Brain Tumor Pathology最新文献

Compared to oligodendrogliomas, astrocytomas may have a relatively higher frequency of intracranial remote recurrence, despite generally favorable prognoses. Previous studies identified 8q gain, particularly in the terminal region, as a poor prognostic factor. This study evaluated MYC expression and its relationship with copy number gain at 8q24.21, in relation to recurrence patterns in astrocytomas, with a particular focus on intracranial remote recurrence. A retrospective analysis was conducted on 27 patients treated between 2006 and 2019. MYC expression was assessed by immunohistochemistry (IHC), and copy number status by metaphase comparative genomic hybridization and next-generation sequencing. Recurrence patterns were categorized as local or remote.Among 43 specimens analyzed by IHC, MYC expression was observed in 72%, with higher positivity in recurrent (80%) than initial (61%) specimens, though the difference was not statistically significant (p = 0.30). Copy number analysis showed a significant increase in 8q24.21 copy number in specimens from cases with remote recurrence compared to those with local recurrence (p = 0.033). However, no significant correlation was found between MYC copy number and protein expression (p = 0.055). These findings suggest that MYC is frequently expressed in astrocytomas, but its expression does not significantly reflect 8q gain or recurrence pattern.

Primary pigmented papillary epithelial tumor of the sella (PPPET) is a recently identified tumor entity that commonly originates in the sella. To date, only three cases have been documented. These tumors are characterized by a papillary structure and significant melanin granule deposition. Notably, molecular characterization of PPPET remains unreported in the literature. A 42-year-old male presented with left-sided visual impairment for 2 weeks. Neuroimaging revealed a round sellar hyperdense mass. Histologically, the tumor exhibited minimal nuclear atypia and was characterized by a papillary architecture and obvious intracellular hyperpigmentation. Immunophenotypically, tumor cells showed diffuse positivity for S-100 and Melan-A, partial or focal positivity for synaptophysin and CD56, and negativity for TTF-1, GFAP, EMA, cytokeratins, and pituitary hormones. The Ki-67 proliferation index was low. The whole exome sequencing (WES) analysis revealed multiple potentially pathogenic gene mutations (AGAP3, DDX10, BBX, NFATC4, SLC6A6) in tumor tissues. Large genomic rearrangements (LGRs) involving PRKRA (exon6-8 del) and SKA3 (exon2-8 del) were detected. Genomic instability analysis indicated whole genome doubling (WGD) and aneuploidy in the tumor cells. Copy number variation (CNV) analysis demonstrated extensive copy number abnormalities at the chromosome arm level in tumor tissues. No classical mutations associated with known tumor types of the sella and choroid plexus were detected. PPPET has unique morphologic, immunohistochemical, and molecular genetic characteristics. Our findings suggest that PPPET may be an independent neurooncological entity.

Glioma, a prevalent primary brain tumor, arises from the supporting cells of the central nervous system (CNS) and is categorized into grades I-IV. Despite advancements in therapeutic strategies, including surgery, chemotherapy, radiotherapy, and targeted therapies, glioma remains associated with high mortality and recurrence rates, often leading to poor patient outcomes. The pathogenesis of glioma is influenced by a combination of environmental factors, genetic mutations, and lifestyle choices. Transforming growth factor-beta (TGF-β) signaling plays a pivotal role in glioma progression by regulating cell proliferation, survival, and differentiation. TGF-β activates Small mothers against decapentaplegic 2/3 (Smad2/3) proteins through specific receptors, forming a complex with Smad4 that translocate to the nucleus to modulate gene expression. In addition, TGF-β-activated kinase 1 (TAK1) initiates mitogen-activated protein kinase (MAPK) cascades, further contributing to tumorigenesis. The TGF-β/Smad pathway can be negatively regulated by inhibitory Smad6/7. Elevated expression of TGF-β isoforms (Ι-Ш) is correlated with increased glioma risk. TGF-β promotes tumor growth by sustaining glioma stem cell self-renewal and suppressing antitumor immune responses. Preclinical studies demonstrate that TGF-β signaling inhibitors reduce glioma viability and invasion in animal models, highlighting their potential as promising therapeutic agents for glioma treatment.

Differentiating pseudoprogression (PsP) from recurrence in cases of glioblastoma (GBM) after chemoradiotherapy is challenging, with neuroimaging as the only non-invasive method. In this study, we aimed to identify a blood biomarker for precise disease monitoring and investigated the role of Ataxin-2 (ATXN2). Blood samples (n = 45) from patients with suspected recurrence, including eight with PSP, were analyzed. In addition, tumor tissue samples (n = 22), including those from seven patients who also provided blood samples, were examined. Protein levels were assessed using quantitative proteomics and ELISA. ATXN2 levels were measured via western blotting, and localization was determined through immunohistochemistry and immunocytochemistry. ATXN2 knockdown was performed in glioma cell lines to assess its effects on proliferation, migration, and invasion. Proteomics identified ATXN2 as a potential biomarker. ELISA showed significantly higher serum ATXN2 levels in recurrence than in PsP (p = 0.028). ATXN2 ≥ 11.0 ng/mL and ≥ 8 months post-chemoradiotherapy distinguished recurrence from PsP (AUC = 0.82, sensitivity = 67.6%, specificity = 87.5%). ATXN2 was highly expressed in GBM tissues, localized in neurons and glioma cells, and its knockdown enhanced proliferation, migration, and invasion via ERK phosphorylation. ATXN2, highly expressed in GBM, may serve as a potential blood biomarker for distinguishing PsP from recurrence.

BRCA (BReast CAncer gene)-associated protein 1 (BAP1) is a tumor suppressor protein encoded by the BAP1 gene. BAP1 mutations and the loss of BAP1 expression on immunohistochemistry are poor prognostic factors for meningiomas. These mutations have been previously reported in papillary and rhabdoid meningiomas. However, BAP1-deficient meningiomas with a trabecular architecture are rare, with only one previous report describing two cases. Here, we present the case of an 80-year-old male who experienced two recurrences of meningiomas over a 14-year period. The initial tumor exhibited a mixture of typical meningothelial meningioma and meningioma with trabecular architecture, whereas the second recurrence was almost entirely trabecular. Immunohistochemical analysis revealed a BAP1 deficiency. This case highlights the importance of the trabecular architecture as a histological pattern that may indicate BAP1 loss and poor prognosis. Given the potential for targeted therapies, further research is needed to establish this histological subtype as an independent entity with poor prognosis.

Pituitary neuroendocrine tumors (PitNETs) are generally benign, but a small subset may demonstrate aggressive behavior or undergo malignant transformation. Neuroendocrine carcinoma (NEC), defined as a high-grade, poorly differentiated neuroendocrine neoplasm, is extremely rare in the pituitary, and its existence as a primary entity remains controversial. We report two cases of corticotroph PitNETs in female patients with Cushing disease, in which NEC components emerged several years after radiotherapy. Case 1 presented as an invasive macroadenoma with cavernous sinus invasion, and Case 2 as a 5 mm microadenoma. In both cases, recurrent tumors developed following subsequent radiotherapy. NEC components exhibited marked nuclear pleomorphism, necrosis, elevated Ki-67 indices, diffuse p53 expression, and loss or reduction of ACTH and TPIT expression. In Case 2, faint TPIT expression and discontinuous tumor growth within the sella raised the possibility of a metastatic NEC to the pituitary could not be excluded. These cases highlight the emergence of NEC features in corticotroph PitNETs, most likely as a result of post-radiotherapy transformation. However, due to faint TPIT expression and an unusual tumor distribution in Case 2, the possibility of a primary NEC or metastatic neuroendocrine neoplasm from another organ cannot be definitively excluded.

In the 2021 WHO Central Nervous System tumor classification, the "Glioblastoma, IDH-wildtype" diagnosis changed markedly. In a Japanese cohort, we compared the clinical backgrounds and prognoses of molecular glioblastoma (mGBM) and conventional glioblastoma (histological glioblastoma, hGBM). We included 270 patients with glioblastoma treated at five institutions during 2011-2023. Driver gene analysis was performed using a brain tumor-specific custom gene panel to verify the association between molecular and clinical information. Patients with mGBM had better preoperative KPS, lower Ki-67, and lower removal rates than did those with hGBM. Overall survival was longer in patients with mGBM than in those with hGBM (1207 vs 599 days, p = 0.037). TP53 mutation (hazard ratio: 5.33, 95% confidence interval: 0.26-108.7, p = 0.012) and histological grade 3 (p = 0.051) were poor prognostic factors for mGBM. Patients with mGBM had better preoperative KPS, worse removal rates, lower Ki-67 labeling index, and better overall survival than did those with hGBM. In addition, the histological grade of mGBM is potentially useful for estimating prognosis. In the WHO CNS5 2021, glioblastoma patients remain a heterogeneous population, and prognostic stratification based on the patient's clinical background and molecular information is desirable.

We report a rare case of extracranial metastases of a glioblastoma, IDH-wildtype, in a 77-year-old man who initially presented with a right frontal tumor, and gross total resection and adjuvant chemoradiotherapy were performed. The tumor was histologically comprised of two cellular components: astrocytic and poorly differentiated astrocytic tumor cells, with each strongly and infrequently positive for glial markers. Importantly, both components were positive for Nestin and CD44, indicating stemness and migratory characteristics. Three-and-a-half months after surgery, the patient presented with a subcutaneous tumor of the scalp at the surgical site and dyspnea. Imaging studies revealed tumors in the scalp, multiple intracranial locations, and the lungs, complicating a pneumothorax. He died of respiratory failure approximately 4.5 months after tumor resection. An autopsy revealed extra-axial tumors involving the sub/epidural, scalp, and intrathoracic regions, each consisting of tumor cells resembling those of the poorly differentiated astrocytic component observed in the original right frontal tumor. Genetic and copy number analysis proved that the extra-axial tumors were metastatic lesions originating from the right frontal glioblastoma, as MET and CDK6 amplification and TERT promoter mutation were shared in all tumors. These genomic alterations and stemness might contribute to the rapid development of extracranial glioblastoma metastasis and a worse prognosis.

The ASPSCR1::TFE3 rearrangement has been described in alveolar soft part sarcoma, MiT family translocation renal cell carcinomas as well as perivascular epithelioid cell tumors (PEComas). However, this rearrangement has not been reported in the primary spinal canal. Here, we report a case of an 18-year-old male who had pain in his left lower limb for 2 months. Neuroimaging revealed a lesion in the spinal canal from thoracic 12 to lumbar 1. Histopathological examination showed the tumor consisting of nested architectural pattern with abundant psammomatous calcification. Tumor cells exhibited strong and diffuse positivity for TFE3 and SOX10, patchy positivity for HMB-45 and S100, while other immunomarkers were negatively stained. RNA sequencing confirmed the ASPSCR1::TFE3 gene rearrangement. The Heidelberg DNA methylation classifier classified this case as "Cranial and Paraspinal Nerve Tumor". This case may represent a novel intraspinal neoplasm entity that expands the spectrum of ASPSCR1::TFE3-rearranged neoplasms by unique histopathological features and potential neural differentiation. We named this case as intraspinal ASPSCR1::TFE3 rearranged tumor with SOX10 expression.