Asbestos exposure and histological subtype of malignant mesothelioma.

BACKGROUND: Malignant mesothelioma (MM) has distinct histological subtypes (epithelioid, sarcomatoid and biphasic) with variable behaviour and prognoses. It is well recognised that survival time varies with the histological subtype of MM. It is not known, however, if asbestos exposure characteristics (type of asbestos, degree of exposure) are associated with different histological subtypes. AIM: To determine if the pathological MM subtype is associated with the type of asbestos or the attributes of asbestos exposure. METHODS: Cases of MM for the period 1962 until 2012, their main histological subtype and their most significant source of asbestos exposure were collected from the Western Australian Mesothelioma Registry. Exposure characteristics included, degree of asbestos exposure (including total days exposed, years since first exposure and, for crocidolite only, calculated cumulative exposure), source of exposure (occupational or environmental), form of asbestos handled (raw or processed) and type of asbestos (crocidolite only or mixed fibres). RESULTS: Patients with the biphasic subtype were more likely to have occupational exposure (OR 1.83, 1.12 to 2.85) and exposure to raw fibres (OR 1.58, 1.19 to 2.10). However, differences between subtypes in the proportions with these different exposure characteristics were small and unlikely to be biologically relevant. Other indicators of asbestos exposure were not associated with the histological subtype of mesothelioma. CONCLUSIONS: There was no strong evidence of a consistent role of asbestos exposure indicators in determining the histological subtype of MM.

Predicting survival in malignant mesothelioma.

Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs. Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis. Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2-1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1-1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0-198), 177 (48-350), 221 (97-504), 238 (108-502) and 301 (134-611) days; ~4 weeks of this apparent improvement can be attributed to earlier diagnosis. With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.

Reactive mesothelial hyperplasia vs mesothelioma, including mesothelioma in situ: a brief review.

In biopsy tissue, discrimination between reactive mesothelial hyperplasia and epithelial mesothelioma can pose a major problem for the surgical pathologist. Confidence in the diagnosis is often proportional to the amount of tissue available for study and depends largely on findings of invasion and the extent and cytologic atypia of the lesion, because there is no marker specific for the mesothelium and that discriminates consistently among normal, hyperplastic, and neoplastic mesothelial tissue. Therefore, mesothelioma in situ is diagnosable only when invasive epithelial mesothelioma is demonstrable in the same specimen, in a follow-up biopsy specimen, or at autopsy. Comparison of 22 cases of mesothelioma in situ that fulfill these requirements for diagnosis with 141 invasive mesotheliomas and 78 reactive mesothelioses indicates that strong linear membrane-related labeling for epithelial membrane antigen and silver-labeled nucleolar organizer region-positive material that occupies 0.6677 microm2 or more of the nucleus in an atypical in situ mesothelial lesion of the pleura are found consistently in neoplastic mesothelial cells. Although these findings may engender suspicion of mesothelioma in situ in high-risk persons, the criteria for diagnosis of pure mesothelial lesions of this type are still under study. Mesothelioma in situ should be considered proved only when unequivocal invasion is identified in a different area of the pleura or at a different time; a diagnosis of pure mesothelioma in situ should not be made in patients not exposed to asbestos.

Adenoid basal carcinoma of the cervix uteri.

This paper describes a case of adenoid basal carcinoma of the uterine cervix, occurring in a woman aged 78 years. In view of the rarity and the limited knowledge of this group of neoplasms, details of the clinical history, the histological appearances, and the histochemical reactions are presented. An attempt is made to define the histogenesis of the tumour and some points on nonmenclature are discussed. It is suggested that the tumour arises from multipotential cervical basal cells and that the adenoid structures rather than being true glands are formed by degeneration of the connective tissue stroma. On the basis of a review of reported cases it seems possible that this tumour will be shown to be one of low-grade malignancy.

Pathological findings after right lung transplantation in a patient with fibrosing alveolitis.

The pathological findings in a patient who died two months after right lung transplantation for fibrosing alveolitis are reported. The cause of death was haemoptysis, due to penetrating ulceration causing a fistula between the surface of the cartilagenous part of the main bronchus of the donor lung and the right upper lobe pulmonary artery. The opening in the donor bronchus was immediately distal to the line of the bronchial anastomosis and through an actively inflamed area. Other parts of the donor bronchus had microscopic changes suggesting ischaemia, emphasizing that inadequacy of blood supply to the donor extrapulmonary bronchus is one of the most serious hazards of lung transplantation. Within the lung, histological features of rejection were mild and there was minimal evidence of infection. Another question raised by this case is whether the donor lung was in the process of developing the original disease, evidence for which was sought electron microscopically but was not proven.

Renal oncocytoma.

Several authors have recently drawn attention to renal oncocytoma, a neoplasm hitherto rarely recognized. Their reports suggest that renal oncocytomas are not uncommon and that they are benign and possess distinctive gross, microscopical, ultrastructural, and behavioral features. Most examples were discovered on re-examination of neoplasms previously classified as renal adenocarcinoma or adenoma. In a survey of renal neoplasms filed in our Department, we identified 8 cases; these are reported and the literature is reviewed.

A case of filariasis diagnosed on gastric cytology.

Cytological examination of gastric washings or brushing is a widely accepted technique used as a diagnostic aid in the detection of gastric malignancy. Occasionally, cytology may also provide valuable information concerning a variety of non-neoplastic disorders. This brief report is of the exceptional experience of finding numerous microfilariae of Loa loa type in a gastric lavage specimen. This observation led to appropriate further investigation and successful treatment.

Detection of tissue CEA-like substance as an aid in the differential diagnosis of malignant mesothelioma.

Sections of various adenocarcinomas and malignant mesotheliomas were tested for carcinoembryonic antigen (CEA) localized in tissues by the immunoperoxidase technique; epithelial mucin was demonstrated with the PAS technique. While CEA and mucin were found in many adenocarcinomas, both were absent in the 43 cases of malignant mesothelioma we investigated. In the problem of distinguishing between adenocarcinoma and mesothelioma, the CEA-test in combination with conventional strains for mucin is a useful technique and clearly identifies most adenocarcinomas. A dual negative result for CEA and mucin, although not proving that a given lesion is a mesothelioma, adds considerable support to this histological diagnosis.

Pleural fluid CEA levels in the diagnosis of malignant mesothelioma.

A study was undertaken to investigate whether the levels of carcino-embryonic antigen (CEA) in serous effusions helped distinguish between primary mesothelioma and metastatic adenocarcinoma in a body cavity. The investigation was designed to assess the role of the assay only when cytological analysis of the fluid had already shown the presence of malignant cells. No case of mesothelioma studied had levels of CEA above 2.9 ng/ml, whereas 67% of the adenocarcinomas tested were above 15 ng/ml. The test is helpful, therefore, in differentiating between these two types of malignant effusions.

Premalignant epithelial lesions of the gall bladder: a prospective study of 120 cholecystectomy specimens.

One hundred and twenty gall-bladders obtained at cholecystectomy for gall bladder diseases formed the basis of a prospective study of premalignant epithelial lesions. Six cases displayed abnormal mucosa (5%); 4 had atypical hyperplasia (dysplasia) and 2 gall-bladders had carcinoma-in-situ; all were associated with chronic cholecystitis and lithiasis. These changes are considered premalignant and are probably precursors of gall-bladder carcinoma. It is impossible to predict which patient with chronic gall-bladder disease is likely to harbour premalignant epithelial changes. In any event, thorough histological examination of all gall bladders removed surgically is more than justified.

The Rye classification of a population based series of Hodgkin's disease patients in Western Australia.

Data are presented on the incidence in Western Australia of subtypes of Hodgkin's disease which were obtained by review of all cases of the disease notified between 1960 and 1974. Observations were also made on within- and between-observer agreement on the use of the Rye classification by a group of 9 surgical pathologists, all in the day-to-day practice of pathology. Although many consensus diagnoses were made only after spirited discussion by the Group, the results suggested that general surgical pathologists can perform nearly as well as lymphoma experts. A comparison of the incidence of Hodgkin's disease and distribution of Rye subtypes in Western Australia with 4 other populations showed a similar overall incidence but appreciable variation in the relative frequency of the subtypes--mainly in the proportions of nodular sclerosing and mixed cellularity.

The concept of mesothelioma in situ: implications for diagnosis and histogenesis.

The concept of mesothelioma in situ is explored by a detailed examination of seven patients, subsequently proven to have pleural malignant mesothelioma, who initially had no evidence of gross tumor and for whom biopsy material was available at this early presentation. The tissue was assessed by routine microscopy, the immunoperoxidase technique for epithelial membrane antigen and silver staining for nucleolar organizer regions. Tiny lesions of the pleura that merged with or were adjacent to microscopically flat monolayered or folded mesothelium with cytological atypia were observed. The atypical cells reacted positively to epithelial membrane antigen, and the nucleolar organizer region counts were elevated. These observations are considered to support the possibility of the presence of mesothelioma in situ. These findings are discussed in the light of the proposed concept of mesothelioma in situ, its histogenesis, and its possible clinical relevance.

Malignant mesothelioma cells in sputum.

In five patients with malignant mesothelioma of pleura, malignant cells, presumably derived from intrapulmonary deposits, were found in sputum specimens. The cells presented mainly as papillary aggregates of epithelial-like cells, in most cases without specific identifiable mesothelial cell features. In one patient, the specimen was received early in the diagnostic work-up and led to a strong consideration of the diagnosis of adenocarcinoma. In the remainder, the finding was incidental, occurring after the diagnosis of mesothelioma had been established. The cases are reported to draw attention to this phenomenon, previously unreported in the cytologic literature, and to emphasize that the finding of malignant cells in sputum does not preclude the diagnosis of malignant mesothelioma.

The cytology of malignant mesothelioma in Western Australia.

The cytology of malignant mesothelioma seen in 12 patients associated with the mining of crocidolite asbestos in Western Australia is described. Two main patterns of mesothelioma were observed: the spindle cell and epithelial varieties. In the more common epithelial variety, five features were found to be of particular value in making a cytologic diagnosis. These include the finding of cell aggregates, multinucleation, the presence of brush-like borders, the close apposition of cell borders, and a characteristic cytoplasm. A diagnosis of malignant mesothelioma may be established by cytologic examination of effusions. The awareness of the possible occurrence of such a primary malignant neoplasm with the features outlined may be helpful in this regard.

Cytologic and tissue culture characteristics of asbestos-induced mesothelioma in rats.

Mesotheliomas were induced in rats by the intrapleural injection of Western Australia crocidolite asbestos. Over a two-year period, 10 of 18 animals in which implants were established developed mesotheliomas, for a 56% success rate. Histologically, most mesotheliomas were biphasic although predominantly spindle celled. Pleural fluid was examined in five of these malignant cases: three had a papillary epithelial picture, one had mainly anaplastic cells, and one contained predominantly spindle-shaped cells. Three types of cell aggregates occurred: classical collagen-containing papillary clusters, spindle-cell aggregates and cystlike spheres. These last structures corresponded to microcystic or adenomatoid growth present in four mesotheliomas. Two of the effusions were cultured successfully; the growth pattern was typically mesothelial, with in vitro production of collagen. Ultrastructurally, long, slender microvilli, cell junctions and intermediate filaments confirmed the mesothelial nature of these asbestos-induced rat malignancies.

Fine needle aspiration cytology of malignant mesothelioma.

The results of fine needle aspiration (FNA) cytology in 19 cases of malignant mesothelioma are presented. Adequate material for a diagnosis of malignancy was obtained in 17 cases, and in 8 cases a specific diagnosis of mesothelioma could be made. In four other cases, the findings were either consistent with or suggestive of mesothelioma; in four, accurate distinction from other neoplasms was not possible, and in two cases, adenocarcinoma was suggested. The spectrum of cytologic findings ranged from neoplasms of purely epithelial appearance through more pleomorphic biphasic neoplasms to anaplastic tumors. A combination of epithelial-like cell clusters, pavement-like sheets of epithelial cells with well-defined cell borders and prominent cell separation, dispersed angular cells with dense cytoplasm and some spindle-cell forms was the most specific cytologic pattern for mesothelioma. In four neoplasms, ultrastructural examination of aspirated material provided the additional evidence for a definitive diagnosis. The identification of hyaluronic acid within intracytoplasmic vacuoles, either in smears or in cell blocks, confirmed the diagnosis in three tumors. Only in one case, with a strong clinical background suggesting mesothelioma, was the cytologic preparation sufficient for diagnosis without ancillary diagnostic methods. FNA is of particular value in the diagnosis of pleural mesothelioma in patients who do not present with a pleural effusion. Obtaining material for cell block preparations, cytochemistry or ultrastructural study is generally necessary for definitive tumor typing.

Breast neoplasms containing bone and cartilage.

A total of 307 breast neoplasms and tumour-like conditions were reviewed to assess the frequency with which bone and/or cartilage occurred. Of 90 fibroadenomas, 1 (1.1%) and 2 of 158 breast carcinomas (1.3%) contained bone, one benign mesenchymoma contained cartilage, and one benign "mixed" tumour (pleomorphic adenoma) displayed cartilage and bone. Twenty-two papillomas and 34 cases of gynaecomastia did not contain any cartilage or bone. This study confirms the impression that the occurrence of bone or cartilage in human breast neoplasms is rare. These lesions are briefly discussed with reference to the pertinent literature.