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(1) Background: The prompt diagnosis of anterior mediastinal lesions is a challenge due to their often being categorized as malignant tumours. Ultrasound-guided Transthoracic Core Needle Biopsy (US-TCNB) is an innovative technique that is arousing increasing interest in clinical practice. However, studies in this area are still scarce. This study aims to compare the diagnostic accuracy and complication rate of US-TCNB with those of traditional surgical methods-Anterior Mediastinotomy and Video Assisted Thoracoscopic Surgery (VATS)-in patients with anterior mediastinal lesions. (2) Methods: This retrospective study involved patients evaluated between January 2011 and December 2021 who had undergone US-TCNB at the Interdepartmental Unit of Internal and Interventional Ultrasound, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy. Personal data, diagnostic questions, and technical information concerning the bioptic procedure, periprocedural complications and histological reports were collected. (3) Results: Eighty-three patients were included in the analysis. Histological examination was performed in 78 cases, with an overall diagnostic accuracy of 94.0% (sensitivity 94%; specificity 100%). Only in 5 patients was a diagnosis not achieved. Complications occurred in 2 patients who were quickly identified and properly treated without need of hospitalization. The accuracy of US-TCNB was comparable to the performance of the main traditional diagnostic alternatives (95.3% for anterior mediastinotomy, and 98.4% for VATS), with a much lower complication rate (2.4% vs. 3-16%). The outpatient setting offered the additional advantage of saving resources. (4) Conclusions: a US-guided needle biopsy can be considered effective and safe, and in the near future it may become the procedure of choice for diagnosing anterior mediastinal lesions in selected patients.
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The differential diagnosis between lymphoplasmacytic lymphoma (LPL) and marginal zone B-cell lymphoma, particularly splenic type (SMZL), can be challenging on onset of bone marrow biopsy (BMB) since morphology and phenotype are not specific and clinical features can overlap or be mildly developed at diagnosis. The LPL-specific L265P mutation in the MYD88 gene is not available in all laboratories, and genetic aberrancies identified in SMZL (del7q, mutations of NOTCH2 and KLF2) are seldom searched in routine practice. The study aim is to investigate the potential role of myeloid nuclear differentiation antigen (MNDA) expression in this specific differential diagnosis. We report MNDA reactivity in 559 patients with small B-cell lymphoma including bone marrow biopsies from 90 LPL and 91 SMZL cases. MYD88 p.Leu265Pro mutation status was assessed and confirmed as positive in 24 of 90 LPL cases, which served as the test set. MNDA staining was negative in 23 of 24 LPL cases in the test set (96%). In the 157 remaining cases (66 LPL, 91 SMZL), which served as the validation set, the MYD88 p.Leu265Pro mutation was unavailable and MNDA was more frequently expressed in SMZL (p < 0.00001). In addition, immunohistochemical features more consistent with SMZL (i.e., presence of CD23+ follicular dendritic cell meshworks, polytypic plasma cells, DBA44 reactivity) were more often present in MNDA-positive cases (statistically significant for 2 such parameters). On the widest case series so far published focusing on LPL and SMZL immunohistochemical diagnosis at onset of BMB, we demonstrated that MNDA expression significantly support the diagnosis of SMZL. This observation may be of particular help in cases where the MYD88 p.Leu265Pro mutational status and/or SMZL-related genetic aberrations are unavailable.
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Leucemia Linfocítica Crônica de Células B , Linfoma de Zona Marginal Tipo Células B , Neoplasias Esplênicas , Macroglobulinemia de Waldenstrom , Antígenos de Diferenciação , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Biomarcadores , Biópsia , Medula Óssea/patologia , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/patologia , Mutação , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Neoplasias Esplênicas/diagnóstico , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/patologiaRESUMO
Peripheral T-cell lymphoma not otherwise specified represents a diagnostic category comprising clinically, histologically, and molecularly heterogeneous neoplasms that are poorly understood. The genetic landscape of peripheral T-cell lymphoma not otherwise specified remains largely undefined, only a few sequencing studies having been conducted so far. In order to improve our understanding of the genetics of this neoplasm, we performed whole exome sequencing along with RNA-sequencing in a discovery set of 21 cases. According to whole exome sequencing results and mutations previously reported in other peripheral T-cell lymphomas, 137 genes were sequenced by a targeted deep approach in 71 tumor samples. In addition to epigenetic modifiers implicated in all subtypes of T-cell neoplasm (TET2, DNMT3A, KMT2D, KMT2C, SETD2), recurrent mutations of the FAT1 tumor suppressor gene were for the first time recorded in 39% of cases. Mutations of the tumor suppressor genes LATS1, STK3, ATM, TP53, and TP63 were also observed, although at a lower frequency. Patients with FAT1 mutations showed inferior overall survival compared to those with wild-type FAT1. Although peripheral T-cell lymphoma not otherwise specified remains a broad category also on molecular grounds, the present study highlights that FAT1 mutations occur in a significant proportion of cases, being provided with both pathogenetic and prognostic impact.
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Biomarcadores Tumorais/genética , Caderinas/genética , Sequenciamento do Exoma , Genes Supressores de Tumor , Sequenciamento de Nucleotídeos em Larga Escala , Linfoma de Células T Periférico/genética , Mutação , Análise de Sequência de RNA , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença , Humanos , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Adulto JovemRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of MCL patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in MCL, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective FIL-MCL0208 phase 3 trial (high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of KMT2D and disruption of TP53 by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding KMT2D mutations and TP53 disruption to the MIPI-c backbone, we derived a new prognostic index, the "MIPI-genetic" ("MIPI- g"). The "MIPI-g" improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-year progression free survival and overall survival of 72.0% and 94.5%); ii) inter-mediate-risk patients (4-year progression free survival and overall survival of 42.2% and 65.8%) and iii) high-risk patients (4-year progression free survival and overall survival of 11.5% and 44.9%). Our results: i) confirm that TP53 disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring KMT2D mutations share the same poor outcome as patients harboring TP53 disruption; and iii) allow to develop a tool for the identification of high-risk MCL patients for whom novel therapeutic strategies need to be investigated. (Trial registered at clinicaltrials.gov identifier: NCT02354313).
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Proteínas de Ligação a DNA/genética , Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto , Proteínas de Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Mutação , Prognóstico , Estudos Prospectivos , Transplante AutólogoAssuntos
Biópsia Guiada por Imagem , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Mediastino/patologia , Ultrassonografia , Adulto , Idoso , Carcinoma/diagnóstico , Carcinoma/patologia , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/patologia , Humanos , Masculino , Mesotelioma/diagnóstico , Mesotelioma/patologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Estudos Retrospectivos , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/patologiaRESUMO
OBJECTIVES: Flow cytometry (FC) has become a useful support for cytomorphologic evaluation (CM) of fine-needle aspirates (FNA) and serous cavity effusions (SCE) in cases of suspected non-Hodgkin lymphoma (NHL). FC results may be hampered by the scarce viability and low cellularity of the specimens. STUDY DESIGN: We developed a single-tube FC assay (STA) that included 10 antibodies cocktailed in 8-color labeling, a cell viability dye, and a logical gating strategy to detect NHL in hypocellular samples. The results were correlated with CM and confirmed by histologic or molecular data when available. RESULTS: Using the STA, we detected B-type NHL in 31 out of 103 hypocellular samples (81 FNA and 22 SCE). Of these, 8 were not confirmed by CM and 2 were considered to be only suspicious. The FC-negative samples had a final diagnosis of benign/reactive process (42/72), carcinoma (27/72), or Hodgkin lymphoma (3/72). CONCLUSIONS: The STA approach allowed obtainment of maximum immunophenotyping data in specimens containing a low number of cells and a large amount of debris. The information obtained by STA can help cytomorphologists not only to recognize but also to exclude malignant lymphomas.
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Carcinoma/diagnóstico , Carcinoma/patologia , Citometria de Fluxo/métodos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/métodos , Humanos , Imunofenotipagem/métodos , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is potentially curative in a variety of hematological malignancies. Graft-vs.-host disease (GvHD) remains a life-threatening complication. Standard treatment is high-dose (HD) corticosteroids. Steroid-refractory (SR) GvHD is associated with poor prognosis. At present, second-line treatment is ill-defined and includes a number of agents. Novel insights into the pathophysiology of acute GvHD (aGvHD) highlight the relevant role of the host inflammatory response governed by several kinase families, including Janus kinases (JAK)1/2. Ruxolitinib, a JAK1/2 inhibitor approved for intermediate-2/high-risk myelofibrosis, was recently employed in SR-GvHD with encouraging overall response rates. Clinical experience however remains limited. CASE PRESENTATION: A 51-year-old male with refractory anemia with excess blast type-2 underwent a myeloablative allogeneic HSCT from a 9/10 HLA-matched unrelated donor after conditioning with busulfan and cyclophosphamide. GvHD prophylaxis consisted of cyclosporine, methotrexate, and thymoglobulin. CD34(+) cells/kg infused were 8.69 × 10(6) kg. On day 29, the patient developed overall grade IV aGvHD with biopsy proven stage IV gastrointestinal (GI) GvHD refractory to HD corticosteroids. Patient conditions rapidly deteriorated and became critical despite the addition of mycophenolate mofetil and budesonide. On day 33, Ruxolitinib was started, and on day 39 the patient clinical conditions gradually improved. Complete resolution of aGvHD was also confirmed by histology on day 54. CONCLUSIONS: At 5 months from HSCT, the patient is well and in continuous hematological complete remission without flare of GvHD. Ruxolitinib was discontinued on day 156. Ruxolitinib is feasible and effective in SR-aGvHD though large prospective clinical trials are warranted.
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Resistência a Medicamentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Pirazóis/uso terapêutico , Terapia de Salvação/métodos , Corticosteroides/farmacologia , Anemia Refratária com Excesso de Blastos/complicações , Anemia Refratária com Excesso de Blastos/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Pirimidinas , Indução de RemissãoRESUMO
Anaplastic large-cell lymphoma (ALCL) is a clinical and biological heterogeneous disease that includes systemic anaplastic lymphoma kinase (ALK)-positive and ALK-negative entities. To discover biomarkers and/or genes involved in ALK-negative ALCL pathogenesis, we applied the cancer outlier profile analysis algorithm to a gene expression profiling data set including 249 cases of T-cell non-Hodgkin lymphoma and normal T cells. Ectopic coexpression of ERBB4 and COL29A1 genes was detected in 24% of ALK-negative ALCL patients. RNA sequencing and 5' RNA ligase-mediated rapid amplification of complementary DNA ends identified 2 novel ERBB4-truncated transcripts displaying intronic transcription start sites. By luciferase assays, we defined that the expression of ERBB4-aberrant transcripts is promoted by endogenous intronic long terminal repeats. ERBB4 expression was confirmed at the protein level by western blot analysis and immunohistochemistry. Lastly, we demonstrated that ERBB4-truncated forms show oncogenic potentials and that ERBB4 pharmacologic inhibition partially controls ALCL cell growth and disease progression in an ERBB4-positive patient-derived tumorgraft model. In conclusion, we identified a new subclass of ALK-negative ALCL characterized by aberrant expression of ERBB4-truncated transcripts carrying intronic 5' untranslated regions.
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Linfoma Anaplásico de Células Grandes/genética , Receptores Proteína Tirosina Quinases/genética , Receptor ErbB-4/genética , Regiões 5' não Traduzidas , Quinase do Linfoma Anaplásico , Animais , Códon sem Sentido , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Linfoma Anaplásico de Células Grandes/classificação , Linfoma Anaplásico de Células Grandes/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Camundongos Transgênicos , Dados de Sequência Molecular , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Células NIH 3T3 , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptor ErbB-4/metabolismoRESUMO
A systematic characterization of the genetic alterations driving ALCLs has not been performed. By integrating massive sequencing strategies, we provide a comprehensive characterization of driver genetic alterations (somatic point mutations, copy number alterations, and gene fusions) in ALK(-) ALCLs. We identified activating mutations of JAK1 and/or STAT3 genes in â¼20% of 88 [corrected] ALK(-) ALCLs and demonstrated that 38% of systemic ALK(-) ALCLs displayed double lesions. Recurrent chimeras combining a transcription factor (NFkB2 or NCOR2) with a tyrosine kinase (ROS1 or TYK2) were also discovered in WT JAK1/STAT3 ALK(-) ALCL. All these aberrations lead to the constitutive activation of the JAK/STAT3 pathway, which was proved oncogenic. Consistently, JAK/STAT3 pathway inhibition impaired cell growth in vitro and in vivo.
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Regulação Neoplásica da Expressão Gênica , Linfoma Anaplásico de Células Grandes/genética , Fator de Transcrição STAT3/metabolismo , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Animais , Linhagem Celular Tumoral , Células HEK293 , Humanos , Janus Quinase 1/genética , Camundongos , Proteínas Mutantes Quiméricas/genética , Proteínas Mutantes Quiméricas/metabolismo , NF-kappa B/genética , Fosforilação , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais , TYK2 Quinase/genéticaRESUMO
OBJECTIVES: The World Health Organization (WHO) thymoma histological classification clinical value remains a controversy. In this study, we evaluated its prognostic significance in patients with thymoma treated with radical intent. METHODS: Six high-volume Italian Thoracic Surgery Institutions collaborated with their own retrospective anonymized datasets. Demographic, clinical, pathological and treatment data were examined. A WHO histological classification (WHO-HC) collapsed scheme (A/AB and B1/B2 types merged) was proposed and compared with the traditional one. Predictors of survival were assessed using a Cox model with shared frailty. Competing-risk regression models were performed to identify the association between individual factors and freedom from recurrence. RESULTS: Between 1990 and 2011, 750 thymomas were operated on in participating centres. Myasthenia gravis was observed in 363 (48%) patients. A complete resection was achieved in 676 (91%) cases. One hundred and nine patients (15%) had a WHO-HC A type, 166 (22%) AB, 179 (24%) B1, 158 (21%) B2 and 135 (18%) B3. The rate of 5-year OS and cumulative incidence of recurrence for all cases was 91% and 0.11, respectively. Five-year survival rates by WHO-HC in the collapsed scheme were A/AB 93%, early-B 90% and advanced-B 85%. Masaoka stage only was demonstrated to be an independent predictor for survival and recurrence. The WHO-collapsed scheme showed a trend in influencing recurrence overall survival development (hazard ratio: 1.32; P = 0.16). CONCLUSIONS: Our results show evidence of lack of significance by WHO-HC in influencing prognosis, even though the proposed collapsed scheme revealed a fair stratification of risk to relapses and better correlation with patients' clinical characteristics.
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Timectomia , Timoma/classificação , Timo/patologia , Neoplasias do Timo/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/patologia , Miastenia Gravis/cirurgia , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Timectomia/mortalidade , Timoma/diagnóstico , Timoma/mortalidade , Timoma/patologia , Timoma/cirurgia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia , Resultado do Tratamento , Organização Mundial da SaúdeRESUMO
BACKGROUND: To evaluate the efficacy of the use of flow cytometry (FC) immunophenotyping together with fine-needle aspiration cytology (FNAC) in the diagnosis of thyroid lymphoma. METHODS: FC was performed in parallel with FNAC in 35 samples of suspected thyroid lymphoma over a 12 years period. Results were correlated with histological or molecular findings and follow-up, when available. RESULTS: A final diagnosis of lymphoma was given in 13 of 35 (37.1%) specimens. Among the 22 cases considered negative for lymphoma by FC, 11 were diagnosed as thyroiditis by cytology, 7 as reactive, 2 were anaplastic carcinoma, and 2 cases were considered cytologically suspicious for lymphoma but were not confirmed by further investigations. Histology on core biopsy or molecular analysis was available in 12 of 13 lymphoma cases (92.3%). Data obtained by the combination cytology/FC were confirmed in all cases on histology biopsies. Correlation with histology showed a sensitivity and a specificity of 100% for the combination cytology/FC. CONCLUSIONS: FC is an important additional test that can contribute with cytology to the identification of lymphomas of the thyroid. FC can detect the presence of small neoplastic lymphocyte populations and may contribute to the diagnosis of cases in which the lymphoid infiltrate is difficult to interpret on cytology alone.
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Biomarcadores Tumorais/análise , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Linfócitos/química , Linfoma de Células B/química , Neoplasias da Glândula Tireoide/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biópsia por Agulha Fina , Comportamento Cooperativo , Diagnóstico Diferencial , Feminino , Humanos , Comunicação Interdisciplinar , Linfócitos/imunologia , Linfócitos/patologia , Linfoma de Células B/genética , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapiaRESUMO
OBJECTIVE: Thymic carcinoma (TC) is a rare and invasive mediastinal tumor, with poor prognosis. Most of the previous published papers are single-institution based, reporting small series of patient, sometimes including palliative resection. This study collected patients with TC treated in 5 high-volume Italian Thoracic Surgery Institutions. METHODS: A multicenter retrospective study of patients operated for TC between 2000 and 2011 was conducted. Exclusion criteria were: Neuroendocrine thymic neoplasms, debulking/palliative resection and tumor biopsy. Cause specific survival (CSS) was the primary endpoint. RESULTS: Four hundred and seventy-eight patients underwent surgery for thymic malignancies: 40 of them (8.4%) had TC. Eleven (27.5%) received induction chemotherapy because of their radiological invasiveness. A complete resection (R0) was achieved in 36 (90%; 9/11 submitted to induction chemotherapy). Adjuvant radio/chemotherapy was offered to 37 patients, according to the type of surgical resection and tumor invasiveness. Three, 5 and 10-year survival rates were 79%, 75% and 58%. Recurrences developed in 10 patients. R0 resection (p<0.0003) and absence of tumor recurrences (p=0.03) resulted significant prognostic factors at univariate analysis. Independent CSS predictor was the achievement of a complete resection (p<0.05). CONCLUSIONS: TC is a rare and invasive mediastinal tumor. A multimodal approach is indicated especially in TC invasive forms. The achievement of a complete surgical resection is fundamental to improve survival.
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Carcinoma/diagnóstico , Carcinoma/cirurgia , Hospitais Especializados , Esternotomia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Terapia Combinada , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Cirurgia Torácica , Neoplasias do Timo/mortalidade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Thymic epithelial tumors include several entities with different biologic behavior. Chemotherapy is indicated in advanced disease, but limited data exist on gene expression correlation with the response to chemotherapeutic agents. PATIENTS AND METHODS: A series of 69 thymic neoplasms (7 A-, 6 AB-, 6 B1-, 10 B2-, 14 B3-thymomas, 22 carcinomas and 4 combined tumors) was collected to assess gene expression of thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), ribonucleotide reductase subunit 1 (RRM1), topoisomerase 2α (TOP2A) and mTOR. RESULTS: A strong linear correlation between TS gene and protein expression was observed (P<0.0001, R=0.40). TS expression was significantly lower in pure A-thymomas and thymic carcinomas (P<0.0001) and progressively decreasing from B1-type to thymic carcinomas (B1>B2>B3>C; P<0.0001). RRM1 and TOP2A mRNA expression levels were significantly correlated with TS levels (both P=0.03) with a similar trend of expression among histotypes. RRM1 and TOP2A high levels were significantly correlated with high TS (P=0.03) and low tumor stages (I-II) (P<0.0001 and P<0.01, respectively). No relevant changes of ERCC1 and mTOR were detected. CONCLUSIONS: Low TS and, to a minor extent, RRM1 and TOP2A expression were detected in aggressive thymic tumors. These findings should be prospectively considered in selecting the most appropriate chemotherapy.
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Reparo do DNA/genética , Timidilato Sintase/metabolismo , Timoma/patologia , Neoplasias do Timo/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Transformação Celular Neoplásica , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases/genética , Endonucleases/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose , RNA Mensageiro/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Timidilato Sintase/genética , Timoma/tratamento farmacológico , Timoma/enzimologia , Timoma/genética , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/enzimologia , Neoplasias do Timo/genética , Adulto Jovem , Fator ral de Troca do Nucleotídeo Guanina/genética , Fator ral de Troca do Nucleotídeo Guanina/metabolismoRESUMO
A retrospective analysis of 1,792 solid tissues suggestive of lymphoma, submitted over a 12-year period, was carried out and flow cytometry (FC) results were compared with histologic findings. The final histologic diagnosis of cases documented in this report is as follows: 1,270 non-Hodgkin's lymphomas (NHL); 17 composite lymphomas; four NHL plus carcinomas; five post-transplant lymphoproliferative disorders; 105 Hodgkin's lymphomas (HL); eight acute leukemias; 42 tissue cancers; and 341 non-neoplastic diseases. A strong correlation between morphology and FC data was observed among hematological malignancies (1,268/1,304, 97.2%) with the exception of HL. Among B-NHL, FC detection of clonally restricted B-cell allowed the identification of lymphomas that were not histologically clear and the differential diagnosis between follicular lymphoma and reactive hyperplasia. A high correlation level (r = 0.83; P < 0.0001) was obtained in comparing proliferation results obtained by FC and immunohistochemistry. Among T-NHL, FC detection of an aberrant phenotype direct histologic diagnosis in cases having less than 20% of neoplastic cells. In nine cases, FC suggested the need to evaluate a neoplastic population, not morphologically evident. Results show that FC routinely performed on tissue samples suspected of lymphomas is a fundamental adjunct to morphology in the diagnosis of NHL and may enhance the performance of the histologic evaluation so as to achieve the final diagnosis. To the best of our knowledge, this is the first report in the literature of a wide series of tissues also studied by FC.
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Citometria de Fluxo , Doença de Hodgkin/diagnóstico , Imunofenotipagem/métodos , Leucemia/diagnóstico , Linfoma não Hodgkin/classificação , Linfoma não Hodgkin/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Hiperplasia , Lactente , Células Matadoras Naturais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T , Adulto JovemRESUMO
AIM: To report unusual CD56 (neural cell adhesion molecule, NCAM) expression on diffuse large B cell lymphoma (DLBCL). METHODS AND RESULTS: CD56 expression was first detected and quantified on tissues obtained from five cases of DLBCL by flow cytometry (FC), then confirmed by immunohistochemistry. The CD56 expression pattern was heterogeneous among the cases [the molecular equivalent of soluble fluorochrome (MESF) level ranged from 2214 to 133 466]. All were CD10 and Bcl-6 positive, suggesting their germinal centre origin; one was also CD5 positive. An extranodal presentation occurred in three of five cases. CONCLUSIONS: CD56 expression in B cell lymphoma is a rare occurrence. FC is able to identify aberrant immunophenotypes that can be useful in the identification and monitoring of B cell lymphoma subtypes. The presence of CD56 reported by the literature on certain DLBCL with extranodal presentation might be related to mechanisms involved in growth and expansion.
Assuntos
Antígeno CD56/metabolismo , Proteínas de Ligação a DNA/metabolismo , Citometria de Fluxo/métodos , Linfoma Difuso de Grandes Células B/diagnóstico , Neprilisina/metabolismo , Adolescente , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-6 , Adulto JovemRESUMO
PURPOSE: Primary testicular lymphoma (PTL) has poor prognosis with failures in contralateral testis, CNS, and extranodal sites. To prevent these events, we designed an international phase II trial (International Extranodal Lymphoma Study Group 10 [IELSG-10]) that addressed feasibility and activity of conventional chemoimmunotherapy associated with CNS prophylaxis and contralateral testis irradiation. The trial was conducted by the IELSG and the Italian Lymphoma Foundation. PATIENTS AND METHODS: Fifty-three patients (age 22 to 79 years) with untreated stage I or II PTL were treated with six to eight courses of rituximab added to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days (R-CHOP21); four doses of intrathecal methotrexate (IT-MTX) and radiotherapy (RT) to the contralateral testis (30 Gy) for all patients and to regional lymph nodes (30 to 36 Gy) for stage II disease. RESULTS: All patients received R-CHOP21, 50 received CNS prophylaxis, and 47 received testicular RT. With a median follow-up of 65 months, 5-year progression-free survival and overall survival rates were 74% (95% CI, 59% to 84%) and 85% (95% CI, 71% to 92%), respectively. Ten patients relapsed or progressed: two in lymph nodes, five in extranodal organs, and three in the CNS. The 5-year cumulative incidence of CNS relapse was 6% (95% CI, 0% to 12%). No contralateral testis relapses occurred. Ten patients died: lymphoma (n = 6), secondary leukemia (n = 2), heart failure (n = 1), and gastric cancer (n = 1). Grade 3 to 4 toxicities were neutropenia, 28%; infections, 4%; and neurologic, 13%. No deaths occurred as a result of toxicity. CONCLUSION: This international prospective trial shows that combined treatment with R-CHOP21, IT-MTX, and testicular RT was associated with a good outcome in patients with PTL. RT avoided contralateral testis relapses, but CNS prophylaxis deserves further investigation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/secundário , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Recidiva , Rituximab , Análise de Sobrevida , Neoplasias Testiculares/patologia , Neoplasias Testiculares/radioterapia , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
Composite lymphoma (CL) is a rare occurrence of 2 or more morphologically and immunophenotypically distinct lymphoma clones in a single anatomic site. A retrospective analysis of 1,722 solid tissue samples clinically suggestive of lymphoma was carried out in our institute during a 12-year period to evaluate the efficacy of flow cytometry (FC) in identifying CL. We report 17 CL cases. A strong correlation between morphologic findings and FC was observed in 13 cases (76%). In the 4 cases diagnosed as non-Hodgkin lymphoma plus Hodgkin lymphoma, although FC did not detect Reed-Sternberg cells, it accurately identified the neoplastic B- or T-cell component. In 3 cases, FC indicated the need to evaluate an additional neoplastic component that was not morphologically evident. Our data demonstrate that FC immunophenotyping of tissues may enhance the performance of the diagnostic morphologic evaluation of CL. To the best of our knowledge, this is the first report in the literature of a wide series of CL studied also by FC.
Assuntos
Linfoma Composto/diagnóstico , Citometria de Fluxo , Doença de Hodgkin/diagnóstico , Linfoma de Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Linfoma Composto/imunologia , Linfoma Composto/metabolismo , Feminino , Doença de Hodgkin/imunologia , Doença de Hodgkin/metabolismo , Humanos , Imunofenotipagem , Linfoma de Células B/imunologia , Linfoma de Células B/metabolismo , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Neuroendocrine tumors of the thymus (NETTs) are unusual thymic neoplasms that were misdiagnosed as thymomas until the 1970s, when they eventually acquired a distinct identity. No collective large series have been published so far, and information about clinical presentation, diagnosis, histology, and treatment is derived from analysis of the case series and case reports published over a long period. NETTs are more aggressive than their pulmonary and abdominal counterparts, presenting at a more advanced stage, often with distant metastases, and are associated with poor long-term survival. Most patients are symptomatic at presentation as a result of the local invasion. Twenty percent to 30% of the cases are associated with endocrine disorders, mostly Cushing syndrome and multiple endocrine neoplasia syndrome. There is no official staging system for these tumors and investigators rely on the Masaoka staging system used for thymomas. Histologically, 2 classification are used: the World Health Organization and the Armed Forces Institute of Pathology classifications. Histologically, most tumors show moderately to poorly differentiated histologic features, reflecting their aggressive clinical behavior. Surgery is the most effective treatment option, although the aggressiveness of the tumor often requires extensive resection. Chemotherapy and radiotherapy may be used either preoperatively or postoperatively, although the small number of patients does not allow the design of standard guidelines about optimal schedules and doses. Survival depends on stage at presentation, histologic degree of differentiation, associated endocrine syndromes, and resectability rate. Recurrences are frequent after surgery and may be locoregional or distant. Surgery is recommended when feasible in the treatment of locoregional recurrences.
Assuntos
Tumores Neuroendócrinos , Neoplasias do Timo , Terapia Combinada , Diagnóstico Diferencial , Humanos , Queratinas/metabolismo , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Prognóstico , Radiografia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia , Neoplasias do Timo/terapiaRESUMO
OBJECTIVE: In thymomas, World Health Organization (WHO) histology, Masaoka stage and myasthenia gravis (MG) have long been considered important for patient management and outcome. Their role has been independently investigated in the past. Few studies, however, focussed on the correlations among these variables. The aim of the present study was to retrospectively evaluate, in our patient population of resected thymomas, the inter-relationships among MG, WHO histology and Masaoka stage, and to look at how and to what extent one variable is associated with the other two in terms of clinical presentation and survival. METHODS: From January 1990 to October 2008, 255 patients received resection of thymoma. MG was present in 105 cases (41%). Histology by WHO was: 25 A (10%), 72 AB (28%), 65 B1 (25%), 69 B2 (27%) and 24 B (9%). Masaoka staging was stage I, 54 cases (21%), stage II, 86(34%), stage III 79 (31%), and stage IVA 36 (14%). Ordinal and logistic regression models were undertaken to analyse correlations among ordinal (WHO histology and Masaoka stage) and categorical (MG, A vs B WHO types) variables. Univariate and multivariate survival analysis were also performed using the same covariates. Overall survival (OS) and disease-free survival (DFS) were calculated. RESULTS: MG was associated with early Masaoka stages (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33-0.62) and B-type thymomas (OR 1.59, 95% CI 1.23-2.05). B-type thymomas were associated with high Masaoka stage (OR 0.46, 95% CI 0.36-0.60). High Masaoka stage was associated with non-MG (OR 3.27; 95% CI 2.00-5.34). In univariate survival analysis, MG (p = 0.01) and Masaoka stage (p = 0.0001) were significant prognostic indicators using OS. Using DFS, WHO histology (A/AB vs B1/B2/B3 types) (p = 0.05) and Masaoka stage (p = 0.0001) had a prognostic significance. In multivariate analysis, only Masaoka stage was an independent prognostic covariate using OS (hazard ratio (HR) 2.57, 95% CI 1.46-4.52, p = 0.001) and DFS (HR 3.18, 95% CI 1.56-6.52, p = 0.001). CONCLUSIONS: In thymomas, MG, WHO histology and Masaoka stage are inter-related. MG has an influence on histology and stage at presentation, while two clinical/histologic patterns are more likely: early Masaoka stage A/AB WHO type and high Masaoka stage/B WHO type. Among the three factors, only Masaoka stage had a prognostic significance on OS and DFS. Our results suggest that a consistent staging system for thymomas should take into account all three variables.