Epithelioid Malignant Mesothelioma Research Articles

Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis.

The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.

High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma.

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location‐specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all‐cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet‐derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p < 0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00–1.03 and HR = 1.05, 95% CI = 1.00–1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence‐based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy.

Malignant Pleural Mesothelioma Epidemiology in the United States From 2000 to 2016.

IntroductionPleural mesothelioma constitutes about 80% of all mesotheliomas. The peak incidence of malignant mesothelioma estimated using the cancer registries was in early 1990 to 2000 in the United States. The disease is primarily associated with asbestos exposure. The latency period between asbestos exposure and the development of malignant pleural mesothelioma (MPM) can range anywhere from 15 to 60 years. Asbestos exposure was peaked during the industrial revolution and World War II due to military and shipyard exposures. It is often difficult for the pathologist to distinguish different histological subtypes; due to the disease's rarity and the inadequate tissue sample obtained. There is no available data on the difference in epidemiology of different subtypes of MPM. Surveillance Epidemiology and End Results (SEER), cancer incidence data include population-based registries covering approximately 34.6% of the U.S. population. Here in our study, we analyze malignant pleural mesothelioma epidemiology in the United States, emphasizing different histological subtypes.MethodsSEER data from 2000 to 2016 was used in our study. The primary site of cancer is selected as pleura, and malignant behavior only is selected as the filter. Data were analyzed using the SEER stat program. Overall epidemiology of MPM and epidemiology of epithelioid, fibrous, and biphasic histological subtypes were analyzed separately. We used annual percentage change (APC) to evaluate the trend in the epidemiology of MPM.Results summaryA total of 11,857 cases of MPM were included in the primary cohort from the SEER 18 registry from 2000 to 2016. The total prevalence of MPM was highest in 2009 and was lowest in 2016. The APC in MPM incidence during this period is -2.0. After removing 5,989 cases with non-specified histology during the same period, the APC for each histological type is -0.7 for fibrous type, 1.8 for epithelioid type, and 2.9 for biphasic type. Out of 17 regional registries included in the study, the greatest statistically significant change in APC was seen in the Hawaiian registry -4.1. In contrast, the lowest statistically significant difference was seen in Seattle (Puget Sound) registry -1.7. The APC in the incidence of MPM among males during the study period was -2.4 while that of females was -0.9. The Iowa registry showed a statistically significant increase in APC of the epithelioid malignant mesothelioma with a statistically insignificant reduction in the overall MPM APC.ConclusionThe overall incidence of MPM in the United States is declining, while the data showed an increase in the incidence of epithelioid and biphasic histological subtypes. The authors believe that these conflicting results can be attributed to improved histological diagnosis and improved biopsy techniques.

Tertiary lymphoid structures in epithelioid malignant peritoneal mesothelioma are associated with neoadjuvant chemotherapy, but not with prognosis.

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. The relationship between a strong adaptive immune response and a better prognosis in malignant solid tumors is widely known. Due to the low incidence of epithelioid malignant peritoneal mesothelioma (EMPM), very little is known about their immune micro-environment. We encountered several cases of tertiary lymphoid structures in EMPM in a previous study and aimed to investigate in the same series the prevalence, clinicopathological features, and the prognostic impact associated with tertiary lymphoid structures in EMPM (TLS-EMPM). Cases of EMPM, from 1995 to 2018, were retrieved from 7 French institutions from the RENAPE Network. The predictions in terms of overall survival (OS) and progression-free survival (PFS) of TLS-EMPM were analyzed. We report 52 cases of TLS-EMPM among a series of 138 cases of EMPM. TLS-EMPM was significantly associated with neoadjuvant chemotherapy, and was not a prognostic indicator for OS (p = 0.652) and PFS (p = 0.804) in our series. TLS is a component of the host immune response to EMPM significantly associated with neoadjuvant chemotherapy, but was not a predictor of prognosis for overall and progression-free survivals in this series. These findings provide another possible etiology for tertiary lymphoid structures.

Minimal Change Disease Associated with Malignant Epithelioid Mesothelioma: A Case Report

We report the case of a 64 year old male patient with a recent diagnose of pulmonary nodules with pleural thickening who was admitted to the nephrology department of our hospital for further evaluation of nephrotic syndrome (NS). Malignant epithelioid mesothelioma (MEM) was diagnosed after pleural biopsy while the renal biopsy showed minimal change disease (MCD) with acute tubular necrosis and interstitial lymphoplasmacytic infiltrate. MCD is the most common cause of nephrotic syndrome in children while it accounts for a smaller proportion of NS in adults. The underlying cause of MCD is unclear (Cameron, 1987). Evidence so far suggests that T-cell dysfunction results in the production of a circulating factor directly affecting the glomerular capillary wall with consequent foot process fusion. MCD as paraneoplastic syndrome is common in hematological disorder while the incidence in lung pulmonary malignancies is rare. Early recognition leads to an early diagnosis of malignancy improving the outcome and diminishing the associated co-morbidities.

Establishment and histopathological study of patient-derived xenograft models and primary cell lines of epithelioid malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare malignancy with few experimental models. This study used the human surgical specimen to establish MPM patient-derived xenograft (PDX) models and primary cell lines to provide a study platform for MPM in vitro and in vivo, and conducted histopathological analysis. Our study used the experimental peritoneal cancer index (ePCI) score to evaluate gross pathology, and the results showed that the ePCI score of the female and male nude mice were 8.80 ± 1.75 and 9.20 ± 1.81 (P=0.6219), respectively. The Hematoxylin and eosin (HE) staining of animal models showed that the tumor was epithelioid mesothelioma and invaded multiple organs. Immunohistochemistry (IHC) staining showed that Calretinin, Cytokeratin 5/6, WT-1 and Ki-67 were all positive. The Swiss-Giemsa and Immunofluorescence (IF) staining of primary cell lines were also consistent with the pathological characteristics of mesothelioma. We also performed the whole-exome sequencing (WES) to identify the mutant genes between models and the patient. And the results showed that 21 mutant genes were shared between the two groups, and the genes related to tumorigenesis and development including BAP1, NF2, MTBP, NECTIN2, CDC23, LRPPRC, TRIM25, and DHRS2. In conclusion, the PDX models and primary cell lines of MPM were successfully established with the epithelioid mesothelioma identity confirmed by histopathological evidence. Moreover, our study has also illustrated the shared genomic profile between models and the patient.

Histological comparison of malignant epithelioid mesothelioma in young and adult cattle.

The histology and immunohistochemistry of pleomorphic and conventional epithelioid mesotheliomas were examined. The former was detected in two young calves aged 2 and 4 months and was characterized by pleomorphic and atypical cells with decreased expression of cytokeratin 7 (CK7). In contrast, the latter was found in a 31-month-old heifer, consisting of tumor cells uniform in size and shape with CK7 expression in nearly all cells. Production of collagen by tumor cells was demonstrated in both histological types, and was considered to be characteristic of bovine epithelioid mesothelioma. Pleomorphic mesothelioma is far more pleomorphic and mitotically active than conventional mesothelioma, and its normal counterpart may be immature mesothelial cells with high proliferation potential, which exist in fetal life and early calfhood.

Role of Cytology in the Current Guidelines for Malignant Mesothelioma: Largest Study from India

Introduction: Cytology provides crucial window for early diagnosis of malignant mesothelioma (MM) since it is often the first and easily available material for evaluation, resulting in early treatment. Still, its role is overlooked in the current treatment guidelines. The aim of this study is to determine the sensitivity of cytomorphology and role of subsequent ancillary techniques in diagnosing MM. Methods: This is a 5-year retrospective analysis of MM in the tertiary oncology center to determine sensitivity of cytomorphology and subsequent role of immunohistochemistry (IHC) in final diagnosis of MM according to the guidelines for cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma (GCDMM) laid by International Mesothelioma Interest Group. Cytomorphology and immunocytochemistry from effusions and fine needle aspirations were analyzed. Results: Sixty-two of 128 cases of MM had cytology and cytomorphological criteria described in GCDMM were fulfilled in 61.3% cases. Architectural atypia was useful in identifying cases with low cytological atypia. Overall sensitivity of cytomorphology was 73.01%. Sensitivity of effusion cytology was 77.8%. Subsequent IHC on cell blocks revealed the sensitivity as 100% for mesothelin, calretinin, and cytokeratin 5/6; 87.5% for thrombomodulin; and 50% for WT1, while CEA and TTF1 showed 100% specificity. Treatment was given based on final diagnosis of MM given after IHC on cytology material in only 25.8% cases. However, it was possible in additional 35.5% cases. Mean survival was 10 months when diagnosed by cytology, compared to 7 months by histology. Conclusions: Rather than ignoring the role of cytology in the diagnosis and treatment guidelines for MM, it is important to understand its strengths and limitations. Standardized guidelines in future can play an important role in more streamlined communication between cytopathologist and clinician.

Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases.

Malignant peritoneal mesothelioma historically carried a grim prognosis, but outcomes have improved substantially in recent decades. The prognostic significance of clinical, morphologic, and immunophenotypic features remains ill-defined. This multi-institutional cohort comprises 225 malignant peritoneal mesotheliomas, which were assessed for 21 clinical, morphologic, and immunohistochemical parameters. For epithelioid mesotheliomas, combining nuclear pleomorphism and mitotic index yielded a composite nuclear grade, using a previously standardized grading system. Correlation of clinical, morphologic, and immunohistochemical parameters with overall and disease-free survival was examined by univariate and multivariate analyses. On univariate analysis, longer overall survival was significantly associated with diagnosis after 2000 (P = 0.0001), age <60 years (P = 0.0001), ECOG performance status 0 or 1 (P = 0.01), absence of radiographic lymph-node metastasis (P = 0.04), cytoreduction surgery (P < 0.0001), hyperthermic intraperitoneal chemotherapy (P = 0.0001), peritoneal carcinomatosis index <27 (P = 0.01), absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001). Among epithelioid malignant mesotheliomas only, longer overall survival was further associated with female sex (P = 0.03), tubulopapillary architecture (P = 0.005), low nuclear pleomorphism (P < 0.0001), low mitotic index (P = 0.0007), and low composite nuclear grade (P < 0.0001). On multivariate analyses, the low composite nuclear grade was independently associated with longer overall and disease-free survival (P < 0.0001). Our data further clarify the interactions of clinical and pathologic features in peritoneal mesothelioma prognosis and validate the prognostic significance of a standardized nuclear-grading system in epithelioid malignant mesothelioma of the peritoneum.

Hyperthermic intraoperative intrapleural chemotherapy and surgical cytoreduction as part of multimodal treatment of malignant pleural mesothelioma – case report

Malignant pleural mesothelioma is one of the most aggressive malignancies with a very poor prognosis. Multimodal treatment consisting of three modalities – chemotherapy, radiotherapy and cytoreductive surgery is optimal. The use of new therapeutic modalities, such as hyperthermic intraoperative intrapleural chemotherapy or photodynamic therapy can improve the current results of mesothelioma treatment. Combined hyperthermic intraoperative chemotherapy and cytoreductive surgery as part of multimodal therapy of malignant mesothelioma has been used since 2017 at the 1st Department of Surgery of University Hospital Olomouc. The authors report the case of a 47-year-old man with malignant epithelioid mesothelioma of the left pleural cavity. Following neoadjuvant chemotherapy, this patient underwent extrapleural pneumonectomy with intraoperative intracavitary hyperthermic chemotherapy. The postoperative period was complicated by circulatory instability and later by tension fluidothorax with signs of heart failure. Currently, 8 months have elapsed from the surgery and the patient remains without any signs of recurrence.

HEART FAILURE OR MALIGNANT MESOTHELIOMA? A RARE PRESENTATION OF A RARE DISEASE

SESSION TITLE: Medical Student/Resident Disorders of the Pleura Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Malignant pleural mesothelioma is a rare asbestos-related neoplasm that typically presents with nonspecific symptoms such as dyspnea, cough, and chest pain. Imaging usually reveals unilateral pleural disease. Here we present a case of a man who presented with bilateral disease and initial suspicion for cardiogenic etiology. CASE PRESENTATION: A 88-year-old man presented with 2 months of progressive dyspnea on exertion, orthopnea, and unintentional weight loss of 30 pounds. Past medical history included nonobstructive coronary artery disease, chronic diastolic heart failure, diabetes, hypertension, and alcohol abuse. Social history was notable for asbestos exposure through building construction. Physical exam revealed a new oxygen requirement and decreased breath sounds on auscultation bilaterally without other signs of hypervolemia. Troponin-T and NT-proBNP were normal. Chest X-ray showed mild cardiomegaly with bilateral pleural effusions and prominence of the pulmonary vasculature. Cardiac stress test showed a partial inferior reversible perfusion defect, which led to plans for catheterization and echocardiogram. Thoracentesis revealed an exudative effusion (protein 4.3, LDH 271) with negative cytology. Pulmonary function testing showed restrictive lung disease with DLCO 48%. A chest CT scan revealed diffuse interstitial thickening with bilateral bronchial wall and pleural thickening, and a medial right lower lobe mass-like consolidation. PET/CT showed FDG-avid pleural thickening bilaterally with multiple FDG-avid lymph nodes. Ultrasound-guided core biopsy of the right pleura revealed epithelioid malignant mesothelioma. DISCUSSION: Malignant pleural mesothelioma can cause exudative pleural effusions and requires a tissue biopsy for definitive diagnosis. Studies suggest the disease is bilateral in only 10% of cases. As seen in this patient, bilateral pleural effusions in the setting of a recent positive stress test with known CHF history may lead providers to initially attribute the effusions to CHF and possibly defer thoracentesis. Rare presentations of rare diseases are likely low on a provider’s initial differential diagnosis, but thoracentesis should be considered for new effusions especially if there is clinical suspicion for an alternative etiology to CHF. Further diagnostic evaluation may be required if thoracentesis does not yield a definitive diagnosis. Had pulmonary work-up not been pursued for this patient, the diagnosis of malignant mesothelioma may have been delayed. CONCLUSIONS: Malignant pleural mesothelioma should be considered when evaluating new pleural effusions in patients with respiratory symptoms and known asbestos exposure. This case also highlights the importance of maintaining a broad differential diagnosis for a patient with new nonspecific respiratory symptoms. Reference #1: Neumann, V.; Löseke, S.; Nowak, D.; Herth, F.J.; Tannapfel, A. Malignant pleural mesothelioma: Incidence, etiology, diagnosis, treatment, and occupational health. Dtsch. Arztebl. Int. 2013;110:319–326. Reference #2: Gill RR. Imaging of mesothelioma. Recent Results Cancer Res. 2011;189:27-43. Reference #3: Karkhanis VS, and Joshi JM. Pleural effusion: diagnosis, treatment, and management. Open Access Emerg. Med. 2012;4:31–52. DISCLOSURES: No relevant relationships by Sydney Bowmaster, source=Web Response No relevant relationships by Matthew Gosse, source=Web Response No relevant relationships by Jeff Wilson, source=Web Response

Headspace analysis of mesothelioma cell lines differentiates biphasic and epithelioid sub-types

Malignant mesothelioma (MM) is an incurable cancer. MM is often misdiagnosed, with a poor 5-year survival and limited treatment options. The discovery of endogenous volatile organic compounds (VOCs) is required in order to accelerate the development of a breath test as an alternative to conventional MM diagnosis. For the first time, this study used solid-phase microextraction and gas chromatography-mass spectrometry to identify VOCs released directly from the biphasic MM cell line MSTO-211H and the epithelioid MM cell line NCI-H28 as well as the non-malignant mesothelial cell line MET-5A. Multivariate statistical analysis showed separation between MSTO-211H, NCI-H28 and MET-5A results. 2-ethyl-1-hexanol was significantly increased in both MSTO-211H and NCI-H28 cells compared to MET-5A controls. In addition, ethyl propionate and cyclohexanol were significantly increased in MSTO-211H cells and dodecane was significantly increased in NCI-H28 cells. This is the first study reporting headspace analysis of these MM cell lines and the first to consider the effects of mesothelioma sub-type on VOC profile. Current results further highlight the potential for a diagnostic mesothelioma breath test as well as providing proof of concept for the differentiation between biphasic and epithelioid mesothelioma based on VOC profiles.

Malignant mesothelioma metastatic to the oral region and latest topics (Review).

Malignant mesothelioma (MM) is a rare neoplasm with poor prognosis that usually develops after exposure to asbestos, and is characterised by aggressive local invasion and metastatic spread. While metastasis to the oral cavity is very rare, a total of 23 cases of MM metastasising to the oral cavity were identifed. Among those, the tongue was the most common site of metastasis (39.1%), and frequently involved the epithelioid MM cell type. Recent studies have elucidated the mechanisms underlying the development of MM. Chronic inflammation has been implicated in promoting MM growth and was shown to play a key role by driving the release of high mobility group box protein 1 following asbestos deposition. Inherited heterozygous germline mutations in the deubiquitylase BRCA-associated protein 1 were shown to increase the incidence of MM in some families. Infection by the simian virus 40 was also found to be associated with the occurrence of MM. Moreover, the increasing incidence rates of MM, together with its propensity to metastasise to the oral cavity, indicate that clinicians and pathologists should be highly aware of this disease. Furthermore, identification of novel serum biomarkers would enable better screening and treatment of MM, and improve the survival outcomes.

Nucleolin and nucleophosmin expression patterns in pulmonary adenocarcinoma invading the pleura and in pleural malignant mesothelioma.

BackgroundVisceral pleural invasion (VPI) in adenocarcinoma of the lung is considered a poor prognostic factor. The purpose of this study was to analyze nucleolin and nucleophosmin expression in pulmonary adenocarcinoma (PA) with VPI and in pleural malignant mesothelioma.MethodsThe study was conducted on the basis of 19 pathologically‐confirmed cases of adenocarcinoma of the lung and 29 cases of epithelioid malignant mesothelioma. The nucleolin and nucleophosmin expression was assessed immunohistochemically and analyzed with image analysis software.ResultsNucleolin expression was lower while nucleophosmin was higher in pleural invasion of pulmonary adenocarcinoma than in the central part of the tumor. Differences in subpopulations of cells with different expression of proteins studied were also found. Malignant mesothelioma showed lower nucleolin expression than adenocarcinoma of the lung but no differences in nucleophosmin expression were found.ConclusionsThe results of our study suggested that lower nucleolin and higher nucleophosmin expression may be related to higher invasiveness of adenocarcinoma of the lung. Differences in nucleolin expression between pulmonary adenocarcinoma and malignant mesothelioma indicate another aspect of biology of these pleura‐invading cancers that requires further study.Key pointsSignificant findings of the studyDifferences in nucleolin and nucleophosmin expression in pleura invading pulmonary adenocarcinoma indicate the involvement of these proteins in its locoregional spread while differences in nucleolin expression between pulmonary adenocarcinoma and malignant mesothelioma suggest another aspect of biology of these cancers.What this study addsThis is the first study on nucleolin and nucleophosmin expression in pleural malignant mesothelioma and pleura‐invading pulmonary adenocarcinoma. Our findings may assist in understanding the mechanisms of locoregional spread of adenocarcinoma and differences between these two pleura‐invading cancers.

Claudin-4 shows superior specificity for mesothelioma vs non–small-cell lung carcinoma compared with MOC-31 and Ber-EP4

The distinction of malignant mesothelioma from non-small-cell lung carcinoma (NSCLC) usually requires immunohistochemistry, but some broad-spectrum carcinoma markers stain mesotheliomas, and it remains unclear which broad-spectrum markers are most valuable for distinguishing these malignancies. Here, we directly compared the sensitivity and specificity of three broad-spectrum carcinoma markers, claudin-4, Ber-EP4, and MOC-31, for distinguishing NSCLC from mesothelioma. Immunohistochemistry was performed on tissue microarrays containing 68 epithelioid mesotheliomas, 31 sarcomatoid mesotheliomas, and 147 non-small-cell lung cancers (53 adenocarcinomas, 60 squamous cell carcinomas, 13 large-cell carcinomas, and 21 sarcomatoid carcinomas). For adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma, claudin-4 staining was present in 103 of 126 cases (82%), MOC-31 staining was present in 112 of 126 cases (89%), and Ber-EP4 staining was present in 113 of 126 cases (90%); these values were not statistically different. Claudin-4 stained 0 of 68 (0%), MOC-31 stained 22 of 68 (32%), and Ber-EP4 stained 24 of 68 (35%) epithelioid mesotheliomas; thus, the specificities for NSCLC versus epithelioid mesothelioma were 100%, 68%, and 65%, respectively. Claudin-4 staining was present in 7 of 21 (33%), MOC-31 staining was present in 8 of 21 (38%), and Ber-EP4 staining was present in 5 of 21 (24%) sarcomatoid carcinomas. All three markers were negative in 12 of 21 (57%) sarcomatoid carcinomas. Sarcomatoid mesotheliomas were not stained with any of these markers. We conclude that claudin-4 has considerably greater specificity and comparable sensitivity to MOC-31 and Ber-EP4 for distinguishing NSCLC from epithelioid malignant mesothelioma. The use of all three markers may be necessary for sarcomatoid neoplasms, given their limited sensitivity.

Effusion cytology of malignant mesothelioma enables earlier diagnosis and recognizes patients with better prognosis.

A conclusive diagnosis of malignant mesothelioma (MM) can be based on effusion cytology using the guidelines for the cytopathologic diagnosis of epithelioid and mixed-type MM. Briefly, the diagnosis is obtained when the mesothelial phenotype of malignant cells is established by ancillary techniques. This study is based on the comparison of the overall survival rates of patients with MM when diagnosed by effusion cytology, histopathology, or a combination of both. A total of 144 patients were diagnosed with epithelioid and mixed-type pleural MM at Karolinska University Hospital between 2004 and 2013. The diagnosis was obtained by histopathology in 74 cases and by cytological examination of pleural effusion in 70 cases. In 29 of the latter cases, a diagnostic biopsy was obtained simultaneously. A total of 104 patients received chemotherapy. All diagnoses were supported by clinical findings, including computer tomography scans. The median time between first symptoms and diagnosis was similar for cytology and histopathology. However, a delay of more than 6 months after first symptoms was seen in many patients in the histopathology group, resulting in late onset of treatment. The overall survival and proportion of long-term survival were significantly better for cases diagnosed by cytology. Similarly, a better survival, following a cytological diagnosis, was also seen in patients who were only provided the best supportive care. Accurate cytological diagnosis enables conclusive diagnosis of MM. Our finding enables the initiation of treatment as soon as the cytological diagnosis is established, avoiding further delay and deterioration of patient survival and possibilities for treatment.

Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary statement from the international mesothelioma interest group, also endorsed by the international academy of cytology and the papanicolaou society of cytopathology. A proposal to be applauded and promoted but which requires updating.

The guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma produced by the International Mesothelioma Interest Group and which are endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology are reviewed and discussed. This (predominantly) evidence-based document provides a robust and useful framework for diagnosticians and guideline producers to emphasise and promote the value, power and role of cytology in mesothelioma diagnosis and management with comments and suggestions about how the guidelines can be updated and improved in the future.

Intraparenchymal epithelioid malignant mesothelioma: A case report

There are very few cases of malignant mesothelioma (MM) presenting as interstitial lung disease (ILD) reported in the literature, and distinguishing this rare subtype of MM from nonmalignant etiologies is crucial to avoid misdiagnosis and delayed treatment. Here we describe a case of ground glass opacities (GGO) identified on radiological imaging that were biopsy proven to represent epithelioid MM.

The phytohormone forchlorfenuron decreases viability and proliferation of malignant mesothelioma cells in vitro and in vivo.

Malignant mesothelioma (MM) is one of the most aggressive cancer types with a patient’s life expectancy of typically less than one year upon diagnosis. The urgency of finding novel therapeutic approaches to treat mesothelioma is evident. Here we tested the effect of the plant-growth regulator forchlorfenuron (FCF), an inhibitor of septin function(s) in mammalian cells, on the viability and proliferation of MM cell lines, as well as other tumor cell lines derived from lung, prostate, colon, ovary, cervix and breast. Exposure to FCF strongly inhibited proliferation of human and mouse (most efficiently epithelioid) MM cells and all other tumor cells in a concentration-dependent manner and led to cell cycle arrest and cell death. The role of septin 7 (SEPT7), a presumably essential target of FCF in MM cells was confirmed by an shRNA strategy. FCF was robustly inhibiting tumor cell growth in vitro at low micromolar (IC50: ≈20-60µM) concentrations and more promisingly also in vivo. Initial experiments with FCF analogous revealed the importance of FCF’s chloride group for efficient cell growth inhibition. FCF’s rather low systemic toxicity might warrant for an extended search for other related and possibly more potent FCF analogues to target MM and putatively other septin-dependent tumors.

2613 A Rare Case of Undifferentiated Malignant Epithelioid Neoplasm

INTRODUCTION: The small bowel is rarely a site for development of tumor malignancy and accounts for less than 1% of all GI malignancies. We present a case of a 53-year-old male with recurrent episodes of gastrointestinal bleeding and negative upper and lower GI endoscopies found to have high-grade undifferentiated high-grade malignant epithelioid neoplasm. CASE DESCRIPTION/METHODS: A 53-year old male with history of peptic ulcer disease, duodenal ulcer perforation presented to the ED with right upper and lower extremity pain for last few weeks along with black stools. He had required several units of blood transfusion with recurrent admissions to hospital and had also lost about 20 lbs in last 2 months. EGD and colonoscopy 3 months before had shown duodenal angiectasia and colonic polyps which were removed. Outpatient capsule endoscopy was recommended but patient did not follow up. Bleeding scan was negative and CT abdomen pelvis with contrast showed thickening in distal jejunum concerning for mass-like lesion. Patient underwent laparoscopic small bowel resection of 18 cm and pathology showed high-grade undifferentiated malignant epithelioid neoplasm with macro-metastatic tumor. The tumor showed diffuse staining for vimentin,pancytokeratin, CK7 with subset moderate cytoplasmic staining for calretinin and CK8/18.Port-A-Cath was placed and patient was started on standard adjuvant chemotherapy including combination of 5-FU, leucovorin, and oxaliplatin. DISCUSSION: Small bowel tumors are very rare and aggressive and have poorer prognosis than colon cancer. They present a diagnostic challenge as access to small bowel is limited during conventional diagnostic procedures and symptoms present late. We present a patient who was having recurrent gastrointestinal bleeding requiring multiple blood transfusions and found to have high-grade undifferentiated high-grade malignant epithelioid neoplasm. The differential for this includes monophonic synovial sarcoma, malignant epithelioid mesothelioma, and large cell lung carcinoma vs others. Video capsule endoscopy has rapidly become the conventional standard for small bowel evaluation, followed by other methods such as magnetic resonance enteroclysis. Standard chemotherapy treatment closely resembles that of large bowel cancer, including combinations of 5-FU, leucovorin, and oxaliplatin/irinotecan/capecitabine.