The significance of asbestos exposure in the diagnosis of mesothelioma: a 28-year experience from a major urban hospital

A continued increase in the incidence of diffuse mesothelioma has been attributed to greater industrial use of asbestos but is also due in part to wider acceptance of this tumor by pathologists. In this retrospective study, the epidemiology, clinical presentation, and pathology of asbestos and non-asbestos-related mesothelioma from a major urban hospital were reviewed. Of the 36 cases of mesothelioma on file, 19 were not associated with exposure to asbestos. Although a retrospective study raises the possibility of inadequate occupational histories, the lack of history of asbestos exposure correlated with postmortem histology by light microscopy. When postmortem material was reviewed, evidence of asbestos exposure was present in all cases of mesothelioma with history of exposure to asbestos, and in no cases in which the patient denied history of asbestos exposure. Using strict histologic and histochemical criteria, the diagnosis of mesothelioma was confirmed in 8 of 9 patients with asbestos-related mesothelioma but in only 4 of 13 cases of non-asbestos-related mesothelioma. The diagnosis of diffuse methelioma is often difficult to make even wtih complete autopsy examinations. It should be entertained only with adherence to strict clinical and pathologic criteria, especially in women with no history to exposure to asbestos dust.     

Ultrastructural features of diffuse malignant mesotheliomas

The distinction of malignant mesothelioma from tumors metastatic to the serosal membranes can often be made based on the results of histochemical or immunohistochemical studies. However, in some cases, these techniques are inadequate to make a firm diagnosis. In these instances, electron microscopic studies with the observation of a constellation of characteristic ultrastructural findings may permit an unequivocal diagnosis of mesothelioma.     

Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography

BACKGROUND: The diagnosis of malignant mesothelioma is a challenging medical problem. CT often cannot differentiate between benign diffuse pleural thickening and malignant mesothelioma, while thoracentesis and CT-guided biopsies are insensitive. We have assessed the value of positron emission tomography (PET) with 2-fluoro-2-deoxy-D-glucose (FDG) in the evaluation of malignant mesothelioma. METHODS: Twenty-eight consecutive patients referred for the evaluation of suspected malignant mesothelioma were evaluated by FDG-PET imaging. Measured attenuation correction was performed in 26 of 28 cases for quantitation with the standardized uptake value (SUV) method. The results of PET imaging were compared with those of video-assisted thoracoscopy or surgical biopsies. RESULTS: Surgical biopsy specimens confirmed the presence of malignant disease in 24 patients and demonstrated benign processes in the remaining four. The uptake of FDG was significantly higher in malignant than in benign lesions (SUV=4.9+/-2.9 and SUV=1.4+/-0.6, respectively; p<0.0001). With a SUV cutoff of 2.0 to differentiate between malignant and benign disease, a sensitivity of 91% and a specificity of 100% could be achieved, although the activity in some epithelial mesotheliomas tended to be close to this threshold. FDG-PET images provided excellent delineation of the active tumor sites. Hypermetabolic lymph node involvement was noted on FDG-PET images in 12 patients, 9 of which appeared normal on CT scans. Histologic examination in six patients confirmed malignant nodal disease in five cases and indicated granulomatous lymphadenitis in one. CONCLUSION: In this highly selected population, FDG-PET imaging was a sensitive method to identify malignant mesothelioma and determine the extent of the disease process.     

The value of antibodies 44-3A6, SM3, HBME-1, and thrombomodulin in differentiating epithelial pleural mesothelioma from lung adenocarcinoma: a comparative study with other commonly used antibodies

The distinction between pleural mesothelioma and peripheral pulmonary adenocarcinoma involving the pleura continues to be a diagnostic problem in surgical pathology. In recent years, the use of various immunohistochemical markers to facilitate this differential diagnosis has become common. In this study, the value of monoclonal antibodies 44-3A6, SM3, HBME-1, and thrombomodulin is compared in the differentiation of these conditions. Fifteen (68.2%) of 22, and 10 (52.6%) of 19 mesotheliomas stained positively with 44-3A6 and SM3, respectively, whereas all 23 (100%) adenocarcinomas reacted with both antibodies. Sixteen (80%) of 20 mesotheliomas and 14 (63.6%) of 22 lung adenocarcinomas reacted with HBME-1, whereas 16 (80%) of 20 mesotheliomas and only three (11.1%) of 27 adenocarcinomas were positive for thrombomodulin. Because thrombomodulin was expressed in most mesotheliomas but in only a few lung adenocarcinomas, this marker may have some diagnostic value when it is included in the standard immunohistochemical panel of markers used in the evaluation of mesotheliomas, especially when a positive marker for mesothelioma is needed. Antibodies 44-3A6, SM3, and HBME-1 have no practical value in discriminating epithelial pleural mesothelioma from lung adenocarcinoma.     

Fluorotyping of HLA-A by sequence-specific priming and fluorogenic probing

AIMS: To determine the value of immunocytochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy using commercially available monoclonal antibodies. METHODS AND RESULTS: A panel of monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), Leu-M1, CD30 (Ber-H2), vimentin and desmin, was applied to 40 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura (16 pulmonary and seven extrapulmonary). Positivities for Ber-EP4, CEA, B72.3 and Leu-M1 were found to have the highest nosologic sensitivities (87.0%, 65.2%, 52.5% and 43.5%, respectively) and specificities (97.5%, 97.5%, 100% and 95%, respectively) for carcinoma. Positive staining for vimentin had the highest sensitivity (87.5%) with 95.7% specificity for mesothelioma. Positive staining for desmin was found in 45% of mesotheliomas and 0% of carcinomas. Diagnostic sensitivity and diagnostic specificity (P-values) were calculated for these markers. In respect to the diagnostic power defined by the clinically relevant predictive values of positive and negative tests, we found that a two-marker panel of antibodies including vimentin and Ber-EP4 is most useful for the histopathological distinction between carcinoma (pulmonary or extrapulmonary) and malignant pleural mesothelioma. CONCLUSIONS: A combination of Ber-EP4 and vimentin provides the most sensitive and specific pair of markers for distinguishing between malignant pleural mesothelioma and carcinoma metastatic to the pleura. The prevalence of the tested tumours should be taken into account when evaluating the clinical value of ancillary techniques in pathology.     

Egg components and hatchling lipid reserves: parental investment in kinosternid turtles from the southeastern United States

PURPOSE: Identification of prognostic factors in patients with malignant pleural mesothelioma based on prospectively collected international data. PATIENTS AND METHODS: From October 1984 to October 1993, 204 eligible adult patients with malignant pleural mesothelioma were entered into five consecutive prospective European Organization for Research and Treatment of Cancer (EORTC) phase II clinical trials designed to assess the efficacy of various anticancer drugs (mitoxantrone, epidoxorubicin, etoposide, and paclitaxel). The Cox model was used to assess 13 factors related to biology and disease history with respect to survival. RESULTS: The median survival duration was 12.6 months from diagnosis and 8.4 months from trial entry. In the multivariate analysis, poor prognosis was associated with a poor performance status, a high WBC count, a probable/possible histologic diagnosis of mesothelioma, male gender, and having sarcomatous tissue as the histologic subtype. Taking these five factors into consideration, patients were classified into two groups: a good-prognosis group (1-year survival rate, 40%; 95% confidence interval [CI], 30% to 50%) and a poor-prognosis group (1-year survival, 12%; 95% CI, 4% to 20%). CONCLUSION: These results may help to design new clinical trials in pleural mesothelioma by selecting more homogenous groups of patients.     

Survival of asbestos insulation workers with mesothelioma

Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available.     

Management of a short femur discovered via ultrasound in utero. Prenatal diagnosis of Stuve-Wiedemann syndrome

BACKGROUND: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously. METHODS: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls. RESULTS: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested. CONCLUSIONS: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos.     

Malignant mesothelioma. Diagnosis and treatment

In over 90% of cases, mesothelioma initially presents as a banal pleural effusion, contributing no orientation to the diagnosis. The pleural fluid can even disappear after initial puncture. For early diagnosis, simple puncture, with or without biopsy, does not suffice. Thoracoscopy is 98% diagnostic. The course depends on the stage, the histological type and the general status. A new international TNM classification has been proposed to allow comparison of series and to choose a treatment appropriate to the stade: at stage I, intrapleural, local immuno-chemotherapy treatment gives good results; at stages II and III, surgery followed by radiation therapy are indicated; at stage IV, symptomatic treatment alone is justified.     

Benign fibrous mesothelioma: report of 8 cases

Benign fibrous mesothelioma (BFM) is a primary, isolated tumor of the pleura. In 80% of patients the tumor originates in the visceral pleura. BFM is rare and localized malignant mesothelioma, whose prognosis and treatment is significantly different, must be considered as a differential diagnosis. We report 8 cases of BFM excised by thoracotomy. In 6 asymptomatic patients, diagnosis was based on radiological images. One patient with a large tumor suffered dyspnea, acropachia and hypertrophic osteoarthropathy. The last patient experienced long-lasting chest pain even though the tumor was small (3 x 3 x 1 cm). Diagnosis was before thoracotomy in 3 cases, 2 by punch biopsy (tru-cut) and the other by thoracoscopy. The results of pleural fluid analysis were nonspecific in 2 of the 3 cases in which pleural effusion was present. Thoracotomy allowed removal of the entire tumor in all patients.     

Retroperitoneal ganglioneuroma. Report of a case

OBJECTIVE: To report an additional case of retroperitoneal ganglioneuroma. METHODS/RESULTS: A case of retroperitoneal ganglioneuroma that had been incidentally discovered in a 27-year-old male during abdominal US evaluation is described. The diagnosis was based on the histopathological findings after US-guided biopsy. The clinical features and the findings of the complementary tests, which included radiological assessment, intravenous urography, CT and cavography are presented, as well as the pathology findings. Treatment was by complete surgical excision of the tumor. CONCLUSION: Treatment of ganglioneuroma is by surgery, since the diagnosis is generally based on the histopathological analysis of the surgical specimen. For those cases with a preoperative diagnosis, some authors advocate surgery for patients with clinical evidence of neuroblastoma or another pathology arising from this disease. Although infrequent, ganglioneuroma coexisting with neuroblastoma can occur. For this reason, complete excision of the tumor is preferred.     

Functional activity of Rh monoclonal antibodies in ADCC assay

A 58-year-old woman with malignant mesothelioma metastatic to the orbit is reported. Malignant pleural mesothelioma was diagnosed by pleural biopsy. Marked reduction of pleural effusion was obtained with intrapleural interleukin-2 therapy. Systemic chemotherapy failed to elicit a response after the first recurrence of the tumor. Multiple systemic metastasis, including metastasis to the orbit, developed and the patient died one year and 4 months after the initial diagnosis. Although malignant mesothelioma is known to spread hematogenously, sometimes producing brain metastasis, there have been few reports of orbital metastasis, and in fact the present report may be the first clinically documented account of its kind.     

Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic larynx

Cystic mesothelioma of peritoneum is a rare neoplasia that was identified as a individual entity by ultrastructural and immunoistochemical studies. It is more frequent in young woman and often it tends to recur. Because of its rarity and difficulty in differential diagnosis, the Authors describe a case of cystic mesothelioma observed.     

The immunohistochemical diagnostic panel for epithelial mesothelioma: a reevaluation after heat-induced epitope retrieval

The immunohistochemical diagnosis between epithelial mesothelioma and adenocarcinoma is currently based on the use of a panel of antibodies to adenocarcinoma-associated antigens and a few antibodies to mesothelial-associated antigens. Since the introduction of epitope retrieval methods, the sensitivity of many antibodies has been enhanced. Thus, a reevaluation of the mesothelioma/adenocarcinoma diagnostic panel becomes necessary. We studied 268 paraffin-embedded formalin-fixed tumor samples that included 57 epithelial mesotheliomas and 211 adenocarcinomas of various origins, comparing an extensive antibody panel with and without heat-induced epitope retrieval (HIER). Marked increase in the sensitivity of several antibodies, with no loss of specificity, was found when HIER was used. After statistical analysis, the antibodies to the epithelial glycoproteins carcinoembryonic antigen, BerEp4, and Bg8 emerged as the best discriminators between adenocarcinoma and epithelial mesothelioma within the entire panel. The mesothelium-associated antibodies, HBME-1, calretinin, and thrombomodulin were less sensitive and less specific than the former, although they were found to be useful on certain cases. Antibodies to cytokeratins and vimentin, although of minor diagnostic value in this context, may be helpful to evaluate the quality of antigen preservation. This study confirms the value of immunohistochemistry to accurately distinguish mesothelioma from adenocarcinoma when an antibody panel approach is used. The addition of heat-induced epitope retrieval methods increases the effectiveness of the procedure and is recommended for most of the antibody panel members.     

A clinicopathological study of infections in burn patients and importance of biopsy

Malignant peritoneal mesothelioma is a rare disease. The most frequent initial symptoms are abdominal pain, anorexia, marked weight loss and ascites. Clinical presentation as fever of unknown origin is exceptional. We report three cases diagnosed over a period of twenty years, two cases as fever of unknown origin and the third as prolonged fever. Three patients died within two months after diagnosis and prolonged fever was the clinical manifestation at the onset of the disease. It is important to take malignant peritoneal mesothelioma in the differential diagnosis of fever unknown origin.     

Actions of nitric oxide on renal epithelial transport

A 55-year-old male who had a remote history of occupational asbestos exposure consulted us because of chest pain. Chest X-ray revealed diffuse pleural thickening and pleural effusion on the right. A diagnosis of malignant mesothelioma, biphasic type was made by needle pleural biopsy. Fourteen months later, the patient died of brain metastasis. At autopsy, malignant mesothelioma of the pleura with metastasis to the brain and bilateral adrenal glands was observed. Brain metastases proven by autopsy are rare in cases of malignant mesothelioma. The ferruginous body count in the lung tissue was 16 per gram of wet weight.     

Lupus syndrome after parvovirus B19 infection

BACKGROUND: Cutaneous leishmaniasis and disseminated histoplasmosis can be diagnosed by direct examination of pathology specimens after Giemsa staining. CASE REPORT: An HIV-infected man developed cutaneous leishmaniasis and disseminated histoplasmosis with buccal lesions concomitantly. Smears stained with the RAL 555 kit provided the diagnosis of these two diseases. DISCUSSION: This case illustrates how direct microscopic examinations can provide inexpensive, rapid and safe diagnosis of infectious diseases. Direct microscopic examinations are routine practice in a tropical dermatology unit.     

Success and constraints in the implementation of WHO guidelines for the management of diarrhoea in Albania

BACKGROUND: Venous thromboembolic disease is a recurring reason for death, it is often well-known but sometimes misunderstood. The right treatment for this pathology should not follow one approach only, but several strategies with respect to the seriousness and extension of the several clinical pictures. In particular the pharmacological therapy tries to find the balance between risks and benefits. It is well-known that a weak treatment may cause an increase in the risk of the pathology extension or of recurrence; on the other hand, a therapy exceeding the well known ranges exposes to important hemorrhagic risk. METHODS: This work presents the personal seven years' experience in patients affected by limb venous thrombosis, in some cases combined with pulmonary embolism. For all patients the pathology seriousness has been assessed by echoduplex scanner and angio-CT, and routine serum electrolite and enzymes analysis and blood counts have been carried out. Different therapies have been investigated, their evolution over the years (on the basis of international and personal experience) and the follow-ups. RESULTS AND CONCLUSIONS: The foudamental implications of this experience are: the more remarkable use of vena cava filters do not improve clinical findings' follow-up. On the contrary, it can cause the extension of pathology; heparin therapy must start early and the therapeutic range must be reached as soon as possible. Any delay, together with immobilization, can cause the extension of the pathology; diagnosis research cannot stop at the acuity moment but it should study also the etiopathogenetic picture. This affects the future therapeutic strategy in the follow-up; fibrinolitic therapy, once recommended for extended femoral-iliac thrombosis, should be used for serious levels of the same pathology and only for patients with low haemorrhage risk, or for patients affected by periodic pulmonary thromboembolism which may compromise haemodynamic system.     

Malignant mesothelioma of the tunica vaginalis testis: review of the literature and assessment of prognostic parameters

BACKGROUND: Only 73 cases of malignant mesothelioma of the tunica vaginalis testis have been reported in the last 30 years. Although these tumors were most often seen in patients between ages 55 and 75 years, 10% of the patients were younger than 25 years. Because prognostic parameters have not yet been reported, the authors present another case of a male age 14 years and a review of the available literature, which they conducted to determine prognostic parameters. METHODS: The medical literature about malignant mesothelioma of the tunica vaginalis testis was reviewed. For the determination of prognostic parameters, a univariate and multivariate Cox regression model was used to assess the relevance of the patient's age, history of asbestos exposure, tumor histology, primary therapeutic approach, and presence of metastatic disease to survival. RESULTS: Previous exposure to asbestos or asbestos-containing materials must be considered a risk factor for the development of malignant mesothelioma. The major difficulty in managing patients with malignant mesothelioma of the tunica vaginalis testis was determining an accurate preoperative diagnosis, which was reported in only two cases. Due to the lack of characteristic symptoms, 97.3% of the cases were diagnosed intraoperatively. Of patients who underwent local resection of the hydrocele wall, 35.7% experienced local tumor recurrence, as compared with 10.5% after scrotal orchiectomy and 11.5% after inguinal orchiectomy. Therefore, radical orchiectomy should be the first-line therapy. The median survival of the patients was 23 months, which decreased to 14 months in cases of recurrence. The overall recurrence rate (local and disseminated) was 52.5%. More than 60% of recurrences developed within the first 2 years of the follow-up. In some cases of disseminated mesothelioma, adjuvant chemotherapy or radiotherapy was given. Although reports on adjuvant treatments were limited, radiotherapy appeared to be more effective than chemotherapy. However, 37.9% died of disease progression. Assessment of prognostic parameters revealed a significant correlation of patient's age with survival (P < 0.01), with a better outcome for younger patients and a worse disease course for patients with primary disseminated disease (P < 0.05) in univariate analysis. A multivariate Cox regression model of prognostic parameters concerning survival did not yield statistically significant results. CONCLUSIONS: Malignant mesotheliomas of the tunica vaginalis testis rarely occur, but the possibility should be considered for all age groups. Univariate analysis determined that a patient's age and the presence of primary disseminated disease were prognostic parameters related to survival. Due to the invasive potential of this disease and the risk of tumor recurrence, radical orchiectomy and close follow-up are strongly recommended.     

Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue

BACKGROUND: DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in man though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe. The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period. METHODS: DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues-namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively. RESULTS: PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma. In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers. The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other. CONCLUSIONS: Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.