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Malignant mesotheliomas (MMs) are malignancies of the mesothelium, with primary deposits originating in the pleura, peritoneum, pericardium and the tunica vaginalis (ie, testicular). Metastatic spread is commonly reported to affect the liver, adrenal glands, kidney and contralateral lung (in cases of malignant pleural mesothelioma). Metastases to distant sites are uncommon. Spread to the oral cavity in particular is very rare. A total of 23 cases of metastatic spread to the oral cavity have been reported in the literature to date; of those, 9 cases have been to the tongue. Given the rarity of the site of metastasis, the management remains challenging. This case highlights a rare site of metastasis in MM, discusses treatment options available and briefly talks about technical limitations in treating a mobile structure such as the tongue. Good palliative and supportive care is crucial in managing cases where no curative treatment is possible.

Mesothelioma in situ has been proposed as a precursor to malignant mesothelioma arising in the pleura or peritoneum. We report a case of malignant peritoneal mesothelioma which progressed from mesothelioma in situ over a 10-mo period in a 24-yr-old woman with stage IV endometriosis. Initial surgery showed deeply infiltrative endometriosis with progestin effect. Postoperatively the patient had intractable pelvic pain and vaginal discharge. Imaging studies were negative. Repeat laparoscopy 10 mo later revealed vesicular lesions on the omentum and pinpoint white lesions studding the small bowel, appendix, and pelvic peritoneum. A diagnosis of epithelioid mesothelioma was established on biopsy of the omentum and confirmed by immunohistochemistry showing complete loss of BRCA1-associated protein-1 (BAP1) nuclear staining. Retrospectively, BAP1 loss was identified in the cytologically bland, single-layer surface mesothelium of the prior resection specimen, consistent with mesothelioma in situ . The patient underwent genetic testing and was found to have a pathogenic germline mutation in BAP1 .

Post-operative adhesions are a leading cause of abdominal surgery-associated morbidity. Exposed fibrin clots on the damaged peritoneum, in which the mesothelial barrier is disrupted, readily adhere to surrounding tissues, resulting in adhesion formation. Here we show that resident F4/80HighCD206− peritoneal macrophages promptly accumulate on the lesion and form a ‘macrophage barrier’ to shield fibrin clots in place of the lost mesothelium in mice. Depletion of this macrophage subset or blockage of CD11b impairs the macrophage barrier and exacerbates adhesions. The macrophage barrier is usually insufficient to fully preclude the adhesion formation; however, it could be augmented by IL-4-based treatment or adoptive transfer of this macrophage subset, resulting in robust prevention of adhesions. By contrast, monocyte-derived recruited peritoneal macrophages are not involved in the macrophage barrier. These results highlight a previously unidentified cell barrier function of a specific macrophage subset, also proposing an innovative approach to prevent post-operative adhesions., Peritoneal adhesions are a major cause of complications after abdominal surgery. Here the authors use a post-operative abdominal adhesion model in mice to show that resident F4/80HighCD206− macrophages form a protective barrier that can be enhanced by IL-4 administration or adoptive transfer of these cells.

Since the original description of pathogenic germline DICER1 variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be associated with DICER1 has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye, and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and DICER1-associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3-14 years). Primary sites of origin included the fallopian tube (four cases), serosal surface of the colon (one case), and pelvic sidewall (two cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB, and the remaining five had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic DICER1 variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of DICER1 pathogenic variation whose pathologic features are also recapitulated in DICER1-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli-Leydig cell tumors with heterologous elements. Tumors arising from the fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor DICER1 testing.

The paper provides a brief data overview of the national and the foreign recent decades literature on various aspects of the morphofunctional organization of the greater omentum in the physiological and various pathological states of the organism (in the process of morphogenesis, in the conditions of age-related alterations, under various experimental exposures, as well as in the postoperative transformations after surgical interventions due to inflammatory and tumor processes). The data on morphofunctional organization of the greater omentum main tissue components (mesothelium, adipose and lymphoid tissues) have been analyzed and summarized.

Introduction. The canal of Nuck is an embryological remnant of the peritoneal pouch that extends into the labium majus of women. Hydrocele is the most common presentation, but only a small number of cases are reported in association with endometriosis.Case Presentation. The patient is a 45-year-old woman who presented with left inguinal mass with persistent pain. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 30 mm cystic mass, and a hydrocele of the canal of Nuck (HCN) was suspected. The excised mass was a cyst containing yellow-tan serous fluid, and the cyst wall was lined by mesothelium. The morphology was consistent with conventional HCN. However, since several foci of endometrial-like epithelium and stroma were identified beneath the mesothelium, the mass was diagnosed with HCN with endometriosis (EM-HCN).Discussion. Right-side dominance of EM-HCN is suggested by several authors, but a thorough review has never been performed. For the first time, we reviewed the literature and statistically confirmed that EM-HCNs dominantly occur on the right side compared to those without endometriosis. We consider that this supports the theory that endometriosis derives from retrograde menstruation of endometrial tissue through fallopian tubes. When endometriosis is discovered in HCN, the clinician should be aware of the possibility of pelvic endometriosis.

Background: Podoplanin (D2-20) stains immunohistochemically lymphatic vessels, regular mesothelium and tumor cells of different tumors, e.g. malignant mesothelioma or seminoma. In squamous cell carcinoma (SCC), the marker has been described as variously expressed. Methods: This study has investigated the value of the immunohistochemical analysis for the prognostic relevance of the expression in 119 SCCs of the larynx and hypopharynx. The clinical data and documentation of follow-up for at least 5 years were available. Results: The collective showed the expected distribution of patient age with accentuation of the male sex and a balanced spread of tumor stages including nodal status. The immunohistochemical stain intensity (negative, weak or strong) and the distribution (equal versus focal) were evaluated. In addition, the accentuation of the staining reaction was separately examined at the border of invasion. SCCs with a strong expression of podoplanin were associated with an unfavorable prognosis. A comparison of grouped cases showed a trend emerging with borderline results (negative to weakly positive, P = 0.51; negative to strongly positive, P = 0.054; weakly positive to strongly positive, P = 0.17). The staining at the border of invasion had no statistical effect on overall survival. Multivariate survival statistics however showed that lymphonodal metastasis and a reaction with podoplanin in tumor cells are associated with significant worse prognosis. Conclusion: In summary, regardless of the exact function of podoplanin in the process of cell migration and tumor progression, an immunohistochemical identification of expression in tumor cells of SCC of the larynx and hypopharynx can give additional information about the expectable prognosis. World J Oncol. 2020;11(2):65-71 doi: https://doi.org/10.14740/wjon1259

Malignant mesothelioma is an aggressive tumor that originates from the lining cells (mesothelium) that cover the serosal surfaces of the pleural and peritoneal cavities, or more rarely the tunica vaginalis testis and the pericardium (Moore et al. 2008). Based on the stage of the disease at the time of diagnosis, mesothelioma may present as discrete multifocal nodules or as a diffuse confluent mass encasing the adjacent organs and/or obliterating the serosal cavity from which the tumor has originated.

Malignant mesothelioma (MM), the primary cancer of the mesothelium, is characterized by dismal prognosis. However, there are other forms of primary mesothelial tumors, which are benign, the adenomatoid tumors (AT) and the well-differentiated papillary mesothelial tumor (WDPMT, formerly called well-differentiated papillary mesothelioma) (1). Interestingly, two recent studies showed that both ATs and WDPMTs harbor mutations in the TRAF7 (2,3), suggesting a possible pathogenetic link between them (1). The authors further proposed that as a possible consequence of this mutation, the L1 cell adhesion molecule (L1CAM), should be expressed in these lesions (2,3). Indeed, after performing immunohistochemistry for this marker, they showed L1CAM expression in both ATs and WDPMTs. Another lesion that could enter the family of benign mesothelial lesions, is the so-called "multicystic mesothelioma" (4). The exact nature of this lesion, reactional or neoplastic, has been a matter of debate since decades, and their varied terminology does prove the uncertainty (4). Given their common mesothelial origin, we aimed to explore the possible expression of L1CAM in a large series of cystic mesothelial lesions.

Congenital diaphragmatic hernia (CDH) is a structural birth defect characterized by a diaphragmatic defect, lung hypoplasia and structural vascular defects. In spite of recent developments, the pathogenesis of CDH is still poorly understood. CDH is a complex congenital disorder with multifactorial etiology consisting of genetic, cellular and mechanical factors. This review explores the cellular origin of CDH pathogenesis in the diaphragm and lungs and describes recent developments in basic and translational CDH research.

A 9-y-old, castrated male, domestic medium-hair cat diagnosed previously with chronic kidney disease developed anorexia and vomiting. Ultrasonography revealed abdominal effusion and a left renal perihilar mass. Cytologic evaluation of the peritoneal fluid and mass identified atypical epithelioid cells suspected to be of renal epithelial or possible mesothelial origin. Immunohistochemical (IHC) evaluation of a formalin-fixed, paraffin-embedded peritoneal fluid cell block indicated both pancytokeratin and vimentin expression in the atypical epithelioid cell population. With scanning electron microscopic evaluation, similar epithelioid cells lacked the cell-surface microvilli expected of mesothelium, supporting an antemortem diagnosis of probable carcinoma. On postmortem examination, the left kidney was effaced by an infiltrative neoplasm with myriad similar nodules throughout the peritoneum. The neoplasm was composed primarily of polygonal-to-spindle-shaped cells with strong vimentin and weak pancytokeratin cytoplasmic immunolabeling. Further IHC characterization with PAX8, CK18, KIT, napsin A, SMA, desmin, CD18, and claudin 5 was performed. Histologic and IHC findings supported a diagnosis of sarcomatoid renal cell carcinoma with peritoneal carcinomatosis. An in vitro cell culture line of neoplastic cells harvested from the primary tumor was successfully established for future research endeavors.

Primary peritoneal malignant mesothelioma (MM) can demonstrate morphologic overlap with low-grade and high-grade tubo-ovarian serous neoplasms; it is also biologically and prognostically distinct from benign mesothelial proliferations. Currently, there is no single biomarker that can definitively distinguish these neoplasms. Sex-determining region Y box 6 (SOX6) immunohistochemistry has been recently described to differentiate pleural epithelioid MM from lung adenocarcinoma, but it has not been evaluated in the peritoneum. SOX6 immunohistochemistry was performed on 43 peritoneal epithelioid MM, 7 peritoneal biphasic MM, 5 well-differentiated papillary mesotheliomas, 5 serous borderline tumors, 29 low-grade serous carcinomas (LGSCs), 20 high-grade serous carcinomas (HGSCs), and 25 cases of peritoneal reactive mesothelial hyperplasia. Quantitative SOX6 expression in epithelioid MM (median, 100% of tumor cells) was significantly greater than in LGSC/serous borderline tumor (median, 90%; P=0.004) and HGSC (median, 45%; P=0.0001). However, when SOX6 is expression is defined as ≥10% of tumor cells, there was no significant difference in the rate of SOX6 positivity between epithelioid MM (41/43, 95%), LGSC (28/29, 97%; P=1.0), and HGSC (17/20, 85%; P=0.16). Quantitative extent of SOX6 expression in epithelioid MM was significantly greater than in biphasic MM (median, 0%; P=0.0001), well-differentiated papillary mesothelioma (median, 20%; P=0.001), and reactive mesothelial hyperplasia (median, 20%; P=0.0001), but not significantly different from flat quiescent mesothelium (median, 90%; P=0.82). SOX6 immunohistochemistry is 95% sensitive for peritoneal epithelioid MM, but is also consistently expressed in LGSC and HGSC, negating its usefulness in this common differential diagnosis. SOX6 also shows variable expression across the spectrum of reactive, benign neoplastic, and malignant mesothelial lesions of the peritoneum, and does not appear to be diagnostically useful in distinguishing benign from malignant mesothelial proliferations.

Summary The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides a first layer of immunological defense within the abdomen. Here, we investigated the mechanisms that mediate the capture of peritoneal contaminants during peritonitis. Single-cell RNA sequencing and spatial analysis of omental stromal cells revealed that the surface of FALCs were covered by CXCL1+ mesothelial cells, which we termed FALC cover cells. Blockade of CXCL1 inhibited the recruitment and aggregation of neutrophils at FALCs during zymosan-induced peritonitis. Inhibition of protein arginine deiminase 4, an enzyme important for the release of neutrophil extracellular traps, abolished neutrophil aggregation and the capture of peritoneal contaminants by omental FALCs. Analysis of omental samples from patients with acute appendicitis confirmed neutrophil recruitment and bacterial capture at FALCs. Thus, specialized omental mesothelial cells coordinate the recruitment and aggregation of neutrophils to capture peritoneal contaminants., Graphical Abstract, Highlights • Specialized Cxcl13+ mesothelial cells cover the surface of FALCs and secrete CXCL1 • CXCL1 mediates the recruitment of neutrophils to omental FALCs during peritonitis • PAD4-dependent neutrophil aggregates mediate the capture of zymosan by the omentum • Neutrophils form NETs on the omentum of patients with appendicitis, For decades, the omentum has been known as the policeman of the abdomen. Jackson-Jones et al. reveal the existence of specialized mesothelial cells within fat-associated lymphoid clusters of the omentum that are responsible for the capture of peritoneal contaminants via the formation of neutrophil aggregates, preventing systemic spread.

A 61-year-old man presented with complaints of abdominal pain, loss of weight, and splenomegaly since past 6 months. On computed tomography, the spleen was totally replaced by multiloculated cysts and splenectomy was performed. Pathological examination revealed a low-grade mucinous adenocarcinoma. Postoperative PET scan was negative, and in the absence of a primary tumor elsewhere, we considered this tumor to be primary in the spleen, and it was presumed that the tumor arose from invaginated capsular mesothelium of the spleen.

Objective: Immunocytochemistry (ICC) of serous effusion is an important tool for the diagnosis of benign and malignant cells. Our aim was to develop a modified liquid-based cytological technique for ICC (i.e., a modified LBC). Methods: Serous effusions of 110 cases were collected for cytological examination: 50 were negative for malignancy albeit benign mesothelium was found, and 60 were confirmed metastatic adenocarcinoma according to the modified LBC preparation. The latter were stained for EMA, Ber-EP4, Calretinin, and p63 then interpreted by both a cytotechnologist and a pathologist. A comparative analysis of the diagnostic results was conducted. Results: The results of the metastatic adenocarcinoma were 100% (60/60) positive for EMA and 91.7% (55/60) positive for Ber-Ep4 but negative for calretinin and p63. Cases negative for malignancy were 100% (50/50) positive for calretinin but negative for carcinoma markers. The difference between ‘positive for metastatic adenocarcinoma’ and ‘negative for malignancy’ in ICC was statistically significant (p < 0.001). Conclusion: The current study demonstrated that a panel marker, comprising EMA, Ber-EP4, and calretinin can be used for differentiating between cases of metastatic adenocarcinoma and benign mesothelium. The serous effusion specimen collected by the modified LBC technique is an effective preparation method for ICC.

Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.

Mesothelial cells line the surface of the pleura, pericardium, peritoneum and internal reproductive organs. One of their main functions is to act as a non-adhesive barrier to protect against physical damage, however, over the past decades their physiological and pathological properties have been revealed in association with a variety of conditions and diseases. Mesothelium has been used in surgical operations in clinical settings, such as omental patching for perforated peptic ulcers and in glutaraldehyde-treated autologous pericardium for aortic valve reconstruction. Various methods for mesothelial cell transplantation have also been established and developed, particularly within the area of tissue engineering, including scaffold and non-scaffold cell sheet technologies. However, the use of mesothelial cell transplantation in patients remains challenging, as it requires additional operations under general anesthesia in order to obtain enough intact cells for culture. Moreover, the current methods of mesothelial cell transplantation are expensive and are not yet available in clinical practice. This review firstly summarizes the history of the use of mesothelial cell transplantation in tissue engineering, and then critically discusses the barriers for the clinical application of mesothelial cell transplantation. Finally, the recent developments in xenotransplantation technologies are discussed to evaluate other feasible alternatives to mesothelial cell transplantation.

The changes associated with condemned lungs in cattle with chronic pleural lesions of the caudal lobes were characterized by histology and immunohistochemistry (IHC). Fibroproliferative pleural lesions were microscopically confirmed. Occasionally, the pleural lesions also included adipose, chondroid, and osseous metaplasia that were covered by mesothelial cells, mostly in the absence of inflammation. Other lungs also showed fibrosis in the subpleural interstitium and interlobular septa. In both condemned and noncondemned lungs, immunoreactivity to Wilms tumor 1 (WT1) was normally observed on surface mesothelial cells but not on the submesothelial fibroblasts and myofibroblasts. Conversely, the myofibroblasts beneath the pleura, but not the mesothelial cells, showed immunoreactivity to alpha smooth muscle actin and calponin. However, in the lungs with myofibroblastic foci in the pleura, the proliferated cells maintained WT1 immunoreactivity similar to those of some metaplastic cells. These findings may reflect the plasticity of mesothelial cells in vivo.

Background Cell blocks and immunohistochemistry (IHC) are increasingly recognized as being complementary tools for cytologic diagnostics, especially for neoplastic diseases. Objectives The study aimed to evaluate the utility of cell tube block (CTB) IHC for refining the diagnosis of effusions in dogs and cats. Methods Cavitary effusions (n = 25) from dogs and cats classified by cytology as reactive, neoplastic, borderline (suspicious of neoplasia), and chylous were studied. CTB sections were stained with H&E, and immunostained with PAX-5, CD3, pancytokeratin (CK), vimentin, and Wilms tumor 1 protein (WT1) antibodies, according to the cytologic diagnoses. A histologic case series of confirmed normal, reactive, and neoplastic mesothelium and several different carcinomas were included to test the utility of WT1 as a marker of mesothelial cells. Results CTBs had a layered appearance with reduced background staining. CD3 and PAX5 immunolabeling allowed immunophenotype assessment in all of the lymphoma cases. In carcinomatous effusions, neoplastic cells were CK-positive, WT1-negative, and vimentin-negative (except for two cases). Wilms tumor 1 protein was positive in the nuclei of normal, reactive, and neoplastic mesothelial cells, and ovarian carcinomatous cells. Other carcinomas and lymphomas were negative. Conclusions CTBs are valuable tools to assist in making a diagnosis of cavitary effusions in dogs and cats, and WT1 is a promising marker to differentiate mesothelial from carcinomatous cells.

There is a significant clinical need for small vascular grafts1 mm in diameter.The structure and composition of swine pulmonary visceral pleura (PVP) were investigated. Two processes, glutaraldehyde (GA) crosslink and decellularization (dc) plus GA crosslink, were used to inhibit the immune response. The thrombosis-resistance of the GA-crosslinked PVP (GA-PVP) was determined with in vitro and in vivo studies. Small vessel grafts with 0.7 diameter mm were constructed using the GA-PVP and surgically interposed in the femoral artery of rats for up to 24 weeks. Blood flow in the GA-PVP grafts were measured and ex vivo vascular reactivity of the prostheses were evaluated along with immuno-histological analysis.The GA-PVP mesothelium contains abundant glycocalyx-like substance and a smooth surface. The mechanical properties of the GA-PVP were similar to the femoral artery of rat in the range of physiological pressures. The in vitro and in vivo studies confirmed poor platelet adhesion on the GA-PVP mesothelial surface in comparison with dc processed PVP (dc-PVP). Patency of the GA-PVP prostheses in femoral arteries of rats was 86% in the 24 weeks postoperative period while patency of dc-PVP in femoral arteries of rats was 33% at 1 week postoperative period. Blood flow in the GA-PVP prostheses were not statistically different than the contralateral femoral artery. Biomarkers of neo-endothelial cells, neo-media smooth muscle cells, and extracellular matrices were observed in the GA-PVP prostheses. The significant agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and further amplified in the 24 weeks postoperative, which suggests self-assembly of functional neo-endothelium and neo-media.The high patency and functionality of the small grafts suggest that the GA-PVP is a promising prosthetic biomaterial for vascular reconstructions.Small artery graft (diameter1 mm) in the peripheral circulation that functionally arterializes has not been possible primarily due to thrombosis. Our findings indicate that lung visceral pleura may address thrombogenicity as the major pitfall in small diameter grafts. Here, grafts of 0.7 mm diameter were constructed from swine pulmonary visceral pleura (PVP) and implanted into femoral artery position of rats up to 24 weeks. The total patency of grafts in femoral arteries of rats was 86% in the 24-week period. The neo-endothelial and -medial layers were assembled in the grafts as evidenced by robust biomarkers of endothelial cells, smooth muscle cells, and extracellular matrices observed in the grafts. Agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and were amplified at 24 weeks. The high patency of the small grafts suggests that the PVP is a promising prosthetic biomaterial for vascular reconstructions.

Post-surgical adhesions are internal scar tissue and a major health and economic burden. Adhesions affect and involve the peritoneal lining of the abdominal cavity, which consists of a continuous mesothelial covering of the cavity wall and majority of internal organs. Our understanding of the full pathophysiology of adhesion formation is limited by the fact that the mechanisms regulating normal serosal repair and regeneration of the mesothelial layer are still being elucidated. Emerging evidence suggests that mesothelial cells do not simply form a passive barrier but perform a wide range of important regulatory functions including maintaining a healthy peritoneal homeostasis as well as orchestrating events leading to normal repair or pathological outcomes following injury. Here, we summarise recent advances in our understanding of serosal repair and adhesion formation with an emphasis on molecular mechanisms and novel gene expression signatures associated with these processes. We discuss changes in mesothelial biomolecular marker expression during peritoneal development, which may help, in part, to explain findings in adults from lineage tracing studies using experimental adhesion models. Lastly, we highlight examples of where local tissue specialisation may determine a particular response of peritoneal cells to injury.

Most multicellular organisms have a major body cavity containing vital organs. This cavity is lined by a mucosa-like serosal surface and filled with serous fluid which suspends many immune cells. Injuries affecting the major body cavity are potentially life-threatening. Here we summarize evidence that unique damage detection and repair mechanisms have evolved to ensure immediate and swift repair of injuries at serosal surfaces. Furthermore, thousands of patients undergo surgery within the abdominal and thoracic cavities each day. While these surgeries are potentially lifesaving, some patients will suffer complications due to inappropriate scar formation when wound healing at serosal surfaces defects. These scars called adhesions cause profound challenges for health care systems and patients. Therefore, reviewing the mechanisms of wound repair at serosal surfaces is of clinical importance. Serosal surfaces will be introduced with a short embryological and microanatomical perspective followed by a discussion of the mechanisms of damage recognition and initiation of sterile inflammation at serosal surfaces. Distinct immune cells populations are free floating within the coelomic (peritoneal) cavity and contribute towards damage recognition and initiation of wound repair. We will highlight the emerging role of resident cavity GATA6+ macrophages in repairing serosal injuries and compare serosal (mesothelial) injuries with injuries to the blood vessel walls. This allows to draw some parallels such as the critical role of the mesothelium in regulating fibrin deposition and how peritoneal macrophages can aggregate in a platelet-like fashion in response to sterile injury. Then, we discuss how serosal wound healing can go wrong, causing adhesions. The current pathogenetic understanding of and potential future therapeutic avenues against adhesions are discussed.

Pancreatic fistula (PF) is a common and challenging complication after pancreatic surgery. The aim of this study was to investigate the efficacy of a new method for preventing PF utilizing self-assembling peptide hydrogel SPG-178 as a preclinical study. The degradability of SPG-178 was confirmed by mixing it with protease. A PF rat model was then established to investigate the efficacy of SPG-178 at preventing PF. After transecting the pancreatic duct toward the spleen, SPG-178 was attached to both sides of the pancreatic stump. The levels of amylase and lipase in both the serum and ascites were measured and surgical specimens investigated pathologically. The hardness of SPG-178 did not change when treated with protease over a short period. The ascitic amylase level was significantly lower in rats treated with SPG-178 than rats who were not 3 days after transection of the pancreatic duct toward the spleen. Pathological examination showed fewer inflammatory cells and presence of a structure body on the surface of the pancreatic stump in the SPG-178-treated group. SPG-178 remained on the surface and many cells that covered it formed fibrous tissue or mesothelium. Self-assembling peptide hydrogel SPG-178 has potential as a tool for preventing PF.

Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1-associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.

Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, generally thought to arise from retrograde menstruation of shed endometrial tissue. While the pathophysiology underlying peritoneal endometriosis lesion formation is still unclear, the interaction between invading endometrial tissue and the peritoneal mesothelial lining is an essential step in lesion formation. In this study, we assessed proteomic differences between eutopic endometrial stromal cells (ESCs) from women with and without endometriosis in response to peritoneal mesothelial cell (PMC) exposure, using single-cell cytometry by time-of-flight (CyTOF). Co-cultured primary eutopic ESCs from women with and without endometriosis with an established PMC line were subjected to immunostaining with a panel of Maxpar CyTOF metal-conjugated antibodies (n = 28) targeting cell junction and mesenchymal markers, which are involved in cell-cell adhesions and epithelial-mesenchymal transition. Exposure of the ESCs to PMCs resulted in a drastic shift in cellular expression profiles in ESCs derived from endometriosis, whereas little effect by PMCs was observed in ESCs from non-endometriosis subjects. The transcription factor SNAI1 was consistently repressed by PMC interactions. ESCs from endometriosis patients are unique in that they respond to PMCs by undergoing changes in adhesive properties and mesenchymal characteristics that would facilitate lesion formation.

Carbon fibers have excellent physicochemical and electrical properties. Vapor-grown carbon fibers are a type of carbon fibers that have a multi-walled carbon tube structure with a high aspect ratio. The representative vapor-grown carbon fiber, VGCFTM-H, is extremely strong and stable and has superior thermal and electrical conductivity. Because some high-aspect-ratio multi-walled carbon nanotubes (MWCNTs) have been reported to have toxic and carcinogenic effects in the lungs of rodents, we performed a 13-week lung toxicity study using VGCFTM-H in comparison with one of MWCNTs, MWNT-7, in rats. Male and female F344 rats were intratracheally administered VGCFTM-H at doses of 0.2, 0.4, and 0.8 mg/kg bw or MWNT-7 at doses of 0.4 and 0.8 mg/kg bw once a week for 8 weeks and then up to week 13 without treatment. The lung burden was equivalent in the VGCFTM-H and MWNT-7 groups; however, the lung weight had increased and the inflammatory and biochemical parameters in the broncho-alveolar lavage fluid and histopathological parameters, including inflammatory cell infiltration, alveolar type II cells proliferation, alveolar fibrosis, pleural fibrosis, lung mesothelium proliferation, and diaphragm fibrosis, were milder in the VGCFTM-H group than in the MWNT-7 group. In addition, the proliferating cell nuclear antigen (PCNA)-positive index in the visceral and pleural mesothelium was significantly higher in the MWNT-7 group than in the controls, but not in the VGCFTM-H group. Thus, the results of this study indicate that the lung and pleural toxicities of VGCFTM-H were less than those of MWNT-7.

The peritoneum is the largest and most complex serous membrane in the human body. The peritoneal membrane is composed of a layer of mesothelium supported by a thin layer of connective tissue. The peritoneum is one continuous sheet, forming two layers and a potential space between them - the peritoneal cavity- which is subdivided into multiple communicating spaces containing small amount of serous fluid that facilitates frictionless movement of mobile intraabdominal viscera. Peritoneum also contributes to fluid exchange mechanism and plays a role in immune response. The peritoneum is subject to many neoplastic and non-neoplastic processes including infections, trauma, developmental and inflammatory processes. Different Nuclear Medicine imaging techniques can be used to diagnose peritoneal diseases, most of these techniques can be customized depending on the clinical scenario and expected findings. Peritoneal scintigraphy can detect abnormal peritoneal communication or compartmentalization. Several nuclear medicine techniques can help characterize intraperitoneal fluid collections and differentiate sterile from infected fluid. PET imaging plays an important role in imaging of different neoplastic and non-neoplastic peritoneal pathologies. Nuclear radiologists need to be familiar with peritoneal anatomy and pathology to interpret peritoneal findings in dedicated peritoneal nuclear medicine imaging studies, as part of more general nuclear medicine scans, or on CT or MRI component of hybrid imaging studies. The purpose of this article is to review the normal peritoneal anatomy, various pathologic processes involving the peritoneum, and different nuclear medicine and hybrid imaging techniques that can help detect, characterize, and follow up peritoneal pathology.

The distinction between reactive mesothelium and carcinoma in serous effusions can be very difficult. Immunocytochemistry (ICC) is the most widely used tool to improve the diagnostic accuracy of body fluid cytology, with several ICC markers being proposed. Ber-EP4 antibody has shown high sensitivity and specificity rates for diagnosing metastatic carcinoma. In our department, we have detected Ber-EP4 positivity in mesothelium in some cytological specimens. We reviewed all articles on Ber-EP4 staining in effusion cytology, summarized current findings and analyzed the staining pattern of all cases expressing Ber-EP4. Some cases showing Ber-EP4 positivity in mesothelium have been reported, most of which showed only weak Ber-EP4 staining or staining of less than 50% of mesothelial cells. However, some cases may show strong positivity both in cytological and histological specimens. Clinicians and pathologists should be aware of this source of misdiagnosis, and ICC results in mesothelium should be always interpreted cautiously and correlated with clinical tests, other ICC markers and patient's previous history.

The mesothelium is a dynamic and specialized tissue layer that covers the somatic cavities (pleural, peritoneal, and pericardial) as well as the surface of the visceral organs such as the lung, heart, liver, bowel and tunica vaginalis testis. The potential therapeutic manipulation of visceral organs has been complicated by the carbohydrate surface layer—here, called the mesopolysaccharide (MPS)—that coats the outer layer of the mesothelium. The traditional understanding of MPS structure has relied upon fixation techniques known to degrade carbohydrates. The recent development of carbohydrate-preserving fixation for high resolution imaging techniques has provided an opportunity to re-examine the structure of both the MPS and the visceral mesothelium. In this report, we used high pressure freezing (HPF) as well as serial section transmission electron microscopy to redefine the structure of the MPS expressed on the murine lung, heart and liver surface. Tissue preserved by HPF and examined by transmission electron microscopy demonstrated a pleural MPS layer 13.01±1.1 um deep—a 100-fold increase in depth compared to previously reported data obtained with conventional fixation techniques. At the base of the MPS were microvilli 1.1±0.35 um long and 42±5 nm in diameter. Morphological evidence suggested that the MPS was anchored to the mesothelium by microvilli. In addition, membrane pits 97±17 nm in diameter were observed in the apical mesothelial membrane. The spatial proximity and surface density (29±4.5%) of the pits suggested an active process linked to the structural maintenance of the MPS. The striking magnitude and complex structure of the MPS indicates that it is an important consideration in studies of the visceral mesothelium.

The existence of an in situ phase of malignant mesothelioma has long been postulated but until recently has been impossible to prove. Here we describe ten patients with mesothelioma in situ, defined by a single layer of surface mesothelial cells showing loss of BAP1 nuclear immunostaining, no evidence of tumor by imaging and/or by direct examination of the pleura/peritoneum, and no invasive mesothelioma developing for at least 1 year. Nine cases were pleural and one peritoneal. Most patients were biopsied for repeated effusions of unknown etiology; in two patients mesothelioma in situ was found incidentally in lung cancer resections. In addition to surface mesothelium with BAP1 loss, one case had a surface papillary proliferation with BAP1 loss, and two cases had a small (few millimeter) nodule with BAP1 loss. CDKN2A was deleted by FISH in one of eight cases. Methylthioadenosine phosphorylase showed partial loss in the surface mesothelium by immunohistochemistry in three cases. Invasive malignant mesothelioma developed in seven patients with time between biopsy and invasive disease from 12 to 92 (median 60) months. Invasive mesothelioma has not developed in the other three patients at 12, 57, and 120 months, but the latter patient, who has pleural plaques, still has repeated pleural effusions, probably representing a so-called "benign asbestos effusion." We conclude that mesothelioma in situ, as diagnosed using the criteria outlined above, is associated with a high risk of developing invasive mesothelioma, but typically over a relatively protracted time, so that curable interventions maybe possible.

Objective. To study up a character and peculiarities of cyto-morphological changes in cellular material of the peripancreatic liquid accumulations (LA) as a criterion of objective estimation of the clinical course severity in an acute complicated pancreatitis (ACP). Маterials and methods. Results of cyto-morphological investigation of the peripancreatic LA sediment, obtained while doing interventional ultrasonography in 51 (88%) observations and videolaparoscopy - in 7 (12%) observations in 58 patients with an ACP, were analyzed. Results. Of intraabdominal LA (n=37) observations in 10 (27 %) of them a domination of proliferating cells of mesothelium with their polymorphism was revealed, while in 15 (41%) - degenerative-dystrophic changes like a bulging of cytoplasm, appearance of large «signet-ring like» cells, in 12 (32%) - аtipically changed cells of mesothelium with signs of anizocytosis and anizonucleosis, as well as cyto-morphological changes like in neoplastic process. In retroperitoneal localization of LA (n=21) a more essential changes in the granulocytes nuclei were registered, including, in 9 (43%) observations their structure have got irreversible disorders: karyopycnosis, karyorexis and karyolysis. The depth of structural cellular changes in mesoteliocytes and neutrophil granulocytes have depended upon the ACP severity. Conclusion. Determination of depth of the cellular content cytomorphological disorders in the LA sediment may serve an objective criterion in the ACP severity estimation.

We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3+CD4+ T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO3 ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan-neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements, which visually resembled neuronal structures. Both disruption of the fragile mesothelial connections or transection of the vagal nerves resulted in the loss of capsular mesothelial acetylcholine esterase staining and reduced splenic mass. Our data indicate that oral NaHCO3 activates a splenic anti-inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells.

Diffuse malignant mesothelioma (DMM) is an aggressive tumor of the mesothelium associated with a poor prognosis. Asbestos exposure is the major cause of the disease. Furthermore, pleural plaques are also caused by asbestos exposure. The authors present a case with malignant pleural mesothelioma and pleural plaques. Keywords: asbestos, asbestos-related diseases, mesothelioma, malignant pleural mesothelioma, pleural plaques

Malignant peritoneal mesothelioma (MPM) is a rare, aggressive, and fatal neoplasm of the abdominal mesothelium with a very abysmal survival if left untreated. MPM with EWSR1-ATF1 fusion is an uncommon entity recently recognized by molecular studies. We report the first case of MPM with EWSR1-ATF1 fusion and aberrant CK20 expression. The patient was a 38-year-old man who presented to our institution with three months history of abdominal pain and distention, a significant weight loss (>30 lb), and failure to thrive. He was working in a construction company with 20 year-history of questionable asbestos exposure. Imaging studies demonstrated radiographic patterns suggestive of extensive peritoneal carcinomatosis. However, serum tumor markers were within the normal limit (CA 19–9, CEA, AFP, and βHCG). Subsequently, he underwent a biopsy of the peritoneal nodules. Biopsy showed a proliferation of epithelioid/round cells with ample cytoplasm and occasional vacuoles, displaying papillary architecture. Immunohistochemistry showed tumor cells were strongly and diffusely positive for WT1, AE1/3, CK7, CK20, desmin, and CD99, focally positive for calretinin, D2-40, and CK5/6, while negative for BerEp4, MOC-31, trypsin, TTF-1, P40, GATA3, CDX2, and PAX8. P16 and BAP1 were retained. Fluorescence in situ hybridization studies showed EWSR1 rearrangement, and the NGS fusion panel revealed EWSR1-ATF1 fusion. A diagnosis of MPM with EWSR1-ATF1 fusion was rendered. Unfortunately, the patient passed away within a month of diagnosis. Pathologists should be aware of this entity, especially when faced with tumors displaying mesothelioma morphology but showing atypical immunoprofile (co-expression of mesothelial markers with strong CK20).

International audience; Fibroblast growth factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both human and mouse lungs. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (AdCont) was performed. Mice were euthanized at days 3, 5, and 14 Expression of FGF9 and markers of inflammation and myofibroblastic differentiation was studied by qPCR and immunohistochemistry. In vitro, rat mesothelial cells were stimulated with FGF9 (20 ng/ml), and we assessed its effect on proliferation, survival, migration, and differentiation. FGF9 was expressed by mesothelial cells in human idiopathic pulmonary fibrosis. FGF receptors, mainly FGFR3, were expressed by mesothelial cells in vivo in humans and mice. AdCont instillation induced diffuse pleural thickening appearing at day 5, maximal at day 14 The altered pleura cells strongly expressed α-smooth muscle actin and collagen. AdFGF9 injection induced maximal FGF9 expression at day 5 that lasted until day 14 FGF9 overexpression prevented pleural thickening, collagen and fibronectin accumulation, and myofibroblastic differentiation of mesothelial cells. In vitro, FGF9 decreased mesothelial cell migration and inhibited the differentiating effect of transforming growth factor-β1. We conclude that FGF9 has a potential antifibrotic effect on mesothelial cells.

The pericardium consists of a visceral mesothelial monolayer (epicardium) that reflects over the great vessels and joins an outer, relatively inelastic fibrous parietal layer of organized collagen and elastin fibers, between which is a potential space that normally contains up to 50 mL of plasma filtrate. Although not essential for life, the pericardium serves important albeit subtle functions in the euvolemic healthy individual that become increasingly important in hypervolemic states and conditions in which the heart enlarges acutely. The pericardial functions can be divided into the mechanical, reflex, membranous, metabolic, ligamentous.

Endometriosis, defined by the presence of ectopic endometrial lesions, is a common disease in reproductive-age women that profoundly affects patients' quality of life. Various pathogenic models have been proposed, but the origin of endometriosis remains elusive. In this article, we propose that the mesothelial barrier, which protects the underlying stroma from endometrial transplants present in retrograde menstrual fluid, can be compromised by activation of the epithelial to mesenchymal transition (EMT) repair mechanism that lead to temporary loss of barrier integrity. Absent of the mesothelial barrier, endometrial cells can more readily adhere to the underlying peritoneal stroma and establish endometrial lesions. The hypothesis is based on the clinical and experimental observations that correlate the location of endometrial lesions with areas of mesothelial damage, together with genetic evidence that 4 genes associated with endometriosis are direct regulators of the actin-cytoskeleton, which coordinates mesothelial barrier integrity. It supports past observations that implicate the peritoneum in the pathogenesis of endometriosis and unifies previously disparate theories that endometriosis may be triggered by infection, mechanical damage, and inflammation since each of these mechanisms can induce EMT in the mesothelium. If the hypothesis is correct, inhibition of EMT in the mesothelial barrier provides a novel paradigm for the prevention and treatment of endometriosis.

Aim Adhesion after pelvic surgery causes infertility, ectopic pregnancy, and ileus or abdominal pain. The materials currently available for clinical use are insufficient. The purpose of this study was to develop an anti-adhesive material that overcomes the limitations of conventional anti-adhesive agents. Methods The adhesion prevention effects of three methods – a two-layered sheet composed of gelatin film and gelatin sponge, Seprafilm and INTERCEED – were evaluated in 37 dogs. Anti-adhesive effects were investigated macroscopically and microscopically in a cauterized uterus adhesion model. Cell growth on the materials in vitro using human peritoneal mesothelial cells, fibroblasts and uterine smooth muscle cells were also evaluated. Results The two-layered gelatin sheet had significantly superior anti-adhesive effects compared to the conventional materials (Seprafilm and INTERCEED). A single-cell layer of mature mesothelium formed three weeks after surgery in the gelatin group. Peritoneum regeneration in the Seprafilm and INTERCEED groups was delayed and incomplete in the early phase. Little inflammation around the materials occurred and cell growth was significantly proliferated with the gelatin sheet. Conclusion The anti-adhesive effects of a two-layered gelatin sheet were superior to conventional agents in a cauterized canine uterus model, demonstrating early regeneration of the peritoneum, little inflammation and material endurance. The newly developed two-layered gelatin sheet is a useful option as an anti-adhesive agent for deeply injured and hemorrhagic sites.

Peritoneal injury is an important cause of technical failure of long-term peritoneal dialysis (PD). Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term PD with potentially life threatening consequences. CD147 is a glycoprotein with diverse functions including modulation of extracellular matrix via induction of matrix metalloproteinases, cell adhesion, and regulation of immune reactions. We hypothesized that CD 147 plays a role in the peritoneal cavity. In this retrospective study, we localized CD147 by immunohistochemistry in peritoneal biopsies from uremic patients not on PD (n = 8), on PD without signs of EPS (n = 7), and in biopsies in patients with the diagnosis of EPS (n = 7). Double immunofluorescence was used to co-localize α-smooth-muscle actin (α-SMA) and CD147 in selected biopsies from each group. Expression was scored semi-quantitatively. In biopsies from uremic controls, CD147 was prominently expressed in mesothelial cells, focally between fat cells and by some perivascular cells. In patients on PD, a similar distribution was present (although mesothelium was rarely conserved), with some focal accentuation. In EPS, layers of fibroblastic cells were positive for CD147. EPS biopsies demonstrated a significantly higher score in a blinded evaluation, compared to uremic patients. Cells expressing CD147 were α-SMA positive myofibroblasts as demonstrated by double immunofluorescence. Mean CD147 scores did not differ between patients with different transporter status. This is the first study demonstrating CD147 on a major part of fibroblastic cells in EPS. Future studies need to address the role of these cells in this severe complication of long-term PD.

We present a model for the transport of a single type of asbestos fibre through the human body. The model captures the transport modes that pertain particularly to the lungs and the mesothelium. Numerical solutions of the system follow observed movement in the body. We compare the accumulation of fibres in the lungs versus the mesothelium, and then we give analysis and results for various cases of exposure level and exposure time. Models, such as the one developed here, can give clues as to how asbestos fibres impact the body, and where to look for major impact.

Nodular mesothelial/histiocytic hyperplasia (NMHH) is a benign reactive phenomenon that can occur at any mesothelial site. We report the case of a 33 year old male who presented with chest pain and a pleural effusion, and after several months of investigation was found to have positive syphilis serology and NMHH of the pleura that was positive for spirochetes on immunohistochemical stain. NHMM has been previously reported to be caused by physical, inflammatory/infectious, or neoplastic irritation of mesothelium at various sites. This is the first reported case of NMHH associated with syphilis. Keywords: Nodular mesothelial/histiocytic hyperplasia, Syphilis, Spirochete

Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Here we established for the first time, hypochlorite-induced porcine model of peritoneal fibrosis in 5-week-old piglets. We showed that administration 15–30 mM hypochlorite, a dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA+ myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated in vitro using human mesothelial cells that hypochlorite-induced fibrosis was likely due to necrosis, but not programmed apoptosis; besides, overexpression of IL1β, CX3CL1 and TGFβ on the peritoneal mesothelium in current model was detected, similar to observations from peritoneal dialysis-induced peritoneal fibrosis in human patients and earlier reported mouse model. Moreover, our novel antemortem evaluation using laparoscopy provided instant feedback on the progression of organ fibrosis/adhesion which allows immediate adjustments on treatment protocols and strategies in alive individuals that can not and never be performed in other animal models.

V-domain Ig-containing suppressor of T-cell activation (VISTA) is an immune checkpoint gene that inhibits anti-tumor immune responses. Since most malignant pleural mesotheliomas do not respond to anti-programmed cell death(-ligand)1 (PD-(L)1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy and given the recent finding of The Cancer Genome Atlas Study that pleural mesothelioma displays the highest expression of VISTA among all cancers studied, we examined VISTA expression in a large pleural mesothelioma cohort. VISTA and PD-L1 immunohistochemistry were performed on tissue microarray of immunotherapy-naive pleural mesotheliomas (254 epithelioid, 24 biphasic and 41 sarcomatoid) and ten whole-tissue sections of benign pleura (VISTA only). Percentages of tumor and inflammatory cells with positive staining were assessed. Optimal prognostic cutoff percentages were determined using maximally selected rank statistics. Overall survival was evaluated using Kaplan–Meier methods and Cox proportional hazard analysis. All benign mesothelium expressed VISTA. Eighty-five percent of 319 and 38% of 304 mesotheliomas expressed VISTA and PD-L1 (88% and 33% of epithelioid, 90% and 43% of biphasic, and 42% and 75% of sarcomatoid), respectively. Median VISTA score was significantly higher in epithelioid (50%) (vs. biphasic [20%] and sarcomatoid [0]) (p

The skin is the largest organ in the human body, and skin defects are very common. Skin flap transplantation is the best treatment for serious wound defects, and donor site tissues are always sacrificed during this process. Decellularized biomaterials, derived mainly from various nonautologous organs and tissues, have promising applications in tissue engineering and repair of wound defects. To date, decellularized mesothelium, intestine, amniotic membrane, dermis, and skin flaps have been developed and applied for skin coverage in animal models and clinical practice. In this review, we discuss recent advances in decellularized biomaterials for skin substitutes and future perspectives. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1849-1859, 2019.

Epicardium, the mesothelium covering the heart, is composed of multipotent cells and is reactivated following myocardial injury in adults. Herein, we provide evidence for activation of atrial epicardium in aged patients with diseased atria and in murine models of atrial remodeling. Epicardial activation contributed to fibro-fatty infiltration of sub-epicardium that contained a number of cells co-expressing markers of epicardial progenitors and fibroblasts. Indeed, using genetic lineage tracing of adult epicardium, we demonstrate the epicardial origin of fibroblasts within fibro-fatty infiltrates. A subpopulation of adult epicardial-derived cells (aEPDCs) expressing PDGFRα, niched in the sub-epicardium, were isolated and differentiated into myofibroblast in the presence of angiotensin-II. Furthermore, single cell RNA-seq analysis identified several clusters of aEPDCs and revealed transition from adipogenic to fibrogenic cells. In conclusion, a subset of aEPDCs, pre-programmed towards a specific cell fate, contributes to fibro-fatty infiltration of sub-epicardium of diseased atria.

The mesothelium is an epithelial structure derived from the embryonic mesoderm. It plays an important role in the development of a number of different organs, including the heart, lungs, and intestines. In this publication, we discuss aspects of the development of the mesothelium, where mesothelial structures can be found, and review molecular and cellular characteristics associated with the mesothelium. Furthermore, we discuss the involvement of the mesothelium in a number of disease conditions, in particular in the pathogenesis of mesotheliomas with an emphasis on malignant pleural mesothelioma (MPM)—a primary cancer developing in the pleural cavity.

The mesothelial lining of the lung, the visceral pleura, and of the heart, the epicardium, derive from a common multipotent precursor tissue, the mesothelium of the embryonic thoracic cavity that also contributes to organ-specific mesenchymal cell types. Insight into mesothelial mobilization and differentiation has prevailedin the developing heart while the mesenchymal transition and fate of the visceral pleura are poorly understood. Here, we use the fact that the early mesothelium of both the lung and the heart expresses the transcription factor gene Wt1, to comparatively analyze mesothelial mobilization in the two organs by a genetic cre-loxP-based conditional approach. We show that epicardial cells are mobilized in a large number between E12.5 and E14.5, whereas pleural mobilization occurs only sporadically and variably in few regions of the lung in a temporally highly confined manner shortly after E12.5. Mesothelium-specific inactivation of unique pathway components using a Wt1creERT2line excluded a requirement for canonical WNT, NOTCH, HH, TGFB, PDGFRA, and FGFR1/FGFR2 signaling in the mesenchymal transition of the visceral pleura but indicated a deleterious effect of activated WNT, NOTCH, and HH signaling on lung development. Epicardial mobilization was negatively impacted on by loss of HH, PDGFRA, FGFR1/2 signaling. Epicardial overactivation of WNT, NOTCH, and HH disturbed epicardial and myocardial integrity. We conclude that mesothelial mobilization in the developing lung and heart differs in timing, quantity and pathway dependency, indicating the organ specificity of the program.

Glisson's capsule is the connective tissue present in the portal triad as well as beneath the liver surface. Little is known about how Glisson's capsule changes its structure in capsular fibrosis (CF), which is characterized by fibrogenesis beneath the liver surface. In this study, we found that the human liver surface exhibits multilayered capsular fibroblasts and that the bile duct is present beneath the mesothelium, whereas capsular fibroblasts are scarce and no bile ducts are present beneath the mouse liver surface. Patients with cirrhosis caused by alcohol abuse or hepatitis C virus infection show development of massive CF. To examine the effect of alcohol on CF in mice, we first injected chlorhexidine gluconate (CG) intraperitoneally and then fed alcohol for 1 month. The CG injection induces CF consisting of myofibroblasts beneath the mesothelium. One month after CG injection, the fibrotic area returns to the normal structure. In contrast, additional alcohol feeding sustains the presence of myofibroblasts in CF. Cell lineage tracing revealed that mesothelial cells give rise to myofibroblasts in CF, but these myofibroblasts disappear 1 month after recovery with or without alcohol feeding. Capsular fibroblasts isolated from the mouse liver spontaneously differentiated into myofibroblasts and their differentiation was induced by transforming growth factor beta 1 (TGF-β1) or acetaldehyde in culture. In alcohol-fed mice, infiltrating CD11b+ Ly-6CLow/- monocytes had reduced mRNA expression of matrix metalloproteinase 13 and matrix metalloproteinase 9 and increased expression of tissue inhibitor of matrix metalloproteinase 1, Tgfb1, and interleukin-10 during resolution of CF. Conclusion: The present study revealed that the structure of Glisson's capsule is different between human and mouse livers and that alcohol impairs the resolution of CF by changing the phenotype of Ly-6CLow/- monocytes.

Benign multicystic mesothelioma is an extremely rare neoplasm usually arising from the visceral mesothelium of the peritoneal cavity typically presenting in young to middle-aged women. It has been deemed an indolent tumour with a possible heritable nature, but also a possible reactive neoplasm secondary to trauma. Diagnosis relies on identifying characteristic histology of cysts separated by loose connective tissue stroma and lined by pale, flat or cuboidal mesothelial cells. A 74-year-old male presented with a painless, enlarging scrotal swelling thought to be either an epididymal cyst or hydrocele. He underwent radical orchiectomy and benign multicystic mesothelioma of the tunica vaginalis was characterized on macroscopy and microscopic examination. The potential for malignant transformation of these tumours has not been demonstrated, but they are known to recur. This infrequent presentation of a rare and poorly understood tumour with description of histologic findings may allow for improved diagnosis in other cases.