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Pleomorphic xanthoastrocytomas (PXAs) harbor CDKN2A homozygous deletion in >90% of cases, resulting in loss of p16 expression by immunohistochemistry. Considering the proximity of MTAP to CDKN2A and their frequent concurrent deletions, loss of MTAP expression may be a surrogate for CDKN2A homozygous deletion. We evaluated p16 and MTAP expression in 38 patient PXAs (CNS WHO grade 2: n = 23, 60.5%; grade 3: n = 15, 39.5%) with available chromosomal microarray data to determine whether MTAP can be utilized independently or in combination with p16 to predict CDKN2A status. CDKN2A, CDKN2B, and MTAP homozygous deletion were present in 37 (97.4%), 36 (94.7%), and 25 (65.8%) cases, respectively. Expression of p16 was lost in 35 (92.1%) cases, equivocal in one (2.6%), and failed in 2 (5.3%), while MTAP expression was lost in 27 (71.1%) cases, retained in 10 (26.3%), and equivocal in one (2.6%). This yielded a sensitivity of 94.6% for p16 and 73.0% for MTAP in detecting CDKN2A homozygous deletion through immunohistochemistry. MTAP expression was lost in the 2 cases with failed p16 staining (combined sensitivity of 100%). Our findings demonstrate that combined p16 and MTAP immunostains correctly detect CDKN2A homozygous deletion in PXA, while MTAP expression alone shows reduced sensitivity.
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Ganglioglioma (GG) with anaplasia (anaplastic ganglioglioma) is a rare and controversial diagnosis. When present, anaplasia involves the glial component of the tumor, either at presentation or at recurrence. To date, most published cases lack molecular characterization. We describe the histologic and molecular features of 3 patients presenting with BRAF p. V600E-mutant GG (CNS WHO grade 1) with high-grade glial transformation at recurrence. The tumors occurred in pediatric patients (age 9-16 years) with time to recurrence from 20 months to 7 years. At presentation, each tumor was low-grade, with a BRAFV600E-positive ganglion cell component and a glial component resembling pleomorphic xanthoastrocytoma (PXA) or fibrillary astrocytoma. At recurrence, tumors resembled anaplastic PXA or high-grade astrocytomas without neuronal differentiation. CDKN2A homozygous deletion (HD) was absent in all primary tumors. At recurrence, 2 cases acquired CDKN2A HD; the third case showed loss of p16 and MTAP immunoexpression, but no CDKN2A/B HD or mutation was identified. By DNA methylation profiling, all primary and recurrent tumors either grouped or definitely matched to different methylation classes. Our findings indicate that malignant progression of the glial component can occur in GG and suggest that CDKN2A/B inactivation plays a significant role in this process.
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Neoplasias Encefálicas , Ganglioglioma , Humanos , Ganglioglioma/genética , Ganglioglioma/patologia , Adolescente , Criança , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Masculino , Feminino , Proteínas Proto-Oncogênicas B-raf/genética , Epigênese Genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologiaAssuntos
Antígenos de Neoplasias , Biomarcadores Tumorais , Enucleação Ocular , Perfilação da Expressão Gênica , Imuno-Histoquímica , Melanoma , Neoplasias Uveais , Humanos , Neoplasias Uveais/genética , Neoplasias Uveais/metabolismo , Melanoma/genética , Melanoma/metabolismo , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica/métodos , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , IdosoRESUMO
Pseudoendocrine sarcoma (PES) is a recently described neoplasm typically arising in paravertebral soft tissues. Histologically, PES resembles well-differentiated neuroendocrine tumors but lacks expression of epithelial/neuroendocrine markers, and most show aberrant nuclear ß-catenin positivity. We describe the clinicopathological and molecular features and DNA methylation profile of one PES. A resected paraspinal soft tissue mass in a 52-year-old man showed a neuroendocrine-like neoplasm, negative for keratin, and synaptophysin and showing diffuse nuclear ß-catenin expression. Targeted NGS confirmed a CTNNB1 (p.S37C) mutation. Whole genome methylation analysis showed no match to any methylation class in the central nervous system tumor (versions 11b6 and 12b6) or sarcoma classifier (calibrated scores of ≤0.3), but clustered together with a recently reported PES in which methylation analysis was also performed. He remained disease-free for 18 months after surgery, followed by chemoradiation. As more cases are examined, our findings suggest that PES may have a unique methylation profiling signature.
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Sarcoma , Neoplasias de Tecidos Moles , Masculino , Humanos , Pessoa de Meia-Idade , beta Catenina/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/genética , Mutação , Epigênese Genética/genética , Biomarcadores Tumorais/genéticaRESUMO
Introduction Neurenteric cysts (NECs) are rare, congenital lesions lined by endodermal cell-derived columnar or cuboidal epithelium. Based on previous studies, gross total removal of the capsule has been presumed to be the ideal surgical goal. Objective This series was undertaken to further understand the risk of recurrence based on the extent of capsule resection. Methods Records were retrospectively reviewed for all patients with radiographic or pathological evidence of intracranial NEC from 1996 to 2021. Results A total of eight patients were identified; four of eight (50%) presented with headache, and four had signs of one or more cranial nerve syndromes. One patient (13%) presented with third nerve palsy, one (13%) had sixth nerve palsy, and two (25%) with hemifacial spasm. One patient (13%) presented with signs of obstructive hydrocephalus. Magnetic resonance imaging demonstrated T2 hyper- or isointense lesions. Diffusion-weighted imaging was negative in all patients (100%) and T1 contrast-enhanced imaging demonstrated minimal rim enhancement in two patients (25%). In three of eight (38%), a gross total resection (GTR) was achieved, while in four (50%), a near-total resection, and in one (13%), a decompression was performed. Recurrences occurred in two (25%) patients, one with decompression and another with near-total resection, among these 1/2 required repeat surgery after a mean follow-up of 77 months. Conclusion In this series, none from GTR group demonstrated recurrence, while 40% of those receiving less than GTR recurred, underpinning the importance of maximally safe resection in these patients. Overall patients did well without major morbidity from surgery.
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Primary leptomeningeal lymphoma is exceedingly rare. We describe 2 rare lymphoma cases with exclusive leptomeningeal disease: 1 ALK-positive (ALK+) anaplastic large cell lymphoma (ALCL) and 1 primary effusion lymphoma (PEL). Case 1: A 19-year-old man presented with symptoms concerning for leptomeningitis. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis. Spine MRI demonstrated pial enhancement from T10 through the conus medullaris and cauda equina enhancement/thickening. A biopsy showed leptomeningeal involvement by large lymphoma cells with hallmark cells and brisk mitotic activity. By immunohistochemistry, cells were CD7/CD30-positive with cytoplasmic ALK staining. No systemic disease was identified. The diagnosis of primary leptomeningeal ALK+ ALCL was made. Despite 2 CSF relapses requiring systemic therapy and autologous bone marrow transplant, the patient was in complete clinical remission 9 years after the diagnosis. Case 2: A 60-year-old, human immunodeficiency virus-positive man presented with symptoms suggestive of leptomeningitis. Brain MRIs revealed multifocal, supratentorial, and infratentorial leptomeningeal enhancement. A right frontal biopsy demonstrated leptomeningeal involvement by large lymphoma cells negative for B-cell immunostains, but CD138, MUM-1, and HHV8-positive, with aberrant CD3 expression. EBV-encoded RNA in situ hybridization was positive. In absence of solid lesions/extracranial involvement, the diagnosis of leptomeningeal PEL was rendered. Despite initial complete remission after chemotherapy, the patient died 9 months later.
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Linfoma Anaplásico de Células Grandes , Neoplasias Meníngeas , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Quinase do Linfoma Anaplásico/genética , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/uso terapêutico , Recidiva Local de Neoplasia , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , FenótipoRESUMO
The 2016 and 2021 World Health Organization (WHO) Classifications of Tumors of the Central Nervous System (CNS) reflect the importance of integrating molecular analysis into CNS tumor diagnosis and classification, adding to the complexity of any surgical neuropathology practice. On the other hand, our evolving understanding of genomic alterations across the spectrum of CNS tumors highlights the importance of utilizing traditional histological and immunohistochemical approaches to first establish as accurate a diagnosis as possible. Such an approach is also essential to recognizing the most appropriate ancillary test(s) needed for accurate classification and grading of CNS tumors. Here, we present an algorithmic approach to be considered while evaluating surgical neuropathology biopsies, which includes a recognition of main histological patterns, and incorporates clinical and radiologic features, to assist with accurate diagnosis and optimal selection of subsequent ancillary testing.
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Neoplasias do Sistema Nervoso Central , Biópsia , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico , Humanos , Organização Mundial da SaúdeRESUMO
Extranodal NK/T-cell lymphoma (ENKTL) is a well-defined cytotoxic lymphoma strongly associated with Epstein-Barr virus (EBV) infection, commonly affecting the nasopharynx and upper aerodigestive tract. Primary central nervous system (CNS) involvement is rare, and only 17 cases were previously reported in the literature. Here, we report the case of a 44-year-old male admitted with a 3-month history of personality changes and progressive right leg weakness. Brain magnetic resonance imaging studies (MRIs) revealed multiple rim-enhancing brain lesions bilaterally. An extensive clinical and laboratory workup was unrevealing, and 2 brain biopsies were initially considered inconclusive. Pertinently, no systemic lymphoproliferative disorder was identified. The patient initially experienced remarkable clinical improvement with dexamethasone, pulse methylprednisolone, and rituximab therapy. However, he eventually had rapid clinical deterioration, was found to have increased brain lesions, and died nearly 6 months after the initial presentation. During this time, the second brain biopsy was found to show involvement by T-cell lymphoma of NK-cell lineage, which was EBV negative. No post-mortem examination was done to identify any systemic lymphoma. This case serves to expand the spectrum of lymphomas involving the CNS.
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Chordoid glioma (CG) is a rare WHO Grade II neoplasm of the anterior third ventricle. We report two cases of CG with new presentation in terms of histopathology and location: a case of CG with osseous metaplasia evident on imaging, and another CG, unusually located in the posterior portion of the third ventricle.
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Neoplasias do Ventrículo Cerebral , Glioma , Terceiro Ventrículo , Neoplasias do Ventrículo Cerebral/diagnóstico por imagem , Neoplasias do Ventrículo Cerebral/cirurgia , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Radiografia , Terceiro Ventrículo/diagnóstico por imagemRESUMO
Angiomatoid fibrous histiocytoma (AFH) is an uncommon soft-tissue neoplasm that arises mostly in the extremities of young people and generally carries a good prognosis. Intracranial location is unusual and frequently associated with myxoid change. EWSR1 gene fusions with members of the CREB family (CREB1, ATF1, and CREM) are well-established events in AFH. These fusions have also been described in other neoplasms including intracranial myxoid mesenchymal tumor, and it is still uncertain whether the latter is a distinct entity or if it represents a myxoid variant of AFH. Here, we describe a rare falcine AFH presenting in a 50-year-old woman. The most striking feature of this tumor was its diffuse rhabdoid morphology with focal high mitotic activity, raising the consideration of rhabdoid meningioma (WHO grade III). The tumor cells were moderately positive for EMA and negative for progesterone receptor and SSTR2 prompting additional studies. Desmin was strongly positive and CD99 showed membranous immunoreactivity. BAP1, INI-1, and BRG1 expressions were retained. Next-generation sequencing analysis demonstrated an EWSR1-ATF1 gene fusion, supporting the diagnosis of an unusual rhabdoid variant of AFH. After gross total resection of this tumor, the patient remains free of disease 5 months after the surgery without additional treatment.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Histiocitoma Fibroso Maligno/diagnóstico , Histiocitoma Fibroso Maligno/genética , Antígeno 12E7/metabolismo , Fator 1 Ativador da Transcrição/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Desmina/metabolismo , Diagnóstico Diferencial , Feminino , Fusão Gênica , Histiocitoma Fibroso Maligno/patologia , Histiocitoma Fibroso Maligno/cirurgia , Humanos , Neoplasias Meníngeas , Meningioma , Pessoa de Meia-Idade , Proteína EWS de Ligação a RNA/genética , Resultado do TratamentoRESUMO
Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encoding either components or regulators of the RAS/MAPK pathway. Herein, we report an 11-year-old boy presenting with café au lait spots and right leg length discrepancy. A fascicular nerve biopsy of the tibial nerve demonstrated a Schwann cell proliferation with prominent onion-bulb formation, satisfying criteria for localized hypertrophic neuropathy. Molecular genetic analysis demonstrated identical KRAS mutations (c38_40dupGCG) in the peripheral nerve lesion and melanocytes from café au lait spots, but not in blood, supporting a diagnosis of a KRAS-mediated rasopathy with mosaicism. Immunohistochemical staining in the peripheral nerve lesion demonstrated strong pERK staining consistent with downstream MAPK pathway activation. This report suggests that at least a subset of localized hypertrophic neuropathies are bonafide, well-differentiated Schwann cell neoplasms developing through oncogenic RAS signaling, which provides new insights into the controversial entity historically known as localized hypertrophic neuropathy.
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Doenças do Sistema Nervoso Periférico/patologia , Células de Schwann/patologia , Criança , Humanos , Hipertrofia/genética , Hipertrofia/patologia , Masculino , Mutação , Doenças do Sistema Nervoso Periférico/genética , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
Congenital corneoscleral epithelial cysts can be associated with scleral thinning secondary to pressure from the expanding cyst. We report a congenital scleral epithelial cyst associated with a likely primary partial-thickness scleral defect. The defect appeared as a full-thickness communication between the cyst and posterior chamber on ultrasound biomicroscopy, most likely because the scleral remnant was too thin to be appreciated on imaging. The cyst was treated surgically by aspiration, excision of the anterior wall, and fibrin glue closure of the cyst cavity, with no recurrence after 14 months of follow-up.
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Cistos , Recidiva Local de Neoplasia , Humanos , Microscopia Acústica , EscleraRESUMO
Conjunctival squamous cell carcinoma (cSCC) and its precursors are among the most frequent ocular surface neoplasms worldwide. Copy gain of 8p11.22 and ADAM3A overexpression have been recently identified in invasive cSCC. We sought to study copy number gains using fluorescent in situ hybridization (FISH) in cSCC and the spectrum of precursor lesions. A total of 54 cases conjunctival squamous intraepithelial neoplasia (CIN), carcinoma in situ (CIS), or cSCC were studied using FISH with an ADAM3A (8p11 locus) probe and a chromosome 8 (Chr 8) centromere reference probe. Eighty one percent (44/54) of the cases presented in men and 19% (10/54) in women. The age at presentation ranged from 12 to 94 years (mean 65.5 years). Severe CIN was diagnosed in 45% (24/54) of the cases, followed by CIS in 31% (17/54), moderate CIN in 15% (8/54), invasive cSCC in 7% (4/54), and mild CIN in 2% (1/54). Nine (of 54) (17%) cases harbored ADAM3A or Chr 8 gains, with one of these cases demonstrating high level amplification. All ADAM3A alterations were restricted to high-grade lesions, including 2/17 (12%) cCIS, 1/4 (24%) cSCC, 5/24 (20%) severe CIN and 1/8 (12%) moderate CIN. Monosomy 8 was detected in 2 (4%) cases. No ADAM3A alterations were detected in non-neoplastic controls. Gains of ADAM3A/chromosome 8 occur in a subset of cSCC and its precursors. Alterations were present in high-grade lesions, sparing non-neoplastic conjunctiva and absent in tested controls. Thus, the specificity of this alteration as a biomarker for ocular SCC deserves further study.
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Proteínas ADAM/genética , Biomarcadores Tumorais/genética , Neoplasias da Túnica Conjuntiva/genética , Amplificação de Genes , Dosagem de Genes , Lesões Pré-Cancerosas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Lesões Intraepiteliais Escamosas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Neoplasias da Túnica Conjuntiva/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Lesões Intraepiteliais Escamosas/patologia , Adulto JovemRESUMO
The presence of Alternative lengthening of telomeres (ALT) and/or ATRX loss, as well as the role of other telomere abnormalities, have not been formally studied across the spectrum of NF1-associated solid tumors. Utilizing a telomere-specific FISH assay, we classified tumors as either ALT-positive or having long (without ALT), short, or normal telomere lengths. A total of 426 tumors from 256 NF1 patients were evaluated, as well as 99 MPNST tumor samples that were sporadic or of unknown NF1 status. In the NF1-glioma dataset, ALT was present in the majority of high-grade gliomas: 14 (of 23; 60%) in contrast to only 9 (of 47; 19%) low-grade gliomas (p = 0.0009). In the subset of ALT-negative glioma cases, telomere lengths were estimated and we observed 17 (57%) cases with normal, 12 (40%) cases with abnormally long, and only 1 (3%) case with short telomeres. In the NF1-associated malignant nerve sheath tumor (NF1-MPNST) set (n = 75), ALT was present in 9 (12%). In the subset of ALT-negative NF1-MPNST cases, telomeres were short in 9 (38%), normal in 14 (58%) and long in 1 (3%). In the glioma set, overall survival was significantly decreased for patients with ALT-positive tumors (p < 0.0001). In the NF1-MPNST group, overall survival was superior for patients with tumors with short telomeres (p = 0.003). ALT occurs in a subset of NF1-associated solid tumors and is usually restricted to malignant subsets. In contrast, alterations in telomere lengths are more prevalent than ALT.
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Neoplasias Encefálicas/genética , Neurofibromatose 1/genética , Homeostase do Telômero/genética , Telômero/genética , Adulto , Feminino , Glioma/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Mutação , Neurofibromina 1/genética , Neurofibrossarcoma/genética , Adulto JovemRESUMO
Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n = 14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of 16), and CD68 (27 of 30), but HAM56, CD163, and IBA-1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), -13q in 4 of 6, and -14 in 4 of 6. Next-generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (P = 0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB-1 (P > 0.05). GCA is a variant of IDH-wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma.
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Astrocitoma/genética , Astrocitoma/metabolismo , Astrocitoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Glioma/patologia , Tumor de Células Granulares/genética , Tumor de Células Granulares/metabolismo , Tumor de Células Granulares/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imuno-Histoquímica , Isocitrato Desidrogenase/genética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Regiões Promotoras Genéticas/genéticaRESUMO
Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fifty-seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3-75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomere-specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3-K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRX- (20/24, 83%) or ALT-/ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3-K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PA-A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3-K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.
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Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Adolescente , Adulto , Idoso , Anaplasia/patologia , Biomarcadores Tumorais/genética , Encéfalo/patologia , Criança , Pré-Escolar , Feminino , Glioma/patologia , Histonas/genética , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Telômero/genética , Telômero/fisiologia , Homeostase do Telômero/genética , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/fisiologiaRESUMO
Members of the miR-125 family are strongly expressed in several tissues, particularly brain, but may be dysregulated in cancer including adult and pediatric glioma. In this study, miR-125 members were downregulated in pilocytic astrocytoma (PA) as a group compared to non-neoplastic brain in the Agilent platform. In the Nanostring platform, miR-125 members were downregulated primarily in pleomorphic xanthoastrocytomas and gangliogliomas. Using CISH for miR-125b, highest levels of expression were present in grade II tumors (11/33, 33% grade II tumors with 3+ expression compared to 3/70, 4% grade I tumors) (p < 0.001). When focusing on the two histologic subgroups with the largest number of samples, PA and diffuse astrocytoma (DA), the highest expression levels were present in DA, in comparison with the PA group (p = 0.01). Overexpression of miR-125b in pediatric low grade glioma (PLGG) derived cell lines (Res186, Res259, and BT66) resulted in decreased growth and invasion, as well as apoptosis. Additionally, miR-125b overexpression in BT66 resulted in senescence. These findings suggest that miR-125 is frequently underexpressed in PLGG, and overexpression results in a decrease in cell growth and induction of apoptosis, findings that deserve further investigation given its potential as a novel therapeutic strategy for PLGG.
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Regulação para Baixo , Perfilação da Expressão Gênica/métodos , Glioma/genética , MicroRNAs/genética , Adolescente , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , Lactente , Masculino , Gradação de Tumores , Invasividade NeoplásicaAssuntos
Cistos/diagnóstico por imagem , Descolamento Retiniano/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Perfurações Retinianas/diagnóstico por imagem , Doença Crônica , Cistos/fisiopatologia , Cistos/cirurgia , Tamponamento Interno , Fluorocarbonos/administração & dosagem , Humanos , Masculino , Imagem Multimodal , Descolamento Retiniano/fisiopatologia , Descolamento Retiniano/cirurgia , Doenças Retinianas/fisiopatologia , Doenças Retinianas/cirurgia , Perfurações Retinianas/fisiopatologia , Perfurações Retinianas/cirurgia , Recurvamento da Esclera , Tomografia de Coerência Óptica , Ultrassonografia , Acuidade Visual/fisiologia , Vitrectomia , Adulto JovemRESUMO
Progressive transformation of germinal centers (PTGC) is a form of follicular hyperplasia recently associated with immunoglobulin G4-related disease (IgG4-RD), but the ophthalmic manifestations of this combination are poorly described. In this retrospective case series, we present three cases of IgG4-related orbital disease (IgG4-ROD) showing varying degrees of PTGC involving the orbit and lacrimal gland. Three adult women presented with ill-defined lacrimal gland enlargement. Histologic sections showed variable fibrosis and large, irregular lymphoid follicles with prominent mantle zones penetrating the germinal centers, highlighted by Bcl-2 and/or IgD immunostains. The interfollicular areas contained a mixture of plasma cells, scattered histiocytes and eosinophils. Mixed T and B-cells were present, and no signs of monoclonality were identified. All cases showed more than 100 IgG4 positive cells per high power field. Epstein-Barr virus in situ hybridization performed in one case was negative. The serum IgG4 level was tested in one case and showed elevation above the normal range. After 2-10â¯months of follow-up, the patients showed either near-complete resolution or no remaining signs of ophthalmic disease. Increasing awareness of these PTGC in extra-nodal locations, including the orbit, may provide a better understanding of the histologic spectrum of this disease.