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BACKGROUND: With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. METHODS: Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. RESULTS: Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4 months and 85.2 months, respectively, longer than that for IDH-wildtype gliomas (5.6 months and 12.0 months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. CONCLUSION: As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype.
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Neoplasias do Tronco Encefálico , Glioma , Isocitrato Desidrogenase , Mutação , Humanos , Isocitrato Desidrogenase/genética , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/terapia , Masculino , Glioma/genética , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/terapia , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Prognóstico , Imageamento por Ressonância Magnética , Adulto JovemRESUMO
Purpose: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). Results: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma.
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Radioisótopos de Flúor , Glioblastoma , Misonidazol/análogos & derivados , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Fluordesoxiglucose F18 , Tomografia Computadorizada por Raios X , Tomografia por Emissão de Pósitrons , Glucose , Hipóxia , RNA Mensageiro , Glucose-6-FosfataseRESUMO
OBJECTIVE: CD44 is a major cell surface receptor involved in cell adhesion and migration. The overexpression of CD44 is a poor prognostic factor in many neoplasms, including meningiomas. The aim of this study was to investigate the association between CD44 gene expression and clinical signatures of primary meningiomas. METHODS: CD44 gene expression was quantitatively evaluated by snap freezing tumor tissues obtained from 106 patients with primary meningioma. The relationships between CD44 expression and clinical signatures of meningiomas, including histological malignancy, tumor volume, and peritumoral brain edema (PTBE), were analyzed. PTBE was assessed using the Steinhoff classification (SC) system (from SC 0 to SC III). RESULTS: CD44 gene expression in WHO grade 2 and 3 meningiomas was significantly higher than that in grade 1 meningiomas. In addition, CD44 expression increased with the severity of PTBE. Particularly, among the grade 1 meningiomas or small-sized tumors (maximum tumor diameter < 43 mm), CD44 expression in tumors with severe PTBE (SC II or III) was significantly higher than that in tumors without or with mild PTBE (SC 0 or I). Multivariate logistic regression analysis also revealed that overexpression of CD44 was an independent significant factor of severe PTBE development in primary meningiomas. CONCLUSIONS: In addition to tumor cell aggressiveness, CD44 expression promotes the development of PTBE in meningioma. Since PTBE is a strong factor of tumor-related epilepsy or cognitive dysfunction in patients with meningioma, CD44 is thus a potential therapeutic target in meningioma with PTBE.
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Edema Encefálico , Receptores de Hialuronatos , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/metabolismo , Meningioma/complicações , Meningioma/patologia , Meningioma/genética , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/genética , Edema Encefálico/metabolismo , Edema Encefálico/etiologia , Edema Encefálico/patologia , Masculino , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/genética , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Relevância ClínicaRESUMO
BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.
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Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.
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Astrocitoma , Neoplasias Encefálicas , Encondromatose , Glioma , Oligodendroglioma , Feminino , Humanos , Adulto Jovem , Adulto , Oligodendroglioma/genética , Oligodendroglioma/patologia , Encondromatose/complicações , Encondromatose/genética , Encondromatose/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Hibridização in Situ Fluorescente , Isocitrato Desidrogenase/genética , Glioma/genética , Astrocitoma/genética , Astrocitoma/patologia , MutaçãoRESUMO
OBJECTIVE: In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. METHODS: The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. RESULTS: Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. CONCLUSIONS: End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.
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Facial nerve function improvement is a challenging goal in facial nerve schwannoma (FNS) surgery. Intraoperative continuous monitoring of evoked facial nerve electromyograms (CFN-EMGs) is performed in acoustic neuroma surgery to preserve facial nerve function. CFN-EMGs were applied in decompression surgery for FNS with severe facial paresis. A 39-year-old woman presented with a sudden onset of vertigo, left hearing disturbance, and severe left facial palsy with House-Brackmann (HB) grade 5. FNS was strongly suspected based on the patient's clinical course and magnetic resonance imaging findings, and the patient underwent surgical decompression of the internal auditory canal (IAC) to improve facial nerve function 9 weeks after onset. CFN-EMG responses suddenly improved after removing the posterior wall of the IAC and incising its dura matter. Since the patient's facial nerve paresis improved to HB grade 2 after surgery, CFN-EMGs could detect the moment of facial nerve decompression. This would be the first report to show that CFN-EMGs applied in decompression surgery for FNS could detect the effects of decompression during surgery in real-time. Thus, CFN-EMGs may be an effective monitoring method in decompression surgery for FNS.
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The aim of this study was to analyze the clinical and radiological characteristics of glioblastomas (GBMs) harboring a BRAF mutation. Sequencing analysis of BRAF, IDH1/2, and TERT promoters was performed on GBM samples of patients older than 15 years. The clinical, pathological, and radiological data of patients were retrospectively reviewed. Patients were classified into three groups according to their BRAF and IDH1/2 status: BRAF group, IDH group, and BRAF/IDH-wild-type (WT) group. Among 179 GBM cases, we identified nine cases with a BRAF mutation and nine with IDH mutation. The WT group had 161 cases. Age at onset in the BRAF group was significantly lower compared to the WT group and was similar to the IDH group. In cases with negative IDH1-R132H staining and age < 55 years, 15.2% were BRAF-mutant cases. Similar to the IDH group, overall survival of the BRAF group was significantly longer compared with the WT group. Among nine cases in the BRAF group, three cases had hemorrhagic onset and prior lesions were observed in two cases. In conclusion, age < 55 years, being IDH1-R132H negative, with hemorrhagic onset or the presence of prior lesions are factors that signal recommendation of BRAF analysis for adult GBM patients.
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Neoplasias Encefálicas , Glioblastoma , Proteínas Proto-Oncogênicas B-raf , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Glioblastoma/diagnóstico por imagem , Glioblastoma/enzimologia , Glioblastoma/genética , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Estudos RetrospectivosRESUMO
The diagnosis of mosaicism is challenging in patients with neurofibromatosis type 2 (NF2) subset due to low variant allele frequency. In this study, we generated induced pluripotent stem cells (iPSCs) were generated from a patient clinically diagnosed with NF2 based on multiple schwannomas, including bilateral vestibular schwannomas and meningiomas. Genetic analysis of the patient's mononuclear cells (MNCs) from peripheral blood failed to detect NF2 alteration but successfully found p.Q65X (c.193C>T) mutation in all separate tumors with three intracranial meningiomas and one intraorbital schwannoma, and confirming mosaicism diagnosis in NF2 alteration using deep sequencing. Five different clones with patient-derived iPSCs were established from MNCs in peripheral blood, which showed sufficient expression of pluripotent markers. Genetic analysis showed that one of five generated iPSC lines from MNCs had the same p.Q65X mutation as that found in NF2. There was no significant difference in the expression of genes related to NF2 between iPSC clones with the wild-type and mutant NF2. In this case, clonal expansion of mononuclear bone marrow-derived stem cells recapitulated mosaicism's genetic alteration in NF2. Patient-derived iPSCs from mosaic NF2 would contribute to further functional research of NF2 alteration.
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Células-Tronco Pluripotentes Induzidas , Neoplasias Meníngeas , Meningioma , Neurofibromatose 2 , Células Clonais/patologia , Genes da Neurofibromatose 2 , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Neoplasias Meníngeas/genética , Meningioma/genética , Mutação , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/genéticaRESUMO
PURPOSE: To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis. METHODS AND RESULTS: A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abducens nerve palsy. At the same time, he complained of fatigue and loss of appetite. Head magnetic resonance imaging demonstrated enlargement of the pituitary stalk and pituitary gland, corresponding to hypophysitis. Hormone stimulation tests showed blunted responses with respect to all anterior pituitary hormones. Central diabetes insipidus was diagnosed on the basis of a hypertonic saline loading test. Taking these findings together, a diagnosis of panhypopituitarism was made. Computed tomography showed enlargement of hilar lymph nodes. Biopsies of the hilar lymph nodes revealed non-caseating epithelioid cell granulomas that were consistent with sarcoidosis. Biopsy of the anterior pituitary revealed mild lymphocyte infiltration in the absence of IgG4-positive cells, non-caseating granulomas, or neoplasia. Western blotting revealed the presence of anti-rabphilin-3A antibody, supporting a diagnosis of lymphocytic panhypophysitis. Because the patient had no visual impairment or severe uveitis, we continued physiological hormone replacement therapy and topical steroid therapy for the uveitis. CONCLUSION: To the best of our knowledge, this is the first case of anti-rabphilin 3A antibody positive lymphocytic panhypophysitis comorbid with sarcoidosis, diagnosed by both pituitary and hilar lymph node biopsy. The utility of anti-rabphilin-3A antibody for the differential diagnosis of hypophysitis like this case should be clarified with further case studies.
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Hipofisite Autoimune , Diabetes Insípido Neurogênico , Hipopituitarismo , Sarcoidose Pulmonar , Sarcoidose , Hipofisite Autoimune/diagnóstico , Hipofisite Autoimune/tratamento farmacológico , Diabetes Insípido Neurogênico/diagnóstico , Humanos , Hipopituitarismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Hipófise/patologia , Sarcoidose/complicações , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/patologiaRESUMO
The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow-Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered.
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Neoplasias Meníngeas , Meningioma , Neurofibromatose 2 , Humanos , Imageamento por Ressonância Magnética , Meningioma/diagnóstico por imagem , Neurofibromatose 2/diagnóstico por imagem , Estudos RetrospectivosRESUMO
We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.
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Neoplasias Encefálicas/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Lesões por Radiação/diagnóstico por imagem , Adolescente , Adulto , Idoso , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Radioisótopos de Carbono/farmacocinética , Criança , Intervalos de Confiança , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Metionina/farmacocinética , Pessoa de Meia-Idade , Necrose , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Lesões por Radiação/patologia , Compostos Radiofarmacêuticos/farmacocinética , Fatores de Tempo , Adulto JovemRESUMO
The majority of oligodendroglial tumors harbor mutations in the telomerase reverse transcriptase (TERT) gene (TERT) promoter and the isocitrate dehydrogenase 1/2 (IDH1/2) gene (IDH1/2), as well as 1p/19q codeletion. Generally, TERT promoter mutations, C250T and C228T, are mutually exclusive. We present a case of oligodendroglioma harboring both C250T and C228T mutations in TERT promoter. A 38-year-old man presented with grand mal seizures and underwent a resection surgery for a left frontal lobe tumor. He was pathologically diagnosed as having oligodendroglioma and was carefully observed. At 48 years of age, he underwent another resection surgery due to tumor regrowth, with the pathological diagnosis of anaplastic oligodendroglioma. Genetic analysis of the initial tumor specimen revealed IDH1 R132H mutation and both C250T and C228T mutations in TERT promoter. Using mutation-specific primers, two mutations were considered to be distributed in different alleles. In the tumor specimen obtained during the second surgery, IDH1 R132H mutation was detected to be similar to that of the initial specimen; however, only C228T mutation was detected in TERT promoter. The 1p/19q codeletion was detected in both the initial and recurrent tumor specimens. According to the sequencing data from the two tumor specimens, although TERT promoter mutation has been considered to be an early genetic event in the tumorigenesis of oligodendroglial tumors, it is likely that the C250T and C228T mutations in TERT promoter are subclonally distributed in the same tumor specimen of the present case.
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Neoplasias Encefálicas/genética , Mutação , Recidiva Local de Neoplasia/genética , Oligodendroglioma/genética , Regiões Promotoras Genéticas , Telomerase/genética , Adulto , Neoplasias Encefálicas/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Oligodendroglioma/patologia , Oligodendroglioma/cirurgiaRESUMO
A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.
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Neoplasias Encefálicas , Calcinose , Neoplasias Neuroepiteliomatosas , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Pré-Escolar , Proteínas Correpressoras/análise , Proteínas Correpressoras/genética , Feminino , Duplicação Gênica , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Radiologia , Proteínas Repressoras/análise , Proteínas Repressoras/genéticaRESUMO
Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient's condition.
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Neoplasias Encefálicas , Glioblastoma , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Procedimentos Cirúrgicos de Citorredução , Glioblastoma/tratamento farmacológico , Glioblastoma/cirurgia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: Most types of intracranial germ cell tumors (IGCTs) are sensitive to chemoradiation. However, biopsy specimens are usually small and thus cannot be used for obtaining an accurate pathological diagnosis. Recently, the cerebrospinal fluid (CSF) placental alkaline phosphatase (PLAP) value has been considered a new biomarker of IGCTs. The present study aimed to evaluate the discriminatory characteristics of the CSF-PLAP value upon diagnosis and at the time of recurrence in patients with IGCTs. METHODS: Between 2015 and 2019, this study included 37 patients with tumors located in the intraventricular and/or periventricular region. The CSF-PLAP level was assessed before the patients received any treatment. The PLAP level was evaluated during and after first-line chemoradiotherapy in 7 patients with IGCTs. The CSF-PLAP values were compared according to histological diagnosis, and the correlation between these values and radiographical features was assessed. The CSF-PLAP values of 6 patients with IGCTs with suspected recurrence were evaluated based on neuroimaging findings. RESULTS: The CSF-PLAP values were significantly higher in patients with IGCTs than in those with other types of brain tumor (n = 19 vs. 18; median: 359.0 vs. <8.0 pg/mL). The specificity and sensitivity were 88 and 95%, respectively, with a cutoff value of 8.0 pg/mL. In patients with IGCT, the CSF-PLAP value was higher in patients with germinoma than in those with nongerminomatous germ cell tumors (n = 12 vs. 7; median: 415.0 vs. 359.0 pg/mL). Regarding the time course, the CSF-PLAP value decreased to below the detection limit after the reception of first-line chemoradiotherapy in all 7 patients. A significant correlation was observed between the initial CSF-PLAP value and the tumor reduction volume after receiving first-line chemoradiotherapy (p < 0.0003, R2 = 0.6165, logY = 1.202logX - 1.727). Among the patients with suspected IGCT recurrence (n = 6), the CSF-PLAP value was high in patients with recurrence (n = 3; median: 259.0 pg/mL), and that in patients (n = 3) without recurrence was below the lower detection limit. CONCLUSIONS: The CSF-PLAP level is a useful biomarker during the initial diagnosis of IGCTs and at the time of recurrence. It may be associated with the volume of germinomatous components of tumors.
Assuntos
Fosfatase Alcalina/líquido cefalorraquidiano , Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias Encefálicas/líquido cefalorraquidiano , Isoenzimas/líquido cefalorraquidiano , Neoplasias Embrionárias de Células Germinativas/líquido cefalorraquidiano , Adolescente , Adulto , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Proteínas Ligadas por GPI/líquido cefalorraquidiano , Germinoma/líquido cefalorraquidiano , Germinoma/patologia , Humanos , Masculino , Recidiva Local de Neoplasia/líquido cefalorraquidiano , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/enzimologia , Neoplasias Embrionárias de Células Germinativas/patologia , Adulto JovemRESUMO
OBJECTIVE: The authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage. METHODS: Patients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors' institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded. RESULTS: Among 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation. CONCLUSIONS: Although the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.
Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/genética , Glioma/complicações , Glioma/genética , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adolescente , Astrocitoma/complicações , Astrocitoma/genética , Ventrículos Cerebrais , Criança , Pré-Escolar , Feminino , Humanos , Hemorragias Intracranianas/complicações , Imageamento por Ressonância Magnética , Masculino , Mutação/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: Although newly diagnosed high-grade glioma patients in Japan can receive bevacizumab (BEV) as first-line chemotherapy, randomized clinical trials have not shown a survival benefit for BEV for these patients. In this study, we investigated whether selective add-on BEV for patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA) improves prognosis, in cases where tumors were continuously growing during radiotherapy concomitant with temozolomide (TMZ). METHODS: We conducted a retrospective survey of the overall survival (OS) of patients with GBM/AAs who were treated in our institution between 2006 and 2016. Patients whose tumors were continuously growing regardless of radiotherapy were categorized as the "progressive" group; remaining patients were categorized as the "non-progressive" group. Since 2013, patients in the "progressive" group received add-on BEV therapy with the Stupp regimen during or just after radiotherapy. RESULTS: Of 151 GBM/AA patients, 34 (22.5%) were categorized in the "progressive" group. Median OSs of the "progressive" and "non-progressive" groups were 13.2 months and 25.3 months, respectively (P<0.001). Twelve patients in the "progressive" group received add-on BEV therapy, and their median OS was 20.2 months; whereas for the remaining 22 patients in the "progressive" group who were treated before the BEV era, their median OS was 10.5 months. In the "progressive" group, add-on BEV significantly extended OS (P=0.018) and was the lone clinical factor of better prognosis. CONCLUSIONS: We found that, for patients with GBM/AAs whose tumors were continuously growing during radiotherapy, add-on BEV treatment resulted in survival benefits.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Prognóstico , Estudos Retrospectivos , Temozolomida/uso terapêuticoRESUMO
PURPOSE: Overexpression of CD44 has been detected in many types of tumor tissues. Moreover, CD44 is recognized as a cancer stem cell marker for many cancers. However, the prognostic value of CD44 for glioma patients has not yet been clarified. The authors tried to explore the impact of CD44 expression on grade II/III glioma patients. METHODS: To assess the RNA expression levels of CD44 in glioma tissues and normal brain tissues, meta-analyses were conducted in the online Oncomine database. The mRNA expression levels of CD44, CD44s, and CD44v2-v10 in 112 grade II/III glioma patients in Hokkaido University Hospital (HUH) were detected by qPCR. The RNA-seq data and clinical data of grade II/III glioma patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. RESULTS: Based on the Oncomine database, CD44 has significantly high expression in glioma tissues as compared with normal tissues. We explored the clinical relevance of CD44 mRNA expression based on the HUH cohorts, the TCGA cohorts, and the CGGA cohorts. In survival analysis, high mRNA expression of CD44 was correlated with poor overall survival and poor progression-free survival in grade II/III glioma patients. Multivariate Cox regression analyses confirmed CD44 as an independent prognostic factor for grade II/III glioma patients. CONCLUSIONS: The present study suggests that overexpression of CD44 is associated with a poor prognosis for grade II/III glioma patients. Moreover, our findings suggest that CD44 could serve as a prognostic biomarker in grade II/III glioma patients.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Glioma/diagnóstico , Glioma/metabolismo , Receptores de Hialuronatos/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Dural reconstruction after transpetrosal approaches is complicated because complete primary closure of presigmoid dura mater is difficult to achieve. To address this problem, we use biocompatible polyglycolic acid (PGA) felt (Durawave) to reconstruct dural defects. To evaluate the use of PGA felt in dural reconstruction, we compared these results with those after conventional duraplasty using autologous fascia grafts. METHODS: We retrospectively surveyed all cases involving a transpetrosal approach reported since 2013. In the conventional procedure, autologous fascia was fixed over the dural defect using stay sutures; any remaining dead space was obliterated by placing abdominal fat grafts. Since April 2017, we have used PGA felt instead of fascia. RESULTS: Of the 37 cases identified, 27 were reconstructed according to the conventional procedure, and the remaining 10 cases were reconstructed using PGA felt. Among the 27 conventional cases, 8 involved cerebrospinal fluid (CSF)-related complications, including 3 cases of rhinorrhea and 5 cases of subcutaneous fluid collection, and 2 cases (7%) required repair surgery. Of the 10 cases involving PGA felt, 1 case (10%) involved subcutaneous fluid collection and required repair surgery, and whereas the remaining 9 cases had no evidence of CSF leakage. In addition, the median dural reconstruction time using PGA felt was 9 minutes, significantly shorter than that when autologous fascia was used (median, 44 minutes). CONCLUSIONS: Using PGA felt for presigmoid dura simplifies dural reconstruction because it obviates the need to suture in a deep field. PGA felt has the potential to prevent CSF-related complications after transpetrosal approaches.