Ultrastructural Pathology

Our medical research library holds 45 studies published in Ultrastructural Pathology (1980–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 41 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 1 study PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Informa Healthcare
• Published: 1980 to the present, England
• Language: English
• ISSN: 0191-3123 (print), 1521-0758 (electronic)
• Its record in the NLM Catalog

2020s

• The diagnosis of asbestosis in the 21st century: a clinicopathological correlation of 102 cases. J.M. Carney, T.A. Sporn, V.L. Roggli, et al. 2024;48(2):137-148. PubMed · Publisher

  Abstract

  Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21st century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.

• Response to Roggli et al. (2020) "Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation". T. Tran, D. Egilman, M. Rigler. 2020;44(3):314-315. Comment PubMed · Publisher

• Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation. V.L. Roggli, J.M. Carney, T.A. Sporn, et al. 2020;44(2):211-218. PubMed · Publisher

  Abstract

  Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.

• Tissue burden evaluation of elongated mineral particles in two individuals with mesothelioma and whose work history included manufacturing tile. R.F. Dodson, L.W. Poye. 2020;44(1):17-31. Case report PubMed · Publisher

  Abstract

  Two cases with diagnosis of mesothelioma were referred to our laboratories with a request for tissue burden analysis in order to determine the presence of ferruginous bodies and uncoated elongated mineral particles in tissue samples. The individuals shared in common a past background of working in tile manufacturing facilities where industrial talc was used in the production of the products. Both were found to have ferruginous bodies in their lung tissues as well as elongated talc fibers/ribbons and elevated numbers of noncommercial amphiboles in their tissues. To our knowledge, this is the first report of tissue assessment for the presence of elongated mineral particles in individuals whose exposures to talc occurred were while working in the manufacture of tile products and who developed the fiber-related cancer - mesothelioma.

2010s

• Comments on "Dimensions of elongated mineral particles with implications for pathogenicity and classification as asbestiform versus cleavage fragments". M.M. Finkelstein. 2019;43(6):326-329. Letter · Comment PubMed · Publisher

  Abstract

  Roggli and Green have reported their study of the dimensions of fibers extracted from the tissues of cases examined in their laboratory, and have drawn conclusions about the pathogenicity of Elongated Mineral Particles and their classification as asbestiform versus cleavage fragments. There are aspects of their methodology and discussion that would benefit from examination. Roggli and Green have relied upon a paper by Harper et al. for their definitions of asbestiform and cleavage fragments. Unfortunately, they have misinterpreted the work of those authors who have concluded that the best criterion is a particle width <1μm. Roggli and Green conclude that 'Our findings demonstrate the lack of pathogenicity of fibers less than 10 μm long or likelihood of cleavage fragments for fibers less than 10μm long and greater than 1.0μm in diameter has little or no effect on the classification of commercial amphibole fibers using our analytical methodology. On the other hand, both lack of pathogenicity and likelihood of cleavage fragments apply to a significant proportion of noncommercial amphiboles identified using our counting scheme.' This is not true. The study of Roggli and Green was a simple fiber counting study with no control population. The design of such a study does not allow the investigator to draw any conclusions about pathogenicity, or lack thereof.

• Dimensions of elongated mineral particles: a study of more than 570 fibers from more than 90 cases with implications for pathogenicity and classification as asbestiform vs. cleavage fragments. V.L. Roggli, C.L. Green. 2019;43(1):1-5. PubMed · Publisher

  Abstract

  Asbestos is well-recognized as the cause of a variety of disorders of the respiratory tract, including neoplastic as well as non-neoplastic conditions. Fiber dimensions and biopersistence are important determinants of the pathologic response, and analytical electron microscopy is a powerful technique for determining the fiber content of lung tissue samples. For decades our laboratory has examined lung tissue samples counting fibers measuring 5 µm or greater in length. More recent observations have indicated that fibers 10 µm or greater in length are pathogenic, and that a length of 10 µm and diameter less than 1.0 µm are useful features for distinguishing asbestiform fibers from cleavage fragments. We examined more than 570 fibers from more than 90 cases to determine the dimensions of fibers that might be classified as asbestos. The vast majority of fibers classified as amosite or crocidolite met the criteria for length greater than 10 µm and diameter less than 1.0 µm. However, a significant proportion of fibers classified as tremolite, actinolite, or anthophyllite did not meet these criteria. These findings have important implications for the identification and classification of elongated mineral particles, both in terms of pathogenicity as well as classification as asbestiform vs. cleavage fragments.

• Asbestos content of lung tissue in patients with malignant peritoneal mesothelioma: A study of 42 cases. G.G. de Ridder, A. Kraynie, E.N. Pavlisko, et al. 2016;40(3):134-41. PubMed · Publisher

  Abstract

  Lung tissue from 42 peritoneal mesothelioma cases was analyzed by light microscopy and scanning electron microscopy/energy dispersive spectrometry. There were 34 men and 8 women with a mean age of 61 ± 10 years. Also, 17% of cases had histologically confirmed asbestosis, and 26% had only parietal pleural plaques. The asbestos body count exceeded our normal range in 22 of 42 cases (52%). Cases with asbestos-related pulmonary disease had higher fiber burdens than those without. The vast majority of fibers were commercial amphiboles (amosite with lesser amounts of crocidolite). These findings concur with previously published epidemiological observations.

• Carcinoma of the lung in the absence of asbestosis: The value of lung fiber burden analysis. V.L. Roggli, T.A. Sporn. 2016;40(3):151-4. Case report PubMed · Publisher

  Abstract

  Asbestos is universally recognized as a carcinogen for the lower respiratory tract. However, asbestos is a contributory factor in a small fraction of lung cancers, the vast majority of which are related to cigarette smoking. The challenge for the pathologist is to determine when a lung cancer may be attributed to past asbestos exposure. The finding of asbestosis either clinically or pathologically is a useful marker for such a determination. However, in the absence of asbestosis, it has been suggested that a fiber burden as determined by analytical electron microscopy within the range of asbestosis is sufficient for determination of a causal contribution. We report here an example of a case of lung cancer in which fiber burden studies showed an asbestos concentration within the range of asbestosis as determined by scanning electron microscopy (SEM).

• Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma. H. Domínguez-Malagón, A.M. Cano-Valdez, C. González-Carrillo, et al. 2016;40(5):254-60. PubMed · Publisher

  Abstract

  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.

• Fiber analysis vignettes: Electron microscopy to the rescue!. V.L. Roggli. 2016;40(3):126-33. Review PubMed · Publisher

  Abstract

  There has been considerable interest in the exposure doses that contribute to the various asbestos-associated diseases. Epidemiological studies have shown important differences in the contributions of the various fiber types to asbestos-related diseases, with the amphiboles showing a greater degree of potency as compared to chrysotile. However, epidemiological studies have occasionally provided misleading results. Over the past several decades, there have been several examples where fiber analysis using electron microscopy produced unexpected results which were important to our understanding of disease-exposure relationships. It is the purpose of this article to summarize these fiber analysis vignettes.

• Malignant mesothelioma not related to asbestos exposure: Analytical scanning electron microscopic analysis of 83 cases and comparison with 442 asbestos-related cases. A. Kraynie, G.G. de Ridder, T.A. Sporn, et al. 2016;40(3):142-6. PubMed · Publisher

  Abstract

  Epidemiological studies indicate that 80-90% of mesotheliomas are asbestos related. This suggests that 10-20% are not. Lung fiber burden analysis provides objective information about past exposures to asbestos. We have performed lung fiber burden analysis on a large cohort of mesothelioma cases and compared the findings with a reference population. Herein we report our findings along with demographic and exposure data.

• Analysis of asbestos concentration in 20 cases of pseudomesotheliomatous lung cancer. R.F. Dodson, S.P. Hammar. 2015;39(1):13-22. PubMed · Publisher

  Abstract

  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.

• Electron microscopy remains the gold standard for the diagnosis of epithelial malignant mesothelioma: a case study. E.A. Oczypok, T.D. Oury. 2015;39(2):153-8. Case report PubMed · Publisher · Free full text

  Abstract

  This is a case of idiopathic epithelial malignant mesothelioma in a 47-year-old mechanic. The advent of a large battery of immunochemical markers has provided new tools for the diagnosis of mesothelioma in recent years; however, immunostaining can often be misleading or inconsistent, as demonstrated in this case. This report highlights the lasting utility of electron microscopy in the diagnosis of mesothelioma. Ultrastructural features of epithelial mesothelioma were discernable using electron microscopy even on somewhat poorly preserved chest wall biopsy specimens from paraffin blocks. These images, combined with immunostains and a fiber analysis from the lungs, allowed for a final diagnosis of a non-asbestos-related malignant epithelial mesothelioma in this patient.

• Biodurability/retention of Libby amphiboles in a case of mesothelioma. R.F. Dodson, E.J. Mark, L.W. Poye. 2014;38(1):45-51. Case report PubMed · Publisher

  Abstract

  Mesothelioma is considered a signal tumor for exposure to asbestos (fibrous materials) and can occur decades after first exposure. The present case study reports on tissue burden of fibrous dust in a person who used a vermiculite material (Zonolite) as an attic insulator some 50 years prior to her death. The exposure occurred in two construction/renovation projects in her private residencies. She potentially had exposures to wall board/joint compounds during renovations. She additionally was reported to occasionally be involved in occupational activity, including drilling holes in presumed asbestos-containing electrical boxes. The tissue burden analysis revealed the presence of noncommercial amphibole asbestos fibers and consistent presence in the lung and lymph samples of Libby amphibole fibers. The findings of Libby amphibole fibers in human tissue can be attributed to exposure to Libby vermiculite. This study illustrates that analytical transmission electron microscopy can distinguish these structures from "asbestos" fibers. Further, the findings indicate that a population of these structures is biodurable and retained in the tissue years after first/last exposure.

• Primary pleural epithelioid mesothelioma of clear cell type: a case report and review of current literature. C. Gkogkou, K. Samitas, M. Foteinou. 2011;35(6):267-70. Case report · Review PubMed · Publisher

  Abstract

  Primary pleural epithelioid mesothelioma with clear cell morphology is a particularly rare neoplasm, with only a few documented cases. Here, the authors report a case of a 76-year-old man, with a history of asbestos exposure, admitted for mild dyspnea. Radiologic examination revealed right pleural effusion and pleural thickening. Cytological examination of aspirated pleural samples was consistent with non-small cell carcinoma. Histological examination of the resected, via VATS, plural specimens was consistent with the diagnosis of clear cell epithelioid mesothelioma. The authors further analyze the main morphological and immunohistochemical features of clear cell epithelioid mesothelioma, emphasizing the algorithm for excluding other clear cell tumors metastatic to the pleura.

• The utility of electron microscopy in cytopathology. D. Etit, M. Selig, W.C. Faquin, et al. 2010;34(5):252-9. PubMed · Publisher

  Abstract

  Background: The use of ultrastructural analysis in the diagnostic work-up of histologic specimens has been well studied but less is known about the utility of electron microscopy (EM) in cytopathology.

  Design: 149,006 non-gynecologic cytology cases at the Massachusetts General Hospital between the years 1993 and 2006 were searched to identify those in which material had been submitted for EM. Cytologic and EM diagnoses were correlated with available histologic diagnoses. The results were put into one of three categories: confirmatory, diagnostic, or insufficient material for diagnosis (IMFD).

  Results: Material for EM was obtained from 178 cytology cases that included 131 fine-needle aspirates (FNA) and 47 exfoliative specimens. EM provided additional diagnostic information beyond that offered by cytologic examination alone in 32% of cases, and in 48% of cases EM confirmed the cytologic findings. Insufficient material and discrepant results were noted for EM evaluation in 19% of cases and in 1% cases respectively. EM was most useful when applied to FNAs for subclassifying tumors as epithelial or mesenchymal (45.6%), for the diagnosis of non-neoplastic processes (15.7%) such as alveolar proteinosis and amyloidosis, and for the identification of microorganisms (12.2%). In our study, although EM was infrequently applied to exfoliative specimens to distinguish mesothelioma from adenocarcinoma, it proved to be very useful in this setting.

  Conclusion: When adequate material is obtained, EM can contribute significantly to the evaluation of both FNA and exfoliative cytology cases, including the diagnosis and subclassification of epithelial and mesenchymal tumors, non-neoplastic processes, and the identification of microorganisms.

2000s

• Crocidolite and mesothelioma. F. Schneider, T.A. Sporn, V.L. Roggli. 2008;32(5):171-7. PubMed · Publisher

  Abstract

  This study reports changes in the frequency of detection of various asbestos fiber types between 1982 and 2005. Crocidolite is increasingly detected in U.S. mesothelioma patients. The percentage of crocidolite fibers detected in lung tissue has risen from 4 to 10%, and the percentage of cases in which crocidolite was detected increased from 19 to 37%. Meanwhile, the frequency of detection of amosite and chrysotile has decreased. The authors performed a detailed analysis of cases in which crocidolite was identified in the absence of amosite. Most of such cases were identified in recent years, a finding of concern since crocidolite is considered the most potent fiber type with respect to the pathogenesis of mesothelioma.

• Characteristics of asbestos concentration in lung as compared to asbestos concentration in various levels of lymph nodes that collect drainage from the lung. R.F. Dodson, S. Shepherd, J. Levin, et al. 2007;31(2):95-133. Case report PubMed · Publisher

  Abstract

  Inhaled dust particulates are able to relocate to the extrapulmonary compartments, particularly the lymph nodes that drain the lung. There is little information about the concentration and type of asbestos in the lymphatics and lymph nodes. Quantitative analysis of asbestos lymph node burden conducted by light and analytical transmission electron microscopy has shown ferruginous bodies in lymph nodes that drain the lung and appreciable numbers of short asbestos fibers accumulate in lymph nodes in occupationally exposed individuals. The location of lymph nodes in the thoracic cavity was categorized according to the Naruke anatomical map. Tissue from eleven individuals with a history of asbestos exposure were selected for a comparative study of the asbestos content of lung with that found in the thoracic lymph nodes. The study used a digestion technique for tissue preparation and evaluated ferruginous body burden and concentration of asbestos fibers (> 0.5 microm in length). Comparison was made between sites and analysis was made as to the population of fibers detectable by light microscopy and defined as "Stanton fibers." The findings indicated the vast majority of all asbestos fiber types in all sites were shorter than 5 microm and would not have been counted in a light microscopy count scheme that included only those fibers > 5 microm. There were reproducible patterns of asbestos types of found in various lymph nodes, although there were variations in the amount of asbestos found in the sites sampled. In summary, asbestos fibers found in thoracic lymph nodes have predominately short fibers and, in this study group, consisted of a mixture of commercial and noncommercial amphiboles. When a long/thin fiber was found in the lung or lymph tissue, its detection required the use of analytical transmission electron microscopy for identification.

• Biologic, cytogenetic, and molecular factors in mesothelial proliferations. J. Hicks. 2006;30(1):19-30. Review PubMed · Publisher

  Abstract

  Although mesothelioma cases may have peaked in the 1990s in developed countries, it is expected that there will be over 70,000 cases diagnosed in the United States over the next 5 decades. With the industrial expansion in Southeast Asia and China and the continued use of asbestos, an epidemic of mesothelioma cases is anticipated over the next several decades. A considerable amount has been learned about the cytogenetic and molecular genetics of mesotheliomas. However, in-depth studies are needed to further define specific factors that may provide for early diagnosis, surgical treatment, oncologic management, and gene therapy. Serologic markers for surveillance of those with asbestos exposure and at risk for mesothelioma are needed. Targeted therapy using molecular markers and gene therapy may provide a means to reverse mesothelial proliferations or stabilize tumor growth and allow for surgical resection. The future holds great promise in identifying mesothelioma gene expression profiles (genomics, gene microarrays) and proteins (proteomics) that may produce the key to dealing with this dismal and devastating neoplasm.

• The role of analytical SEM in the determination of causation in malignant mesothelioma. V.L. Roggli. 2006;30(1):31-5. PubMed · Publisher

  Abstract

  The causative relationship between asbestos exposure and mesothelioma is firmly established. Some information in this regard comes from analysis of the fiber content of lung tissue by means of analytical electron microscopy. The author has had the opportunity to study the lung asbestos content of 396 cases of mesothelioma, including 28 peritoneal cases, by means of analytical scanning electron microscopy. The highest fiber levels occurred in patients who also had asbestosis, which was found in 12% of pleural and 43% of peritoneal cases. Elevated tissue asbestos content was identified in 87% of pleural and 75% of peritoneal cases. Peritoneal cases that are asbestos related have on average a higher lung fiber burden than pleural cases. Mesotheliomas in women have elevated tissue asbestos content in about 60% of cases, and many of these had a history of exposure as a household contact of an asbestos worker. The main fiber type identified in our series was amphibole, predominantly amosite. These fibers have been demonstrated to reach the target tissue, the pleura.

• Asbestos burden in cases of mesothelioma from individuals from various regions of the United States. R.F. Dodson, R. Graef, S. Shepherd, et al. 2005;29(5):415-33. PubMed · Publisher

  Abstract

  Mesothelioma is a rare tumor that is considered an asbestos marker disease. It occurs in individuals following a longer latency period from first exposure than other asbestos-related diseases. The tumor also occurs in individuals with a wide range of exposures, including individuals with lower level or secondary exposures. In the present study lung tissue from 54 individuals with a pathological diagnosis of mesothelioma was evaluated for ferruginous body and uncoated asbestos fiber content. The data were compared with an earlier study of mesothelioma cases from the northwestern United States. Tissue was prepared via a digestion procedure, with the collected digestate reviewed by light microscopy for quantification of asbestos bodies and analytical transmission electron microscopy for determination of uncoated fiber burden. Twenty-seven cases in the present study had over 1000 ferruginous bodies per gram of dry tissue. The data suggest that amosite provides a more likely stimulus for ferruginous coating than the other forms of asbestos. All individuals were found to have asbestos fibers in their lung tissue. Amosite was the most commonly found fiber, with anthophyllite being the second most commonly found type of asbestos. The finding of tremolite in the tissue most often was associated with the finding of anthophyllite. A limited number of asbestos fibers of each type would have been seen in the light microscope, with the least detected being chrysotile. The majority of all fiber types were found as short fibers (< 8 mum), although some longer fibers were represented in each type of asbestos. The majority of the individuals were found to have mixed types of asbestos in their lungs.

• Lymphohistiocytoid mesothelioma: a clinical, immunohistochemical and ultrastructural study of four cases and literature review. D.X. Yao, J. Shia, R.A. Erlandson, et al. 2004;28(4):213-28. Case report PubMed · Publisher

  Abstract

  Lymphohistiocytoid mesothelioma (LHM) is a term proposed to designate a variant of mesothelioma that assumes a histiocytoid morphology and contains intense lymphocytic infiltrates. Reports on this variant are few, and its clinicopathologic and ultrastructural characteristics are still to be defined. The authors have studied 4 such cases that were identified among 120 mesotheliomas in the electron microscopy (EM) files of a single institution between 1982 and 2002. Histologically, all 4 lesions were composed of diffuse proliferations of cells with a histiocytoid appearance, admixed with an intense lymphocytic infiltrate. All 4 were associated with an unequivocal sarcomatoid component. Immunohistochemical (IHC) studies showed that the majority of histiocytoid cells were positive for CD68 and vimentin in all 4 cases, suggesting fibrohistiocytic differentiation. Immunoreactivity for calretinin and AE1:AE3 was only very focally identified in 3 of 4 cases. All cases were negative for CEA (M), Leu-M1, and B72.3. The lymphocytic component in all 4 cases was almost entirely composed of CD3- and CD8-positive, small, mature T cells, with only a minor component of CD20-positive cells and occasional eosinophils. Although all cases contained numerous CD68 positive atypical cells, co-expression of CD68 and either calretinin or keratin by individual cells was difficult to demonstrate by immunohistochemistry. Ultrastructurally, 3 of the 4 cases demonstrated very focal mesothelial differentiation as evidenced by long and slender surface microvilli, including the case with negative immunoreactivity for calretinin and cytokeratin. Review of the literature yielded 6 additional LHM cases. Analysis of all 10 cases showed a male predominance (8:2) with a mean age of 58 years (31-73 years). All 10 cases involved the pleura. Three of 10 patients had known asbestos exposure. Six of 10 patients died of disease at 2-20 months after the diagnosis (mean, 6.9 months). The findings suggest that LHM is a distinct morphological variant of sarcomatoid mesothelioma for which mesothelial differentiation is difficult to document. Many of the cells composing these tumors exhibit fibrohistiocytic differentiation. The unusual morphological pattern of LHM makes a combined modality approach, including IHC, EM, and a knowledge of the clinical/radiologic findings, essential in achieving a correct diagnosis.

• Deciduoid mesothelioma: a report of 5 cases and literature review. J. Shia, R.A. Erlandson, D.S. Klimstra. 2002;26(6):355-63. Review PubMed · Publisher

  Abstract

  Deciduoid mesothelioma was first described in young females and in the peritoneum, which led to the suggestion that deciduoid mesothelioma was a distinct subtype with specific clinical and pathologic features. Later reports, however, have shown that this type of mesothelioma may also occur in elderly people and in the pleura. Cases reported in the literature so far are limited, and the disease is not well defined. The authors report the histologic, immunohistochemical, ultrastructural, and clinical findings of 5 cases of deciduoid mesothelioma, and review the literature reports. The results demonstrate that the presence of numerous cytoplasmic intermediate filaments, either dispersed or bundled, appear to be the likely ultrastructural basis for the deciduoid histologic appearance. Twenty-one cases of deciduoid mesothelioma were identified in the literature. Analyses of these 21 cases and the authors' 5 cases showed an age range of 13-78 years (median 53 years) and a slight female predominance (female to male ratio of 1.4:1). Fourteen of 26 cases (54%) occurred in the peritoneum. Seven of 20 patients (35%) had a documented history of asbestos exposure. Fifteen of 20 patients died, with a mean survival time of 7.33 months (range 1-21 months). Five of 20 patients were alive at a follow-up time of 8 months to 5 years. These findings suggest that the so-called deciduoid mesothelioma has some clinical and pathologic features that are dissimilar to mesothelioma in general. Whether it truly represents a pathogenetically distinct variant or merely an expansion of the morphologic spectrum awaits further studies.

• Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases. V.L. Roggli, A. Sharma, K.J. Butnor, et al. 2002;26(2):55-65. PubMed · Publisher

  Abstract

  Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.

• Ultrastructurally "invasive" microvilli in an aggressively metastasizing biphasic malignant mesothelioma. Y. Zu, G.S. Sidhu, R. Wieczorek, et al. 2002;26(6):403-9. Case report PubMed · Publisher

  Abstract

  The presence of long, slender, often branching microvilli on cell surfaces is a characteristic feature of malignant and benign mesothelial cells. However, these typical microvilli are seen only in better-differentiated lumens within epithelial areas of malignant mesotheliomas. Presented here are the clinical and ultrastructural findings in a biphasic malignant mesothelioma that lacked lumens, but possessed very long microvilli. These invaginated deeply into the cytoplasm of neighboring tumor cells, as well as into the surrounding stromal matrix. The tumor cells had well-formed intercellular desmosomal junctions. The primary tumor was localized to the pleura and invaded the chest wall, but only minimally the lung. Lobectomy demonstrated the presence of metastatic tumor in 2 peribronchial lymph nodes. The disease progressed rapidly and, within 6 months, killed the patient. An autopsy revealed widespread metastases in multiple systemic organs. The authors speculate that the unique ultrastructural features of this case may be a clue to the unusually aggressive course of the neoplasm.

• Phagocytosis of hemozoin (native and synthetic malaria pigment), and Plasmodium falciparum intraerythrocyte-stage parasites by human and mouse phagocytes. P. Olliaro, L. Lombardi, S. Frigerio, et al. 2000;24(1):9-13. PubMed · Publisher

  Abstract

  Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary, whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.

1990s

• Analysis of asbestos fiber burden in lung tissue from mesothelioma patients. R.F. Dodson, M. O'Sullivan, C.J. Corn, et al. 1997;21(4):321-36. PubMed · Publisher

  Abstract

  Mesothelioma is a rare neoplasm that occurs most frequently in individuals with previous asbestos exposure. Differences for risk of development of asbestos-related mesothelioma and lung cancer have been attributed to the various types of asbestos, as well as to the dimension of the inhaled fibers. In the present study, 55 individuals with the pathological diagnosis of mesothelioma were evaluated as to ferruginous body and fiber content in lung tissue. The procedures used in the analysis included tissue digestion and analysis of the collected material for ferruginous bodies by light microscopy and for uncoated fibers by analytical transmission electron microscopy. Forty-six of the samples had ferruginous body concentrations of over 1000/per gram dry weight of lung tissue. The majority of the cores of these ferruginous bodies were amosite. Likewise, the most common uncoated asbestos fiber in the tissue was amosite. Only a small percentage of each type of asbestos would have been visible by light microscopy or even potentially by electron microscopy if the magnification was not sufficient to detect those with thin (< 0.2 micron) diameters. The consistent finding in most of the cases was a considerable presence of asbestos, often of mixed types.

• Adenocarcinoma simulating mesothelioma. B. Corrin, A. Dewar. 1996;20(4):327-9. Case report PubMed · Publisher

  Abstract

  Pleural biopsy in a 45-year-old woman with a haemorrhagic pleural effusion showed malignant cells. Stains for mucin and carcinoembryonic antigen were positive and adenocarcinoma was diagnosed. Some ultrastructural features were more typical of mesothelioma.

• Malignant epithelial mesothelioma of the peritoneum: observations on a problem case. B.P. Eyden, S. Banik, M. Harris. 1996;20(4):337-44. Case report PubMed · Publisher

  Abstract

  A 71-year-old asbestos-exposed male with symptoms suggestive of asbestosis for the previous 8 years presented with abdominal distension and ascites. Clinically, a diagnosis of mesothelioma carcinoma was made. Light microscopy of an omental biopsy failed to advance the diagnosis: The tumor was a solid, papillary, and glandular neoplasm lacking mucin and hyaluronidase-sensitive Alcian blue staining material. Immunohistochemistry gave positive results for Ber-EP4, LeuM1, and CEA, markers, favoring carcinoma. Electron microscopy revealed processes in channels and lumina, which were long, slender, and uncoated with a length: diameter ratio of 19.7. A few possessed small rootlets. A glycocalyx and glycocalyceal bodies were not seen. Other features included tonofibrils, a basal lamina, and desmosomes. The patient died 3 months following the onset of abdominal symptoms. Autopsy findings included solid and papillary tumor throughout the peritoneum, but no intrinsic tumor of the gastrointestinal tract or elsewhere. Arriving at a final diagnosis was complicated by immunohistochemistry, which favored carcinoma, and ultrastructure, which suggested mesothelioma. Taking into account all lines of evidence, it was concluded that the tumor was probably a mesothelioma but one with some features developed to an extent more typical of carcinoma.

• Giant desmosomes in tumors. F.N. Ghadially, P.U. Rippstein, S. Cavell, et al. 1995;19(6):469-74. PubMed · Publisher

  Abstract

  The lengths of desmosomal profiles were measured in sections of tumor tissue from cases of mesothelioma, adenocarcinoma, squamous cell carcinoma, thymoma, and meningioma. Giant desmosomes (length of profile 1 micron or greater than 1 micron) were found in all the above-mentioned tumors except adenocarcinomas. The largest desmosomal profile in adenocarcinoma was approximately 0.8 micron long; the largest in mesothelioma was approximately 2 microns long. Our observations suggest that one of the ways in which giant desmosomes arise is by growth and fusion of adjacent desmosomes. Giant desmosomes may at times help in distinguishing mesothelioma from adenocarcinoma, but this is a rather rare phenomenon. In this study giant desmosomes were found in only 2 out of 10 cases of mesothelioma.

• Pleural mesothelioma with initial presentation as cervical lymphadenopathy. E.J. Wills. 1995;19(5):389-94. Case report PubMed · Publisher

  Abstract

  A 41-year-old woman presented with a left neck mass. Light microscopy suggested metastatic large cell carcinoma, but subsequent electron microscopy demonstrated typical epithelial mesothelioma. Initial clinical investigations were negative and the primary pleural tumor remained inapparent for a further 8 months. The woman ultimately died from the effects of superior vena caval obstruction. Mesotheliomas frequently metastasize late in the course of the disease, but it is exceptional for them to present as a metastatic tumor of unknown primary origin.

• Is malignant mesothelioma being overdiagnosed?. H.J. Sobel. 1994;18(3):iii-iv. Editorial PubMed · Publisher

• Confronting cisternae and ciliated cells in malignant pleural mesothelioma: an ultrastructural study. C. Torikata, T. Kawai, M. Nakayama. 1991;15(3):249-56. PubMed · Publisher

  Abstract

  The incidence of malignant mesothelioma of the pleura has recently increased in Japan, and ultrastructural and immunohistochemical studies can help in the histopathologic diagnosis. Confronting cisternae consist of dense laminae between the cisternae of rough endoplasmic reticula. Cylindric confronting cisternae have recently been found in patients with acquired immunodeficiency syndrome. The pathologic significance of this unusual structure is still obscure, but it has been proposed that trapped ribosomes on the confronting unit membranes of rough endoplasmic reticula produce the dense laminae. In this study, prominent confronting cisternae were found in more than half the tumor cells, and accumulation of an electrondense fine granular substance surrounded by Golgi vesicles (so-called vesicular rosettes) were noted and found to be continuous with the dense laminae. The nature and origin of the vesicular rosettes are important with regard to the formation and significance of confronting cisternae. Oligocilia have been found in various metaplastic and neoplastic cells and are thought to be nonspecific. There has been only one report of ciliated cells and confronting cisternae in a malignant peritoneal mesothelioma, however, indicating that these unusual cytoplasmic structures might be related to some epithelial-type mesotheliomas.

• Malignant mesothelioma of peritoneum. N. Weidner. 1991;15(4-5):515-20. Case report PubMed · Publisher

  Abstract

  A 57-year-old man with malaise, ascites, and abdominal pain was found to have a peritoneum studied with numerous, small nodular tumor masses. Light microscopy revealed an anaplastic malignant tumor of uncertain differentiation. Mucin stains were negative. Electron microscopy revealed pleomorphic tumor cells with diffusely distributed cytoplasmic tonofilaments and well-developed true desmosomes. No long, thin, branching microvilli were present, yet tumor cells were strongly positive for both callus keratin (polyclonal) and monoclonal cytokeratin (AE1/3) in a diffuse cytoplasmic distribution (a pattern corresponding to the diffuse cytoplasmic tonofilaments). Tumor cells were negative for Leu-M1 and carcinoembryonic antigen. The findings were most consistent with malignant mesothelioma, and additional questioning, after tissue diagnosis, revealed a work history of asbestos exposure.

• Solitary fibrous tumor of the mediastinum. N. Weidner. 1991;15(4-5):489-92. Case report PubMed · Publisher

  Abstract

  A 62-year-old woman presented with an asymptomatic anterior mediastinal mass. Clinically considered to be a thymoma, the tumor was solid, firm, and composed of hypocellular dense collagen and cytologically bland, spindled fibroblastlike cells growing in a patternless pattern. There was no apparent connection to pleura or pericardium, yet the clinicopathologic features clearly fit with solitary fibrous tumor (SFT) of mediastinum. SFTs occur most commonly in pleura but have been reported in other locations, including the mediastinum, where aggressive behavior has been more common when these tumors are compared to those occurring in pleura. Although it is difficult to predict behavior for all cases of SFT occurring in the mediastinum by cytologic features alone, morphologic criteria for benign and malignant forms have been described. Roughly half the malignant forms will progress, yet the single most important indicator of clinical outcome is whether the tumor can be initially totally excised.

• Unusual primary lung neoplasms: spindle cell and undifferentiated lung carcinomas expressing only vimentin. S.P. Hammar, K.O. Hallman. 1990;14(5):407-22. Case report PubMed · Publisher

  Abstract

  Two unusual primary carcinomas of the lung are described. One occurred in a 31-year-old man and was composed of large, undifferentiated, ovoid to polygonal cells. The other occurred in a 72-year-old man, was composed of spindle-shaped cells, and was initially diagnosed as a localized fibrous mesothelioma. The neoplastic cells of these tumors expressed only vimentin intermediate filaments and showed no other immunohistochemical features of epithelial neoplasms, although they exhibited a metastatic pattern characteristic of lung carcinomas. These two malignant neoplasms further expand the spectrum of unusual lung neoplasms, and suggest that there are pulmonary carcinomas that contain only vimentin intermediate filaments.

1980s

• Desmosomes of epithelial malignant mesothelioma. T.R. Burns, E.H. Johnson, J. Cartwright, et al. 1988;12(4):385-8. PubMed · Publisher

  Abstract

  Morphometric examination of desmosomes by electron microscopy may help distinguish epithelial malignant mesotheliomas (EMM) from adenocarcinomas (AC). The lengths of 225 desmosomes from 10 AC and 296 desmosomes from 12 EMM were measured. The mean desmosome length was not significantly different in the two groups. However, only one desmosome greater than 1-micron length was found among the 225 AC desmosomes, whereas seven such "giant" desmosomes were found among 296 EMM desmosomes (p less than 0.001). These long desmosomes ranged up to 4.2 micron in length and involved 4 of 12 cases of EMM. The longest AC desmosome was 1.34 micron. Thus, it is suggested that giant desmosomes be defined as measuring greater than 1 micron in length and that such desmosomes are found much more commonly in EMM than AC and tend to attain greater lengths in EMM.

• High-resolution electron microscopy of interlysosomal junctions. D. Beju. 1988;12(3):307-16. PubMed · Publisher

  Abstract

  Five different malignant tumors and two nasal polyps were examined by electron microscopy for diagnosis purposes. In all cases occasional large cells containing lysosomes interconnected by characteristic junctions were observed. The interlysosomal junctions appeared organized in zig-zag and ladder like configurations. The ultrastructural and morphometric analyses of these junctions postulated that the two configurations represented the same structure viewed in two different sectioning planes. High-resolution electron microscopic evidence suggests that the interlysosomal junction is organized as a 35-40 A thick pleated ribbon extending between a 200-A wide interlysosomal space, in close contact with the adjoining lysosomal membranes, without apparent integration into the membrane.

• Lymphohistiocytoid mesothelioma: a rare lymphomatoid variant of predominantly sarcomatoid mesothelioma. D.W. Henderson, H.D. Attwood, T.J. Constance, et al. 1988;12(4):367-84. Case report · Review PubMed · Publisher

  Abstract

  Of 394 "definite" mesotheliomas entered in the Australian Mesothelioma Surveillance Program, three bore a striking resemblance to malignant lymphoma by conventional light microscopy, and each was misinterpreted at some stage as lymphoma. The lymphoma-like morphology was a combined result of intense lymphoplasmacytic infiltration and the histiocytoid appearances of the underlying neoplastic cell population. Immunocytochemical analysis demonstrated cytokeratins coexpressed with vimentin within the tumor cells, whereas immunoreactivity for leukocyte common antigen was confined to the smaller lymphoid cells. Electron microscopy of two cases revealed a polymorphous population of fibrohistiocytic cells resembling those typical of malignant fibrous histiocytoma, admixed with lymphocytes and plasma cells, but sporadic cells expressed mesothelial properties in the form of sinuous villiform processes, intracytoplasmic neolumina lined by microvilli, and intermediate filaments that were aggregated into tonofilament bundles in some cells. The ultrastructural appearances, the localization of the tumors to the pleura, with effusion, and absence of anterior mediastinal mass lesions facilitated exclusion of lymphocyte-rich thymoma. In addition, a history of prior occupational exposure to asbestos was elicited in each instance. There was no apparent response to radiotherapy or chemotherapy, and the patients died at 4, 5, and 8 months after presentation. Our observations suggest that immunocytochemical or ultrastructural evaluation is mandatory for accurate diagnosis of all pleura-based lymphomatoid lesions with a mixed large and small cell pattern.

• Diagnostic electron microscopy using fine needle aspiration biopsies. B. Mackay, T. Fanning, J.M. Bruner, et al. 1987;11(5-6):659-72. Case report PubMed · Publisher

  Abstract

  Electron microscopy can be a valuable aid to light microscopy in the interpretation of fine needle aspiration biopsies of tumors, but considerable care in procuring and processing the specimen is necessary to recover the tumor cells and avoid altering their fine structure. Fixation followed by filtration through a cloth screen is recommended. Experience with this technique is briefly reviewed.

• Diffuse epithelial mesothelioma: a review of the ultrastructural spectrum. I. Dardick, M. Jabi, W.T. McCaughey, et al. 1987;11(5-6):503-33. Case report · Review PubMed · Publisher

  Abstract

  Traditionally, diffuse epithelial mesotheliomas are mainly identified at the ultrastructural level by the numerous, long, wavy-appearing surface microvilli. By electron microscopy of a series of diffuse mesotheliomas of varying subtype (epithelial, biphasic, sarcomatous, and poorly differentiated), it can be demonstrated that the differentiation of this specialized surface organelle is quite variable even in well-differentiated lesions. The presence of only a few, scattered, short microvilli does not exclude a diagnosis of epithelial mesothelioma, particularly if historical, surgical, and radiologic findings support this diagnostic conclusion. Indeed, even the complete absence of surface microvilli is compatible with a diagnosis of diffuse epithelial mesothelioma. It is important to become aware of the spectrum of tumor cell differentiation in serosal tumors, as all of the fine structural diagnostic criteria in mesotheliomas are expressed to varying degrees in individual cases.

• Electron microscopy in the diagnosis of percutaneous fine needle aspiration specimens. E.J. Wills, S. Carr, J. Philips. 1987;11(4):361-87. PubMed · Publisher

  Abstract

  Five years experience in the application of electron microscopy to fine needle aspiration biopsy specimens is reviewed. In an initial evaluation, 200 consecutive unselected specimens were examined; 89 proved diagnostic and, in a third of these, electron microscopy gave additional information that was often essential to diagnosis. Negative specimens resulted almost entirely from failure to obtain an adequate amount of material. Results were improved by the adoption of a preparation technique involving concentration of the cells in bovine serum albumin and by the inspection of a rapidly stained smear at the time of the aspiration procedure, with a further needle pass for electron microscopy being performed if necessary. Despite the small size of specimens, adequate examination was usually possible and electron microscopy has proved of value in the diagnosis of tumor samples acquired by fine needle aspiration in the same way as has been established with the larger sized specimens obtained by conventional biopsy and surgical resection.

• Embryonic ultrastructure as a guide in the diagnosis of tumors. G.R. Dickersin. 1987;11(5-6):609-52. PubMed · Publisher

  Abstract

  The purpose of this article has been to illustrate the applications and limitations of comparing the ultrastructural morphology of certain poorly differentiated neoplasms with normal human embryonic tissues. The examples used--embryonal rhabdomyosarcoma, Wilms' tumor, and fibrous mesothelioma, in comparison with embryonic mesoderm and its early derivatives--are but a few of the entities that can be investigated in this manner. Ewing's sarcoma was included in the report because of the long-standing and unsolved mystery concerning its histogenesis and because we believe it probably fits into the same category of poorly differentiated mesodermal neoplasms as the other lesions described. However, unlike the other more definite examples of primitive neoplasms manifesting focal markers of secondary mesenchymal differentiation, Ewing's sarcomas exhibit no ultrastructural evidence for myogeneous, nephrogenic, or mesothelial lines of maturation. Nor are there any morphologic indications of ectodermal or endodermal differentiation. The questions arise as to whether the category of Ewing's sarcoma has been perpetuated by so classifying all small-cell neoplasms having no recognizable line of differentiation, and whether this category may include cells of more than one type, that is, cells that are biologically determined to develop along several different pathways. This concept would be one explanation for the occurrence of Ewing's tumors in soft tissue as well as in bone, and we know that the cells contained in somites are ultrastructurally very similar to the least-differentiated cells making up the myotomes and sclerotomes. Apparently, questions such as these cannot be answered by morphologic studies alone. However, a number of other useful diagnostic and academic points of information can be gleaned.

• Sarcomatoid pleural mesothelioma. S.P. Hammar, J.W. Bolen. 1985;9(3-4):337-43. Case report PubMed · Publisher

• A case for the panel: anemone cell tumor. R. Sibley, J. Rosai, W. Froehlich. 1980;1(3):449-53. Case report PubMed · Publisher

  Summary

  This letter presented a puzzling case to an expert panel and published the panel's comments. The patient was a 49-year-old man who had swelling of the lymph nodes in the right and then the left back of the neck, at two times some years before the current admission. The first biopsy was diagnosed as metastatic carcinoma and the second as histiocytic lymphoma. After the second biopsy he received 4000 rads to each cervicosupraclavicular region and responded. Later he developed a 2 x 1-cm mass in the left nasopharynx and a 1.5-cm left posterior neck mass, and both were biopsied. Light microscopy showed round and polygonal tumor cells filling the lymph node sinuses. Electron microscopy showed oval cells with very prominent branching filopodia, 80-200 nm in diameter. Basal lamina, cell junctions, tonofilaments and secretory products other than lipids were absent. Metastatic mesothelioma, nasopharyngeal carcinoma, lymphoma, hairy cell leukemia and malignant histiocytosis were considered but not supported, so the tumor was called an "anemone cell tumor." Four panel responses followed. Two said mesothelioma could not be excluded, although the clinical history was hard to reconcile with it. One suggested a metastatic undifferentiated adenocarcinoma. One had never seen this appearance. One panelist raised the possibility of a previously unrecognized entity. No definite diagnosis was reached.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

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