Journal of Clinical Pathology

Our medical research library holds 57 studies published in Journal of Clinical Pathology (1967–2020). 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. 46 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 2 studies 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: BMJ Pub. Group
• Published: 1947 to the present, England
• Language: English
• ISSN: 0021-9746 (print), 1472-4146 (electronic)
• Its record in the NLM Catalog

2020s

• Biphasic malignant mesothelioma with epithelioid and sarcomatoid components (dedifferentiated mesothelioma) and intrapulmonary growth: a rare entity mimicking desquamative interstitial pneumonia. J. Laforga, A. Gonzalez Garcia. 2020;73(12):e8. Case report PubMed · Publisher

2010s

• Small intestinal intussusception in an adult. K. Takada, N. Fujimoto, T. Ozeki, et al. 2019;72(7):510. Case report PubMed · Publisher

• Use of cholesterol and soluble tumour markers CEA and syndecan-2 in pleural effusions in cases of inconclusive cytology. M. Gulyas, J. Fillinger, A.D. Kaposi, et al. 2019;72(8):529-535. PubMed · Publisher · Free full text

  Abstract

  Aims: In order to improve diagnostics in pleural effusions, additional value of effusion cholesterol, carcinoembryonic antigen (CEA) and syndecan-2 assays to cytology was studied.

  Methods: Biomarkers were measured in effusion supernatants from 247 patients, of whom 126 had malignant pleural involvement, and their additional diagnostic efficacy to cytology was assessed.

  Results: Syndecan-2 measurement, although gave detectable concentrations in all effusions with highest median value in mesotheliomas, was non-discriminative between different pathological conditions. CEA concentrations exceeding 5 ng/mL cut-off point indicated carcinomas, regardless of pleural involvement, which gave a sensitivity of 62% and specificity of 100% for carcinoma. Cholesterol concentration over 1.21 mmol/L cut-off value indicated neoplastic pleural involvement with 99% sensitivity and 'merely' 69% specificity, the latter mainly due to raised levels being associated also with benign inflammatory effusions. Combined CEA and cholesterol determinations increased the sensitivity for diagnosing carcinomatosis from 70% with cytology alone to 84% and established the correct diagnosis in 16 of 31 carcinomatosis cases with inconclusive cytology. Cholesterol measurement alone, with elevated level, in combination with absence of substantial number of inflammatory cells in effusion sediment proved to be a magnificent marker for neoplastic pleural involvement with 99% efficacy, and recognised all 36 such cases with inconclusive cytology.

  Conclusions: Simultaneous measurement of CEA and cholesterol concentrations in effusion, or at least cholesterol alone, in combination with non-inflammatory fluid cytology, provides additional specific information about neoplastic pleural involvement, and can therefore be used as an adjunct to cytology, above all, in inconclusive cases.

  © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

• Malignant peritoneal mesothelioma in patients with endometriosis. K.J. Butnor, J. Rueckert, E.N. Pavlisko, et al. 2018;71(11):971-974. PubMed · Publisher

  Abstract

  Aims: Florid mesothelial hyperplasia is known to result from endometriosis. Well-differentiated papillary mesothelioma and multiloculated peritoneal inclusion cysts have also been described in women with endometriosis. To our knowledge, peritoneal diffuse malignant mesothelioma (MM) arising in the setting of endometriosis has not been reported. The purpose of this study is to report the clinicopathological characteristics of women with MM and endometriosis.

  Methods: The surgical pathology files of a tertiary academic medical centre and the consultation files of one of the study authors were reviewed for cases of MM in females with and without endometriosis.

  Results: Six women with MM and endometriosis ranging in age from 29 to 55 years (median=45 years) were identified. All had peritoneal MM and endometriosis involving the peritoneum and/or adnexa. Five had epithelioid MM and one had biphasic MM. Two had paraoccupational exposure to asbestos. The median age of women with MM and endometriosis (44.5 years) was significantly less than the median age of cases without endometriosis (58.0 years) (p value=0.01).

  Conclusions: To our knowledge, this is the first report of MM in women with endometriosis. Interestingly, MM in the setting of endometriosis has only been observed in the peritoneum and not in other serosal cavities. The findings in the present study suggest that chronic serosal inflammation secondary to endometriosis may be an inducing factor in rare cases of MM of the peritoneum.

  © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

• p16. S. Serra, R. Chetty. 2018;71(10):853-858. Review PubMed · Publisher

  Abstract

  The p16 gene belongs to INK4 family of genes and is made up of four members: p16 INK4A , p15 INK4B , p18 INK4C and p19 INK4D , all of which share biological properties, namely, inhibition of cell growth and tumour suppression. After p53, p16 is the second most common tumour suppressor gene. It has been regarded as the familial melanoma gene. Immunohistochemistry for p16 has a well-defined role in distinct pathological scenarios. It is used to distinguish desmoplastic melanoma from reactive fibrous proliferation, with former showing strong nuclear positivity. In other types of melanoma, p16 protein expression is lost. Spitz nevi show retention of nuclear staining for p16. Benign mesothelial proliferations tend to retain nuclear p16 immunoreactivity, while malignant mesotheliomas lose expression. However, p16 fluorescent in-situ hybridisation analysis is recommended in the workup of malignant mesothelioma. Another common application of p16 immunohistochemistry is as an indicator for human papillomavirus (HPV) infection and p16 protein is overexpressed in HPV-associated tumours. In this context, p16 immunopositivity should be strong, diffuse, nuclear or nuclear and cytoplasmic in location. Another use for p16 is demonstration of p16 immunopositivity in well-differentiated and dedifferentiated liposarcoma.

  © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.

• Malignant peritoneal mesothelioma and Crohn disease. K.J. Butnor, E.N. Pavlisko, T.A. Sporn, et al. 2017;70(3):228-232. PubMed · Publisher

  Abstract

  Aims: Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD.

  Methods: A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD.

  Results: Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure.

  Conclusions: Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

• Myxoid variant epithelioid pleural mesothelioma defines a favourable prognosis group: an analysis of 191 patients with pleural malignant mesothelioma. F.S. Alchami, R.L. Attanoos, A.R. Bamber. 2017;70(2):179-182. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how morphological phenotype impacted upon overall survival. 191 cases of malignant pleural mesothelioma with available follow-up were identified, examined and classified according to histological types. The epithelioid mesotheliomas were further subdivided according to morphological subtypes: myxoid, microcystic, tubulopapillary, solid epithelioid, micropapillary and pleomorphic; biphasic mesotheliomas were divided into epithelioid component dominant and sarcomatoid component dominant; pure sarcomatoid mesotheliomas were divided into not otherwise specified, leiomyoid, desmoplastic and heterologous. All cases were confirmed by two experienced observers. Myxoid variant malignant pleural epithelioid mesothelioma was observed to have a favourable overall survival compared with pleomorphic form (p=0.00008). Pleomorphic phenotype had the worst overall survival. Morphological phenotype is an important histological factor that should be included in pathology reports to convey potential favourable prognostic subgroups of patients with mesothelioma.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

• An immunohistochemical comparison of two TTF-1 monoclonal antibodies in atypical squamous lesions and sarcomatoid carcinoma of the lung, and pleural malignant mesothelioma. S. Klebe, A. Swalling, L. Jonavicius, et al. 2016;69(2):136-41. PubMed · Publisher · Free full text

  Abstract

  Unlabelled: Immunohistochemical detection of thyroid transcription factor-1 (TTF-1) plays an important role in the diagnosis and subclassification of non-small cell carcinomas of the lung in biopsy and some cytology samples, specifically for identification of squamous cell carcinoma (classically negative) and non-mucinous adenocarcinoma (positive in most cases) and for discrimination between lung adenocarcinoma and pleural malignant mesothelioma (classically negative).

  Aims And Methods: We carried out a comparison of the widely used mouse monoclonal TTF-1 antibody based on the 8G7G3/1 clone versus the more recently introduced rabbit monoclonal antibody (MAb) based on the SP141 clone.

  Results: Both antibodies labelled alveolar epithelium in normal lung parenchyma, but the SP141 antibody also labelled bronchial mucosal basal cells. All 13 cases of atypical squamous lesions (including one case of bronchial squamous dysplasia) were negative with the 8G7G3/1 antibody, but 6/13 cases of squamous carcinoma/dysplasia showed positive nuclear labelling with the SP141 antibody in the same tissue biopsy. All 35 cases of adenocarcinoma of the lung were positive with both antibodies. For 12 cases of sarcomatoid carcinoma of the lung, two cases were labelled with the 8G7G3/1 antibody, whereas positive labelling of 4/12 cases was observed with SP141. All 66 cases of epithelioid malignant mesothelioma were negative with both antibodies, but 8/19 cases of sarcomatoid mesothelioma showed positive nuclear labelling with the SP141 antibody (0/19 with 8G7G3/1).

  Conclusions: Our findings indicate differences in the rates of positive and negative labelling with these two antibodies, and suggest the potential for misclassification of a proportion of squamous carcinomas of the lung as adenocarcinoma, and for misdiagnosis of some sarcomatoid mesotheliomas as sarcomatoid carcinoma of the lung. If the results of SP141 are assigned overriding significance, our findings further indicate that in isolation, neither negative labelling with either 8G7G3/1 or SP141 nor positive labelling with the SP141 MAb discriminates between sarcomatoid carcinoma and sarcomatoid mesothelioma, whereas positive labelling with the 8G7G3/1 MAb favours a diagnosis of sarcomatoid carcinoma. The literature suggests that these seemingly 'aberrant' results with the SP141 antibody are not 'false' positives, but rather real detection of low levels of TTF-1 protein in a broader range of tumours than is widely recognised.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

• Gene of the month: BAP1. A. Wang, A. Papneja, M. Hyrcza, et al. 2016;69(9):750-3. Review PubMed · Publisher

  Abstract

  The BAP1 gene (BRCA1-associated protein 1) is a tumour suppressor gene that encodes a deubiquitinating enzyme (DUB), regulating key cellular pathways, including cell cycle, cellular differentiation, transcription and DNA damage response. Germline BAP1 mutations cause a novel cancer syndrome characterised by early onset of multiple atypical Spitz tumours and increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma and various other malignancies. Recognising the clinicopathological features of specific BAP1-deficient tumours is crucial for early screening/tumour detection, with significant impact on patient outcome.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

• Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses. T. Kawai, S. Tominaga, S. Hiroi, et al. 2016;69(8):706-12. PubMed · Publisher

  Abstract

  Aims: Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging.

  Methods: To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs.

  Results: Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs.

  Conclusions: Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

• Comparison of genomic abnormality in malignant mesothelioma by the site of origin. M. Takeda, T. Kasai, Y. Enomoto, et al. 2014;67(12):1038-43. PubMed · Publisher

  Abstract

  Aims: Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes are losses in 9p21, 1p36, 22q12 and 14q32, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. We have examined various genomic losses and gains in MM and benign mesothelial proliferation by fluorescence in situ hybridisation (FISH) analysis. 9p21 deletion was reported to be less frequent in peritoneal than in pleural MMs. This study analysed various genomic losses and gains in MM by the site of origin using FISH analysis.

  Materials And Methods: We performed FISH analysis using paraffin-embedded tissues from 54 cases (40 pleural and 14 peritoneal) of MMs and compared the frequency of genomic abnormality by the site of origin.

  Results: 9p21 deletion was shown in 34 of 40 cases (85%) of pleural MMs, and was less frequent in five of 14 cases (36%) of peritoneal MMs (p<0.001) by FISH analysis. By contrast, 5p15 and 7p12 amplification was more significantly frequent in peritoneal than in pleural MMs. No difference between the two sites of MM in other genes was found.

  Conclusions: 9p21 homozygous deletion assessed by FISH has been reported to be useful for differentiating MM from reactive mesothelial proliferation, but it should be noted that 9p21 deletion was less frequent in peritoneal MM. Our study suggests that the pathway of the genetic abnormality might vary between pleural and peritoneal MM.

  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

• CD24: a potential new marker in differentiating malignant mesothelioma from pulmonary adenocarcinoma. D.J. Pinato, P. Nya, R. Sharma, et al. 2013;66(3):256-9. PubMed · Publisher

  Abstract

  Background: The differential diagnosis between malignant mesothelioma (MM) and metastatic lung adenocarcinoma (MLA) often relies on immunohistochemical studies, with no individual immunomarker holding satisfactory discrimination ability.

  Methods: We investigated the diagnostic accuracy of CD24 immunoreactivity on 134 patients including 69 cases of MM and 65 MLA.

  Results: The expression of CD24 favoured MLA, with 57/65 cases showing positive cytoplasmic staining compared with 9/69 MM (p<0.001), whose immunopositivity pattern was prevalently membranous (7/9 cases).

  Conclusions: CD24 positivity can accurately discriminate MM from MLA. Prospective studies are warranted to clarify whether CD24 could integrate with other immunomarkers to facilitate the diagnosis of mesothelial malignancies.

• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA. D.W. Henderson, G. Reid, S.C. Kao, et al. 2013;66(10):854-61. Review PubMed · Publisher

  Abstract

  Pleural malignant mesothelioma (MM) includes several unusual and even rare but distinctive histological subtypes, in addition to the usual subdivision into epithelioid, biphasic and sarcomatoid MM. Criteria for discrimination between fibrous pleuritis versus desmoplastic mesothelioma include evidence of neoplastic invasion for diagnosis of desmoplastic MM, but this histological assessment is complicated by the recently-described 'fake fat phenomenon' in cases of fibrous pleuritis. The distinction between biphasic and monophasic synovial sarcoma of the pleura versus biphasic and sarcomatoid MM can be problematical and is most cogently based upon molecular detection of the t(X;18) translocation, whereas a clear diagnosis of MM for a pleural tumour histologically resembling synovial sarcoma is favoured by a negative result for this translocation and, probably, microRNA evidence supportive of a diagnosis of MM. Aquaporin-1 (AQP1) is a molecule involved in the growth of MM cells, and yet is a factor reported to correlate with improved survival rates for MM with an epithelioid component, in comparison to AQP1-poor MM, as assessed from AQP1 expression by epithelioid MM cells only (apart from co-expression by stromal endothelial cells in addition to the tumour cells). Recent reports have also focused upon germline mutations in the BRCA1-associated protein 1 (BAP1), not only in cases of familial mesothelioma, but also BAP1 deletion in sporadic MM. Prognostic factors for MM include not only the histological subtypes, but other independent variables that include (among others), AQP1 expression by mesothelioma cells, the clinical status of the patient, the serum neutrophil:lymphocyte ratio and blood thrombocytosis.

• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers. D.W. Henderson, G. Reid, S.C. Kao, et al. 2013;66(10):847-53. Review PubMed · Publisher

  Abstract

  The detection of neoplastic invasion remains the linchpin for a clear diagnosis of malignant mesothelioma. Cytology-only diagnosis of epithelioid mesothelioma on aspirated effusion fluid remains controversial. A major problem is poor sensitivity, although cytodiagnosis is achievable in many cases at a high order of specificity, especially when a large volume of effusion fluid is submitted for cytological evaluation, enabling the preparation of cell-block sections for immunohistochemical investigation and when the cytological findings can be correlated with imaging studies to assess the anatomical distribution of the lesion and evidence of nodularity of the pleural disorder and, in some cases, to demonstrate evidence of invasion. Although 'positive' and 'negative' immunohistochemical markers have proved remarkably effective in distinguishing between epithelioid mesothelioma and secondary carcinoma and other malignant tumours metastatic to serosal membranes, no mesothelial marker has 100% sensitivity and specificity for mesothelioma diagnosis, so that panels of 'positive' antibodies and markers with negative predictive value are required. At present, no tissue or serum marker (including the molecular detection of p16/CDKN2A) has been proved to have sufficient specificity, consistency and reproducibility that it can replace evidence of invasion as the decisive marker for diagnosis when there is any uncertainty concerning a diagnosis of epithelioid mesothelioma and in the case of atypical fibrous lesions of the pleura (especially collagen-rich lesions, namely fibrous pleuritis vs desmoplastic mesothelioma), in which even the assessment of invasion can be problematical as illustrated in part 2 of this review.

• Extrapulmonary small cell carcinoma mimicking malignant pleural mesothelioma. K. Noguchi, N. Fujimoto, M. Asano, et al. 2013;66(5):450-1. Case report · Letter PubMed · Publisher

• Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma. Y. Enomoto, T. Kasai, M. Takeda, et al. 2012;65(6):522-7. PubMed · Publisher

  Abstract

  Background: Epidermal growth factor receptor (EGFR) gene mutation at the kinase domain and EGFR gene amplification are reported to be predictors of the response to EGFR tyrosine kinase inhibitors in lung cancer cases. In malignant mesothelioma (MM), the role of EGFR is less clear.

  Methods: Thirty-eight MM specimens were submitted to EGFR mutation evaluation, and compared with the results of immunohistochemical staining and fluorescence in situ hybridization (FISH) analysis. DNA was extracted from paraffin blocks and PCR was performed to amplify exon regions 18-21 of the EGFR gene. Direct sequencing of the purified PCR products was performed.

  Results: Five EGFR missense mutations were detected in six of the 38 patients (16%); two of these mutations were novel, two were originally detected in non-small cell lung carcinoma, and one resembled a location previously noted for malignant peritoneal mesothelioma.

  Conclusion: As far as the authors are aware there has been no report of the EGFR mutation of MM in Japanese cases, but in this study EGFR missense mutations were detected in some cases. EGFR mutation results were not related to immunohistochemical and FISH analysis.

• Genomic gains and losses in malignant mesothelioma demonstrated by FISH analysis of paraffin-embedded tissues. M. Takeda, T. Kasai, Y. Enomoto, et al. 2012;65(1):77-82. PubMed · Publisher

  Abstract

  Aims: Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes were losses in 9p21, 1p36, 14q32 and 22q12, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. Although the diagnostic utility of 9p21 homozygous deletion by fluorescence in situ hybridisation (FISH) analysis in MM has been reported recently, alterations of other genes have not been examined to any great extent. This study analysed the frequency of various genomic gains and losses in MM using FISH analysis.

  Materials And Methods: The authors performed a FISH analysis using paraffin-embedded tissues from 42 cases of MM.

  Results: Chromosomal losses in MM were found at 9p21 (83%), 1p36 (43%), 14q32 (43%) and 22q12 (38%), whereas gains were found at 5p15 (48%), 7p12 (38%) and 8q24 (45%). There were no cases of adenomatoid tumour, benign mesothelial multicystic tumour, reactive mesothelial hyperplasia or pleuritis showing any gains or losses. At least one genomic abnormality was identified in all cases of MM. Among various histological subtypes, the chromosomal abnormality tended to be more common in cases showing sarcomatous elements (biphasic or pure sarcomatoid) than in cases showing an epithelioid histology.

  Conclusions: The authors found various genomic gains and losses in MM by FISH analysis. The frequency of each genomic gain or loss examined in MM by FISH analysis almost agreed with the comparative genomic hybridisation technique in previous studies. This study suggests that genomic evaluation by FISH analysis might be helpful in distinguishing MM from benign mesothelial proliferation.

• Mesothelioma of the tunica vaginalis with BerEp4 and LeuM1 expression: identification of cytoplasmic tonofilaments by electron microscopy is a key diagnostic feature. D. Shelton, N. Dalal. 2012;65(10):958-9. Case report · Letter PubMed · Publisher

• The expression of Dishevelled-3 and glutamine metabolism in malignant pleural mesothelioma. T. Li, S.C. Hou, J.H. Mao, et al. 2012;65(9):855-8. Letter PubMed · Publisher · Free full text

  Summary

  This short report examined whether expression of Dishevelled-3 (Dvl3), a Wnt pathway protein, and two glutamate-handling proteins, excitatory amino acid transporter 1 (EAAT1) and glutamine synthetase (GS), were associated with each other and with survival in malignant pleural mesothelioma (MPM). The authors used clinical data from 39 patients with primary MPM between 1997 and 2009 and 38 mesothelioma tissue samples. Seven of these samples included adjacent normal pleura, and normal pleura from three further patients was on tissue microarray sections. They also studied six mesothelioma cell lines and one normal mesothelial cell line (LP9). Methods were immunohistochemistry, real-time PCR, western blot, Kaplan–Meier and log-rank analysis, and Cox regression. EAAT1 staining was positive in 97.4% (37/38) of mesothelioma samples and 50% (5/10) of normal pleura samples. GS was positive in 91.7% (33/36) and 80% (8/10), and Dvl3 in 97.0% (32/33) and 43% (3/7). EAAT1 staining was associated with survival (p=0.028), as was Dvl3 staining (p=0.001; Cox regression p=0.007). GS staining correlated with EAAT1 (p=0.002) and Dvl3 (p=0.036) staining but not with survival (p=0.353). Disease stage correlated with survival (p<0.01). EAAT1 and GS staining was positive in five mesothelioma cell lines and negative in H28 and LP9. The authors concluded that stronger EAAT1 staining went with shorter survival and that EAAT1, GS and Dvl3 need further study as possible therapeutic targets.

  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.

• Peritoneal mesothelial hyperplasia associated with gynaecological disease: a potential diagnostic pitfall that is commonly associated with endometriosis. R. Oparka, W.G. McCluggage, C.S. Herrington. 2011;64(4):313-8. PubMed · Publisher

  Abstract

  Aims: To describe the clinicopathological features of florid peritoneal mesothelial hyperplasia associated with gynaecological disease.

  Methods: Review of a series of 44 cases where there was significant peritoneal mesothelial proliferation, usually on the surface of the ovary, which resulted in diagnostic problems, often including a consideration of malignancy.

  Results: Florid mesothelial proliferation was associated with a variety of benign and malignant lesions, most commonly endometriosis. The most characteristic morphological appearance was that of small bland tubules and nests and cords of cells often embedded in fibrous tissue, sometimes with a linear arrangement. In a minority of cases, there were closely packed small glands and papillae resulting in mimicry of a serous proliferation; psammoma bodies were present in one such case. In several cases, the groups of mesothelial cells either exhibited true lymphovascular invasion or were surrounded by spaces closely simulating lymphovascular invasion. Although most cases were appreciated to represent a reactive mesothelial proliferation, several were referred with a presumed or possible diagnosis of mesothelioma, low-grade serous carcinoma, adenocarcinoma, adenomatoid tumour or Sertoli cell tumour. Positive staining with calretinin and negative staining with Ber-EP4 often helped to identify the cells as mesothelial rather than epithelial.

  Conclusions: Florid peritoneal mesothelial hyperplasia can occur in association with a variety of gynaecological disorders. Recognition of this phenomenon and appreciation that it can produce worrisome histological patterns, particularly when associated with endometriosis, is key to reaching the correct diagnosis.

• FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma. C.T. Chung, C. Santos Gda, D.M. Hwang, et al. 2010;63(7):630-4. PubMed · Publisher · Free full text

  Abstract

  Aims: To develop a fluorescence in-situ hybridisation (FISH) assay for detecting p16/CDKN2A deletion on paraffin tissue sections for use as an ancillary test to distinguish reactive from malignant mesothelial proliferations.

  Method: Dual-colour FISH for p16/CDKN2A and chromosome 9 (CEP-9) was performed on 11 benign mesothelial proliferations and 54 malignant pleural mesothelioma (MPM) cases to establish cut-off values for p16/CDKN2A deletion. A third MYC probe was used to verify cases showing homozygous deletion. Eight equivocal biopsies were used for assay testing.

  Results: Cut-off values for p16/CDKN2A deletion were calculated based on FISH signalling patterns obtained from the benign controls (mean percent nuclei plus three standard deviations). Hemizygous deletion was defined as >44% of nuclei showing the hemizygous (one p16/CDKN2A, two CEP-9 signals) or >15% of nuclei showing the monosomy (one p16/CDKN2A, one CEP-9 signal) deletion patterns. None of the benign cases showed a homozygous deletion pattern (no p16/CDKN2A, at least one CEP-9 signal). In the malignant cases, the percentage of nuclei showing homozygous deletion ranged from 1% to 87%. Therefore, the cut-off value for homozygous deletion was defined as >10%. P16/CDKN2A deletion was detected in 61% (33/54) of MPM cases. Among the equivocal biopsies, four showed homozygous and one showed hemizygous p16/CDKN2A deletion. Age over 60 years, asbestos exposure and p16/CDKN2A deletion were associated with a worse prognosis.

  Conclusion: Distinction between benign and malignant mesothelial proliferations can be diagnostically challenging. FISH for p16/CDKN2A deletion is a useful test for confirming the diagnosis of MPM.

• The role of endobronchial ultrasound guided transbronchial needle aspiration cytology in the investigation of mediastinal lymphadenopathy and masses, the North Tees experience. S. Natu, J. Hoffman, M. Siddiqui, et al. 2010;63(5):445-51. PubMed · Publisher

  Abstract

  Aim: To assess the diagnostic role of endobronchial ultrasound (EBUS) guided transbronchial fine needle aspiration (TBNA) cytology, in the investigation of mediastinal lymphadenopathy and masses, with emphasis on pathology, criteria for adequacy, and use of liquid based cytology (LBC).

  Methods: In January 2008, EBUS guided TBNA was introduced for the staging of lung cancers and for the investigation of unexplained mediastinal lymphadenopathy and masses. Initially, the material was processed conventionally. In May 2008, the laboratory procured the Cytyc T2000.

  Results: 250 specimens (229 patients) were included from January 2008 to August 2009. The overall inadequate rate was 12%; 16.6% with the conventional method, 17.2% when both conventional and LBC were used, and 9.8% with LBC. With the conventional method, an average of 7.5 slides and one cell block were received per case. With LBC, one slide and one cell block were used for diagnosis. In 72 cases (28.8%) the aspirate showed no evidence of malignancy. In 122 cases (48.8%), there was metastatic disease. In five cases (2%), a diagnosis of atypia, suspicious for non-small cell malignancy, was made. One case (0.4%) each of amyloidosis and mediastinal goitre, 3 cases (1.2%) of lymphoma, 14 cases (5.6%) of sarcoidosis and 1 case (0.4%) each of sarcoma and mesothelioma were seen.

  Conclusions: EBUS guided TBNA, in our experience, is a reliable technique for staging of lung cancers, and investigation of unexplained mediastinal lymphadenopathy and masses. LBC reduces the number of slides from 7.5 per case to 1 slide, reducing time required for diagnosis.

2000s

• Comparative genomic hybridisation in malignant deciduoid mesothelioma. A. Scattone, A. Pennella, M. Gentile, et al. 2006;59(7):764-9. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. This tumour generally has poor prognosis, and can be asbestos related.

  Aim: To identify peculiar genetic changes responsible for critical phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic relevance.

  Methods: Comparative genomic hybridisation was carried out in six cases of malignant pleural deciduoid mesothelioma, four sporadic and two familial. All cases were found to be asbestos related. Four patients died during follow-up and the mean survival was 29.5 (SD 14.2, range 12-43) months.

  Results: Genetic abnormalities were found in all the tumour tissues, the most frequent being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and 9p. Survival was found to be longer in those patients who presented a smaller number of losses (< or =2) in the tumorous chromosomes.

  Conclusions: Although numerous genetic changes are presented by deciduoid mesotheliomas, certain chromosomal regions are preferentially affected. The clinical outcome for this mesothelioma subtype is predicted by the number of losses.

• Primary pleural epithelioid haemangioendothelioma with metastases to the skin. A case report and literature review. M. Al-Shraim, B. Mahboub, P.C. Neligan, et al. 2005;58(1):107-9. Case report · Review PubMed · Publisher · Free full text

  Abstract

  Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour of intermediate behaviour. It can arise from various sites including the liver, spleen, pleura, or lung. Cutaneous EHE can be primary or secondary. This report describes the case of a 51 year old man who presented with a history of dry cough, shortness of breath, and pleural effusion, and who developed two cutaneous nodules in the anterior abdominal wall a few weeks later. He had a previous history of asbestos exposure. Computed tomography scan showed a left sided pleural effusion and nodular pleural mass. Histology of both the pleural and cutaneous lesions was compatible with EHE. Electron microscopic examination demonstrated the presence of Weibel-Palade bodies. The patient underwent elliptical excision of the metastatic cutaneous nodules after decortication of the primary pleural tumour and adjuvant treatment. A few reports have described metastasis of intrathoracic EHE to the skin. Despite treatment with interferon, the patient developed more cutaneous lesions two years after the initial diagnosis. Even though the tumour has the classic light histological and ultrastructural features of EHE, it behaved in an aggressive manner.

• HPV infections and lung cancer. K.J. Syrjänen. 2002;55(12):885-91. Review PubMed · Publisher · Free full text

  Abstract

  Because of the major clinical impact of bronchial cancer worldwide, the possibility that human papillomavirus (HPV) contributes to its pathogenesis as a co-carcinogen is an intriguing one. Bronchial squamous cell carcinoma develops through well defined precursor lesions, often at the sites of squamous metaplasia. Benign squamous cell papillomas are rare but HPV DNA has been found in almost half of those studied, implicating a causal association. In invasive bronchial cancer, morphological changes seen in HPV lesions elsewhere are often seen. HPV DNA has been detected in 21.7% of the 2,468 bronchial carcinomas analysed to date and the same high risk types implicated in other squamous cell cancers have been identified. Clearly, more effort should be focused on assessing the role of HPV in bronchial carcinogenesis, by analysing the synergistic effects of carcinogenic agents (cigarette smoke, radiation, asbestos, etc) and HPV in different experimental settings.

• Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. A.S. Abutaily, B.J. Addis, W.R. Roche. 2002;55(9):662-8. PubMed · Publisher · Free full text

  Abstract

  Aim: The value of immunohistochemical staining in differentiating between malignant mesothelioma and pulmonary adenocarcinoma was re-examined using newly available commercial antibodies, with the aim of increasing the sensitivity and specificity of diagnosis, and simplifying the antibody panel required.

  Methods: Forty one malignant mesotheliomas and 35 lung adenocarcinomas were studied. Commercial antibodies to calretinin, E-cadherin, N-cadherin, surfactant apoprotein A (SP-A), thyroid transcription factor 1 (TTF-1), thrombomodulin, and cytokeratin 5/6 were applied using the streptavidin-biotin-peroxidase complex procedure on formalin fixed, paraffin wax embedded tissue.

  Results: E-cadherin was expressed in all adenocarcinomas and in 22% of the mesotheliomas. TTF-1 expression was detected in 69% of the adenocarcinomas and none of the mesotheliomas. Positive staining with polyclonal anticalretinin was detected in 80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed in 6% of the adenocarcinomas and in 53% of the mesotheliomas. Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and 63% of the mesotheliomas. The results were compared with the standard laboratory panel for mesothelioma diagnosis: anticarcinoembryonic antigen (anti-CEA), LeuM1, BerEP4, and HBME-1.

  Conclusion: Of the antibodies used in this study, E-cadherin was 100% sensitive for pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary adenocarcinoma. The application of these two antibodies alone was adequate for the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TTF-1 is negative and E-cadherin is positive, a secondary panel of antibodies, including BerEP4 and LeuM1 (CD15) and antibodies directed against CEA, calretinin, cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation between malignant mesothelioma and pulmonary adenocarcinoma.

• Florid cystic endosalpingiosis of the uterus. M.K. Heatley, P. Russell. 2001;54(5):399-400. Case report PubMed · Publisher · Free full text

  Abstract

  A 73 year old woman presented with a right sided adnexal cystic mass. At laparotomy, this proved to be a benign serous ovarian cyst and an aggregation of thin walled subserosal and soft tissue cysts and spongy nodules up to 16 mm in diameter involving the side wall of the uterus and adjacent parametrium. These were removed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histologically, the cystic spaces and smaller acini were lined by benign tubo-endometrioid epithelium, with smaller areas typical of serous differentiation and rare microfoci of endocervical-type mucinous epithelium. These features indicated multidirectional Mullerian differentiation in a process that, overall, was consistent with so called florid cystic endosalpingiosis. This lesion is to be distinguished from other benign conditions including multicystic mesothelioma, endometriosis, endocervicosis, florid deep glands of the uterine cervix, and deep Nabothian cysts of the uterine cervix.

1990s

• Malignant mesothelioma eight years after a diagnosis of atypical mesothelial hyperplasia. J. Scurry, M.A. Duggan. 1999;52(7):535-7. Case report PubMed · Publisher · Free full text

  Abstract

  The separation of mesothelial hyperplasia from early malignant mesothelioma remains one of the most difficult problems in histopathology. Inconclusive cases are termed "atypical mesothelial hyperplasia" and treated expectantly. A 49 year old male pipeline engineer was diagnosed as having atypical mesothelial hyperplasia in appendiceal serosa by the US-Canadian Mesothelioma Panel. Eight years later, he developed overtly malignant peritoneal and pleural mesothelioma. In hindsight, histological similarities between the diffuse malignant mesothelioma and the atypical mesothelial proliferation suggested malignancy from the outset. The most important of these features were the degree of mesothelial proliferation, micronodularity, architectural complexity, superficial invasion, uniform mild cytological atypia, and the absence of a clinical cause for a benign mesothelial proliferation. Ancillary investigations including immunohistochemistry were of no benefit in determining whether the atypical mesothelial hyperplasia was benign or malignant. Careful histological examination remains the mainstay of the diagnosis of early mesothelioma.

• Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas. F.G. Mayall, G. Jacobson, R. Wilkins. 1999;52(4):291-3. PubMed · Publisher · Free full text

  Abstract

  Aim: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure.

  Methods: Paraffin sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraffin sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic differential mineral fibre counts were performed on dried lung tissue at a specialist referral centre.

  Results: The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The difference in frequency of SV40 detection was significant at the p < 0.05 level.

  Conclusions: Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further.

• HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of pleura. A.D. Kennedy, G. King, K.M. Kerr. 1997;50(10):859-62. PubMed · Publisher · Free full text

  Abstract

  Aims: To determine the usefulness of antibodies HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of the pleura.

  Methods: Using microwave antigen retrieval and streptavidin-biotin complex horseradish peroxidase immunohistochemistry the above antibodies were used to stain sections of 57 malignant mesotheliomas, 17 reactive pleural hyperplasias, 23 cases of carcinoma metastatic in pleura, 20 primary ovarian cell carcinomas, and 20 primary renal cell carcinomas.

  Results: Eighty six per cent of mesotheliomas and 82% of reactive mesothelial hyperplasias stained strongly with HBME-1. However, 48% of carcinomas metastatic to pleura also stained, as did all serous ovarian carcinomas. Seventy two per cent of mesotheliomas and 24% of reactive mesothelial hyperplasias stained strongly with the antithrombomodulin antibody; 86% and 88%, respectively, of these cases showed staining of any type. While 26% of metastatic carcinomas showed some staining with antithrombomodulin, only one third of these (9%) showed strong, yet focal, staining. Of 40 ovarian and renal carcinomas only two (5%) showed any staining with antithrombomodulin.

  Conclusions: HBME-1, although a sensitive mesothelial marker, is not sufficiently specific to be useful diagnostically, as almost half of carcinomas metastatic to pleura also stained positive. Antithrombomodulin is also a sensitive mesothelial marker and is sufficiently specific to be a useful discriminator, positively identifying, in appropriate circumstances, the mesothelial nature of a cell population.

• Malignant mesothelioma of the pleura: interobserver variability. A. Andrion, C. Magnani, P.G. Betta, et al. 1995;48(9):856-60. PubMed · Publisher · Free full text

  Abstract

  Aims: To assess the consistency of histopathological diagnosis of pleural malignant mesothelioma by estimating interobserver agreement between five pathologists.

  Methods: Eighty eight histological sets pertaining to original diagnoses of pleural malignant mesothelioma were reviewed separately by each pathologist. Diagnostic likelihood was graded as definite (A), probable (B), possible (C), improbable (D), and definitely not (E) malignant mesothelioma. The following indexes were estimated: observed proportion of agreement (Po), kappa statistics and proportion of agreement for "positive" (Ppos) and "negative" (Pneg) diagnoses.

  Results: Sixty cases (68.2%) were rated by at least three reviewers as A or B and by none of the others as D or E. Five (5.7%) were rated by at least two reviewers as D or E and by none of the others as A or B. Nine (10.2%) showed a serious disagreement, rated A or B and D or E. Agreement for sets obtained at necropsy/surgery (median kappa w = 0.57) was similar to that for endoscopic material (median kappa w = 0.54). Agreement was poor on material obtained by needle biopsy (median kappa w = 0.21). The median value of Ppos varied between 0.94 (necropsy/surgery) and 0.67 (needle biopsy) and that of Pneg between 0.78 (necropsy/surgery) and 0.34 (unspecified biopsy). Interobserver agreement on histological typing was good overall (median kappa = 0.59).

  Conclusions: Of the original histological diagnoses, 70% were consistently reproduced through panel review. Most indexes of agreement between pathologists ranged from poor (needle biopsy) to moderate (necropsy/surgery). Agreement in confirming malignant mesothelioma was greater than that regarding exclusion of this diagnosis. Of the cases finally considered to have malignant mesothelioma, the reproducibility of histological typing was relatively satisfactory.

• Desmoplastic malignant mesothelioma: a review of 17 cases. G.E. Wilson, P.S. Hasleton, A.K. Chatterjee. 1992;45(4):295-8. PubMed · Publisher · Free full text

  Abstract

  Aims: To identify the histological features of desmoplastic mesothelioma, and to determine its incidence and prognosis.

  Methods: Two hundred and fifty five cases of malignant mesothelioma were examined over seven years (1982-9) to identify the desmoplastic variant. Sections were cut at 5 microns and stained with haemotoxylin and eosin and with CAM 5.2 (Dakopatts). Asbestos fibre counts were carried out by light microscopy in 14 cases using the potash digestion method.

  Results: Seventeen cases were identified as desmoplastic mesothelioma giving an incidence of 6.6%. In 11 cases the cell type in more cellular areas was sarcomatous and in six others it was biphasic. The mean survival time from onset of symptoms to death was 5.8 months for the sarcomatous variant and 6.8 months for the biphasic variant. Twelve of 16 patients had had previous occupational exposure to asbestos, ranging from five months to 43 years. The diagnosis of desmoplastic mesothelioma was only accepted if acellular connective tissue comprised 50% or more of the tumour bulk. Also seen was collagen necrosis, anastomosing bands of often hyalinised collagen with a prominent storiform pattern, and where cellular detail was present there were hyperchromatic nuclei.

  Conclusions: Desmoplastic mesothelioma is a rare variant of malignant mesothelioma with a storiform collagen pattern, collagen necrosis, bland acellular collagen and focal cytological features of malignancy. Though rare, it is important to recognise this variant and distinguish it from a pleural plaque, nonspecific reactive pleural fibrosis, pleurisy, rheumatoid disease, or, rarely, spindle cell sarcomas.

• Well differentiated (benign) papillary mesothelioma of the tunica vaginalis. R. Chetty. 1992;45(11):1029-30. Case report PubMed · Publisher · Free full text

  Abstract

  An unusual mesothelial lesion occurred in the tunica vaginalis of the testis. It conformed histologically and immunohistochemically to well differentiated papillary mesothelioma of the peritoneum. Its aetiology remains uncertain, but this lesion, more than likely, is innocuous. It is important to recognise this entity, which is not well documented in the tunica vaginalis, because it may be misdiagnosed as a malignant mesothelioma and the patient may be subjected to unnecessary treatment.

1980s

• Lectin binding properties of cells from serous effusion and peritoneal washing specimens. P.W. Shield. 1989;42(11):1178-83. PubMed · Publisher · Free full text

  Abstract

  The diagnostic value of staining cells from serous effusion and peritoneal washing specimens with a panel of four lectins was investigated and the results compared with those achieved with polyclonal anti-carcinoembryonic antigen (anti-CEA) sera. Cell blocks from 42 pleural effusions, 25 peritoneal effusions, and 14 peritoneal washing specimens were stained with Con A (D-mannosyl, D-glucosyl), WGA (n-acetyl glucosamine), UEA-1 (L-fucose), SBA (n-acetyl galactosamine) and anti-CEA. Con A and WGA were not useful in discriminating mesothelial cells from adenocarcinomas. In contrast, UEA-1 and SBA binding was present in 30 of 46 (65%) and in 31 of 46 (67%), respectively, of adenocarcinomas tested, but negative in 21 cases with reactive mesothelial cells, 10 cases with benign mesothelial cells, and one case of mesothelioma. All mesothelial cells were also negative for CEA, but 24 of 46 (52%) of adenocarcinomas were positive. All three cases of lymphoma were negative with UEA-1, SBA, and anti-CEA. UEA-1 and SBA lectins identified a higher proportion of metastatic adenocarcinomas than CEA and stained most cases of adenocarcinomas metastatic from sites which usually fail to express CEA. Combination of staining results for UEA-1, SBA, and anti-CEA produced a test with high sensitivity and specificity, identifying 40 of 46 (87%) of adenocarcinomas tested, with no false positive results. It is concluded that UEA-1 and SBA staining of effusion specimens warrants further study, and may provide a useful adjunct to CEA staining.

• Detection of asbestos fibres by dark ground microscopy. K.R. James, T.B. Bull, B. Fox. 1987;40(10):1259-60. PubMed · Publisher · Free full text

• Immunocytological staining reactions of anti-carcinoembryonic antigen, Ca, and anti-human milk fat globule monoclonal antibodies on benign and malignant exfoliated mesothelial cells. A.K. Ghosh, E.B. Butler. 1987;40(12):1424-7. PubMed · Publisher · Free full text

  Abstract

  A panel of three monoclonal antibodies were used in an immunoalkaline phosphatase staining method on a series of serous effusion samples from cases of mesothelioma, lung carcinoma, and benign disease. The antibodies used were anti-carcinoembryonic (CEA) antigen, Ca, and anti-human milk fat globule membrane antigen. Antibodies to the Ca antigen and human milk fat globule membrane antigen stained 75% and 83% of mesothelioma and 75% of cases of lung carcinoma, respectively. The anti-CEA antibody stained most cases of lung carcinoma strongly but was negative on 11 of 12 cases of mesothelioma and showed weak staining on one case. Benign cases were negative with all three antibodies. These three antibodies may be useful in distinguishing benign and malignant mesothelial cells and lung carcinoma in serous effusions.

• Immunohistological staining of reactive mesothelium, mesothelioma, and lung carcinoma with a panel of monoclonal antibodies. A.K. Ghosh, K.C. Gatter, M.S. Dunnill, et al. 1987;40(1):19-25. PubMed · Publisher · Free full text

  Abstract

  A panel of seven monoclonal antiepithelial antibodies of different specificities, including anticytokeratin, human milk fat globule membrane, C, and carcinoembryonic antigen (CEA) were used with the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique to determine their value in the differentiation between benign and malignant mesothelial cells and lung carcinoma in histological preparations. The anticytokeratin antibody reacted strongly with all cases of reactive mesothelium, mesothelioma, and lung carcinoma. Antibodies to human milk fat globule membrane and the Ca antigen stained mesothelioma and carcinoma and 43% of cases of reactive mesothelium. Staining for carcinoembryonic antigen was not detected in reactive mesothelium or mesothelioma, but was present in most of the lung carcinomas. CEA seemed to be the single most useful marker in distinguishing carcinoma from mesothelioma in that a positive reaction for CEA would indicate carcinoma rather than mesothelioma.

• Microwave polymerisation of epoxy resin: rapid processing technique in ultrastructural pathology. A.L. McLay, J.D. Anderson, W. McMeekin. 1987;40(3):350-2. PubMed · Publisher · Free full text

  Summary

  The authors tested whether microwave irradiation could polymerise epoxy resin when preparing tissue for electron microscopy. With conventional ovens this step needs at least half an hour. The work was done at the University Department of Pathology, Glasgow Royal Infirmary. Tissue fixed in 4% phosphate buffered glutaraldehyde went through a standard four and a half hour pre-polymerisation schedule and was embedded in EMIX resin in EMcap capsules. Control blocks were polymerised overnight (16 hours) in a 70°C oven. Test blocks were polymerised in a 400W Sharp microwave oven (Model R4060). Two primary tissue samples, fixed for more than 24 hours, were used. One fresh sample also received 60 seconds of microwave-assisted fixation. The microwave field was uneven, with a strong central zone. One minute or more in the centre caused almost explosive polymerisation and distorted the capsules. Consistent results came from capsules placed in a row at the front of the oven, given seven 15 second and two 30 second pulses separated by 30 second cooling intervals. Microwave and conventionally polymerised blocks from the same specimen, a secondary deposit of malignant mesothelioma, showed no noticeable difference in quality or cutting. Blocks more than 2mm across polymerised slightly unevenly. A lymphoma sample given both microwave fixation and polymerisation was of very acceptable quality. The authors concluded that microwave polymerisation is practicable, although its general usefulness remained to be established.

  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.

• Production of reactive oxygen metabolites induced by asbestos fibres in human polymorphonuclear leucocytes. M. Hedenborg, M. Klockars. 1987;40(10):1189-93. PubMed · Publisher · Free full text

  Abstract

  The ability of quartz and various asbestos fibres to induce the production of reactive oxygen metabolites in human polymorphonuclear leucocytes was assessed. A chemiluminescence assay showed that the activation of polymorphonuclear leucocytes was induced in the following order of effect: quartz; chrysotile A; crocidolite; chrysotile B; amosite; and anthophyllite. Only slight chemiluminescence was produced by cells exposed to wollastonites and titanium dioxide. A positive correlation was seen between production of chemiluminescence and red cell haemolysis. Our results suggest that the potential of various environmental particles and mineral fibres to induce inflammation, fibrosis, and cancer of the lung could be related to their ability to induce inflammatory cells to produce reactive oxygen metabolites.

• Use of antimesothelial cell antibody and computer assisted quantitative analysis for distinguishing between reactive and neoplastic serosal tissues. A. Donna, P.G. Betta, F. Robutti. 1987;40(12):1428-31. PubMed · Publisher · Free full text

  Abstract

  Nine malignant mesotheliomas and 12 specimens of benign reactive mesothelial hyperplasia were examined using a specific antimesothelial cell antibody. Immunostaining intensity was subsequently estimated by means of image analysis. The mean and standard deviation of integrated optical density in the malignant mesotheliomas differed significantly from those in the mesothelial hyperplasias. In all mesotheliomas but one the integrated optical density was greater than in reactive mesothelial hyperplasia. No significant difference in optical density was observed between the two groups; the standard deviation was significantly higher in the reactive lesions. This technique may be adopted to complement the traditional morphological assessment of primary lesions of the serosal cavities.

• Comparison of the results of asbestos fibre dust counts in lung tissue obtained by analytical electron microscopy and light microscopy. F.D. Pooley, D.L. Ranson. 1986;39(3):313-7. PubMed · Publisher · Free full text

  Abstract

  The efficiency of the light microscope with that of the electron microscope in detecting asbestos fibres in human lung tissue was computed. Necropsy material from 55 patients who had died from asbestos related diseases was analysed independently by phase contrast microscopy and electron microscopy. As expected the number of fibres identified using electron microscopy was higher than that identified by light microscopy. By adjusting the electron allow for the limited resolving power of the light microscope, however, a significant correlation of the number of fibres identified using the two methods was obtained. The best correlation was found with specimens containing crocidolite (correlation coefficient 0.79) and amosite (correlation coefficient 0.74), while chrysotile gave a much lower correlation (correlation coefficient 0.15). The cumulated fibre diameter distribution obtained using the electron microscope suggests that the light microscope is able to visualise only 5% of crocidolite, 26.5% of amosite, and 0.14% of chrysotile present in lung tissue. Therefore, although it is possible, using the electron microscope, to predict the asbestos fibre count that would be obtained by light microscopy, the reserve prediction cannot be made: it is impossible to determine the proportion of the various asbestos mineral types using the light microscope.

• Diagnosing tumours on routine surgical sections by immunohistochemistry: use of cytokeratin, common leucocyte, and other markers. R.N. Poston, Y.S. Sidhu. 1986;39(5):514-23. PubMed · Publisher · Free full text

  Abstract

  Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours.

• New marker for mesothelioma: an immunoperoxidase study. A. Donna, P.G. Betta, D. Bellingeri, et al. 1986;39(9):961-8. PubMed · Publisher · Free full text

  Abstract

  An antibody was raised against a protein isolated from the cytoplasm of mesothelioma cells. It was subsequently used in an immunoperoxidase procedure on formalin fixed, paraffin embedded tissue sections. A representative sample of benign and malignant tumours from all the systems of the human body was examined. All the tumours derived from coelomic surfaces (mesotheliomas of pleura, peritoneum, and ovary, and adenomatoid tumour of epididymis) reacted with the antibody. No other tumour tested in this study expressed the protein. These findings indicate that the antibody may be useful in the identification of mesothelioma cells in both histological and cytological diagnostic routine practice when morphological interpretation is in doubt.

• Peritoneal cystic mesothelioma: an electron microscopic and immunohistochemical study of two male patients. I.K. Sienkowski, A.J. Russell, S.A. Dilly, et al. 1986;39(4):440-5. Case report PubMed · Publisher · Free full text

  Abstract

  The clinical, pathological, and ultrastructural features of two cases of peritoneal cystic mesothelioma occurring in men were studied. The results of immunohistochemical staining for CAM 5.2, epithelial membrane antigen, carcinoembryonic antigen, and Factor VIII related antigen are reported for the first time and compared with the staining results of two peritoneal cystic lymphangiomas. Although resembling cystic lymphangioma by light microscopy, cystic mesothelioma may have a greater tendency for local recurrence. Staining for CAM 5.2 or epithelial membrane antigen may facilitate the differentiation of these two entities.

• Primary mesothelioma of atrioventricular node: cause of sudden death. E.H. Hemsted. 1986;39(8):926. Case report · Letter PubMed · Publisher · Free full text

• Use of antibodies to carcinoembryonic antigen and human milk fat globule to distinguish carcinoma, mesothelioma, and reactive mesothelium. R.J. Marshall, A. Herbert, S.G. Braye, et al. 1984;37(11):1215-21. PubMed · Publisher · Free full text

  Abstract

  Antibodies raised against human milk fat globule (HMFG 1 and 2) and carcinoembryonic antigen were used in an immunoperoxidase technique to differentiate mesothelioma, carcinoma, and benign, reactive mesothelium. Sixteen mesotheliomas, 27 lung carcinomas, and 13 specimens of reactive mesothelium were examined. Staining for carcinoembryonic antigen was not seen in reactive mesothelium or mesothelioma but was present in 22 of 27 carcinomas. Mesothelioma and carcinoma usually stained with HMFG 1 and 2; reactive mesothelium did not. These three antibodies may help to distinguish carcinoma, mesothelioma, and reactive mesothelium.

• Use of antisera to epithelial membrane antigen for the cytodiagnosis of malignancy in serous effusions. A. To, D.V. Coleman, D.P. Dearnaley, et al. 1981;34(12):1326-32. PubMed · Publisher · Free full text

  Abstract

  A new human antigen, designated epithelial membrane antigen (EMA), has recently been described on surface membranes of a wide variety of normal epithelium but not on connective tissue cells. The antigen is only weakly expressed on normal or reactive mesothelium. Increased expression of the antigen has been observed in most neoplasms of epithelial origin and in malignant mesothelioma. We have investigated the possibility of using this difference in the expression of the antigen to distinguish between mesothelial cells and malignant cells in cytological smears of serous effusions. This distinction cannot always be made on morphological grounds alone and problems of differential diagnosis are encountered in about 15% of all specimens of serous effusions sent for cytological examination. Using antisera to EMA we have applied an indirect immunoalkaline phosphatase technique to alcohol-fixed smears prepared from serous effusions and have found that intense staining of the antigen is confined to effusions from patients in whom there is either clinical or cytological evidence of malignancy. The technique proved to be especially useful in cytologically equivocal cases, where there were problems of differential diagnosis.

1970s

• Epidemiological and quantitative relationships between mesothelioma and asbestos on Tyneside. T. Ashcroft. 1973;26(11):832-40. PubMed · Publisher · Free full text

  Abstract

  Thirty-five necropsied cases of diffuse malignant mesothelioma of pleura and six cases of mesothelioma of peritoneum are reported. Occupational histories from 40 cases showed that 32 cases (80%) were definitely exposed to asbestos; six cases (15%) were probably exposed and two (5%) had no known exposure. The mean latent interval was 34 years. Occupational histories of 56 control patients matched in pairs for age and sex with 28 of the mesothelioma cases revealed definite exposure to asbestos in 12 controls (21%), probable exposure in 11 (20%), and no evidence of exposure in 33 (59%). The difference in incidence of exposure between mesotheliomas and controls is statistically highly significant. Six-micron histological sections of lung, available in 39 mesothelioma cases, contained coated asbestos fibres in 36 cases (92%). Sixteen cases of mesothelioma showing fibres were free of asbestosis; asbestosis was slight in 14 cases, moderately severe in five cases, and severe in one case. The incidence of asbestos bodies in sections from mesothelioma cases was significantly higher than in a previously reported series of routine necropsies examined by lung smear. Counts of coated and uncoated asbestos fibres were performed on samples of lung tissue from 33 mesothelioma cases. No fibres were identified in one case and only occasional coated fibres in a second case. The remainder gave counts ranging from 154 thousand to 684 million fibres per gram dry weight. Uncoated fibres were invariably present and usually comprised 50 to 80% of the count. No relationship was found between total fibre count and the latent period of the mesothelioma. Fibre counts were also performed on lung samples from 18 smear-positive and 30 smear-negative routine necropsies. Cases with numerous coated fibres in the smear gave total fibre counts similar to those of mesothelioma cases without asbestosis. Routine cases with only one fibre in the smear usually yielded only occasional fibres on analysis. Coated and uncoated fibres were found in 13 out of 30 smear-negative cases, indicating a true incidence of 56% of exposure to asbestos in the whole necropsy series. When compared with the mesothelioma series the difference in incidence of fibres remains statistically significant. The data suggest that, on Tyneside, exposure to asbestos sufficient to cause an appreciable risk of developing mesothelioma has usually occurred through occupational exposure rather than by general environmental pollution by asbestos.

• The optical and electron microscopic determination of pulmonary asbestos fibre concentration and its relation to the human pathological reaction. T. Ashcroft, A.G. Heppleston. 1973;26(3):224-34. PubMed · Publisher · Free full text

  Abstract

  The quantitative extraction of asbestos fibres from asbestotic lung by alkali digestion has been refined by maceration of the tissue without prior drying, the minimum use of centrifugation, and the adoption of phase contrast microscopy. Preliminary experiments suggested that, using this technique, asbestos fibre counts were accurate to within at least +/- 20% and in most instances to within +/- 10%. The method was used to assess asbestos concentrations in lung tissue showing various degrees and forms of fibrosis. The results, as determined by light microscopy, indicated that uncoated fibres generally outnumbered coated fibres. In mild and moderate asbestosis there was a progressive increase in concentration of asbestos fibres, both coated and uncoated, with increasing severity of fibrosis, whereas in severe asbestosis no correlation existed between the fibre concentration and the form or the extent of the pathological reaction. It is suggested that the severe fibrosis results from the supervention of non-specific inflammatory processes. Asbestos fibre diameter distributions, gauged by electron microscopy, were fairly constant irrespective of the degree of fibrosis. Optically visible fibres constituted between 12 and 30% of the total, so that an optical count may be said to give an approximate indication of the total asbestos concentration and, so far as asbestosis is concerned, may well serve for comparative purposes. The relation between asbestos and neoplasia will, however, require identification and quantitation of particular types of the mineral by microanalytical techniques.

• Exfoliative cytology of diffuse mesothelioma. G.H. Roberts, G.M. Campbell. 1972;25(7):577-82. PubMed · Publisher · Free full text

  Abstract

  The exfoliative cytology of 14 diffuse mesothelioma (11 pleural and three peritoneal) is described. Malignant cells were identified in 10 patients; in eight malignant cells still retaining the characteristics of mesothelial cells were found. It is suggested that only if malignant cells of this type are recognized should the probable diagnosis of diffuse mesothelioma be made.

• Significance of asbestos in lung tissue. J.C. Wagner. 1972;25(6):557. PubMed · Publisher · Free full text

• Asbestos in tumours. C. Gold. 1971;24(5):481. PubMed · Publisher · Free full text

• The pathology of parietal pleural plaques. G.H. Roberts. 1971;24(4):348-53. PubMed · Publisher · Free full text

  Abstract

  The incidence, morbid anatomy, histology, and relationship of hyaline pleural plaques to exposure to asbestos has been studied. Plaques were found in 12.3% of 334 hospital necropsies (in an urban population in Glasgow, 41 cases). In 85.3% (35 cases) asbestos bodies were found in the lungs. There is evidence of a dose-response relationship between the number of asbestos bodies found in the lungs and the presence of pleural plaques. The selective distribution of plaques within the pleural cavities suggests that mechanical factors play a part in their localization. Histological examination contributed little to understanding the mechanism of plaque formation; that asbestos bodies have been detected in only a few cases suggest that their presence in the parietal pleura is not essential to plaque formation. The suggested mechanisms of plaque formation are discussed.

• Identification of mineral particles in pneumoconiotic lungs. W.J. Henderson, J. Gough, J. Harse. 1970;23(2):104-9. PubMed · Publisher · Free full text

  Abstract

  An extraction replication technique has been used for the study, by electron microscopy, of lung tissue from a number of different cases of pneumoconiosis. The technique provides a relatively simple means of studying the surface area of replicated tissues, and any foreign particles present which are either replicated or extracted from the tissue can be identified. A set of standard micrographs of different types of mineral particles likely to be encountered should be kept for reference. Most of the particles identified by this technique were beyond the limits of resolution of optical microscopy. Furthermore, the procedure involves the minimum of chemical and physical treatment. The histochemical diagnosis and industrial history was confirmed in the first two cases described, by the electron microscopy investigations. The third case presented an uncertain histological and industrial history, but an electron microscopy study confirmed the presence of the mineral particle considered responsible for the clinical condition. The fourth and fifth cases described illustrate the use of this technique in identifying a particular type of pleomorphic mineral, and illustrating its position in situ in relation to surrounding tissue.

• Mesonephroid tumours of the ovary. M.C. Anderson, F.A. Langley. 1970;23(3):210-8. PubMed · Publisher · Free full text

  Abstract

  Thirty cases of mesonephroid tumour of the ovary were studied. The differential diagnosis is discussed and it is concluded that mesonephroid tumours form a distinct entity. An attempt is made to correlate the histological appearance of the tumours with the clinical course and criteria are suggested which might be a guide to prognosis. Views on histogenesis are discussed but at present there seems insufficient evidence to justify any particular hypothesis.

1960s

• Asbestos levels in human lungs. C. Gold. 1969;22(4):507. PubMed · Publisher · Free full text

• Asbestos bodies in lungs at necropsy. G.H. Roberts. 1967;20(4):570-3. PubMed · Publisher · Free full text

  Abstract

  This study was made in Glasgow, Scotland, near an industrial area where ship building is an important industry. Asbestos bodies were found in 23% of 100 consecutive hospital necropsies, bodies were present in 37% of the 62 males, none were found in 38 females. These findings are compared with results of other similar surveys. In 85.4% of cases showing asbestos bodies, hyaline pleural plaques were found. There was one case of asbestosis and three of bronchial carcinoma in the cases showing asbestos bodies.

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