Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis?

AIMS: Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin-specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft-tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6-rearranged tumours resembling NF with atypical features have been reported. METHODS AND RESULTS: One index case of LGMS of the deltoid in a 56-year-old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break-apart probe identified two additional cases. These cases were investigated with RNA-sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low-quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast-like multinucleated giant cells, and peripheral lymphoid aggregates. CONCLUSION: Our findings support the notion that among soft-tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.

Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase.

BACKGROUND: Drug-resistant epilepsy is a common condition in patients with brain neoplasms. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathogenetic mechanisms, the increase in glutamate concentration has been proposed. Glutamate transporters, glutamine synthetase and pyruvate carboxylase are involved in maintaining the physiological concentration of glutamate in the intersynaptic spaces. In our previous research on angiocentric gliomas, we demonstrated that all tumors lacked the expression of the main glutamate transporter EAAT2, while the expression of glutamine synthetase and pyruvate carboxylase was mostly preserved. METHODS: In the present study, we evaluated the immunohistochemical expression of EAAT2, glutamine synthetase and pyruvate carboxylase in a heterogeneous series of 25 long-term epilepsy-associated tumors (10 dysembryoplastic neuroepithelial tumors, 7 gangliogliomas, 3 subependymal giant cell astrocytomas, 3 rosette forming glioneuronal tumors, 1 diffuse astrocytoma MYB- or MYBL1-altered and 1 angiocentric glioma). In order to evaluate the incidence of variants in the SLC1A2 gene, encoding EAAT2, in a large number of central nervous system tumors we also queried the PedcBioPortal. RESULTS: EAAT2 protein expression was lost in 9 tumors (36 %: 3 dysembryoplastic neuroepithelial tumors, 1 ganglioglioma, 3 subependymal giant cell astrocytomas, 1 diffuse astrocytoma MYB- or MYBL1-altered and 1 angiocentric glioma). Glutamine synthetase protein expression was completely lost in 2 tumors (8 %; 1 ganglioglioma and 1 diffuse astrocytoma MYB- or MYBL1-altered). All tumors of our series but rosette forming glioneuronal tumors (in which neurocytic cells were negative) were diffusely positive for pyruvate carboxylase. Consultation of the PedcBioPortal revealed that of 2307 pediatric brain tumors of different histotype and grade, 20 (< 1%) had variants in the SLC1A2 gene. Among the SLC1A2-mutated tumors, there were no angiocentric gliomas or other LEATs CONCLUSIONS: In conclusion, unlike angiocentric gliomas where the EAAT2 loss is typical and constant, the current study shows the loss of EAAT2 expression only in a fraction of the LEATs. In these cases, we may hypothesize some possible epileptogenic role of the EAAT2 loss. The retained expression of pyruvate carboxylase may contribute to determining a pathological glutamate excess unopposed by glutamine synthetase that resulted expressed to a variable extent in the majority of the tumors. Furthermore, we can assume that the EAAT2 loss in brain tumors in general and in LEATs in particular is more conceivably epigenetic.

Brief report: pediatric high-grade gliomas treated with vinorelbine and valproic acid added to temozolomide.

Children and young adult with high grade gliomas (HGG) have dismal prognoses and treatment options remain limited. We present 19 patients diagnosed with anaplastic astrocytoma (AA) or glioblastoma (GBM) treated with concomitant and adjuvant 20-30 mg/m2/dose of vinorelbine and 30 mg/kg/day valproic acid (VA) in combination to consolidated TMZ and focal RT after maximal surgery. We evaluated the feasibility of treating children diagnosed with HGG. The median follow-up time was 51.4 months (range, 6.2-106.6 months). The 5-year OS was 57.9% (CI 95%, 33.2-76.3) and the 5-year PFS was 57.9% (CI 95%, 33.2-76.3). Eight patients (42.1%) have progressed so far, with a median time to progression of 9 months from diagnosis (range, 4.6-34.7 months). All of them died for disease progression. At time of analysis, 11 patients were still alive with no evidence of disease. It is notable that all events occurred within 35 months from the start of therapy. All 19 treated patients reported low-grade drug-related adverse events (AEs). The treatment was well tolerated in our limited cohort of patients without significant toxicity. Further studies of the efficacy and safety of combination of vinorelbine/VA to consolidated RT/TMZ therapy in children with HGG are underway in a clinical trial setting.

Sinonasal nodular fasciitis: report of a case with USP6 rearrangement.

Nodular fasciitis (NF) is a benign myofibroblastic proliferation characterized by rapid growth, a self-limiting course, and USP6 gene rearrangement. Although it can arise in the head and neck region, very few cases of NF involving the sinonasal tract have been reported to date. Herein we report a case of NF involving the nasal cavity presenting as a polypoid well-defined mass causing obstructive symptoms in a male with a history of multiple local surgeries. Although the mass had an unusual clinical presentation, the histopathologic and immunohistochemical findings were consistent with NF. Fluorescent in situ hybridization performed with break-apart probes flanking the USP6 locus on chromosome 17p13 revealed the presence of USP6 gene rearrangement. The patient remained free of disease 124 months after surgical treatment. Considering its remarkably benign behavior despite its alarming clinical and histologic features, the distinction of NF from sinonasal malignant tumors is essential.

SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome.

We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant. Family segregation study detected the SMARCE1 variant in the asymptomatic father and in the asymptomatic sister who, nevertheless, presents 2 spinal lesions. Germline heterozygous loss-of-function (LoF) variants in SMARCE1, encoding a protein of the chromatin-remodeling complex SWI/SNF, have been described in few familial cases of susceptibility to meningioma, in particular the CCM subtype. Our case confirms the role of NGS in investigating predisposing genes for meningiomas (multiple or recurrent), with specific regard to SMARCE1 in case of pediatric CCM. In addition to the age of onset, the presence of familial clustering or the coexistence of multiple synchronous meningiomas also supports the role of a genetic predisposition that deserves a molecular assessment. Additionally, given the incomplete penetrance, it is of great importance to follow a specific screening or follow-up program for symptomatic and asymptomatic carriers of pathogenic variants in SMARCE1.

Dysplasia and tumor discrimination in brain tissues by combined fluorescence, Raman, and diffuse reflectance spectroscopies.

Identification of neoplastic and dysplastic brain tissues is of paramount importance for improving the outcomes of neurosurgical procedures. This study explores the combined application of fluorescence, Raman and diffuse reflectance spectroscopies for the detection and classification of brain tumor and cortical dysplasia with a label-free modality. Multivariate analysis was performed to evaluate classification accuracies of these techniques-employed both in individual and multimodal configuration-obtaining high sensitivity and specificity. In particular, the proposed multimodal approach allowed discriminating tumor/dysplastic tissues against control tissue with 91%/86% sensitivity and 100%/100% specificity, respectively, whereas tumor from dysplastic tissues were discriminated with 89% sensitivity and 86% specificity. Hence, multimodal optical spectroscopy allows reliably differentiating these pathologies using a non-invasive, label-free approach that is faster than the gold standard technique and does not require any tissue processing, offering the potential for the clinical translation of the technology.

Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome.

The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise in children (defined as "paediatric") based on clinical and molecular characteristics."). However, paediatric-type gliomas may occasionally be present in younger adults and occasionally adult-type gliomas may occur in children. Diffuse low-grade paediatric glioma includes diffuse astrocytoma altered by MYB or MYBL1, low-grade polymorphic juvenile neuroepithelial tumour, angiocentric glioma, and diffuse low-grade glioma with an altered MAPK pathway. Here, we examine these newly recognised entities according to WHO diagnostic criteria and propose an integrated diagnostic approach that can be used to separate these clinically and biologically distinct tumor groups.

Case Report: Congenital Perineal Lipoma Associated With Additional External Genitalia Anomalies.

Perineal lipoma is an uncommon congenital benign tumor sometimes associated with genitourinary or anorectal malformations. Accessory scrotum and accessory labioscrotal fold are infrequent features, often concurrent with perineal tumors. We describe a single institution experience with three consecutive cases of perineal lipoma associated with external genital anomalies, and a literature review.

Pediatric High Grade Glioma Classification Criteria and Molecular Features of a Case Series.

Pediatric high-grade gliomas (pHGGs) encompass a heterogeneous group of tumors. Three main molecular types (H3.3 mutant, IDH mutant, and H3.3/IDH wild-type) and a number of subtypes have been identified. We provide an overview of pHGGs and present a mono-institutional series. We studied eleven non-related pHGG samples through a combined approach of routine diagnostic tools and a gene panel. TP53 and H3F3A were the most mutated genes (six patients each, 54%). The third most mutated gene was EGFR (three patients, 27%), followed by PDGFRA and PTEN (two patients each, 18%). Variants in the EZHIP, MSH2, IDH1, IDH2, TERT, HRAS, NF1, BRAF, ATRX, and PIK3CA genes were relatively infrequent (one patient each, 9%). In one case, gene panel analysis documented the presence of a pathogenic IDH2 variant (c.419G>A, p.Arg140Gln) never described in gliomas. More than one-third of patients carry a variant in a gene associated with tumor-predisposing syndromes. The absence of constitutional DNA did not allow us to identify their constitutional origin.

NTRK Fusions Detection in Paediatric Sarcomas to Expand the Morphological Spectrum and Clinical Relevance of Selected Entities.

Undifferentiated round cell sarcomas (URCS) of soft tissue and bone and tumours of uncertain differentiation (TUD) are commonly ascribed to a subset of neoplasms with low frequency of NTRK gene fusions. However, more recently NTRK-rearranged round and spindle cell tumours have been noted in case reports and in limited or heterogeneous cohorts. The aim of our study was to investigate the presence of NTRK gene fusions in a large retrospective cohort of paediatric URCS and TUD after a systematic review of the diagnosis, according to the recently updated WHO classification scheme. One-hundred and five patients with diagnosis of URCS or TUD, involving the bone or soft tissue, were retrospectively evaluated. After the case selection and the histopathological review of the case cohort, pan-Trk immunohistochemistry (IHC) testing was performed on formalin-fixed paraffin-embedded (FFPE) tissues. Tumour RNA was extracted from FFPE tissue and subjected to next-generation sequencing (NGS) library preparation, using a 10-gene NGS fusion panel, sequenced on an Illumina MiSeq. The NGS-positive cases were further confirmed by real-time PCR. On immunohistochemical screening, 12/105 (11.4%) cases were positive using the pan-Trk antibody, showing three different staining patterns with the cytoplasmic distribution being most common. Molecular analysis using NGS and confirmed by the real-rime PCR detected two positive cases for the ETV6-NTRK3 fusion. The histological pattern of the two positive cases, together with the demonstration of the NTRK rearrangement, leaded to re-classify these previously not otherwise specified sarcomas with uncertain differentiation into the emerging category of NTRK-rearranged neoplasms. In addition, we found the two NTRK fused neoplasms showing a clinical indolent course, in contrast with literature.

New insights in gastrointestinal "pediatric" neoplasms in adult patients: pancreatoblastoma, hepatoblastoma and embryonal sarcoma of the liver. A practical approach by GIPPI-GIPAD Groups.

Pediatric solid neoplasms are rare and very different from those observed in adults. The majority of them are referred to as embryonal because they arise as a result of alterations in the processes of organogenesis or normal growth and are characterized by proliferation of primitive cells, reproducing the corresponding tissue at various stages of embryonic development. This review will focus on embryonal gastrointestinal pediatric neoplasms in adult patients, including pancreatoblastoma, hepatoblastoma, and embryonal sarcoma of the liver. Although they are classically considered pediatric neoplasms, they may (rarely) occur in adult patients. Hepatoblastoma represents the most frequent liver neoplasm in the pediatric population, followed by hepatocellular carcinoma and embryonal sarcoma of the liver; while pancreatoblastoma is the most common malignant pancreatic tumor in childhood. Both in children and adults, the mainstay of treatment is complete surgical resection, either up front or following neoadjuvant chemotherapy. Unresectable and/or metastatic neoplasms may be amenable to complete delayed surgery after neoadjuvant chemotherapy. However, these neoplasms display a more aggressive behavior and overall poorer prognosis in adults than in children, probably because they are diagnosed in later stages of diseases.

Not only a small liver - The pathologist's perspective in the pediatric liver transplant setting.

Pediatric liver transplantation represents a safe and long-lasting treatment option for various disease types, requiring the pathologist's input. Indeed, an accurate and timely diagnosis is crucial in reporting and grading native liver diseases, evaluating donor liver eligibility and identifying signs of organ injury in the post-transplant follow-up. However, as the procedure is more frequently and widely performed, deceptive and unexplored histopathologic features have emerged with relevant consequences on patient management, particularly when dealing with long-term treatment and weaning of immunosuppression.In this complex and challenging scenario, this review aims to depict the most relevant histopathologic conditions which could be encountered in pediatric liver transplantation. We will tackle the conditions representing the main indications for transplantation in childhood as well as the complications burdening the post-transplant phases, either immunologically (i.e., rejection) or non-immunologically mediated. Lastly, we hope to provide concise, yet significant, suggestions related to innovative pathology techniques in pediatric liver transplantation.

Growth arrest-specific 5 lncRNA as a valuable biomarker of chemoresistance in osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumour in children and teenagers, and it is characterised by drug resistance and high metastatic potential. Increasing studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) as oncogenes or tumour suppressors as well as new biomarkers and therapeutic targets in osteosarcoma. The growth arrest-specific 5 (GAS5) lncRNA can function as a tumour suppressor in several cancers. The present study aimed to validate GAS5 and other chemoresistance-associated lncRNAs as biomarkers in a cohort of primary osteosarcoma samples, to obtain predictive information on resistance or sensitivity to treatment. The GAS5 and a panel of lncRNAs related to chemoresistance [SNGH1, FOXD2-AS1, deleted in lymphocytic leukemia (DLEU2) and LINC00963] were evaluated in a cohort of osteosarcoma patients enrolled at the Careggi University Hospital. Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections and the expression levels of the lncRNAs were quantified by qPCR. A bioinformatic analysis on deposited RNA-seq data was performed to validate the qPCR results. Clustering analysis shows that GAS5 could be linked to the expression of isoforms 02 and 04 of the lncRNA DLEU2, whereas the DLEU2 isoform 08 is linked to the lncRNA LINC00963. We found that GAS5 is significantly increased in patients with a good prognosis and is expressed differently between chemosensitive and chemoresistant osteosarcoma patients. However, the results obtained are not concordant with the in-silico analysis performed on the TARGET osteosarcoma dataset. In the future, we would enlarge the case series, including different disease settings.

Infantile hemangiomas ß3-adrenoceptor overexpression is associated with nonresponse to propranolol.

BACKGROUND: Propranolol (antagonist of ß1-/ß2-AR but minimally active against ß3-AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of ß2-AR. However, its success rate is ~60%. Considering the growing interest in the angiogenic role of ß3-ARs, we evaluated a possible relationship between ß3-AR expression and response to propranolol. METHODS: Fifteen samples of surgical biopsies were collected from patients with IH. Three were taken precociously from infants and then successfully treated with propranolol (responder group). Twelve were taken later, from residual lesions noncompletely responsive to propranolol (nonresponder group). A morphometrical analysis of the percentage of ß1-, ß2-, and ß3-ARs positively stained area was compared between the two groups. RESULTS: While no difference was found in both ß1- and ß2-AR expression level, a statistically significant increase of ß3-AR positively stained area was observed in the nonresponder group. CONCLUSIONS: Although the number of biopsies is insufficient to draw definitive conclusions, and the different ß-AR pattern may be theoretically explained by the different timing of samplings, this study suggests a possible correlation between ß3-AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH. IMPACT: Propranolol (unselective antagonist of ß1 and ß2-ARs) is currently the first-line treatment for IHs, with a success rate of ~60%. Its effectiveness has been attributed to its ability to block ß2-ARs. However, ß3-ARs (on which propranolol is minimally active) were significantly more expressed in hemangioma biopsies taken from patients nonresponsive to propranolol. This study suggests a possible role of ß3-ARs in hemangioma pathogenesis and a possible new therapeutic target.

Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.

Clinical-pathological study of 28 glial and mixed neuronal-glial tumors diagnosed within the first year of life.

Our purpose was to investigate the incidence of gliomas and neuronal-glial tumors, their outcome, and H3.3K27M, BRAFV600E, and IDH status in children within 1 year of age affected by CNS tumor. We collected 28 consecutive gliomas and mixed tumors. Immunohistochemistry and/or molecular analyses were performed on formalin-fixed/paraffin-embedded specimens. 24 (86%) tumors were supratentorial. 15 (54%) tumors were astrocytomas (5 glioblastomas, 1 anaplastic astrocytoma, 1 pilocytic astrocytoma, 3 pilomixoid astrocytomas, 2 subependymal giant cell astrocytomas, 3 astrocytomas not otherwise specified (NOS)), 4 (14%) were anaplastic ependymomas, and 9 (32%) were mixed tumors (5 gangliogliomas, 2 gangliocytomas, 2 desmoplastic infantile gangliogliomas (DIGs)). Alive patients were: 4 (67%) affected by high-grade astrocytoma (mean follow-up 64 months), 4 (67%) affected by low-grade astrocytoma (mean follow-up 83 months), 2 (67%) affected by astrocytoma NOS (mean follow-up 60 months), 1 (25%) affected by anaplastic ependymoma (follow-up 12 months), and 9 (100%) affected by mixed tumors (mean follow-up 74 months). H3.3K27M and IDH were not-mutated in any tumor (100%). BRAFV600E mutation was documented in 6 (21%) tumors (4 gangliogliomas, 1 gangliocytoma, and 1 astrocytoma NOS resulted as anaplastic pleomorphic xanthoastrocytoma 8 years later). Gliomas and mixed tumors diagnosed within 1 year of age are morphologically heterogeneous. Moreover, analogously to those affecting older children, they are IDH1-2 and H3.3K27M (when located outside midline) not-mutated while BRAFV600E mutation is typical of gangliogliomas/gangliocytomas and pleomorphic xanthoastrocytomas. High-grade astrocytomas have a more favorable prognosis compared with the same lesions occurring later in life while ependymomas have a poorer outcome.

Primary Intracerebral Alveolar Soft Part Sarcoma: Report of a Case and Review of the Literature.

Alveolar soft part sarcomas (ASPSs) are rare malignant tumors representing ∼1% of all soft tissue sarcomas. Most ASPS occurring in the central nervous system are metastases. In contrast, primary intracranial ASPSs are extremely rare and only 8 cases have been previously reported in English literature. Here, we report a case of primary alveolar soft part sarcoma in a 16-year-old female patient with no evidence of primary extracranial tumors. Histologically this case fulfilled the criteria of ASPS, and a molecular confirmation has been archived. To date, only 9 primary intracranial ASPS cases, including ours, have been reported in the literature. This report highlights the clinical and pathological characteristics, differential diagnosis, and molecular analysis of primary ASPS of the central nervous system.

Dysembryoplastic neuroepithelial tumors: A single-institutional series with special reference to glutamine synthetase expression.

Dysembryoplastic neuroepithelial tumors (DNT) is a benign (World Health Organisation, WHO, grade I) glioneuronal tumor and it represent one of the most frequent neoplasm in patient affected by seizures. The epileptic neuronal activity can be determined by abnormal synchronization, excessive glutamate excitation and\or inadequate GABA inhibition. Increasing evidence suggests that the astrocytes might be involved in this process even if neurons play a relevant role. In particular astrocytes promote the clearance of glutamate, a potent excitatory neurotransmitter of the central nervous system. Indeed, elevated concentrations of extracellular glutamate may determine iper-excitability and seizures as well as other neurological disorders. So, astrocytes, converting glutamate into glutamine via the enzyme glutamine synthetase (GS), could play a protective anti-seizures role. In the present study, we analyzed the immunohistochemical expression of GS in 20 DNTs specimens documenting a constant immunoistochemical expression of GS in astrocytes of the lesional tissue and of the cerebral cortex.

Genetic signature and treatment of pediatric high-grade glioma.

Pediatric high-grade glioma (HGG) is a type of malignancy that carries a poor prognosis. The genetic analysis of HGGs has previously identified useful mutations, the targeting of which has improved prognosis. Thus, further research into the more common mutations, such as H3 histone variants (HIST1H3B and H3F3A) and BRAF V600E, may be useful in identifying tumors with different prognoses, as the mutations are considered to drive two distinct oncogenic programs. The present study performed a retrospective analysis of pediatric HGGs. In total, 42 cases of HGG, including 32 cases (76.1%) of anaplastic astrocytoma and 10 cases (23.8%) of glioblastoma multiforme (GBM), were assessed. The median age of the patients was 7 years (range, 0-32 years). Mutations on histone H3, in particular the K27M and G34R mutations in the distinct variants HIST1H3B and H3F3A, in addition to the presence of the BRAF V600E mutation, were analyzed in 24 patients. The H3F3A K27M mutation was identified in 7 patients (29.1%), while the HIST1H3B K27M mutation was only observed in 1 patient with GBM. In addition, 5 patients harbored a BRAF V600E mutation (21%), while the H3F3A G34R mutation was not recorded in any of the patients. The overall survival of the wild-type patients at 20 months was 68% [confidence interval (CI): 38-85%] compared with 28% (CI: 0.4-60%) in patients with the H3F3A K27M mutation. These results suggested that patients with the H3F3A K27M mutation had a worse prognosis compared with wild-type patients (P=0.0045). Moreover, 3/5 patients with the BRAF V600E mutation had HGGs that were derived from a previous low-grade glioma (LGG; P=0.001). In conclusion, these results suggested that histone H3 mutations may help predict the outcome in patients with HGG. In addition, the BRAF V600E mutation was found to be associated with an increased risk of anaplastic progression. The novel data of the present study may help better define the clinical and radiological characteristics of glioma.