HAM56-Immunoreactive Macrophages in Untreated Infiltrating Gliomas

2001 ◽  
Vol 125 (5) ◽  
pp. 637-641
Author(s):  
Thomas J. Cummings ◽  
Christine M. Hulette ◽  
Sandra H. Bigner ◽  
Gregory J. Riggins ◽  
Roger E. McLendon

Abstract Context.—Classic diagnostic neuropathologic teachings have cautioned against making the diagnosis of neoplasia in the presence of a macrophage population. The knowledge of macrophage distribution should prove useful when confronted with an infiltrating glioma containing macrophages. Objective.—To identify macrophages in untreated, infiltrating gliomas using the monoclonal antibody HAM56, and to confirm their presence in an untreated glioblastoma multiforme (GBM) with the serial analysis of gene expression (SAGE) method. Methods.—We evaluated the presence of macrophages in 16 cases of untreated, supratentorial infiltrating gliomas with the macrophage monoclonal antibody HAM56. We performed SAGE for one case of GBM and for normal brain tissue. Results.—In World Health Organization (WHO) grade II well-differentiated astrocytoma and oligodendroglioma, HAM56 reactivity was noted only in endothelial cells, and unequivocal macrophages were not identified. In WHO grade III anaplastic astrocytoma and anaplastic oligodendroglioma, rare HAM56-positive macrophages were noted in solid areas of tumor. In WHO grade IV GBM, HAM56-positive macrophages were identified in areas of solid tumor (mean labeling index, 8.6%). In all cases of GBM, nonquantitated HAM56-positive macrophages were identified in foci of pseudopalisading cells abutting necrosis and in foci of microvascular proliferations. In none of the cases were granulomas or microglial nodules found, and there was no prior history of surgical intervention, radiation therapy, chemotherapy, or head trauma in these cases. By SAGE, the macrophage-related proteins osteopontin and macrophage-capping protein were overexpressed 12-fold and eightfold, respectively, in one untreated GBM compared with normal brain tissue. In this case, numerous HAM56-positive macrophages (labeling index, 24.5%) were present in the solid portion of tumor, and abundant nonquantified macrophages were identified in foci of pseudopalisading cells abutting necrosis and in foci of microvascular proliferations. Conclusions.—This study confirms the utility of the monoclonal antibody HAM56 in identifying macrophages within untreated infiltrating gliomas. The overexpression of macrophage-related proteins in one case of GBM as detected by SAGE signifies that macrophages may be present in untreated GBMs.

2021 ◽  
Author(s):  
Kosuke Nakajo ◽  
Takehiro Uda ◽  
Toshiyuki Kawashima ◽  
Yuzo Terakawa ◽  
Kenichi Ishibashi ◽  
...  

Abstract Purpose: This study aimed whether the uptake of amino tracer positron emissiontomography (PET) can be used as an additional imaging biomarker to estimatethe prognosis of glioma.Methods: Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) gradeⅡ-Ⅳ astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution.Results: Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (PFS) (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10-0.41, p<0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95%CI 1.23-22.8, p=0.025; glioblastoma: HR 11.52, 95%CI 2.27-58.47, p=0.0032), preoperative KPS≥80 (HR 0.23, 95%CI 0.09-0.62, p=0.004), maximum lesion-to-contralateral normal brain tissue (LN max)≥4.03 (HR 0.24, 95%CI 0.08-0.71, p=0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95%CI 1.81-109.2, p=0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max≥ 4.03 (29.3 months) than in patients with LN max<4.03 (not reached; p=0.03). OS differed significantly between patients with IDH mutant/LN max<4.03 and patients with IDH mutant/LN max ≥4.03.Conclusions: LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO gradeⅡ-Ⅳ astrocytic glioma.


2019 ◽  
Vol 23 (1) ◽  
pp. 61
Author(s):  
E. V. Stupak ◽  
S. E. Titov ◽  
Yu. A. Versyaskina ◽  
L. G. Akhmerova ◽  
I. E. Zhimulyov ◽  
...  

<p><strong>Aim.</strong> To identify novel microRNA markers as survival predictors in patients with supratentorial gliomas.<br /><strong>Methods.</strong> This study involved the analysis of tumour and normal brain tissue biopsy samples obtained from patients undergoing combination treatment for supratentorial gliomas of different World Health Organization (WHO) grades. Real-time polymerase chain reaction was used to determine the expression profiles of ten microRNAs, following comparison with clinical treatment results: tumour morphology, WHO grade, patient age, Karnofsky scale, treatment type, postsurgical survival rate and histological diagnosis. The mean age of surgically treated patients [62 (57.9%) males and 45 (42.1%) females] was 48.8 ± 14 years. There were 17 (16%), 30 (28%) and 60 (56%) patients with grade II, III and IV (glioblastoma) gliomas, respectively. Statistical analysis was performed using Statistica version 10.0 and GraphPad Prism version 5.<br /><strong>Results.</strong> Four microRNAs (miRNA-31, miRNA-21, miRNA-223 and miRNA-221) were strongly correlated with worse survival, when over-expressed, indicating their potential utility as survival predictors in glioma patients. Overexpression of these microRNAs in glioma tissue, lack of adjuvant therapy such as chemotherapy or radiotherapy and age &gt; 48 years were identified as factors for worse prognosis.</p><p><strong>Funding:</strong> This work was supported by the program of fundamental scientific research on the topic 0310-2019-0003.</p><p><strong>Conflict of interest:</strong> The authors declare no conflict of interest.</p>


2010 ◽  
Vol 112 (5) ◽  
pp. 925-933 ◽  
Author(s):  
Susan L. McGovern ◽  
Kenneth D. Aldape ◽  
Mark F. Munsell ◽  
Anita Mahajan ◽  
Franco DeMonte ◽  
...  

Object Despite a favorable outcome for most patients with WHO Grade I meningiomas, a subset of these patients will have recurrent or progressive disease that advances to a higher grade and requires increasingly aggressive therapy. The goal of this study was to identify clinical characteristics associated with the recurrence of benign meningiomas and their acceleration to atypical and malignant histological types. Methods Records of 216 patients with WHO Grade I, II, or III meningioma that were initially treated between 1965 and 2001 were retrospectively reviewed. Median follow-up was 7.2 years. Results Patients with non–skull base cranial meningiomas (82 of 105 [78%]) were more likely to have undergone a gross-total resection than patients with skull base meningiomas (32 of 78 [41%]; p < 0.001). Consequently, patients with Grade I non–skull base cranial meningiomas had better 5-year recurrence-free survival (69%) than patients with Grade I skull base meningiomas (56%) or Grade II or III tumors at any site (50%; p = 0.005). Unexpectedly, patients with non–skull base tumors who experienced a recurrence (8 of 22 [36%]) were more likely than patients with skull base tumors (1 of 19 [5%]) to have a higher grade tumor at recurrence (p = 0.024). Furthermore, the median MIB-1 labeling index of Grade I non–skull base cranial meningiomas (2.60%) was significantly higher than that of Grade I skull base tumors (1.35%; p = 0.016). Conclusions Cranial meningiomas that occur outside of the skull base are more likely to have a higher MIB-1 labeling index and recur with a higher grade than those within the skull base, suggesting that non–skull base cranial tumors may have a more aggressive biology than skull base tumors.


2021 ◽  
Author(s):  
Kosuke Nakajo ◽  
Takehiro Uda ◽  
Toshiyuki Kawashima ◽  
Yuzo Terakawa ◽  
Kenichi Ishibashi ◽  
...  

Abstract Purpose: This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma.Methods: Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) gradeⅡ-Ⅳ astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution.Results: Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (PFS) (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10-0.41, p<0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95%CI 1.23-22.8, p=0.025; glioblastoma: HR 11.52, 95%CI 2.27-58.47, p=0.0032), preoperative KPS≥80 (HR 0.23, 95%CI 0.09-0.62, p=0.004), maximum lesion-to-contralateral normal brain tissue (LN max)≥4.03 (HR 0.24, 95%CI 0.08-0.71, p=0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95%CI 1.81-109.2, p=0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max≥ 4.03 (29.3 months) than in patients with LN max<4.03 (not reached; p=0.03). OS differed significantly between patients with IDH mutant/LN max<4.03 and patients with IDH mutant/LN max ≥4.03.Conclusions: LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO gradeⅡ-Ⅳ astrocytic glioma.


2003 ◽  
Vol 279 (5) ◽  
pp. 3694-3698 ◽  
Author(s):  
Vladka Čurin Šerbec ◽  
Mara Bresjanac ◽  
Mara Popović ◽  
Katrina Pretnar Hartman ◽  
Vesna Galvani ◽  
...  

Author(s):  
Deepti Narasimhaiah ◽  
Bejoy Thomas ◽  
Mathew Abraham ◽  
Rajalakshmi Poyuran

AbstractDiffuse midline glioma, H3 K27M-mutant, is a World Health Organization (WHO) grade IV glioma arising in pons, thalamus, and spinal cord. They show mutations resulting in replacement of lysine at position 27 by methionine (K27M) of histone genes, H3F3A, HIST1H3B, and HIST1H3C. The H3 K27M mutant protein is identified in tumor tissue by immunohistochemistry. As these mutations are clonal and homogeneous, the mutant protein is normally identified in all tumor cells. Here we report a case of diffuse midline glioma with mosaic pattern of expression of H3 K27M mutant protein and discuss the diagnostic and therapeutic implications of this unusual pattern.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariano Guardia Clausi ◽  
Alexander M. Stessin ◽  
Zirun Zhao ◽  
Stella E. Tsirka ◽  
Samuel Ryu

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.


Author(s):  
Mizuho Inoue ◽  
Mohamed Labib ◽  
Alexander Yang ◽  
A. Samy Youssef

AbstractA case of a recurrent sphenocavernous meningioma is presented. The patient is a 42-year-old male who presented with an episode of transient right-sided numbness. A magnetic resonance imaging (MRI) revealed a large left sphenocavernous meningioma. The patient underwent a frontotemporal craniotomy for tumor resection. Near total resection was achieved with minimal residual in the left cavernous sinus (CS) and orbital apex. The pathology was consistent with meningioma, World Health Organization (WHO) grade I. A follow-up MRI was done 9 months after surgery and showed a growth of the residual tumor, which was treated with intensity modulated radiotherapy. Tumor growth was detected on serial imaging over a 4-year period. Surgical resection was offered. A left frontotemporal craniotomy with pretemporal transcavernous approach was performed. The bone flap was reopened and the dura was opened in a Y-shaped fashion. The roof of the optic canal was drilled off, and the falciform ligament was opened to decompress the optic nerve. The tumor was disconnected from the anterior clinoid region (the anterior clinoid process was eroded by the tumor) and reflected off the wall of the lateral CS. Tumor was adherent to the V2 fascicles (the lateral CS wall was resected in the first surgery) and was sharply dissected off. Gross total resection was achieved. The pathology was consistent with meningioma, WHO grade I. The patient had an unremarkable postoperative course without any new neurological deficits.The link to the video can be found at: https://youtu.be/KVBVw_86JqM.


BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jessica Rossi ◽  
Lucia Giaccherini ◽  
Francesco Cavallieri ◽  
Manuela Napoli ◽  
Claudio Moratti ◽  
...  

Abstract Background Glioblastoma (GBM) is known for its devastating intracranial infiltration and its unfavorable prognosis, while extracranial involvement is a very rare event, more commonly attributed to IDH wild-type (primary) GBM evolution. Case presentation We present a case of a young woman with a World Health Organization (WHO) grade II Astrocytoma evolved to WHO grade IV IDH mutant glioblastoma, with subsequent development of lymphatic and bone metastases, despite the favorable biomolecular pattern and the stability of the primary brain lesion. Conclusions Our case highlights that grade II Astrocytoma may evolve to a GBM and rarely lead to a secondary metastatic diffusion, which can progress quite rapidly; any symptoms referable to a possible systemic involvement should be carefully investigated.


2016 ◽  
Vol 140 (5) ◽  
pp. 437-448 ◽  
Author(s):  
Joo Young Kim ◽  
Seung-Mo Hong

Context.—Gastrointestinal (GI) and pancreatobiliary tracts contain a variety of neuroendocrine cells that constitute a diffuse endocrine system. Neuroendocrine tumors (NETs) from these organs are heterogeneous tumors with diverse clinical behaviors. Recent improvements in the understanding of NETs from the GI and pancreatobiliary tracts have led to more-refined definitions of the clinicopathologic characteristics of these tumors. Under the 2010 World Health Organization classification scheme, NETs are classified as grade (G) 1 NETs, G2 NETs, neuroendocrine carcinomas, and mixed adenoneuroendocrine carcinomas. Histologic grades are dependent on mitotic counts and the Ki-67 labeling index. Several new issues arose after implementation of the 2010 World Health Organization classification scheme, such as issues with well-differentiated NETs with G3 Ki-67 labeling index and the evaluation of mitotic counts and Ki-67 labeling. Hereditary syndromes, including multiple endocrine neoplasia type 1 syndrome, von Hippel-Lindau syndrome, neurofibromatosis 1, and tuberous sclerosis, are related to NETs of the GI and pancreatobiliary tracts. Several prognostic markers of GI and pancreatobiliary tract NETs have been introduced, but many of them require further validation. Objective.—To understand clinicopathologic characteristics of NETs from the GI and pancreatobiliary tracts. Data Sources.—PubMed (US National Library of Medicine) reports were reviewed. Conclusions.—In this review, we briefly summarize recent developments and issues related to NETs of the GI and pancreatobiliary tracts.


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