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High-grade oligodendroglioma (HGOG) is the most common type of glioma in dogs and expresses platelet-derived growth factor receptor-α (PDGFR-α). Microvascular proliferation is often observed in HGOG. Therefore, the present study investigated the functional relationships between PDGFR-α, microvascular proliferation, and tumor cell proliferation in canine HGOG. The expression of PDGFR-α and PDGF-subunit A (PDGF-A) in tumor cells, as well as endothelial cells and pericytes of tumor-associated microvascular proliferations, in 45 canine HGOGs were examined immunohistochemically. Microvascular proliferation was observed in 24/45 cases (53%). PDGFR-α expression in tumor cells and microvascular proliferations was observed in 45/45 (100%) and 2/24 cases (8%), respectively. Furthermore, PDGF-A expression in tumor cells and microvascular proliferations was detected in 13/45 (29%) and 24/24 cases (100%), respectively. In vitro, stimulation of the canine HGOG cell line AOFB-01 with PDGF-A showed that the doubling time of AOFB-01 cells was significantly shorter with PDGF-A than without PDGF-A. Crenolanib (a PDGFR inhibitor) inhibited AOFB-01 cell proliferation. In vivo, the AOFB-01 xenograft mouse model was treated with crenolanib. Tumor xenografts were smaller in crenolanib-treated mice than in untreated control mice. PDGFR-α expression in tumor cells and PDGF-A expression in microvascular proliferations and tumor cells suggest autocrine and paracrine effects of PDGF-A in canine HGOG. The results of in vitro assays indicate that canine HGOG expresses functional PDGFR-α, which responds to PDGF-A. Therefore, PDGF-A produced by microvascular proliferations and tumor cells may promote the proliferation of PDGFR-α-expressing tumor cells in canine HGOG. PDGFR-α signaling has potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background and purpose: Cervical Spondylotic Myelopathy (CSM), the most common cause of spinal cord dysfunction globally, is a degenerative disease that results in non-violent, gradual, and long-lasting compression of the cervical spinal cord. The objective of this study was to investigate whether microvascular proliferation could positively affect neural function recovery in experimental cervical spondylotic myelopathy (CSM). Methods: A total of 60 male adult Sprague–Dawley (SD) were randomly divided into four groups: Control (CON), Compression (COM), Angiostasis (AS), and Angiogenesis (A G),with 15 rats in each group. Rats in the AS group received SU5416 to inhibit angiogenesis, while rats in the AG group received Deferoxamine (DFO) to promote angiogenesis. Motor and sensory functions were assessed using the Basso Beattie Bresnahan (BBB) scale and somatosensory evoked potential (SEP) examination. Neuropathological degeneration was evaluated by the number of neurons, Nissl bodies (NB), and the de-myelination of white matter detected by Hematoxylin & Eosin(HE), Toluidine Blue (TB), and Luxol Fast Blue (LFB) staining. Immunohistochemical (IHC) staining was used to observe the Neurovascular Unit (NVU). Results: Rats in the CON group exhibited normal locomotor function with full BBB score, normal SEP latency and amplitude. Among the other three groups, the AG group had the highest BBB score and the shortest SEP latency, while the AS group had the lowest BBB score and the most prolonged SEP latency. The SEP amplitude showed an opposite performance to the latency. Compared to the COM and AS groups, the AG group demonstrated significant neuronal restoration in gray matter and axonal remyelination in white matter. DFO promoted microvascular proliferation, especially in gray matter, and improved the survival of neuroglial cells. In contrast, SU-5416 inhibited the viability of neuroglial cells by reducing micro vessels. Conclusion: The microvascular status was closely related to NVU remodeling an-d functional recovery. Therefore, proliferation of micro vessels contributed to function -al recovery in experimental CSM, which may be associated with NVU remodeling. [ABSTRACT FROM AUTHOR]

Abstract Background Episodic growth due to microvascular proliferations (MVP) has been reported in congenital arteriovenous malformations (AVM), which are normally quiescent lesions composed of mature malformed vessels. Since AVM also may worsen under conditions of hormonal dysregulation, we hypothesized that hormonal influences may stimulate this process of vasoproliferative growth through potential interactions with hormone receptors (HR). Methods 13 Cases of AVM tissue with histologically documented vasoproliferative growth were analyzed quantitatively for the presence and tissue localization of estrogen receptor (ER), progesterone receptor (PGR), growth hormone receptor (GHR) and follicle-stimulating hormone receptor (FSHR) in relation to resident cells of interest (endothelial cells (EC), smooth muscle cells (SMC) and mast cells (MC)) by applying multiplex immunohistochemistry (IHC) staining. Expression patterns in lesions with MVP and mature vessels were quantified and compared. Available fresh frozen tissues of 3 AVM samples were used to confirm the presence of HR using Reverse-Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR). Results All four HR studied were expressed in all cases within EC and SMC in areas of MVP and mature vessels, but not in normal skin tissue. ER, GHR, and FSHR showed more expression in EC of MVP and in SMC of mature vessels. RT-qPCR confirmed presence of all 4 HR in both areas. Conclusion Expression of ER, PGR, GHR, and FSHR in vasoproliferative areas of congenital AVM could explain onset of sudden symptomatic growth, as has observed in a subpopulation of patients. These findings may have implications for eventual anti-hormonal targeted therapy in the lesions involved.

Background: Discrepancies have been noted between the clinical and histologic diagnosis of vascular malformations. Objective: To evaluate the effectiveness of the International Society for Study of Vascular Anomalies (ISSVA) classification in diagnosing benign vascular anomalies based on clinical and (immuno) histologic parameters, focusing on lymphatic differentiation and vascular proliferation. Method: A retrospective study of 121 consecutive patients with benign skin and soft-tissue vascular anomalies located in the head and neck region (pyogenic granulomas and angioma senilis were excluded) by applying multiplex immunohistochemistry staining for lymph vessels (D2-40), endothelial blood vessels, and proliferating cells (Ki67). Clinical and histologic diagnosis was revised after the ISSVA classification. Results: Initially, 64 lesions were diagnosed as tumors and 57 as malformations. Revision diagnosis following the ISSVA classification revealed 27 tumors, 90 malformations (22.2% lymphatic), and 4 non-ISSVA. Immunostaining showed lymphatic differentiation in 24 (19.8%) of 121 cases, of which 20 were malformations. Proliferative activity (Ki67+) was found in 41 (33.8%) of 121 cases, of which 8 were arteriovenous malformations. Limitation: Quality and size of materials (biopsies vs resections) and clinical information. Conclusion: The diagnostic accuracy of combined histologic and clinical approaches for identifying vascular anomalies following the ISSVA classification can be substantially enhanced by incorporating additional immunostaining techniques to evaluate lymphatic differentiation and proliferative activity, particularly in identifying the occurrence of vascular malformations.

Background: Episodic growth due to microvascular proliferations (MVP) has been reported in congenital arteriovenous malformations (AVM), which are normally quiescent lesions composed of mature malformed vessels. Since AVM also may worsen under conditions of hormonal dysregulation, we hypothesized that hormonal influences may stimulate this process of vasoproliferative growth through potential interactions with hormone receptors (HR). Methods: 13 Cases of AVM tissue with histologically documented vasoproliferative growth were analyzed quantitatively for the presence and tissue localization of estrogen receptor (ER), progesterone receptor (PGR), growth hormone receptor (GHR) and follicle-stimulating hormone receptor (FSHR) in relation to resident cells of interest (endothelial cells (EC), smooth muscle cells (SMC) and mast cells (MC)) by applying multiplex immunohistochemistry (IHC) staining. Expression patterns in lesions with MVP and mature vessels were quantified and compared. Available fresh frozen tissues of 3 AVM samples were used to confirm the presence of HR using Reverse-Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR). Results: All four HR studied were expressed in all cases within EC and SMC in areas of MVP and mature vessels, but not in normal skin tissue. ER, GHR, and FSHR showed more expression in EC of MVP and in SMC of mature vessels. RT-qPCR confirmed presence of all 4 HR in both areas. Conclusion: Expression of ER, PGR, GHR, and FSHR in vasoproliferative areas of congenital AVM could explain onset of sudden symptomatic growth, as has observed in a subpopulation of patients. These findings may have implications for eventual anti-hormonal targeted therapy in the lesions involved. [ABSTRACT FROM AUTHOR]

Abstract Background The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification. Methods Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts’ supervision, achieving an accuracy of 88.8% of overlay. Spearman’s correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples. Results Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p

Astrocytomas are relatively common primary brain tumours of humans and companion animals. In dogs, they represent approximately 17-28% of primary central nervous system tumours. However, extracranial metastasis is extremely rare. This case report describes a grade IV astrocytoma (glioblastoma) in the cerebrum of a young Cane Corso dog with pulmonary metastases. The diagnosis was obtained via histopathological morphology and immunophenotyping, which showed strong positivity for glial fibrillary acidic protein, vimentin and connexin-43. The glioblastoma in this Cane Corso had epithelioid morphology with histological features of malignancy including high mitotic count, microvascular proliferation, serpentine necrosis and subventricular zone involvement. Epithelioid glioblastoma is a rare subtype that has only relatively recently been formally acknowledged in human medicine and it can also pose a diagnostic challenge in veterinary medicine., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship or publication of this article. This study was carried out for the small animal module in fulfilment of the MSc in Veterinary Pathology at the University of Liverpool., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In POLA cohort, three pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis)., Methods: 494 patients from the POLA cohort, with a median follow up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement in group 1 on overall survival (OS) or progression free survival (PFS), survival curves were obtained (Kaplan-Meier method) and compared (log-rank test). Prognostic value of clinical factors and CDKN2A homozygous deletion HD were also tested. Multivariate analysis was performed., Results: Survival analysis demonstrated that the pathological groups were associated with both progression-free survival (PFS P=0.01) and overall survival (OS P=0.001). In group 1, patients with contrast enhancement (1CE+) had a poorer prognosis compared to those without (OS P=0.028, PFS P=0.006). Further stratification into group 1CE-, group 1CE+, group 2, and group 3 provided clearer prognostic distinctions (OS P=0.002, PFS P<0.0001). Other prognostic factors included age (OS P<0.0001, PFS P=0.002), extent of surgical resection (OS P=0.001, PFS P=0.003), KPS (OS P<0.0001, PFS P=0.002), postoperative treatment (OS P=0.007, PFS P<0.0001), and CDKN2A HD (OS and PFS P<0.0001). The pathological groups remained of prognostic significance for PFS in multivariate analysis., Conclusion: Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH mutant and 1p/19q co-deleted. Besides, in group 1 patients, lack of contrast enhancement is a factor of better prognosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification.Methods: Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts' supervision, achieving an accuracy of 88.8% of overlay. Spearman's correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples.Results: Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2-2.5 times higher rCBV values in IDH-wildtype glioblastoma samples.Conclusions: The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification. [ABSTRACT FROM AUTHOR]

Background: Despite extensive investigations, the exact etiology of chronic subdural hematoma (CSDH) remains elusive. Organized CSDHs are a distinct but less-understood type of CSDH. Case Description: A 50-year-old hypertensive woman experienced headache without any previous head injury. At presentation, the patient showed no focal neurological deficits. Cranial computed tomography (CT) revealed a slightly compressive subdural hematoma that spontaneously regressed and no intracranial vascular lesions. Cerebral magnetic resonance imaging identified a non-enhancing nodular lesion in the subdural hematoma. After the patient presented disorientation and aphasia on post hospitalization day 14, CT showed a considerable enlargement of the subdural hematoma. Partial removal of the bi-layered hematoma was performed through a parietal craniotomy. Histological examination revealed microvascular proliferation in both the outer membrane and the nodular lesion. On postoperative day 35, CT demonstrated a remarkable resolution of the residual hematoma. Conclusion: Development of microvascular proliferation in the clots of an acute subdural hematoma may lead to its rapid enlargement as an organized CSDH. Organized CSDH can be managed by partial removal of the outer membrane and hematoma through a craniotomy. [ABSTRACT FROM AUTHOR]

Background/Aim: Better diagnostic and prognostic markers are required for a more accurate diagnosis and an earlier detection of glioma progression and for suggesting better treatment strategies. This retrospective study aimed to identify actionable gene variants to define potential markers of clinical significance. Materials and Methods: 56 glioblastomas (GBM) and 44 grade 2-3 astrocytomas were profiled with next generation sequencing (NGS) as part of routine diagnostic workup and bioinformatics analysis was used for the identification of variants. CD34 immunohistochemistry (IHC) was used to measure microvessel density (MVD) and Log-rank test to compare survival and progression in the presence or absence of these variants. Results: Bioinformatic analysis highlighted frequently occurring variants in genes involved in angiogenesis regulation (KDR, KIT, TP53 and PIK3CA), with the most common ones being KDR (rs1870377) and KIT (rs3822214). The KDR variant was associated with increased MVD and shorter survival in GBM. We did not observe any correlation between the KIT variant and MVD; however, there was an association with tumour grade. Conclusion: This study highlights the role of single-nucleotide variants (SNVs) that may be considered non-pathogenic and suggests the prognostic significance for survival of KIT rs3822214 and KDR rs1870377 and potential importance in planning new treatment strategies for gliomas. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cervical Spondylotic Myelopathy (CSM), the most common cause of spinal cord dysfunction globally, is a degenerative disease that results in non-violent, gradual, and long-lasting compression of the cervical spinal cord. The objective of this study was to investigate whether microvascular proliferation could positively affect neural function recovery in experimental cervical spondylotic myelopathy (CSM)., Methods: A total of 60 male adult Sprague-Dawley (SD) were randomly divided into four groups: Control (CON), Compression (COM), Angiostasis (AS), and Angiogenesis (A G),with 15 rats in each group. Rats in the AS group received SU5416 to inhibit angiogenesis, while rats in the AG group received Deferoxamine (DFO) to promote angiogenesis. Motor and sensory functions were assessed using the Basso Beattie Bresnahan (BBB) scale and somatosensory evoked potential (SEP) examination. Neuropathological degeneration was evaluated by the number of neurons, Nissl bodies (NB), and the de-myelination of white matter detected by Hematoxylin & Eosin(HE), Toluidine Blue (TB), and Luxol Fast Blue (LFB) staining. Immunohistochemical (IHC) staining was used to observe the Neurovascular Unit (NVU)., Results: Rats in the CON group exhibited normal locomotor function with full BBB score, normal SEP latency and amplitude. Among the other three groups, the AG group had the highest BBB score and the shortest SEP latency, while the AS group had the lowest BBB score and the most prolonged SEP latency. The SEP amplitude showed an opposite performance to the latency. Compared to the COM and AS groups, the AG group demonstrated significant neuronal restoration in gray matter and axonal remyelination in white matter. DFO promoted microvascular proliferation, especially in gray matter, and improved the survival of neuroglial cells. In contrast, SU-5416 inhibited the viability of neuroglial cells by reducing micro vessels., Conclusion: The microvascular status was closely related to NVU remodeling an-d functional recovery. Therefore, proliferation of micro vessels contributed to function -al recovery in experimental CSM, which may be associated with NVU remodeling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Wang, Hu and Hu.)

Myxopapillary ependymomas (MPE) are considered benign (World Health Organization (WHO) grade I) neoplasms with favorable prognosis. However, malignant behavior occurs in a small subset. To our knowledge, only five anaplastic MPEs have been reported without consensus on diagnostic criteria. We retrieved 14 anaplastic MPEs from the pathology archives of six institutions. Each tumor included at least two of the following features: ≥5 mitoses per 10 high power fields, Ki‐67 labeling index (LI) ≥10%, microvascular proliferation (MVP) and spontaneous necrosis. These features were typically encountered in the foci of hypercellularity and reduced mucin. There were eight male and six female patients (age range 6–57 years, median = 16.5). Ten tumors displayed anaplasia at initial resection, and 4 were anaplastic at a second surgery for recurrence (ranging from 9 months to 14 years following initial resection). The Ki‐67 LI ranged between 8% and 40% in the anaplastic foci and <3% in the foci of classic MPE. There was documented cerebrospinal fluid (CSF) dissemination in seven cases, recurrence following an anaplastic diagnosis in three cases and bone or soft tissue invasion in two cases. One patient suffered lung metastases. Two cases evaluated by targeted next‐generation sequencing and one evaluated by fluorescence in situ hybridization (FISH) showed nonspecific chromosomal gains. We conclude that although rare, anaplastic MPE occurs in both pediatric and adult patients, similar to other ependymomas. At a minimum, closer follow‐up is recommended, given the concern for aggressive biologic potential. Further study is needed to determine WHO grading criteria and genetic indicators of tumor progression. [ABSTRACT FROM AUTHOR]

Gain-of-function mutations in isocitrate dehydrogenase (IDH) genes result in excessive production of (D)-2-hydroxyglutarate (D-2HG) which intrinsically modifies tumor cell epigenetics and impacts surrounding noncancerous cells through nonepigenetic pathways. However, whether D-2HG has a paracrine effect on endothelial cells in the tumor microenvironment needs further clarification. We quantified microvessel density by immunohistochemistry using tissue sections from 60 high-grade astrocytic gliomas with or without IDH mutation. Microvessel density was found to be reduced in tumors carrying an IDH mutation. Ex vivo experiments showed that D-2HG inhibited endothelial cell migration, wound healing, and tube formation by suppressing cell proliferation but not viability, possibly through reduced activation of the mTOR/STAT3 pathway. Further, D-2HG reduced fluorescent dextran permeability and decreased paracellular T-cell transendothelial migration by augmenting expression of junctional proteins thereby collectively increasing endothelial barrier function. These results indicate that D-2HG may influence the tumor vascular microenvironment by reducing the intratumoral vasculature density and by inhibiting the transport of metabolites and extravasation of circulating cells into the astrocytoma microenvironment. These observations provide a rationale for combining IDH inhibition with antitumor immunological/angiogenic approaches and suggest a molecular basis for resistance to antiangiogenic drugs in patients whose tumors express a mutant IDH allele., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT. [ABSTRACT FROM AUTHOR]

Objective Although microvascular proliferation is a key feature in the diagnosis of high-grade glioma, the characteristics of metastatic tumour vessels in smear preparations have not been documented. In this study, the vascular changes in metastatic brain tumours, using squash cytology to examine the vascular patterns in brain metastases, were reviewed. Methods One hundred and forty-three squash smears of brain tissue, including 25 normal or reactive tissue, 23 malignant lymphomas, 8 grade I glioma (pilocytic astrocytoma), 23 grade II glioma (diffuse astrocytoma and oligodendroglioma), 42 grade IV glioma (glioblastoma), and 22 metastasis, were assessed. Two vascular patterns were assessed: thick and branching, and glomeruloid. The vessel density, nuclear layer and the number of vessel branches were compared. Furthermore, tumour vessels of brain metastases were analysed by histology and for immunohistochemical expression of CD34, α-smooth muscle actin (SMA) and high-molecular-weight caldesmon (h-CD). Results Among 22 metastatic tumours, thick and branching vessels were found in 17 (77%) and glomeruloid vessels in 13 (59%). These incidences of microvascular proliferation patterns were similar to those of glioblastomas or pilocytic astrocytomas. Vessel density, nuclear layer and vessel wall branches were significantly higher in metastatic tumours than malignant lymphomas, grade II gliomas or normal brain tissues. Glomeruloid vessels consisted of CD34-positive cells and α-SMA-positive cells, and α-SMA-positive cells had a low h-CD expression. These immunohistochemical patterns were similar to those of high-grade gliomas. Conclusions The vascular features of metastatic brain tumours are similar to those of glioblastomas, suggesting that these microvascular proliferations contribute to the progression of metastatic tumours. [ABSTRACT FROM AUTHOR]

Background: Discrepancies have been noted between the clinical and histologic diagnosis of vascular malformations., Objective: To evaluate the effectiveness of the International Society for Study of Vascular Anomalies (ISSVA) classification in diagnosing benign vascular anomalies based on clinical and (immuno) histologic parameters, focusing on lymphatic differentiation and vascular proliferation., Method: A retrospective study of 121 consecutive patients with benign skin and soft-tissue vascular anomalies located in the head and neck region (pyogenic granulomas and angioma senilis were excluded) by applying multiplex immunohistochemistry staining for lymph vessels (D2-40), endothelial blood vessels, and proliferating cells (Ki67). Clinical and histologic diagnosis was revised after the ISSVA classification., Results: Initially, 64 lesions were diagnosed as tumors and 57 as malformations. Revision diagnosis following the ISSVA classification revealed 27 tumors, 90 malformations (22.2% lymphatic), and 4 non-ISSVA. Immunostaining showed lymphatic differentiation in 24 (19.8%) of 121 cases, of which 20 were malformations. Proliferative activity (Ki67+) was found in 41 (33.8%) of 121 cases, of which 8 were arteriovenous malformations., Limitation: Quality and size of materials (biopsies vs resections) and clinical information., Conclusion: The diagnostic accuracy of combined histologic and clinical approaches for identifying vascular anomalies following the ISSVA classification can be substantially enhanced by incorporating additional immunostaining techniques to evaluate lymphatic differentiation and proliferative activity, particularly in identifying the occurrence of vascular malformations., Competing Interests: None disclosed., (© 2023 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Glioblastoma (GBM) is the highly malignant glioma and exhibits microvascular proliferation. PCR mRNA arrays and immunohistochemical stains on tissue microarray demonstrated that the expression level of PDGFRB in GBM microvascular proliferation was significantly higher than that in GBM tumor cells while the expression level of EGFR was lower in microvascular proliferation than in GBM tumor cells. PDGFRB protein was selectively expressed in pericytes in GBM microvascular proliferation. By analyzing The Cancer Genome Atlas (TCGA) datasets for GBM, it was found that genomic DNA alterations were the main reason for the high expression of EGFR in GBM tumor cells. Our miRNA microarray data showed that microRNAs (miRNAs) (miR-193b-3p, miR-518b, miR-520f-3p, and miR-506-5p) targeting PDGFRB were downregulated in microvascular proliferation, which might be the most likely reason for the high expression of PDGFRB in GBM microvascular proliferation. The increase of several miRNAs (miR-133b, miR-30b-3p, miR-145-5p, and miR-146a-5p) targeting EGFR in GBM microvascular proliferation was one of the reasons for the lack of expression of EGFR in GBM microvascular proliferation. These findings implicated that miRNAs, such as miR-506, miR-133b, miR-145, and miR-146a, that target PDGFRB or EGFR, might be potential therapeutic agents for GBM. A new generation of targeted therapeutic agents against both EGFR and PDGFRB might be developed in the future. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary malignant brain tumor. Microvascular proliferation is one of the characteristic pathologic features of GBM. Mitochondrial dysfunction plays an important role in the pathogenesis of GBM. In this study, microvascular proliferation from GBM and normal brain blood vessels were laser microdissected and total RNA was isolated from these microvasculatures. The difference of mRNA expression profiles among GBM microvasculature, normal brain blood vessels and GBM tumor cells was evaluated by mitochondria and metabolism PCR gene arrays. It was found that the mRNA levels of ATP5A1 and ATP5B in GBM tumor cells as well as microvascular proliferation were significantly higher compared with normal brain blood vessels. Immunohistochemical stains with anti-ATP5A1 antibody or anti-ATP5B antibody were performed on tissue microarray, which demonstrated strongly positive expression of ATP5A1 and ATP5B in GBM tumor cells and GBM microvascular proliferation while normal blood vessels were negative. By analyzing The Cancer Genome Atlas data sets for GBM and other cancers, genomic DNA alterations (mutation, amplification or deletion) were less likely the reason for the high expression of ATP5A1 and ATP5B in GBM. Our miRNA microarray data showed that miRNAs that target ATP5A1 or ATP5B were down-regulated, which might be the most likely reason for the high expression of ATP5A1 and ATP5B in GBM tumor cells and microvascular proliferation. These findings help us better understand the pathogenesis of GBM, and agents against ATP5A1 and/or ATP5B might effectively kill both tumor cells and microvascular proliferation in GBM. MiRNAs, such as Let-7f, miR-16, miR-23, miR-100 and miR-101, that target ATP5A1 or ATP5B, might be potential therapeutic agents for GBM. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most highly malignant brain tumor in the human central nerve system. In this paper, we review new and significant molecular findings on angiogenesis and possible resistance mechanisms. Expression of a number of genes and regulators has been shown to be upregulated in GBM microvessel cells, such as interleukin-8, signal transducer and activator of transcription 3, Tax-interacting protein-1, hypoxia induced factor-1 and anterior gradient protein 2. The regulator factors that may strongly promote angiogenesis by promoting endothelial cell metastasis, changing the microenvironment, enhancing the ability of resistance to anti-angiogenic therapy, and that inhibit angiogenesis are reviewed. Based on the current knowledge, several potential targets and strategies are proposed for better therapeutic outcomes, such as its mRNA interference of DII4-Notch signaling pathway and depletion of b1 integrin expression. We also discuss possible mechanisms underlying the resistance to anti-angiogenesis and future directions and challenges in developing new targeted therapy for GBM. [ABSTRACT FROM AUTHOR]

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently described novel type of primary brain tumor that was included into the current WHO classification of CNS tumors. It is a very rare, slowly growing, mixed neoplasm at cerebellar localization with distinctive morphological pattern. We present an unusual case of a 20-year-old patient with RNGT of the fourth ventricle with advanced microvascular proliferation. MRI revealed the solid-cystic tumor mass largely involving the cerebellar vermis and left hemisphere with compression of the fourth ventricle. Microscopically, the tumor showed classical architectural pattern with two distinctive components. The main component consisted of neurocytic rosettes formed by round, isomorphic nuclei arranged around eosinophilic, fibrillar cores with strong synaptophysin expression. The perivascular rosettes with cell arrangement along blood vessels were observed only sporadically. The second neoplastic component consisted of spindle or stellate astroglial cells with piloid process and Rosenthal fibers, strongly resembling pilocytic astrocytoma. Focally, the astroglial cells showed increased cellularity but without marked nuclear atypia. The glial part of the tumor revealed advanced proliferation of microvessels. The vessels of glomeruloid type exhibited multilayered endothelial proliferation and marked mitotic activity. MIB1 labelling index was generally low; however, in areas exhibiting microvascular proliferation its expression was significantly increased up to 20%. This report demonstrates the unique case of RGNT with conspicuous microvascular proliferation of glomeruloid type and extensive endothelial proliferation. As there is still limited clinical experience with RGNT, further studies are necessary to evaluate the biology of this type of tumor. [ABSTRACT FROM AUTHOR]

Background: This study was designed to evaluate the narrow band imaging (NBI) system for its ability to differentiate between malignant neoplasm and benign neoplasm by real-time image during nasopharyngoscopy, the quality of the visualization, and the limitation of the NBI in nasopharyngeal lesions. Methods: Between June 2009 and May 2010, 63 patients who had a suspected nasopharyngeal tumor via nasopharyngoscopy at Taipei Veterans General Hospital, Taiwan, were included in this study. All of the patients received nasopharyngoscopy with conventional view and NBI view and nasopharyngeal biopsy. The patients were divided into two groups depending on the pathological results: nasopharyngeal carcinoma (NPC) and lymphoid hyperplasia/chronic inflammation (LH). Results: Forty-one patients were in the NPC group and 22 patients were in the LH group. The pattern of the NBI view showed regular cobblestone in the LH group, except for one patient. The pattern of the NBI view showed an irregular engorged vascular pattern and/or microvascular proliferative pattern in 32 of 41 NPC patients (78.0%). The sensitivity, specificity, positive predictive value, and negative predictive value of NBI in nasopharynx (NP) were 78.0, 95.5, 97.0, and 70.0%, respectively, in NP neoplasm. Conclusion: NBI could be helpful in differentiating benign and malignant neoplasm in the NP region. Using NBI in NP regions had some limitations, including bleeding and mucus coating. [ABSTRACT FROM AUTHOR]

Brain gliomas are characterized by invasive growth and neovasculafisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with turnout histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP) and microvessel density (MVD). Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following anti-bodies were used Ki-67 and PCNA (DAKO). Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO). The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade. [ABSTRACT FROM AUTHOR]

Abstract: Cystic meningiomas are uncommon. Contrast enhancement of the cyst wall of peritumoral cysts on radiological imaging is generally thought to indicate that the wall contains tumor cells. The authors present a patient with a peritumoral cyst that enhanced despite the absence of tumor cells. Histological analysis demonstrated a gliotic cyst wall with numerous microvascular proliferations (MVPs) adjacent to a mixed transitional and angiomatous/microcystic meningioma. Immunoreactivity for vascular endothelial growth factor (VEGF) and its receptor, flt-1, was observed in the endothelial cells of both intratumoral vessels and cyst wall MVPs. Immunoreactivity for tenascin-C was strongly observed within and around the vascular wall of MVPs and in gliotic tissue adjacent to the meningioma. These changes are unusual in the peritumoral brain parenchyma of a slow-growing convexity meningioma and the MVPs may account for the atypical contrast enhancement of the cyst wall despite the absence of tumor cells. [Copyright &y& Elsevier]

A subset of oligodendrogliomas and oligoastrocytomas has been associated with 1p /19q deletion. Subsequently, this genetic alteration was linked to chemosensitivity and classic histology of oligodendrogliomas. Tumoural progression includes deletions of 9p , 10q and alterations of CDKN2A . However, these (epi)genetic changes have not been associated with specific histological features. In a series of 45 gliomas including oligodendrogliomas, oligoastrocytomas and astrocytomas, deletions of chromosomal regions implied in these tumours (1p , 9p , 10 , 17p13 , 19q and 22 ) were looked for by microsatellite analysis. Tumours that were deleted for 1p and 19q were selected. Subsequently, presence of deletions in the other studied regions, (epi)genetic changes in p14 [sup ARF ] , CDKN2A and CDKN2B , as well as histological features, were associated to these tumours. 1p/19q deletion was observed in 22 tumours. Twenty-one of them presented regions of classic histology of oligodendroglioma. A deletion of 9p was found in eight of them, always in association with tumour necrosis and/or microvascular proliferation. In addition, (epi)genetic alterations of CDKN2A were observed in 71% of these tumours. Presence of regions of classic histology of oligodendroglioma in a tumour sample is predictive of 1p/19q deletions. Necrosis and/or microvascular proliferation are signs of an additional 9p deletion. Finally, as CDKN2A (epi)genetic alterations were found in 71% of the 1p/19q/9p -deleted oligodendrogliomas, CDKN2A may have a role in oligodendroglioma-associated microvascular proliferation. [ABSTRACT FROM AUTHOR]