Multicystic peritoneal tumor in two layer hens.

In chicken, peritoneal cystic lesions have not been clearly categorized. In this study, diffuse peritoneal multiple cysts were observed in two layer hens. The cysts in the serosa were lined with single layers of squamous or cuboidal cells. The papillary proliferations of columnar cells were also observed in one case. The smooth muscle layer or mass were observed around the cysts in both cases. The cystic lining cells were positive for pan-cytokeratin, vimentin, S100 and Wilms tumor 1. Ultrastructurally, they had sparsely microvilli on the luminal surface. The histological results indicated the present cases were multicystic mesothelioma, but also had characteristics of Mullerian epithelium. This is the first report describing the detailed pathological feature of unique multicystic tumor in chicken.

Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma.

The diagnosis of malignant pleural mesothelioma (MPM) is challenging and requires immunohistochemistry or electron microscopy assays to specifically differentiate MPM from lung adenocarcinoma. An ultrastructural study of fresh tissue is considered to be the "gold standard." In most cases, the first diagnostic approach is performed on pleural effusion, and in some patients, this is the only available sample for diagnosis. The aim of the present study is to evaluate if an examination of pleural effusion samples based on electron microscopy (EMpe) is a useful tool for the differential diagnosis of MPM and lung adenocarcinoma. An EMpe study was performed in 25 pleural effusion samples. Histological and immunohistochemical markers confirmed the diagnosis of either mesothelioma (5) or adenocarcinoma (20). Of the five cases that were diagnosed with mesothelioma, two samples (40%) showed cells with "bushy" microvilli, which are characteristic of mesothelioma, by EMpe, and three were acellular (60%). Of the 20 cases of adenocarcinoma, EMpe showed cells with short microvilli in 9 (45%), and 11 were acellular (55%). EMpe identifies unequivocal morphological changes that are useful for the differential diagnosis of MPM or adenocarcinoma when the pleural effusion sample contains evaluable tumor cells.

Use of Anti-Noxa Antibody for Differential Diagnosis between Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia.

OBJECTIVES: The histological differential diagnosis between epithelioid mesothelioma (EM) and reactive mesothelial hyperplasia (RMH) is not always straightforward. The aim of the present study was to search for new immunohistochemical markers to distinguish EM from RMH. METHODS: We evaluated and compared the expression of apoptosis-related genes in EM and RMH by real-time RT-PCR array analysis followed by clustering of significant gene expression. Immunohistochemical staining and statistical analysis of Noxa expression in 81 cases of EM and 55 cases of RMH were performed and compared with the utility of other previously reported antibodies such as Desmin, EMA, GLUT-1, IMP-3 and CD146. RESULTS: Noxa mRNA expression levels were found to be increased in EM when compared to RMH by RT-PCR array analysis. In the immunohistochemical analysis, Noxa showed sensitivity of 69.0%, specificity of 93.6% and positive predictive value of 93.0% as a positive marker of EM in distinguishing it from RMH, and these values were almost similar to IMP-3. CONCLUSION: Noxa is a marker with relatively high specificity, and can be used to distinguish EM from RMH. It would be a valuable addition to the current antibody panel used for the differential diagnosis of EM and RMH.

Cytomorphologic findings of malignant mesothelioma in FNA biopsies and touch preps of core biopsies.

BACKGROUND: Given the lack of recent literature regarding the aspiration cytology of immunohistochemically confirmed malignant mesothelioma (MM), we were interested in reviewing the experience of our institution and establishing useful morphologic criteria. METHODS: Seventeen aspiration and touch preparation specimens with a diagnosis of MM obtained between 2002-2013 were reviewed along with 20 cases of adenocarcinoma and 16 cases of squamous cell carcinoma. The utility of a number of morphologic features was evaluated. RESULTS: In most cases of MM, a consistent pattern emerged. Aspirates and touch preps were cellular with irregularly shaped 2 and 3 dimensional clusters. The individual cells were predominantly angulated and had dense cytoplasm with eccentric nuclei. In every case, a minority of tumor cells contained prominent microvacuoles. The chromatin pattern tended to be fine with small nucleoli. While most cases were cytologically monotonous, five cases displayed striking pleomorphism and three cases contained occasional large atypical cells. Two cases contained metachromatic background material. Features which were most useful in discriminating MM from adenocarcinoma were angulated cell shape(P = 0.0002), dense cytoplasm(P = 0.0001), and cytoplasmic microvacuoles(P = 0.0001). In our material, cases of squamous cell carcinoma were often difficult to distinguish from MM. Useful discriminatory features present in squamous cell carcinoma included ink dot nuclei(P = 0.0003), a "dirty" cystic, necrotic background (P = 0.0027) and tumor balls with peripheral spindling(P = 0.0041). CONCLUSION: Most cases of MM have a consistent appearance in core biopsy touch preps and FNAs. Distinguishing MM from adenocarcinoma and squamous cell carcinoma can be facilitated by evaluating a few key morphologic features.

The expression and clinical effects of alpha-methylacyl-CoA racemase (AMACR/ P504S) as an immunohistochemical marker in malign pleural mesothelioma.

BACKGROUND/AIM: Alpha-methylacyl-CoA racemase (AMACR), an intracellular enzyme involved in lipid metabolism, has emerged as an immunohistochemical marker for many types of cancer. Recent studies about the role of lipid metabolism in pathogenesis of mesothelioma have brought up some positive results. This study was conducted to investigate AMACR expression in the diagnosis of malignant pleural mesothelioma (MPM) and the correlation of this marker with clinical characteristics and survival. MATERIALS AND METHODS: The clinicopathologic characteristics and resection materials of 71 patients were reviewed retrospectively. AMACR expression was evaluated immunohistochemically. The correlations among AMACR expression, clinicopathologic factors, and survival were investigated. RESULTS: AMACR expression was detected in 42.3% of the study group. The specificity and sensitivity of AMACR immunostaining in detecting mesothelioma were 41.1% and 42.3%, respectively. AMACR-positive and negative groups were similar for age, sex, smoking history, tumor diameter, lymph node involvement, differentiation, T-N factor, and stage. Overall survival was not significantly different between the groups, either. CONCLUSION: The sensitivity of immunostaining was not high enough to use AMACR as a diagnostic tool in MPM. AMACR expression did not have a prognostic value in MPM, either.

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.

OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

Analytical Transmission Electron Microscopy of Amphibole Fibers From the Lungs of Quebec Miners.

The objective of this study is to describe the morphology, molecular structure, and chemistry of amphibole fibers from lung samples from workers in the chrysotile mines at Asbestos and Thetford Mines, Quebec. A fibrous tremolite-actinolite contaminant in an asbestos ore sample from the deposit at Asbestos was used for comparison. Lattice imaging was performed using high-resolution transmission electron microscopy (HRTEM). Silica-rich amorphous coatings (SIRA) that may be related to carcinogenesis are noted on all of the HRTEM photographs of fibers retained in lung, but not on fiber surfaces of the bulk comparison sample. Fibers found in lung samples and in a bulk comparison sample are produced primarily by splitting of thicker crystals and, as such, might not be considered asbestos fibers on the basis of certain mineralogical criteria. Implications of SIRA coatings with respect to carcinogenesis are worthy of further study.

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.

Mesothelioma with signet-ring cell features: report of 23 cases.

Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum. For comparison purposes and in order to determine the value of these techniques in the differential diagnosis of these tumors, seven cases of signet-ring cell lung adenocarcinoma were also studied. All signet-ring cell mesotheliomas were positive for calretinin, keratin 5/6, keratin 7, and mesothelin, 93% for podoplanin, and 91% for WT1; whereas, none reacted for MOC-31, CEA, TAG-72, CD15, TTF-1, napsin A, or CDX2. Among signet-ring cell lung adenocarcinomas, 100% were positive for keratin 7, CEA, and napsin A, 86% each for TTF-1 and TAG-72, 71% for CD15, and 14% for mesothelin, while all were negative for calretinin, keratin 5/6, WT1, podoplanin, and CDX2. After analyzing the results, it is concluded that the panels of markers used in the differential diagnosis of this mesothelioma variant should include those markers that are usually expressed in mesotheliomas (eg, calretinin, keratin 5/6, WT1, and podoplanin), broad-spectrum carcinoma markers that are frequently expressed in adenocarcinomas regardless of their site of origin (eg, MOC-31 and CEA), and organ-associated markers (eg, TTF-1 and napsin A for lung), which allow the site of origin of a metastatic adenocarcinoma to be established. Electron microscopy can be very useful as it permits the identification of characteristic ultrastructural mesothelioma and adenocarcinoma markers, and it also allows a better understanding of the morphologic features seen on routine light microscopy. Pathologists should be aware of this mesothelioma subtype as it can potentially be confused with other tumors that exhibit signet-ring features.

Deciduoid mesothelioma: report of 21 cases with review of the literature.

Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma that was initially considered to occur exclusively in the peritoneum of young women who had no history of asbestos exposure and to be characterized by an aggressive clinical course, but it was later demonstrated that this tumor could also occur in the pleura of older men and women who had been exposed to asbestos. Some subsequent studies have also indicated that the clinical course is no different from that of conventional epithelioid mesothelioma. Herein are reported 21 cases of deciduoid mesothelioma that were investigated using a large panel of immunohistochemical markers, 9 of which were also studied by electron microscopy. Fifteen of the patients were male and 6 were female (mean age, 60 years). Seventeen of the cases originated in the pleura and four in the peritoneum. Histologically, all of the cases were composed of large, polygonal or ovoid cells with well-defined cell borders, dense eosinophilic cytoplasm, and single or multiple nuclei. In some cases, the cells exhibited a wide variation in their size and shape, frequent loss of cell cohesion, marked nuclear atypia, and high mitotic activity (>5 per 10 HPF); whereas, in others, the cells were more cohesive, less pleomorphic, and the mitotic activity low. As the survival of patients in the first group of cases was shorter (mean, 7 months), when compared with that of the latter (mean, 23 months), it is concluded that the differences in prognosis reported in deciduoid mesothelioma are due to the existence of a high-grade subgroup that presents highly aggressive clinical behavior. Therefore, when a high-grade deciduoid mesothelioma is present, it should be reported as it can significantly affect prognosis and treatment. The use of immunohistochemistry and electron microscopy in assisting in the differential diagnosis of deciduoid mesothelioma is also discussed.

Pleomorphic mesothelioma: report of 10 cases.

Mesotheliomas with pleomorphic features are rare and only a few studies on this mesothelioma variant have been published. Little information regarding the immunoprofile of these tumors and none on their electron microscopic features was included in these studies. Herein are reported 10 cases of pleomorphic mesothelioma that were investigated using a large panel of immunohistochemical markers, 4 of which were also studied by electron microscopy. All of the patients were men and seven had a history of asbestos exposure. Nine of the cases originated in the pleura and one in the peritoneum. Histologically, the tumors were characterized by being composed of large, often discohesive, cells that varied in size and shape, had dense abundant eosinophilic cytoplasm, and single or multiple irregular nuclei, which often contained one or several large nucleoli. Mitotic activity was high and atypical mitoses frequent. Immunoreactivity for pan-keratin and keratin 7 was strong in all of the cases. Expression for calretinin, WT1, podoplanin, mesothelin and keratin 5/6 was also frequent, but variable. All cases were negative for MOC-31, carcinoembryonic antigen, CD15, TAG-72 and thyroid transcription factor-1. Electron microscopy often showed the presence of abundant long, slender microvilli on the cell membrane of the neoplastic cells. These findings demonstrate that, contrary to what has been suggested by some investigators, both immunohistochemistry and electron microscopy can be very helpful in assisting in the diagnosis of pleomorphic mesotheliomas. That the seven patients who underwent extrapleural pneumonectomy had extensive lymph node metastasis and that the median survival of those patients for whom follow-up information was available was only 8.2 months indicates that mesotheliomas with pleomorphic features are associated with highly aggressive clinical behavior. Therefore, when this subtype of epithelioid mesothelioma is present, it should be reported as it can significantly affect the prognosis and treatment of the patient.

Mesotheliomas with crystalloid structures: report of nine cases, including one with oncocytic features.

Although the presence of crystalloids has historically been of largely academic interest or simply an intriguing curiosity, these structures have occasionally been useful in the differential diagnosis of some tumors. Crystalloids have only rarely been reported in mesotheliomas, and their presence in these tumors has not been sufficiently investigated, nor has their potential value as an ultrastructural marker for mesothelioma been established. The finding of a case of mesothelioma in which the vast majority of the neoplastic cells contained intracytoplasmic crystalloids prompted a search for these structures in 69 consecutive cases of mesothelioma (59 epithelioid, 7 sarcomatoid, 3 mixed-epithelioid sarcomatoid). Crystalloids were found in 9 (15%) of the 59 epithelioid mesotheliomas, indicating that these structures are not as rare as had been thought. That these inclusions were demonstrated in tumors exhibiting diverse histological patterns and were not confined to a single subtype of epithelioid mesothelioma indicates that, because of their unique morphology, when present, they can assist in the diagnosis of these tumors. In addition, oncocytic features were also seen in one of the cases with crystalloid inclusions. Pathologists should be aware of the fact that, even though uncommon, mesotheliomas can present oncocytic morphology and, therefore, these tumors should be included in the differential diagnosis of those neoplasms that display similar morphological features, and which can metastasize to the serosal membranes. To my knowledge, an oncocytic mesothelioma has not previously been reported.

Disseminated lipid-rich peritoneal mesothelioma in a horse.

A 9-year-old Haflinger mare presented to the Liphook Equine Hospital with a history of weight loss, azotemia, and repeated episodes of ascites over a period of 10 days. The horse was euthanized after exploratory laparotomy revealed large numbers of variably sized masses distributed throughout the peritoneal cavity. Macroscopically, some masses were papillary, while others were nodular. Histologically, the masses were comprised of large to giant, variably shaped, and occasionally multinucleated neoplastic cells with marked anisokaryosis and anisocytosis and a high mitotic rate. Small to moderate numbers of neoplastic cells were swollen by 1 to several, moderately sized to large, clear, circular or ovoid vacuoles, which stained positive with oil red O. Immunohistochemically, the neoplastic cells co-expressed vimentin and cytokeratin. Electron microscopy demonstrated tumor cells with tight junctions, microvilli, and numerous intracytoplasmic lipid droplets. These findings are consistent with a lipid-rich form of mesothelioma, which should be considered as a differential diagnosis if lipid vacuoles are present in potentially neoplastic cells in equine abdominocentesis samples.

Pathologic evaluation of malignant pleural mesothelioma.

Pathologists play an important role in the surgical management of diffuse malignant pleural mesothelioma, which relies heavily on accurate diagnosis and staging. The pathologist provides crucial input to the determination of many prognostic factors including histologic subtype, extent of local disease progression, resection margins, and nodal status. They consult with the clinical care team at multiple points along the treatment spectrum, preoperatively, intraoperatively, and postoperatively. Finally, they are increasingly called on to guide selection of chemotherapy and measure treatment response.

Endoscopic ultrasound-guided fine needle aspiration for staging of malignant pleural mesothelioma.

BACKGROUND: Radical surgery for malignant pleural mesothelioma does not improve survival in patients with nodal metastases. Imaging is poor at predicting nodal involvement and mediastinoscopy, though frequently used, is of low sensitivity. As endobronchial ultrasound (EBUS) and esophageal endoscopic ultrasound (EUS) are accurate for nodal staging of lung cancer, we hypothesized that they would be at least as sensitive as cervical video-mediastinoscopy for nodal staging of mesothelioma. METHODS: Eighty-five patients with mesothelioma who were potential candidates for radical surgery underwent preoperative staging with mediastinoscopy (n = 50) or EBUS (n = 38). Eleven patients also underwent EUS. RESULTS: Diagnostic yield (specimens containing lymphocytes or tumor cells) was 100% for mediastinoscopy and 84% for EBUS (p < 0.001). Mediastinoscopy identified 7 of 50 (14%) patients with nodal metastases. Thirty-eight (76%) mediastinoscopy-negative patients underwent surgery with nodal sampling and there were 18 false negatives. Endobronchial ultrasound identified 13 of 38 (34%) patients with nodal metastases. Twenty-two (58%) EBUS-negative patients underwent surgery with nodal sampling and there were 10 false negatives. Sensitivity and negative predictive value for mediastinoscopy were 28% and 49%, and 59% and 57% for EBUS. Eleven patients had EUS preoperatively, which revealed infradiaphragmatic nodal metastases in 5 patients. CONCLUSIONS: Although this study is retrospective, EBUS had higher sensitivity than either mediastinoscopy or imaging studies for detection of nodal metastases. Nevertheless, the ability to accurately identify nodal involvement preoperatively in patients with mesothelioma remains suboptimal. Esophageal ultrasound may complement EBUS particularly in cases where infradiaphragmatic nodal metastases are suspected.

A biphasic malignant mesothelioma of the peritoneum and pleura in a horse.

This report describes the macroscopic, histologic, immunohistologic and ultrastructural characteristics ofa biphasic malignant mesothelioma in the peritoneal and pleural cavity of a 13-year-old Icelandic pony mare, which exhibited recurrent ascites clinically. Immunohistology was performed employing multiple monoclonal antibodies against cytokeratins (CK) and vimentin. The ultrastructural examination included the quantitative evaluation of the length to diameter ratio of the microvilli. Post mortem examination revealed a severe ascites and hydrothorax. The serosal surfaces of the peritoneum and pleura displayed poorly-demarcated, multifocal to coalescing laminar masses and small nodules. Histology revealed a bimorphic mass consisting of spindle-shaped cells and microcystic epithelioid areas. A transcoelomic and local invasive growth pattern as well as lymph node metastases were noticed. Immunohistology revealed a strong expression of CK. Though a low and moderate expression of CK5/6 and CK20 was present, respectively, CK7 and CK10-antigens were lacking. Ultrastructurally, the epithelioid mesothelioma cells displayed long microvilli, cytoplasmic tonofilaments, and desmosomes. Quantitative evaluation of the length to diameter ratio of the 10 longest microvilli revealed a mean value of approximately 16.2. Summarized, this report described the case of a malignant biphasic mesothelioma with an atypical CK20 expression but a characteristic ultrastructural morphology including long microvilli.

[Size distribution of amphibole fibres from lung and pleural tissues sampled from mesothelioma cases due to environmental exposure]. / Caratterizzazione dimensionale di fibre anfiboliche nel polmone e nella pleura di casi di mesotelioma da esposizione ambientale.

BACKGROUND: It has been suggested that malignant mesothelioma might be mainly or only connected with the action of short and ultrathin fibres. On the basis of this hypothesis fibres less than 5 microm long and 0.2-0.1 microm thick would enter the pulmonary-pleura barrier and reach the parietal pleura thus inducing mesothelioma. The hypothesis raised a stimulating scientific discussion. OBJECTIVES: The aim of this communication is to report the initial results obtained comparing the size of amphibole fibres from healthy lung tissue with those from pleural tissue sampled from subjects whose death cause of death was mesothelioma. METHODS: Four mesothelioma cases due to environmental exposure were studied; the fibres were categorized by scanning electron microscopy; for every fibre, length and diameter were measured and the mineral type was defined by its chemical composition determined by X-ray microanalysis. RESULTS: The most important characteristics of the detected fibres were: the average length offibres from the lung and pleural tissues taken from the same subject did not difer, in all cases, by more than 10-12%; 95% offibres found in the lung tissues of all subjects had a length greater than 5 microm; 98% of fibres found in the pleural tissues had a length greater than 5 microm; the average diameter of the fibres found in the pleural tissues was 70% of the diameter of the fibres from the lung tissues. CONCLUSIONS: The experimental data obtained in this study confirm the correlation between malignant mesothelioma and the presence in the lung and pleural tissues of fibres with a length greater, even much greater, than 4-5 microm; thus the hypothesis that the chief factors inducing mesothelioma are the "ultrashort" and "ultrathin" fibres appears rather weak.

[Asbestos fibre lung burden and exposure indices in asbestos-cement workers]. / Carico polmonare di fibre di asbesto e indici di esposizione cumulativa in lavoratori del cementoamianto.

BACKGROUND: In many previous studies, the asbestos fibres retained in the lung were regarded as a good index of cumulative occupational asbestos exposure. Twelve workers suffering from asbestos-related diseases and had been employed in an asbestos-cement factory operating from 1961 to 1994 underwent post mortem investigations in the course of a criminal law suit. OBJECTIVES: Samples of lung tissues were collected for electron microscopy analysis to measure the asbestos fibre burden of the lungs in workers with high exposure, and assess the possible correlation between asbestos fibre lung burden and the estimated levels of cumulative exposure. METHODS: Samples of lung parenchyma obtained from a consecutive series of 12 post-mortem examinations that were performed between 1994 and 2007and included 5 cases of malignant pleural mesothelioma, 4 lung cancers, 1 case of asbestosis and2 ofpleuralplagues, were collected, stored and analysed by SEM electron microscopy, according to the methods suggested by the current scientific literature. For each worker, all males, a detailed occupational history was reconstructed by means ofpersonal interviews; both the measurements of airborne asbestos fibresperformed by the factory in the 1970's and the duration of each single job in the plant were taken into account to estimate an individual cumulative exposure index. RESULTS: A wide variation of total asbestos fibre concentrations in the lung (1,320-118 million) was observed; in all 12 workers, the lung amphibole fibre burden exceeded 1,000,000 fibres per g/dry tissue, The highest values were detected in the mesothelioma cases, in which the mean fibre concentrations differed statistically (t=2.29, p=0.045) from the mean calculated for the other asbestos-related diseases; in 9 subjects only amphibole fibres were detected. There was a good correlation between total asbestos fibre concentration and cumulative exposure index (r=0.91, p<0.0001). CONCLUSION: This study, which was numerically the biggest ever performed in Italy for this category of workers, confirms a wide range of total asbestos fibre burden in heavily occupationally exposed workers and showed that of the asbestos-related diseases, the highest lung concentrations of asbestos fibres were reached in cases of mesothelioma. It was also observed that almost the entire lung burden consists of only amphibole fibres, all exceeding 1 million per gramme of dry tissue. This study tested a synthetic cumulative occupational exposure index, which appears to be well correlated to the level of exposure established by biological analysis.