Brain Tumor Pathology最新文献

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.

Few robust radiological markers have been identified for predicting the molecular status of gliomas. Recently, gyriform infiltration (GI) has been identified as an imaging biomarker for molecular glioblastoma (mGBM). This study aimed to validate the diagnostic value of GI in predicting the molecular status of diffuse gliomas. Clinical data were retrospectively collected from patients treated at a single center. Their imaging findings, including GI and the status of molecular markers, including IDH TERT were compared. This study enrolled 137 patients, 16 (12%) of whom, were diagnosed with GI. The vast majority of GI-positive cases were IDH-wildtype (15/16 cases), including four mGBM and six histologically diagnosed glioblastoma cases. The diagnostic sensitivity and specificity of GI in predicting mGBM were 24% and 90%, respectively, and its diagnostic sensitivity and specificity in predicting IDH-wildtype gliomas were 15% and 97%, respectively. GI was also observed in IDH-wildtype gliomas without the molecular and histological features of glioblastoma. All five GI-positive cases with available ¹¹C-methionine positron emission tomography scans showed increased tracer uptake in the GI area. GI is highly specific to IDH-wildtype gliomas. It delineates the tumor invasion burden and should be included as a target for local therapy, including radiation therapy.

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.