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2.
Sci Rep ; 12(1): 18519, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323745

RESUMO

Diagnostic markers of malignant mesothelioma (MM) have been extensively investigated. Immunohistochemistry (IHC) markers, such as calretinin, have been used for pathologic diagnosis. However, more diagnostic markers are required to improve the specificity and sensitivity of pathologic diagnosis. This study proposed two proteins as diagnostic markers for epithelioid MM. One is RhoA, an MM mutation-susceptible locus-derived protein, and another is vigilin, a lung small cell carcinoma marker. IHC was performed using 93 MM (epithelioid, 71 cases; sarcomatoid, 13 cases; and biphasic, 9 cases), 64 lung adenocarcinoma (LAC), 60 lung squamous cell carcinoma (LSC), and 14 normal mesothelial (NM) tissues. The majority of epithelioid MM cases were positive for both RhoA and vigilin, whereas both IHCs showed lower stainability in biphasic and sarcomatoid MM. Besides, both IHCs showed significantly higher stainability for RhoA and vigilin in epithelioid MM than in LAC and LSC (p < 0.05). Chi-square tests showed that both RhoA and vigilin IHC positive rate in epithelioid MM was not significantly different from that of calretinin (p > 0.05). In the differential diagnosis of MM from lung cancer, the accuracy and specificity of RhoA, vigilin, and calretinin staining were almost equivalent. Further, H-score test showed that there was no significant difference between RhoA versus calretinin and vigilin versus calretinin in IHC positivity in epithelioid MM (p > 0.05). In conclusion, RhoA and vigilin may be candidates for immunohistochemical markers for epithelioid MM.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Humanos , Calbindina 2/metabolismo , Mesotelioma/patologia , Biomarcadores Tumorais/metabolismo , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Diagnóstico Diferencial , Carcinoma de Células Escamosas/diagnóstico , Proteína rhoA de Ligação ao GTP/metabolismo
3.
J Cancer Res Ther ; 18(6): 1683-1691, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412430

RESUMO

Background: Malignant peritoneal mesotheliomas (MPMs) are rare tumors with overlapping clinical and histopathological features, especially with epithelial ovarian carcinomas (EOCs). There is no substantial documentation on these rare tumors from our country. Objective: To study the clinicopathological features including immunohistochemical (IHC) profile and clinical outcomes of 14 MPMs, diagnosed at our institution. Materials and Methods: This was a retrospective study, wherein 14 cases of MPM, occurring in female patients, diagnosed at our institution, between January 2008 and May 2019 were included, after a critical review. Results: Median age was 54.5 years. Most patients presented with ascites, omental nodularity, and fat stranding. Microscopically, most cases (11, 78.6%) displayed epithelioid morphology, followed by biphasic pattern (2, 14.3%) and a single case of well-differentiated MPM. IHC, diagnostic sensitivity and specificity of calretinin were 100% (13/13) and 85.7%; of HBME1 were 100% (5/5) and 100%; and of podoplanin (D2-40) were 60% (2/5) and 100%. Other positively expressed immunomarkers were epithelial membrane antigen (n = 2/5, 40%), cytokeratin 5/6 (n = 4/4, 100%), and WT1 (n = 9/10, 90%). Most patients (5/12, 41.7%) were treated with chemotherapy. The 3-year disease-free and overall survival rates were 25.7% and 54%, respectively, including improved survival trend in patients with epithelioid type of MPMs. Conclusion: MPMs are diagnosed with a combination of clinicopathological features and optimal IHC markers. Their differentiation from EOCs and other metastatic carcinomas is imperative in view of significant treatment implications.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imuno-Histoquímica , Biomarcadores Tumorais , Mesotelioma/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia
4.
Int J Mol Sci ; 23(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36293328

RESUMO

Malignant mesothelioma is an aggressive tumour of the pleura (MPM) or peritoneum with a clinical presentation at an advanced stage of the disease. Current therapies only marginally improve survival and there is an urgent need to identify new treatments. Carcinoma-associated fibroblasts (CAFs) represent the main component of a vast stroma within MPM and play an important role in the tumour microenvironment. The influence of CAFs on cancer progression, aggressiveness and metastasis is well understood; however, the role of CAF-derived extracellular vesicles (CAF-EVs) in the promotion of tumour development and invasiveness is underexplored. We purified CAF-EVs from MPM-associated cells and healthy dermal human fibroblasts and examined their effect on cell proliferation and motility. The data show that exposure of healthy mesothelial cells to EVs derived from CAFs, but not from normal dermal human fibroblasts (NDHF) resulted in activating pro-oncogenic signalling pathways and increased proliferation and motility. Consistent with its role in suppressing Yes-Associated Protein (YAP) activation (which in MPM is a result of Hippo pathway inactivation), treatment with Simvastatin ameliorated the pro-oncogenic effects instigated by CAF-EVs by mechanisms involving both a reduction in EV number and changes in EV cargo. Collectively, these data determine the significance of CAF-derived EVs in mesothelioma development and progression and suggest new targets in cancer therapy.


Assuntos
Fibroblastos Associados a Câncer , Vesículas Extracelulares , Mesotelioma Maligno , Mesotelioma , Humanos , Fibroblastos Associados a Câncer/metabolismo , Proteínas de Sinalização YAP , Linhagem Celular Tumoral , Mesotelioma/patologia , Vesículas Extracelulares/metabolismo , Carcinogênese/metabolismo , Sinvastatina , Microambiente Tumoral
5.
Int J Mol Sci ; 23(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36232554

RESUMO

Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.


Assuntos
Proteína HMGB1 , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Ciclina D1 , Ciclo-Oxigenase 2 , Hormônio Liberador de Hormônio do Crescimento , Humanos , Fator de Crescimento Insulin-Like I/uso terapêutico , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz/genética , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , NF-kappa B/metabolismo , Pemetrexede/farmacologia , Pemetrexede/uso terapêutico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Int J Mol Sci ; 23(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36233258

RESUMO

Malignant pleural mesothelioma (MPM) is a rare but aggressive thoracic malignancy with limited treatment options. One of the standard treatments for MPM is chemotherapy, which consists of concurrent treatment with pemetrexed and cisplatin. Pemetrexed limits tumor growth by inhibiting critical metabolic enzymes involved in nucleotide synthesis. Cisplatin causes direct DNA damage, such as intra-strand and inter-strand cross-links, which are repaired by the nucleotide excision repair pathway, which depends on relatively high nucleotide levels. We hypothesized that prolonged pretreatment with pemetrexed might deplete nucleotide pools, thereby sensitizing cancer cells to subsequent cisplatin treatment. The MPM cell lines ACC-MESO-1 and NCI-H28 were treated for 72 h with pemetrexed. Three treatment schedules were evaluated by initiating 24 h of cisplatin treatment at 0 h (concomitant), 24 h, and 48 h relative to pemetrexed treatment, resulting in either concomitant administration or pemetrexed pretreatment for 24 h or 48 h, respectively. Multicolor flow cytometry was performed to detect γH2AX (phosphorylation of histone H2AX), a surrogate marker for the activation of the DNA damage response pathway. DAPI staining of DNA was used to analyze cell cycle distribution. Forward and side scatter intensity was used to distinguish subpopulations based on cellular size and granularity, respectively. Our study revealed that prolonged pemetrexed pretreatment for 48 h prior to cisplatin significantly reduced long-term cell growth. Specifically, pretreatment for 48 h with pemetrexed induced a cell cycle arrest, mainly in the G2/M phase, accumulation of persistent DNA damage, and induction of a senescence phenotype. The present study demonstrates that optimizing the treatment schedule by pretreatment with pemetrexed increases the efficacy of the pemetrexed-cisplatin combination therapy in MPM. We show that the observed benefits are associated with the persistence of treatment-induced DNA damage. Our study suggests that an adjustment of the treatment schedule could improve the efficacy of the standard chemotherapy regimen for MPM and might improve patient outcomes.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Histonas , Humanos , Neoplasias Pulmonares/patologia , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Nucleotídeos , Pemetrexede/farmacologia , Pemetrexede/uso terapêutico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia
7.
Tissue Cell ; 79: 101920, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36182716

RESUMO

OBJECTIVES: Malignant mesothelioma (MM) is a primary malignant tumour with a very bad prognosis, which develops from the mesothelial cells lining the serosal surfaces. Because MM can show a wide variety of histological patterns and its cytomorphological features are quite extensive, it is often confused with lung adenocarcinomas (LAC) and reactive mesothelial hyperplasia (RMH). The immunohistochemical examination method is the most useful method for discrimination. In this study, we aimed to determine the value of suprabasin and DARS2 markers in the differential diagnosis of RMH, MM and LAC. METHODS: Thirty MM, 30 LAC and 30 RMH samples selected from the archive of Firat University Hospital Pathology Department Laboratory were included in this study. Suprabasin and DARS2 markers were applied to the samples immunohistochemically and their place in the differential diagnosis was examined. RESULTS: Although DARS2 expression was observed in RMH, MM and adenocarcinoma samples, Suprabasin expression was only observed in adenocarcinoma. There was a significant difference between the groups in terms of DARS2 and Suprabasin expression. No suprabasin expression was detected in MM and RMH. CONCLUSION: Suprabasin and DARS2 may be proposed as new biomarkers to differentiate MM from LAC.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Aspartato-tRNA Ligase , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Humanos , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores , Diagnóstico Diferencial , Hiperplasia/diagnóstico , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Mesotelioma/patologia
8.
Urologie ; 61(11): 1186-1196, 2022 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-36173458

RESUMO

Physicians are obliged to report the suspected presence of an occupational disease to the German Social Accident Insurance Institutions or to the state authority responsible for occupational health and safety. In the field of urology, tumors of the urinary tract are the most common, followed by the less common renal cell cancer and mesothelioma of the tunica vaginalis testis; however, for such a suspicion to arise at all, sufficient knowledge of urological occupational diseases must be present and the occupational or work history over the entire training and working life since the beginning of employment must be collected. In daily life the notification often fails at this point. In addition to the legal foundation and the principal course of the procedure, this article explains how a relevant comprehensive medical history by means of questionnaires can contribute to the fact that neither too many or all tumor diseases are unreflectedly reported, nor that occupational diseases are overlooked due to the lack of a medical history or detailed knowledge (or fear of this). Urological sequelae of accidents are often not adequately appreciated in the primary process or may take a long time to develop. In this case reporting the aggravation of the consequences of the accident is essential.


Assuntos
Neoplasias Renais , Mesotelioma Maligno , Mesotelioma , Doenças Profissionais , Masculino , Humanos , Acidentes de Trabalho , Doenças Profissionais/diagnóstico , Mesotelioma/patologia
9.
Lung Cancer ; 173: 49-52, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36122471

RESUMO

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a malignant disease of the pleura which recently can be treated with immune checkpoint inhibitors (ICI). To optimize this treatment, a better understanding of the tumor micro environment is needed. We investigated subgroups of immune cells in subsequent tumor biopsies of patients treated with ICI. METHODS: Biopsies from MPM patients included in two clinical ICI trials (nivolumab alone and an ipilimumab/nivolumab combination) were examined. At baseline and after 6 weeks of treatment, pleural biopsies were taken to examine the tumor microenvironment (CD20+, CD4+, CD8+, FoxP3+ and PD-1+ ). Cell density was defined as the number of marker positive cells per mm2. Radiological responses were evaluated as partial response, stable disease or progressive disease according to modified RECIST criteria. RESULTS: Thirty-four and 36 patients were included in the nivolumab and ipiliumumab/nivolumab trial respectively. In the nivolumab trial, no significant differences in cell densities were seen in baseline biopsies of patients with partial response versus progressive disease. In contrast, in the ipilimumab/nivolumab trial, a higher cell density of CD4+, CD8+, FoxP3+ and PD-1+ cells at baseline was significantly correlated with partial responses. On-treatment biopsies of both trials did not show significant changes when compared to baseline biopsies. CONCLUSION: Biopsies from patients responding to nivolumab plus ipilimumab treatment show a significant higher cell density of CD4+, CD8+, FoxP3+ and PD-1+ cells, without a change after 6 weeks of treatment. This observation is a first step in exploring the tumor microenvironment as predictor of response in ICI treatment in MPM.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores de Transcrição Forkhead , Inibidores de Checkpoint Imunológico , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/patologia , Nivolumabe/uso terapêutico , Neoplasias Pleurais/patologia , Receptor de Morte Celular Programada 1 , Microambiente Tumoral , Ensaios Clínicos como Assunto
10.
Arkh Patol ; 84(5): 28-34, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36178219

RESUMO

The article contains an overview of the new WHO classification of thoracic tumors (2021). As in the previous edition of 2015, considerable attention is paid to neoplasms of the lungs and pleura. The article presents current data on molecular genetic features and morphological manifestations of a number of new lung tumors, with a detailed histological and immunohistochemical data. Thoracis undifferentiated tumor with SMARCA4 deficiency and bronchiolar adenoma are described. Emphasis is placed on the algorithms of morphological diagnostics, including a complete description of the tumor and facilitating the study in the practice of a pathologist. The main morphological criteria of mesothelial tumors of the pleura are given; describes in detail the procedure for assessing the degree of malignancy of diffuse epithelioid pleural mesothelioma and non-mucinous lung adenocarcinomas.


Assuntos
Neoplasias Pulmonares , Mesotelioma , Neoplasias Pleurais , DNA Helicases , Diagnóstico Diferencial , Humanos , Pulmão/patologia , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/classificação , Mesotelioma/diagnóstico , Mesotelioma/patologia , Proteínas Nucleares , Pleura/patologia , Neoplasias Pleurais/classificação , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia , Fatores de Transcrição , Organização Mundial da Saúde
11.
Diagn Cytopathol ; 50(11): 532-537, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36069384

RESUMO

Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy with a poor prognosis. Because of this tumor rarity and overlapping histologic features with other malignancy types, the histopathological findings and diagnostic immunohistochemical workup are essential in establishing the final diagnosis of MPMs. We aimed to review the diagnostic criteria, WHO tumor classification updates, and immunohistochemical staining markers diagnostic value to achieve an appropriate clinical diagnosis.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Biomarcadores Tumorais , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia , Coloração e Rotulagem , Organização Mundial da Saúde
12.
Rev Esp Patol ; 55 Suppl 1: S27-S31, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075659

RESUMO

Malignant pleural mesothelioma is a neoplasm involving mesothelial cells of the pleura. Both local and distant metastases may develop, although the latter are less common and it is extremely rare for cutaneous metastases to appear as a solitary lesion on the scalp. We present the case of a 54-year-old woman with a 2-year history of unresectable left pleural mesothelioma treated with chemotherapy, who had developed a painful lump on the scalp one month prior to consultation. Skin metastases of mesothelioma must be differentiated from primary neoplasms, and immunohistochemistry is fundamental to determine the origin of such lesions, which can be correctly identified through the use of a panel of markers.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Neoplasias Cutâneas , Diagnóstico Diferencial , Feminino , Humanos , Mesotelioma/diagnóstico , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Couro Cabeludo/patologia , Neoplasias Cutâneas/tratamento farmacológico
13.
Rev Esp Patol ; 55 Suppl 1: S32-S38, 2022 09.
Artigo em Espanhol | MEDLINE | ID: mdl-36075660

RESUMO

Deciduoid mesothelioma is an uncommon histological variant of epithelial mesothelioma which is extremely clinically aggressive. We report 3 cases of pleural caducoid mesothelioma in women of 75, 74 and 23 years of age. All patients presented with dyspnoea, vomiting and pelvic pain. Their imaging studies showed nodular pleuropericardic thickening, a parietal pleuropericardic solid mass and a large thoracic mass, respectively. Only one of them could be treated with chemotherapy, surgery and radiotherapy. Post diagnostic survival was 24 days, 1 month and 17 months respectively (mean 6.2 months). We describe the clinicopathological and immunohistochemical findings together with a review of the relevant literature.


Assuntos
Mesotelioma , Neoplasias Pleurais , Diagnóstico por Imagem , Feminino , Humanos , Mesotelioma/diagnóstico , Mesotelioma/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia
14.
World J Surg Oncol ; 20(1): 317, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171577

RESUMO

BACKGROUND: Desmoid-type fibromatosis (DTF) is a rare benign lesion that usually arises from the abdominal wall or extremities and rarely from the mesentery or intrabdominal organs. Malignant peritoneal mesothelioma is also a rare, yet aggressive disease. To our knowledge, this is the first case report of desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma. CASE PRESENTATION: An early 30-year-old female was referred to our center for large intra-abdominal mass concerning for recurrent malignant peritoneal mesothelioma after previous cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Further investigation revealed a large mesenteric mass, which was resected en bloc with the cecum and terminal ileum. Pathologic findings confirmed a surprising diagnosis of desmoid-type fibromatosis. CONCLUSIONS: No adjuvant therapy was offered to this patient due to negative tumor margins; however, close follow-up will be provided for recurrence of both malignant peritoneal mesothelioma and desmoid-type fibromatosis, which can be differentiated in the future via biopsy in this patient.


Assuntos
Fibromatose Agressiva , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Adulto , Feminino , Fibromatose Agressiva/patologia , Humanos , Mesotelioma/patologia , Mesotelioma/cirurgia , Recidiva Local de Neoplasia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/cirurgia , Doenças Raras
15.
Thorac Cancer ; 13(19): 2792-2798, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36052736

RESUMO

Surgery is part of a multimodal therapeutic approach to malignant pleural mesothelioma (MPM) although its real beneficial effect is still controversial. The optimal precise sequence of treatments within the trimodality is unclear, and should be decided upon a multidisciplinary consensus for each individual patient. Here, we analyzed the perioperative data of 19 MPM patients who underwent extended pleurectomy/decortication (EPD) with curative intent. The mean age at diagnosis was 67 years; 11 males and eight females. Ten patients were diagnosed with MPM via medical thoracoscopy (MT), and nine via video-assisted thoracoscopic surgery (VATS). The vast majority of cases harbored epitheliod forms. We compared neoadjuvant chemotherapy (NCT) followed by surgery (11 cases) versus surgery followed by adjuvant chemotherapy (ACT, 8 cases) within a 3-year period. All patients had extended pleurectomy/decortication and none had an extended pneumonectomy. Analysis of survival curves suggested that the short-term outcomes are better with upfront EDP followed by ACT if compared to EDP preceded by NCT. Although limited, the data highlighted the safety and feasibility of EPD, with manageable postoperative complications and no major burden for the patients.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Idoso , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Mesotelioma Maligno/cirurgia , Neoplasias Pleurais/patologia , Pneumonectomia , Cirurgia Torácica Vídeoassistida , Resultado do Tratamento
16.
J Thorac Oncol ; 17(12): 1428-1432, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36075530

RESUMO

INTRODUCTION: Primary pericardial mesothelioma (PPM) has no accepted standard-of-care treatment options with management and outcomes often extrapolated from diffuse pleural mesothelioma. Disease-specific research is needed to better define PPM. We report our institutional experience with PPM highlighting the potential role for multimodality therapy. METHODS: Patients with PPM diagnosed by a multidisciplinary team of medical oncologists, thoracic surgeons, thoracic pathologists, and radiologists between January 2011 and January 2022 were followed to February 2022. Clinicopathologic features and treatment outcomes were annotated. Overall survival (OS) was defined from the date of pathologic diagnosis. RESULTS: The median age at diagnosis of the 12 patients identified with having PPM was 51 (range: 21-71) years old. Most patients were of female sex (n = 8; 67%), 75% of the samples were epithelioid (n = 9), and 25% were nonepithelioid (two sarcomatoid and one biphasic). Most cases (92%, 11 of 12) had expression of at least two mesothelial markers on immunohistochemistry. The median OS of the cohort was 25.9 months. Five patients had an OS greater than 12 months; four of whom received pericardial radiation. Three of the patients who received radiation did so as part of a trimodality approach (surgical resection, adjuvant chemotherapy, and radiation); the OS for patients who received trimodality therapy was 70.3 months versus 8.2 months for those who did not. CONCLUSIONS: PPM represents a distinct disease with no universally accepted treatment options. Our findings suggest that trimodality therapy may improve outcomes in selected patients with PPM.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Neoplasias do Timo , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/patologia , Neoplasias Pleurais/patologia , Mesotelioma/patologia , Terapia Combinada
17.
Semin Nucl Med ; 52(6): 806-815, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35965111

RESUMO

Malignant mesothelioma is an aggressive tumor originating from the mesothelial cells and presenting in general with a very poor prognosis. The pleural localization represents the prevailing disease site, while peritoneal involvement is commonly rare. The WHO classifies mesotheliomas into epithelioid, biphasic, and sarcomatoid histotypes, having diverse outcome with the sarcomatoid or biphasic forms showing the poorest prognosis. Given the peculiar rind-like pattern of growth, mesothelioma assessment is rather challenging for medical imagers. Conventional imaging is principally based on contrast-enhanced CT, while the role of functional and metabolic imaging is regarded as complementary. By focusing essentially on the staging and restaging role of [18F]FDG PET/CT in malignant mesotheliomas, the present review will summarize the available data present in literature and provide some hints on alternative imaging and future perspectives. Given the prevailing incidence of pleural disease, the majority of the information will be addressed on malignant pleural mesothelioma, although a summary of principal characteristics and imaging findings in patients with peritoneal mesothelioma will be also provided.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma Maligno/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Mesotelioma/diagnóstico por imagem , Mesotelioma/metabolismo , Mesotelioma/patologia
18.
Br J Cancer ; 127(9): 1691-1700, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35999269

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is a lung pleural cancer with very poor disease outcome. With limited curative MPM treatment available, it is vital to study prognostic biomarkers to categorise different patient risk groups. METHODS: We defined gene signatures to separately characterise intrinsic and extrinsic features, and investigated their interactions in MPM tumour samples. Specifically, we calculated gene signature scores to capture the downstream pathways of major mutated driver genes (BAP1, NF2, SETD2 and TP53) as tumour-intrinsic features. Similarly, we inferred the infiltration levels for major immune cells in the tumour microenvironment to characterise tumour-extrinsic features. Lastly, we integrated these features with clinical factors to predict prognosis in MPM. RESULTS: The gene signature scores were more prognostic than the corresponding genomic mutations, mRNA and protein expression. High immune infiltration levels were associated with prolonged survival. The integrative model indicated that tumour features provided independent prognostic values than clinical factors and were complementary with each other in survival prediction. CONCLUSIONS: By using an integrative model that combines intrinsic and extrinsic features, we can more correctly predict the clinical outcomes of patients with MPM.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma/patologia , Prognóstico , Neoplasias Pulmonares/patologia , RNA Mensageiro , Biomarcadores , Biomarcadores Tumorais/genética , Microambiente Tumoral
20.
J Am Soc Cytopathol ; 11(6): 385-393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35945149

RESUMO

INTRODUCTION: Serous effusion is often the first sign of mesothelioma. Diagnosis based on cytologic material from the effusions remains controversial and complementary biopsy is usually required. However, obtaining representative tissue sample may be challenging, while obtaining cytologic material is a minimally invasive procedure, providing potential for an earlier diagnosis. Loss of BRCA1-associated protein (BAP1), combined with loss of methylthionadenosine phosphorylase (MTAP) detected by immunohistochemistry, have shown to be reliable markers in the diagnosis of mesothelioma on histologic sections. Here we evaluate the value of these biomarkers in cytologic specimens. MATERIALS AND METHODS: The BAP1 and MTAP expression in specimens of 162 mesothelioma patients (156 pleural, 6 peritoneal)-71 cytologic, 91 histologic (44 epithelioid, 31 biphasic, 16 sarcomatoid)-and 20 patients with reactive mesothelial proliferations were investigated. RESULTS: The loss of BAP1 and/or MTAP was highly sensitive and specific in differentiating mesothelioma from reactive mesothelial proliferations, with no significant difference between pleural effusions and biopsies, specificity of 100% in both and a sensitivity of 78.9% and 80.2%, respectively (P = 0.3). There was a 100% concordance of the expression of BAP1 and MTAP in cytologic and corresponding histopathologic samples. Loss of BAP1 and/or MTAP in histologic sections discriminated sarcomatoid, biphasic, and epithelioid mesothelioma from reactive mesothelial proliferations with a sensitivity of 81.2%, 83.9%, and 77.3% respectively. CONCLUSION: Loss of expression of BAP1 and/or MTAP differentiated mesothelioma from reactive mesothelial proliferations with excellent specificity and high sensitivity in cytologic samples, comparable to histopathologic sections.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Sarcoma , Humanos , Ubiquitina Tiolesterase/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/metabolismo , Mesotelioma/diagnóstico , Mesotelioma/patologia , Biópsia , Fosforilases
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