RESUMO
BACKGROUND: Primary brain rhabdomyosarcoma is a rare primary brain malignancy with few case reports. The vast majority of cases of primary brain rhabdomyosarcoma occur in pediatric patients, and immunohistochemistry can distinguish it from embryonal subtypes; however, few cases of primary brain rhabdomyosarcoma in adults have been reported in the literature. CASE PRESENTATION: We report the case of a 26-year-old White male patient who was found to have primary brain alveolar rhabdomyosarcoma after developing headaches for several months. A brain MRI revealed a mixed cystic and solid tumor along the vermis of the cerebellum. The patient underwent a gross total surgical resection, which confirmed the diagnosis of alveolar rhabdomyosarcoma. Further staging workup for another primary focus or disseminated disease yielded negative results, confirming the diagnosis of primary alveolar rhabdomyosarcoma of the brain. CONCLUSION: The standard of care for managing this rare type of brain tumor involves surgery with adjuvant chemoradiotherapy. Further studies should be conducted for a better diagnostic and therapeutic understanding.
Assuntos
Neoplasias Encefálicas , Rabdomiossarcoma Alveolar , Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Adulto , Humanos , Masculino , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Imageamento por Ressonância Magnética , Rabdomiossarcoma Alveolar/diagnóstico por imagem , Rabdomiossarcoma Alveolar/terapia , Rabdomiossarcoma Embrionário/diagnósticoRESUMO
Diffuse gliomas are the most common primary malignancies of the central nervous system (CNS). The 2016 edition of the World Health Organization (WHO) classification of CNS tumors opted to integrate current molecular data with the traditional histologic diagnosis in the definition of the disease. This integrated diagnosis offers a greater level of objectivity and helps in establishing more definitive diagnoses for tumors that may have been controversial on histology alone. The classification of gliomas may require FISH technique to identify chromosomal abnormalities. FISH is commonly used to identify 1p/19q codeletion, but many challenges are encountered in the process. In this study, we review the FISH results for 1p/19q codeletion of n = 85 diffuse glioma samples examined at a tertiary care center in the Middle East over a period of 8 years. We also conduct a literature review to study the potential role of DNA-microarray in the identification of 1p/19q deletions. Glioblastoma (GBM), WHO grade IV is the most common glioma type identified (n = 24; 29%). All oligodendrogliomas show 1p/19q codeletion (26/26) while 12.5% of GBMs have 1p/19q codeletion (3/24). Isolated 1p deletions are only identified in one case of diffuse astrocytoma, WHO grade II. Isolated 19q deletions are identified in oligoastrocytoma, anaplastic astrocytoma, and glioblastoma. FISH is the most commonly used technique to diagnose oligodendroglioma because it is a simple, effective, and accessible technique in settings with limited resources. However, the optimization process remains highly variable between laboratories. Microarray is a more objective technique that can provide more information about the genetic alterations of the tumor for better diagnosis and sub-classification of diffuse glioma types.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/diagnóstico , Glioma/genética , Humanos , Mutação , Oligodendroglioma/genética , Centros de Atenção TerciáriaRESUMO
Papillary tumors of the pineal region (PTPR) can be observed among adults with poor prognosis and high recurrence rates. Standards of therapy involve total surgical excision along with radiation therapy, with no promising prospects for primary adjuvant chemotherapy, as long-term treatment options have not been explored. Chromosome 10 loss is characteristic of PTPR, and PTEN gene alterations are frequently encountered in a wide range of human cancers and may be treated with mTORC1 inhibitors such as everolimus. In parallel, there are no reports of treating PTPR with everolimus alone as a monopharmacotherapy. We report the case of a patient diagnosed with PTPR (grade III) characterized by a PTEN R130Q alteration with chromosome 10 loss that was treated with everolimus pharmacotherapy alone, resulting in an asymptomatic course and tumor regression, a rare yet notable phenomenon not described in the literature so far with potential to alter the management approach to patients with PTPR.
Assuntos
Neoplasias Encefálicas , Glândula Pineal , Pinealoma , Adulto , Cromossomos Humanos Par 10 , Everolimo/uso terapêutico , Humanos , Recidiva Local de Neoplasia , PTEN Fosfo-Hidrolase/genéticaRESUMO
BACKGROUND: Bladder cancer is the ninth most common cancer worldwide, and the third most common cancer in Lebanon. Immunohistochemistry (IHC) has been used to stratify muscle-invasive bladder cancer (MIBC) into different subtypes. However, to our knowledge, there exists no study that investigates the use of this low-cost technique to predict prognosis in bladder cancer patients in our region. AIM: To examine the feasibility of low-cost triple-marker IHC assessment for MIBC subtyping in order to predict patients' survival and cisplatin sensitivity. METHODS AND RESULTS: We collected the specimens of deceased patients diagnosed with MIBC on pathology at our institution. For each case, tumor tissue blocks were retrieved and stained for hematoxylin and eosin in addition to three molecular markers by IHC: cytokeratin 5/6, cytokeratin 14 staining basal BC, and GATA3 staining luminal BC. A cut-off of ≥20% was set as positive. Kaplan-Meier curves were built, factored by BC subtype, to predict overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Hazard ratios in Cox regression were also created accounting for oncological factors and BC subtype. We categorized specimens as either luminal (GATA3 positive only) (n = 21; 56.7%) or as double-positive (GATA3 and basal cytokeratin 5/6 or cytokeratin 14 positive) (n = 16; 43.3%). The overall median survival was similar between the two categories (27.0 ± 4.82 months). Numbers favored luminal disease for PFS (Breslow P = .032). After adjusting for covariates, luminal molecular expression predicted PFS (0.28; [0.09-0.94]). Yet, the Cox model was not able to identify any predictors of OS or DSS. CONCLUSION: Specimens enriched with only a luminal molecular profile were more likely to exhibit cisplatin sensitivity. Despite the absence of guidelines recommending the utilization of molecular profiling in clinic practice, triple-marker IHC could serve as a potential low-cost prognostic indicator to identify patients at high risk of progression.
Assuntos
Biomarcadores Tumorais/análise , Músculos/patologia , Neoplasias da Bexiga Urinária/mortalidade , Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Cistectomia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Fator de Transcrição GATA3/análise , Fator de Transcrição GATA3/metabolismo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Queratina-14/análise , Queratina-14/metabolismo , Queratina-5/análise , Queratina-5/metabolismo , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
OBJECTIVE: Meningioma is the most common intracranial primary brain tumor. Risk factors such as age and exposure to radiation as well as prognostic factors such as grade, location, and extent of surgical resection have been reported in the literature worldwide; however, to our knowledge, data from the Middle East is still warranted. In this study, we aim to identify the characteristics, risk factors and outcomes of meningioma patients treated at a multidisciplinary regional referral center in the Middle East. PATIENTS AND METHODS: This is a retrospective chart review with a prospective follow up of outcomes. It included patients diagnosed with meningioma between January 2005 and December 2015 at the American University of Beirut Medical Center. Patient's demographics, risk factors and outcomes were first retrospectively collected. Then, we conducted phone calls to all included alive patients to update their disease status and outcomes. RESULTS: One-hundred and ninety-five patients were included. 69 % had grade I tumors and around 31 % with grades II and III meningiomas. The means of the overall survival and progression free survival (PFS) were 198 and 126 months, respectively. The residence area (city vs. countryside), occupation, alcohol use, oral contraceptive use, family history of meningioma, previous head trauma, radiation exposure for head/brain imaging, cell phone use, and finally, the tumor Ki-67 protein level did not correlate with the survival outcomes. The meningioma grade and extent of resection were significant predictors of the PFS on the univariate analysis, whereas, in the multivariate analysis only previous radiotherapy was significant in prolonging PFS. CONCLUSION: In our study cohort, that included around 30 % grades II and III tumors, previous radiotherapy use was the only significant prognostic factor for longer PFS in patients diagnosed with meningioma. Future prospective studies should be conducted to evaluate genetic and molecular factors that could possibly be linked to meningioma grade and prognosis in our population of Middle Eastern patients.
Assuntos
Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Adulto , Idoso , Feminino , Humanos , Líbano , Masculino , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/terapia , Meningioma/patologia , Meningioma/terapia , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
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.
Assuntos
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
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.
Assuntos
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
Giant cell arteritis is an inflammatory lesion of the large- and medium-sized arteries, usually involving the temporal arteries of older women. Rarely, the breast has been reported as the primary site of involvement. Patients usually present with breast masses that are tender or painful in most reported cases. The disease may be associated with constitutional symptoms that resemble polymyalgia rheumatica, but most reported cases do not have an established diagnosis of autoimmune disease. Clinically, giant cell arteritis of the breast may mimic breast carcinoma. Establishing the diagnosis is important because most patients achieve remission of symptoms after treatment with prednisone.
Assuntos
Doenças Mamárias/diagnóstico , Doenças Mamárias/patologia , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/patologia , Neoplasias da Mama/diagnóstico , Diagnóstico Diferencial , Feminino , HumanosRESUMO
Leptomeningeal dissemination of low-grade Schwann cell neoplasms is an exceptionally rare occurrence and has not been well documented in the literature. We encountered 2 cases of leptomeningeal dissemination of low-grade Schwann cell neoplasms. Patient 1 was a 63-year-old woman with neurofibromatosis type 1 and a progressive low-grade malignant peripheral nerve sheath tumor developing from a diffuse/plexiform orbital neurofibroma that arose in childhood. The neoplasm demonstrated local and leptomeningeal dissemination intracranially leading to the patient's death. There was partial loss of H3K27 tri-methylation, p16 and collagen IV. Patient 2 was a 60-year-old man without neurofibromatosis type 1 who presented with cranial nerve symptoms and a disseminated neoplasm with a Schwann cell phenotype. The neoplasm stabilized after irradiation and chemotherapy, but the patient died of medical complications. Autopsy findings documented disseminated leptomeningeal disease in the intracranial and spinal compartment. H3K27M tri-methylation was preserved. The clinicopathologic and autopsy findings are studied and presented, and the literature is reviewed.
Assuntos
Neoplasias Meníngeas/secundário , Neurilemoma/secundário , Neurofibromatose 1/patologia , Células de Schwann/patologia , Idoso , Autopsia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Colágeno Tipo IV/análise , Inibidor p16 de Quinase Dependente de Ciclina/análise , Metilação de DNA , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/química , Neoplasias Meníngeas/genética , Pessoa de Meia-Idade , Gradação de Tumores , Neurilemoma/química , Neurilemoma/genética , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Fenótipo , Células de Schwann/química , Resultado do TratamentoAssuntos
Degeneração Lobar Frontotemporal/complicações , Degeneração Lobar Frontotemporal/patologia , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Feminino , Degeneração Lobar Frontotemporal/genética , Humanos , Proteína FUS de Ligação a RNA/metabolismoRESUMO
Urachal carcinoma is rare comprising less than 1% of all bladder carcinomas. Metastases of urachal carcinoma have been reported to meninges, brain, ovary, lung, and maxilla. Cytologic features of metastatic urachal carcinoma have not been previously reported. We present a case of metastatic urachal adenocarcinoma in bronchial brushings and review the use of immunohistochemistry in its diagnosis. A 47-year-old female was seen initially in 2007 with adenocarcinoma of the bladder dome for which she underwent partial cystectomy. She presented in 2011 with a left lung mass and mediastinal adenopathy. Bronchoscopy showed an endobronchial lesion from which brushings were obtained. These showed numerous groups of columnar cells with medium sized nuclei and abundant cytoplasm. The cells were positive for CK20 and CDX2 and negative for CK7. The cytomorphological findings were similar to those in the previous resection specimen and concurrent biopsy. This is the first case report of bronchial brushings containing metastatic urachal carcinoma. No specific immunohistochemical profile is available for its diagnosis. The consideration of a second primary was a distinct possibility in this case due to the lapse of time from primary resection, absence of local disease, and lack of regional metastases.
RESUMO
Gliosarcoma, a recognized subtype of glioblastoma, is a biphasic tumor exhibiting distinct glial and sarcomatous components. Ependymosarcomas are rarer, biphasic ependymal tumors exhibiting sarcomatous change. Genetic abnormalities associated with this curious phenotype are not well understood. We are presenting the first karyotype of ependymosarcoma with identification of a clonal t(1;19)(q12;p13). Fluorescence in situ hybridization (FISH) was performed with a probe set targeting 1q23 and 19p13.3. Although the tumor did not show evidence of t(1;19)(q23;p13.3) by FISH, increased ploidy was a feature of the sarcomatous component. On clinical followup the patient is doing well without evidence of recurrence 55 months after initial resection, and postoperative treatment with irradiation and temozolomide. The significance of the genetic alterations we describe associated with sarcomatoid change in ependymal neoplasms, and ultimately their prognostic relevance, merits further study.