Clinical Neuropathology最新文献

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.

Objective: The risk of meningioma recurrence depends mainly on the extent of resection and tumor grade. In a series of 196 meningiomas, we investigated the influence of clinical and histopathological criteria and sought to identify simple and reproducible criteria associated with meningioma recurrence.

Materials and methods: Clinical data (age, sex, location), preoperative embolization (POE), presence of peritumoral edema, Simpson grade, histological grade and histopathological parameters (Ki-67 index labeling index (LI), mitotic index, hypercellularity, small cells, prominent nucleoli, sheeting pattern, necrosis, nuclear atypia, microvascular proliferation as well as infiltration of the dura mater, bone and brain), and dura mater were collected. The prognostic value of each parameter for recurrence-free survival (RFS) was assessed using the Kaplan-Meier method and log-rank test. Multivariate analysis was carried out using a Cox regression model on single features identified by univariate analysis.

Results: The Ki-67 LI was the factor most strongly associated with recurrence. In multivariate analysis, independent factors for shorter RFS were male sex, subtotal resection, and a Ki-67 LI > 5%, which was the most significant factor. In addition, a Ki-67 LI > 5% was strongly associated with shorter RFS (p = 9.79e-05) for grade 1 meningiomas in multivariate analysis. Ki-67 LI assessment and POE did not modify the Ki-67 LI evaluation.

Conclusion: Importantly, for grade 1 meningiomas, which are tumors that lack histological criteria for aggressiveness, a Ki-67 > 5% is a predictive factor for recurrence. These data, which are easy to collect and reproduce, could be used in practice to select patients who would benefit from closer clinical follow-up or to identify tumors requiring further molecular analysis at the time of first surgery.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a novel and rare entity commonly described as a systemic disease affecting infants, while isolated systemic involvement including the central nervous system (CNS) have been reported in older children and young adults. We report 2 cases of CNS ALK-positive histiocytosis, with detailed histopathological and radiological information, and provide a review of literature. Two patients, a child and a young adult, presented with extra-axial mass lesion. The radiological differentials considered were meningioma and schwannoma. The histopathological examination of both cases showed sheets of cells resembling histiocytes admixed with scattered Touton-type and foreign body giant cells. These tumors do not have any distinct diagnostic radiological, features and hence histopathological examination is crucial in the diagnosis of these tumors. The cells were immunopositive for CD68, CD163, and ALK. Understanding the histopathological spectrum of ALK-positive histiocytosis is important as targeted therapy (ALK inhibitor therapy) exists and the prognosis is better.

Toxoplasmosis is a common opportunistic infection in immunocompromised patients. Cerebral toxoplasmosis can be the initial manifestation of acquired immunodeficiency syndrome (AIDS). We report a case diagnosed at autopsy as the primary presentation of an undiagnosed human immunodeficiency virus (HIV)-positive patient. Histological examination revealed a prominent rim of periventricular necrosis involving the frontal, temporal, and occipital horns of the lateral ventricle, third and fourth ventricle. The ependymal lining was denuded with numerous encysted bradyzoites and scattered tachyzoites of Toxoplasma dispersed in the necro-inflammatory areas. Hydrocephalus due to cerebral toxoplasmic ventriculitis is very rare in adults. Mortality was significantly higher in cases with ventriculitis as compared to patients with only hydrocephalus due to mass lesions. Choroid plexus involvement in toxoplasmic ventriculitis could indicate a hematogenous spread from reactivation of latent systemic infection rather than reactivation of latent brain lesion. This case report emphasizes the importance of evaluation of HIV status in the presence of complex periventricular enhancement and the importance of a high degree of clinical suspicion for toxoplasmic ventriculitis in HIV patients with hydrocephalus, as an early institution of empirical anti-toxoplasma treatment could play a crucial role in cure.