206 results on '"M., Pekmezci"'
Search Results
2. THE EFFECT OF VARIOUS HORMONE TYPES ON IN VITRO PROPAGATION OF STRAWBERRY
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M. Pekmezci, L. Kaynak, Nafiye Adak, and H. Gubbuk
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Tissue culture ,Horticulture ,Thidiazuron ,visual_art ,Botany ,Shoot ,visual_art.visual_art_medium ,Biology ,Charcoal ,In vitro ,Hormone - Published
- 2009
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Catalog
3. THE EFFECT OF DIFFERENT THIDIAZURON AND INDOLE BUTYRIC ACID CONCENTRATIONS ON IN VITRO PROPAGATION OF 'GRAND NAIN' AND 'BASRAI' BANANA CULTIVARS
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M. Pekmezci and H. Gubbuk
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Indole test ,Grand Nain ,Horticulture ,Biology ,biology.organism_classification ,In vitro ,Butyric acid ,chemistry.chemical_compound ,Tissue culture ,chemistry ,Thidiazuron ,Botany ,Cultivar - Published
- 2009
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4. EFFECTS OF PHYSICAL TREATMENTS ON STORAGE DECAY AND QUALITY OF EGGPLANTS
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I. Karasahin and M. Pekmezci
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Toxicology ,media_common.quotation_subject ,Environmental science ,Quality (business) ,Horticulture ,media_common - Published
- 2008
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5. Multinodular and vacuolating neuronal tumour.
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M. K., Rosenblum, F., Giangaspero, C., Giannini, J. T., Huse, T., Komori, and M., Pekmezci
- Published
- 2021
6. Comparison of open‐field and protected cultivation of banana(Musaspp. AAA) in the coastal area of Turkey
- Author
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H. Gubbuk and M. Pekmezci
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geography ,geography.geographical_feature_category ,Coastal plain ,Greenhouse ,Horticulture ,Biology ,Circumference ,Altitude ,Protected cultivation ,Yield (wine) ,Agronomy and Crop Science ,Finger length ,Annual percentage yield - Abstract
This study was conducted to determine the yield and quality of ‘Dwarf Cavendish’ banana (Musa spp. AAA), cultivated in open fields and also in protected (plastic greenhouse) cultivation. The site is located in the central south coastal region (altitude 50 m, latitude 36°33'N) of Turkey. In both cultivation systems we determined the following: pseudostem circumference, pseudostem height, total leaf number, bunch stalk circumference, days from shooting to harvest, number of hands, number of fingers, finger circumference, finger length, and bunch weight. Protected cultivation was found to be better than open‐field cultivation in terms of total production, expressed as the number of hands and fingers per bunch and bunch weight. Average annual yield under plastic greenhouse was 53% higher than in the open field (65.5 t/ha compared with 42.8 t/ha). more...
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- 2004
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7. MODIFIED ATMOSPHERE STORAGE AND ETHYLENE ABSORBENT ENABLES PROLONGED STORAGE OF 'HAYWARD' KIWIFRUITS
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H. Gübbük, I. Karaşahin, I. Uzun, M. Erkan, and M. Pekmezci
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chemistry.chemical_compound ,Materials science ,Ethylene ,chemistry ,Chemical engineering ,Modified atmosphere ,Polymer chemistry ,Horticulture - Published
- 2004
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8. CDKN2A LOSS IS ASSOCIATED WITH SHORTENED SURVIVAL IN INFILTRATING ASTROCYTOMAS BUT NOT OLIGODENDROGLIOMAS OR MIXED OLIGOASTROCYTOMAS
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A. Perry, G. F. Reis, M. Pekmezci, H. M. Hansen, R. E. Marshall, T. Rice, J. F. Wiencke, M. R. Wrensch, and K. M. Walsh
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Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,education.field_of_study ,Oligoastrocytoma ,IDH1 ,Population ,Astrocytoma ,Biology ,medicine.disease ,abstracts ,Internal medicine ,Glioma ,medicine ,Oligodendroglial Tumor ,Neurology (clinical) ,Oligodendroglioma ,education ,neoplasms ,Anaplastic astrocytoma - Abstract
BACKGROUND: Infiltrating WHO grade II and III gliomas are devastating and difficult to treat neoplasms classified as astrocytoma (A2), oligodendroglioma (O2), oligoastrocytoma (OA2), or anaplastic astrocytoma (A3), oligodendroglioma (O3), and oligoastrocytoma (OA3). Anaplastic grade is critically dependent on the presence of mitoses (astrocytomas) or high mitotic activity (oligodendroglial tumors), with CDKN2A deletion considered the most common mechanism for associated cell cycle dysregulation. We therefore sought to determine if p16 loss by immunohistochemistry (IHC) or CDKN2A gene by fluorescence in situ hybridization (FISH) are associated with patient survival across histologic groupings after controlling for age, grade, and other molecular markers. METHODS: Adults (18 years of age) with infiltrating gliomas (grades II or III) were selected from the UCSF Adult Glioma Study (N = 157). The population consisted of 90 males (average age = 43.2) and 67 females (average age = 40.7). Isocitrate dehydrogenase (IDH) status (IDH1 and IDH2) was known for all cases. Histology and grade were as follows: 53 O2, 33 A2, 29 OA2, 20 O3, 15 A3, 7 OA3. CDKN2A FISH was performed using commercial probes and immunostains for p16 and MIB1 (Ki-67) were similarly performed using commercial antibodies. The end point for the analysis was overall survival, analyzed using Cox proportional hazards, stratified by tumor histology and with adjustment for sex, age, grade, and various tumor markers. A total of 61 events (deaths) were observed, and median follow-up time across all subjects was 6.4 years. RESULTS: After controlling for age, sex, and grade, CDKN2A deletion was associated with decreased survival in astrocytoma patients (P = 0.045; HR = 3.1; 95%CI = 1.03-9.2) but not in oligodendroglioma or oligoastrocytoma patients (P = 0.57 and P = 0.67, respectively). A strong inverse association between IDH mutation and CDKN2A deletion was observed in astrocytomas, and the association of CDKN2A deletion with survival was attenuated after controlling for IDH status (P = 0.34). Interestingly, CDKN2A loss was observed in 83% of IDH wild-type versus 33% of IDH-mutant astrocytomas (P = 0.029). CDKN2A loss was only weakly associated with decreased p16 expression (p = 0.09), and the p16 labeling index (LI) was not associated with outcome. There was also no clear association between CDKN2A deletion and MIB1 LI (P = 0.92). CONCLUSIONS: CDKN2A deletion by FISH is associated with shortened survival in astrocytoma patients, but not in patients with oligodendroglial tumors. The strong inverse association between IDH mutation and CDKN2A deletion suggests that CDKN2A status may have prognostic value in the clinical work-up of grade II and III astrocytoma patients. SECONDARY CATEGORY: n/a. more...
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- 2014
9. THE EFFECTS OF DIFFERENT STORAGE TEMPERATURES AND POSTHARVEST TREATMENTS ON STORAGE AND CHILLING INJURY OF 'WASHINGTON NAVEL' ORANGES
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M. Pekmezcİ and M. Erkan
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Fungicide ,Horticulture ,Agronomy ,Postharvest ,Cold storage ,Chilling injury ,Biology - Published
- 2000
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10. INVESTIGATIONS ON GROWING POSSIBILITIES OF BANANA IN TURKEY
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H. Gübbük, Mustafa Erkan, and M. Pekmezci
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Horticulture ,Biology - Published
- 1998
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11. THE EFFECTS OF DIFFERENT PLANTING SYSTEMS ON EARLINESS, YIELD AND QUALITY IN SOME STRAWBERRY CULTIVARS
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M. Pekmezci, H. Gübbük, E. Polat, and Mustafa Erkan
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Agronomy ,media_common.quotation_subject ,Yield (finance) ,Sowing ,Quality (business) ,Cultivar ,Horticulture ,media_common ,Mathematics - Published
- 1997
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12. STUDIES ON CA-STORAGE OF POMEGRANATE (PUNICA GRANATUM L., CV. HICAZ)
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M. Pekmezci, W. Kupper, and J. Henze
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Horticulture ,biology ,Punica ,biology.organism_classification - Published
- 1995
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13. Pre-operative flexion contracture determines the functional outcome of haemophilic arthropathy treated with total knee arthroplasty
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B, Atilla, O, Caglar, M, Pekmezci, Y, Buyukasik, A M, Tokgozoglu, and M, Alpaslan
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Adult ,Contracture ,Knee Joint ,Middle Aged ,Hemophilia A ,Radiography ,Young Adult ,Treatment Outcome ,Area Under Curve ,Hemarthrosis ,Preoperative Period ,Humans ,Range of Motion, Articular ,Arthroplasty, Replacement, Knee ,Follow-Up Studies ,Retrospective Studies - Abstract
End-stage haemophiliac arthropathy can be successfully treated with total knee arthroplasty. However, the functional results may not be as good as anticipated and certain pre-op knee characteristics may alter the functional results. The purpose of this study was to evaluate the functional outcome of TKA in haemophilic patients with specific attention to final range of motion and residual flexion contracture of the joint. Twenty-one consecutive patients were retrospectively reviewed. The average age was 34 years with an average follow-up of 5.7 years. Functional status was evaluated with Hospital for Special Surgery Knee Score. Receiving Operating Characteristics analysis was used to determine the threshold of pre-operative flexion contracture degree to avoid residual knee contracture. The range of motion was increased in 16 joints and unchanged in three joints and decreased in the remaining two. Preoperative average range of motion was 37.6°, improved to 57.1° post-operatively. The average knee score increased from 27.85 (15-30) points pre-operatively to 79.42 (12-94) points at the last follow-up. The degree of pre-operative flexion contracture was found to be a good predictor for residual flexion contracture. (Specificity: 85.7%, sensitivity: 100%, cut-off: 27.5°). Total knee replacement improves the quality of life in patients with advanced haemophilic arthropathy. Statistical analysis revealed that pre-op flexion contracture of 27.5° is an important threshold. Patients should be operated before that stage to gain maximum benefit with minimal gait abnormalities. more...
- Published
- 2011
14. STUDIES ON THE STORAGE OF LEMON FRUITS (cv.Kütdiken)
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M. Pekmezci
- Subjects
Horticulture ,Biology - Published
- 1983
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15. COMPARISON OF DRIP AND BASIN IRRIGATION SYSTEMS IN BANANA ORCHARDS ON THE SOUTHERN COAST OF TURKEY
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O. Tekinel, N. Yaylali, S. Paydas, B. Cevik, M. Pekmezci, and N. Kaska
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Irrigation ,Geography ,Agroforestry ,Forestry ,Horticulture ,Structural basin - Published
- 1988
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16. EFFECTS OF ETHREL AND ETHYLENE ON THE RIPENING OF BANANAS
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M. Pekmezci, J. Henze, C.U. Ziraat Fakültesi, and H. Baumann
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chemistry.chemical_compound ,Horticulture ,Ethylene ,chemistry ,Ripening - Published
- 1983
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17. The diagnostic utility of SOX11 Immunohistochemical expression in malignant peripheral nerve sheath tumors and their potential mimickers.
- Author
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Tasar Kapakli E, Pekmezci M, Katipoglu K, Soylemezoglu F, Gedikoglu G, Tihan T, and Kosemehmetoglu K
- Abstract
Malignant peripheral nerve sheath tumor (MPNST) comprises 5-10 % of all soft tissue sarcomas, and their diagnosis may be challenging given the absence of robust immunohistochemical and molecular signatures. SOX11 expression has previously been shown to be present in a small subset of MPNST. In the present study, we evaluated a group of MPNST for SOX11 expression by immunohistochemistry. We similarly assessed a group of benign and malignant spindle cell tumors that are in the differential diagnosis of MPNST, to more expansively establish the specificity of the antibody. In total, 59 MPNSTs, 27 synovial sarcomas, 19 leiomyosarcomas, 19 rhabdomyosarcomas, 19 solitary fibrous tumors, 4 clear cell sarcomas of soft tissue, 19 malignant melanomas, 22 schwannomas (11 classical, 11 cellular), 9 neurofibromas (4 plexiform, 2 atypical, and 3 classical) and 9 nodular fasciitis were included. SOX11 was strongly positive in 41 of 59 MPNSTs (67 %), 16 of 27 synovial sarcomas (59 %), 11 of 19 rhabdomyosarcomas (58 %), 1 of 4 clear cell sarcomas (25 %), and 5 of 9 nodular fasciitis (56 %). In contrast, neurofibromas(n=11)), schwannomas (n=22), leiomyosarcomas (n=22), and solitary fibrous tumors (n=19) were either negative or showed only weak and focal expression for SOX11. The sensitivity and specificity of strong SOX11 expression in differentiating MPNST from its mimickers were 70 % and 73 %, respectively. In conclusion, the diagnostic utility of SOX11 expression for MPNST is limited, but the absence of significant SOX11 expression in benign/atypical nerve sheath tumors is interesting and deserves further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.) more...
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- 2025
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18. Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses.
- Author
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Lucas CG, Al-Adli NN, Young JS, Gupta R, Morshed RA, Wu J, Ravindranathan A, Shai A, Oberheim Bush NA, Taylor JW, de Groot J, Villanueva-Meyer JE, Pekmezci M, Perry A, Bollen AW, Theodosopoulos PV, Aghi MK, Chang EF, Hervey-Jumper SL, Raleigh DR, Molinaro AM, Costello JF, Diaz AA, Clarke JL, Butowski NA, Phillips JJ, Chang SM, Berger MS, and Solomon DA more...
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- Humans, Male, Prognosis, Middle Aged, Female, Mutation, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Temozolomide therapeutic use, Phenotype, Adult, Aged, Biomarkers, Tumor genetics, Longitudinal Studies, Survival Rate, Follow-Up Studies, Promoter Regions, Genetic, DNA Modification Methylases, Tumor Suppressor Proteins, DNA Repair Enzymes, Glioblastoma genetics, Glioblastoma pathology, Glioblastoma drug therapy, Glioblastoma therapy, Isocitrate Dehydrogenase genetics, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms drug therapy, Brain Neoplasms therapy, DNA Methylation
- Abstract
Background: Despite recent advances in the biology of IDH-wildtype glioblastoma, it remains a devastating disease with median survival of less than 2 years. However, the molecular underpinnings of the heterogeneous response to the current standard-of-care treatment regimen consisting of maximal safe resection, adjuvant radiation, and chemotherapy with temozolomide remain unknown., Methods: Comprehensive histopathologic, genomic, and epigenomic evaluation of paired initial and recurrent glioblastoma specimens from 106 patients was performed to investigate the molecular evolution and cellular phenotypes underlying differential treatment responses., Results: While TERT promoter mutation and CDKN2A homozygous deletion were early events during gliomagenesis shared by initial and recurrent tumors, most other recurrent genetic alterations (eg, EGFR, PTEN, and NF1) were commonly private to initial or recurrent tumors indicating acquisition later during clonal evolution. Furthermore, glioblastomas exhibited heterogeneous epigenomic evolution with subsets becoming more globally hypermethylated, hypomethylated, or remaining stable. Glioblastoma that underwent sarcomatous transformation had shorter interval to recurrence and were significantly enriched in NF1, TP53, and RB1 alterations and the mesenchymal epigenetic class. Patients who developed somatic hypermutation following temozolomide treatment had significantly longer interval to disease recurrence and prolonged overall survival, and increased methylation at 4 specific CpG sites in the promoter region of MGMT was significantly associated with this development of hypermutation. Finally, an epigenomic evolution signature incorporating change in DNA methylation levels across 347 critical CpG sites was developed that significantly correlated with clinical outcomes., Conclusions: Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.) more...
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- 2025
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19. Foundation models for fast, label-free detection of glioma infiltration.
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Kondepudi A, Pekmezci M, Hou X, Scotford K, Jiang C, Rao A, Harake ES, Chowdury A, Al-Holou W, Wang L, Pandey A, Lowenstein PR, Castro MG, Koerner LI, Roetzer-Pejrimovsky T, Widhalm G, Camelo-Piragua S, Movahed-Ezazi M, Orringer DA, Lee H, Freudiger C, Berger M, Hervey-Jumper S, and Hollon T more...
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- Humans, Prospective Studies, Male, Female, ROC Curve, Adult, Middle Aged, Time Factors, Neoplasm Invasiveness, Glioma pathology, Glioma surgery, Glioma diagnosis, Glioma diagnostic imaging, Brain Neoplasms surgery, Brain Neoplasms pathology, Brain Neoplasms diagnostic imaging
- Abstract
A critical challenge in glioma treatment is detecting tumour infiltration during surgery to achieve safe maximal resection
1-3 . Unfortunately, safely resectable residual tumour is found in the majority of patients with glioma after surgery, causing early recurrence and decreased survival4-6 . Here we present FastGlioma, a visual foundation model for fast (<10 s) and accurate detection of glioma infiltration in fresh, unprocessed surgical tissue. FastGlioma was pretrained using large-scale self-supervision (around 4 million images) on rapid, label-free optical microscopy, and fine-tuned to output a normalized score that indicates the degree of tumour infiltration within whole-slide optical images. In a prospective, multicentre, international testing cohort of patients with diffuse glioma (n = 220), FastGlioma was able to detect and quantify the degree of tumour infiltration with an average area under the receiver operating characteristic curve of 92.1 ± 0.9%. FastGlioma outperformed image-guided and fluorescence-guided adjuncts for detecting tumour infiltration during surgery by a wide margin in a head-to-head, prospective study (n = 129). The performance of FastGlioma remained high across diverse patient demographics, medical centres and diffuse glioma molecular subtypes as defined by the World Health Organization. FastGlioma shows zero-shot generalization to other adult and paediatric brain tumour diagnoses, demonstrating the potential for our foundation model to be used as a general-purpose adjunct for guiding brain tumour surgeries. These findings represent the transformative potential of medical foundation models to unlock the role of artificial intelligence in the care of patients with cancer., Competing Interests: Competing interests: C.F., D.A.O. and T.H. are shareholders in Invenio Imaging. The other authors declare no competing interests., (© 2024. The Author(s).) more...- Published
- 2025
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20. High-Grade Progression, Sarcomatous Transformation, and/or Metastasis of Pituitary Neuroendocrine Neoplasms (PitNENs): The UCSF Experience.
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Terry M, Nguyen MP, Tang V, Guney E, Bharani KL, Dahiya S, Choutka O, Borys E, Reis G, Blevins L, Aghi MK, Kunwar S, DeGroot J, Raleigh DR, Pekmezci M, Bollen AW, Cha S, Joseph NM, and Perry A
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Aged, Cell Transformation, Neoplastic pathology, Neoplasm Metastasis pathology, Young Adult, Sarcoma pathology, Sarcoma genetics, Neoplasm Grading, Neuroendocrine Tumors pathology, Pituitary Neoplasms pathology, Pituitary Neoplasms genetics, Disease Progression
- Abstract
Pituitary neuroendocrine tumors (PitNET) that metastasize comprise ~ 0.2% of adenohypophyseal tumors are aggressive and are challenging to treat. However, many non-metastatic tumors are also aggressive. Herein, we review 21 specimens from 13 patients at UCSF with metastatic PitNETs (CSF or systemic, N = 7 patients), high-grade pituitary neuroendocrine neoplasms (HG-PitNEN, N = 4 patients), and/or PitNETs with sarcomatous transformation (PitNET-ST, N = 5 patients). We subtyped cases using the World Health Organization (WHO) and International Agency for Research on Cancer (IARC) criteria for neuroendocrine neoplasms (NENs). Lineage subtypes included acidophil stem cell, null cell, thyrotroph, corticotroph, lactotroph, and gonadotroph tumors. The median Ki-67 labeling index was 25% (range 5-70%). Lack of p16 was seen in 3 cases, with overexpression in 2. Strong diffuse p53 immunopositivity was present in 3 specimens from 2 patients. Loss of Rb expression was seen in 2 cases, with ATRX loss in one. Molecular analysis in 4 tumors variably revealed TERT alterations, homozygous CDKN2A deletion, aneuploidy, and mutations in PTEN, TP53, PDGFRB, and/or PIK3CA. Eight patients (62%) died of disease, 4 were alive at the last follow-up, and 1 was lost to the follow-up. All primary tumors had worrisome features, including aggressive lineage subtype, high mitotic count, and/or high Ki-67 indices. Additional evidence of high-grade progression included immunohistochemical loss of neuroendocrine, transcription factor, and/or hormone markers. We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).) more...
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- 2024
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21. Revised Diagnosis From Histiocytic Neoplasm to Optic Chiasm Glioblastoma After Genetic Analysis.
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Magharious MM, Pekmezci M, Mamlouk MD, Horton JC, and Levin MH
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- Humans, Male, Middle Aged, Genetic Testing, Mutation, Positron Emission Tomography Computed Tomography, Biopsy, Diagnosis, Differential, Glioblastoma diagnosis, Glioblastoma genetics, Optic Chiasm pathology, Magnetic Resonance Imaging, Optic Nerve Neoplasms diagnosis, Optic Nerve Neoplasms genetics
- Abstract
Abstract: A 46-year-old man presented with left eye blurring. Automated visual field testing showed an incongruous right hemianopia, with sparing of the lower temporal quadrant in the right eye. MRI revealed foci of gadolinium enhancement in the optic chiasm and optic tracts. Serologic testing (including myelin oligodendrocyte glycoprotein and neuromyelitis optica antibodies) and cerebrospinal fluid analysis were negative. Whole-body PET/CT scan found no malignancy. Biopsy of the optic chiasm revealed a moderately cellular neoplasm composed of atypical, discohesive cells with enlarged nuclei, prominent eosinophilic nucleoli, and abundant vacuolated cytoplasm. Immunohistochemical stains for CD68 and S100 were positive, whereas those for GFAP, OLIG2, SOX10, and multiple others were negative, supporting a diagnosis of histiocytic neoplasm. Five weeks later, results became available from next-generation sequencing targeting the coding regions of hundreds of malignancy-associated genes and select introns. Alterations associated with histiocytic neoplasms (i.e. BRAF and MAP2K1 mutations) were absent. However, there was a nonsense mutation in the PTEN gene, a hotspot mutation in the TERT gene promotor, and focal amplifications of the CDK4 and MDM2 genes. Additionally, there was chromosome 6q loss, 7 gain, and 10q loss. Based on these findings, the diagnosis was revised to glioblastoma, IDH-wildtype, CNS WHO grade 4. The patient began treatment with temozolomide while continuing radiation therapy. This case illustrates how next-generation sequencing can at times provide more accurate diagnostic information than standard tissue histopathology., Competing Interests: Dr. Levin serves as a consultant for Jazz Pharmaceuticals and Vanda Pharmaceuticals; he also receives royalties from the University of California. The remaining authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.) more...
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- 2024
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22. Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1).
- Author
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Lucas CG, Gross AM, Romo CG, Dehner CA, Lazar AJ, Miettinen M, Pekmezci M, Quezado M, Rodriguez FJ, Stemmer-Rachamimov A, Viskochil D, and Perry A
- Abstract
Consensus recommendation published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation to enable appropriate intervention for affected patients. To this end, we assembled a multi-institutional expert pathology working group as part of a "Symposium on Atypical Neurofibroma: State of the Science". Herein, we provide a suggested framework for adequate interventional radiology and surgical sampling, and recommend molecular profiling for clinically or radiologically worrisome non-cutaneous lesions in patients with NF1 to identify diagnostically-relevant molecular features, including CDKN2A/B inactivation for ANNUBP, as well as SUZ12, EED, or TP53 inactivating mutations, or significant aneuploidy for MPNST. We also propose renaming "low-grade MPNST" to "ANNUBP with increased proliferation" to avoid the use of the "malignant" term in this group of tumors with persistent unknown biologic potential. This refined integrated diagnostic approach for NF1-associated peripheral nerve sheath tumors should continue to evolve in concert with our understanding of these neoplasms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.) more...
- Published
- 2024
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23. A High-Grade Glioma, Not Elsewhere Classified in an Older Adult with Discordant Genetic and Epigenetic Analyses.
- Author
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Yuen CA, Bao S, Kong XT, Terry M, Himstead A, Zheng M, and Pekmezci M
- Abstract
The World Health Organization's (WHO) classification of central nervous system (CNS) tumors is continually being refined to improve the existing diagnostic criteria for high-grade gliomas (HGGs), including glioblastoma. In 2021, advances in molecular analyses and DNA methylation profiling were incorporated to expand upon the diagnostic criteria for HGG, including the introduction of high-grade astrocytoma with piloid features (HGAP), a new tumor entity for which a match to the HGAP class in DNA methylation profiling is an essential criterion. We present an equivocal case of a 72-year-old male with an HGG exhibiting features of both HGAP and glioblastoma, but which did not conform to any existing 2021 WHO classification of CNS tumor entities. This "no match" in DNA methylation profiling resulted in a final diagnosis of HGG not elsewhere classified (NEC), for which standard treatment options do not exist. more...
- Published
- 2024
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24. Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL).
- Author
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Craig A, Güney E, Pekmezci M, Bloomer M, Laszik Z, Ohgami RS, Toland A, Vogel H, Forns T, Wang E, Rubenstein J, and Wen KW
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- Humans, Male, Female, Middle Aged, Aged, Adult, Tumor Microenvironment, Eye Neoplasms pathology, Eye Neoplasms metabolism, Eye Neoplasms diagnosis, Immunohistochemistry, Aged, 80 and over, Biomarkers, Tumor metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse diagnosis, B7-H1 Antigen metabolism, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Programmed Cell Death 1 Receptor metabolism, Lymphoma, B-Cell, Marginal Zone diagnosis, Lymphoma, B-Cell, Marginal Zone metabolism, Lymphoma, B-Cell, Marginal Zone pathology
- Abstract
Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common. Diagnostic utility in challenging cases, as well as treatment options using immune checkpoint inhibitors, are unclear in ocular lymphomas. We herein investigated the PD-1, PD-L1, and IDO1 staining patterns in 20 cases of ocular lymphomas, including EMZL (n=14), EMZL with increased large cells (n=2), and DLBCL (n=4). PD-1, PD-L1, and IDO1 staining was not detected in lymphoma cells in any cases but was observed within the tumor microenvironment in all cases. Positivity for PD-1, PD-L1, and IDO1 in inflammatory cells was seen either intratumorally or peritumorally. In all 6 cases with significantly more large B cells, the density of PD-1, PD-L1, and IDO1 expression in the tumor microenvironment was higher than that of the remaining 14 cases without large B cells ( P -value<0.0001), whereas other clinicopathologic features showed no statistical correlation. Increased expression of PD-1, PD-L1, and IDO1 in the inflammatory milieu in cases with large cells may provide diagnostic utility in small biopsies as well as therapeutic potential., Competing Interests: J.R. receives research funding from Incyte and from NURIX. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) more...
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- 2024
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25. Stromal Keratitis Associated With Cytomegalovirus Anterior Uveitis.
- Author
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Pisitpayat P, Mentreddy A, Pekmezci M, Hwang D, Shantha J, Benador-Shen C, Terry M, Pothikamjorn T, and Gonzales J
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- Humans, Middle Aged, Male, Retrospective Studies, Female, Adult, Aged, Aged, 80 and over, Aqueous Humor virology, Polymerase Chain Reaction, Keratitis virology, Keratitis diagnosis, Antiviral Agents therapeutic use, Uveitis, Anterior virology, Uveitis, Anterior diagnosis, Eye Infections, Viral virology, Eye Infections, Viral diagnosis, Cytomegalovirus Infections virology, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections complications, Corneal Stroma virology, Corneal Stroma pathology, Cytomegalovirus genetics, Cytomegalovirus isolation & purification, DNA, Viral analysis, DNA, Viral genetics
- Abstract
Purpose: Human cytomegalovirus (CMV) has commonly been reported as a cause of anterior uveitis and corneal endotheliitis. Unlike its other herpetic family members, herpes simplex virus and varicella zoster virus, involvement of the corneal stroma in CMV is uncommon. In this case series, we describe patients with CMV stromal keratitis., Methods: This was a retrospective chart review of patients seen at a tertiary referral center from 1999 to 2023 with stromal keratitis who tested positive for CMV by directed polymerase chain reaction of aqueous fluid or corneal tissue., Results: This series describes 5 patients, 4 of whom presented with anterior uveitis and stromal keratitis and were confirmed to be positive for CMV through the polymerase chain reaction of aqueous fluid. The fifth patient experienced recurrent corneal graft failures, with the most recent failed graft being positive for CMV based on immunohistochemical stains of the corneal stroma. The average age of patients was 62 years (range 36-80 years). Only 1 patient (20%) exhibited elevated intraocular pressure with stellate keratic precipitates at the initial presentation, whereas 3 other patients (60%) had a known history of glaucoma., Conclusions: Uveitis specialists are well aware of CMV as a cause of recurrent, hypertensive anterior uveitis but should also consider CMV in cases featuring stromal keratitis. The corneal endothelium may serve as a reservoir for both anterior uveitis and development of corneal stromal inflammation as demonstrated by the immunohistopathology exhibited in 1 case., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) more...
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- 2024
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26. Metastatic glioblastoma to the lungs: a case report and literature review.
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Yuen CA, Pekmezci M, Bao S, and Kong XT
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- Female, Humans, Middle Aged, Brain Neoplasms diagnostic imaging, Brain Neoplasms genetics, Brain Neoplasms pathology, Glioblastoma pathology, Glioblastoma genetics, Glioblastoma secondary, Glioblastoma diagnostic imaging, Lung Neoplasms pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms secondary
- Abstract
Glioblastoma is the most common malignant primary brain tumor. Despite its infiltrative nature, extra-cranial glioblastoma metastases are rare. We present a case of a 63-year-old woman with metastatic glioblastoma in the lungs. Sarcomatous histology, a reported risk factor for disseminated disease, was found. Genomic alterations of TP53 mutation, TERT mutation, PTEN mutation, and +7/-10 were also uncovered. Early evidence suggests these molecular aberrations are common in metastatic glioblastoma. Treatment with third-line lenvatinib resulted in a mixed response. This case contributes to the growing body of evidence for the role of genomic alterations in predictive risk in metastatic glioblastoma. There remains an unmet need for treatment of metastatic glioblastoma. more...
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- 2024
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27. Epigenetic reprogramming shapes the cellular landscape of schwannoma.
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Liu SJ, Casey-Clyde T, Cho NW, Swinderman J, Pekmezci M, Dougherty MC, Foster K, Chen WC, Villanueva-Meyer JE, Swaney DL, Vasudevan HN, Choudhury A, Pak J, Breshears JD, Lang UE, Eaton CD, Hiam-Galvez KJ, Stevenson E, Chen KH, Lien BV, Wu D, Braunstein SE, Sneed PK, Magill ST, Lim D, McDermott MW, Berger MS, Perry A, Krogan NJ, Hansen MR, Spitzer MH, Gilbert L, Theodosopoulos PV, and Raleigh DR more...
- Subjects
- Humans, Epigenesis, Genetic, Cellular Reprogramming genetics, Tumor Microenvironment genetics, Neurilemmoma genetics, Neurilemmoma pathology
- Abstract
Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy., (© 2023. The Author(s).) more...
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- 2024
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28. Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance.
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Vasudevan HN, Payne E, Delley CL, John Liu S, Mirchia K, Sale MJ, Lastella S, Nunez MS, Lucas CG, Eaton CD, Casey-Clyde T, Magill ST, Chen WC, Braunstein SE, Perry A, Jacques L, Reddy AT, Pekmezci M, Abate AR, McCormick F, and Raleigh DR more...
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- Animals, Humans, Mice, Mitogen-Activated Protein Kinase Kinases metabolism, Schwann Cells metabolism, Drug Resistance, Neoplasm genetics, Neurilemmoma genetics, Neurilemmoma pathology, Neurofibromatoses metabolism, Neurofibromatoses pathology, Neurofibromatosis 1 genetics, Neurofibromatosis 1 metabolism, Neurofibromatosis 2 genetics, Neurofibromatosis 2 pathology
- Abstract
Schwann cell tumors are the most common cancers of the peripheral nervous system and can arise in patients with neurofibromatosis type-1 (NF-1) or neurofibromatosis type-2 (NF-2). Functional interactions between NF1 and NF2 and broader mechanisms underlying malignant transformation of the Schwann lineage are unclear. Here we integrate bulk and single-cell genomics, biochemistry, and pharmacology across human samples, cell lines, and mouse allografts to identify cellular de-differentiation mechanisms driving malignant transformation and treatment resistance. We find DNA methylation groups of Schwann cell tumors can be distinguished by differentiation programs that correlate with response to the MEK inhibitor selumetinib. Functional genomic screening in NF1-mutant tumor cells reveals NF2 loss and PAK activation underlie selumetinib resistance, and we find that concurrent MEK and PAK inhibition is effective in vivo. These data support a de-differentiation paradigm underlying malignant transformation and treatment resistance of Schwann cell tumors and elucidate a functional link between NF1 and NF2., (© 2024. The Author(s).) more...
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- 2024
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29. Pembrolizumab in an HIV-infected patient with glioblastoma.
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Yuen CA, Bao S, Pekmezci M, Mo F, and Kong XT
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- Humans, Male, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological adverse effects, Middle Aged, Glioblastoma drug therapy, Glioblastoma therapy, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, HIV Infections drug therapy, HIV Infections complications, Brain Neoplasms drug therapy
- Abstract
Persons living with human immunodeficiency virus (PLWH) carry increased risk for developing malignancies, including glioblastoma. Despite extensive investigations, both human immunodeficiency virus (HIV) and glioblastoma are incurable. Treatment for a patient with combined glioblastoma and HIV remains an unexplored need. Preliminary evidence suggests that immunotherapy may be effective for the simultaneous treatment of both HIV and cancer by reversing HIV latency and T cell exhaustion. We present a case of glioblastoma in a PLWH who was treated with pembrolizumab. Treatment was well tolerated and safe with a mixed response. Our patient did not develop any opportunistic infections, immune-related adverse events, or worsening of his immunodeficiency. To our knowledge, this is the first reported case of a PLWH and glioblastoma treated with immunotherapy. more...
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- 2024
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30. "De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade.
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Hadad S, Gupta R, Oberheim Bush NA, Taylor JW, Villanueva-Meyer JE, Young JS, Wu J, Ravindranathan A, Zhang Y, Warrier G, McCoy L, Shai A, Pekmezci M, Perry A, Bollen AW, Phillips JJ, Braunstein SE, Raleigh DR, Theodosopoulos P, Aghi MK, Chang EF, Hervey-Jumper SL, Costello JF, de Groot J, Butowski NA, Clarke JL, Chang SM, Berger MS, Molinaro AM, and Solomon DA more...
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- Adult, Humans, Child, Middle Aged, Aged, Immune Checkpoint Inhibitors, Homozygote, Prospective Studies, Sequence Deletion, Mutation genetics, Isocitrate Dehydrogenase genetics, Glioblastoma genetics, Glioblastoma pathology, Brain Neoplasms genetics, Brain Neoplasms pathology
- Abstract
Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant "ultrahypermutation". The median age at diagnosis was 50 years (range 27-78), compared with 63 years for the other 450 patients with conventional glioblastoma (p < 0.01). All tumors had histologic features of the giant cell variant of glioblastoma. They lacked EGFR amplification, lacked combined trisomy of chromosome 7 plus monosomy of chromosome 10, and only rarely had TERT promoter mutation or CDKN2A homozygous deletion, which are hallmarks of conventional IDH-wildtype glioblastoma. Instead, they harbored frequent inactivating mutations in TP53, NF1, PTEN, ATRX, and SETD2 and recurrent activating mutations in PDGFRA. DNA methylation profiling revealed they did not align with known reference adult glioblastoma methylation classes, but instead had unique globally hypomethylated epigenomes and mostly classified as "Diffuse pediatric-type high grade glioma, RTK1 subtype, subclass A". Five patients were treated with immune checkpoint blockade, four of whom survived greater than 3 years. The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that "De novo replication repair deficient glioblastoma, IDH-wildtype" represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade., (© 2023. The Author(s).) more...
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- 2023
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31. Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs.
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Williams EA, Ravindranathan A, Gupta R, Stevers NO, Suwala AK, Hong C, Kim S, Yuan JB, Wu J, Barreto J, Lucas CG, Chan E, Pekmezci M, LeBoit PE, Mully T, Perry A, Bollen A, Van Ziffle J, Devine WP, Reddy AT, Gupta N, Basnet KM, Macaulay RJB, Malafronte P, Lee H, Yong WH, Williams KJ, Juratli TA, Mata DA, Huang RSP, Hiemenz MC, Pavlick DC, Frampton GM, Janovitz T, Ross JS, Chang SM, Berger MS, Jacques L, Song JS, Costello JF, and Solomon DA more...
- Subjects
- Humans, INDEL Mutation, Transcriptional Activation, Mutation, SOXE Transcription Factors genetics, SOXE Transcription Factors metabolism, Neurilemmoma genetics, Neurilemmoma pathology, Neuroma, Acoustic pathology, Nerve Sheath Neoplasms
- Abstract
Background: Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas., Methods: We performed comprehensive genomic profiling on a cohort of 96 human schwannomas, as well as DNA methylation profiling on a subset. Functional studies including RNA sequencing, chromatin immunoprecipitation-DNA sequencing, electrophoretic mobility shift assay, and luciferase reporter assays were performed in a fetal glial cell model following transduction with wildtype and tumor-derived mutant isoforms of SOX10., Results: We identified that nearly one-third of sporadic schwannomas lack alterations in known nerve sheath tumor genes and instead harbor novel recurrent in-frame insertion/deletion mutations in SOX10, which encodes a transcription factor responsible for controlling Schwann cell differentiation and myelination. SOX10 indel mutations were highly enriched in schwannomas arising from nonvestibular cranial nerves (eg facial, trigeminal, vagus) and were absent from vestibular nerve schwannomas driven by NF2 mutation. Functional studies revealed these SOX10 indel mutations have retained DNA binding capacity but impaired transactivation of glial differentiation and myelination gene programs., Conclusions: We thus speculate that SOX10 indel mutations drive a unique subtype of schwannomas by impeding proper differentiation of immature Schwann cells., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.) more...
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- 2023
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32. Pathological perspectives in pilocytic astrocytomas: Extent of resection as the sole critical factor for recurrence-free survival, and the challenge of evaluating conclusions derived from limited data.
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Kulac I, Yenidogan I, Oflaz Sozmen B, Baygul A, Cha S, Pekmezci M, and Tihan T
- Abstract
Introduction: Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience, there are still diagnostic and treatment challenges and unresolved issues regarding risk factors associated with recurrence, most often due to conclusions of publications with limited data. We analyzed 499 patients with PA diagnosed in a single institution over 30 years in order to provide answers to some of the unresolved issues. Materials and Methods: We identified pilocytic astrocytomas diagnosed at the University of California, San Francisco, between 1989 and 2019, confirmed the diagnoses using the WHO 2021 essential and desirable criteria, and performed a retrospective review of the demographic and clinical features of the patients and the radiological, pathologic and molecular features of the tumors. Results: Among the patients identified from pathology archives, 499 cases fulfilled the inclusion criteria. Median age at presentation was 12 years (range 3.5 months - 73 years) and the median follow-up was 78.5 months. Tumors were predominantly located in the posterior fossa (52.6%). There were six deaths, but there were confounding factors that prevented a clear association of death to tumor progression. Extent of resection was the only significant factor for recurrence-free survival. Recurrence-free survival time was 321.0 months for gross total resection, compared to 160.9 months for subtotal resection (log rank, p <0.001). Conclusion: Multivariate analysis was able to identify extent of resection as the only significant variable to influence recurrence-free survival. We did not find a statistically significant association between age, NF1 status, tumor location, molecular alterations, and outcome. Smaller series with apparently significant results may have suffered from limited sample size, limited variables, acceptance of univariate analysis findings as well as a larger p value for biological significance. PA still remains a predominantly surgical disease and every attempt should be made to achieve gross total resection since this appears to be the most reliable predictor of recurrence-free survival. more...
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- 2023
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33. A Case of Orbital Sarcoidosis with Caseating Granulomatous Inflammation.
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Meer E, Ahmad M, Pekmezci M, and Kersten RC
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- Male, Humans, Middle Aged, Granuloma diagnosis, Granuloma pathology, Orbit diagnostic imaging, Orbit pathology, Inflammation, Sarcoidosis complications, Sarcoidosis diagnosis, Orbital Diseases diagnosis
- Abstract
The authors report a rare case of orbital sarcoidosis with caseating granulomatous inflammation. A 55-year-old man presented with a 2-month history of progressively worsening diplopia and proptosis of the OS. Orbital CT demonstrated a diffuse orbital mass. Diagnostic anterior orbitotomy demonstrated caseating granulomas. Infectious testing, including special stains, cultures, and polymerase chain reaction testing, were negative for infectious causes. Chest CT demonstrated the presence of hilar lymphadenopathy with bronchoscopic biopsy showing noncaseating granulomas, supporting a diagnosis of sarcoidosis. The patient achieved clinical and symptomatic improvement at 8-month follow-up on methotrexate. While sarcoidosis is typically characterized by non-necrotizing granulomatous inflammation, sarcoid granulomas with necrosis have been previously described in pulmonary histopathology. This case emphasizes the importance of a comprehensive systemic workup, keeping systemic sarcoidosis on the differential, for necrotizing granulomatous inflammation of the orbit., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.) more...
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- 2023
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34. Poorly differentiated orbital neuroendocrine carcinoma.
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Zhang YS, Jiro M, Pekmezci M, and Winn B
- Subjects
- Male, Humans, Adipose Tissue, Orbital Neoplasms diagnostic imaging, Orbital Neoplasms drug therapy, Neuroendocrine Tumors, Carcinoma, Neuroendocrine diagnostic imaging, Carcinoma, Neuroendocrine drug therapy, Angioedema
- Abstract
A man in his 70s presented with painless bilateral eyelid oedema and vertical diplopia. Evaluation showed a restrictive pattern of extraocular motility testing with MRI demonstrating significant enlargement of the right superior rectus and left superior oblique muscles along with right orbital fat stranding. Subsequent right orbital biopsy revealed poorly differentiated high-grade neuroendocrine carcinoma without a systemic primary site on further diagnostic workup. The patient was treated with carboplatin and etoposide and passed away from an infection a month after diagnosis. This case along with a review of other published cases highlights the varied presentation of orbital neuroendocrine carcinomas that may mimic a broad differential of orbital processes, thus requiring careful diagnostic workup. Subsequently, additional considerations in metastatic evaluation should be based on tumour histological features., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.) more...
- Published
- 2023
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35. Molecular profiling identifies at least 3 distinct types of posttransplant lymphoproliferative disorder involving the CNS.
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Guney E, Lucas CG, Singh K, Pekmezci M, Fernandez-Pol S, Mirchia K, Toland A, Vogel H, Bannykh S, Schafernak KT, Alexandrescu S, Mobley BC, Powell S, Davidson CJ, Neltner J, Boué DR, Hattab E, Ferris SP, Ohgami RS, Rubenstein JL, Bollen AW, Tihan T, Perry A, Solomon DA, and Wen KW more...
- Subjects
- Humans, Lymphoproliferative Disorders etiology, Lymphoproliferative Disorders genetics, Epstein-Barr Virus Infections
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- 2023
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36. Next-generation sequencing of a large uveal melanoma with whole genome doubling and a PBRM1 mutation.
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Ahmad TR, Pekmezci M, Bloomer MM, Grenert JP, and Afshar AR
- Abstract
Purpose: To report a large uveal melanoma with extra-scleral extension which underwent spontaneous infarction and its unique molecular signature profile., Observations: An 81-year-old female presented with a blind, painful eye. Intraocular pressure was 48 mm Hg. There was a large subconjunctival melanotic mass overlying a choroidal melanoma with anterior extension involving the ciliary body and the iridocorneal angle and iris. Ultrasonography confirmed a dome-shaped anterior cilio-choroidal mass with extra-scleral extension. The patient underwent enucleation and pathologic evaluation confirmed cilio-choroidal melanoma. The posterior half of the tumor involving the ciliary body and the extra-scleral component were spontaneously infarcted and were composed of large melanophages. Next-generation sequencing demonstrated a splice site mutation in PBRM1 and whole-genome doubling in addition to a GNAQ hotspot mutation, chromosome 3 loss and 8q gain., Conclusions and Importance: This case of a large, auto-infarcted uveal melanoma demonstrates a PBRM1 mutation and whole-genome doubling., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.) more...
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- 2023
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37. Prognostic Value of BAP1 and Preferentially Expressed Antigen in Melanoma (PRAME) Immunohistochemistry in Uveal Melanomas.
- Author
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Han LM, Lee KW, Uludag G, Seider MI, Afshar AR, Bloomer MM, and Pekmezci M
- Subjects
- Adult, Humans, Prognosis, Immunohistochemistry, Retrospective Studies, Tumor Suppressor Proteins genetics, Ubiquitin Thiolesterase genetics, Antigens, Neoplasm, Uveal Melanoma, Melanoma pathology, Uveal Neoplasms metabolism
- Abstract
Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and despite excellent local control, more than 50% of patients develop and die from metastatic disease. Loss of BAP1 nuclear staining, a surrogate marker of BAP1 mutation, and preferentially expressed antigen in melanoma (PRAME) messenger RNA overexpression, as assessed using qPCR, have previously been shown to correlate with increased metastasis rate in UM. In this study, we demonstrated that UM could be successfully risk-stratified using a combination of BAP1 and PRAME immunohistochemical (IHC) stains. We retrospectively reviewed 318 UM cases with sufficient tissue and performed BAP1 and PRAME IHC to stratify them as BAP1+/PRAME- (group 1, n = 135), BAP1+/PRAME+ (group 2, n = 43), BAP1-/PRAME- (group 3, n = 94), and BAP1-/PRAME+ (group 4, n = 46). Increasing the study risk group on the basis of loss of BAP1 expression and positive PRAME staining was associated with a higher rate of metastasis and disease-specific death and lower metastasis-free survival (MFS) and disease-specific survival (DSS). Among tumors with loss of BAP1 staining, PRAME positivity was associated with shorter MFS (P = .018) and showed a trend toward shorter DSS (P = .061). Among tumors with retained BAP1 staining, PRAME positivity was associated with shorter MFS and DSS (P = .001 and P = .021, respectively). In summary, a combination of BAP1 and PRAME IHC can be used for risk stratification of UMs., (Published by Elsevier Inc.) more...
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- 2023
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38. Sarcomatous Transformation of a Medically Treated Lactotroph Pituitary Neuroendocrine Tumor?
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Terry M, Reis G, Horvai A, Pekmezci M, and Perry A
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- Humans, Pituitary Gland pathology, Lactotrophs pathology, Neuroendocrine Tumors therapy, Neuroendocrine Tumors pathology, Pituitary Neoplasms therapy, Pituitary Neoplasms pathology, Pituitary Diseases, Sarcoma pathology
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- 2023
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39. Uterine Inflammatory Myofibroblastic Tumors: Proposed Risk Stratification Model Using Integrated Clinicopathologic and Molecular Analysis.
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Ladwig NR, Bean GR, Pekmezci M, Boscardin J, Joseph NM, Therrien N, Sangoi AR, Piening B, Rajamanickam V, Galvin M, Bernard B, Zaloudek C, Rabban JT, Garg K, and Umetsu SE
- Subjects
- Female, Humans, Middle Aged, Anaplastic Lymphoma Kinase genetics, Receptor Protein-Tyrosine Kinases genetics, Uterus pathology, Risk Assessment, Neoplasms, Connective and Soft Tissue, Granuloma, Plasma Cell pathology
- Abstract
Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare mesenchymal tumor with largely benign behavior; however, a small subset demonstrate aggressive behavior. While clinicopathologic features have been previously associated with aggressive behavior, these reports are based on small series, and these features are imperfect predictors of clinical behavior. IMTs are most commonly driven by ALK fusions, with additional pathogenic molecular alterations being reported only in rare examples of extrauterine IMTs. In this study, a series of 11 uterine IMTs, 5 of which demonstrated aggressive behavior, were evaluated for clinicopathologic variables and additionally subjected to capture-based next-generation sequencing with or without whole-transcriptome RNA sequencing. In the 6 IMTs without aggressive behavior, ALK fusions were the sole pathogenic alteration. In contrast, all 5 aggressive IMTs harbored pathogenic molecular alterations and numerous copy number changes in addition to ALK fusions, with the majority of the additional alterations present in the primary tumors. We combined our series with cases previously reported in the literature and performed statistical analyses to propose a novel clinicopathologic risk stratification score assigning 1 point each for: age above 45 years, size≥5 cm,≥4 mitotic figures per 10 high-power field, and infiltrative borders. No tumors with 0 points had an aggressive outcome, while 21% of tumors with 1 to 2 points and all tumors with ≥3 points had aggressive outcomes. We propose a 2-step classification model that first uses the clinicopathologic risk stratification score to identify low-risk and high-risk tumors, and recommend molecular testing to further classify intermediate-risk tumors., Competing Interests: Conflicts of Interest and Source of Funding: This study was funded by the UCSF Department of Pathology Clinical Research Endowment awards granted to N.R.L., K.G., and S.E.U. J.T.R. reports that his spouse receives salary and stock options from Merck and Co. For the remaining authors none were declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.) more...
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- 2023
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40. Rapid pre-retinal ossification presenting as a vascularized lesion over an area of chronic retinal detachment.
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Ma CJ, Pekmezci M, and Stewart JM
- Abstract
Purpose: To describe the clinical, optical coherence tomography (OCT), and histopathological findings of a patient who was found to have ossification of a pre-retinal membrane after multiple surgical repairs for retinal detachment., Methods: The patient had comprehensive ophthalmic examinations during seven years of follow-up and underwent surgical removal of her pre-retinal membrane., Results: A 24-year-old woman with a history of retinal detachment and multiple retina surgeries presented with baseline vision of 20/200 and refractory glaucoma in the left eye (right eye with no light perception due to prior failed retinal detachment repair). OCT showed a thick epiretinal membrane with hypo-reflective intraretinal spaces in the macula, and exam revealed a chronic retinal detachment superotemporally surrounded by laser barricade. She was stable for six years and then experienced vision loss and decreasing eye pressure, concurrent with rapid evolution of pre-retinal fibrosis, leading to a vascularized consolidation in the mid-periphery, for which she underwent vitrectomy and membrane peel. The vascularized lesion over the area of detachment in the superotemporal retina was removed en bloc through the anterior chamber. Pathological findings revealed woven bone formation anterior to the internal limiting membrane, and the tissue was GFAP negative., Conclusions: Our case adds to the limited knowledge of the chronology, presentation, and surgical management of intraocular ossification, especially of the rarer pre-retinal type. Our patient highlights that development of ossification can happen more quickly than previously thought (year or years rather than decades), can be hidden under vascularized lesions, and is dynamic, with simultaneous release of traction in one area and increased traction in another. Diligent follow-up is indicated even in cases of vitreous membranes from retinal detachment that otherwise appear to have been stable for years., Competing Interests: The following authors have no financial disclosures: CJM, MP, JMS., (© 2023 The Authors.) more...
- Published
- 2022
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41. Iris and Ciliary Body Melanocytomas Are Defined by Solitary GNAQ Mutation Without Additional Oncogenic Alterations.
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Solomon DA, Ramani B, Eiger-Moscovich M, Milman T, Uludag G, Crawford JB, Phan I, Char DH, Shields CL, Eagle RC Jr, Bastian BC, Bloomer MM, and Pekmezci M
- Subjects
- Humans, GTP-Binding Protein alpha Subunits genetics, GTP-Binding Protein alpha Subunits metabolism, DNA Mutational Analysis, Ciliary Body pathology, Retrospective Studies, Case-Control Studies, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, Mutation, Iris pathology, Uveal Neoplasms diagnosis, Uveal Neoplasms genetics, Uveal Neoplasms pathology, Melanoma pathology, Nevus, Pigmented pathology, Skin Neoplasms pathology
- Abstract
Objective: To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication., Design: Retrospective case-control study., Subjects: Patients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea., Methods: Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features., Main Outcome Measures: Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence., Results: Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized., Conclusions: In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions., (Published by Elsevier Inc.) more...
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- 2022
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42. Prospective genomically guided identification of "early/evolving" and "undersampled" IDH-wildtype glioblastoma leads to improved clinical outcomes.
- Author
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Zhang Y, Lucas CG, Young JS, Morshed RA, McCoy L, Oberheim Bush NA, Taylor JW, Daras M, Butowski NA, Villanueva-Meyer JE, Cha S, Wrensch M, Wiencke JK, Lee JC, Pekmezci M, Phillips JJ, Perry A, Bollen AW, Aghi MK, Theodosopoulos P, Chang EF, Hervey-Jumper SL, Berger MS, Clarke JL, Chang SM, Molinaro AM, and Solomon DA more...
- Subjects
- Adult, Humans, Isocitrate Dehydrogenase genetics, Mutation, Prospective Studies, Astrocytoma genetics, Brain Neoplasms diagnosis, Brain Neoplasms genetics, Brain Neoplasms pathology, Glioblastoma diagnosis, Glioblastoma genetics, Glioma pathology
- Abstract
Background: Genomic profiling studies of diffuse gliomas have led to new improved classification schemes that better predict patient outcomes compared to conventional histomorphology alone. One example is the recognition that patients with IDH-wildtype diffuse astrocytic gliomas demonstrating lower-grade histologic features but genomic and/or epigenomic profile characteristic of glioblastoma typically have poor outcomes similar to patients with histologically diagnosed glioblastoma. Here we sought to determine the clinical impact of prospective genomic profiling for these IDH-wildtype diffuse astrocytic gliomas lacking high-grade histologic features but with molecular profile of glioblastoma., Methods: Clinical management and outcomes were analyzed for 38 consecutive adult patients with IDH-wildtype diffuse astrocytic gliomas lacking necrosis or microvascular proliferation on histologic examination that were genomically profiled on a prospective clinical basis revealing criteria for an integrated diagnosis of "diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV" per cIMPACT-NOW criteria., Results: We identified that this diagnosis consists of two divergent clinical scenarios based on integration of radiologic, histologic, and genomic features that we term "early/evolving" and "undersampled" glioblastoma, IDH-wildtype. We found that prospective genomically guided identification of early/evolving and undersampled IDH-wildtype glioblastoma resulted in more aggressive patient management and improved clinical outcomes compared to a biologically matched historical control patient cohort receiving standard-of-care therapy based on histomorphologic diagnosis alone., Conclusions: These results support routine use of genomic and/or epigenomic profiling to accurately classify glial neoplasms, as these assays not only improve diagnostic classification but critically lead to more appropriate patient management that can improve clinical outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.) more...
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- 2022
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43. Multiplatform molecular analyses refine classification of gliomas arising in patients with neurofibromatosis type 1.
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Lucas CG, Sloan EA, Gupta R, Wu J, Pratt D, Vasudevan HN, Ravindranathan A, Barreto J, Williams EA, Shai A, Whipple NS, Bruggers CS, Maher O, Nabors B, Rodriguez M, Samuel D, Brown M, Carmichael J, Lu R, Mirchia K, Sullivan DV, Pekmezci M, Tihan T, Bollen AW, Perry A, Banerjee A, Mueller S, Gupta N, Hervey-Jumper SL, Oberheim Bush NA, Daras M, Taylor JW, Butowski NA, de Groot J, Clarke JL, Raleigh DR, Costello JF, Phillips JJ, Reddy AT, Chang SM, Berger MS, and Solomon DA more...
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- Adult, Homozygote, Humans, Sequence Deletion, Astrocytoma genetics, Brain Neoplasms genetics, Glioma genetics, Glioma pathology, Neurofibromatosis 1 complications, Neurofibromatosis 1 genetics
- Abstract
Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas. The first harbored biallelic NF1 inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology "pilocytic astrocytoma, arising in the setting of NF1". The second subgroup harbored additional oncogenic alterations including CDKN2A homozygous deletion and ATRX mutation, occurred primarily during adulthood, followed a more aggressive clinical course, and was epigenetically diverse, with most tumors aligning with either high-grade astrocytoma with piloid features or various subclasses of IDH-wildtype glioblastoma. Several patients were treated with small molecule MEK inhibitors that resulted in stable disease or tumor regression when used as a single agent, but only in the context of those tumors with NF1 inactivation lacking additional oncogenic alterations. Together, these findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population., (© 2022. The Author(s).) more...
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- 2022
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44. Intratumor and informatic heterogeneity influence meningioma molecular classification.
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Vasudevan HN, Choudhury A, Hilz S, Villanueva-Meyer JE, Chen WC, Lucas CG, Braunstein SE, Oberheim Bush NA, Butowski N, Pekmezci M, McDermott MW, Perry A, Solomon DA, Magill ST, and Raleigh DR
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- Biomarkers, Tumor, Genetic Heterogeneity, Humans, Informatics, Mutation, Meningeal Neoplasms genetics, Meningioma genetics
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- 2022
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45. Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma.
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Lucas CG, Davidson CJ, Alashari M, Putnam AR, Whipple NS, Bruggers CS, Mendez JS, Cheshier SH, Walker JB, Ramani B, Cadwell CR, Sullivan DV, Lu R, Mirchia K, Van Ziffle J, Devine P, Goldschmidt E, Hervey-Jumper SL, Gupta N, Oberheim Bush NA, Raleigh DR, Bollen A, Tihan T, Pekmezci M, Solomon DA, Phillips JJ, and Perry A more...
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- Adolescent, Adult, Clonal Evolution, Cyclin-Dependent Kinase Inhibitor p16 genetics, DNA, Female, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Male, Mutation genetics, Proto-Oncogene Proteins B-raf genetics, Sequence Deletion, Young Adult, Astrocytoma genetics, Astrocytoma pathology, Brain Neoplasms genetics, Brain Neoplasms pathology, Ganglioglioma pathology
- Abstract
Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...
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- 2022
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46. Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.
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Sloan EA, Gupta R, Koelsche C, Chiang J, Villanueva-Meyer JE, Alexandrescu S, Eschbacher JM, Wang W, Mafra M, Ud Din N, Carr-Boyd E, Watson M, Punsoni M, Oviedo A, Gilani A, Kleinschmidt-DeMasters BK, Coss DJ, Lopes MB, Reddy A, Mueller S, Cho SJ, Horvai AE, Lee JC, Pekmezci M, Tihan T, Bollen AW, Rodriguez FJ, Ellison DW, Perry A, von Deimling A, Chang SM, Berger MS, and Solomon DA more...
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- Adolescent, Adult, Biomarkers, Tumor genetics, Child, Child, Preschool, Epigenesis, Genetic, Epigenomics, Humans, Oncogene Proteins, Fusion genetics, RNA-Binding Protein EWS genetics, Young Adult, Brain Neoplasms genetics, Brain Neoplasms pathology, Hemangioma genetics, Histiocytoma, Malignant Fibrous genetics, Meningeal Neoplasms genetics, Meningioma genetics, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms pathology
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'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial mesenchymal tumor, FET-CREB fusion-positive') that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity., (© 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.) more...
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- 2022
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47. Plexiform Neurofibroma With Activating KRAS Mutation and Segmental Presentation Involving the Unilateral Eyelid.
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Stallworth JY, Smith LD, Vagefi MR, and Pekmezci M
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- Eyelids pathology, Humans, Mutation, Neurofibromatoses, Proto-Oncogene Proteins p21(ras) genetics, Neurofibroma, Neurofibroma, Plexiform diagnosis, Neurofibroma, Plexiform genetics, Neurofibromatosis 1 diagnosis, Neurofibromatosis 1 genetics
- Abstract
Plexiform neurofibromas are classically thought to be pathognomonic for neurofibromatosis type 1. However, isolated forms may occur, particularly as a manifestation of segmental neurofibromatosis related to postzygotic mosaicism in the NF1 gene. Most cases occur on the head and neck, trunk, and extremities with very few cases reported in the periorbital area. The authors report a case of plexiform neurofibroma with perineuriomatous features of the right upper eyelid in a patient with no other stigmata of neurofibromatosis. While suggestive of segmental neurofibromatosis, genetic analysis revealed activating KRAS mutation and inactivating mutation in PHF6 with no evidence of NF1 mutation in germline or tumor tissue. Neither KRAS nor PHF6 have been previously reported in association with neurofibroma., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.) more...
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- 2022
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48. TRAF7 somatic mosaicism in a patient with bilateral optic nerve sheath meningiomas: illustrative case.
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Kaidonis G, Pekmezci M, Van Ziffle J, Auguste KI, and Horton JC
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Background: In the past decade, next-generation sequencing has spurred significant progress in the understanding of cytogenetic alterations that occur in meningiomas. Eighty percent of adult meningiomas harbor pathogenic somatic variants involving NF2 , TRAF7 , SMARCB1 , KLF4 , PI3K , or POLR2A. Somatic variants in TRAF7 associated with meningiomas usually localize to the gene's WD40 domains but are mutually exclusive to germline mutations, which cause a distinctive autosomal dominant syndrome., Observations: This case involved a 15-year-old girl with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis, and syndromic features, including craniosynostosis, brain anomalies, syndactyly, brachydactyly, epicanthus, and patent ductus arteriosus. Genetic testing of the meningioma specimen 7 years after biopsy showed a pathogenic p.R641C variant within the WD40 domain of the TRAF7 gene. Additional testing of unaffected tissues identified the same variant at lower allele frequencies, consistent with postzygotic somatic mosaicism., Lessons: The authors report postzygotic somatic mosaicism for a p.R641C variant in the TRAF7 gene in a patient with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis and a constellation of systemic findings previously recognized in patients with germline mutations of this gene. This is the first report of optic nerve sheath meningioma in a patient with mutation in the TRAF7 gene., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2022 The authors.) more...
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- 2022
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49. A genetically distinct pediatric subtype of primary CNS large B-cell lymphoma is associated with favorable clinical outcome.
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Güney E, Lucas CG, Qi Z, Yu J, Zhang R, Ohgami RS, Rubenstein JL, Boué DR, Schafernak K, Wertheim GB, Dahiya S, Giulino-Roth L, Attarbaschi A, Barth MJ, Kothari S, Abla O, Cohen AL, Mendez JS, Bollen A, Perry A, Tihan T, Pekmezci M, Solomon DA, and Wen KW more...
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- Child, Humans, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Non-Hodgkin pathology
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- 2022
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50. Towards Development of a Standard Terminology of the World Health Organization Classification of Tumors of the Central Nervous System in the Turkish Language, and a Perspective on the Practical Implications of the WHO Classification for Low and Middle Income Countries.
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Soylemezoglu F, Oz B, Egilmez R, Pekmezci M, Bozkurt S, Danyeli AE, Onguru O, Kulac I, and Tihan T
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- Developing Countries, Humans, Language, Pandemics, World Health Organization, COVID-19, Central Nervous System Neoplasms diagnosis
- Abstract
In our manuscript, we propose a common terminology in the Turkish language for the newly adopted WHO classification of the CNS tumors, also known as the WHO CNS 5th edition. We also comment on the applicability of this new scheme in low and middle income countries, and warn about further deepening disparities between the global north and the global south. This division, augmented by the recent COVID-19 pandemic, threatens our ability to coordinate efforts worldwide and may create significant disparities in the diagnosis and treatment of cancers between the "haves" and the "have nots". more...
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- 2022
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