Brain Tumor Pathology最新文献

The coexistence of three lesions in the sellar region is exceedingly rare. Only two cases with three histopathologically distinct lesions have been reported. However, here, we present a unique case of a 54-year-old female with pituitary adenoma (PA), xanthogranulomatous hypophysitis (XGH), and a Rathke cleft cyst (RCC). Clinically, the patient manifested symptoms of mass compression, such as moderate-intensity headaches and progressive visual acuity decrease. Relevant endocrinological evaluation revealed elevated free thyroxine levels without clinical manifestations. MRI revealed a suprasellar mass compatible with a macroadenoma. The patient underwent transsphenoidal endoscopic resection, resulting in a non-functional macroadenoma with associated XGH due to the rupture of RCC. Furthermore, in this article, we analyze the possible mechanisms involved in the pathogenesis of these lesions, emphasizing the type of spectrum to which they belong and the manifestations present.

Craniopharyngiomas (CPs) are rare benign brain tumors that are classified as WHO grade I, with two subtypes: adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP). ACP is caused by somatic mutations in exon 3 of the CTNNB1 gene activating the Wnt signaling pathway. PCP is associated with somatic BRAF p.V600E mutations activating the MAPK signaling pathway. Understanding their molecular differences is crucial for diagnosis and treatment. This study aimed to analyze common somatic alterations in ACP and PCP using bulk transcriptome sequencing and in situ spatial transcriptomics. RNA sequencing and high-resolution spatial profiling were used to detect mutations and examine gene expression differences among ACP, PCP, and healthy pituitary tissue. Whole transcriptome sequencing was performed on 24 tumor samples, with healthy pituitary data from the GTEx portal. Bioinformatics analysis utilized the CTAT mutation pipeline, with Sanger sequencing for validation. Results confirmed BRAF p.V600E mutations in all PCP samples and CTNNB1 mutations in all ACP samples. Differential gene expression analysis highlighted distinct molecular profiles and reinforced the involvement of Wnt and MAPK signaling. Spatial profiling identified 41 differentially expressed genes between ACP and PCP. This study provides critical insights into CP biology, supporting improved diagnostics and potential therapeutic strategies.

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.

A limited number of cases involving non-midline lesions have been documented in diffuse midline glioma (DMG), H3K27-altered, for which a definitive classification has yet to be developed. Additionally, no studies have investigated the temporal evolution of imaging features in diffuse non-midline gliomas. We herein report a case of DMG, H3K27-altered, initially presenting with a gliomatosis cerebri-like appearance, cystic lesions in the right frontal lobe, and progression toward the brainstem. Histopathological analysis and comprehensive genomic profiling indicated glioblastoma (GBM) or DMG, H3K27-altered. The patient was diagnosed with GBM because of imaging characteristics atypical for DMG; however, 9 months after the initial diagnosis, a pontine glioma emerged. This case indicates that DMG, H3K27-altered, may exhibit atypical characteristics, including non-midline cystic lesions, that can subsequently progress to pontine gliomas. Considering the limited therapeutic options available for this malignancy, the early recognition of such atypical presentations is crucial for achieving a timely and accurate diagnosis of DMG, H3K27-altered.

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.

Primary papillary epithelial tumor of the sella (PPETS) is a rare sellar neoplasm characterized by distinctive papillary architecture and thyroid transcription factor 1 (TTF-1) expression. DNA methylation profiling suggests its classification within the posterior pituitary tumor category. Here, we report a case of PPETS in a 37 year-old female presenting with amenorrhea, featuring unique morphological and immunohistochemical characteristics. The tumor exhibited atypical reversed nuclear polarity and, notably, demonstrated positive expression of paired box 8 (PAX-8) and synaptophysin-findings not previously reported in PPETS. Following comprehensive evaluation, including DNA methylation analysis and exclusion of metastatic disease, the tumor was classified as a posterior pituitary tumor, confirming the diagnosis of PPETS. This case expands the known morphological and immunohistochemical spectrum of PPETS, highlighting the importance of careful differential diagnosis from pituitary adenomas and metastatic carcinomas. Further investigation is warranted to fully characterize the morphological variants and immunophenotypic diversity of this rare tumor type.