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Brunner gland lesions (BGLs) encompass benign proliferations of the homonymous glands and have been designated as hyperplasia, adenoma (BGA), hamartoma or nodule. In general terms, lesions larger than 0.5 cm are considered true neoplasia with unknown malignant potential and unclear pathogenesis. Genetic alterations have seldom been reported in BGL, and include SMAD4/DPC4 and LRIG1, but not KRAS (Kirsten rat sarcoma viral oncogene homologue) to the best of our knowledge.We present the case of a man in his 60s, evaluated for iron deficiency anaemia harbouring a 1.5 cm BGA found by duodenoscopy. Immunohistochemistry failed to reveal microsatellite instability, and next-generation sequencing revealed a KRAS G12D point mutation.
Assuntos
Adenoma , Glândulas Duodenais , Neoplasias Duodenais , Humanos , Glândulas Duodenais/patologia , Neoplasias Duodenais/genética , Neoplasias Duodenais/patologia , Duodenoscopia , Mutação , Adenoma/diagnóstico por imagem , Adenoma/genética , Adenoma/patologia , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
Although acute lymphoblastic leukemia (ALL) and monoclonal B cell lymphocytosis (MBL) are common neoplasia, a simultaneous presentation is very unusual. Here, we present two different B cell clones, MBL and B-ALL, cocirculating in a 78-year-old African American male. Detailed molecular characterization revealed an unusual MPL (T487I) point mutation and unmutated VH4-39. After nonstandard chemotherapy, the patient remains in morphologic remission. These findings may stimulate further research to clarify the pathogenesis of hematologic neoplasms.
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The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of the highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from the H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing Abs and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with the H5N1 virus of a different clade. In addition to having potential as a universal influenza vaccine, in the event of an impending pandemic the Wyeth/IL-15/5Flu is also readily amenable to bulk production to cover the global population. For those individuals for whom the use of the Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago.
Assuntos
Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/imunologia , Interleucina-15/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Vaccinia virus/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Linhagem Celular , Surtos de Doenças/prevenção & controle , Desinfetantes , Cães , Feminino , Vetores Genéticos/imunologia , Interleucina-15/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vaccinia virus/genéticaRESUMO
Esophageal cancer has a strikingly low survival rate mainly due to the lack of diagnostic markers for early detection and effective therapies. In the U.S., 75% of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) are of African descent. African American ESCC (AA ESCC) is particularly aggressive, and its biological underpinnings remain poorly understood. We sought to identify the genomic abnormalities by conducting whole exome sequencing of 10 pairs of matched AA esophageal squamous cell tumor and control tissues. Genomic analysis revealed diverse somatic mutations, copy number alterations (SCNAs), and potential cancer driver genes. Exome variants created two subgroups carrying either a high or low tumor mutation burden. Somatic mutational analysis based on the Catalog of Somatic Mutations in Cancer (COSMIC) detected SBS16 as the prominent signature in the high mutation rate group suggesting increased DNA damage. SBS26 was also detected, suggesting possible defects in mismatch repair and microsatellite instability. We found SCNAs in multiple chromosome segments, encoding MYC on 8q24.21, PIK3CA and SOX2 on 3q26, CCND1, SHANK2, CTTN on 11q13.3, and KRAS on 12p12. Amplifications of EGFRvIII and EGFRvIVa mutants were observed in two patients, representing a novel finding in ESCC that has potential clinical relevance. This present exome sequencing, which to our knowledge, represents the first comprehensive exome analysis exclusively in AA ESCC, and highlights novel mutated loci that might explain the aggressive nature of AA ESCC and lead to the development of diagnostic and prognostic markers as well as therapeutic targets.
Assuntos
Negro ou Afro-Americano/genética , Análise Mutacional de DNA/métodos , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Sequenciamento do Exoma/métodos , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Feminino , Predisposição Genética para Doença , Humanos , MasculinoRESUMO
BACKGROUND: The rise in human papillomavirus (HPV) infection rates over the last few decades in the USA has contributed to a significant increase in the overall incidence of patients diagnosed with squamous cell carcinoma of the head and neck. These head and neck carcinomas develop in the oropharynx, with more than 90% of them caused by infection with high-risk HPV type 16. Patients diagnosed with HPV-induced oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis and treatment response than those diagnosed with head and neck cancers caused by alcohol consumption and tobacco use. To identify patients with HPV-positive OPSCC, new guidelines recommend positive staining of oropharyngeal tissues for p16 INK4a (p16) by immunohistochemistry (IHC). Herein we discuss the testing algorithm that was adopted to address discrepant results between p16 IHC and a DNA in situ hybridization (ISH) test used routinely to diagnose HPV-positive OPSCC patients. METHODS: A DNA polymerase chain reaction (PCR) test that amplifies HPV16 and HPV18 E7 was developed to aid in the diagnosis of HPV-positive OPSCC in a subset of patients. Specimens from these patients stained positive for p16 by an IHC test, but negative for high-risk HPV by a commercial DNA ISH test. Moreover, these results did not match the histopathological characteristics of the specimens, nor the clinical presentations of the patients. RESULTS: Of 21 patients' specimens that were tested for p16 by IHC, 11 specimens showed concordant results with the high-risk HPV 16/18 DNA ISH test. Whereas, in eight p16 IHC positive specimens, HPV viral DNA was not detected by HPV16/18 DNA ISH, and two specimens were not tested by DNA ISH. When these eight p16 IHC positive specimens with discrepant p16 IHC and DNA ISH results were further tested by DNA PCR, six specimens showed concordance with p16 IHC with positive results for HPV16 E7, while two specimens were negative for HPV16 E7 by DNA PCR. All tested specimens were negative for HPV18 E7 by DNA PCR. Thus, the addition of the HPV16 and HPV18 E7 DNA PCR test identified a significant number of false negative test results by the HPV16/18 DNA ISH test and likely several false positive results by p16 IHC. CONCLUSIONS: Inclusion of an HPV16 E7 DNA PCR test improved the robustness of HPV-associated OPSCC diagnosis in patients with discrepant results from p16 IHC staining and a DNA ISH test, and identified patients for proper management with less misclassification.
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The genetically-inbred Balb/c mouse strain shows heightened sensitivity to the ability of MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, to raise the threshold voltage necessary to precipitate tonic hindlimb extension and elicit irregular episodes of intense jumping behavior (referred to as "popping"), relative to other inbred mouse strains and the outbred NIH Swiss mouse. Moreover, an allosteric modulatory effect of sarcosine, a glycine reuptake inhibitor, on MK-801's antagonism of electrically precipitated seizures was detected 24 h after Balb/c mice were forced to swim in cold water for up to 10 min; this was not observed in unstressed Balb/c mice or stressed or unstressed NIH Swiss mice. Phencyclidine (PCP), a noncompetitive NMDA receptor antagonist that binds to the same hydrophobic channel domain as MK-801, precipitates a schizophreniform psychosis in susceptible individuals that shares descriptive similarities with schizophrenia. This observation has led to the hypothesis that NMDA receptor hypofunction (NRH) is involved in the pathophysiology of schizophrenia and the testing of pharmacotherapeutic strategies to facilitate NMDA receptor-mediated neurotransmission in patients with this disorder (e.g., glycine reuptake inhibitors). The heightened behavioral sensitivity of the Balb/c mouse to MK-801 suggests that this mouse strain may be a useful model to study "psychosis-proneness" and screen for positive allosteric modulators of NMDA receptor-mediated neurotransmission. Conceivably, strain differences in the pharmacology of the NMDA receptor are due to differences in the relative expression of individual NMDA receptor subunits to each other (i.e., combinatorial regulation). The current study compared the normal protein expression patterns of six of the eight identified splice variant isoforms of the NR1 NMDA receptor subunit, and NR2A and NR2B subunits in the hippocampus and cerebral cortex of Balb/c and NIH Swiss mice. The heightened behavioral sensitivity of the Balb/c genetically-inbred mouse strain to MK-801, compared to the outbred NIH Swiss mouse strain, does not appear to result from relative alterations of expression of these NMDA receptor protein subunits that were examined.
Assuntos
Comportamento Animal/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/genética , Animais , Western Blotting , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Densitometria , Eletroforese em Gel Bidimensional , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fenciclidina/farmacologia , Receptores de N-Metil-D-Aspartato/biossíntese , Especificidade da EspécieRESUMO
Synovial sarcoma, one of the most common types of soft tissue sarcomas, usually presents in the proximal or middle portions of the extremities, often as a large mass with an aggressive clinical behavior. Gland-forming biphasic and spindle cell fibrous monophasic tumors are the most common subtypes. In this study, we evaluated 21 minute synovial sarcomas, <1 cm in diameter, from the hands and feet. These tumors occurred in 14 females and 7 males with a median age of 29 years (range, 8-60 years). Clinically, all tumors were thought to be benign processes such as a ganglion cyst or glomus tumor, and on microscopic examination, they were also often initially misinterpreted as benign lesions such as nerve sheath or (myo) fibroblastic tumors. Histologically, 7 tumors were biphasic and 14 were monophasic spindle cell variants. Microscopic calcifications were present in 8 cases and were prominent in 3 tumors. All monophasic tumors tested had elements positive for EMA, and all but one had reactivity for a keratin cocktail. S-100 protein-positive neuroma-like neural proliferations were commonly present in the monophasic but not in biphasic tumors. SYT-SSX fusion transcripts were demonstrated in 5 cases studied by polymerase chain reaction assay. All tumors were enucleated, followed by local reexcision of the site, and often combined with postoperative radiation. Three patients had amputation of the involved digit or metatarsal. Four patients had local recurrences, 2 of which were successfully treated; 2 of these patients were lost to follow-up. Despite some variation in treatment, all 12 patients with complete follow-up were alive and well, 2 to 32.2 years after surgery (median, 14.7 years), including 2 patients who received neither amputation nor postoperative radiation. Minute synovial sarcomas of hands and feet are clinically favorable tumors if completely excised; there is some evidence to suggest that they may be managed more conservatively than larger tumors. These tumors should be recognized as part of the spectrum of synovial sarcomas.
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Pé/patologia , Mãos/patologia , Sarcoma Sinovial/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Criança , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Proteínas de Fusão Oncogênica , Reação em Cadeia da Polimerase , Prognóstico , Sarcoma Sinovial/genética , Sarcoma Sinovial/metabolismo , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismoRESUMO
Synovial sarcomas comprise approximately 5% of soft tissue sarcomas and occur primarily in young adults. The t(X;18) (p11.2;q11.2) has been demonstrated to be highly characteristic of synovial sarcomas, and the resulting SYT-SSX fusion transcripts have been shown to be useful diagnostic markers. We have developed a real-time, reverse transcriptase-polymerase chain reaction (RT-PCR) multiplex assay for the identification of the primary fusion transcript types (SYT-SSX1 and SYT-SSX2) from formalin-fixed, paraffin-embedded (FFPE) tissues. Twenty-nine of 30 (96.7%) histologically diagnosed FFPE synovial sarcomas were positive for the presence of either the SYT-SSX1 or SYT-SSX2 fusion transcripts. Ten of 16 (62.5%) and five of 16 (31.25%) monophasic fibrous synovial sarcomas were positive for SYT-SSX1 and SYT-SSX2, respectively. One of 16 (6.25%) monophasic fibrous synovial sarcomas was negative for either SYT-SSX fusion transcript. Twelve of 14 (85.7%) and 2 of 14 (14.3%) biphasic synovial sarcomas were positive for SYT-SSX1 and SYT-SSX2, respectively. All 13 non-synovial sarcomas tested were negative for SYT-SSX1 and SYT-SSX2 fusion transcripts. This method is a relatively simple and rapid procedure for the detection of the t(X;18)(p11.2;q11.2).
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Biomarcadores Tumorais/genética , DNA de Neoplasias/análise , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Sarcoma Sinovial/genética , Neoplasias de Tecidos Moles/genética , Cromossomos Humanos Par 18 , Primers do DNA/química , Diagnóstico Diferencial , Humanos , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma Sinovial/patologia , Neoplasias de Tecidos Moles/patologia , Translocação Genética , Células Tumorais Cultivadas , Cromossomo XRESUMO
Recent molecular genetic testing methods for hereditary hemochromatosis (HH) and single nucleotide polymorphisms are summarized. Comparisons of various sample preparation and detection instrumentation are made in terms of automation, cost, high-throughput and feasibility of implementation in a clinical laboratory. Examples are given for the analysis of the two mutations associated with hereditary hemochromatosis (HH) by high-performance liquid chromatography, capillary electrophoresis and mass spectrometry based on single nucleotide extension. The trends for developing better genetic testing are discussed.
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Hemocromatose/diagnóstico , Hemocromatose/genética , Técnicas de Diagnóstico Molecular , Testes Genéticos/métodos , Humanos , Técnicas de Diagnóstico Molecular/instrumentação , Mutação , Análise de Sequência de DNA/métodosRESUMO
Interleukin-15 (IL-15) is a pleiotropic cytokine with a broad range of biological functions in many diverse cell types. It plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems. This review provides an overview of the mechanisms by which IL-15 modulates the host response to infectious agents and its utility as a cytokine adjuvant in vaccines against infectious pathogens.
Assuntos
Imunidade , Inflamação/imunologia , Interleucina-15/imunologia , Interleucina-15/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Animais , Células Dendríticas/imunologia , Interações Hospedeiro-Patógeno , Humanos , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Mastócitos/imunologia , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Neutrófilos/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia , Viroses/imunologia , Viroses/virologia , Vírus/imunologia , Vírus/patogenicidadeRESUMO
CONTEXT: Activation-induced cytidine deaminase, necessary for immunoglobulin somatic hypermutation and class switch recombination, is usually expressed within the follicular dendritic network but is also expressed in a population of interfollicular large B cells outside the germinal center. OBJECTIVE: To report 7 cases of diffuse large B-cell lymphoma with a distinct paracortical distribution. Expression of activation-induced cytidine deaminase, previously described in interfollicular large B cells, was evaluated. DESIGN: A panel of immunohistochemical markers, including double staining for activation-induced cytidine deaminase and CD20, was used to illustrate the cases. Molecular studies were performed by polymerase chain reaction in the paraffin-embedded tissue for t(14;18) chromosomal translocation and immunoglobulin heavy chain and T-cell receptor rearrangements. RESULTS: Patients included 3 males and 4 females ranging in age from 11 to 59 years (mean, 39 years). All specimens were lymph nodes (4 from the groin, 2 from the neck, and 1 from the axilla). Malignant lymphocytes were positive for CD20 and negative for CD5 and CD10. Staining for CD30, CD43, and BCL-2 was variable. The malignant cells showed at least focal staining with activation-induced cytidine deaminase. All cases were found to be monoclonal by immunoglobulin heavy-chain gene rearrangement or showed light-chain restriction. None of the tested cases showed t(14;18). CONCLUSIONS: Diffuse large B-cell lymphoma with a paracortical distribution is unusual and may be a distinct morphologic variant. More study is necessary to determine the stage of B-cell development and the cell of origin of these tumors. However, activation-induced cytidine deaminase expression suggests they may arise from a putative interfollicular large B cell.
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Citidina Desaminase/biossíntese , Regulação Enzimológica da Expressão Gênica , Linfoma Folicular/enzimologia , Linfoma Difuso de Grandes Células B/enzimologia , Adolescente , Adulto , Antígenos CD20/metabolismo , Biomarcadores Tumorais/metabolismo , Criança , Células Clonais , Citidina Desaminase/genética , Ativação Enzimática , Feminino , Humanos , Linfonodos/patologia , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Ciclina D1/genética , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Ciclina D1/análise , Ciclina D1/metabolismo , Humanos , Linfoma de Célula do Manto/metabolismo , Valor Preditivo dos Testes , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , RNA Neoplásico/genética , Microglobulina beta-2/análise , Microglobulina beta-2/genética , Microglobulina beta-2/metabolismoRESUMO
Classic Kaposi sarcoma is rare and occurs predominantly in Mediterranean and Middle Eastern men. Since the emergence of acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma, the incidence, clinicopathologic features, and molecular human herpesvirus 8 (HHV-8) association of American Classic Kaposi Sarcoma has not been fully explored. This study compares Classic Kaposi Sarcoma to AIDS-related Kaposi Sarcoma over the same two decade time period. There were 438 histologically and clinically confirmed Classic Kaposi Sarcoma patients. The ethnic/racial distribution included Caucasian/American (56%), Mediterranean (22%), South American Hispanic (18%), Black (10%), western European (4%), Middle East (4%), Scandinavian (2%), and other (2%). Classic Kaposi Sarcoma was more common in men, 7:1, with a mean age of 74 years. The lesions presented in the lower extremity (69%), in the nodular stage (83%), and HHV-8 was detected by PCR in 40/41 randomly selected cases. A second, non-Classic Kaposi Sarcoma, malignancy was present in 42% (n=45) of the 108 Classic Kaposi Sarcoma patients with complete clinical information, 73% (33 patients) with a higher incidence over the general population. Follow-up of <1-19 years (mean=4.8 years) revealed that 24% of patients died of second malignancy, 22% died of other medical conditions, 2% died of treatment-related complications, and 2% patients died of widespread disease. Thirty-five percent are alive with no evidence of disease and 15% with persistent disease. Human immunodeficiency virus-related Kaposi Sarcoma was observed in 354 cases. There was a male predominance and more aggressive behavior, with higher rates of visceral and disseminated disease. While Classic Kaposi Sarcoma in the United States is an indolent disease and rarely accounts for patient demise, predominantly affecting Caucasian/American males on the lower extremity in the nodular phase, it more importantly may denote an underlying other malignancy. Current PCR probes detect HHV-8 in 98% of Classic Kaposi Sarcoma cases. In comparison, AIDS-related Kaposi Sarcoma is predominately multicentric, visceral, and disseminated, with more aggressive behavior.
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Infecções por HIV/complicações , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Southern Blotting , Feminino , Herpesvirus Humano 8 , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/epidemiologia , Reação em Cadeia da Polimerase , Distribuição por Sexo , Estados UnidosRESUMO
Primary pulmonary and mediastinal synovial sarcoma is rare and poses a diagnostic challenge particularly when unusual histological features are present. We present 60 cases of primary pulmonary and mediastinal synovial sarcoma (29 male and 27 female subjects; mean age, 42 years) and compare our results with five prior series to better define unusual histological features. Clinically, patients with mediastinal synovial sarcoma were younger with a male gender bias. Radiologically, tumors were well delineated with distinctive magnetic resonance imaging features and little vascular enhancement. In all, 21/46 patients died of disease within 5 years. Histologically, all tumors had dense cellularity, interlacing fascicles, hyalinized stroma, and mast cell influx. Hemangiopericytoma-like vasculature (48/60), focal myxoid change (30/60), and entrapped pneumocytes (23/60) were seen. Calcification was not prevalent (10/60). Unusual histological features included Verocay body-like formations (7/60), vague rosettes (6/60), well-formed papillary structures (3/60), adenomatoid change (3/60), and rhabdoid morphology (2/60). Immunohistochemistry demonstrated expression of pancytokeratin (39/58), epithelial membrane antigen (29/53), cytokeratin 7 (26/40), cytokeratin 5/6 (5/7), calretinin (15/23), CD99 (19/23), bcl-2 (24/24), CD56 (11/11), S-100 (9/51), and smooth muscle actin (8/32). In total, 92% (36/39) of primary pulmonary and mediastinal synovial sarcomas studied were positive for t(x;18). In conclusion, our study confirms the clinical, histological, immunohistochemical, and molecular data from previous large series of primary pulmonary and mediastinal synovial sarcoma. Compared with soft tissue synovial sarcoma, primary pulmonary and mediastinal synovial sarcoma has less calcification, less obvious mast cell influx, and less radiologic vascularity, but similar magnetic resonance imaging features, percentage of poorly differentiated tumors, and number of t(x;18)-positive tumors. Awareness of focal unusual histology can prevent misdiagnosis particularly in t(x;18)-negative tumors.
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Neoplasias Pulmonares/patologia , Neoplasias do Mediastino/patologia , Sarcoma Sinovial/patologia , Antígeno 12E7 , Adulto , Antígenos CD/análise , Antígeno CD56/análise , Calbindina 2 , Moléculas de Adesão Celular/análise , Cromossomos Humanos Par 18/genética , Cromossomos Humanos X/genética , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína G de Ligação ao Cálcio S100/análise , Proteínas S100/análise , Sarcoma Sinovial/genética , Sarcoma Sinovial/metabolismo , Taxa de Sobrevida , Translocação GenéticaAssuntos
Linfoma de Efusão Primária/diagnóstico , Linfoma de Efusão Primária/tratamento farmacológico , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/tratamento farmacológico , Idoso , Doxiciclina/administração & dosagem , Herpesvirus Humano 8 , Humanos , Linfoma de Efusão Primária/virologia , Masculino , Paracentese , Derrame Pleural Maligno/virologia , PleurodeseRESUMO
CONTEXT: Reed-Sternberg cells in classic Hodgkin lymphoma are enigmatic and difficult to study because they are so sparse. Tissue microdissection allows for the isolation of single Reed-Sternberg cells. Isolated Reed-Sternberg cells show clonal immunoglobulin gene rearrangement indicating a B-cell origin. Rarely, Reed-Sternberg cells in classic Hodgkin lymphoma express T-cell antigens, suggesting a possible T-cell origin. OBJECTIVE: To determine whether there is a difference in genotype between classic Hodgkin lymphoma and classic Hodgkin lymphoma expressing T-cell antigens and to document T-cell clonality. DESIGN: We studied 4 cases of Hodgkin lymphoma with a characteristic phenotype and immunoreactivity for CD2 and CD3. Single CD30+ Reed-Sternberg cells from each case were isolated by laser capture microdissection for immunoglobulin heavy chain and T-cell receptor-gamma genes by polymerase chain reaction studies. Comparative genomic hybridization was performed in all cases. RESULTS: Two of 4 cases showed clonal rearrangement of the T-cell receptor-gamma; none showed immunoglobulin heavy chain rearrangement. Two control cases were negative for T cell receptor-gamma but 1 showed immunoglobulin heavy chain rearrangement. Comparative genomic hybridization analysis revealed significant overlap in genomic alteration in Hodgkin lymphoma cases regardless of genotype or phenotype and several regions of imbalance specific to CD3+ Hodgkin lymphoma cases. All patients are alive with no evidence of disease from 10 to 44 months. CONCLUSIONS: Our findings suggest that a T-cell phenotype classic Hodgkin lymphoma can be supported by genotypic studies and that there may be cytogenetic differences between classic Hodgkin lymphoma and Hodgkin lymphoma expressing T-cell antigens.
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Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Doença de Hodgkin/genética , Doença de Hodgkin/imunologia , Hibridização de Ácido Nucleico/métodos , Células de Reed-Sternberg/imunologia , Adolescente , Adulto , Células Clonais , Feminino , Genótipo , Doença de Hodgkin/patologia , Humanos , Imuno-Histoquímica , Lasers , Linfonodos/patologia , Microdissecção , Células de Reed-Sternberg/patologiaRESUMO
Ewing sarcoma family tumors originating in the palate or adrenal gland are extremely rare and may cause difficulty in diagnosis. More common tumors primary to these sites need to be excluded before one arrives at the correct diagnosis. We have recently diagnosed 2 such cases. The 1st case was that of a 24-year-old woman who presented with a swelling in the right side of the hard palate. The 2nd case was diagnosed in a 28-year-old woman who presented with a mass in the right adrenal gland. In both cases, the diagnosis of Ewing sarcoma family of tumors was confirmed by immunohistochemical studies and reverse transcriptase-polymerase chain reaction (RT-PCR). The hard palate case is the 1st and the adrenal gland the 3rd case of Ewing sarcoma family of tumors arising in these sites, in which the diagnosis was confirmed by RT-PCR and/or cytogenetics. Accurate diagnosis of Ewing sarcoma family of tumors is crucial for the management of patients, and when found in such rare locations, diagnosis should be supported by immunohistochemical and/or molecular genetic studies.