Anaplastic Glioneuronal Tumor With KIAA1549/BRAF Fusion

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S102-S102
Author(s):  
Zhenggang Xiong ◽  
Prithvi Narayan
Keyword(s):  
Neoplastic Cell ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
High Grade ◽  
Left Frontal Lobe ◽  
Ki 67 ◽  
Blurry Vision ◽  
Immunohistochemical Assessment ◽  
Braf Fusion ◽  
Glioneuronal Tumors

Abstract Introduction Glioneuronal tumors are usually low grade and have a favorable prognosis. The anaplastic glioneuronal tumor with KIAA1549/BRAF fusion has not yet been documented. This article reports a pediatric case of glioneuronal tumor with anaplasia and KIAA1549/BRAF fusion to illuminate the importance of KIAA1549/BRAF fusion in the tumorigenesis and clinical management of high-grade glioneuronal tumors. Case Presentation A 10-year-old boy presented with 1 year of headache and 3 months of blurry vision and proptosis. Ophthalmologic evaluation revealed bilateral papilledema. Magnetic resonance imaging showed a large mixed cystic and solid mass in the left frontal lobe of cerebrum. Histologic analysis demonstrated a glioneuronal tumor with papillary/pseudopapillary growth pattern, focal necrosis, microcalcification, and brisk mitotic activity with a high Ki-67 labeling index of focally up to 20%. Immunohistochemical assessment identified a mixed glial and neuronal neoplastic cell population. Molecular studies revealed a KIAA1549/BRAF fusion. Conclusion KIAA1549/BRAF fusion may play an important role in the oncogenesis of high-grade glioneuronal tumors. In view of the fact that effective, targeted therapies for the tumors with KIAA1549/BRAF fusion are clinically available, detection of KIAA1549/BRAF fusion for glioneuronal tumors, particularly high-grade glioneuronal tumors, is helpful.

scholarly journals LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii371-iii371
Author(s):  
Andge Valiakhmetova ◽  
Ludmila Papusha ◽  
Ludmila Yasko ◽  
Alexander Druy ◽  
Alexander Karachunsky ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Braf Inhibitor ◽  
Complete Response ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Conventional Chemotherapy ◽  
Diffuse Leptomeningeal Glioneuronal Tumor ◽  
Braf Fusion

Abstract Diffuse leptomeningeal glioneuronal tumor (DLGNT) is an extremely rare disease, newly recognized in the 2016 WHO classification of tumors of the CNS. Most DLGNTs are low-grade neuroepithelial tumors with variable elements of neuronal/neurocytic and glial differentiation, have diffuse leptomeningeal enhancement on MRI, and typically harbor KIAA1549-BRAF fusions. Other alterations, such as the BRAF V600E substitution, are less common. Here, we present three cases of DLGNT with different presentations and outcomes. The first patient is a 2yr-old male with KIAA1549-BRAF fusion, and was treated with Carbo/VCR chemotherapy after a biopsy, with resultant ongoing stable disease for 3.5 years. The second patient, an 8yr-old male had the BRAF V600E point mutation and was treated with conventional chemotherapy (VCR/carboplatin). On progression, he received the BRAF inhibitor vemurafenib, achieving a complete response which last 14 month. The third patient, a 27 month old male, harbored a KIAA1549-BRAF fusion and was treated at diagnosis with the MEK inhibitor trametinib. The tumor has been radiographically stable in the context of clinical improvement for 21 months since the treatment initiation, ongoing 24 month. In summary, we present further evidence of MAPK pathway alterations in children with DLGNT. We describe a range of molecular presentations and clinical outcomes, including one patient treated with conventional chemotherapy with further stabilization of disease during 3.5 years and two patients who were successfully treated with targeted therapy.

Increased proteasome degradation of cyclin-dependent kinase inhibitor p27 is associated with a decreased overall survival in mantle cell lymphoma

Blood ◽  
2000 ◽  
Vol 95 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Roberto Chiarle ◽  
Leo M. Budel ◽  
Jeffrey Skolnik ◽  
Glauco Frizzera ◽  
Marco Chilosi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Degradation ◽  
Mantle Cell Lymphoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Cell Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Mantle Cell

Mantle cell lymphoma (MCL) is an aggressive neoplasm characterized by the deregulated expression of cyclin D1 by t(11;14). The molecular mechanisms responsible for MCL's clinical behavior remain unclear. The authors have investigated the expression of p53, E2F-1, and the CDK inhibitors p27 and p21 in 110 MCLs, relating their expression to proliferative activity (Ki-67). For comparison, they have similarly analyzed low-grade (12 MALT, 16 CLL/SLL) and high-grade (19 DLCL) lymphomas. p53 was detected more frequently in large-cell MCL (l-MCL; 5 of 7) than in classical MCL (s-MCL; 13 of 103) and DLCL (8 of 19). In MCL and DLCL, the percentage of E2F-1+ nuclei was high, correlating with high Ki-67 expression. Most MCLs (91 of 112) and DLCLs (12 of 19) showed a loss of p27; MALT and CLL/SLL, however, were p27 positive. Reverse transcription–polymerase chain reaction and in vitro protein degradation assays demonstrated that MCLs have normal p27 mRNA expression but increased p27 protein degradation activity via the proteasome pathway. Correlation of MCL p53 and p27 expression with clinical data showed an association between reduced overall survival rates and the overexpression of p53 (P = .001), the loss of p27 (P = .002), or both. Loss of p27 identified patients with a worse clinical outcome among p53 negative cases (P = .002). These findings demonstrated that MCL has a distinct cell cycle protein expression similar to that of high-grade lymphoma. The loss of p27 and the overexpression of p53 in MCL are prognostic markers that identify patients at high risk. The demonstration that low levels of p27 in MCL result from enhanced proteasome-mediated degradation should encourage additional clinical trials. (Blood. 2000;95:619-626)

Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Muhammad Masood Hassan ◽  
Tammey Naab ◽  
Ali Afsari
Keyword(s):  
Urothelial Carcinoma ◽  
Proliferation Index ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Prostate Hyperplasia ◽  
History Of ◽  
Papillary Urothelial Carcinoma ◽  
Artery Disease ◽  
Umbrella Cells

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.

Correlation of PD-L1 with VEGF and KI-67 index in patients with primary glioma.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 94-94
Author(s):  
Song Xue ◽  
Man Hu ◽  
Jinming Yu ◽  
Bingjie Fan ◽  
Ji Ma
Keyword(s):  
Immune Escape ◽  
Treatment Strategies ◽  
High Grade Glioma ◽  
Continuous Variable ◽  
Low Grade ◽  
High Grade ◽  
Grade Group ◽  
Ki 67 ◽  
Primary Glioma ◽  
The Mean

94 Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p <0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.

Unusual high-grade features in pediatric diffuse leptomeningeal glioneuronal tumor: comparison with a typical low-grade example

2017 ◽  
Vol 70 ◽  
pp. 105-112 ◽  
Author(s):  
Katherine E. Schwetye ◽  
Akash P. Kansagra ◽  
James McEachern ◽  
Robert E. Schmidt ◽  
Karen Gauvain ◽  
...  
Keyword(s):  
Glioneuronal Tumor ◽  
Low Grade ◽  
High Grade ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

scholarly journals Claudins and Ki-67

2011 ◽  
Vol 59 (11) ◽  
pp. 1022-1030 ◽  
Author(s):  
Péter Törzsök ◽  
Péter Riesz ◽  
István Kenessey ◽  
Eszter Székely ◽  
Áron Somorácz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Expression Pattern ◽  
Cell Cancer ◽  
Urothelial Cell ◽  
Low Grade ◽  
High Grade ◽  
Specific Expression ◽  
Ki 67 ◽  
Normal Tissues

Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins’ specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome.

scholarly journals Ki-67 expression in anal intraepithelial neoplasia in AIDS

2001 ◽  
Vol 119 (3) ◽  
pp. 119-121 ◽  
Author(s):  
Edenilson Eduardo Calore ◽  
Carmen Ruth Manzione ◽  
Sidney Roberto Nadal ◽  
Maria José Cavalieri ◽  
Nilda Maria Perez Calore ◽  
...  
Keyword(s):  
Lower Layer ◽  
Intraepithelial Neoplasia ◽  
Cell Counting ◽  
Biological Behavior ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Staining Techniques ◽  
The Mean ◽  
Group 2

CONTEXT: AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. OBJECTIVE: We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. DESIGN: A retrospective study of hiltological specimens. SETTING: University referral unit. SAMPLE: 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). MAIN MEASUREMENTS: The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. RESULTS: The mean number of Ki-67 positive cells in group 1 was 19.68 ± 10.99; in group 2 (area A) it was 46.73 ± 10.409; and in area B it was 36.43 ± 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. CONCLUSIONS: Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.

scholarly journals Pulmonary mucoepidermoid carcinoma: Clinicopathological characteristics of 20 cases and a literature review

2020 ◽  
Author(s):  
Jing Zhang ◽  
Yan Xiao Chen ◽  
Jun Zi Qian ◽  
Ping Yue ◽  
Jialei Wang ◽  
...  
Keyword(s):  
Tumor Markers ◽  
Medical Records ◽  
Mucoepidermoid Carcinoma ◽  
Clinicopathological Characteristics ◽  
Smoking History ◽  
Categorical Variables ◽  
Low Grade ◽  
High Grade ◽  
Alk Rearrangement ◽  
Ki 67

Abstract Background: Pulmonary mucoepidermoid carcinoma is a rare tumor of the lung. The clinicopathological characteristics of pulmonary mucoepidermoid carcinoma are not well defined due to the low incidence. This study was performed to provide more supplementary clues for the identification and understanding of pulmonary mucoepidermoid carcinoma. Methods: We reviewed the medical records since January 1, 2000 to December 31, 2018. The patients’ medical records，including age at the time of diagnosis , gender, smoking history, preoperative evaluations, operative procedures, tumor location, tumor size, tumor stage, lymph node metastasis, pathological markers, prognosis and survival information were extracted and reviewed. Categorical variables were presented as parameters and percentages. A comparison was performed between patients with high and low grade of pulmonary mucoepidermoid carcinoma. Results: 20 patients were identified and the age span is from 18 to 67 year-old with the average age is 45. Mucoepidermoid carcinomas were commonly found in men（60%）. 80% patients had clinical presentations and the positive rate of tumor markers was 78%, although no specific tumor markers were found. TTF-1 were negative in all cases. ALK rearrangement was identified in a non-smoking woman with high grade pulmonary mucoepidermoid carcinoma. Surgery is the main procedure. 3-year survival rate is 72% and 80% patients achieved disease-free alive. High-grade patients tend to harbor older age (p=0.035), larger tumor volume (p=0.026) and higher index of ki-67(p=0.0005). Conclusions: Pulmonary mucoepidermoid carcinoma could occur in a wide age span. Early diagnosis and complete surgical resection may promise a good prognosis. Grading is a key factor to predict the overall survival time. Combined TTF-1 and MAML2 will benefit the identification of pulmonary mucoepidermoid carcinoma from other lung tumors. Future prospective randomized controlled trials and larger, multi-centric series are needed.

Correlation of Ki-67 and p53 With the New World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia

2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein
Keyword(s):  
Papillary Carcinoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Papillary Lesions ◽  
Flat Lesions ◽  
Papillary Hyperplasia ◽  
Health Organization ◽  
Papillary Neoplasm

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.

Mo1478 KI-67 Cytological Index Can Distinguish Low Grade From High Grade Pancreatic Neuroendocrine Tumors: a Comparative Cyto-Histological Study of 53 Cases

2014 ◽  
Vol 79 (5) ◽  
pp. AB452
Author(s):  
Gabriele Carlinfante ◽  
Paola Baccarini ◽  
Paolo Cecinato ◽  
Debora Berretti ◽  
Tiziana Cassetti ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Histological Study ◽  
Low Grade ◽  
High Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67
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