Brain Tumor Pathology最新文献

Astroblastoma is an extremely rare brain tumor that has recently attracted attention owing to its association with MN1 gene alteration. However, its long-term clinical course remains unclear. We report a late recurrence of MN1-altered astroblastoma with unique pathological findings. A 24-year-old woman presented with seizures due to a left frontal lobe tumor. Gross total resection (GTR) was achieved, and the diagnosis was MN1-altered astroblastoma, which presented cell wrapping, i.e., presence of tumor cells enveloping one another. She received local radiotherapy (50 Gy). However, the tumor recurred after 12 years, and its size increased rapidly. The second surgery achieved GTR and confirmed increasing anaplasia. The patient was tumor-free for 1 year without any neurological deficits. This case implies the importance of long-term follow-up of MN1-altered astroblastoma. The pathological significance of cell wrapping in this case is unclear, but it may be associated with MN1-altered astroblastoma and should be noted in future cases.

In 2017, WHO published an updated classification of the pituitary adenomas according to the lineages defined by the transcription factors, PIT1, SF1 and TPIT. Nomenclature of the pituitary tumors follows the mature cell types such as somatotroph (GH), lactotroph (LH), thyrotroph, corticotroph, and gonadotroph (FSH, LH). Null cell adenomas are defined by the absence of expression of any hormones and transcription factors. Not infrequently, the pituitary adenomas are invasive to the adjacent structures and are designated as aggressive adenomas. Knosp grading is often used to define the aggressiveness of the tumor. Sparsely granulated somatotroph adenomas and Crooke cell corticotroph adenomas are representative aggressive adenomas. Recently, genomics regarding various adenomas have been clarified, such as GNAS for somatotrophs and USP8 for corticotrophs. Familial pituitary adenomas are another aspect which has been clarified such as MEN1, Carney's complex, familial isolated pituitary adenoma and McCune-Albright syndrome. The pituitary adenomas often produce GH or PRL, hormones of PIT1 transcription factor. It has been agreed that the pituitary adenomas share the characteristics of neuroendocrine neoplasms. The terminology of pituitary neuroendocrine tumor has been discussed. This review article covers various aspects of pituitary adenomas.

The WHO 2016 classification introduced brain invasion as a standalone criterion for grade II meningioma (GIIM). We systematically reviewed studies published after 2000 and performed a PRISMA-compliant meta-analysis of the hazard ratios (HRs) for progression-free survival (PFS) between brain-invasive and noninvasive meningiomas. In five studies that included both benign and higher-grade meningiomas, brain invasion was a significant risk factor for recurrence (HR = 2.45, p = 0.0004). However, in 3 studies comparing "brain-invasive meningioma with otherwise benign histology (BIOB)" with grade I meningioma, brain invasion was not a significant predictor of PFS (HR = 1.49, p = 0.23). Among GIIM per the WHO 2000 criteria, brain invasion was a significant predictor of shorter PFS than noninvasive GIIM (HR = 3.40, p = 0.001) but not per the WHO 2016 criteria (HR 1.13, p = 0.54), as the latter includes BIOB. Meta-regression analysis of seven studies of grade II meningioma showed that more frequent BIOB was associated with lower HRs (p < 0.0001). Hence, there is no rationale for brain invasion as a standalone criterion for grade II meningioma, although almost all studies were retrospective and exhibited highly heterogeneous HRs due to differences in brain-tumor interface data availability.

Angiomatoid fibrous histiocytoma (AFH) is an uncommon soft-tissue neoplasm that arises mostly in the extremities of young people and generally carries a good prognosis. Intracranial location is unusual and frequently associated with myxoid change. EWSR1 gene fusions with members of the CREB family (CREB1, ATF1, and CREM) are well-established events in AFH. These fusions have also been described in other neoplasms including intracranial myxoid mesenchymal tumor, and it is still uncertain whether the latter is a distinct entity or if it represents a myxoid variant of AFH. Here, we describe a rare falcine AFH presenting in a 50-year-old woman. The most striking feature of this tumor was its diffuse rhabdoid morphology with focal high mitotic activity, raising the consideration of rhabdoid meningioma (WHO grade III). The tumor cells were moderately positive for EMA and negative for progesterone receptor and SSTR2 prompting additional studies. Desmin was strongly positive and CD99 showed membranous immunoreactivity. BAP1, INI-1, and BRG1 expressions were retained. Next-generation sequencing analysis demonstrated an EWSR1-ATF1 gene fusion, supporting the diagnosis of an unusual rhabdoid variant of AFH. After gross total resection of this tumor, the patient remains free of disease 5 months after the surgery without additional treatment.

Meningeal solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) were categorized as the same entity in the World Health Organization (WHO) 2016 classification of tumors of the central nervous system (CNS). Although NAB2-STAT6 fusion protein can be used to distinguish most of SFT/HPC from the other sarcomas, additional biomarkers were requested to separate meningeal SFT/HPC from meningioma and the molecular pathological difference between meningeal SFT/HPC and extra-CNS SFT/HPC still remains unclear. In this study, we evaluated the expression of TTF-1 in 67 meningeal SFT/HPC, 62 extra-CNS SFT/HPC and 201 meningiomas samples with immunohistochemistry (IHC) assays. The results showed that TTF-1 was detected in 23 of 67 (34.3%) meningeal SFT/HPC, 3 retroperitoneum SFT/HPC and none of meningiomas. Meanwhile, the copy number variation and mRNA expression of TTF-1 were measured by real-time quantitative PCR (qPCR) in meningeal SFT/HPC. These results demonstrated that TTF-1 protein expression level was significantly correlated with its transcription level, but independently related to the gene copy number variant. In conclusion, our study suggested that a large proportion of meningeal SFT/HPC was positive to TTF-1, while very few extra CNS SFT/HPC cases and no meningiomas were stained. So TTF-1 has value as an auxiliary diagnostic marker for meningeal SFT/HPC.

Primary tumors of the spinal cord are rare, accounting for 3-6% of tumors in the central nervous system, particularly in children. KIAA1549-BRAF fusion is more common in pilocytic astrocytoma (PA) and IDH1 R132H mutation is rare in infratentorial tumors. Here, we report a 10-year-old male patient who presented with weakness in lower limbs that progressed to difficulty walking. Magnetic resonance imaging (MRI) revealed an intramedullary solid-cystic lesion from the medulla oblongata to the thoracic spin 4 level, with the expansion of the spinal cord. The lesion exhibited patchy enhancement at C4-T1, indicating a tentative diagnosis of astrocytoma. The patient underwent resection of the lesion in the spinal canal from the cervical 6 level to the thoracic 2 level. Histopathology confirmed diagnosis of astrocytoma, WHO grade 2. Genetic analysis showed both IDH1 R132H mutation and KIAA1549-BRAF fusion. Therefore, our integrated diagnosis was astrocytoma, IDH mutation, WHO grade 2. Its molecular analyses include IDH1 R132H mutation and KIAA1549-BRAF fusion. After the operation, the patient did not receive chemo- or radiotherapy, and underwent an aggressive rehabilitation regiment. Follow up 10 months later, symptoms improved. To our best knowledge, this is the first case of concomitant IDH mutation and BRAF fusion in pediatric spinal cord astrocytoma.

Medulloblastoma, a common malignant brain tumor in children, comprises four molecular subgroups WNT, SHH, Group 3, and Group 4. In the present study, we performed a deep proteome-based investigation of SHH, Group 3 and Group 4 tumors. The adult SHH medulloblastomas were found to have a distinct proteomic profile. Several RNA metabolism-related pathways including mRNA splicing, 5' to 3' RNA decay, 3' to 5' RNA decay by the RNA exosome, and the N6-methyladenosine modification of RNA were enriched in adult SHH tumors. The heightened expression of the RNA surveillance pathways is likely to be essential for the viability of adult SHH subgroup medulloblastomas, which carry mutations in U1snRNA encoding gene and thus could be a vulnerability of these tumors. Group 3 and Group 4 medulloblastomas, on the other hand, are known to have an overlap in their expression profiles and underlying genetic alterations. Group 3 proteome was found to be distinctively enriched in several metabolic pathways including glycolysis, gluconeogenesis, glutamine anabolism, glutathione-mediated anti-oxidant pathway, and drug metabolism pathway suggests that the extensive metabolic rewiring is likely to be responsible for the aggressive clinical behavior of Group 3 tumors. This comprehensive proteomic analysis has provided valuable insight into the biology of Group 3 and adult SHH medulloblastomas, which could be further explored for effective treatment of these tumors.

We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM-/GFAP-, NM +/GFAP-, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2β was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM-/GFAP-, NM + /GFAP-, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP-  and GFAP + , and TOP2β-IR was frequently observed only in NM +/GFAP-  medulloblastomas. In fluorescent immunostaining, TOP2β-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing, TOP2β expression was elevated in CMAS/DCX-positive, but not in GFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.