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1.
Cancer Res Commun ; 4(4): 1004-1015, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38592450

ABSTRACT

Asbestos and BAP1 germline mutations are risk factors for malignant mesothelioma (MM). While it is well accepted that amphibole asbestos is carcinogenic, the role of serpentine (chrysotile) asbestos in MM has been debated. To address this controversy, we assessed whether minimal exposure to chrysotile could significantly increase the incidence and rate of MM onset in germline Bap1-mutant mice. With either crocidolite or chrysotile, and at each dose tested, MMs occurred at a significantly higher rate and earlier onset time in Bap1-mutant mice than in wild-type littermates. To explore the role of gene-environment interactions in MMs from Bap1-mutant mice, we investigated proinflammatory and protumorigenic factors and the tumor immune microenvironment (TIME). IHC and immunofluorescence staining showed an increased number of macrophages in granulomatous lesions and MMs. The relative number of CD163-positive (CD163+) M2 macrophages in chrysotile-induced MMs was consistently greater than in crocidolite-induced MMs, suggesting that chrysotile induces a more profound immunosuppressive response that creates favorable conditions for evading immune surveillance. MMs from Bap1-mutant mice showed upregulation of CD39/CD73-adenosine and C-C motif chemokine ligand 2 (Ccl2)/C-C motif chemokine receptor 2 (Ccr2) pathways, which together with upregulation of IL6 and IL10, promoted an immunosuppressive TIME, partly by attracting M2 macrophages. Interrogation of published human MM RNA sequencing (RNA-seq) data implicated these same immunosuppressive pathways and connections with CD163+ M2 macrophages. These findings indicate that increased M2 macrophages, along with upregulated CD39/CD73-adenosine and Ccl2/Ccr2 pathways, contribute to an immunosuppressive TIME in chrysotile-induced MMs of Bap1-mutant mice, suggesting that immunotherapeutic strategies targeting protumorigenic immune pathways could be beneficial in human BAP1 mutation carriers who develop MM. SIGNIFICANCE: We show that germline Bap1-mutant mice have enhanced susceptibility to MM upon minimal exposure to chrysotile asbestos, not only amphibole fibers. Chrysotile induced a more profound immune tumor response than crocidolite in Bap1-mutant mice by upregulating CD39/CD73-adenosine and Ccl2/Ccr2 pathways and recruiting more M2 macrophages, which together contributed to an immunosuppressive tumor microenvironment. Interrogation of human MM RNA-seq data revealed interconnected immunosuppressive pathways consistent with our mouse findings.


Subject(s)
Mesothelioma, Malignant , Mesothelioma , Neoplasms, Mesothelial , Humans , Animals , Mice , Asbestos, Serpentine , Asbestos, Amphibole , Asbestos, Crocidolite/toxicity , Tumor Microenvironment/genetics , Mesothelioma/chemically induced , Adenosine , Immunosuppressive Agents , Germ Cells
2.
Diagn Cytopathol ; 52(4): 211-216, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38243885

ABSTRACT

BACKGROUND: Mesothelioma is a malignant neoplasm with a poor survival rate. We aimed to investigate the importance of BAP1, MTAP (IHC), and p16/CDKN2A homozygous deletion (FISH) in cytologic material obtained from pleural effusion sampling, which is a less invasive procedure in the diagnosis of mesothelioma. METHODS: Our study discussed pleural cytology samples of cases with histopathologically proven mesothelioma diagnoses between 2017 and 2022. As the control group, materials that had pleural effusion sampling for other reasons and reactive mesothelial hyperplasia were included in the study. Cell blocks prepared from these materials were subjected to fluorescent in situ hybridization for p16/CDKN2A homozygous deletion and immunohistochemistry for BAP1 and MTAP. RESULTS: The specificity of the P16/CDKN2A homozygous deletion in diagnosing mesothelioma is 100%. Its sensitivity is 68.75%. The specificity of BAP1 immunohistochemical nuclear expression loss is 95%, while the sensitivity is 60%. Loss of nuclear expression of MTAP alone has the lowest specificity and sensitivity, with a specificity of 86% and a sensitivity of 43%. The highest sensitivity is reached when BAP1 loss and p16/CDKN2A homozygous deletion are evaluated together, increasing to 81%. The specificity is 95%. CONCLUSION: It has been determined that any marker alone cannot be used for a definitive mesothelioma diagnosis in pleural effusion cytological specimens; however, sensitivity increases in some combinations. The combination of BAP1 immunohistochemistry and p16/CDKN2A homozygous deletion detected by FISH, which has a higher specificity and sensitivity, can be routinely used in the diagnosis of mesothelioma under the guidance of clinical and radiologic information.


Subject(s)
Mesothelioma, Malignant , Mesothelioma , Neoplasms, Mesothelial , Pleural Effusion , Humans , Cytology , Homozygote , In Situ Hybridization, Fluorescence , Sequence Deletion , Mesothelioma/diagnosis , Mesothelioma/genetics , Mesothelioma, Malignant/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics
3.
Arch Pathol Lab Med ; 148(5): e77-e89, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38190277

ABSTRACT

CONTEXT.­: Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most diffuse mesotheliomas lack oncogenic kinase mutations and instead harbor alterations involving tumor suppressors and chromatin regulators, a minor subset of tumors is characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion. OBJECTIVE.­: To provide updates on the salient molecular features of diffuse mesothelioma, mesothelioma in situ, and other mesothelial lesions: well-differentiated papillary mesothelial tumor, adenomatoid tumor, peritoneal inclusion cyst, and others. We consider the diagnostic, prognostic, and predictive utility of molecular testing in mesothelial lesions. DATA SOURCES.­: We performed a literature review of recently described genetic features, molecular approaches, and immunohistochemical tools, including BAP1, MTAP, and merlin in mesothelioma and other mesothelial lesions. CONCLUSIONS.­: Our evolving understanding of the molecular diversity of diffuse mesothelioma and other mesothelial lesions has led to considerable changes in pathology diagnostic practice, including the application of immunohistochemical markers such as BAP1, MTAP, and merlin (NF2), which are surrogates of mutation status. In young patients and/or those without significant asbestos exposure, unusual mesothelioma genetics such as germline mutations, ALK rearrangement, and ATF1 rearrangement should be considered.


Subject(s)
Biomarkers, Tumor , Immunohistochemistry , Mesothelioma , Tumor Suppressor Proteins , Ubiquitin Thiolesterase , Humans , Mesothelioma/diagnosis , Mesothelioma/genetics , Mesothelioma/metabolism , Mesothelioma/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Neoplasms, Mesothelial/diagnosis , Neoplasms, Mesothelial/genetics , Neoplasms, Mesothelial/metabolism , Neoplasms, Mesothelial/pathology , Mesothelioma, Malignant/diagnosis , Mesothelioma, Malignant/genetics , Mesothelioma, Malignant/pathology , Mesothelioma, Malignant/metabolism , Mutation
4.
Histopathology ; 84(1): 136-152, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37694811

ABSTRACT

This review article examines some new and some problem areas in mesothelial pathology, four of which are discussed, as follows. (1) The concept of mesothelioma in situ: this lesion is defined as a single layer of bland mesothelial cells without evidence of invasion, but that have lost BAP1 and/or MTAP by immunohistochemistry. Benign reactions can exactly mimic mesothelioma in situ, but a hint to the correct diagnosis is a story of recurrent pleural effusions/ascites of unknown aetiology without radiological or direct visual evidence of tumour. (2) The nature of well-differentiated papillary mesothelial tumour (WDPMT): WDPMT has a long history of arguments regarding its behaviour, and this uncertainty can now be seen to arise, in part, from the observation that some forms of mesothelioma in situ microscopically look exactly like WDPMT. Hence, it is recommended to always run at least a BAP1 stain on any lesion that looks like WDPMT. Both flat and WDPMT-like mesothelioma in situ are strongly associated with eventual development of invasive mesothelioma, but this process is relatively slow. (3) New immunostains for separating mesothelioma from other tumours: here, it is proposed that in most cases, and particularly when the differential is epithelioid mesothelioma versus non-small cell lung cancer, one can make this separation with extremely high sensitivity and specificity using just two stains: HEG1 and claudin-4. (4) Markers for separating benign from malignant mesothelial proliferations: this topic is briefly reviewed, with an indication of which markers are generally accepted and the best utilisation and possible limitations of each marker.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Neoplasms, Mesothelial , Pleural Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/pathology , Biomarkers, Tumor , Tumor Suppressor Proteins , Mesothelioma, Malignant/diagnosis , Mesothelioma/diagnosis , Mesothelioma/pathology , Neoplasms, Mesothelial/diagnosis , Diagnosis, Differential , Ubiquitin Thiolesterase , Pleural Neoplasms/pathology
5.
Cytopathology ; 35(1): 16-22, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37795809

ABSTRACT

The International System for Reporting Serous Fluid Cytology (TIS) has been proposed by an expert working team composed of the International Academy of Cytology and the American Society of Cytopathology, following an international survey. Since its introduction, the TIS has gained worldwide acceptance, and this review aims to assess its global impact. A literature search revealed 25 studies which have presented data on the impact of the TIS. Most of them provide data, including risk of malignancy (ROM) for each diagnostic category, separately for pleural, peritoneal and pericardial effusions, while a few do not separate them. A few studies focus on specific diagnoses like mesothelioma on specific types of fluids or more specific issues like the optimal fluid volume for cytology or interobserver variability. A synopsis of the data from the literature search is presented in four tables. The ROM assessment is discussed, as well as interobserver variability and the use of ancillary diagnostic immunochemistry. In conclusion, our review of the published data suggests that the TIS is a valid classification scheme that has been widely accepted by pathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management.


Subject(s)
Mesothelioma, Malignant , Mesothelioma , Neoplasms, Mesothelial , Pericardial Effusion , Humans , Mesothelioma, Malignant/pathology , Mesothelioma/pathology , Cytodiagnosis , Pericardial Effusion/pathology , Neoplasms, Mesothelial/pathology
6.
Radiographics ; 43(3): e220128, 2023 03.
Article in English | MEDLINE | ID: mdl-36757881

ABSTRACT

A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics. While malignant mesotheliomas are biologically aggressive malignancies that occur primarily in patients exposed to asbestos with attendant poor survival rates, well-differentiated papillary mesothelial tumors and adenomatoid tumors charter a benign clinical course with an excellent prognosis. Mesothelioma in situ is a newly characterized entity represented by recurrent unexplained pleural effusions without any identifiable mass at imaging or thoracoscopy. Immunohistochemical markers based on BAP1, MTAP, CDKN2A, and TRAF7 gene mutations help differentiate diffuse mesotheliomas from benign mesothelial proliferations and localized mesotheliomas. Cross-sectional imaging modalities, including US, CT, MRI, and fluorine 18-fluorodeoxyglucose (FDG) PET/CT, permit diagnosis and play a major role in staging and assessing surgical resectability. Imaging studies are invaluable in providing noninvasive and quantitative assessment of tumor response in patients with unresectable disease. Owing to significant overlap in patient characteristics and pathomorphology, accurate diagnosis based on advanced histopathology techniques and genetic abnormalities is imperative for optimal management and prognostication. While patients with nonepithelioid pleural mesotheliomas benefit from immunotherapy, novel targeted therapies for CDKN2A-, NF2-, and BAP1-altered mesotheliomas are under consideration. © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.


Subject(s)
Adenomatoid Tumor , Mesothelioma, Malignant , Mesothelioma , Neoplasms, Mesothelial , Pleural Neoplasms , Humans , Positron Emission Tomography Computed Tomography , Mesothelioma/diagnostic imaging , Mesothelioma/therapy , Pleural Neoplasms/pathology , Biomarkers, Tumor
9.
Mod Pathol ; 35(1): 69-76, 2022 01.
Article in English | MEDLINE | ID: mdl-34480081

ABSTRACT

We report nine examples of a previously undescribed type of peritoneal circumscribed nodular mesothelial tumor characterized by nests or sheets of mesothelial cells with sharp cell borders and extremely bland, sometimes grooved, nuclei. In some cases, nests were separated by fibrous bands. All patients were women, age range 30-72 years (median 52 years). All tumors were incidental findings during surgery and grossly were either solitary nodules or a few small nodules on the peritoneal surface. Referring pathologic diagnoses included diffuse malignant mesothelioma, localized malignant mesothelioma, well-differentiated papillary mesothelioma, and adenomatoid tumor. No tumor showed BAP1 loss by immunohistochemistry nor deletion of CDKN2A by FISH. RNA-seq revealed that these tumors clustered together and were distinct from peritoneal diffuse malignant mesotheliomas. Very few mutations or translocations were found, none of them recurrent from tumor to tumor, and no tumor showed an abnormality in any of the genes typically mutated/deleted in diffuse malignant mesothelioma. Array CGH on three cases revealed two with a completely flat profile and one with a small deletion at 3q26-3q28. On follow-up (range 5-60, median 34 months), there were no deaths, no recurrences, and no evidence of metastatic disease nor local spread; one case that initially had scattered nodules on the pelvic peritoneum had the same pattern of nodules at a second look operation 2 years later. We propose the name solid papillary mesothelial tumor for these lesions. These appear to be either benign or very low-grade tumors that need to be separated from malignant mesotheliomas.


Subject(s)
Carcinoma, Papillary/pathology , Neoplasms, Mesothelial/pathology , Peritoneal Neoplasms/pathology , Adult , Aged , Carcinoma, Papillary/genetics , Chi-Square Distribution , Cluster Analysis , Cohort Studies , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization, Fluorescence , Incidental Findings , Middle Aged , Mutation , Neoplasms, Mesothelial/genetics , Peritoneal Neoplasms/genetics , Prognosis , Sequence Analysis, RNA , Signal Transduction , Time Factors , Translocation, Genetic
12.
PLoS One ; 15(12): e0241500, 2020.
Article in English | MEDLINE | ID: mdl-33270665

ABSTRACT

The presence of ascites in the peritoneal cavity leads to morphological and functional changes of the peritoneal mesothelial cell layer. Cells loose cell-cell interactions, rearrange their cytoskeleton, activate the production of fibronectin, and change their cell surface morphology in a proinflammatory environment. Moreover, ovarian cancer cell adhesion has been shown to be facilitated by these changes due to increased integrin- and CD44-mediated binding sites. In this study, the biological responsiveness of the human pleural mesothelial cell line MeT-5A to patient-derived and artificial ascites was studied in vitro and adhesion of ovarian cancer cells, i.e. SKOV-3 cells, investigated. Changes were mainly observed in cells exposed to artificial ascites containing higher cytokine concentrations than patient-derived ascites. Interestingly, reduced cell-cell interactions were already observed in untreated MeT-5A cells and effects on tight junction protein expression and permeability upon exposure to ascites were minor. Ascites induced upregulation of CDC42 effector protein 2 expression, which affects stress fiber formation, however significant F-actin reorganization was not observed. Moreover, fibronectin production remained unchanged. Analysis of mesothelial cell surface characteristics showed upregulated expression of intercellular adhesion molecule 1, slightly increased hyaluronic acid secretion and decreased microvillus expression upon exposure to ascites. Nevertheless, the observed changes were not sufficient to facilitate adhesion of SKOV-3 cells on MeT-5A cell layer. This study revealed that MeT-5A cells show a reduced biological responsiveness to the presence of ascites, in contrast to published studies on primary human peritoneal mesothelial cells.


Subject(s)
Cell Adhesion/drug effects , Cytokines/pharmacology , Neoplasms, Mesothelial/drug therapy , Ovarian Neoplasms/drug therapy , Ascites/metabolism , Ascites/pathology , Cell Line, Tumor , Cytokines/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hyaluronan Receptors/genetics , Integrin beta1/genetics , Intercellular Adhesion Molecule-1/genetics , Neoplasms, Mesothelial/genetics , Neoplasms, Mesothelial/metabolism , Neoplasms, Mesothelial/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Patients , Peritoneum/chemistry , Peritoneum/metabolism , Signal Transduction/genetics , cdc42 GTP-Binding Protein/genetics
13.
Cell Mol Biol (Noisy-le-grand) ; 66(6): 98-104, 2020 Sep 30.
Article in English | MEDLINE | ID: mdl-33040793

ABSTRACT

Capsaicin is one of the most extensively studied phytochemicals and its cytotoxicity on various types of cancer has been demonstrated both in vitro and in vivo. The evaluation of its effect on mesothelioma, however, has remained quite limited. In this study, we investigated the anti-mesothelioma potential of capsaicin by observing its cytotoxicity on healthy, immortalized and cancerous cells of mesothelium in vitro and how this potential be affected by lowered Cyclin E levels, a key regulator of G1/S transition of cell cycle. For this purpose, we determined and compared the IC50 values of capsaicin in both FBS (Fetal Bovine Serum) containing and FBS-deprived medium of each cell population studied. Additionally, we examined the changes in both protein and mRNA levels of caspase-3 upon capsaicin exposure as well as conducted a series of experiments through which the relatively long term effect of capsaicin on the growth rate of the cells was assessed. As a result, the reduced Cyclin E obtained through the absence of FBS in growth medium was found not only to decrease IC50 values for all cell types dramatically (p<0.05) but also to cause a considerable difference between the values determined for cancerous and non-cancerous populations (p<0.05), which had not been observed in regular medium. Moreover, along with the fact that capsaicin exposure did not have an impact on the cell growth in long term in most cases, caspase-3 levels also remained the same when exposed to capsaicin, suggesting a mechanism of cell death independent of caspases.


Subject(s)
Capsaicin/pharmacology , Cyclin E/metabolism , Epithelium/drug effects , Neoplasms, Mesothelial/drug therapy , Oncogene Proteins/metabolism , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Death/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Epithelium/metabolism , Humans , Neoplasms, Mesothelial/metabolism
14.
Diagn Cytopathol ; 48(12): E22-E26, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32621636

ABSTRACT

Emperipolesis is a physiologic or pathologic phenomenon characterized by the presence of intact viable cells within the cytoplasm of another cell. It has been described in normal tissues and in a variety of inflammatory and neoplastic lesions such as Rosai-Dorfman disease, tumors, hematopoietic disorders and rarely lymphomas. Emperipolesis by mesothelial cells is rare. Few cases of mesothelial emperipolesis of neoplastic lymphocytes in pleural effusions involved by lymphomas have been reported in the literature. Its etiopathogenesis and significance are controversial and speculative. We report a case of a 36-year-old man who presented with cough, chest pain, breathing difficulty, pericardial, and bilateral pleural effusions secondary to mediastinal T-lymphoblastic lymphoma. Pleural fluid cytology slides and cell block sections showed numerous single dispersed neoplastic lymphoblasts with occasional giant multinucleated mesothelial cells with emperipolesis of lymphocytes. The background showed scattered and clumped apoptotic karyorrhexis debris and reactive mesothelial cells. Cell block immunohistochemistry showed CD3, CD5, CD7, CD10, CD99, and TdT positive lymphocytes, consistent with involvement by T-lymphoblastic lymphoma. The giant cells were positive for cytokeratin, calretinin and WT1 confirming their mesothelial origin. Lymphoid effusions with emperipolesis may raise a potential diagnostic pitfall because they may morphologically be confused with other inflammatory and neoplastic lesions. This cell-in-cell phenomenon can be a helpful clue in the differential diagnosis of lymphocyte-rich effusions since it has been described in association with lymphomas. It might shed some light on the lymphocyte-mesothelial interaction and the potential phagocytic antigen-presenting properties of mesothelial cells under certain circumstances.


Subject(s)
Emperipolesis/physiology , Epithelium/pathology , Lymphocytes/pathology , Neoplasms, Mesothelial/pathology , Pleural Effusion/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Adult , Biomarkers, Tumor/metabolism , Epithelium/metabolism , Humans , Lymphocytes/metabolism , Male , Neoplasms, Mesothelial/metabolism , Pleural Effusion/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism
15.
Ecotoxicol Environ Saf ; 198: 110640, 2020 Jul 15.
Article in English | MEDLINE | ID: mdl-32330788

ABSTRACT

Fluoro-edenite (FE) is a silicate mineral identified in the lava products of Monte Calvario from stone quarries located in the southeast of Biancavilla, a small city of the Etnean volcanic complex (Sicily, Italy). Inhalation of FE fibers has been associated with a higher incidence of Malignant Mesothelioma (MM), a highly aggressive neoplasm of the serosal membranes lining the pleural cavity. Only 5% of MM patients are diagnosed at an early stage and the median survival is approximate 6-12 months. Many diagnostic biomarkers have been proposed for MM. Several studies demonstrated that microRNAs (miRNAs) may be used as good non-invasive diagnostics, as well as prognostic biomarkers for various human diseases, including cancer. On these bases, the aim of the present study was to identify a set of miRNAs involved in the development and progression of MM and potentially used as diagnostic biomarkers. For these purposes, in silico analyses were performed on healthy/exposed to asbestos fibers subjects vs. patients with MM. These analyses revealed a set of miRNAs strictly involved in MM by merging the lists of miRNAs found differentially expressed in the three miRNA expression datasets analyzed. The result of these computational evaluations allowed the execution of functional in vitro experiments performed on normal pleural mesothelial cell line (MeT-5A) and MM cell line (JU77) in order to test the carcinogenetic effects and epigenetic modulation induced by FE exposure. The in vitro results showed that the expression levels of hsa-miR-323a-3p vary significantly in both supernatant- and cell-derived miRNAs derived from treated and untreated cells. Secreted and cellular hsa-miR-101-3p in MeT-5A treated with FE fibers and JU77 cells showed different trends of expression. As regard hsa-miR-20b-5p, there was no differential expression between secreted and cellular hsa-miR-20b-5p. This miRNA has been shown a significant up-regulation in JU77 cells vs. control and treated MeT-5A. As a future plan, translational analyses will be performed on a subset of patients chronically exposed to FE fibers to further verify the clinical role of such miRNAs in high-risk individuals and their possible use as biomarkers of FE exposure or MM early onset.


Subject(s)
Asbestos, Amphibole/toxicity , Asbestos/toxicity , Cell Transformation, Neoplastic/chemically induced , Environmental Exposure , Epithelium/drug effects , MicroRNAs/genetics , Neoplasms, Mesothelial/chemically induced , Adult , Biomarkers/analysis , Cell Line , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Neoplasms, Mesothelial/diagnosis , Sicily
16.
Cell Transplant ; 28(11): 1384-1389, 2019 11.
Article in English | MEDLINE | ID: mdl-31366210

ABSTRACT

The cytology of peritoneal washing fluids for gastric cancer is the most basic method for judging peritoneal micrometastasis. However, the clinical value of this method is not clear at present. A retrospective analysis was performed on 277 patients with pathologically proven and surgically treated gastric cancer. The peritoneal washing fluids were collected after opening the abdomen and before the operation, and were sent to the cytology laboratory for screening of occult cancer cells in the collected washing fluids. The number of cases diagnosed as cancer cells, reactive mesothelial cells, serosal balls, and traumatic mesothelial cells were 42, 18, 27, and 190, respectively. Typical adenocarcinoma cell nests were found in eight of 10 T4b samples, whereas 34 cases of cancer cells in T3 and T4a showed that these cell nests usually contained mesothelial cells, and the three-dimensional stereoscopic sense of the nests was not obvious. In the specific subcellular morphological changes of both reactive mesothelial cells and serosal balls, the changes of both the contour of nuclear membrane and the polarity of cell alignment were present only in stage T3 and T4a. The presence or absence of mesothelial cells in the nests of cancer cells and the changes of the contour of nuclear membrane and of the polarity of cell alignment in reactive mesothelial cells or serosal balls may help us to predict the depth of invasion of cancer cells.


Subject(s)
Adenocarcinoma/secondary , Ascitic Fluid/cytology , Neoplasms, Mesothelial/secondary , Stomach Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Ascitic Fluid/pathology , Epithelium/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasms, Mesothelial/diagnosis , Neoplasms, Mesothelial/pathology , Neoplasms, Mesothelial/surgery , Retrospective Studies , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery
17.
Cytopathology ; 30(6): 592-600, 2019 11.
Article in English | MEDLINE | ID: mdl-31165505

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the utility of BRCA1-associated protein-1 (BAP1), glucose transporter (GLUT)-1 and desmin expression by immunohistochemistry in the discrimination between reactive and malignant mesothelial proliferations. METHODS: A total of 88 biopsies and 30 effusions from mesothelioma cases were studied. Control groups were composed of 35 tissues and 30 cell blocks. The 88 mesothelioma cases were from 43 males and 45 females (mean age 56 years). Tumours were mostly localised to pleura (66/88, 75%) and of epithelioid histology (75/88, 85%). Cytology samples were from 17 males and 13 females (mean age 58 years), and 16 pleural and 14 peritoneal effusions. Twenty cytology cases had corresponding tissue biopsies. RESULTS: BAP1 loss was detected in 61/88 (69%) tissues and in 20/30 (67%) cytology samples from mesothelioma with a specificity of 100% for both sampling methods. BAP1 loss was observed more frequently in pleural and biphasic tumours. GLUT-1 immunoreactivity was identified in 54/81 (67%) and 23/25 (92%) malignant tissues and effusions, and in 6/33 (18%) and 6/30 (20%) benign tissues and effusions, respectively. Desmin loss was observed in 74/80 (92%) malignant biopsy samples, 16/21 (76%) malignant effusions and 10/34 (29%) of benign tissues, but in none of the reactive effusions. Concordance rate of results between biopsy and cytology was as follows: BAP1 20/20 (100%); GLUT-1 13/18 (72%); and desmin 10/14 (71%). CONCLUSIONS: BAP1, GLUT-1 and desmin are useful markers in the discrimination between reactive and malignant mesothelial proliferations. BAP1 loss seems to be diagnostic for mesotheliomas both in biopsy and cytology samples.


Subject(s)
Desmin/genetics , Glucose Transporter Type 1/genetics , Lung Neoplasms/diagnosis , Mesothelioma/diagnosis , Neoplasms, Mesothelial/diagnosis , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Biomarkers, Tumor/genetics , Cell Proliferation/genetics , Cytodiagnosis , Diagnosis, Differential , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Immunohistochemistry/methods , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Mesothelioma/genetics , Mesothelioma/pathology , Mesothelioma, Malignant , Middle Aged , Neoplasms, Mesothelial/genetics , Neoplasms, Mesothelial/pathology , Pleural Effusion, Malignant
18.
Occup Med (Lond) ; 69(2): 118-125, 2019 Apr 13.
Article in English | MEDLINE | ID: mdl-30949692

ABSTRACT

BACKGROUND: The Health and Safety Executive's new Health and Work Strategy is based on an up-to-date assessment of workplace health priorities. Rather than replicating traditional prioritization approaches, a broader assessment of health and work priorities was carried out using a range of stakeholders. AIMS: To develop a set of health priorities for further research and intervention activity. METHODS: Four exercises were carried out, including internal prioritization, two external web-hosted questionnaire studies of younger workers and occupational health professionals, focus groups and tele-depth interviews with workplace health and safety professionals. RESULTS: The highest rated internal priorities (weighted priority scores) were identified as mesothelioma (70), lung cancer (69.25), chronic obstructive pulmonary disease (COPD; 69), musculoskeletal disorders (MSDs; 66.25), hearing loss (65.75), stress (65.5), asthma (64.5) and hand-arm vibration syndrome (61.5). Using the three highest ranked criteria developed by occupational health professionals ((i) the preventability of the condition, (ii) the impact of the condition and (iii) the number of workers affected), mesothelioma, lung cancer, COPD, MSDs, hearing loss, stress and asthma were identified as the top seven priorities. Generic issues identified included ageing and work, obesity, newer technologies, and ethnicity and cultures of workforces. Apprentices identified stress, depression, anxiety, musculoskeletal and respiratory disorders, fatigue and workload as important workplace health considerations. CONCLUSIONS: This process identified a number of expected and new areas of health research interest. We believe the findings reflect the real world requirements of work as assessed by occupational health and safety practitioners and workers.


Subject(s)
Chronic Disease/therapy , Evidence-Based Practice/organization & administration , Health Priorities/organization & administration , Occupational Diseases/therapy , Occupational Health , Focus Groups , Health Personnel , Humans , Lung Neoplasms , Musculoskeletal Diseases , Neoplasms, Mesothelial
19.
Clin Lung Cancer ; 20(2): e152-e157, 2019 03.
Article in English | MEDLINE | ID: mdl-30594459

ABSTRACT

Primary pericardial mesothelioma (PPM) is a rare cancer for which there is no consensus on treatment. We evaluated and summarized a large contemporary population of published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Using Ovid and PubMed, literature published from 2000 through 2016 was searched using the terms "primary pericardial mesothelioma," "pericardial mesothelioma," and "malignant pericardial mesothelioma." We identified 6 case series and 84 case reports for a total of 103 PPM cases published from 2000 through 2016. The median age at diagnosis was 55 years, and the median overall survival was 6 months. In univariate analyses of clinical characteristics including gender, asbestos exposure, tobacco use, prior radiation exposure, histologic subtype, and metastasis and/or mediastinal spread, only the presence of metastasis and/or mediastinal spread was a significant predictor of decreased survival (P = .015). Surgery did not provide a statistically significant survival benefit (P = .12). A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months, P = .002), specifically chemotherapy with a platinum agent with or without pemetrexed. In multivariate analysis, only the receipt of chemotherapy was associated with improved survival. PPM remains a rare and poorly understood malignancy with unclear etiology and a poor prognosis. In this retrospective systematic review, a survival benefit was seen in patients who received chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Heart Neoplasms/therapy , Neoplasms, Mesothelial/therapy , Pemetrexed/therapeutic use , Platinum/therapeutic use , Asbestos/adverse effects , Environmental Exposure/adverse effects , Heart Neoplasms/mortality , Humans , Neoplasms, Mesothelial/mortality , Pericardium , Risk Factors , Survival Analysis , Treatment Outcome
20.
Rev. int. androl. (Internet) ; 16(2): 82-86, abr.-jun. 2018. ilus, tab
Article in Portuguese | IBECS | ID: ibc-174629

ABSTRACT

Os tumores adenomatoides são tumores benignos raros, de origem mesotelial que, no homem, afetam principalmente o epidídimo. Representam mais de um terço dos tumores paratesticulares e o tratamento de eleição é a excisão cirúrgica. Extremamente rara é a origem no parênquima testicular ou na túnica albugínea. Os sinais clínicos e estudos de imagem são frequentemente inconclusivos, não permitindo o diagnóstico diferencial com a neoplasia testicular maligna, resultando em orquidectomias radicais desnecessárias. Os autores descrevem um caso clínico de tumor adenomatoide da túnica albugínea, em que a suspeita clínica e exame anatomopatológico intraoperatório conduziram à realização de uma orquidectomia parcial


The adenomatoid tumors are rare benign mesothelial lesions that in males affect mainly the epididymis. They account for over one third of paratesticular tumors, and the treatment of choice has been surgical excision. The origin in testicular parenchyma or the tunica albuginea is extremely rare. Clinical signs and imaging studies are often inconclusive in differentiate from a more common malignant intratesticular solid tumour, which can result in unnecessary orchiectomies. We present a case of adenomatoid tumor of tunica albuginea where clinical suspicion and intraoperative frozen section analysis led to a partial orchiectomy


Subject(s)
Humans , Male , Middle Aged , Adenomatoid Tumor/diagnostic imaging , Testicular Neoplasms/diagnostic imaging , Adenomatoid Tumor/pathology , Neoplasms, Mesothelial/diagnostic imaging , Scrotum/diagnostic imaging , Scrotum/pathology , Immunohistochemistry/methods
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