is a common pathological feature of MSA with a unique spreading pattern, and with correlations to duration of disease and tracheostomy, thereby highlighting its potential as a biomarker for disease progression.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive embryonal tumor that most commonly affects young children, with primary spinal involvement being exceedingly rare in adults. We highlight a rare case of a 26-year-old female who presented with paraparesis and was found to have a well-defined, homogeneously enhanced intradural extramedullary lesion at the D9 - D10 level on magnetic resonance imaging (MRI), initially suggestive of a benign nerve sheath tumor. Surgical excision followed by histopathological evaluation revealed undifferentiated tumor cells arranged in nests and cords within a hyalinized stroma. Immunohistochemistry demonstrated strong glial fibrillary acidic protein (GFAP) and focal epithelial membrane antigen (EMA) positivity, CD99 positivity, and complete loss of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily B, member 1 (SMARCB1) integrase interactor 1 (INI1) expression in tumor cells, confirming the diagnosis of AT/RT. The lesion lacked hemorrhage or necrosis, adding to its benign radiological mimicry. This case highlights the diagnostic pitfalls in adult spinal AT/RT, especially when radiological findings overlap with benign tumor and histological features overlap with other small round cell tumors such as Ewing sarcoma, metastatic carcinoma, or CIC-rearranged sarcomas. The distinct nested and cord-like architecture observed in this case broadens the familiar histopathological spectrum of AT/RT. The patient received postoperative radiotherapy, and emerging data suggest potential benefit from multimodal approaches including surgery, radiotherapy, chemotherapy, and targeted therapies such as mechanistic target of rapamycin (mTOR), enhancer of zeste homolog 2 (EZH2), and cyclin dependent kinase 4/6 (CDK4/6) inhibitors. This report stresses the need to consider AT/RT in the differential diagnosis of adult intradural extramedullary spinal lesions and reinforces the diagnostic utility of SMARCB1 (INI1) immunohistochemistry. Molecular subtyping may further guide therapeutic decisions and improve prognostication in this rare and challenging tumor.

Background: Surgical pathology specimens from patients with hypertrophic pachymeningitis are infrequently encountered. After excluding infectious and neoplastic causes, autoimmune conditions should be considered, especially neurosarcoidosis, rheumatoid arthritis, granulomatosis with polyangiitis (GPA), and IgG4-related disease (IgG4-RD) before the case is designated "idiopathic". However, even if histological findings strongly favor one of these conditions, clinical and serological correlation is mandatory. Further complicating the issue is evolving thinking that suggests there may be overlap between GPA and IgG4-RD.

Materials and methods: We report clinical, histological, serological, and follow-up data on 2 seronegative cases of pachymeningitis with histological features identical to GPA, providing comparison with a seropositive pachymeningitis case from the author's files.

Results: Two men, ages 73 and 75 years, presented with blurred vision and focal seizures, respectively; neuroimaging revealed dural thickening. Surgical resection specimens of hypertrophic dura proved histologically identical to GPA, with extensive non-storiform fibrosis, dense lymphoplasmacytic and histiocytic infiltrates, multinucleated giant cells, and dirty necrosis. Tumor, rheumatoid nodules with palisading histiocytes, and small compact granulomas were absent; stains for microorganisms were negative. Case 2 additionally showed medium-sized vessel vasculitis with fragmented elastic lamina, as seen in GPA. IgG4 cells were increased in each (170/HPF, IgG4 : IgG ratio = 26%, 65/HPF, IgG4 : IgG ratio = 10 - 15%), respectively.

Conclusion: Hypertrophic pachymeningitis cases are challenging. Pathologists should offer likely differential diagnoses based on histological features, but refrain from rendering a definitive diagnosis pending clinical-serological correlation. Whether seronegative examples represent a GPA variant, a new disease, or, in the case of high IgG4+ cells, two coincident disorders is unknown.