Brain Tumor Pathology最新文献

While tumor-associated macrophages (TAMs) have been extensively studied, the role of tumor-associated astrocytes (TAAs) in glioma progression is less explored. Astrocytes are crucial in maintaining lipid homeostasis by synthesizing cholesterol and apolipoprotein E (APOE) in the brain. However, the contribution of astrocytes in supporting the metabolic needs of tumor cells within the tumor microenvironment (TME) is still poorly understood. This study aims to investigate how astrocytes contribute to the unique brain TME by examining the spatial distribution of APOE and its correlation with glial cells. This study examined the spatial distribution of APOE in gliomas with two murine brain tumor models: ALTS1C1 and GL261. To validate astrocyte APOE secretion, in situ hybridization (ISH) for APOE mRNA and immunofluorescence (IF) staining for GFAP were performed. Immunofluorescence (IF) staining showed that APOE was accumulated at the tumor edge. ISH analysis confirmed that activated astrocytes were the primary cells responsible for the increased APOE in this region. Flow cytometry and IF staining demonstrated that TAMs were also associated with increased APOE expression in the tumor core. This study provides the first evidence that astrocytes at the tumor edge are activated and upregulated for APOE secretion. These brain tumor edge-associated astrocytes are responsible for the accumulation of APOE in this region and create a unique metabolic environment, which may contribute to brain tumor invasion and resistance to therapy.

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.

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.

Rosette formation, a characteristic histopathological feature of various paediatric brain tumours, appears to be linked with cerebrospinal fluid (CSF) dissemination. Tumours like medulloblastoma, ependymoma, retinoblastoma, pineal region, and embryonal tumours, known for their rosette formations, also exhibit a propensity for CSF spread, which can manifest as drop metastases and leptomeningeal involvement. CSF dissemination is detected early in the disease course and contributes to significant diagnostic and management challenges. The structure of rosettes, consisting of tumour cells arranged in a circular halo around a central lumen, may facilitate tumour spread along CSF pathways, potentially through interactions with interstitial fluid and CSF dynamics. Recent insights into the glymphatic system, which regulates fluid flow between brain parenchyma and CSF, suggest that tumours infiltrating perivascular spaces, particularly those expressing aquaporins such as aquaporin-4, may exploit these pathways for metastasis. Tumours with marked rosette formation also show a higher risk of associated hydrocephalus, which may persist post-tumour resection. Additionally, the mechanical and chemical affinities of rosette-forming tumour cells for interstitial and CSF spaces could drive this spread. Understanding the relationship between rosette formation and CSF dissemination offers potential therapeutic targets, including aquaporin modulation, to prevent metastasis and manage CSF-related complications in brain tumours.

A teratoma with somatic-type malignancy is a rare subtype of germ cell tumor (GCT) characterized by the presence of a histologically distinct component resembling a somatic cancer within a teratoma feature. To date, only 14 cases have been reported in the central nervous system (CNS), and its diagnosis remains challenging due to the limited availability of pathological findings. A case of a pineal GCT that recurred as an adenocarcinoma 25 years after the initial chemoradiotherapy is reported. Although the histological features of teratoma were not observed, transformation into a teratoma with somatic-type malignancy was suspected. DNA methylation analysis classified the tumor within the CNS GCT cluster, specifically aligning with teratomas. Furthermore, whole-exome sequencing demonstrated multiple somatic mutations including two MAPK pathway gene alterations. These findings support the hypothesis that a GCT can evolve into a somatic cancerous phenotype over time, providing deep biological insights into the carcinogenesis of teratomas.

Ependymosarcoma is an exceedingly rare variant of ependymoma characterized by a mixture of ependymomatous and sarcomatous components. We report a case of supratentorial ependymosarcoma harboring a ZFTA::RELA fusion in a 10-year-old girl. Histologically, the tumor comprised an ependymomatous component resembling clear cell ependymoma and a sarcomatous component. ZFTA::RELA fusion was confirmed in both components. Genome-wide methylation profiling classified both components as supratentorial ependymoma, ZFTA fusion-positive by the German Cancer Research Center (DKFZ) CNS tumor classifier v12b8. However, their copy number alteration profiles were distinct. The ependymomatous component exhibited a gain of chromosome 1q and a loss of chromosomes 1p, 9, and 19q, while the sarcomatous component showed a loss of chromosome 14. These findings suggest that both components may have differentiated from a common precursor despite their distinct morphologies. The patient underwent gross total resection followed by adjuvant chemoradiotherapy and remains recurrence-free eight years post-treatment. Further investigation of additional cases is warranted to better understand the pathogenesis of this rare tumor.

Functioning gonadotroph pituitary neuroendocrine tumors (Gn-PitNETs) cause ovarian hyperstimulation. We report Gn-PitNETs, including a distant metastasis case responsive to a dopamine agonist (DA), cabergoline. A 10-year-old girl presented with ovarian enlargement and elevated FSH levels (33.7 mIU/mL). A pituitary tumor was resected and confirmed as a Gn-PitNET. Radiotherapy for residual tumor improved ovarian enlargement. At age 20, ovarian enlargement recurred and cabergoline relieved symptoms and decreased FSH levels. At age 35, ovarian enlargement recurred after discontinuing cabergoline but improved with its reinstatement. Liver biopsy confirmed metastatic Gn-PitNET and DRD2 positivity. A 26-year-old woman presented with ovarian enlargement and elevated FSH levels (31.6 mIU/mL). A pituitary tumor was resected and confirmed as a Gn-PitNET with negative DRD2. FSH levels normalized, and ovarian size improved. A 48-year-old man presented with bitemporal hemianopia. FSH levels were elevated (251.4 mIU/mL) without testicular enlargement. The pituitary tumor was resected, improving hemianopia and normalizing FSH levels. Histopathology confirmed a Gn-PitNET with strong FSH staining and DRD2 positivity. In a rare case of metastatic Gn-PitNET, cabergoline was associated with tumor stability and hormone control. Further studies may clarify whether DRD2 expression can help predict DA responsiveness in refractory tumors.(200/200 words).

Glomus tumor (GT) is a mesenchymal neoplasm composed of modified perivascular cells exhibiting smooth muscle-like features, resembling those of the normal glomus body. The lesions often occur in areas rich in glomus vascularis, most of which occur in the distal limbs, while the sellar GT is extremely rare. Here, we present a case of primary sellar GT harboring a BRAF K601E mutation, identified through next-generation sequencing. The patient has been followed for 10 years, with tumor recurrence noted in the fourth year post-surgery. This report highlights the histological features, biological behavior, clinical manifestations, and prognosis of sellar GTs with a BRAF K601E mutation. Literature review suggests that determining the biological behavior of sellar GTs remains challenging, complicating diagnosis and treatment planning. We summarize the clinical and pathological characteristics of sellar GTs and propose considerations for pathological diagnosis based on our findings.