Cases Of Malignant Mesothelioma Research Articles

Metastatic Mesothelioma of the Tunica Vaginalis Presenting as Scrotal and Abdominal Nodules: A Case Report and Review of the Literature.

Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

A Case of Malignant Pleural Mesothelioma with a Metastatic Tumor of the Ascending Colon

A Case of Malignant Pleural Mesothelioma with a Metastatic Tumor of the Ascending Colon

Characterization and potential toxicity of asbestiform erionite from Gawler Downs, New Zealand

Abstract Erionite is the name for a zeolite mineral series originating from diagenesis or hydrothermal alteration of volcanic rocks. The particular erionite “species” is based on the dominant extra-framework cation, erionite-Ca, erionite-K, or erionite Na. Irrespective of the species, erionite can display a fibrous/asbestiform morphology and has been linked with cases of malignant mesothelioma, a disease typically associated with asbestos exposure. Characterization of new discoveries of erionite is therefore important to assess any potential exposure hazards. This study describes a new asbestiform erionite from vesicles within the Upper Cretaceous Mt. Somers Volcanics Group (MSVG), Canterbury, New Zealand. The erionite is within the Hinds River Dacite, the youngest unit within the MSVG at Gawler Downs, ~100 km west of Christchurch, in the foothills of the Southern Alps. A multi-analytical approach was taken to analyze the sample which included micro-Raman spectroscopy, thermogravimetric analysis, electron microscopy, electron microprobe analysis, and X-ray powder diffraction with the Rietveld method. Results confirmed the mineral as fibrous erionite-K. The chemical composition of the mineral is unique due to the presence of higher levels of Mg. While Fe was also identified, this was due to smectite flakes occurring on the surface of the erionite fibers. According to the World Health Organization (WHO) respirable mineral fiber definition, where length ≥5 μm, width ≤3 μm, and aspect ratio (L/w) ≥3:1, the Gawler Downs erionite fibers are respirable, while the fibers themselves exceed respirable thickness. In addition to morphology, a value for the potential toxicity model was computed to be 2.28 for the Gawler Downs erionite. This is similar to those of other carcinogenic erionites from Karain, Turkey (2.33), and Nevada, U.S.A. (2.28). Taken together, results indicate Gawler Downs erionite represents an environmental hazard. Nevertheless, further investigation is required to determine potential environmental exposure pathways by which erionite may become airborne and assess the actual environmental risk in the Gawler Downs area.

A Rare Case of Canine Pericardial Malignant Mesothelioma: Clinicopathologic Findings, Diagnostic Investigations, and Clinical Course with Epirubicin Treatment

A Rare Case of Canine Pericardial Malignant Mesothelioma: Clinicopathologic Findings, Diagnostic Investigations, and Clinical Course with Epirubicin Treatment

Identifying malignant mesothelioma by a pathological survey using the São Paulo state hospital cancer registry, Brazil.

To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil. Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM. Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review. Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.

A case of malignant mesothelioma with numerous psammoma bodies in the pleural effusion

A case of malignant mesothelioma with numerous psammoma bodies in the pleural effusion

Case of Peritoneal Malignant Mesothelioma in a 60-year-old Lady Presenting Clinically With Huge Abdominopelvic Mass: A Diagnostic Challenge

Peritoneal malignant mesothelioma is a rare tumour that poses diagnostic challenges due to vague clinical symptoms, a variable histologic picture and being a common site for metastasis from GI organ, ovary, kidney and several other organs. We presented a case of peritoneal malignant mesothelioma in a 60-year-old lady who presented clinical symptoms of abdominal obstruction due to an omental cyst on a Computed Tomography (CT) scan. The case has been diagnosed as peritoneal malignant mesothelioma on histology along with a panel of immunohistochemical stains like calretinin (diffuse nuclear and cytoplasmic positivity), WT1 (diffuse nuclear positivity), CK 7 (focal positivity), PAX8 (focal positivity), CK20 (negative). At least two positive immunohistochemical markers and one negative marker help to distinguish mesothelioma from other entities. There was no history of active or passive asbestos exposure. She has been referred to a nearby regional cancer centre and managed accordingly. During her first postoperative check-up, she was asked about the history of asbestos exposure either in active or in passive form, which she denied. The present case report discusses the diagnostic dilemma in routine Haematoxylin &amp; Eosin (H&amp;E) stained tissue sections with a list of differential diagnoses as: 1) Primary tumour (peritoneal malignant mesothelioma versus primary serous carcinoma); 2) Sex cordstromal tumour of ovarian origin; 3) Metastatic adenocarcinoma from neighbouring organ.

A rare case of primary malignant epithelioid mesothelioma of spermatic cord - Known yet unknown entity

A rare case of primary malignant epithelioid mesothelioma of spermatic cord - Known yet unknown entity

A case of malignant peritoneal mesothelioma diagnosed by laparoscopic surgery

A case of malignant peritoneal mesothelioma diagnosed by laparoscopic surgery

A Case of Malignant Pleural Mesothelioma with Spermatic Cord and Peritoneal Involvement That Responded to Ipilimumab+Nivolumab Combination Therapy

A Case of Malignant Pleural Mesothelioma with Spermatic Cord and Peritoneal Involvement That Responded to Ipilimumab+Nivolumab Combination Therapy

Comprehensive bioinformatics analysis of the role of VWF in the tumor microenvironment of malignant mesothelioma.

To explore the influence and effect of tumor microenvironment on the development of malignant mesothelioma using machine learning methods. 87 open cases were downloaded from the Cancer Genome Atlas database including transcriptome data, clinical data, and mutation data. The immune, stromal, and estimate scores were calculated for each case by using the ESTIMATE algorithm, and then the cases were grouped according to high and low stromal scores to predict all-cause survival in malignant mesothelioma cases. Their mutation data were analyzed to reveal the differences in mutated genes between the 2 groups, and then the von Willebrand factor (VWF) and FCRL3 genes were identified according to the intersection of DEGs and high-frequency mutated genes. Lastly, the correlation between VWF and the immune checkpoint of 22 kinds of immune cells was analyzed by using the CIBERSORT package of R software. A significant difference was found in the survival time of patients between the high and low stromal score groups. High expression of the VWF gene was negatively correlated with the prognosis of malignant mesothelioma, and the expression of VWF was positively correlated with naive B cells and activated CD4 memory T cells and negatively correlated with NK cells. The results revealed that high expression of VWF may involve in the development of malignant mesothelioma, and the anti-CTLA4 immune checkpoint treatment may have certain efficacy.

Incidence of mesothelioma in young people and causal exposure to asbestos in the Italian national mesothelioma registry (ReNaM)

IntroductionThe epidemiological surveillance of mesothelioma incidence is a crucial key for investigating the occupational and environmental sources of asbestos exposure. The median age at diagnosis is generally high, according to...

Difference in carcinogenicities of two different vapor grown carbon fibers with different physicochemical characteristics induced by intratracheal instillation in rats

BackgroundCarbon fibers are high aspect ratio structures with diameters on the submicron scale. Vapor grown carbon fibers are contained within multi-walled carbon tubes, with VGCF™-H commonly applied as a conductive additive in lithium-ion batteries. However, several multi-walled carbon fibers, including MWNT-7, have been reported to induce lung carcinogenicity in rats. This study investigated the carcinogenic potential of VGCF™-H fibers in F344 rats of both sexes with the vapor grown carbon fibers VGCF™-H and MWNT-7 over 2 years. The carbon fibers were administered to rats by intratracheal instillation at doses of 0, 0.016, 0.08, and 0.4 mg/kg (total doses of 0, 0.128, 0.64, and 3.2 mg/kg) once per week for eight weeks and the rats were observed for up to 2 years after the first instillation.ResultsHistopathological examination showed the induction of malignant mesothelioma on the pleural cavity with dose-dependent increases observed at 0, 0.128, 0.64, and 3.2 mg/kg in rats of both sexes that were exposed to MWNT-7. On the other hand, only two cases of pleural malignant mesothelioma were observed in the VGCF™-H groups; both rats that received 3.2 mg/kg in male. The animals in the MWNT-7 groups either died or became moribund earlier than those in the VGCF™-H groups, which is thought related to the development of malignant mesothelioma. The survival rates were higher in the VGCF™-H group, and more carbon fibers were observed in the pleural lavage fluid (PLF) of the MWNT-7 groups. These results suggest that malignant mesothelioma is related to the transfer of carbon fibers into the pleural cavity.ConclusionsThe intratracheal instillation of MWNT-7 clearly led to carcinogenicity in both male and female rats at all doses. The equivocal evidence for carcinogenic potential that was observed in male rats exposed to VGCF™-H was not seen in the females. The differences in the carcinogenicities of the two types of carbon fibers are thought due to differences in the number of carbon fibers reaching the pleural cavity. The results indicate that the carcinogenic activity of VGCF™-H is lower than that of MWNT-7.

Principles of Surgical Management of Peritoneal Mesothelioma.

Malignant peritoneal mesothelioma (MPeM) is a rare malignancy and represents 5% to 30% of malignant mesothelioma cases. The primary curative therapy for MPeM is radical cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with the strongest predictor of long-term survival being complete cytoreduction. There is a paucity of high-quality evidence available to guide management in MPeM; however, NCCN Guidelines for the management of MPeM were updated this year. In well-selected patients, 5-year overall survival exceeds 65%, but achieving optimal results requires careful preoperative evaluation and expert surgical management. Preoperative patient selection includes histology review and staging with cross-sectional imaging. Ideal candidates for curative intent surgery are those with epithelioid MPeM, a low peritoneal cancer index, and a good performance status. Contraindications to curative intent surgery include the sarcomatoid MPeM, distant metastases, extensive nodal metastases, and extensive small bowel serosal or mesentery involvement not amenable to complete cytoreduction. Those with biphasic histology, bicavitary disease, and metastatic lymphadenopathy may be considered for surgery following response to neoadjuvant therapy. CRS involves resection of all peritoneal disease, the extent of which varies case by case. Key aspects involve careful evaluation of all peritoneal surfaces, complete parietal peritonectomy and omentectomy, and evaluating suspicious abdominal lymph node basins. Once maximum cytoreduction is achieved, HIPEC is performed using a platinum-based perfusate. Postoperative protocols are recommended to optimize recovery and mitigate HIPEC-specific complications, namely chemotherapy-mediated nephrotoxicity and bone marrow suppression.

Use of PET/CT in Diagnosis and Staging of Malignant Pleural Mesothelioma

Background The pleural space is formed by two pleural membranes: the parietal pleura and the visceral pleura. Each is comprised of a single layer of mesothelial cells, a basement membrane, and a layer of connective tissue which contains blood vessels and lymphatics. Various benign, malignant, and tumor-like conditions can involve the pleura. Malignant neoplasms are more common than benign neoplasms. Pleural tumors can have a varied imaging spectrum – may be unilateral or bilateral, calcified, or noncalcified, and focal or diffuse. Aim of the Work To elucidate the role of PET/CT in diagnosing and staging of malignant pleural mesothelioma (MPM) patients. Patients and Methods A cross sectional analysis of all cases of malignant mesothelioma referred to Elmaadi Military hospital during the period from Nov. 2020 to Jun. 2021 for assessment of the role of F18-FDG PET/CT in staging, restaging and monitor of therapy response compared to CT. The total number of patients with mesothelioma was 30 patients, 20 males and 10 females. Results In the present study, 27 patients out of 30 patients evaluated with PET/CT showed positive findings at primary sites in pleura and accurately localized tumor sites in them. Also 9 patients of them had local lesions in pleura only with 6 patients had loco-regional lesions. Furthermore 12 patients had loco-regional and metastatic lesions. We demonstrate that PET/CT has high sensitivity than CT in detecting MPM lesions specially intrathoracic lymph node and extrathoracic metastasis as (37% vs. 18 %) of PET/CT and CT respectively. Conclusion FDG PET/CT increases the accuracy of overall staging in patients with MPM and significantly improves the selection of patients for curative surgical resection. Specifically, FDG PET/CT is particularly useful in identifying mediastinal lymph node involvement and detection of distant metastases.

Analysis of clinicopathological features of 68 cases of malignant pleural mesothelioma

Objective: To analyze the clinicopathological characteristics of diffuse malignant pleural mesothelioma (MPM), and explore the diagnostic methods in order to improve the early diagnosis rate. Methods: In January 2019 to January 2022, the clinical features, auxiliary examination and immunohistochemical results of 68 cases of MPM were analyzed retrospectively. The pathogenic features, histopathological morphology and the expression of related antibodies including Calretinin (CR), D2-40 and WT-1 were summarized. Results: Among the 68 patients, 40 male (58.82%), 28 female (41.18%), male to female ratio was 1.43%, median age was 58 years old; 50% of patients in Dayao County, epithelial mesothelioma 59 cases (86.76%), occurred in right chest in 39 cases (57.35%), left chest in 25 cases (36.76%), and 4 cases in both sides (5.89%). The most common initial clinical manifestations were pleural effusion (95.59%), chest pain (36.75%), chest tightness and shortness of breath (30.88%). The main imaging findings were pleural effusion in 49 cases (98.00%) and pleural thickening in 46 cases (92.00%). MPM tumor cells often expressed Calretinin, CK5/6, WT1 and D2-40, while TTF-1, NapsinA and CEA, the main markers differentiated from lung adenocarcinoma were negative. Serum CYFRA21-1 and CEA have high value in differential diagnosis of benign and malignant pleural effusions. Conclusion: Diffuse MPM has diverse histological and cytological morphology, which needs to be differentiated from a variety of diseases. Correct diagnosis of diffuse MPM through immunohistochemistry requires the combined application of a group of Mesothelium related antibodies.

The crystal structure of the killer fibre erionite from Tuzköy (Cappadocia, Turkey).

Erionite is a non-asbestos fibrous zeolite classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen and is considered today similar to or even more carcinogenic than the six regulated asbestos minerals. Exposure to fibrous erionite has been unequivocally linked to cases of malignant mesothelioma (MM) and this killer fibre is assumed to be directly responsible for more than 50% of all deaths in the population of the villages of Karain and Tuzköy in central Anatolia (Turkey). Erionite usually occurs in bundles of thin fibres and very rarely as single acicular or needle-like fibres. For this reason, a crystal structure of this fibre has not been attempted to date although an accurate characterization of its crystal structure is of paramount importance for our understanding of the toxicity and carcinogenicity. In this work, we report on a combined approach of microscopic (SEM, TEM, electron diffraction), spectroscopic (micro-Raman) and chemical techniques with synchrotron nano-single-crystal diffraction that allowed us to obtain the first reliable ab initio crystal structure of this killer zeolite. The refined structure showed regular T-O distances (in the range 1.61-1.65 Å) and extra-framework content in line with the chemical formula (K2.63Ca1.57Mg0.76Na0.13Ba0.01)[Si28.62Al7.35]O72·28.3H2O. The synchrotron nano-diffraction data combined with three-dimensional electron diffraction (3DED) allowed us to unequivocally rule out the presence of offretite. These results are of paramount importance for understanding the mechanisms by which erionite induces toxic damage and for confirming the physical similarities with asbestos fibres.

Comprehensive epithelial biomarker analysis of malignant mesothelioma: EpCAM positivity is a potential diagnostic pitfall.

Epithelial cell adhesion molecule (EpCAM) is frequently used to distinguish carcinoma from background mesothelial cells during cytologic examination of body cavity fluids. Previously, the authors identified one malignant mesothelioma case with strong and diffuse membranous EpCAM staining, making it indistinguishable from carcinoma. In this study, the authors evaluated all available effusion specimens from patients with malignant mesothelioma, including the above-mentioned index case, obtained at Stanford Health Care, from 2011 to 2021 (N=17) as well as control cases (N=5). Analyses included an immunohistochemistry (IHC) assay for EpCAM and claudin-4, a multiplexed immunofluorescent (IF) assay for EpCAM, and an RNA in situ hybridization assay targeting EpCAM. The authors detected EpCAM positivity of variable intensity and percentage in four malignant mesothelioma cases (23.5%; although only two showed positivity for the epithelial-specific IHC marker MOC31 in ≥40% of cells) and claudin-4 negativity in all cases, with two cases displaying focal and weak claudin-4 staining in <1% of cells. Multiplexed IF staining on the cases with EpCAM IHC positivity showed strong, membranous EpCAM staining in one of four cases. RNA in situ hybridization also was used to assess the correlation between EpCAM positivity by IHC/IF and RNA expression levels. Strong EpCAM RNA expression was detected in the three malignant mesothelioma cases. The current findings revealed that a subset of epithelioid malignant mesothelioma cases mimic or exhibit the immunophenotypic features of carcinoma when evaluating for EpCAM only. Additional biomarker testing, such as claudin-4, may help avoid this potential pitfall to yield accurate diagnoses.

A study of somatic BRCA variants and their putative effect on protein properties in malignant mesothelioma.

The aim of this study is to analyze the prevalence of somatic mutations in BRCA1 and BRCA2 in malignant mesothelioma and their putative impact on protein properties. Eighteen cases of malignant mesothelioma were retrieved from the archives and for next generation sequencing analysis of BRCA1 and BRCA2 genes. Variants were analyzed using Ensembl VEP17, Polyphen 2.0 software, SIFT software, MutpredV2, and SWISS-MODEL homology-modeling pipeline server. BRCA2 variants were found in significantly higher percentage (22%) of cases (p=0.02). Five missense variants were identified. These were p.A2351P, p.T2250A, p.A895V, pG1771D, and p.R2034C. The SIFT scores of all except one were ≥ 0.03. The Polyphen scores of these four alterations were ≤0.899. In case of p.A2315, the SIFT score was 0.01, while the Polyphen 2 score was 0.921. MutPred2 scores were ≤0.180 for all. Loss of intrinsic disorder was predicted (Pr=0.32, p=0.07) for p.R2034C, while gain of intrinsic disorder was predicted for p.A2351P (Pr=0.36, p=0.01) and p.G1771D (Pr=0.34, p=0.02). BRCA2 somatic variants were identified in 22% cases of malignant mesotheliomas in this study. The variants localize more frequently to the disordered regions of the protein and are predicted to affect the level of disorder.

Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.

Pleural mesothelioma is rare cancer linked to asbestos exposure. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results(SEER)-Medicare database. Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders. Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy. The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.