Macroscopic,Histologic, Histochemical,Immunohistochemical, and Ultrastructural Features of Mesothelioma

Mesotheliomas are uncommon neoplasms that arise from the cells forming the serosal membranes of the body cavities. Approximately 90–95% of mesotheliomas arise in the pleural cavity and 5–10% in the peritoneal cavity. Rare mesotheliomas arise in the pericardium and in the tunica vaginalis. Unlike many neoplasms, mesotheliomas grow in a diffuse distribution and tend to encase the organs in the various body cavities. A combination of histochemical, immunohistochemical, and ultrastructural features are often necessary to accurately diagnose mesotheliomas. These techniques are highlighted in this review article on mesothelioma.     

Absence of HHV-8 DNA sequences in malignant mesothelioma.

Human herpesvirus 8 (HHV-8) associated primary effusion lymphomas arise and grow in the body cavities as effusions, but it is not known whether the lining of body cavities and mesothelium derived malignancies are potential targets of HHV-8 infection. We examined a series of 13 diffuse malignant mesotheliomas and four mesothelial cell rich effusion samples of non-neoplastic aetiology from non-immunodepressed patients using the polymerase chain reaction to detect HHV-8 specific sequences. HHV-8 amplification products were absent in diffuse malignant mesotheliomas and in non-neoplastic effusions samples. These results suggest that HHV-8 has a selective tropism among body cavity based tumours, being confined to primary effusion lymphomas.     

Analysis of Asbestos Concentration in 20 Cases of Pseudomesotheliomatous Lung Cancer

Mesothelioma is a rare neoplasm caused by asbestos exposure. The majority of mesotheliomas arise from the pleural lining of the thoracic cavity, but also involve the peritoneal and pericardial cavities. Another type of neoplasm referred to as pseudomesotheliomatous adenocarcinoma is rare. Most “pseudomesotheliomas” arise in the pleural tissue of the chest cavity and resemble pleural mesotheliomas, macroscopically and histologically. While most arise in the pleura, there are some that metastasize to the pleura from another site. We evaluated asbestos fiber concentrations in 20 cases of pseudomesotheliomatous lung cancer and found a significant number to contain an elevated concentration of asbestos in their lung tissue, which is similar with our study of 55 mesothelioma cases published in 1997. This would provide evidence that some pseudomesotheliomatous lung cancers are caused by asbestos.     

Mucin-Positive Epithelial Mesotheliomas: A Histochemical, Immunohistochemical, and Ultrastructural Comparison with Mucin-Producing Pulmonary Adenocarcinomas

Pathologists routinely use histochemistry, immunohistochemistry, and electron microscopy to differentiate epithelial mesotheliomas from pulmonary adenocarcinomas. Epithelial mesotheliomas are usually mucicarmine-, PAS-diastase, and carcinoembryonic antigen-negative, whereas about 60-75% of pulmonary adenocarcinomas are mucicarmine- and PAS-diastase-positive, and about 90% express polyclonal carcinoembryonic antigen. During a pathologic evaluation of pleural neoplasms between 1975 and 1990, 10 epithelial mesotheliomas were identified that were mucicarmine- and in some instances PAS-diastase-positive (diagnosis of mesothelioma confirmed by ultrastructural examination), with four mesotheliomas focally expressing carcinoembryonic antigen. The mucicarmine, PAS-diastase, and carcinoembryonic antigen staining were usually eradicated or reduced in intensity by pretreatment of the tissue sections with hyaluronidase, suggesting that hyaluronic acid was responsible for the positive mucin reactions. In three cases the epithelial mesotheliomas showed focal regions of mucicarmine, PAS-d-, and Alcian blue-hyaluronidase-resistant staining. In contrast, 10 mucicarmine-, PAS-diastase-, Alcian blue-, and carcinoembryonic antigen-positive pulmonary adenocarcinomas were not affected by hyaluronidase pretreatment of the tissue. Besides the usual ultrastructural features of well- to moderately well-differentiated epithelial mesotheliomas, the mucin-positive epithelial mesotheliomas often showed medium-electron-dense secretory material covering the microvilli, aggregates of medium electron-dense material in association with the microvilli, producing an ultrastructural morphology that has been observed only in epithelial mesotheliomas.     

Immunohistochemical differentiation of sarcomatoid mesotheliomas from other spindle cell neoplasms

A sizable proportion of pleural malignant mesotheliomas are sarcomatoid (22%) or biphasic (24%) and may need to be distinguished from other spindle cell neoplasms that occur as primary or metastatic tumors of the chest wall or lungs. To determine the utility of immunohistochemistry in the differentiation of sarcomatoid malignant mesotheliomas from other spindle cell neoplasms, the authors studied the immunostaining patterns of nine antibodies in four sarcomatoid mesotheliomas, one desmoplastic mesothelioma, two epithelial mesotheliomas, four spindle cell squamous carcinomas, and eight sarcomas of various differentiation. Three of the four sarcomatoid mesotheliomas and the desmoplastic mesothelioma had positive results for cytokeratin, which distinguishes them from sarcomas but not from spindle cell squamous carcinomas. The immunostaining pattern of 14 examples of benign spindle cell mesothelial proliferation was similar to that of the sarcomatoid mesotheliomas, which supports the theory that these tumors are mesothelial in origin. Although other antibodies occasionally may be helpful, depending on the differentiation of the sarcoma, cytokeratin immunostaining appears to be the best method to discriminate sarcomatoid mesotheliomas from sarcomas.     

CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity

B1 cells are a predominant cell type in body cavities and an important source of natural antibody. Here we report that in mice lacking the chemokine, CXCL13, B1 cells are deficient in peritoneal and pleural cavities but not in spleen. CXCL13 is produced by cells in the omentum and by peritoneal macrophages, and in adoptive transfers, B1 cells home to the omentum and the peritoneal cavity in a CXCL13-dependent manner. CXCL13(-/-) mice are deficient in preexisting phosphorylcholine (PC)-specific antibodies and in their ability to mount an anti-PC response to peritoneal streptococcal antigen. These findings provide insight into the mechanism of B1 cell homing and establish a critical role for B1 cell compartmentalization in the production of natural antibodies and for body cavity immunity.     

Oxyphilic proliferations of the respiratory tract and paranasal sinuses.

Neoplasms of the upper respiratory comprised primarily of eosinophilic cells are, in general, rare, and they include a diverse group of lesions. Low-grade oncocytic neuroendocrine neoplasms (so-called oncocytic carcinoids) can be encountered in several locations throughout the respiratory tract. The oncocytoma and related entities, lesions that presumably arise from minor gland tissue, can likewise be seen from the nasal cavity to the lung; differences in clinical significance may relate to the location of such lesions, and are discussed herein. Granular cell tumor is another entity that can involve both the upper respiratory tract and lungs, and specific features of this lesion in different anatomic sites are highlighted. The oncocytic variant of Schneiderian papilloma is an important nasal lesion to recognize, because of important therapeutic and prognostic implications of that diagnosis. Finally, unique oncocytic variants of glomus tumor and pulmonary alveolar adenoma are discussed, as well as eosinophilic varieties of pulmonary carcinomas and mesotheliomas.     

Flow cytometric analysis of malignant pleural mesotheliomas

Forty-six cases of malignant pleural mesothelioma were analyzed for histologic subtype, DNA content, and cell cycle characteristics. Sixty-five percent of cases were diploid in DNA content, with intermediate to low proliferative rates. Thirty-one nonmesothelial malignant neoplasms of the lung, of histologic types most easily confused with malignant mesothelioma, were also examined. In contrast to the mesotheliomas, 85% of these nonmesothelial malignant neoplasms of the lung were aneuploid; the aneuploid neoplasms exhibited higher mean proliferative rates (S = 10.6%) than diploid nonmesothelial neoplasms of the lung (S less than 6%). Unlike most malignant neoplasms, mesotheliomas most often display diploid DNA contents and low proliferative rates despite their clinically aggressive behavior.     

Ultrastructural histochemistry of mesotheliomas and adenocarcinomas in malignant effusions

The results of electron microscopic examination of cytologic specimens from six cases of mesothelioma and 10 cases of metastatic carcinoma of different origins are presented. The formation of cell clusters in malignant effusions from the two neoplasms has been thoroughly investigated: in mesotheliomas, cells had longer, more slender microvilli than in carcinomas and more abundant bundles of intermediate filaments; the central cavity often seen in the clusters frequently contained collagen and showed basement membrane production. The application of periodic acid-silver methenamine (PASM) and phosphotungstic acid (PTA) demonstrated a peculiar ultrastructural difference in cell coat staining in the two tumor types: in mesotheliomas, PTA and PASM were consistently negative along the outer surface of the cell aggregates, while carcinomas displayed a positive reaction either on the outer surface or on both inner and outer surfaces of the clusters. The diagnostic significance of the above-mentioned difference between the two neoplasms will require further investigation in a larger number of cases.     

胸腰椎爆裂骨折后路内固定术后椎体空洞形成的危险因素与疗效分析

目的 观察胸腰椎爆裂骨折采用后路内固定复位术后椎体内空洞形态,分析空洞产生的危险因素及空洞对临床疗效的影响。 方法 选取胸腰椎爆裂骨折后路内固定复位术治疗患者52例,随访2年以上,观察椎体内空洞形态;将患者按椎体内有无明显空洞分为2组,对比两组临床和影像学特点,分析导致空洞的危险因素及空洞对临床疗效的影响。 结果 椎体完全愈合23.1%（12/52）,存在空洞76.9%（40/52）。椎体空洞的形态有几种类型：终板空洞22.5%（9/40）;椎体空洞47.5%（19/40）;椎体劈裂30%（12/40）。椎体空洞组男性比例较高、脊髓神经损伤较严重。术后随访平均37.8个月,患者的腰痛及腰椎功能恢复良好,两组间VAS及ODI评分无统计学差异。 结论 胸腰椎爆裂骨折后路伤椎置钉复位术未行椎体植骨者容易导致椎体内空洞,骨折爆裂程度越高,越容易导致椎体空洞;实施伤椎螺钉置入术后椎体高度复位的程度较大是导致椎体中前部出现空洞的重要原因。椎体内出现空洞或劈裂,短期不影响患者的腰椎疼痛及功能。     

SV40 induces mesotheliomas in hamsters.

In the course of studies to elucidate the relative contribution of simian virus 40 (SV40) large T and small t proteins during oncogenesis, we observed the appearance of pericardial and pleural tumors in 100% of Syrian hamsters injected in the pleural space with wild type SV40. When SV40 was injected via the intracardiac or intraperitoneal routes, more than 50% of hamsters developed mesothelial tumors. Macroscopic, microscopic, ultramicroscopic, and histochemical characteristics identify these neoplasms and derived cell lines as mesotheliomas and mesothelioma-derived cell lines. The SV40 genome was integrated and expressed in the mesotheliomas and derived cell lines. The absence of mesotheliomas in hamsters injected with SV40 small t deletion mutants indicates that the small t protein plays an important role in the development of SV40-induced mesotheliomas. To the best of our knowledge, this is the first definitive report of virus-induced mesotheliomas in mammals.     

Pleural mesothelioma of connective tissue type, localized fibrous tumour of the pleura, and reactive submesothelial hyperplasia. An immunohistochemical comparison

Ten diffuse pleural mesotheliomas of connective tissue type have been compared with 14 examples of pleural granulation tissue and 7 localized fibrous tumours of the pleura, using immunohistochemistry to identify cytokeratins of low and high molecular weight and vimentin. Low molecular weight cytokeratin and vimentin were both detected in 8 of the 10 mesotheliomas and in 12 of the 14 reactive lesions. High molecular weight cytokeratin was rarely detected in either lesion. The seven localized fibrous tumours of the pleura were all positive for vimentin and negative for both cytokeratins. These findings support an origin of connective tissue type mesotheliomas from multipotential submesothelial spindle cells and of localized fibrous tumours of the pleura from either conventional fibroblasts or resting submesothelial spindle cells. Antibodies to cytokeratin help distinguish these two neoplasms but provide no assistance in the more difficult diagnostic problem of distinguishing mesotheliomas of connective tissue type from pleural reactions characterized by abundant granulation tissue.     

Tumour spread in serosal cavities: What have we learned?

During the Montebello Conference on malignant serosal tumours at Lillehammer, Norway, in June 2004, a group of 30 international experts addressed the biologic and genetic aspects of malignant tumours affecting serosal cavities in the human body. Three neoplasms were mainly dealt with: mesotheliomas arising locally, ovarian carcinomas developing in close proximity to the serosa, and breast tumours in which the spread came from some distance. New, important data on the tumour microenvironment and the process of carcinogenesis with progression and acquisition of invasive properties shed new lights on the mechanisms, including proliferative properties, alterations of signal transduction pathways, and tissue remodelling by proteolytic enzymes in the metastasizing cells. Several of these markers have considerable diagnostic and clinical interest. In addition, new aspects of morphologic and immunocytochemical characteristics of the cells as well as genetic markers may soon become powerful tools for practical use. The molecular fingerprint of the individual tumours may also give guidelines for chemotherapy as well as biologic therapies, including induction of apoptosis. The easy accessibility of tumours from serosal fluids and possibilities for specific discrimination of the neoplastic cells from admixed leukocytes and other cells are promising avenues for cytodiagnostics.     

Polycystic mesothelioma of the peritoneum. Description of 4 cases]

Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.     

A comparative immunohistochemical study of peritoneal and ovarian serous tumors, and mesotheliomas.

The distinction between serous neoplasms of the peritoneum in women and conventional mesothelioma can be difficult. In order to determine any significant immunohistochemical differences, formalin-fixed, paraffin-embedded sections of 10 peritoneal serous tumors (PST), 10 ovarian serous tumors (OST), and 10 epithelial mesotheliomas were evaluated with a panel of 10 antibodies directed against carcinoembryonic antigen (CEA: polyclonal, monoclonal), high molecular weight keratin (34 beta E12), low molecular weight keratin (35 beta H11), Leu-M1, TAG-72 (monoclonal antibody B72.3), human milk fat globulin (HMFG-2), vimentin, placental alkaline phosphatase (PLAP), and S-100 protein. The antibodies CEA, Leu-M1, and B72.3 had the most discriminatory value in differentiating serous tumors from mesothelioma. Eighty-five percent of PSTs and OSTs (17 of 20) were positive with CEA, Leu-M1, and/or B72.3. None of the mesotheliomas stained for CEA or Leu-M1; three mesotheliomas had very focal positivity with B72.3 (1% or less). Vimentin, PLAP, HMGF-2, keratin, and S-100 had no significant discriminatory value. Epithelial mucin was present in 80% of serous tumors, while the mesotheliomas lacked epithelial mucin. Leu-M1, CEA, and/or B72.3 positivity in a peritoneal tumor supports a diagnosis of serous tumor. However, since some PST do not stain for any of the three antibodies and the focal nature of positive reactions in some cases may be difficult to interpret, exclusion of mesotheliomas is enhanced by the use of mucin stains.     

A new, safer, controllable field-of-view endoscope avoiding movement inside body cavities

One of the greatest difficulties in endoscopic surgery is the limited field-of-view (FOV) of endoscopes. During endoscopic manipulation in body cavities to expand the FOV, there is the risk of inadvertent damage to body tissues, nerves, and internal organs. The risk increases especially in surgery that is performed inside a very small cavity, or in which body tissues are very fragile. To overcome these issues, we developed a novel endoscope that can provide various FOVs without moving or bending the endoscope itself inside the body cavity and investigated the feasibility of using the new endoscope in vivo. A beam splitter was used to visualize both forward and side views, and two polarization plates and observation windows were used to avoid overlap of the two views. An endoscope having a 7-mm diameter was fabricated through which both views were clearly visualized in vivo. It took only 0.7s to change the FOV with high repeatability, with a maximum distance error of 2.8%. The new endoscope can provide forward and panoramic views without moving the endoscope; therefore, the risk of inadvertent damage to fragile body tissues can be significantly decreased.     

An optimized battery of eight antibodies that can distinguish most cases of epithelial mesothelioma from adenocarcinoma

An immunocytochemical battery comprising 9 antibodies specifically distinguishes 80% of the epithelial malignant mesotheliomas from adenocarcinomas. The discriminatory power of antibodies to calretinin was tested together with this battery to determine whether the performance thereby could be improved. The study comprises 119 mesotheliomas of epithelial or mixed phenotype and 57 adenocarcinoma metastases in the pleural cavity. The differences between the 2 groups were highly significant for all recorded parameters, but typical reactivity for all parameters was seen in only 6 (5.0%) of the 119 mesotheliomas. An algorithm based on stepwise logistic regression was used to interpret divergent reaction patterns. Most diagnostic information was obtained with 8 of the parameters studied. The resulting algorithm identified almost 90% of the mesotheliomas with high specificity. The battery can be performed in 2 steps: several adenocarcinomas first are diagnosed with a few antibodies, applying the rest of the battery on the remaining unresolved cases.     

Malignant peritoneal mesothelioma: Quantitative analysis of asbestos burden

Malignant mesotheliomas develop commonly in the pleural cavity and rarely arise in the peritoneal cavity. It is well established that asbestos exposure is related to malignant pleural mesothelioma, but the asbestos burden in the abdominal cavity in patients with malignant peritoneal mesothelioma has not been well studied. The purpose of the present study was therefore to report on an autopsy case of malignant peritoneal mesothelioma with quantitative analysis of the asbestos burden in tissues from the pleura and organs in the abdominal cavity. The patient was a 67-year-old man with a history of asbestos exposure. The peritoneum was thickened with diffuse tumor proliferation. This patient was diagnosed as having malignant peritoneal epithelioid mesothelioma. The number of asbestos fibers was >10 000/g dry tissue in all samples examined except in the small intestine. The number of asbestos fibers in the stomach was 53 000/g, which was higher than that in a control asbestosis subject. The existence of numerous asbestos fibers found in the abdominal cavity suggests that asbestos stimuli are related to the tumorigenesis of malignant peritoneal mesothelioma.     

From the archives of MD Anderson Cancer Center: Primary effusion lymphoma with simultaneous involvement of the retroperitoneum and pleural cavity

Primary effusion lymphoma (PEL) is a rare neoplasm that arises in the context of severe immunosuppression. Acquired immunodeficiency syndrome (AIDS) as a result of human immunodeficiency virus (HIV) infection is the most common cause of immunodeficiency in patients who develop PEL. These neoplasms usually involve one or more body cavities, so-called classic PEL. The pleural cavity is most often involved, followed by the peritoneal and pericardial cavities. Involvement of the cerebrospinal fluid (CSF) and meninges is rare. A subset of patients can present with a tissue-based mass, known as the extracavitary variant. We encountered a patient with HIV infection and severe immunosuppression who presented initially with mediastinal, retroperitoneal mass and bilateral pleural effusions. He subsequently developed CSF involvement. Despite therapy, the patient relapsed with chest wall disease 6 months later and died shortly thereafter. Our literature review yielded about 400 cases of PEL reported previously. About 65 % of PEL patients have had AIDS, but a subset of patients had immunosuppression attributable to organ transplantation or physiological immunosenescence. CSF involvement has been reported in ~2 % of patients, and about 10 % of patients had both body cavity and extracavitary disease. The pathologic findings in this case were typical of extracavitary PEL. The neoplastic cells had features of plasmablasts and were positive for HHV-8, Epstein-Barr virus encoded RNA (EBER) and plasma cell associated markers, and were negative for B-cell antigens. The prognosis of patients with PEL is usually poor with a median survival less than one year in most studies. We use this patient's case as an illustration of PEL and we review the clinicopathologic findings and differential diagnosis of PEL.