American Journal of Clinical Pathology

About the journal

Publisher: Oxford University Press
Published: 1931 to the present, England
Language: English
ISSN: 0002-9173 (print), 1943-7722 (electronic)
Its record in the NLM Catalog

2010s

p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer. T. Ito, M. Hamasaki, S. Matsumoto, et al. 2015;143(6):830-8. PubMed · Publisher

Abstract

Objectives: It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC.

Methods: p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion.

Results: According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%.

Conclusions: Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected.

Copyright© by the American Society for Clinical Pathology.
Carbonic anhydrase IX (CAIX) does not differentiate between benign and malignant mesothelium. V. Ananthanarayanan, M. Tretiakova, A.N. Husain, et al. 2014;142(1):82-7. PubMed · Publisher

Abstract

Objectives: To examine carbonic anhydrase IX (CAIX), a marker of renal cell carcinoma that recently has been described in malignant effusions.

Methods: Pleural and peritoneal fluids with the following diagnoses-reactive (n = 23), carcinoma (n = 17), and "suspicious for mesothelioma" (n = 4)-were immunostained for CAIX, calretinin, Ber-EP4, and MOC31. A tissue microarray of epithelioid (n = 27) and sarcomatoid (n = 8) mesotheliomas and three cases of benign mesothelium were also immunostained for CAIX.

Results: Mesothelial cells in both reactive (18/23) and malignant effusions (18/21) were positive for CAIX (P > .05). In carcinomatous effusions, CAIX expression was restricted to the mesothelial cells. Agreement between CAIX and calretinin expression was present in 89% of cases. In tissues, CAIX was positive in 100% of benign and 91% of malignant mesothelium.

Conclusions: CAIX can be a useful ancillary marker for identifying mesothelial cells. There is no difference in CAIX expression between benign and malignant mesothelium. Caution should be exercised while evaluating for metastasis from renal cell carcinoma.

Copyright© by the American Society for Clinical Pathology.
Comparative immunohistochemical analysis of IMP3, GLUT1, EMA, CD146, and desmin for distinguishing malignant mesothelioma from reactive mesothelial cells. H. Minato, N. Kurose, M. Fukushima, et al. 2014;141(1):85-93. PubMed · Publisher

Abstract

Objectives: To identify useful biomarkers for differentiating between malignant mesothelioma (MM) and reactive mesothelial cells (RMCs).

Methods: Formalin-fixed, paraffin-embedded (FFPE) tissues from 34 MM and 40 RMC samples were analyzed using immunohistochemistry, and the findings were compared.

Results: Positive markers for MM included insulin-like growth factor 2 messenger RNA binding protein 3 (IMP3), glucose transporter 1 (GLUT1), epithelial membrane antigen (EMA), and CD146, which showed sensitivities of 94%, 85%, 79%, and 71% and specificities of 78%, 100%, 88%, and 98%, respectively. In sarcomatoid MM, EMA had significantly lower expression than did IMP3, GLUT1, and CD146 (P < .001). The areas under receiver operating characteristic curves were the highest for IMP3 (0.95), followed by GLUT1 (0.93). When the optimal cutoff points for IMP3 (30%) and GLUT1 (10%) were used, the sensitivity of IMP3 and GLUT1 for MM was 100%, and the specificity of both for MM was 95%.

Conclusions: The combination of IMP3 and GLUT1 is most appropriate for distinguishing MM from RMC using FFPE sections.
Mesothelial proliferations: useful marker is not the same as a diagnostic one. A.N. Husain. 2014;141(2):152-3. Editorial · Comment PubMed · Publisher

Summary

This editorial discussed the difficulty of distinguishing benign from malignant mesothelial proliferations, especially in small biopsy specimens without invasion of pre-existing tissue or obvious expansile growth, and in cytologic specimens. The author noted that expert panels in the United States, Canada and France had disagreed in 22% to 47% of circulated cases on whether a process was benign or malignant. The editorial commented on a study by Minato et al, published in the January 2014 issue of the journal. That study examined immunohistochemical staining for IMP3, GLUT1, EMA, CD146 and desmin in 34 malignant mesotheliomas and 40 reactive mesothelial cases. It reported 100% sensitivity and specificity using cutoffs of 40% for IMP3 and 0% for GLUT1. The author pointed out that these results came from a retrospective analysis of clear-cut, larger tissue samples. She also noted that the French MesoPath panel had concluded that desmin, EMA and p53 had no diagnostic usefulness in individual cases. The author discussed homozygous deletion of 9p21 (p16/CDKN2A). Almost all sarcomatoid mesotheliomas had this deletion, no reactive lesions tested so far had it, and only about 60% to 70% of pleural epithelioid mesotheliomas had it. The author concluded that larger studies were needed. The term "atypical mesothelial proliferation" was still recommended, to avoid giving unnecessary chemotherapy.

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.
Tumor/stromal caveolin-1 expression patterns in pleural mesothelioma define a subgroup of the epithelial histotype with poorer prognosis. L. Righi, M.C. Cavallo, G. Gatti, et al. 2014;141(6):816-27. PubMed · Publisher

Abstract

Objectives: Malignant pleural mesothelioma (MPM) is a highly aggressive disease for which new prognostic biomarkers need to be identified. Caveolin-1 (CAV1), the most important member of caveolae, has been described as deregulated in MPM at the genomic level, but detailed histologic information on its distribution and prognostic role is still lacking.

Methods: A series of 131 MPMs (91 epithelial, 17 biphasic, and 23 sarcomatous histotype) were investigated for CAV1 expression with immunohistochemistry and correlated with clinical-pathologic variables and outcome.

Results: CAV1 was detected in neoplastic cells of 70 (77%) of 91 epithelial, 17 (100%) of 17 biphasic, and 23 (100%) of 23 sarcomatous MPMs. Furthermore, in the epithelial group, CAV1 expression in spindle-shaped stromal cells was detected in 61 (67%) of 91 cases.

Conclusions: The presence of stromal CAV1 expression was associated with a worse patient outcome. In MPM, CAV1 is differentially expressed according to low- to high-grade histotypes. Furthermore, in the MPM epithelial group, additional stromal CAV1 expression is associated with a worse prognosis.

Copyright© by the American Society for Clinical Pathology.
Well-differentiated papillary mesothelioma of the peritoneum: a diagnostic dilemma on fine-needle aspiration cytology. J.G. Nasit, G. Dhruva. 2014;142(2):233-42. Case report · Review PubMed · Publisher

Abstract

Objectives: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is an uncommon subtype of epithelioid mesothelioma. Usually, WDPMP has a benign course, while a few patients have multiple recurrence and malignant transformation on long-term follow-up. The histology of WDPMP has been well studied compared with the cytology. Although accurate diagnosis is based only on histology and immunohistochemical stains, knowledge of the cytologic features of WDPMP in context with clinical and radiologic features is essential to predict a preoperative diagnosis and guide proper management, after excluding reactive mesothelial hyperplasia, malignant mesothelioma, and serous neoplasms of the ovaries and peritoneum. Surgical excision gives a favorable outcome.

Methods: We describe a case of 28-year-old woman who sought treatment for chronic lower abdominal pain, dysuria, and dyspareunia.

Results: Radiologic findings suggested multiple metastatic peritoneal deposits. Ultrasound-guided fine-needle aspiration cytology showed many papillae, tubulopapillary and spheroid groups, monolayered pavement-like sheets, and many dispersed cells. Papillae showed many layers of round to ovoid cells, with minimal atypia. Atypical mitoses and necrosis were not found. A cytologic diagnosis of WDPMP was suggested. After complete resection of all the tumor nodules, histopathology and immunohistochemical findings were compatible with WDPMP. On follow-up, she developed tumor recurrence at 9 months and was managed successfully with adjuvant chemotherapy.

Conclusions: This article highlights the cytologic features of WDPMP with relevant review of the literature and differential diagnosis.

Copyright© by the American Society for Clinical Pathology.
CD90 is a diagnostic marker to differentiate between malignant pleural mesothelioma and lung carcinoma with immunohistochemistry. K. Kawamura, K. Hiroshima, T. Suzuki, et al. 2013;140(4):544-9. PubMed · Publisher

Abstract

Objectives: To pathologically distinguish mesothelioma from lung carcinoma, particularly adenocarcinoma.

Methods: We conducted immunohistochemical analyses on clinical specimens, including 26 cases of mesothelioma, 28 cases of lung adenocarcinoma, and 33 cases of lung squamous cell carcinoma.

Results: We found that CD90 expression was useful in making a differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma, whereas sarcomatoid mesothelioma and lung carcinoma specimens, irrespective of the histologic types, were negative in general. The sensitivity and specificity of CD90 expression in epithelioid mesothelioma and lung adenocarcinoma were comparable to those of well-established markers used for the differential diagnosis.

Conclusions: These data collectively indicate that CD90 is a novel diagnostic marker that contributes to a diagnosis of epithelioid mesothelioma.
Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis. D. Wu, K. Hiroshima, S. Matsumoto, et al. 2013;139(1):39-46. PubMed · Publisher

Abstract

The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.
Morphologic and immunocytochemical performances of effusion cell blocks prepared using 3 different methods. X. Jing, Q.K. Li, U. Bedrossian, et al. 2013;139(2):177-82. PubMed · Publisher

Abstract

With increased use of the ThinPrep method for nongynecologic specimens, cell blocks are more commonly prepared by harvesting cells that are fixed in CytoLyt solution. The current study compared morphologic and immunocytochemical performance of effusion cell blocks prepared using CytoLyt-prefixed thrombin clot (CTC) with plasma thrombin clot (PT) and HistoGel (HG) preparation. The study included a total of 25 malignant or benign serous fluids. Three individual cell block materials were simultaneously prepared from each of the 25 effusion specimens using the CTC, PT, or HG method. H&E staining and immunostaining for pancytokeratin (pan-CK), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), B72.3, HBME-1, estrogen receptor (ER), progesterone receptor (PR), CD45, CD20, and CD3 were then performed. The CTC preparation revealed compatible cellularity and good cellular details. In addition, CTC cell blocks revealed a similar percentage of cells with positive immunostaining along with the strongest intensity and the least background staining. The CTC method can be used reliably as an adjunct to other preparation techniques.
Value of claudin-4 immunostaining in the diagnosis of mesothelioma. N.G. Ordóñez. 2013;139(5):611-9. PubMed · Publisher

Abstract

Claudin-4 (CL-4) is a tight junction-associated protein that is expressed in most epithelial cells but absent in mesothelial cells. The purpose of this study is to evaluate the utility of CL-4 immunostaining for assisting in the differential diagnosis of mesothelioma. Sixty mesotheliomas (40 epithelioid, 10 biphasic, and 10 sarcomatoid), 185 carcinomas of different origins that can potentially be confused with mesotheliomas, 37 soft-tissue sarcomas, and 5 melanomas were investigated for CL-4 expression. All 60 mesotheliomas were CL-4 negative. In contrast, 169 (91%) of 185 carcinomas expressed this marker. Five of 8 desmoplastic small round cell tumors and the epithelial component of all 5 biphasic synovial sarcomas were CL-4 positive, whereas none of the remaining soft-tissue sarcomas or melanomas expressed this marker. It is concluded that CL-4 is a highly specific and sensitive immunohistochemical marker for assisting in distinguishing epithelioid mesotheliomas from metastatic carcinomas to the serosal membranes.
Pericardial synovial sarcoma, a potential for misdiagnosis: clinicopathologic and molecular cytogenetic analysis of three cases with literature review. Y. Cheng, W. Sheng, X. Zhou, et al. 2012;137(1):142-9. Case report · Review PubMed · Publisher

Abstract

Synovial sarcomas arising in unexpected locations may lead to diagnostic challenges. In this report, we describe 3 cases of synovial sarcoma that manifested clinically as primary pericardial lesions. All 3 cases occurred in men in their fourth decade. Fever, cough, chest pain, and chest distress were the most common symptoms. Histologically, 2 of the tumors were spindle cell monophasic, and 1 tumor was biphasic. By immunohistochemical studies, the tumor cells were positive for cytokeratins and epithelial membrane antigen. In addition, the tumor cells displayed focal immunoreactivity for calretinin, cytokeratin 5/6, and HBME-1, resulting in the initial interpretations of malignant mesotheliomas. None of the 3 cases were diagnosed correctly until subsequent molecular cytogenetic assays demonstrated the presence of SYT gene rearrangements. As there are overlapping morphologic features between pericardial synovial sarcoma and mesothelioma, molecular analysis is essential for differential diagnoses.
PRAME (preferentially expressed antigen of melanoma) is a novel marker for differentiating serous carcinoma from malignant mesothelioma. K. Brenne, D.A. Nymoen, R. Reich, et al. 2012;137(2):240-7. PubMed · Publisher

Abstract

The PRAME (preferentially expressed antigen of melanoma) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared with malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the messenger RNA (mRNA) and protein levels. Quantitative real-time polymerase chain reaction analysis of 126 müllerian carcinomas and 23 malignant mesotheliomas showed significantly higher PRAME mRNA expression in the former tumor (P < .001; test sensitivity and specificity, 89% and 91%, respectively). PRAME protein was expressed in 41 of 50 müllerian carcinomas and 0 of 30 mesotheliomas using Western blotting (P < .001; test sensitivity and specificity, 82% and 100%, respectively). PRAME levels in müllerian carcinoma were unrelated to survival; however, PRAME protein expression was up-regulated in solid metastases compared with primary carcinoma and effusions (P < .001). Our data confirm that PRAME effectively differentiates müllerian carcinoma from malignant mesothelioma at the mRNA and protein levels, suggesting a role in the diagnostic workup of serosal cancers.
The diagnostic utility of p16 FISH and GLUT-1 immunohistochemical analysis in mesothelial proliferations. S.E. Monaco, Y. Shuai, M. Bansal, et al. 2011;135(4):619-27. PubMed · Publisher

Abstract

Two promising ancillary tests used in the diagnosis of mesothelioma include GLUT-1 immunohistochemical analysis and fluorescence in situ hybridization (FISH) testing for the p16 deletion. This study compared the diagnostic usefulness of p16 FISH and GLUT-1 immunohistochemical analysis in the diagnosis of mesothelial proliferations in 158 cases with a diagnosis of benign (45.4%), atypical (10.4%), or malignant/mesothelioma (44.2%). Of the 70 benign cases, none had a deletion of p16 and 5 cases (7%) were positive for GLUT-1. Of the 68 mesotheliomas, 40 (59%) had a deletion of p16 (sensitivity, 59%; specificity, 100%) and 27 (40%) were positive for GLUT-1 (sensitivity, 40%; specificity, 93%). GLUT-1 showed lower sensitivity in pleural (56% vs 70%) and peritoneal (29% vs 51%) mesotheliomas (P = .004). Our results demonstrate that p16 FISH is a more sensitive and specific test than GLUT-1 immunohistochemical analysis and can be a more reliable ancillary tool to support the diagnosis of mesothelioma.

2000s

Prognostic role of osteopontin expression in malignant pleural mesothelioma. S. Cappia, L. Righi, D. Mirabelli, et al. 2008;130(1):58-64. PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) represents highly aggressive neoplasms with a mean survival of approximately 10 months. Osteopontin, a glycoprotein involved in cell-matrix interactions correlated with invasion and metastatic spread in several tumors, has recently been proposed as a serum marker of MPM in asbestos-exposed subjects. The aim of this study was to define the prognostic role of osteopontin in MPM. For the study, 32 long-term survivors (>24 months) and a random sample of 69 short-term survivors (<or=24 months) were matched according to the main clinicopathologic features. Immunohistochemical osteopontin expression in tissue specimens was quantified through the HScore (histologic scoring) method and correlated with clinicopathologic parameters and survival. Osteopontin expression was significantly lower in long-term compared with short-term survivors (P< .0001), and overall survival analysis showed that low osteopontin expression was associated with longer survival; multivariate analysis confirmed the value of osteopontin expression as an independent prognostic factor (P< .0001).
Criteria for attributing lung cancer to asbestos exposure. P.T. Cagle. 2002;117(1):9-15. Comment · Editorial PubMed · Publisher

Summary

This editorial commented on a study by Mollo and coworkers of 924 consecutive lobectomies and pneumonectomies for lung cancer in northwest Italy. That study attributed 6% of the cancers to asbestos because of a histologic diagnosis of asbestosis. It raised the possibility that another 0.5% were asbestos-related: cases with interstitial fibrosis, no asbestos bodies on histologic section, but an elevated asbestos body concentration on digestion study. The author discussed criteria for attributing an individual lung cancer to asbestos. He stated that tobacco smoking causes about 90% of lung cancers and that asbestos is estimated to account for 2% to 5%, or about 3,400 to 8,500 new US cases each year. He argued that one or a few asbestos bodies on tissue sections, or pleural plaques, are not reliable criteria by themselves because they can occur below the exposure needed for lung cancer risk. He cited a series of 234 cases by Roggli and Sanders in which all patients with more than 50,000 amphibole fibers per gram of wet lung had asbestosis except 10 patients. He noted that occult asbestosis, if it exists, is extremely rare, and that the fibrosis in the Mollo cases might have other causes, including the cancer itself and smoking. He reported that no unique molecular marker for asbestos-related lung cancer has been identified. He concluded that asbestosis is currently the only consistently reliable marker, especially in smokers.

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.
The attribution of lung cancers to asbestos exposure: a pathologic study of 924 unselected cases. F. Mollo, C. Magnani, P. Bo, et al. 2002;117(1):90-5. PubMed · Publisher

Abstract

We studied a series of 924 nonselected surgical cases of lung carcinoma (without occupational history in clinical records) by histologic examination and light microscopic determination of asbestos body (AB) concentration to determine cancers attributable to asbestos exposure. Lower lobes showed higher concentrations, but no significant associations were recorded between concentrations and histologic type of the lung carcinomas. Histologic asbestosis was demonstrated in 56 cases considered definitely asbestos-related. In 12 of them, the demonstration of asbestosis was attained only after repeated examination of additional sections, suggested by thefinding of more than 1,000 ABs per gram of dry weight (gdw), an indicator of occupational asbestos exposure. In the 56 cases, the media
Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies. F. Roberts, C.M. Harper, I. Downie, et al. 2001;116(2):253-62. PubMed · Publisher

Abstract

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.
Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. O. Kaufmann, E. Fietze, J. Mengs, et al. 2001;116(6):823-30. PubMed · Publisher

Abstract

To facilitate the differential diagnosis of poorly differentiated metastatic carcinomas of unknown primary site, we evaluated p63 and cytokeratin (CK) 5/6 as immunohistochemical markers for squamous cell carcinomas. The study cases were as follows: squamous cell carcinoma of the lungs, head/neck, esophagus, cervix uteri, or anal canal, 73; non-squamous cell carcinomas of various primary sites, 141; and urothelial carcinoma, 20. We also tested 14 malignant mesotheliomas. Immunoreactivity for p63 was as follows: squamous cell carcinomas, 59 (81%); urothelial carcinoma, 14 (70%), most often with diffuse staining patterns; non-squamous cell carcinomas, 20 (14.2%), resulting in a specificity of 0.86 of p63 for squamous cell carcinomas. Coexpression of p63 and CK5/6 had a sensitivity of 0.77 and a specificity of 0.96 for squamous cell carcinomas. Increasing the minimal criterion of positive immunostaining for both markers to more than 50% of immunoreactive tumor cells resulted in a specificity of 0.99, although the sensitivity diminished to 0.66. All malignant mesotheliomas were negative for p63. Our data suggest that positive immunostaining for both p63 and CK5/6 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin.
Lymphohistiocytoid mesothelioma. An often misdiagnosed variant of sarcomatoid malignant mesothelioma. H.S. Khalidi, L.J. Medeiros, H. Battifora. 2000;113(5):649-54. Case report PubMed · Publisher

Abstract

Three cases of lympho-histiocytoid mesothelioma, a rare variant of pleural sarcomatoid malignant mesothelioma, are described. Histologically, the neoplasms were characterized by a diffuse discohesive proliferation of atypical histiocytoid cells intermixed with a marked lymphocytic and lesser plasmacytic infiltrate. One case initially was misdiagnosed as a ganglioneuroma, a second case was misinterpreted as malignant lymphoma, and a third case was sent in consultation with the differential diagnosis of inflammatory pseudotumor vs mesothelioma. Immunohistochemical studies showed strong and generalized expression of cytokeratins and vimentin by the neoplastic histiocytoid cells in all 3 cases. Two cases were positive for calretinin, one of which also was positive for HBME-1, thrombomodulin, and LeuM1. None of the cases stained with the epithelial glycoprotein markers carcinoembryonic antigen, B72.3, and Ber-EP4, or the blood group antigen, BG-8. The immunophenotype of the lymphoplasmacytic infiltrate revealed predominantly reactive, mature T cells, with fewer polytypic plasma cells, histiocytes, and B cells. In lymphohistiocytoid mesothelioma, as in the usual examples of sarcomatoid mesothelioma, the demonstration of cytokeratin expression by the neoplastic cells is the most useful diagnostic finding that allows exclusion of other neoplasms with which this entity may be confused.
Mesothelial proliferations. An increasing morphologic spectrum. M.R. Wick, S.E. Mills. 2000;113(5):619-22. Comment · Editorial · Review PubMed · Publisher

Summary

This editorial accompanied a report in the same journal issue by Khalidi and colleagues describing 3 cases of lymphohistiocytoid (lymphoma-like) malignant mesothelioma, a rare variant first reported in 1988 by Henderson and colleagues from the Australian Mesothelioma Surveillance Program. The authors noted that the incidence of malignant mesothelioma rose sharply through the 1970s and 1980s before reaching a plateau. They reviewed how the classification of mesothelial tumors had been revised over the previous 25 years. Lesions once called benign fibrous mesothelioma were now recognized as solitary fibrous tumor of the pleura, and adenomatoid tumor was now considered mesothelial. The authors preferred to interpret multicystic and well-differentiated papillary mesothelioma as complex hyperplasias. They also described an expanding range of epithelioid, biphasic and sarcomatoid patterns and the tumors each pattern can mimic, including metastatic carcinoma, melanoma, synovial sarcoma and other sarcomas. They discussed the roles of immunohistochemistry, electron microscopy, fluorescence in situ hybridization, polymerase chain reaction and cytogenetics, and stated that testing should be tailored to the tumor's appearance. They argued that separating mesothelioma from its mimics generally did not change treatment or prognosis at the time. In their view, the effort was driven mainly by personal injury litigation, because some mesotheliomas have been linked to amphibole asbestos exposure. They concluded that accurate diagnosis remained worthwhile because future treatments might benefit particular tumor types differently.

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.

1990s

Role of immunohistochemistry in differentiating epithelial mesothelioma from adenocarcinoma. Review and update. N.G. Ordóñez. 1999;112(1):75-89. Review PubMed · Publisher

Summary

This review examined the immunohistochemical markers most commonly used to tell malignant epithelial mesothelioma apart from adenocarcinoma that has spread to the serosal membranes. The author described this distinction as difficult with histochemical stains and electron microscopy alone. Because no specific marker for mesothelioma had been recognized, diagnosis depended on panels of antibodies. The author summarized published studies and his own experience at the University of Texas M. D. Anderson Cancer Center. He emphasized newer markers that can be used on formalin-fixed, routinely processed tissue. In his studies, cytokeratin 5/6 was found in 40 of 40 mesotheliomas but in none of 30 pulmonary adenocarcinomas. Calretinin was strongly expressed in 38 of 38 epithelial mesotheliomas, while 14 (9%) of 155 adenocarcinomas showed focal staining. Vimentin, desmin, polymorphic epithelial mucins, 44-3A6, S-100 protein, HBME-1 and OV632 were judged to have little or no practical value. The author concluded that calretinin and cytokeratin 5/6 appeared to be the most useful positive markers for mesothelioma. MOC-31, CEA, B72.3 and the BG-8 anti-Lewis(y) antibody were the best negative markers. Leu-M1, Ber-EP4 and thrombomodulin could be used as secondary markers when other results were equivocal. N-cadherin and E-cadherin needed further study.

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.
Reactive mesothelial hyperplasia vs mesothelioma, including mesothelioma in situ: a brief review. D.W. Henderson, K.B. Shilkin, D. Whitaker. 1998;110(3):397-404. Review PubMed · Publisher

Abstract

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.
The diagnosis of desmoplastic malignant mesothelioma and its distinction from fibrous pleurisy: a histologic and immunohistochemical analysis of 31 cases including p53 immunostaining. W.E. Mangano, P.T. Cagle, A. Churg, et al. 1998;110(2):191-9. PubMed · Publisher

Abstract

We studied 31 patients with fibrotic pleural lesions and classified them as desmoplastic malignant mesothelioma (DMM) or fibrous pleurisy (FP) using predetermined histologic criteria, including a paucicellular fibrotic pleural lesion with a storiform pattern or the "patternless pattern " of Stout, plus 1 or more of the following: invasion of chest wall or lung, bland necrosis, frankly sarcomatoid areas, and distant metastases. Staining for p53 was performed in 22 cases. Follow-up was obtained on all cases and compared with the histologic diagnoses. For 24 cases, the consensus diagnosis was DMM; 19 of these displayed frankly sarcomatoid areas, 16 showed invasion, and 8, bland necrosis. Of the 24, 23 patients died of disease and 1 was alive with disease. The remaining 7 cases were classified as FP, and all were alive without disease. The concordance among 3 pathologists using the criteria was excellent. Staining for p53 was more common in DMM than in FP, but the difference was not statistically significant. The concordance in interpreting the p53 stains by the same 3 pathologists was moderate. The distinction between DMM and FP in a predominantly fibrotic pleural lesion can be made in most cases with adequate sampling and the use of specific criteria.
The diagnosis of desmoplastic malignant mesothelioma. T.V. Colby. 1998;110(2):135-6. Comment · Editorial PubMed · Publisher

Summary

This editorial commented on a study by Mangano and colleagues, published in the same issue, that proposed histologic criteria for telling desmoplastic malignant mesothelioma (DMM) apart from fibrous pleurisy (FP). The author noted a mesothelioma "epidemic" that was at least partly the result of asbestos exposure in the shipbuilding and construction trades in the 1940s to 1960s, with cases often reviewed as part of asbestos litigation. He stated that DMM made up about 10% of mesotheliomas and that almost all patients died within 18 months. In the study of 31 cases, three observers agreed on the diagnosis in 26 (84%), with a kappa of 0.73. In the other 5 cases, the majority diagnosis matched follow-up. Of the patients with DMM, 23 died of disease and 1 was alive with disease. All 7 patients with FP were alive without disease. DMM was diagnosed in a diffuse fibrosing pleural lesion with storiform or "patternless" areas plus one or more of the following: chest wall or lung invasion (18 cases), bland necrosis (8), frankly sarcomatoid foci (19), or distant metastases (none). The author discussed these features and noted that cytokeratin staining could help in assessing chest wall invasion. He judged underdiagnosis preferable to overdiagnosis and said large specimens were more suitable than closed pleural biopsies. He concluded that the study would likely become the standard for diagnosing DMM.

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Thrombomodulin expression in transitional cell carcinoma. N.G. Ordóñez. 1998;110(3):385-90. PubMed · Publisher

Abstract

Thrombomodulin (TM) is a surface glycoprotein reported to be expressed in a variety of tumors, including mesotheliomas, endothelial vascular tumors, squamous carcinomas, and various adenocarcinomas. This study evaluated TM expression in transitional cell carcinomas (TCCs) and determined whether immunostaining for TM has practical value in the diagnosis of TCCs. TM expression was observed in 96 of 106 primary tumors (bladder, 64/72; renal pelvis, 12/14; ureter, 3/3; prostate, 17/17) and in 21 of 23 metastatic TCCs. Among the adenocarcinomas, only 3 of 18 originating in the bladder, 7 of 46 in the lung, 4 of 21 in the breast, 2 of 24 in the ovary, and 2 of 4 in the pancreas expressed this marker. No staining was observed in the 22 renal cell carcinomas or the 35 adenocarcinomas of the prostate, 13 of the endometrium, or 12 of the colon. Nearly all squamous cell carcinomas (lung, 21/27; skin, 7/7; uterine cervix, 6/6; esophagus, 2/2; bladder, 2/2) reacted for TM. TM is a sensitive marker for TCC. TM immunostaining can assist in distinguishing this tumor from others, especially renal cell carcinomas and adenocarcinomas of the prostate, colon, and bladder, but it has no value in separating TCC from squamous cell carcinomas.
Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The M.D. Anderson experience and a critical review of the literature. N.G. Ordóñez. 1998;109(1):85-9. Review PubMed · Publisher

Abstract

Although most studies have indicated that Ber-EP4 immunostaining can assist in differentiating epithelial pleural mesotheliomas from adenocarcinomas that metastasize to the pleura, the percentage of positive cases has varied greatly among different studies. Authors of a recent publication concluded that Ber-EP4 has no diagnostic utility in separating these conditions. To determine whether Ber-EP4 has any value in distinguishing mesothelioma from adenocarcinoma, 70 formalin-fixed epithelial pleural mesotheliomas, 20 pulmonary adenocarcinomas, 59 nonpulmonary adenocarcinomas, 4 squamous cell carcinomas of the lung, 6 transitional cell carcinomas, and 31 adenocarcinomas of unknown origin that metastasized to the pleura were stained with this antibody. Reactivity was observed in 18 (26%) of 70 mesotheliomas and in all 20 (100%) of the pulmonary adenocarcinomas, in 55 (93%) of the 59 nonpulmonary adenocarcinomas, in 4 (100%) of 4 squamous cell carcinomas of the lung, in 4 (67%) of 6 transitional cell carcinomas, and in 26 (84%) of 31 adenocarcinomas of unknown origin that metastasized to the pleura. The staining in the mesotheliomas was focal and restricted to a limited number of cells, in contrast with staining in the pulmonary adenocarcinomas in which it was invariably diffuse. The extent of the staining in the nonpulmonary adenocarcinomas and the metastatic adenocarcinomas of unknown origin was less consistent--negative or focal in some cases and diffuse in others. Therefore, while Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas, its value in distinguishing mesotheliomas from other tumors metastatic to the pleura is more limited and depends largely on the site of origin of the metastatic tumor.
Effusion cytology after extrapleural pneumonectomy for treatment of malignant mesothelioma. A.A. Renshaw, D. Nappi, S. Swanson, et al. 1997;107(2):206-10. PubMed · Publisher

Abstract

Extrapleural pneumonectomy to treat malignant mesothelioma may offer a significant survival advantage for selected patients. The role of effusion cytology in these patients has not been previously examined. To evaluate this, cytology, pathology, and medical records of 26 cases in 21 patients who underwent extrapleural pneumonectomy because of malignant mesothelioma were reviewed. Positive cytologic results were noted on average 13 months later than negative results. Recurrence was most common in the peritoneum, followed by the ipsilateral thorax and contralateral thorax. Five of 11 true-negative results were secondary to infection; cytologic analysis revealed neutrophils in each case. Four of 5 false-negative cases were from the ipsilateral thorax, and no mesothelial cells were found. When these 4 cases are excluded, the sensitivity of cytologic examination in this setting was 91%, and specificity was 100%. Effusion cytology in patients after extrapleural pneumonectomy is an effective means of diagnosing recurrent malignant mesothelioma.
The applicability of a keratin 7 monoclonal antibody in routinely Papanicolaou-stained cytologic specimens for the differential diagnosis of carcinomas. J.H. Baars, J.L. De Ruijter, F. Smedts, et al. 1994;101(3):257-61. PubMed · Publisher

Abstract

The monoclonal antibody OV-TL 12/30, which detects keratin 7, was tested for its usefulness in cytologic diagnosis by reincubating previously Papanicolaou-stained slides. For this purpose malignant effusions of 73 patients with histologically confirmed cancers of the colon, ovary, mesothelium, breast, lung, esophagus, pancreas, urinary bladder, stomach, kidney, and prostate were used. All malignant cells from ovarian adenocarcinomas were positive, whereas malignant cells from colonic adenocarcinomas and malignant mesotheliomas were negative. Adenocarcinomas of gastric, renal, pancreatic, esophageal, and mammary origin demonstrated variable staining. Transitional cell carcinomas were positive, whereas squamous and small cell lung carcinomas were negative. Because OV-TL 12/30 does not react with normal and atypical mesothelial cells in these preparations, this reagent is a valuable tool in distinguishing benign mesothelial cells and adenocarcinoma cells. The authors' results demonstrate that this antibody is an excellent tool in the differential diagnosis of malignant cells in effusions and can be used in routinely stained cytologic specimens to determine primary tumor localization. In addition to its ability to distinguish between ovarian and colonic adenocarcinomas, its negativity in mesotheliomas may prove helpful in several diagnostic considerations.
Extraskeletal myxoid chondrosarcoma of the pleura. Report of a case clinically simulating mesothelioma. S.P. Goetz, R.A. Robinson, S.K. Landas. 1992;97(4):498-502. Case report PubMed · Publisher

Abstract

A primary extraskeletal myxoid chondrosarcoma of the pleura that clinically mimicked a malignant mesothelioma in a 66-year-old man with a history of asbestos exposure is described. Although exceedingly rare in this location, the characteristic histologic features, immunohistochemical reactivities, and ultrastructural features support the diagnosis of extraskeletal myxoid chondrosarcoma. Many ferruginous (asbestos) bodies consistent with the exposure history were found in the lung tissue sections and confirmed by energy-dispersive spectrometry. This case demonstrates an unusual pleural primary neoplasm associated with asbestos.
Comparative immunohistochemical staining for desmin and muscle-specific actin. A study of 576 cases. S. Rangdaeng, L.D. Truong. 1991;96(1):32-45. PubMed · Publisher

Abstract

Muscle-specific actin (MSA) and desmin are considered to be sensitive and specific markers for muscle differentiation. The authors compared staining patterns for these markers in 576 samples of normal, reactive, and neoplastic tissues. The standard avidin-biotin-peroxidase complex technique was performed with the use of two commercial antibodies against MSA (HHF35; Enzo Biochemical, Inc., New York, NY) and desmin (DER11; DAKO Corporation, Santa Barbara, CA), respectively, on consecutive paraffin-embedded tissue sections from these cases. Both MSA and desmin were found in all 80 normal muscle samples. Although MSA appeared diffusely in all vascular smooth muscle samples, desmin was demonstrated focally in vascular smooth muscle cells in 100 of 196 samples. MSA but not desmin always was found in myoepithelial cells (25 samples), pericytes (286 samples), and decidual cells (7 samples). Among 76 cases of myofibroblast-containing lesions, 14 and 54 were found to have desmin and MSA, respectively. MSA and desmin were found in 4 of 4 cardiac rhabdomyomas, 34 of 34 rhabdomyosarcomas, and 5 of 6 leiomyomas. Among 22 leiomyosarcomas, 7 displayed either MSA or desmin and 7 showed both markers. In general, more tumor cells showed staining for MSA than desmin, but the reverse was true in some cases. Tissue fixed in Zenker's solution seemed to show a significant decrease in MSA immunoreactivity, but no significant change for desmin staining was observed. None of the 154 normal tissues and 22 benign nonmyogenic tumors expressed MSA or desmin. Among 133 malignant nonmyogenic tumors, positive staining for both desmin and MSA was found in 3 of 8 cases of glioblastoma multiforme, 1 of 10 malignant schwannomas, and 1 of 14 malignant fibrous histiocytomas; staining for only MSA was found in 3 of 14 malignant fibrous histiocytomas, 1 of 10 malignant schwannomas, 6 of 6 fibromatoses, 1 of 1 mammary myofibroblastoma, and 1 of 7 malignant mesotheliomas; and staining for desmin only was seen in 1 of 7 malignant mesotheliomas.(ABSTRACT TRUNCATED AT 400 WORDS)
Immunocytochemical panel for the identification of malignant cells in serous effusions. K.V. Nance, J.F. Silverman. 1991;95(6):867-74. PubMed · Publisher

Abstract

The cytologic diagnosis of malignancy in serous effusions can be challenging. An immunocytochemical (ICC) panel using commercially available antibodies (to carcinoembryonic antigen [CEA], epithelial membrane antigen [EMA], B72.3, Leu-M1, cytokeratin [CK], leukocyte common antigen [LCA], S-100 protein, and vimentin) was applied to cell blocks fixed in methyl Carnoy's solution that were from 55 consecutive pleural, peritoneal, and pericardial fluid specimens. The results were correlated with data from clinical records and routine cytologic studies. Final cytologic diagnoses included 26 of adenocarcinoma and 1 of mesothelioma. The remaining 28 cases were considered to be benign (reactive) proliferations. EMA, CEA, B72.3, and Leu-M1 were present in 96%, 77%, 58%, and 42% of adenocarcinomas, respectively. These determinants were absent in the mesothelioma and the reactive effusions, although anti-CEA yielded strong background staining of inflammatory cells. The CK markers identified malignant cells in 93% of cases, but consistently stained mesothelial cells as well. Antivimentin strongly labeled mesothelial cells in all cases, with weak to absent staining of malignant cells. In 3 of 26 carcinoma cases (12%), the ICC panel identified malignant cells that were not recognized initially on routine cytologic examination. In 1 of 26 cases (4%), the panel was falsely negative. Use of this approach can improve the diagnostic accuracy of cytologic examination of serous fluids. The ICC panel is especially helpful when atypical mesothelial proliferation is present, or in cases that are clinically suspect for malignancy, but cytologically negative because there are only a few malignant cells, or those that are cytologically bland.
Cystic mesothelioma of the peritoneum. A report of three cases. S. Villaschi, F. Autelitano, G. Santeusanio, et al. 1990;94(6):758-61. Case report PubMed · Publisher

Abstract

Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis.
Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. K. Sheahan, M.J. O'Brien, B. Burke, et al. 1990;94(2):157-64. PubMed · Publisher

Abstract

To evaluate the role of carcinoembryonic antigen (CEA) in solving problems of tumor histogenesis in surgical pathology, monoclonal antibodies to four distinct epitopes of CEA (E-Z-EM) were applied to paraffin sections of 303 epithelial neoplasms from multiple sites. Two epitopes were CEA specific (D14 and B7.1), one was shared with nonspecific cross-reacting antigen (NCA) (B7.8), and the fourth (B18) was common to CEA, NCA, and biliary glycoprotein antigen (BGP). A sample of the tumors (n = 110) was also stained with a polyclonal anti-CEA (DAKO). Gastrointestinal adenocarcinomas, including esophageal and gastric (n = 19), small intestinal (n = 8), colorectal (n = 56), biliary tract (n = 8), and pancreatic adenocarcinomas (n = 14), were consistently positive with all five antibodies. Other predominantly gland-forming carcinomas tested, comprising lung (n = 22), ovary (n = 18), and endometrium (n = 12), were either invariably negative with all five antibodies (endometrial adenocarcinoma, non-mucinous ovarian adenocarcinoma) or demonstrated selective and variable positivity (lung: D14, 50%; ovarian mucinous: D14, 50%). Among large polygonal cell carcinomas (hepatocellular carcinoma, renal cell carcinoma, melanoma, and adrenal carcinoma), only hepatomas stained positively, showing a distinctive canalicular staining pattern with the B18 (BGP epitope) (55%) and polyclonal antibody (50%). In the small polygonal cell carcinoma category, true CEA positivity was rare in breast (D14, 10% and B7.1, 14%) and never seen in prostatic carcinomas and carcinoid tumors. A subset of these breast (8 of 42), prostate (4 of 22), and carcinoids (4 of 7) showed exclusive positivity for the B18 antibody (NCA/BGP epitope). Ovarian serous papillary carcinomas (n = 14), papillary carcinomas of thyroid (n = 12), transitional cell carcinomas of the bladder (n = 11), and mesotheliomas (n = 3) were negative with all monoclonal antibodies. Metastatic carcinomas (n = 74) showed a similar pattern of reactivity to primary tumors. The authors conclude that CEA immunostaining may assist in identifying the histogenesis of epithelial tumors in several morphologic categories; that differential reactivities of the CEA monoclonal antibody panel exceed those of the polyclonal antibody; and that the discriminating power of the monoclonal panel is related to whether (1) CEA is or is not produced or (2) NCA or BGP is produced without concomitant CEA production. There is little evidence to support a concept of site-specific CEA species.

1980s

Immunohistochemical differentiation of sarcomatoid mesotheliomas from other spindle cell neoplasms. P.T. Cagle, L.D. Truong, V.L. Roggli, et al. 1989;92(5):566-71. PubMed · Publisher

Abstract

A sizable proportion of pleural malignant mesotheliomas are sarcomatoid (22%) or biphasic (24%) and may need to be distinguished from other spindle cell neoplasms that occur as primary or metastatic tumors of the chest wall or lungs. To determine the utility of immunohistochemistry in the differentiation of sarcomatoid malignant mesotheliomas from other spindle cell neoplasms, the authors studied the immunostaining patterns of nine antibodies in four sarcomatoid mesotheliomas, one desmoplastic mesothelioma, two epithelial mesotheliomas, four spindle cell squamous carcinomas, and eight sarcomas of various differentiation. Three of the four sarcomatoid mesotheliomas and the desmoplastic mesothelioma had positive results for cytokeratin, which distinguishes them from sarcomas but not from spindle cell squamous carcinomas. The immunostaining pattern of 14 examples of benign spindle cell mesothelial proliferation was similar to that of the sarcomatoid mesotheliomas, which supports the theory that these tumors are mesothelial in origin. Although other antibodies occasionally may be helpful, depending on the differentiation of the sarcoma, cytokeratin immunostaining appears to be the best method to discriminate sarcomatoid mesotheliomas from sarcomas.
Localized fibrous tumor of the serosal cavities. Immunohistochemical, electron-microscopic, and flow-cytometric DNA study. A.K. el-Naggar, J.Y. Ro, A.G. Ayala, et al. 1989;92(5):561-5. PubMed · Publisher

Abstract

Localized fibrous tumor of the serosal cavities (localized fibrous mesothelioma) is a generally benign spindle cell neoplasm of uncertain histogenesis. Fourteen histologically similar primary tumors from different mesothelium-lined sites (11 pleural and 1 each in the pericardium, peritoneal cavity, and pouch of Douglas) and 2 recurrences of those tumors (pericardium and pouch of Douglas) were examined histopathologically and by flow cytometry to relate histologic features and DNA ploidy to biologic behavior (follow-up, 48-255 months among 13 patients). All 16 tumors (14 primaries and 2 recurrences) displayed diploid DNA pattern, and none of 13 patients died of disease (1 patient was lost to follow-up). To elucidate the histogenesis, seven primary tumors were examined for vimentin and keratin immunostaining and six primary tumors were assessed by electron microscopy. All cases exhibited spindle-fibroblastic cell proliferation with a prominent hemangiopericytic pattern. All cases so examined had positive results for vimentin and negative results for keratin. Ultrastructurally, the tumor cells showed mesenchymal-fibroblastic features. These results support a mesenchymal origin, most likely from submesothelial fibroblasts. Further, this neoplasm may recur but retain its basic histologic features, diploidy, and benign outcome.
1987 H. P. Smith award lecture. Eyes for the epidemiologist: the pathologist's role in shaping our understanding of the asbestos-associated diseases. J.E. Craighead. 1988;89(2):281-7. Historical article PubMed · Publisher

Abstract

Asbestosis was first recognized as an entity at autopsy by a pathologist in 1900. Pathologists also discovered the unique relationship of mesothelioma and bronchogenic carcinoma with exposure to asbestos. The observations of preceding pathologists have provided insights that have served as the basis for epidemiologic studies associating asbestos with disease in humans.
Flow cytometric analysis of ploidy in immunohistochemically confirmed examples of malignant epithelial mesothelioma. H.F. Frierson, S.E. Mills, J.F. Legier. 1988;90(3):240-3. PubMed · Publisher

Abstract

Flow cytometry was used to compare the DNA content of 28 fresh effusion specimens that contained abundant proliferating mesothelial cells, with the ploidy profiles for 19 formalin-fixed, paraffin-embedded examples of malignant epithelial mesothelioma. Each mesothelioma lacked staining with periodic acid-Schiff (PAS) after diastase pretreatment. Nineteen of 19 mesotheliomas were immunoreactive for cytokeratin, 13 of 19 for epithelial membrane antigen, 0 of 19 for Leu-M1, and 0 of 19 for carcinoembryonic antigen. Each benign fluid specimen was DNA diploid. Nine of the deparaffinized mesotheliomas were DNA diploid, and seven had additional G0G1 peaks signifying DNA aneuploidy. Histograms from the remaining three mesotheliomas showed G0G1 peaks with prominent shoulders, probably indicating low-degree hyperdiploidy. The results suggest that ploidy analysis by flow cytometry might be useful for the separation of mesothelioma from proliferating mesothelial cells in effusion specimens. Although only 53% of the mesotheliomas were DNA aneuploid, the finding of DNA aneuploidy in an effusion specimen that contains atypical mesothelial cells would strongly support a diagnosis of mesothelioma.
Intrapulmonary localized fibrous tumor. Intraparenchymal so-called localized fibrous mesothelioma. S.A. Yousem, S.D. Flynn. 1988;89(3):365-9. Case report PubMed · Publisher

Abstract

This report describes three cases of intrapulmonary fibromas which are histologically identical to localized fibrous tumors of pleura (localized fibrous mesothelioma). Morphologically these tumors are characterized by a haphazard proliferation of cytologically bland spindle cells separated by variable amounts of wavy hyalinized collagen. Entrapped bronchiolar and alveolar epithelium is common. These spindle cells lack expression of cytoplasmic keratin, S-100 protein, desmin, and epithelial membrane antigen, but are strongly decorated for intracellular vimentin. The clinical behavior, differential diagnosis, and histogenesis of these lesions are discussed.
Pulmonary and pleural thymoma. Diagnostic application of lymphocyte markers to the thymoma of unusual site. M. Fukayama, Y. Maeda, N. Funata, et al. 1988;89(5):617-21. Case report PubMed · Publisher

Abstract

Two cases of the thymoma of the unusual sites were examined immunohistochemically. The one was intrapulmonary, and the other was diffuse pleural tumors. The infiltrating lymphocytes were T-cells showing OKT 6 positivity and nuclear immunoreactivity for terminal deoxynucleotidyl transferase (TdT) in the intrapulmonary tumor, like lymphocytes in the mediastinal thymoma of predominantly lymphocytic or mixed types. Although lymphocytes were dispersed in the pleural tumor, there were some TdT(+) OKT 6(-) lymphocytes and the similar finding was observed in the thymoma of predominantly epithelial type. In lung carcinomas and pleural mesotheliomas, there were no TdT(+) OKT 6(+/-) lymphocytes. Immunohistochemical studies using lymphocyte markers may be an useful tool for the diagnosis of the thymoma of ectopic site or unusual presentation.
Immunohistochemical staining in malignant mesotheliomas. J.G. Strickler, B.G. Herndier, R.V. Rouse. 1987;88(5):610-4. PubMed · Publisher

Abstract

The immunoreactivity of five antibodies was evaluated on six routinely processed mesotheliomas to evaluate their ability to distinguish mesothelioma from metastatic adenocarcinoma. The diagnosis in all cases was confirmed by electron microscopic examination and histochemical stains for neutral mucin (periodic acid-Schiff-diastase) and acid mucin (alcian blue with and without hyaluronidase). AE1, a monoclonal antikeratin antibody that stains most carcinomas, reacted with all six cases of mesothelioma. HMFG-2 and anti-epithelial membrane antigen (antibodies reactive with human milk fat globule proteins), two other closely related antibodies reactive with most carcinomas, also reacted with all of the mesotheliomas in the authors' series. A polyclonal antibody to carcinoembryonic antigen (anti-CEA) did not stain any of the mesotheliomas in their series. Anti-Leu-M1 did not react with the mesotheliomas. The authors conclude that none of these antibodies, when used alone on routinely fixed paraffin-embedded material, is both sensitive and specific in the distinction of mesothelioma from adenocarcinoma. However, immunoperoxidase studies using anti-CEA and anti-Leu-M1 may occasionally be helpful when used in conjunction with other histochemical stains and electron microscopic examination in distinguishing mesothelioma from metastatic adenocarcinoma.
The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. A comprehensive immunohistochemical study on formalin- and alcohol-fixed tumors. N. Azumi, H. Battifora. 1987;88(3):286-96. PubMed · Publisher

Abstract

Vimentin has been regarded as the intermediate filament characteristic of normal and neoplastic mesenchymal cells and keratins as typical of epithelial cells and the neoplasms derived from them. However, many epithelial cells in tissue culture or in effusion, as well as cells in some solid epithelial neoplasms such as renal, endometrial, ovarian, pulmonary, and thyroid adenocarcinomas, have been shown to coexpress vimentin and keratin. The recent availability of monoclonal antibodies that work reasonably well in paraffin-embedded tissue led us to carry out a comprehensive immunohistochemical study on formalin- and alcohol-fixed specimens of neoplasms in which we used monoclonal antibodies against vimentin. These results were compared with our previous study in which the same tumor tissues were investigated using antibodies against keratin. The antigenicity of vimentin was found to be preserved in all alcohol-fixed specimens and in 63% of formalin-fixed tissues. Vimentin was the sole intermediate filament present in virtually all sarcomas, meningiomas, schwannomas, and melanomas. In addition, variable percentages (10-57%) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas, and mesotheliomas were positive for vimentin, which, except in the neuroblastomas, was coexpressed with keratins. Among the adenocarcinomas, more than 50% of papillary carcinomas of the thyroid, as well as renal, endometrial, ovarian, and lung carcinomas, coexpressed keratins and vimentin. A distinctive paranuclear and basal localization of vimentin was observed in the cells of many of these tumors, in contrast to the predominantly apical distribution of the keratins. The authors conclude that coexpression of vimentin and keratin is more widespread than previously reported and that antibodies to vimentin, by themselves, are of limited value for the differentiation of epithelial from mesenchymal neoplasms.
Distinct keratin patterns demonstrated by immunoperoxidase staining of adenocarcinomas, carcinoids, and mesotheliomas using polyclonal and monoclonal anti-keratin antibodies. H.J. Kahn, P.S. Thorner, H. Yeger, et al. 1986;86(5):566-74. PubMed · Publisher

Abstract

The authors assessed whether distinct patterns for keratin could be demonstrated in 10 adenocarcinomas, 10 carcinoids, and 4 mesotheliomas by an immunoperoxidase reaction using 3 polyclonal and 3 monoclonal antibodies to keratin. When color development in diaminobenzidine (DAB) was allowed to proceed for less than 2 minutes, distinct patterns for keratin could be demonstrated using two polyclonal and two monoclonal antibodies; these were plasma membrane and/or web-like in the adenocarcinomas, punctate or crescentic in the carcinoids, and perinuclear in the mesotheliomas consisting of tumor cells with abundant cytoplasm. Immunoelectron microscopy using protein A colloidal gold confirmed these results. When color development in DAB was allowed to proceed for more than 2 minutes, only diffuse staining was seen. The distinct patterns of immunostaining for keratin obtained with the shorter color development were helpful in differentiating adenocarcinomas, carcinoids, and mesotheliomas.
Pleural malignant mesothelioma following Wilms' tumor. M.B. Austin, R.E. Fechner, V.L. Roggli. 1986;86(2):227-30. Case report PubMed · Publisher

Abstract

A 28-year-old woman had a left pleural malignant mesothelioma develop, which resulted in her death. At age four, she had undergone a left nephrectomy for Wilms' tumor and had received radiation therapy to the left renal fossa and to the right lung, the latter for a presumed diagnosis of metastatic tumor. Asbestos body counts of digested lung tissue were within the normal range. This is the fourth reported case of malignant mesothelioma following Wilms' tumor and is the first to provide quantitative analysis of asbestos in the lung.
Asbestos link to lymphoid neoplasms still just a hypothesis. P. Silcocks. 1984;81(3):410. Letter PubMed · Publisher
Lymphoid and plasma cell malignancies: asbestos-related disorders of long latency. E. Kagan, R.J. Jacobson. 1983;80(1):14-20. PubMed · Publisher

Abstract

We have identified 13 asbestos workers with lymphoplasmacytic neoplasms: six with chronic lymphocytic leukemia, four with IgG myeloma, two with IgA myeloma, and one with histiocytic lymphoma. The subjects' occupations were varied, but all had experienced protracted asbestos exposure (ranging from 3-37 years). Tumor latency periods were similar to other known asbestos-related malignancies and ranged from 16-41 years. Stigmata of asbestos-related pulmonary disease were evident in 12 subjects. Malignant pleural mesotheliomas co-existed with IgG myelomas in two individuals, an association which seems unlikely to be fortuitous. It has been speculated previously that asbestos may be a lymphoid system carcinogen. Our findings strongly support this view and indicate that patients presenting de novo with lymphoproliferative neoplasms should be investigated for previous occupational or environmental exposure to asbestos.
Adenomatoid tumors of the uterus. J.C. Quigley, W.R. Hart. 1981;76(5):627-35. PubMed · Publisher

Abstract

Adenomatoid tumors arising in the uterus are not well-recognized and are sometimes mistaken for other benign or malignant neoplasms. This study is a clinicopathologic analysis of 12 uterine adenomatoid tumors. Characteristically, they were small nodular lesions (mean diameter 2.1 cm) in the subserosa or outer wall of the myometrium. Four distinctive histologic types (adenoid, angiomatoid, solid, and cystic) were identified; each tumor consisted of a combination of one major and at least one minor type. The nodular proliferation of smooth muscle which accompanied some tumors was regarded as a non-neoplastic hyperplasia of myometrium. In two cases, small foci of serosal endosalpingiosis were adjacent to the tumor. Theories of histogenesis are discussed, and classification of the adenomatoid tumor as a type of benign mesothelioma is endorsed.
Pulmonary fibrosis, carcinoma, and ferruginous body counts in amosite asbestos workers. A study of six cases. V.L. Roggli, S.D. Greenberg, L.H. Seitzman, et al. 1980;73(4):496-503. PubMed · Publisher

Abstract

The Tyler Asbestos Workers Program is a continuing study of 1,105 former amosite asbestos workers. This report includes a study of six former workers, five of whom died and had autopsies, and one who underwent a lobectomy. Five of these men were exposed to asbestos for three months or less. Four had lung cancer, and one a rectal carcinoma. All were cigarette smokers. Ferruginous (asbestos) body content of the upper and lower lobes of the lungs was quantitated by a digestion technic. Tissue sections from upper and lower lobes were independently quantitated for fibrosis and ferruginous bodies, and chest roentgenograms were examined for interstitial fibrosis. (Control lung tissue was obtained from consecutive autopsies of 52 adults who did not have a known occupational exposure to asbestos.) Relatively low ferruginous body counts (less than 700/g lung tissue) were associated with mild degrees of fibrosis, and higher counts (greater than 10,000/g) with moderate to severe fibrosis. Mild to moderate pulmonary fibrosis could be identified on tissue sections before interstitial changes were detectable by chest roentgenograms.

1970s

Hepatic tumors of long duration with eventual metastases. Two cases of leiomyosarcomatosis possibly arising from hamartomas of liver. R.A. Echevarria, V.M. Arean, L. Galindo. 1978;69(6):624-31. Case report PubMed · Publisher

Abstract

The cases of two patients who had hepatic tumors of long duration interpreted as hamartomas in whom, after many years, widespread metastases of malignant smooth muscle cells developed in a pattern of "carcinomatous lymphangitis" in the lungs are described. In one of the cases calcification of the hepatic nodules was prominent. The smooth muscle origin of the malignant cells was established only on electron microscopic examination. These cases appear similar to others variously reported as mixed tumors, hepatic cell carcinomas, and mesotheliomas.
A simple method for preparing ferruginous bodies for electron microscopic examination. A. Churg, N. Sakoda, M.L. Warnock. 1977;68(4):513-7. PubMed · Publisher

Abstract

A new method of preparing ferruginous (asbestos) bodies for electron-optical examination is described. Pulmonary tissue is dissolved in bleach and the residue collected on a Millipore filter. The ferruginous bodies are localized by light microscopy, and a portion of the filter containing a body is cut out and mounted on a coated electron microscope grid. The filter is dissolved in acetone vapor in a condensation washer, leaving the bodies, as well as uncoated submicroscopic fibers, on the grid. This method can be used to obtain bodies from the lungs of individuals after all degress of asbestos exposure, but it is particularly useful when dealing with minimally exposed or non-exposed individuals whose lungs contain very few bodies. The procedure allows easy identification of body cores by electron diffraction or electron microprobe analysis.
Diffuse malignant mesothelioma. M. Klima, H.J. Spjut, W.D. Seybold. 1976;65(5):583-600. PubMed · Publisher

Abstract

Thirteen cases of diffuse malignant mesothelioma, 12 pleural and one peritoneal, were examined and reviewed from the clinical and morphologic points of view. The most frequent symptom and sign were pain and effusion. Periods of survival varied, with one patient surviving 11 years despite morphologic features of the pleural tumor. The diagnosis can be made only on the basis of excised tumor tissue. The best control of the tumor is attained by repeated surgical removal. Neither radiation nor chemotherapy altered significantly the growth of the tumors.
Pseudomesotheliomatous carcinoma of the lung. A variant of peripheral lung cancer. T.R. Harwood, D.R. Gracey, H. Yokoo. 1976;65(2):159-67. Case report PubMed · Publisher

Abstract

Six cases of primary lung cancer that closely mimic malignant pleural mesothelioma clinically and anatomically are compared with four proven cases of malignant pleural mesothelioma. Findings on roentgenograms of the chest, clinical history, and gross examination of the lung specimens are not helpful in distinguishing between these two neoplasms. Microscopic examination of the hematoxylin and eosin-stained tissues is often inconclusive. Tissues were stained with hematoxylin and eosin, PAS with and without diastase treatment (DPAS), mucicarmine, alcian blue, toluidine blue, and colloidal iron with and without digestion by testicular hyaluronidase. Among these histochemical methods, DPAS was found to be particularly useful in distinguishing the primary lung cancers from the mesotheliomas. All primary lung cancers except one showed DPAS-positive material (mucin) in both the cytoplasm of the cancer cells and within the lumina of neoplastic glands. In contrast, none of the mesotheliomas showed the presence of DPAS-positive material. Histologically, all lung cancers were glandular. Five were classified as bronchiolar carcinoma, the remaining one as poorly differentiated adenocarcinoma. In two of the bronchiolar carcinomas, a small subpleural primary focus was demonstrated. This finding suggests a possible origin of these cancers as a small subpleural tumor that became widely disseminated via the subpleural lymphatics. This form of primary lung cancer possesses sufficient gross and microscopic characteristics that recognition should be given to it as a variant of primary lung cancer, with emphasis on differentiating it from pleural mesothelioma.
Pulmonary cytopathology of former asbestos workers. Report of the first year. S.D. Greenberg, G.A. Hurst, S.C. Christianson, et al. 1976;66(5):815-22. PubMed · Publisher

Abstract

Five hundred fifty-four workers, 84% of whom are chronic cigarette smokers, have been examined during the past year with emphasis on the role of sputum cytopathology in the early detection and diagnosis of lung cancer. Of the 554, 232 (42%) have shown squamous metaplasia, 44 (8%), mild to moderate atypias, 18 (3.2%), severe atypias, and two (0.4%), squamous carcinoma. Both of the carcinomas were in x-ray negative, cytopathology-positive elderly cigarette smokers. Ferruginous bodies have been found in the sputa of 187 (33%) workers. Ferruginous bodies in the sputum do not appear to be a marker for severe atypias; rather, their presence correlates best with duration and extent of industrial exposure to asbestos.
"Mesothelioma of the atrioventricular node" with long-standing complete heart block. Report of a case. I.R. Wanless, B.W. Mielke, B. Jugdutt, et al. 1975;63(3):377-83. PubMed · Publisher

Abstract

A case of mesothelioma of the atrioventricular node is presented. The patient had complete heart block for many years before death. The origin of the tissue in this apparently congenital tumor is discussed with reference to the literature.
Ferruginous (abestos) bodies and primary carcinoma of the colon. P. Rosen, A. Savino, M. Melamed. 1974;61(1):135-8. PubMed · Publisher

Abstract

There is considerable evidence that asbestos may contribute to the development of mesothelioma and pulmonary carcinoma. It has also been suggested that asbestos could participate in the genesis of colonic carcinoma. In this study we sought to isolate ferruginous (asbestos) bodies from 21 specimens of bowel. The majority were from patients with primary carcinoma of the colon. No true ferruginous (asbestos) bodies were recovered. The significance of these results is discussed. (Key words: Ferruginous bodies; Asbestos; Carcinoma; Large intestine; Colon.)

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.
Ferruginous bodies in benign fibrous pleural plaques. P. Rosen, P. Gordon, A. Savino, et al. 1973;60(5):608-12. PubMed · Publisher

Abstract

Some pathologic and epidemiologic evidence suggests that benign fibrous plaques may form in the pleura as a reaction to inspired asbestos. The ferruginous bodies formed in reaction to asbestos and other respirable fibers have virtually never been demonstrated in these lesions by study of tissue sections. Using a tissue digestion and microfiltration technic the authors identified small numbers of typical ferruginous bodies in three of eight specimens studied. Also found was another type of iron-coated structure which was designated an "atypical ferruginous body." These may be endogenous or exogenous in origin. Ferruginous bodies probably are of little significance in the genesis of fibrous pleural plaques.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

Researchers at a New York cancer hospital looked for ferruginous bodies in benign fibrous pleural plaques from eight patients. Ferruginous bodies are iron-coated fibers of the kind usually linked with asbestos exposure. The plaques were collected over 12 months at autopsy or surgery. The researchers dissolved 5-gram samples of plaque, and of lung where available, and filtered what remained to concentrate any bodies. Typical ferruginous bodies turned up in three of the eight plaque samples, in very small numbers (2, 7 and 6 per 5 grams), and only in parietal pleura. All six lung samples, which came from five patients, contained them, at counts from 41 to more than 250 per 5 grams. The team also found segmented iron-coated structures they called "atypical ferruginous bodies". These were more common in plaques than in lungs, and the authors could not say where they came from. Asbestos work histories were available for the three patients with the most bodies in their lungs. The authors concluded that ferruginous bodies are scarce in pleural plaques and may not play an important role in forming them.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.
A method for extracting ferruginous bodies from sputum and pulmonary tissue. M.J. Smith, B. Naylor. 1972;58(3):250-4. PubMed · Publisher

Abstract

A method for extracting ferruginous bodies from sputum and fixed or unfixed lung is described. The principle is to digest the sputum or tissue completely in domestic laundry bleach (5.25% sodium hypochlorite) and to collect the solid residue on a membrane filter. This method allows one to extract from a specimen virtually every ferruginous body that is visible with the light microscope. With this method, ferruginous bodies were found in pulmonary tissue from each of 100 consecutive necropsies of patients 16 years old and over. In one case, ferruginous bodies were found in a concentration of about 750,000 per Gm. of wet fixed pulmonary tissue.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

1960s

Malignant peritoneal mesothelioma. A. Bolio-Cicero, J. Aguirre, R. Perez-Tamayo. 1961;36:417-26. PubMed · Publisher

Abstract

This paper deals with the clinical and pathologic features of 5 examples of peritoneal mesothelioma observed at autopsy and 1 diagnosed by means of biopsy. Emphasis is given to the similarity of clinical course and gross and microscopic structure. Several reasons are discussed for regarding malignant peritoneal mesotheliomas as a well defined clinicopathologic entity, and some useful criteria are outlined that may serve to establish the diagnosis.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.
Localized mesotheliomas of the pleura. The pathologic evaluation of 18 cases. E.A. Foster, L.V. Ackerman. 1960;34:349-64. PubMed · Publisher

1950s

Malignant mesothelioma associated with hypoglycemia; report of a case. K.A. Nesbitt, J.T. Boswell, M.A. Dejesusgonzales, et al. 1958;30(2):148-57. Case report PubMed · Publisher

Abstract

A case of malignant mesothelioma of the peritoneal cavity associated with hypoglycemia of convulsive levels in a former mild diabetic is presented. The subject of nonpancreatic tumors associated with hypoglycemia is briefly reviewed. It is suggested that the term "mesodermal" might be more generally applicable than "fibrogenic" in classifying a group of rare tumors associated with hypoglycemia and now of considerable interest. It is important that pathologists and clinicians be on the alert to bio-assay tumor tissue in similar future cases for insulin activity and insulinase-inhibitors. Such additional studies are essential for a better understanding of the relationships of carbohydrate metabolism and these neoplasms.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.
Occupational cancer of the urinary bladder in dyestuffs operatives and of the lung in asbestos textile workers and iron-ore miners. G.M. Bonser, J.S. Faulds, M.J. Stewart. 1955;25(2):126-34. PubMed · Publisher
Silicosis, asbestosis, and cancer of the lung. W.C. Hueper. 1955;25(12):1388-90. PubMed · Publisher

Summary

This editorial reviewed published evidence on whether dust-related lung diseases are linked to lung cancer. For silica, the author cited data indicating that lung cancer was not excessively frequent among coal and silica-exposed workers. Merewether found carcinoma of the lung at postmortem in 99 of 6884 silicosis cases (1.32 per cent), and Sporlein found lung cancer in 7 of 383 autopsied men with silicosis (1.8 per cent) against an expected 9.9 to 12 per cent. Sporlein suggested a possible antagonism between the two conditions. For asbestosis, the author described the evidence for a causal relationship with lung cancer as quite substantial. He counted 127 recorded cases (United States 21, Canada 6, Great Britain 88, Germany 12), including 10 among 21 autopsied asbestos textile plant employees in a Pennsylvania community. Lung cancer frequency in asbestosis autopsy series ranged from 7.5 to 50 per cent, and was 15.5 per cent across 738 collected autopsies. Among 56 cases, 29 were squamous cell, 15 round cell-anaplastic, 7 adenocarcinomas and 5 mixed. Tumors often involved the lower lobes. Exposure periods ranged from 6 months to 42 years, and the lag after exposure ended could be as long as 20 years. The author concluded that the evidence was adequate to recognize asbestosis cancer of the lung as an occupational disease for medicolegal purposes. He noted possible 'neighborhood' cases near asbestos plants. He stated that the increased risk appeared limited to people with asbestosis.

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.
Mesothelioma of the female genital tract; review of the literature and report of five cases involving the uterus. R.C. Horn, G.C. Lewis. 1951;21(3):251-9. PubMed · Publisher

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