Histopathology

About the journal

Publisher: Blackwell Scientific Publications
Published: 1977 to the present, England
Language: English
ISSN: 0309-0167 (print), 1365-2559 (electronic)
Its record in the NLM Catalog

2020s

BRCA1-associated-protein-1 inactivated melanocytic tumours: characterisation of the clinicopathological spectrum and immunohistochemical expression pattern of preferentially expressed antigen in melanoma. Y. Xu, A.A. Gru, T. Brenn, et al. 2025;86(2):294-301. PubMed · Publisher · Free full text

Abstract

Aims: BRCA1-associaed protein-1 (BAP1) inactivated tumours (BIMT) are rare melanocytic tumours that may be mistaken for Spitz tumours or melanoma. They occur sporadically or in association with the BAP1 tumour predisposition syndrome (BAP1-TPDS), which may be complicated by uveal or cutaneous melanoma, mesothelioma, basal cell carcinoma and renal cell carcinoma. The aim of this study was to characterise the clinicopathological features and the immunohistochemical expression pattern of preferentially expressed antigen in melanoma (PRAME) of BIMT in a large patient cohort.

Methods And Results: Ethical approval was obtained, haematoxylin and eosin-stained slides were reviewed, PRAME immunohistochemistry was performed and clinical follow-up was obtained from patient records. Sixty-five BIMT from 38 patients (F:M = 4.4:1) were identified. BIMT were typically located on the trunk and head and neck (median size = 0.5 cm). Seven patients with BAP1-TPDS (range = 16-66 years, median = 25) had multiple BIMT (median = 5), while sporadic BIMT were solitary (median patient age = 39 years). One of seven patients with BAP1-TPDS developed additional malignancies (mesothelioma and cutaneous spindle cell melanoma) and died of complications of mesothelioma. All other patients are alive without recurrence of BIMT (median follow-up = 42 months). BIMT presented as intradermal, nodular aggregates of epithelioid melanocytes with low mitotic activity and moderate to severe cytological atypia in 63% of cases. A background conventional naevus was present in 64%. PRAME immunohistochemistry showed negative or weakly patchy positive staining in all BIMT.

Conclusions: BIMT are more common in a sporadic setting and behave indolently, despite worrying cytological atypia. PRAME immunohistochemistry is a reassuring tool in distinguishing BIMT from melanoma.

© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.
Giant cell interstitial pneumonia: case series with comprehensive ultrastructural analyses of "not only" hard metal pneumoconiosis. F. Fortarezza, M. Perilli, M. Della Barbera, et al. 2025;86(3):450-459. Case report PubMed · Publisher

Abstract

Aims: Giant cell interstitial pneumonia (GIP) is a fibrosing lung disease histologically characterized by centrilobular pulmonary fibrosis and cannibalistic intra-alveolar multinucleated giant cells. It is considered a form of pneumoconiosis caused particularly by secondary exposure to hard metals (cemented carbide or tungsten carbide). Hard metals are commonly used in various industrial applications, such as cutting tools, drilling tools, machine inserts, and other wear-resistant components. However, cases with unknown exposure that recurred in transplanted lungs have been described. This has led to the hypothesis of a complex etiopathogenesis, likely multifactorial, involving the coparticipation of immune mechanisms. We aimed to identify all the elements present in a series of GIP lung samples to better understand the pathogenic mechanisms of the disease.

Methods And Results: We describe five cases of histologically diagnosed GIP in patients with occupational exposure to metallic dust using ultrastructural characterization to identify metal dust and to quantify asbestos fibres. We found that tungsten was present in three cases, albeit in trace amounts in two of them. Numerous elements were identified in all samples, including asbestos fibres in patients with endstage pulmonary fibrosis. Furthermore, in one of the described cases the recurrence of the disease was also observed in transplanted lungs.

Conclusion: These findings support the hypothesis that GIP may be due to elements other than hard metals, with asbestos possibly representing a contributory factor in the expression of a more severe fibrotic disease. The recurrence of GIP observed in transplanted organs strengthens the hypothesis of the existence of a not yet fully understood etiopathogenic immune mechanism.

© 2024 John Wiley & Sons Ltd.
Loss of MTAP expression is not an accurate surrogate for CDKN2A homozygous deletions in peritoneal mesothelioma. A. Quaranta, A. Marzullo, F. Fortarezza, et al. 2025;87(4):526-535. PubMed · Publisher · Free full text

Abstract

Aims: Mesothelioma is a malignant neoplasm of the serosal membranes originating from mesothelial cells. Peritoneal mesothelioma is the second most common mesothelial neoplasm after pleural mesothelioma, accounting for approximately 6%-15% of cases. Due to its high morphological variability, often mimicking other lesions, mesothelioma remains a diagnostic challenge. CDKN2A homozygous deletion has been established as a highly accurate biomarker for differentiating mesothelioma from benign mesothelial proliferations. MTAP immunohistochemistry (IHC) has been proposed as a cheaper and more reproducible surrogate for CDKN2A homozygous deletion (HD) detected by FISH in pleural mesothelioma. The aim of our study was to evaluate the reliability of MTAP IHC as a surrogate marker for CDKN2A HD in peritoneal mesothelioma.

Methods And Results: Thirty-nine FFPE tissue samples of PeM were analysed for CDKN2A copy number status by FISH. MTAP IHC was performed using antibody clone 2G4, and cytoplasmic positivity was evaluated using two different cut-offs (1% and 30%). Agreement between IHC and FISH was assessed using Cohen's Kappa. A ROC curve analysis was performed to evaluate the overall diagnostic performance of MTAP IHC. McNemar's test was used to identify statistically significant discordance between the techniques, and a power analysis was conducted to confirm the adequacy of the sample size. Additionally, 14 benign peritoneal lesions were included as external controls and underwent both FISH and IHC. All control samples showed preserved MTAP expression and no CDKN2A deletion. CDKN2A HD was detected in 27/39 cases. MTAP loss was observed in 13 cases, while the remaining 26 cases showed variable levels of MTAP positivity (15%-100%; mean: 36.4%; median: 25%). Cohen's Kappa revealed a low, non-significant concordance between MTAP IHC and CDKN2A HD (cut-off 1%: Kappa = 0.091, P = 0.462; cut-off 30%: Kappa = 0.083, P = 0.326). ROC curve analysis (AUC = 0.569) confirmed the poor discriminatory performance of MTAP IHC. McNemar's test showed a statistically significant discordance between MTAP IHC and CDKN2A FISH results. Power analysis confirmed that the sample size (n = 39) was adequate.

Conclusions: These findings may reflect biological and pathogenetic differences between pleural and peritoneal mesotheliomas. Larger, multicentric studies are needed to validate the diagnostic role of MTAP IHC in peritoneal mesothelioma.

© 2025 The Author(s). Histopathology published by John Wiley & Sons Ltd.
Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR). S. Klebe, M. Judge, L. Brcic, et al. 2024;84(4):633-645. Review PubMed · Publisher

Abstract

Aims: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers.

Methods And Results: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading.

Conclusion: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).

© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.
STK11 (LKB1) immunohistochemistry is a sensitive and specific marker for STK11 adnexal tumours. A. Dehghani, A.E. Sharma, S.E. Siegmund, et al. 2024;85(5):769-782. PubMed · Publisher · Free full text

Abstract

Aims: STK11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz-Jeghers syndrome. [Correction added on 3 October 2024, after first online publication: 'ST11' in preceding sentence has been corrected to 'STK11' in this version.] It predominantly originates from the para-adnexal soft tissues and often shows secondary involvement of the fallopian tube and ovary. STK11 adnexal tumours have a broad differential diagnosis due to their variable morphology and non-specific immunoprofile, and diagnostic confirmation currently requires sequencing to identify an STK11 mutation. We investigate the diagnostic utility of STK11 (LKB1) immunohistochemistry (IHC) in a cohort of STK11 adnexal tumours and morphological mimics.

Methods And Results: IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (10 female adnexal tumours of Wolffian origin, 22 adult granulosa cell tumours, 10 juvenile granulosa cell tumours, four Sertoli-Leydig cell tumours, two Leydig cell tumours, one Sertoli cell tumour, one steroid cell tumour, four extra-ovarian sex cord-stromal tumours, 16 ovarian endometrioid carcinomas, eight tubo-ovarian high-grade serous carcinomas, five ovarian mesonephric-like adenocarcinomas, 14 ovarian carcinosarcomas, five peritoneal malignant mesotheliomas, two pelvic plexiform leiomyomata and one ovarian solid pseudopapillary tumour). All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11. All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high-grade serous carcinoma with subclonal loss.

Conclusions: STK11 is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from its histological mimics, and can obviate the need for confirmatory molecular studies in the appropriate morphological context.

© 2024 John Wiley & Sons Ltd.
High mesothelin expression by immunohistochemistry predicts improved survival in pleural mesothelioma. G.J. Chu, A. Linton, S. Kao, et al. 2023;83(2):202-210. PubMed · Publisher · Free full text

Abstract

Aims: Mesothelin (MSLN) is a cancer-associated antigen that is overexpressed in malignancies such as mesothelioma, pancreatic and ovarian cancer. It is also a target for novel personalised therapies, including antibodies, antibody-drug conjugates and chimeric antigen receptor T cells. Immunohistochemistry may predict those who would best respond to anti-mesothelin therapies and guide decisions in therapeutic strategy. This study aimed to assess the intensity and distribution of MSLN immunostaining in mesothelioma, and to determine the prognostic value of MSLN expression by histochemical-score (H-score).

Methods And Results: The MN1 anti-MSLN antibody was used to stain a formalin-fixed paraffin-embedded tissue microarray of histologically confirmed mesothelioma from 75 consecutive patients who had undergone pleurectomy with or without decortication. MSLN positivity, the staining intensity, distribution of staining and H-score were evaluated. The correlation of H-score with prognosis was investigated. Sixty-six per cent of epithelioid tumours were MSLN-positive (with expression in > 5% tumour cells). Of MSLN-expressing epithelioid tumours, 70.4% had moderate (2+) or strong (3+) intensity MSLN immunostaining, although only 37% of samples had staining in ≥ 50% of tumour cells. In multivariate analysis, MSLN H-score as a continuous variable and an H-score ≥ 33 were independent predictors of improved survival (P = 0.04 and P < 0.001, respectively).

Conclusions: MSLN expression was more heterogenous in epithelioid mesothelioma than reported previously. Therefore, it would be appropriate to perform an immunohistochemical assessment of MSLN expression to stratify and assess patient suitability for mesothelin-targeted personalised therapies, such as chimeric antigen receptor T cells.

© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.
Correlation of methylthioadenosine phosphorylase (MTAP) protein expression with MTAP and CDKN2A copy number in malignant pleural mesothelioma. D.B. Chapel, A.M. Dubuc, J.L. Hornick, et al. 2021;78(7):1032-1042. PubMed · Publisher

Abstract

Aims: Methylthioadenosine phosphorylase (MTAP) immunohistochemical expression is a specific marker of CDKN2A deletion in malignant mesothelioma. However, the relationship of MTAP expression with MTAP copy number remains unexplored.

Methods And Results: Forty malignant pleural mesotheliomas were characterised by targeted next-generation sequencing (29), single-nucleotide polymorphism microarray (seven), or both (four). MTAP and CDKN2A copy numbers were correlated with MTAP expression. Twenty-seven (68%) tumours showed CDKN2A deletion (14 heterozygous; 13 homozygous), of which 20 (74%) showed MTAP codeletion (15 heterozygous; five homozygous). No tumours showed MTAP deletion without CDKN2A codeletion. Loss of MTAP expression was seen in 16 (40%) tumours, and was 75% sensitive and 95% specific for MTAP deletion, and 59% sensitive and 100% specific for CDKN2A deletion. Nine of 40 (23%) tumours showed heterogeneous MTAP staining, and the percentage of tumour cells with MTAP loss correlated with molecular detection of MTAP deletion.

Conclusions: MTAP is frequently codeleted with CDKN2A in pleural mesothelioma. However, homozygous deletion of both genes occurs in a minority of tumours (5/40; 13%); CDKN2A deletion often co-occurs with heterozygous MTAP deletion or neutral MTAP copy number; and MTAP expression correlates inconsistently with heterozygous MTAP deletion. Correspondingly, MTAP immunohistochemistry is a highly specific but only moderately sensitive assay for CDKN2A deletion.

© 2021 John Wiley & Sons Ltd.
L1CAM expression in cystic mesothelial lesions: a comparison with adenomatoid tumours, well-differentiated papillary mesothelial tumours and malignant mesotheliomas. G. Karpathiou, F. Casteillo, M. Dridi, et al. 2021;79(2):272-274. Letter PubMed · Publisher

Summary

This letter reported a study of whether L1 cell adhesion molecule (L1CAM) is expressed in cystic mesothelial lesions. Earlier studies had found TRAF7 mutations and L1CAM expression in adenomatoid tumours (ATs) and well-differentiated papillary mesothelial tumours (WDPMTs). The authors, from pathology departments in Saint-Etienne, France, and Ioannina, Greece, retrospectively studied 57 consecutive cystic mesothelial lesions. These were solitary (38) or multiple (19), and peritoneal (47) or pericardial (10). For comparison they included 18 ATs, 7 WDPMTs and 24 pleural epithelioid malignant mesotheliomas (MMs). Immunohistochemistry for L1CAM (clone UJ127.11) was performed on whole tissue sections, and staining was recorded by intensity and extent. None of the cystic mesothelial lesions expressed L1CAM. L1CAM expression was found in 13 of 18 ATs (72.2%), focal in 6, and in 3 of 7 WDPMTs (42.8%), with mild and focal staining. None of the MMs expressed L1CAM. The authors concluded that the absence of L1CAM probably suggests a different etiopathogenetic model for cystic mesothelial lesions than for ATs and WDPMTs. They also concluded that L1CAM may not be universally expressed by ATs and WDPMTs and should be interpreted with caution if used for diagnosis. With this clone, positivity would favour AT/WDPMT over MM or cystic lesions. However, they noted that this clone shows the lowest positivity of L1CAM antibodies and that other clones are expressed by MMs.

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.

In plain English

This was a short research letter by pathologists at university hospitals in Saint-Etienne, France, and Ioannina, Greece. They looked back at tissue from 57 consecutive cystic mesothelial lesions, which are fluid-filled lesions of the lining of body cavities. Of these, 47 were in the peritoneum (abdominal lining) and 10 in the pericardium (lining around the heart). They stained the tissue for a protein called L1CAM. For comparison, they also stained 18 adenomatoid tumours and 7 well-differentiated papillary mesothelial tumours, both benign, and 24 malignant mesotheliomas, all pleural and epithelioid. None of the 57 cystic lesions and none of the 24 malignant mesotheliomas showed L1CAM. The protein was found in 13 of the 18 adenomatoid tumours (focal in 6) and in 3 of the 7 papillary tumours (mild and focal). The authors concluded that L1CAM is not found in cystic mesothelial lesions, which probably suggests these lesions arise differently from the two benign tumours. They also said L1CAM staining should be interpreted with caution when used for diagnosis, partly because the antibody they used detects L1CAM least often of the available antibodies. The article does not discuss asbestos exposure.

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.
Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesothelioma. A. Bilecz, P. Stockhammer, D. Theegarten, et al. 2020;77(1):55-66. PubMed · Publisher

Abstract

Aims: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study.

Methods And Results: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours.

Conclusions: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.

© 2020 The Authors. Histopathology published by John Wiley & Sons Ltd.
Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade. Y.Z. Zhang, C. Brambilla, P.L. Molyneaux, et al. 2020;77(3):423-436. PubMed · Publisher

Abstract

Aims: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (i) externally validate the prognostic role of pleomorphic features in E-MPM and (ii) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication.

Methods And Results: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared to those without (5.4 versus 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 versus 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous.

Conclusions: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.

© 2020 The Authors. Histopathology published by John Wiley & Sons Ltd.

2010s

Expression analysis of HMGB1 in histological samples of malignant pleural mesothelioma. E. Rrapaj, E. Trisolini, L. Bertero, et al. 2018;72(6):1039-1050. PubMed · Publisher

Abstract

Aims: High mobility group box 1 (HMGB1) is a chromatin structural protein, expressed ubiquitously in the nuclei of mammalian cells. When transported extracellularly, it acts as a tumour suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of HMGB1 have been related to a poor prognosis. Conversely, the significance of HMGB1 expression in MPM tissues is still unclear.

Methods And Results: Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semiquantitative system that sums the intensity (0-3) and the percentage (from 0 to 4) of positively stained cells in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated using the ΔΔCt method. High expression levels of HMGB1 as total (P = 0.0011) and cytoplasmic score (P = 0.0462) were related to a worse disease-specific survival (DSS) in the entire cohort and in the clinicopathological subgroups. No significant correlation was found between HMGB1 gene expression and DSS.

Conclusions: These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma.

© 2018 John Wiley & Sons Ltd.
Grade 4 asbestosis does not extend directly from the respiratory bronchiole to the peripheral lung. Y. Kawabata, T. Kasai, Y. Kobashi, et al. 2018;73(1):29-37. PubMed · Publisher

Abstract

Aims: To confirm whether or not grade 4 asbestosis progresses from the respiratory bronchiole to the peripheral lung.

Methods And Results: We examined retrospectively the autopsy or lobectomy specimens from 31 cases (29 males; mean age 64 years) satisfying the pathological criteria of grade 4 asbestosis. Asbestos bodies (ABs) were quantified in samples of dissolved lung and in tissue preparations on glass slides. Respiratory bronchiolar lesions were graded as 0, 1 and ≥2. Grade 4 asbestosis was subdivided into an atelectatic induration (AI) and usual interstitial pneumonia pattern (UIP pattern). Five, 10, and 16 cases had grades 0, 1 or ≥2 lesions, respectively, with mean respective numbers of ABs in dissolved lung of 117 000/g dry lung, 468 000/g and 968 000/g; and in specimens on glass slides of seven ABs/cm2 of tissue slice, 34 ABs /cm2 and 195 ABs /cm2 . The differences were significant. Fifteen and 16 cases showed AI and UIP patterns, respectively, with mean respective numbers of ABs in dissolved lung of 1 006 000/g dry lung and 354 000/g, and 186 and 56 ABs/cm2 on glass slides. The differences were significant. AI patterns originated in subpleural lobules or subpleural zonal areas and UIP patterns originated in subpleural, peripheral lobules.

Conclusions: Grade 4 asbestosis does not start in the respiratory bronchiole. The presence of a grade 1 lesion is not required for the diagnosis of grade 4 asbestosis.

© 2018 John Wiley & Sons Ltd.
Malignant mesothelioma in situ. A. Churg, H. Hwang, L. Tan, et al. 2018;72(6):1033-1038. Case report PubMed · Publisher

Abstract

Aims: The existence of malignant mesothelioma in situ (MIS) is often postulated, but there are no accepted morphological criteria for making such a diagnosis.

Methods And Results: Here we report two cases that appear to be true MIS on the basis of in-situ genomic analysis. In one case the patient had repeated unexplained pleural unilateral effusions. Two thoracoscopies 9 months apart revealed only visually normal pleura. Biopsies from both thoracoscopies showed only a single layer of mildly reactive mesothelial cells. However, these cells had lost BRCA1-associated protein 1 (BAP1) and showed loss of cyclin-dependent kinase inhibitor 2 (CDKN2A) (p16) by fluorescence in-situ hybridisation (FISH). NF2 was not deleted by FISH but 28% of the mesothelial cells showed hyperploidy. Six months after the second biopsy the patient has persisting effusions but no evidence of pleural malignancy on imaging. The second patient presented with ascites and minimal omental thickening on imaging, but no visual evidence of tumour at laparoscopy. Omental biopsy showed a single layer of minimally atypical mesothelial cells with rare tiny foci of superficial invasion of fat. BAP1 immunostain showed loss of nuclear BAP1 in all the surface mesothelial cells and the invasive cells. There was CDKN2A deletion, but no deletion of NF2 by FISH.

Conclusions: These cases show that morphologically bland single-layered surface mesothelial proliferations with molecular alterations seen previously only in invasive malignant mesotheliomas exist, and presumably represent malignant MIS. More cases are need to understand the frequency of such changes and the time-course over which invasive tumour develops.

© 2018 John Wiley & Sons Ltd.
Malignant mesothelioma with squamous differentiation. H. Tanaka, Y. Akiyama, A. Kitamura, et al. 2018;72(7):1216-1220. Case report PubMed · Publisher

Abstract

Aims: We report the autopsy findings of a 58-year-old man with malignant mesothelioma in the left pleural cavity.

Methods And Results: The patient had a history of asbestos exposure, and the chest computed tomography scan on initial admission demonstrated an extrapleural sign, suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, he died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumour lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumour was composed of a mixture of mesothelioma and tumour cells with squamous differentiation mimicking squamous cell carcinoma.

Conclusions: To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English-language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.

© 2018 John Wiley & Sons Ltd.
The epithelioid BAP1-negative and p16-positive phenotype predicts prolonged survival in pleural mesothelioma. A. Chou, C.W. Toon, A. Clarkson, et al. 2018;72(3):509-515. PubMed · Publisher

Abstract

Aims: Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within 1 year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help to guide treatment. We therefore sought to investigate the role of p16 immunohistochemistry (IHC) both alone and in combination with other markers as a potential predictor of prolonged survival in mesothelioma.

Methods And Results: P16 IHC was performed on unselected pleural mesotheliomas biopsied from 1991 to 2014; 153 of 208 (74%) cases were p16-negative, which correlated significantly with poor overall survival in both univariate (median survival 7.6 versus 13.6 months; P = 0.001) and multivariate analysis [hazard ratio (HR): 1.632; 95% confidence interval (CI): 1.103-2.415; P = 0.014]. Other independent factors associated with prolonged survival included loss of expression of BAP1 and epithelioid morphology. We therefore stratified patients further based on these three independent prognostic variables and demonstrated an unusually prolonged survival in mesotheliomas which were epithelioid, BAP1 IHC negative and p16 IHC positive (12% of cases, median survival 31.7 months, P < 0.0001).

Conclusions: In conclusion, p16 IHC is an independent prognostic biomarker in pleural mesothelioma. When used in combination with BAP1 IHC and morphological subtyping, patients with exceptionally prolonged survival can potentially be identified.

© 2017 John Wiley & Sons Ltd.
Diagnostic application of BAP1 immunohistochemistry to differentiate pleural mesothelioma from metastatic pleural tumours. M. Yoshimura, Y. Kinoshita, M. Hamasaki, et al. 2017;71(6):1011-1014. Letter PubMed · Publisher

Summary

This letter reported a study of whether loss of BRCA-associated protein 1 (BAP1), detected by immunohistochemistry, could distinguish malignant pleural mesothelioma (MPM) from tumours that had spread to the pleura from elsewhere. The authors, from Fukuoka University and Kyushu University in Japan, first reviewed tumours that had metastasised to the pleura at their university hospital from 2000 to 2015. The most common primary tumours were lung carcinoma (9 cases), breast carcinoma (4) and signet ring cell carcinoma (3). They then stained 318 cases of MPM and of 10 tumour types that can metastasise to the pleura for BAP1. Staining could be assessed in 299 cases. BAP1 loss was found in 23 of 41 MPM cases (56%): 19 of 29 epithelioid cases (66%) and 2 of 6 cases each of biphasic and sarcomatoid MPM (33%). Among the other tumours, BAP1 loss occurred only in clear cell renal cell carcinoma (5 of 23, 22%). For separating MPM from metastatic tumours, BAP1 loss had a sensitivity of 56.1% and a specificity of 98.1%. Nineteen cases (6%) were excluded because of absent or faint staining of internal control cells or unclear staining of tumour cells. The authors concluded that, when properly assessed, BAP1 loss distinguishes MPM from most metastatic pleural tumours. They noted that clear cell renal cell carcinoma, intrahepatic cholangiocarcinoma and some melanocytic tumours can also show BAP1 loss.

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.
Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma. A. Shinozaki-Ushiku, T. Ushiku, S. Morita, et al. 2017;70(5):722-733. PubMed · Publisher

Abstract

Aims: Malignant mesothelioma is a highly aggressive cancer that is usually diagnosed at advanced stages; thus, highly sensitive and specific markers are necessary for its early definitive diagnosis. The aim of this study was to evaluate the diagnostic utility and prognostic significance of BAP1 and EZH2 in malignant mesothelioma.

Methods And Results: The expression of BAP1 and EZH2 was investigated by immunohistochemistry in 32 malignant mesotheliomas and 44 benign mesothelial proliferative lesions, including well-differentiated papillary mesothelioma (n = 4), mesothelial inclusion cyst (n = 22), and reactive mesothelial hyperplasia (n = 18). BAP1 loss and high EZH2 expression were observed in 17 (53%) and 22 (66%) malignant mesothelioma cases, respectively, whereas none of the benign lesions showed BAP1 loss or high EZH2 expression. The combination of BAP1 loss and high EZH2 expression as markers to differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions was highly sensitive (90%) and specific (100%). There were no statistically significant associations between parameters such as age and sex of patients, tumour location, asbestos exposure, treatment, histology, and BAP1 or EZH2 expression. Survival analysis revealed that BAP1 loss, but not high EZH2 expression, was associated with a better prognosis.

Conclusions: BAP1 loss and high EZH2 expression were highly specific to malignant mesothelioma in differentiating it from benign mesothelial proliferations, and the combination of these two markers improved the diagnostic accuracy.

© 2016 John Wiley & Sons Ltd.
Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma. K. Kushitani, V.J. Amatya, Y. Okada, et al. 2017;70(3):375-384. PubMed · Publisher

Abstract

Aims: The aims of this study were to clarify the usefulness of immunohistochemistry in the differential diagnosis of epithelioid mesothelioma with a solid growth pattern [solid epithelioid mesothelioma (SEM)] and poorly differentiated squamous cell carcinoma (PDSCC), and to confirm the validity of a specific type of antibody panel. Additionally, we aimed to clarify the pitfalls of immunohistochemical analyses.

Methods And Results: Formalin-fixed paraffin-embedded specimens from 36 cases of SEM and 38 cases of PDSCC were immunohistochemically examined for calretinin, podoplanin (D2-40), Wilms' tumour gene product (WT1), cytokeratin (CK) 5/6, p40, p63, carcinoembryonic antigen (CEA), epithelial-related antigen (MOC31), claudin-4, thyroid transcription factor-1 (TTF-1), and napsin A. WT1 showed the highest diagnostic accuracy (85.1%) as a mesothelial marker, and CEA, p40 and claudin-4 showed higher diagnostic accuracies (95.9%, 94.6%, and 93.2%, respectively) as carcinoma markers. Calretinin (diagnostic accuracy: 75.7%), D2-40 (diagnostic accuracy: 67.6%), CK5/6 (diagnostic accuracy: 63.5%), TTF-1 (diagnostic accuracy: 55.4%) and napsin A (diagnostic accuracy: 52.7%) could not differentiate between SEM and PDSCC. Among these markers, the combination of calretinin and WT1 showed the highest diagnostic accuracy (86.5%) as a positive marker, and the combination of p40 and CEA showed the highest diagnostic accuracy (97.3%) as a negative marker. The combination of CEA and claudin-4 also showed relatively high diagnostic accuracy (94.6%) as a negative marker.

Conclusions: We recommend the combination of WT1 and calretinin as a positive maker, and the combination of CEA and claudin-4 as a negative marker, for differential diagnoses of SEM and PDSCC.

© 2016 John Wiley & Sons Ltd.
Anaplastic lymphoma kinase (ALK) translocation in paediatric malignant peritoneal mesothelioma: a case report of novel ALK-related tumour spectrum. K. Loharamtaweethong, N. Puripat, N. Aoonjai, et al. 2016;68(4):603-7. Case report PubMed · Publisher

Abstract

Aims: To report a case of paediatric malignant peritoneal mesothelioma (MPM) with evidence of anaplastic lymphoma kinase (ALK) translocation.

Methods And Results: We describe a 10-year-old girl who presented with abdominal pain and progressive abdominal distension. She had no history of asbestos exposure. Histopathological, immunohistochemical and ultrastructural analyses were performed and showed a biphasic malignant mesothelioma. In addition, we also studied on a selected set of immunomarkers which may be the potential therapeutic molecular targets including ALK, c-kit (CD117), epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2)/neu, as well as corresponding molecular analysis. Consequently, we identified ALK expression by immunohistochemistry, together with evidence of ALK translocation by fluorescent in-situ hybridization (FISH) analysis.

Conclusions: Paediatric MPM is associated with ALK translocation in our case. The results may open up a new avenue for the study of molecular genesis of paediatric malignant mesothelioma in the future and help to determine whether patients MMs with ALK translocation would benefit from ALK inhibitor treatment.

© 2015 John Wiley & Sons Ltd.
Asbestos exposure increases the incidence of histologically confirmed usual interstitial pneumonia. Y. Kawabata, Y. Shimizu, E. Hoshi, et al. 2016;68(3):339-46. PubMed · Publisher

Abstract

Aims: We hypothesized that asbestos exposure increases the incidence of macroscopically visible and histologically confirmed usual interstitial pneumonia (histological UIP).

Methods And Results: We retrospectively examined 1718 cases (1202 males; mean age 66.7 years) who underwent lobectomy for resection of pleuropulmonary tumours. Objective markers for asbestos exposure included: the presence of malignant pleural mesothelioma, the presence of pleural plaques (PPs) and asbestos bodies in the histological specimen. Risk factors for histological UIP were examined. Two separate groups were studied: 183 with asbestos exposure, and 239 with histological UIP. The 183 cases with asbestos exposure had higher rates of positive occupational history and histological UIP (31%) than the remaining 1535. Among the asbestos-exposed group, small numbers of asbestos bodies were found in histological specimens of 21 cases of histological UIP. PPs and asbestos bodies were more frequent in the 239 patients with histological UIP than in the remaining 1479 UIP-negative patients. Multivariate analysis showed that asbestos exposure, especially positivity for asbestos bodies, that does not meet the current criteria for asbestosis increases the risk of histological UIP (P < 0.0001).

Conclusions: Asbestos exposure causes asbestosis and increases the incidence of histological UIP.

© 2015 John Wiley & Sons Ltd.
Prognostic significance of morphological growth patterns and mitotic index of epithelioid malignant peritoneal mesothelioma. A.M. Krasinskas, A.C. Borczuk, D.J. Hartman, et al. 2016;68(5):729-37. PubMed · Publisher

Abstract

Aims: The prognostic significance of histological subtyping of epithelioid pleural mesotheliomas has been recently reported, but similar data are lacking for peritoneal mesotheliomas. The aim of this study was to investigate possible relationships between histological growth patterns of epithelioid peritoneal mesotheliomas, clinicopathological features, and patient outcome.

Methods And Results: Eighty-four cases of chemotherapy-naive epithelioid peritoneal mesothelioma were classified into tubulopapillary, micropapillary, papillary, tubular, solid and trabecular growth patterns. Pathological features such as depth of invasion, lymphocytic host response, mitotic count, nuclear grade, lymphovascular invasion, lymph node metastasis and stromal desmoplasia were analysed. The most common histological patterns were solid (n = 37, 44%), tubulopapillary (n = 24, 29%), and micropapillary (n = 11, 13%). The overall median survival was 36 months. Patients with solid mesothelioma had shorter overall survival (median, 29 months) than patients with tubulopapillary and micropapillary growth patterns (median, 51 and 53 months, respectively; P = 0.053). A high mitotic index (>5 in 50 high-power fields) was found to be associated with poor survival (P < 0.03). A moderate to severe lymphocytic host response was associated with longer median survival (P = 0.13).

Conclusions: Our study highlights the prognostic importance of the solid growth pattern among diffuse epithelioid peritoneal mesotheliomas, and reaffirms mitotic index as a predictor of overall survival.

© 2015 John Wiley & Sons Ltd.
Solid cell nests of the thyroid gland: morphological, immunohistochemical and genetic features. M. Manzoni, G. Roversi, C. Di Bella, et al. 2016;68(6):866-74. PubMed · Publisher

Abstract

Aims: The correct identification of solid cell nests (SCNs) is an important issue in thyroid pathology because of the spectrum of differential diagnoses of this type of lesion.

Methods And Results: Ten cases of 295 consecutive thyroidectomies showed the presence of SCNs at histological examination. The identification of the exact SCN type required the distinction of the cystic and solid pattern; SCNs were usually composed of a mixture of main cells (MCs) and C-cells (CCs). The immunohistochemical calcitonin stain identified CCs easily, both inside SCNs and dispersed in islets at the periphery. For the characterization of MCs, we added the utility of p40 to p63. The use of thyroid transcription factor-1 (TTF-1) helped in their identification, as MCs did not react with this marker; the combination of TTF-1 and p40 or p63 IHC stains was useful for the characterization of cystic SCNs of both types 3 and 4. The negativity of mouse monoclonal mesothelioma antibody (HMBE-1) and a very low proliferative index (MIB-1) supported the diagnosis. [Correction added on 23 November 2015, after online publication: MIB-1 was incorrectly defined, the expanded form was deleted.] We discourage the use of galectin-3 (Gal-3) and cytokeratin-19 (CK-19), as they have an important overlap with papillary thyroid carcinoma. The complete absence of any B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations is an additional fundamental finding.

Conclusions: We reviewed the most relevant morphological and immunohistochemical features of SCNs and have provided a genetic analysis of the BRAF gene because of its expanding use in thyroid pathology.

© 2015 John Wiley & Sons Ltd.
Usual interstitial pneumonia in asbestos-exposed cohorts - concurrent idiopathic pulmonary fibrosis or atypical asbestosis?. R.L. Attanoos, F.S. Alchami, F.D. Pooley, et al. 2016;69(3):492-8. PubMed · Publisher

Abstract

Aims: To determine whether usual interstitial pneumonia (UIP) pattern fibrosis is seen in asbestosis.

Methods And Results: The occurrence of UIP pattern fibrosis was studied in four asbestos cohorts systematically referred following postmortem to the UK Pneumoconiosis Unit, Cardiff. The combined exposed workforce comprised >25 000 persons. Over the 17-year period, 233 subjects were identified; 210 had degrees of interstitial fibrosis with a fibrotic non-specific interstitial pneumonia pattern and subpleural accentuation, and three showed UIP pattern fibrosis. All three of these cases showed grade 4 fibrosis (honeycombing) with no asbestos fibre dose-response correlation. A Poisson distribution of probability analysis indicated that the observed cases of UIP in this workforce could be wholly accounted for by the prevalence of idiopathic pulmonary fibrosis (IPF) in the population.

Conclusions: UIP pattern fibrosis is rarely observed in asbestos-exposed subjects, and shows no dose-response correlation with asbestos fibres on mineral analysis; this points to an alternative disease, such as IPF. The results indicate that UIP pattern fibrosis should not be regarded as genuine asbestosis, irrespective of the status of asbestos biomarkers, and this impacts upon the postmortem handling of asbestos-related deaths.

© 2016 John Wiley & Sons Ltd.
Pseudomesotheliomatous small-cell neuroendocrine carcinoma of the lung with calretinin expression. G.D. Exarchos, R.L. Attanoos. 2015;66(6):895-6. Case report · Letter PubMed · Publisher
The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review. C. Fisher. 2014;64(1):134-50. Review PubMed · Publisher

Abstract

Many soft tissue sarcomas have chromosomal translocations with resultant formation of new fusion genes. Among the genes that can be rearranged, the EWSR1 gene has been identified as a partner in a wide variety of clinically and pathologically diverse sarcomas as well as some non-mesenchymal tumours. The former include Ewing sarcoma and similar (Ewing-like) small round cell sarcomas, desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue and clear cell sarcoma-like tumours of the gastrointestinal tract, primary pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic examples of low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma and mesothelioma. EWSR1 is a 'promiscuous' gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours. EWSR1 can, conversely, partner with the same genes in morphologically and behaviourally different neoplasms. This paper reviews the diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene.

© 2013 John Wiley & Sons Ltd.
Utility of PAX8 mouse monoclonal antibody in the diagnosis of thyroid, thymic, pleural and lung tumours: a comparison with polyclonal PAX8 antibody. A. Toriyama, T. Mori, S. Sekine, et al. 2014;65(4):465-72. PubMed · Publisher

Abstract

Aims: The purpose of this study was to compare the immunohistochemical staining profiles of PAX8-polyclonal, PAX8-monoclonal, PAX5-monoclonal and PAX6-monoclonal antibodies in several histological types of primary thoracic and thyroid tumours. In addition, we analysed PAX8 mRNA expression by using in-situ hybridization.

Methods And Results: We compared polyclonal PAX8 and monoclonal PAX8, PAX5 and PAX6 antibodies in 962 samples (687 lung carcinomas, 40 malignant pleural mesotheliomas, 138 thymic tumours and 97 thyroid tumours) using the tissue microarray technique. Among thyroid tumours, the monoclonal and polyclonal PAX8 antibodies showed a high positive rate (98.0%). Of 167 polyclonal PAX8 antibody-positive tumours, except for thyroid tumours, 54 cases tested positive for PAX5 and/or PAX6 (31 lung carcinomas and 23 thymic tumours). No PAX8 mRNA expression was detected using RNAscope (in-situ hybridization technique) other than in thyroid tumours. A portion of polyclonal PAX8 antibody-positive tumours showed cross-reactivity for PAX5 or PAX6 protein.

Conclusions: Monoclonal PAX8 antibody showed high specificity to thyroid tumours and was superior to the polyclonal antibody.

© 2014 John Wiley & Sons Ltd.
Well-differentiated papillary mesothelioma: a clinicopathological and immunohistochemical study of 18 cases with additional observation. X. Chen, W. Sheng, J. Wang. 2013;62(5):805-13. PubMed · Publisher

Abstract

Aims: To present our experience with 18 cases of well-differentiated papillary mesothelioma (WDPM), with an emphasis on its relationship to adenomatoid tumour and multicystic mesothelioma.

Methods And Results: Eighteen cases of WDPM were retrieved. Twenty cases of multicystic mesothelioma were selected for comparative study. The WDPM patients comprised 14 females and four males, with age ranging from 18 to 60 years (median 37 years). The tumour involved the abdominal or pelvic peritoneum (14 cases), the pleura (two cases), and the testicular tunica vaginalis (two cases). The majority of WDPMs were incidental findings during surgery for a wide variety of conditions. Histologically, 13 cases were consistent with classical WDPM. Two cases had a combined component of adenomatoid tumour, and three cases contained coexisting areas of multicystic mesothelioma. Among the multicystic mesothelioma cases, four had adenomatoid tumour-like foci present in the stroma. Immunohistochemically, all cases of WDPM and multicystic mesothelioma, as well as the coexisting combined components, were positive for mesothelial markers, with a low Ki67 index. This study also showed that WDPM was negative for epithelial membrane antigen and desmin.

Conclusions: The simultaneous occurrence of WDPM, adenomatoid tumour and multicystic mesothelioma in some cases suggested histogenetic relationships among these three less aggressive mesotheliomas.

© 2012 Blackwell Publishing Ltd.
Diffuse pleural mesothelioma with epithelioid and angiosarcomatous components--a hitherto undescribed pattern of differentiation. A. Klabatsa, A.G. Nicholson, K. Dulay, et al. 2012;60(7):1164-6. Case report · Letter PubMed · Publisher

Summary

This letter described a case of diffuse pleural mesothelioma with a pattern of differentiation that the authors stated had not previously been published. The patient was an 82-year-old man with occupational exposure to asbestos who presented with left-sided chest pain and breathlessness of gradual onset over several weeks. CT showed a large left pleural effusion, a collapsed left lung, thickened pleura in the left basal region and pleural plaques. He had never received thoracic irradiation and was anaemic, requiring blood transfusion. Video-assisted thoracoscopy found a 900 ml haemorrhagic effusion with clots of blood, and pleural biopsies were taken before talc pleurodesis. Microscopy showed two components. The larger was an infiltrative tumour of malignant epithelioid and spindle-shaped cells that stained positive for calretinin, WT1 and CK5/6 and negative for CD31, CD34, factor VIIIrAg and TTF-1. A lesser, superficial component of irregular vascular channels lined by atypical endothelial cells stained positive for factor VIIIrAg, CD34 and CD31 and negative for pancytokeratin and mesothelial markers. In areas the two components blended. The tumour was classified as epithelioid mesothelioma with angiosarcomatous de-differentiation. Two separate co-located tumours were considered less likely. The authors concluded that positive vascular marker staining should no longer exclude mesothelioma, and that angiosarcomatous de-differentiation should be added to the recognised variations of pleural mesothelioma.

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.
High level of Ets-related gene expression has high specificity for prostate cancer: a tissue microarray study of 11 483 cancers. S. Minner, A.M. Luebke, M. Kluth, et al. 2012;61(3):445-53. PubMed · Publisher

Abstract

Aims: TMPRSS2-ERG fusion resulting in strong Ets-related gene (ERG) overexpression occurs in about 50% of prostate cancers. This study was undertaken to determine the prevalence of ERG overexpression in other tumour types as well as in normal tissues.

Methods And Results: A total of 11 483 tumours and 72 different normal tissue types were analysed in a tissue microarray format. Strong nuclear ERG overexpression was found in 36.7% of prostate carcinomas as well as in various vascular tumours, including Kaposi sarcomas (91.7%), angiosarcomas (100%) and haemangiomas (90.9%). Moderate to strong nuclear ERG immunostaining was also observed in thymoma (6.1%). Weak to moderate ERG staining was found in a small number of squamous cell carcinomas of the skin, squamous carcinomas of the lung, malignant mesotheliomas, carcinosarcomas of the uterus, gastrointestinal stromal tumours, hepatocellular carcinomas, teratomas of the testis, anaplastic carcinomas of the thyroid, giant cell tumours of the tendon sheath and benign fibrous histiocytomas of the skin. ERG overexpression was not seen in 8886 samples from 132 other tumour types and subtypes. Within normal tissues, immunohistochemically detectable ERG overexpression was restricted to endothelial cells and subsets of lymphocytes.

Conclusions: The high specificity of ERG expression in both normal and neoplastic tissues suggests a very narrow biological role for ERG in highly selected tissues.

© 2012 Blackwell Publishing Ltd.
High Wilms' tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma. A. Scattone, G. Serio, A. Marzullo, et al. 2012;60(3):472-81. PubMed · Publisher

Abstract

Aims: To evaluate the use of the Wilms' tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM).

Methods And Results: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. High-grade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (≤25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05-3.71] versus 31.5 months (95% CI: 20.4-42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively).

Conclusions: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

© 2012 Blackwell Publishing Limited.
The diagnostic value of immunohistochemically detected methylthioadenosine phosphorylase deficiency in malignant pleural mesotheliomas. Z.G. Zimling, A. Jørgensen, E. Santoni-Rugiu. 2012;60(6B):E96-105. PubMed · Publisher

Abstract

Aims: Malignant pleural mesothelioma (MPM) often causes diagnostic difficulties for pathologists. We assessed whether loss of methylthioadenosine phosphorylase (MTAP), a key enzyme in the intracellular recycling of adenosine triphosphate (ATP) often deleted in MPM, could be detected with immunohistochemistry (IHC) and used as a diagnostic marker for MPM.

Methods And Results: We used IHC to detect MTAP in a cohort of 99 MPMs and 39 reactive mesothelial proliferations (RP) (reactive mesothelial hyperplasia n = 33, reactive pleural fibrosis n = 6). MTAP staining was assessed by an H score. The median H score of the RP cohort was set as a reference point. Cases with H scores below this reference point were considered to have decreased MTAP expression. We found that 64 of 99 (65%) of the investigated MPMs had decreased MTAP expression, while this was only true for nine of 39 (23%) of the RPs (P = 0.001). We further evaluated MTAP expression in a cohort of coagulated pleural effusions from 14 patients with MPM and 20 patients with RP by using a double-staining technique with Wilms tumour 1 (WT1) as a mesothelial marker. In these samples, decreased MTAP expression diagnosed MPM with a sensitivity of 71% and a specificity of 90%.

Conclusions: Decreased MTAP expression could potentially be useful in combination with other markers in the diagnosis of MPM.

© 2012 Blackwell Publishing Ltd.
Expression of calretinin by breast carcinoma and the potential for misdiagnosis of mesothelioma. G. Powell, H. Roche, W.R. Roche. 2011;59(5):950-6. PubMed · Publisher

Abstract

Aims: Calretinin and cytokeratin (CK)5/6 are frequently used to differentiate between metastatic breast cancer and primary malignant mesothelioma in pleural biopsies, but both tumours may express these markers. This study was aimed at evaluating the frequency of calretinin expression in primary breast carcinomas, and assessing the characteristics of the calretinin-positive tumours.

Methods And Results: Fifty-three primary breast adenocarcinomas were analysed for immunohistochemical expression of calretinin. CK5/6 and epidermal growth factor receptor (EGFR) immunostaining were performed on the calretinin-positive subset. Tumours were classified as basal-like if they met standard morphological and immunohistochemical criteria. Fifteen per cent (8/53) of the breast tumours were positive for calretinin. Eighty-eight per cent (7/8) of the calretinin-positive tumours were grade 3, as compared with 20% (9/45) of the calretinin-negative tumours (P<0.001). Only 13% (1/8) of the calretinin-positive tumours were also oestrogen receptor (ER)-positive, as compared with 87% (39/45) of the calretinin-negative tumours (P<0.001). Eleven per cent (6/53) of the tumours were classified as basal-like. Of these, four were positive for calretinin and two were negative (P=0.003).

Conclusions: Fifteen per cent of breast carcinomas stain with calretinin. These tumours are more likely to be high-grade, ER-negative, and display a basal-like phenotype. These tumours may be misdiagnosed as malignant mesothelioma when they metastasize to the pleura.

© 2011 Blackwell Publishing Limited.
The importance of retaining post mortem tissue--'pseudomesotheliomatous' Merkel cell carcinoma of the pleura. G.D. Leopold, R.L. Attanoos. 2011;58(7):1180-2. Case report · Letter PubMed · Publisher
Myogenic antigen expression is useful for differentiation between epithelioid mesothelioma and non-neoplastic mesothelial cells. H. Tsukiji, Y. Takeshima, V.J. Amatya, et al. 2010;56(7):969-74. Letter PubMed · Publisher

Summary

This research letter examined whether desmin and other myogenic (muscle-related) markers help pathologists distinguish epithelioid mesothelioma (EM) from non-neoplastic mesothelial cells (NMC), a distinction the authors described as often difficult. The authors, from the Department of Pathology at Hiroshima University, Japan, retrieved 63 EM cases (57 pleural, six peritoneal) and 44 cases of pleural or peritoneal NMC from their surgical files. NMC were grouped as normal-looking mesothelial cells (19 cases), reactive mesothelial cells (20 cases) and reactive mesothelial hyperplasia (5 cases, per the summary table). Tissue sections were stained for desmin, smooth muscle actin (SMA), calponin, muscle-specific actin (MSA), CD10 and h-caldesmon, and graded by the percentage of positive cells. Desmin was positive in 38/44 NMC (86.4%) but only 6/60 EM (10%) (P < 0.001), and all six positive EMs scored only 1+. SMA (22/52, 42.3%) and calponin (7/18, 38.9%) were more often positive in EM than in NMC (9.1% and 4.5%). MSA (10/19, 52.6%), CD10 (11/32, 34.4%) and h-caldesmon (3/57, 5.3%; not significant) were positive only in EM. The authors stated that the higher expression of these other markers in EM was not of practical use for differential diagnosis. They concluded that desmin was the most useful myogenic marker, followed by SMA and MSA.

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.

2000s

An approach to industrial post mortems. R.L. Attanoos, A.R. Gibbs. 2009;54(1):134-42. Review PubMed · Publisher

Abstract

Industrial-related deaths represent a specialized aspect of autopsy practice. The purpose of this review is to assist the pathologist in the handling of such deaths. The diseases associated with the three most significant mineral dusts (asbestos, coal and silica) are described, together with a selection of less well-known mineral dust diseases. This review addresses the complex issues of ascribing disease to industrial exposures and the role of mineral analysis. The authors discuss the common medical legal issues that are encountered at post mortem and at inquest deposition.
Osteopontin is linked to p65 and MMP-9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma. A.B. Frey, A. Wali, H. Pass, et al. 2007;50(6):720-6. PubMed · Publisher

Abstract

Aims: Osteopontin (OPN) is a matricellular protein involved in tissue remodelling, cell-mediated immunity and malignant transformation. High OPN serum levels predict poor prognosis in non-small cell carcinoma and set patients with malignant pleural mesothelioma (MM) apart from disease-free asbestos-exposed individuals. Yet neither the spectrum of tissue expression nor the signalling pathways of OPN in MM and pulmonary adenocarcinoma have been characterized, although in vitro evidence links OPN to the epidermal growth factor receptor (EGFR) pathway. The aim of this study was to address these deficiencies.

Methods And Results: OPN expression was investigated immunohistochemically in 104 adenocarcinomas and 38 MM and correlated with histological features, including tumour type, grade and proliferation and with expression of activated intermediary EGFR signalling pathway molecules p65, p-AKT, p-ERK, p-STAT-3, and of metalloproteinase (MMP)-1, MMP-2 and MMP-9. In MM, OPN expression was widespread (36/38) and independent of the molecular parameters studied. In adenocarcinoma, high OPN expression was correlated with expression of p65, p-ERK and MMP-9.

Conclusions: Frequent OPN expression is typical of, but not specific for MM, whereas it appears to select adenocarcinoma cases with p65 and MMP-9 expression, suggesting a link with EGFR signalling pathways.
Pulmonary histiocytosis X in a patient with epithelioid mesothelioma. J. Morrison, S. Stamenkovic, W.S. Walker, et al. 2006;49(3):320-1. Case report · Letter PubMed · Publisher
What is a significant lung asbestos fibre result?. S.K. Suvarna, C. Layton. 2006;48(2):203-4. Letter PubMed · Publisher
Simultaneous non-Hodgkin's lymphoma and mesothelioma presenting as a collision tumour. L.D. Gudur, M. Munavvar, A. Walsham, et al. 2005;47(5):546-8. Case report · Letter PubMed · Publisher
Coexistent atypical adenomatous hyperplasia, primary lung adenocarcinoma and pleural mesothelioma in an asbestos-exposed subject. D.H. Thomas, R.L. Attanoos, A.R. Gibbs. 2004;45(5):540-2. Case report · Letter PubMed · Publisher
Collision tumour of the pleura composed of small cell carcinoma and malignant mesothelioma. A.H. Lee, I.N. Soomro. 2004;45(3):305-6. Case report · Letter · Comment PubMed · Publisher

Summary

In a letter responding to a report by Attanoos et al. of three cases of mesothelioma intimately admixed with another tumour type, the authors described a case of pleural malignant mesothelioma mixed with small cell carcinoma. They stated that this combination did not appear to have been described before. The patient was an 81-year-old man who had been exposed to asbestos while working in a power station and who also smoked. He died 9 months after pleural malignant mesothelioma was diagnosed on pleural biopsy. At postmortem examination, firm white tumour replaced the lower two-thirds of the right pleura. Pleural plaques were present elsewhere, and tumour deposits were found in the liver, pancreas, adrenals and thyroid gland. Sections of the right pleural tumour showed intermingled malignant mesothelioma and small cell carcinoma. Cytokeratin 5/6, calretinin, HBME-1 and vimentin were expressed only in the mesothelioma. CD56, thyroid transcription factor-1 and carcinoembryonic antigen were expressed only in the small cell carcinoma. Asbestos bodies were noted in the lung, but there was no interstitial pulmonary fibrosis. All metastases showed small cell carcinoma only. The authors concluded that the asbestos exposure history and asbestos bodies were consistent with asbestos causing the mesothelioma. Because there was no asbestosis, they considered that the small cell carcinoma could not be attributed to asbestos and was likely related to smoking. They stated that the small cell carcinoma was the important contributor to death, and that the case emphasized the importance of histology at postmortem examination of mesothelioma.

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.
Familial pleural mesothelioma with environmental asbestos exposure: losses of DNA sequences by comparative genomic hybridization (CGH). G. Serio, A. Scattone, M. Gentile, et al. 2004;45(6):643-5. Case report · Letter PubMed · Publisher

Summary

This letter reported a genetic analysis of malignant pleural mesothelioma in two sisters, aged 23 and 32 years, from a nine-member family who had been environmentally exposed to asbestos. Both sisters also had Marfan's syndrome. They died 39 and 24 months, respectively, after histological diagnosis. In both cases the tumour was the deciduoid subtype, a rare variant of epithelioid mesothelioma. The authors performed comparative genomic hybridization (CGH) on paraffin-embedded tumour samples. The two cases showed largely concordant chromosomal changes, and gains were more frequent than losses. Both tumours had gains on 1p31.3-pter, 4p15.3-pter, 8q24.1-qter, 10q25.1-qter, 11q12-q13, 11q22-qter and 12q24.1-qter, and trisomy of chromosome 19 and 22q. Both tumours had losses at 13q21.1-q22 and on 6q (6q12-q21 in case 1, 6q12-q14 in case 2). Case 2 also had losses at 2q32.1-q33, 4p13-q21.1 and 9p22-pter. The authors noted that losses at 6q12-q21 and 13q21.1-q22 had previously been found in another familial case and in some sporadic mesotheliomas. They concluded that these regions might contain tumour suppressor genes. They said their results supported a possible genetic component in mesothelioma and provided evidence for a recessive mechanism. They suggested that familial mesotheliomas might be a useful model for studying the relationship between genetic risk and environmental asbestos exposure.

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 pathology associated with therapeutic procedures in malignant mesothelioma. R.L. Attanoos, A.R. Gibbs. 2004;45(4):393-7. PubMed · Publisher

Abstract

Aims: To describe iatrogenic pathological lesions in malignant pleural mesothelioma.

Methods And Results: All cases of malignant pleural mesothelioma confirmed by antemortem pleural biopsy and undergoing post mortem examination over a 7-year period (1995-2001) formed the study group. This comprised 48 malignant pleural mesotheliomas [epithelioid (n = 21), biphasic (n = 14) and sarcomatoid (n = 13)]. Twenty-eight of 48 (58%) had received chemical (talc) pleurodesis, 30/48 (63%) palliative localized radiotherapy, 6/48 (13%) chemotherapy, and 14/48 (30%) surgery [12/48 (26%) pleural decortication and 2/48 (4%) pleuropneumonectomy].

Conclusions: Talc pleurodesis induces a marked pseudosarcomatous fibroblastic proliferation which may impart a biphasic pattern to the neoplasm. In more chronic cases, paucicellular fibrosis with a foreign body giant cell reaction is noted. The talc is polarizable and deposited in linear fashion within the tumour. In 2/28 (7%) pleurodesis cases platyform ferruginous bodies were seen in the peripheral alveolated lung parenchyma and these mimicked asbestos bodies. An awareness of this is important to prevent false attribution to asbestos. Talc could be identified by transmission electron microscopic mineral analysis in 5/15 (33%) cases examined. Tumour nodules developing subjacent to iatrogenic wound sites were noted in 8/48 (17%) cases. In 6/8 (75%) of these cases, comparative assessment of the locally irradiated subcutaneous chest wall tumour, with background pleural mesothelioma, showed no morphological difference in architectural tumour growth pattern, extent of necrosis, cytological or nuclear pleomorphism, mitotic activity or tumour immunophenotype. In 2/8 (25%) cases the locally irradiated tumour showed prominent bizarre multinucleated tumour giant cells and intense mixed inflammation, a feature not seen in the background (non-irradiated) tumour. All six malignant pleural mesotheliomas receiving chemotherapy appeared refractory to treatment in that chemotherapy did not appear to have any significant effect on the tumour morphology, cytonuclear pleomorphism, mitotic activity, extent of necrosis or immunophenotype. In the 12 decortication specimens and two pleuropneumonectomy resections, post mortem examination identified evidence of residual malignant mesothelioma of similar morphological subtype and immunophenotype to the resected tumour.
'Pseudomesotheliomatous' carcinomas of the pleura: a 10-year analysis of cases from the Environmental Lung Disease Research Group, Cardiff. R.L. Attanoos, A.R. Gibbs. 2003;43(5):444-52. PubMed · Publisher

Abstract

Aims: To undertake a clinicopathological study of diffuse serosal neoplasms of epithelial histogenesis which clinically and pathologically mimic malignant pleural mesothelioma.

Methods And Results: Over a 10-year (1990-2000) study period 53 carcinomas mimicking diffuse pleural mesothelioma ('pseudomesotheliomatous' carcinoma) were identified. The study group comprised 50 men and three females, age range 33-77 (median 68) years. In 46 (87%) cases there was a history of smoking and in 40 (76%) cases a history of asbestos exposure. Histologically the pleural 'pseudomesotheliomatous' carcinomas could be divided into two broad groups: primary pulmonary carcinomas with florid pleurotropic growth (n = 47), of which 34 (70%) were adenocarcinomas; and diffuse carcinomatous involvement of the pleura by metastatic tumour (n = 6). This latter group comprised two transitional cell carcinomas of bladder, one renal (clear) cell carcinoma, one ductal pancreatic adenocarcinoma, one prostatic adenocarcinoma and one squamous cell carcinoma of parotid gland origin. Follow-up data were available in 35 cases. Regardless of tumour type, survival was poor (median 8 months) and comparable to diffuse pleural mesothelioma.

Conclusions: Pleural 'pseudomesotheliomatous' carcinomas are uncommon (comprising 6% of referrals), pathologically heterogeneous tumours with poor prognosis. Tissue diagnosis should be obtained in all cases of suspected diffuse pleural neoplasia. By light microscopy and immunophenotype many of the tumours mimicked malignant mesothelioma. In particular, an awareness that all neoplasms exhibiting squamous differentiation may express cytokeratin 5/6 and thrombomodulin is important to prevent misinterpretation. In this respect, calretinin is regarded as the most specific and sensitive mesothelial marker. Misdiagnosis may have medico-legal implications in asbestos-related compensation claims.
Synchronous diffuse malignant mesothelioma and carcinomas in asbestos-exposed individuals. R.L. Attanoos, D.H. Thomas, A.R. Gibbs. 2003;43(4):387-92. PubMed · Publisher

Abstract

Aims: The development of synchronous diffuse malignant mesothelioma and carcinoma in individuals exposed to asbestos is rare. We report nine cases and discuss the medico-legal implications.

Methods And Results: Five hundred patients seeking compensation for asbestos-related diffuse malignant mesothelioma were reviewed with access to post-mortem data. The study group comprised cases in which a second (non-mesothelial) neoplasm was identified. The study group comprised eight males, one female, mean age 68 years (range 60-75). All individuals gave a history of asbestos exposure. Synchronous malignant mesothelioma with carcinoma was identified in 9/500 (1.8%). Eight malignant mesotheliomas were pleural, one was primary peritoneal in origin. By morphological subtyping there were four epithelioid, three biphasic and two sarcomatoid mesotheliomas. In 6/9 (67%) the second tumour was a primary bronchogenic carcinoma (three adenocarcinomas, two squamous cell carcinomas and one small-cell carcinoma). In 3/9 (33%) the second tumour was a non-bronchogenic carcinoma (colonic, pancreatic and breast ductal adenocarcinoma). No other neoplasms were identified in the cohort of malignant mesotheliomas studied. Five persons had pathological evidence of asbestosis (four had bronchogenic carcinomas, one colorectal adenocarcinoma). Two persons with non-bronchogenic carcinomas had identifiable asbestos bodies but no interstitial fibrosis. In two cases the second neoplasms (primary bronchogenic squamous cell and small-cell carcinomas) were associated with diffuse interstitial fibrosis but no asbestos bodies were seen on light microscopy. In each case transmission electron microscopic mineral analysis revealed an asbestos fibre burden within the background population range for control subjects and well below that seen in cases of established asbestosis. These cases were considered to represent cryptogenic fibrosing alveolitis in subjects with a history of asbestos exposure.

Conclusions: Synchronous malignant mesothelioma with carcinomas in asbestos-exposed workers is rare and identified in 1.8% of 500 malignant mesotheliomas in this series. In most cases the carcinoma represents a primary bronchogenic neoplasm. Primary lung carcinomas are recognized to be asbestos related only when occurring in association with asbestosis. In this series this combination (bronchogenic carcinoma and asbestosis) was seen in four (0.8%) cases. In post-mortem cases for possible malignant mesothelioma it is important to identify any other neoplasia and determine whether it is related to asbestos. Their presence impact upon anticipated life expectancy and in the presence of malignant mesothelioma will affect the compensation settlement.
Unusual contaminant fibres on mineral analysis. R.L. Attanoos, D.M. Griffiths, A.R. Gibbs. 2003;43(4):405-6. Case report · Letter PubMed · Publisher
Can pulmonary sclerosing haemangioma be accurately diagnosed by intra-operative frozen section?. A.C. Chan, J.K. Chan. 2002;41(5):392-403. PubMed · Publisher

Abstract

Aims: Pulmonary sclerosing haemangioma is a rare benign tumour with a characteristic variegated histological pattern. In this retrospective study we aimed to identify features that can aid in making a correct diagnosis and avoiding potential pitfalls at the time of intra-operative frozen section.

Methods And Results: Twenty cases of pulmonary sclerosing haemangioma with intra-operative frozen section were reviewed. The four major histological patterns (solid, sclerotic, papillary and haemorrhagic) were found in various combinations in the frozen sections. In 17 cases, three or more patterns were present. There could be focal areas mimicking epithelioid haemangioendothelioma or carcinoid tumour. Intra-operative imprint/scrape cytology served as a helpful adjunct in confirming the cytological blandness, although occasional atypical cells could be present. An intra-operative frozen section diagnosis of 'sclerosing haemangioma' or 'benign tumour' was given in 14 cases; the diagnosis was deferred in six cases. Retrospective analysis of the deferred cases showed that a definitive intra-operative diagnosis could have been made in three, because three or more major histological patterns were present. One case showed a pure papillary pattern at frozen section, mimicking the appearance of papillary adenocarcinoma (primary or secondary), bronchioloalveolar carcinoma, epithelioid mesothelioma or papillary adenoma; two tumours from a patient with multicentric disease showed widespread significant cytological atypia in the tumours raising a serious consideration of malignancy.

Conclusion: A diagnosis of pulmonary sclerosing haemangioma can be made at intra-operative frozen sections in most cases based on the tumour circumscription and variegated histological patterns. When only a single histological pattern is identified or when there is significant cytological atypia, distinction from other tumours can be problematic, and the diagnosis is best deferred.
Foamy cell mesothelioma. A. Cavazza, G. Pasquinelli, L. Agostini, et al. 2002;41(4):369-71. Case report · Letter PubMed · Publisher

Summary

This letter reported a malignant epithelial mesothelioma of the pleura in which part of the tumour cells had abundant foamy cytoplasm. The authors described this pattern as deceptively bland and largely unrecognized among pathologists. The patient was a 56-year-old woman, a smoker with no history of asbestos exposure, who presented with thoracic pain and dyspnoea. Imaging showed a left pleural effusion with no lesions elsewhere. Thoracoscopy revealed nodules involving the parietal pleura, diaphragm and pericardium, and multiple biopsies were taken. She received palliative therapy and died of disease 6 months after diagnosis; no autopsy was done. The biopsies showed a solid and tubulo-papillary tumour of large cells. In about 40% of the tumour cells the cytoplasm was clear and foamy, and these cells merged with eosinophilic cells. Both components were strongly positive for cytokeratin AE1/AE3, calretinin and CD10, and negative for CEA, BER-EP4, B72.3, CD68, CD15 and TTF-1. Electron microscopy showed long, slender microvilli of the mesothelial type. The authors reviewed earlier reports of foamy or clear cells in mesothelioma. They stressed recognizing the malignant nature of foamy cell mesothelioma and distinguishing it from other clear cell tumours, particularly metastatic renal carcinoma. They noted that CD10 positivity could mislead, because CD10 reacts with about 90% of renal cell carcinomas but is also positive in 18% of mesotheliomas. They concluded that clinico-radiological findings, areas of more traditional mesothelioma and a limited immunohistochemical panel enable the correct diagnosis.

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.
Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival. G. Serio, A. Scattone, A. Pennella, et al. 2002;40(4):348-52. Case report PubMed · Publisher

Abstract

Aims: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival.

Methods And Results: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively).

Conclusions: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.
Primary thymic epithelial tumours of the pleura mimicking malignant mesothelioma. R.L. Attanoos, F. Galateau-Salle, A.R. Gibbs, et al. 2002;41(1):42-9. PubMed · Publisher

Abstract

Aims: To illustrate the macroscopic, light microscopic and immunophenotypic similarities that exist between primary pleural thymic epithelial tumours and diffuse malignant mesothelioma. To investigate the expression of the mesothelial markers, cytokeratin (CK) 5/6, calretinin and thrombomodulin in a series of mediastinal thymic epithelial tumours.

Methods And Results: Over a 10-year period, 64 diffuse pleural tumours of non-mesothelial histogenesis were identified in the files of referrals to the South Wales regional thoracic centre (Llandough Hospital, Cardiff). Of these, five pleural tumours were diagnosed as primary pleural thymic epithelial neoplasms. From the files of the Mesopath group, Caen, three additional cases of thymic epithelial tumours with pleural involvement were identified. The study group comprised eight cases (four males, four females) with median age at presentation of 56 years (range 19-75 years). In one case there was a history of asbestos exposure. Macroscopically, seven tumours formed diffuse pleural masses. No mediastinal abnormality or intraparenchymal lesions were seen in five cases. By light microscopy, seven thymic epithelial neoplasms showed a lobulated architecture, one appeared extensively cystic. The tumours were of varied morphological subtypes: one medullary (WHO Type A), two mixed (WHO Type AB), three predominantly cortical (WHO Type B1) and two cortical (WHO Type B1). The subtypes morphologically mimicked sarcomatoid, biphasic, lymphohistiocytoid variant and epithelioid mesothelioma. The pleural thymic epithelial tumours showed immunoreactivity with broad spectrum cytokeratin AE1/AE3 (8/8; 100%), CK5/6 (8/8; 100%), and 1/8 (13%) expressed thrombomodulin. Calretinin showed variable nuclear and cytoplasmic expression in all cases, but equivocally in the thymic epithelial cell component. In 7/8 (88%) the thymic epithelial cells exhibited focal aberrant expression of CD20. Epithelial membrane antigen (EMA) showed focal expression in the perivascular and organoid areas in 6/8 (75%) cases. Carcinoembryonic antigen (CEA) and CD34 were uniformly negative. In 4/8 (50%) cases the lymphoid cell component was of immature phenotype expressing CD99, terminal deoxynucleotidyl transferase (TdT) and lymphoid precursors had a high proliferation fraction with Ki67. In the series of 20 primary mediastinal thymic epithelial tumours tested, mesothelial marker expression revealed CK5/6 (20/20), thrombomodulin (3/20; 15%) and calretinin (0/20; 0%). Varying amounts of calretinin-positive stromal cells were present.

Conclusion: Primary pleural thymic epithelial tumours are rare but may mimic malignant mesothelioma by forming diffuse serosal-based masses. In addition, both tumours may show morphological diversity (with epithelial, spindled and mixed components present). An awareness that thymic epithelial tumours may variably express the mesothelial markers CK5/6, calretinin and thrombomodulin prevents misdiagnosis. In the distinction from malignant mesothelioma a lobulated architecture and organoid features favour a thymic epithelial neoplasm. The presence of aberrant CD20 expression in a cytokeratin-positive epithelial neoplasm and/or the presence of an immature lymphoid population (by demonstration of CD1a, CD2, CD99 and TdT) indicates a thymic epithelial neoplasm. In contrast, nuclear calretinin expression favours malignant mesothelioma.
The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas. M. Osborn, N. Pelling, M.M. Walker, et al. 2002;41(4):301-7. PubMed · Publisher

Abstract

Aims: Despite increasing usage of mesothelium-associated antibodies in diagnosis, a meta-analysis of studies analysing these antibodies in relation to distinguishing mesothelioma from renal cell carcinoma shows a paucity of published data. Given the clinical importance of elucidating this differential diagnosis, we compared the phenotypes of these two tumours using a panel of antibodies comprising recently described 'mesothelium-associated' antibodies and the more established 'epithelium-associated' antibodies.

Methods And Results: We applied an antibody panel comprising calretinin, cytokeratin (CK)5/6, thrombomodulin, carcinoembryonic antigen (CEA), BerEP4 and BCA225 to 37 cases of pleural mesotheliomas and 40 cases of renal cell carcinoma (27 primary tumours and 13 metastatic to the pleura). All mesotheliomas were either purely epithelioid or of mixed type. Cases of renal cell carcinoma were graded and classified as to cell type and architecture. For mesotheliomas, 0% stained for CEA, 16% for BerEP4, 83% for BCA225, 78% for CK5/6, 86% for thrombomodulin and 97% showed nuclear staining for calretinin. For renal cell carcinomas, 0% stained for CEA, 50% for BerEP4, 88% for BCA225, 5% for CK5/6, 32% for thrombomodulin and 10% showed nuclear staining for calretinin.

Conclusion: Calretinin, CK5/6 and BerEP4 appear the most useful antibodies in helping to distinguish between renal cell carcinomas and mesotheliomas, although BerEP4 was not particularly sensitive for renal cell carcinomas. Thrombomodulin was not as specific as the other 'mesothelium-associated' antibodies in this study, reflecting how staining for mesothelium-associated antibodies varies in carcinomas from different primary sites, and such variations should be taken into account when assessing the differential diagnosis of mesothelioma. In cases where doubt remains over distinguishing metastatic renal cell carcinoma from mesothelioma, data from such a panel should be viewed with caution and assessed in association with clinical, imaging and morphological features.
Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum. R.L. Attanoos, R. Webb, S.D. Dojcinov, et al. 2002;40(3):237-44. PubMed · Publisher

Abstract

Aims: To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum.

Methods And Results: Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas.

Conclusions: Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.
Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura. C. González-Lois, C. Ballestín, M.T. Sotelo, et al. 2001;38(6):528-34. PubMed · Publisher

Abstract

Aims: To determine the value of immunohistochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy we optimized a double panel of MOC-31 and HBME-1 and compared the results with others from the literature.

Methods And Results: A multi-antibody panel was applied to biopsy samples from 44 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura. We used monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), LeuM1, vimentin, desmin, epithelial related antigen (MOC-31) and mesothelial cell (HBME-1). Positivity for MOC-31 and Ber-EP4 was found to have the highest nosologic sensitivity (94.1% and 84.6%, respectively) and specificity (86.3% both antibodies) for carcinoma. Positive staining for HBME-1 and vimentin had the highest sensitivity (90.9% and 100%, respectively) and specificity (91.3% and 60%, respectively) for mesothelioma. A two-marker antibody panel with HBME-1 and MOC-31 was the most efficient for the distinction between carcinoma and malignant pleural mesothelioma.

Conclusion: A combination of MOC-31 (an anti- epithelial marker) and HBME-1 (an anti-mesothelial marker) has a diagnostic efficiency of 76.1% for the distinction between carcinoma and mesothelioma in pleura.
Deciduoid pleural mesothelioma. H. Monaghan, A. Al-Nafussi. 2001;39(1):104-6. Case report · Letter PubMed · Publisher

Summary

This letter reported a case of deciduoid pleural mesothelioma in a man with previous asbestos exposure. The authors noted that deciduoid peritoneal mesotheliomas are uncommon, with nine previously reported cases, and that pleural deciduoid mesotheliomas are rarer, with six previously reported cases. A 66-year-old man with a history of asbestos exposure presented with a 6-week history of night sweats and lethargy, without preceding pneumonic symptoms. Radiology showed a pleural-based mass in the posterior right lower chest. Thoracoscopy showed nodular, thickened visceral pleura and an extensive pleural mass, which was biopsied. Under the microscope, the pleura was replaced by sheets of large round, ovoid and polygonal cells with sharp outlines, abundant eosinophilic cytoplasm and round vesicular nucleoli. There was focal cytoplasmic vacuolation, a scattered chronic inflammatory infiltrate and rare mitotic figures. Immunohistochemistry showed staining for pan-cytokeratin, human milk factor globulin, CK5/6 and calretinin, and no staining for hCG, CEA or BG8. The authors stated that this pattern strongly favoured deciduoid pleural mesothelioma. They reviewed the literature. Deciduoid mesothelioma was first described in the peritoneum of young women without prior asbestos exposure, and those tumours behaved aggressively. Some mesotheliomas have been reported to produce hCG. The authors concluded that the case supported the view that deciduoid morphology is part of a spectrum of appearances in epithelioid mesothelioma and is not confined to the peritoneum or to young females. They stated that it can occur with previous asbestos exposure and in some cases may be associated with hCG production.

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.
Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1. Y. Soini, A. Puhakka, K. Kahlos, et al. 2001;39(2):179-86. PubMed · Publisher

Abstract

Aims: To investigate endothelial nitric oxide synthase (eNOS) expression in malignant mesothelioma and its association with expression of vascular endothelial growth factor (VEGF), its receptors FLK1 and FLT1, and vascular density.

Methods And Results: eNOS, VEGF, FLK1 and FLT1 were studied in 36 histological mesothelioma samples by immunohistochemistry. Two mesothelioma (M14K, M38K) and one non-neoplastic mesothelial cell line (MET-5A) were studied for eNOS mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). Vascular density was determined by staining the samples with an antibody to factor VIII. RT-PCR showed that mesothelioma cells synthesize eNOS in vitro. eNOS immunoreactivity was found in 32/36 (89%) tumours. VEGF, FLK1 and FLT1 expression was found in 17 (45%), 24 (69%) and 25 (71%) cases, respectively. FLK1 or FLT1 immunoreactivity was more often seen in epithelioid and biphasic mesotheliomas than in sarcomatoid ones (P=0.007 and P=0.011, respectively). There was a significant association between FLK1 and FLT1 immunoreactivity (P=0.032). No significant association was found between FLK1, FLT1, VEGF and eNOS immunoreactivity and vascular density.

Conclusions: eNOS is strongly expressed in malignant mesothelioma. Since eNOS did not associate with VEGF, FLK1 or FLT1, its synthesis seems not to be regulated through VEGF in malignant mesothelioma as has been shown in non-neoplastic endothelial cells.
Immunohistochemical evidence for mesothelial origin of paratesticular adenomatoid tumour. B. Delahunt, J.N. Eble, J.N. Nacey, et al. 2001;38(5):479. Letter PubMed · Publisher
Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern. R.L. Attanoos, R. Webb, S.D. Dojcinov, et al. 2001;39(6):584-8. PubMed · Publisher

Abstract

Aims: Malignant epithelioid mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how immunoreactivity with mesothelial markers related to histological pattern.

Methods And Results: Ninety-two cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) were examined and classified as exhibiting tubulopapillary, adenomatoid, solid, small cell or pleomorphic patterns. All cases were immunohistochemically stained with thrombomodulin, calretinin, CD44H, and cytokeratin 5/6. Cases of malignant mesothelioma exhibited a number of different histological forms. Immunohistochemical expression of each mesothelial marker tested was not homogeneous across different histological patterns of malignant epithelioid mesothelioma, even within the same tumour section. Calretinin (with nuclear expression) was identified to show the highest overall sensitivity and lowest range variation in staining (67% sensitivity in small cell areas to 100% expression in pleomorphic areas). Cytokeratin 5/6 and thrombomodulin yielded similar overall sensitivity. Thrombomodulin appeared to demonstrate higher sensitivity for small cell variant tumour (83% sensitivity). A notable advantage with cytokeratin 5/6 was that expression was more diffuse in nature rather than the focal membranous elaboration seen in thrombomodulin. The widest range of staining was seen in small cell mesothelioma (83% sensitivity with thrombomodulin to 17% sensitivity with cytokeratin 5/6) and in tubulopapillary areas (90% sensitivity with calretinin to 38% sensitivity with CD44H).

Conclusions: Calretinin appears most useful and shows the highest overall sensitivity for malignant epithelioid mesothelioma, with good expression in areas displaying a tubulopapillary, adenomatoid, solid and pleomorphic pattern. For small cell mesothelioma, thrombomodulin appears to confer higher sensitivity and is advocated, in this setting, as the first line mesothelial marker. Cytokeratin 5/6 is a useful and easily interpretable mesothelial marker. CD44H is not of particular use in the diagnosis of malignant epithelioid mesothelioma. Accurate interpretation of immunohistochemistry in mesothelioma requires an awareness of the immunophenotypic heterogeneity identified in different histological forms of the tumour, and this is of particular importance in small biopsies.
Monoclonal antibody SM047 as an immunohistochemical marker of ovarian adenocarcinoma. W.G. McCluggage, P. Maxwell, H. Veenstra, et al. 2001;38(6):542-9. PubMed · Publisher

Abstract

Aims: This study describes the generation of a monoclonal antibody designated SM047 which binds to an epitope that is displayed by a multivalent antigen associated with the glycocalyx of ovarian adenocarcinoma cells. The study also investigates SM047 staining in adenocarcinomas of diverse sites in order to determine whether the antibody is specific for ovarian adenocarcinoma and of value in the confirmation of an ovarian origin when the site of primary tumour is unknown.

Methods And Results: SM047, an IgM monoclonal antibody, was the product of hybridoma cells derived from fusion of SP2 myeloma cells with splenocytes of a mouse that had been immunized with a membrane preparation of tumour (ovarian serous cystadenocarcinoma) and boosted with cells from a cell line established from a similar tumour in a different patient. Sixty-two primary ovarian adenocarcinomas (28 serous, 23 mucinous, five endometrioid and six clear cell), 69 adenocarcinomas arising primary at other sites and 10 mesotheliomas were stained with SM047. There was positive membrane staining, which was usually strong and widespread, in 27 of 28 ovarian serous carcinomas and in all ovarian endometrioid and clear cell carcinomas. Most ovarian mucinous tumours were negative or exhibited weak cytoplasmic staining. Staining was variable in the other tumours but there was positive staining of most endometrial, endocervical and pancreatic adenocarcinomas. Most colonic adenocarcinomas were negative or exhibited weak cytoplasmic staining.

Conclusions: SM047 is strongly expressed in most ovarian serous adenocarcinomas and in other female genital tract adenocarcinomas, with the exception of ovarian mucinous tumours. The antibody may be useful in confirming the ovarian origin of an adenocarcinoma when used as part of a larger panel. This is especially so in the distinction between a non-mucinous ovarian adenocarcinoma, which usually exhibits strong membranous staining, and a colonic adenocarcinoma which is usually negative or exhibits weak cytoplasmic staining. These findings need to be confirmed by further study of larger numbers of cases.
Staining of malignant mesothelioma for the trefoil protein pS2. E. Murphy, S.K. Suvarna. 2001;38(4):381-2. Letter PubMed · Publisher
'Mucin-positive' epithelial mesothelioma of the peritoneum: an unusual diagnostic pitfall. D.S. Cook, R.L. Attanoos, S.S. Jalloh, et al. 2000;37(1):33-6. Case report PubMed · Publisher

Abstract

Aims: The histopathological, immunohistochemical and ultrastructural features of a primary 'mucin-positive' epithelial mesothelioma of the peritoneum are reported to draw attention to a potential cause of diagnostic error.

Methods And Results: Light microscopy showed an infiltrative neoplasm within the gastric wall and omentum which was composed of sheets of 'signet- ring' tumour cells and contained abundant diastase-resistant periodic acid-Schiff-positive material. Immunohistochemistry supported a mesothelial phenotype (cytokeratin AE1/3, thick membranous HBME-1, focal thrombomodulin and calretinin expression and no reactivity for carcinoembryonic antigen, Leu-M1 and Ber-EP4). Ultrastructural features showed large cells with prominent intercellular desmosomes and numerous delicate, elongated microvilli. Within intracytoplasmic neolumina, crystalloidal 'fern-like' bodies were identified with features similar to the ultrastructural appearances of hyaluronic acid crystals. Repeat histochemical analysis following hyaluronidase pretreatment revealed a significantly diminished diastase-resistant periodic acid-Schiff reaction.

Conclusions: This case of primary peritoneal 'mucin-positive' epithelial mesothelioma demonstrates morphological and histochemical mimicry with diffuse gastric adenocarcinoma. A similar case has not been previously reported in the peritoneum and an awareness of the tumour (with application of suitable ancillary studies) prevents misdiagnosis and assists in potentially difficult medicolegal cases.
HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma. J. Oates, C. Edwards. 2000;36(4):341-7. PubMed · Publisher

Abstract

Aims: To evaluate HBME-1, WT1, calretinin and MOC-31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung.

Methods And Results: Paraffin-embedded formalin-fixed blocks from six reactive pleuras, 42 mesotheliomas and 40 adenocarcinomas were used. Sections were stained for Leu-M1, HBME-1, calretinin, WT1 and MOC-31. Leu-M1 was positive or equivocal in 34% of mesotheliomas and in 78% of adenocarcinomas; reactive pleuras were all negative. HBME-1 was positive or equivocal in 76% of mesotheliomas and in 73% of adenocarcinomas; five reactive pleuras were positive. Calretinin was positive or equivocal in 92% of mesotheliomas and in 73% of adenocarcinomas; two reactive pleura were equivocal and four were positive. WT1 was positive or equivocal in 72% of mesotheliomas (excluding autopsy cases) and in 20% of adenocarcinomas; all reactive pleuras were positive. MOC-31 was positive or equivocal in 5% of mesotheliomas and in 90% of adenocarcinomas; all reactive pleuras were negative. The reaction with Leu-M1 was graded as equivocal in 25% of the adenocarcinomas. All 24 of the autopsy cases of mesothelioma were negative for WT1 and in many operative specimens only the periphery was stained.

Conclusions: Neither calretinin nor HBME-1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC-31 is confirmed, and outperforms Leu-M1.
Primary malignant gonadal mesotheliomas and asbestos. R.L. Attanoos, A.R. Gibbs. 2000;37(2):150-9. Case report PubMed · Publisher

Abstract

Aims: The clinicopathological, immunohistochemical and aetiological aspects, with respect to asbestos, of seven primary gonadal mesotheliomas (three intratesticular, four ovarian) are described and compared. These tumours are extremely rare, poorly described and the knowledge of their natural history is very limited.

Methods And Results: The cases were collated from the UK Health and Safety Executive Mesothelioma Register over a 24-year period (1968-91). Primary mesotheliomas of the tunica vaginalis and ovary comprised 0. 09% (10 cases) and 0.03% (three cases) of mesothelioma deaths, respectively. No primary intratesticular (non-tunica vaginalis) malignant mesotheliomas have been described. In this study, we present seven (three intratesticular, four ovarian) primary malignant gonadal mesotheliomas. In both genders the tumours show a similar age distribution (with median onset in the sixth decade), a similar association with asbestos (in approximately 50% cases), a diverse histological spectrum (with predominantly tubulopapillary epithelial subtype tumours) and an immunophenotype that is comparable with malignant pleural and peritoneal mesothelioma. The clinical course appears variable (mean, 26 months; range, 9-50 months). All tumours in the study presented as localized masses and their prognosis appeared more favourable than that of diffuse pleural and peritoneal cases.

Conclusions: An awareness of the existence of these rare forms of malignant mesothelioma is important to prevent misdiagnosis. Immunohistochemistry has an important role in confirmation of the diagnosis. The accurate diagnosis of primary gonadal mesothelioma has potentially important medicolegal compensation considerations as a significant proportion of these cases are associated with asbestos.

1990s

E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma. M.P. Leers, M.M. Aarts, P.H. Theunissen. 1998;32(3):209-16. PubMed · Publisher

Abstract

Aims: To assess the diagnostic accuracy of combinations of antibodies in the differential diagnosis of metastatic carcinomas and mesotheliomas in pleural lesions.

Methods And Results: The specificity and sensitivity of the commercially available antibodies Ber-EP4, MOC-31, CEA, B72.3, CD15, E-cadherin and calretinin were evaluated using an indirect immunoperoxidase staining technique. This technique was applied to formalin-fixed, paraffin-embedded tissue blocks of pleural lesions. Twenty-one patients with metastatic carcinoma (MC) and 20 patients with malignant mesothelioma (MM) were included. The combination E-cadherin/calretinin had the highest specificity (MC 100% and MM 91%) and sensitivity (MM 100% and MC 91%) considering both categories of tumours.

Conclusions: The combination of E-cadherin/calretinin appears to be a suitable panel for distinguishing metastatic carcinomas and mesotheliomas in pleural lesions. The additional value of other markers is limited.
Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases. A.G. Nicholson, P. Goldstraw, C. Fisher. 1998;33(6):508-13. Case report PubMed · Publisher

Abstract

Aims: Synovial sarcomas are rare tumours occasionally arising in the pleural cavity, a site where their histological characteristics may be mistaken for those of malignant mesothelioma. We examined three cases of primary pleural synovial sarcoma in order to look for clinicopathological features that may help in distinguishing them from both mesotheliomas and other sarcomas that may arise in the pleura.

Methods And Results: All three patients were male, aged 42, 28 and 42, respectively, and had no known exposure to asbestos. One biphasic tumour contained neutral mucin in focal epithelial elements that also stained positively for BerEP4 and AUA1. All three tumours showed focal positivity for either keratin or EMA in the sarcomatous elements, and they also stained positively for bcl-2 protein and MIC2 gene product (CD99).

Conclusions: Our results emphasize the importance of being aware of synovial sarcoma as a possible primary pleural malignancy, especially in a young patient with a localized mass. In addition, the presence of bcl-2 protein perhaps represents a useful marker in distinguishing synovial sarcoma, especially monophasic variants, from mesothelioma within a panel of antibodies.
CD44H expression in reactive mesothelium, pleural mesothelioma and pulmonary adenocarcinoma. R.L. Attanoos, R. Webb, A.R. Gibbs. 1997;30(3):260-3. PubMed · Publisher

Abstract

Malignant mesotheliomas are known to produce hyaluronic acid, in contrast to most pulmonary adenocarcinomas which produce neutral mucin. CD44H is the major cell surface receptor for hyaluronic acid. The aim of this study was to investigate immunohistochemically the expression of this antigen in reactive mesothelium, pleural mesothelioma and pulmonary adenocarcinoma and to assess its diagnostic utility in distinguishing the two tumours. Diffuse and intense membranous CD44H immunoreactivity was seen in 15 of 20 (75%) mesotheliomas and in all 20 biopsies of reactive mesothelium. In contrast, focal (< 10% tumour) expression of CD44H was seen in only three of 20 (15%) pulmonary adenocarcinomas. We advocate the use of CD44H as a positive mesothelial marker for incorporation alongside other established immunohistochemical markers used to distinguish mesothelioma from adenocarcinoma.
Pathology of malignant mesothelioma. R.L. Attanoos, A.R. Gibbs. 1997;30(5):403-18. Review PubMed · Publisher

Abstract

The diagnosis of malignant mesothelioma can pose several problems to the surgical pathologist. First, the morphological appearances of the tumour are known to be diverse with mimicry of a range of both reactive and neoplastic conditions. Second, due to the relative inaccessibility of the serosa, biopsy material is often scanty and fragmentary, producing a plethora of interpretive ambiguities. Third, adjunct techniques such as mucin histochemistry and immunohistochemistry, whilst useful in excluding malignant mesothelioma have little role in confirming the diagnosis. The accurate diagnosis of diffuse malignant mesothelioma is important for two reasons: (1) In relation to prognosis as it has an almost invariable fatal outcome, which contrasts with the other mesothelial neoplasms such as the benign adenomatoid tumour and the borderline malignant tumours, namely the well-differentiated papillary mesothelioma and multicystic mesothelioma; (2) In relation to occupational-related compensation claims following asbestos exposure. This review summarizes the aetiology of asbestos-induced neoplasia, possible mechanisms of tumour development and highlights potential diagnostic pitfalls.
Primary epithelioid haemangioendothelioma of the peritoneum: an unusual mimic of diffuse malignant mesothelioma. R.L. Attanoos, N.S. Dallimore, A.R. Gibbs. 1997;30(4):375-7. Case report PubMed · Publisher

Summary

The authors reported a case of epithelioid haemangioendothelioma, an uncommon low-grade sarcoma of endothelial origin, that arose primarily from the peritoneum and mimicked diffuse malignant mesothelioma both clinically and histologically. A 51-year-old man presented with a short history of increasing abdominal discomfort and distension and had marked ascites. Basic laboratory investigations were normal. Laparotomy showed a confluent multinodular pink tumour covering most of the greater omentum, which was biopsied. Extensive clinical and radiological investigations found no other primary tumour site. The patient deteriorated after surgery, received no specific treatment and died 3 months later. No autopsy was performed. Microscopy showed a broad papillary tumour with a submesothelial proliferation of vacuolated and polygonal epithelioid cells and focal intracytoplasmic lumina containing erythrocytes. Admixed atypical mesothelial cells gave the tumour a biphasic appearance. The mesothelial cells were positive for cytokeratin and focally for thrombomodulin. The underlying tumour was negative for both but strongly positive for von Willebrand factor and QBEnd10 (CD34), which confirmed its endothelial nature. The authors stated that recognising this tumour is important for two reasons. The first is asbestos-related compensation claims: unlike peritoneal mesothelioma, there is no evidence linking epithelioid haemangioendothelioma with asbestos exposure. The second is prognosis. They added that the 3-month survival may indicate a poor outlook for peritoneal tumours with diffuse serosal growth regardless of their histogenesis.

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.
Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural mesothelioma. G. Falconieri, R. Bussani, M. Mirra, et al. 1997;30(5):419-24. Case report PubMed · Publisher

Abstract

We report two cases of autopsy confirmed angiosarcoma in adult males, presenting as diffuse pleuropulmonary tumours and simulating malignant mesothelioma. Both the lesions grew along the serosal surfaces and were characterized by variably thick rinds of tissue encasing the lung. The pulmonary parenchyma showed diffuse, dark red, subpleural consolidations and multiple cavitations. Histologically, the lesions were composed by atypical spindle and polygonal, epithelioid cells showing rudimentary vascular differentiation and exhibiting strong positivity for factor VIII, CD31, CD34 and vimentin, We conclude that angiosarcoma may present with preponderant or exclusive involvement of pleura and peripheral lung and that it should be added to the list of tumours capable of simulating malignant mesothelioma.
Smooth muscle tumours of the pleura. C.A. Moran, S. Suster, M.N. Koss. 1997;30(1):97-8. Comment · Letter PubMed · Publisher

Summary

In this letter, Moran, Suster and Koss, of the Armed Forces Institute of Pathology in Washington DC, replied to a commentary by Dr A.R. Gibbs on their 1995 paper describing smooth muscle tumours presenting as pleural neoplasms. They stated that four tumours were large (10–18 cm), ill-defined masses and one was a diffuse tumour encasing the right lung in a fashion reminiscent of mesothelioma. None was well localized, encapsulated or polypoid. They argued against a diagnosis of localized (solitary) fibrous tumour for several reasons: the bulky, diffuse, infiltrative growth; the absence of sclerosis on extensive sampling; diffuse, strong actin and desmin positivity; and negative CD34 staining performed after publication. The letter says this staining was done in four cases but lists only cases 1, 3 and 5. They rejected Dr Gibbs's suggestion that case 4 was a 'leiomyoid' mesothelioma, because immunohistochemistry and electron microscopy showed no epithelial differentiation, and kept their diagnosis of leiomyosarcoma. They accepted that submesothelial cells can show smooth muscle differentiation. In a printed reply, Dr Gibbs considered the absence of CD34 their most convincing argument, while noting that not all solitary fibrous tumours express this antigen. He found the leiomyosarcoma classification less convincing, stating that sarcomatous mesotheliomas may lack epithelial features and that the authors' criteria would be too restrictive for diagnosing sarcomatous mesothelioma.

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.
Value of thrombomodulin immunostaining in the diagnosis of mesothelioma. N.G. Ordóñez. 1997;31(1):25-30. PubMed · Publisher

Abstract

Aims: Even with the benefit of immunohistochemistry and electron microscopy, the differential diagnosis between epithelial mesothelioma and pulmonary adenocarcinoma is often difficult. In most instances, the diagnosis of mesothelioma must be reached by the use of immunohistochemical markers that react with adenocarcinomas, but not with mesotheliomas. The purpose of this study is to determine the value of thrombomodulin (TM) as a positive marker for mesothelioma when distinguishing epithelial pleural mesothelioma from pulmonary adenocarcinoma.

Methods And Results: TM was expressed in 28 (80%) of 35 epithelial pleural mesotheliomas, but only five (10.9%) of 46 pulmonary adenocarcinomas had appreciable reactivity for this marker.

Conclusion: It is concluded that TM can be useful in separating pulmonary adenocarcinoma from epithelial mesothelioma, but it should be used only in conjunction with other immunohistochemical markers that are currently employed in distinguishing between these two types of malignancies.
Composite multicystic mesothelioma and adenomatoid tumour of the uterus: different morphological manifestations of the same process?. J.K. Chan, M.H. Fong. 1996;29(4):375-7. Case report PubMed · Publisher
Diffuse malignant mesothelioma arising in a paracolostomy hernial sac. P.B. Bethwaite, R. Evans, D.K. Naik, et al. 1996;29(3):282-4. Case report PubMed · Publisher

Summary

The authors reported what they described as the first documented case of malignant mesothelioma arising in a longstanding paracolostomy hernia sac, from Wellington, New Zealand. An 87-year-old Caucasian man presented with a 3-month history suggestive of small bowel obstruction. Ten years earlier he had undergone abdominoperineal resection for a Dukes C rectal adenocarcinoma, with a left iliac fossa end-colostomy. He had no occupational or recreational history of asbestos exposure. At laparotomy, a firm white tumour infiltrated the hernial sac, stoma and abdominal wall, and there was a moderate peritoneal effusion. There was no local recurrence of the rectal cancer. After small bowel resection, colostomy resiting and hernia repair, he collapsed and died on the seventh post-operative day. No autopsy was performed. The specimen showed a 38 mm x 35 mm mass around the stoma, continuous with a 65 mm x 40 mm hernial sac, and mesenteric nodules up to 20 mm. Microscopy showed invasive tubulo-papillary mesothelioma. The tumour cells were CEA-negative, cytokeratin-positive and strongly EMA-positive, which distinguished the tumour from recurrent colonic adenocarcinoma. Ascitic fluid cytology also showed malignant mesothelioma. The sac wall contained foci of mesothelial hyperplasia. Mean AgNOR counts and PCNA indices were 4.40 and 10.2% in the hyperplastic mesothelium, and 5.59 and 36.7% in the invasive tumour. The authors concluded that these values supported both a reactive and a malignant component. They stated that the case supports the idea that occasional peritoneal mesotheliomas may arise after long-standing chronic irritation and mesothelial hyperplasia.

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-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma. R.L. Attanoos, H. Goddard, A.R. Gibbs. 1996;29(3):209-15. PubMed · Publisher

Abstract

The aim of this study was to examine the expression of three putative mesothelioma-binding antibodies, thrombomodulin, OV 632 and HBME-1 in 42 malignant mesotheliomas (27 pleural and 15 peritoneal) and 32 pulmonary adenocarcinomas. Evaluation of their use in differentiating between the mesotheliomas and pulmonary adenocarcinomas was assessed. Thrombomodulin was expressed by 22 of 42 (52%) mesotheliomas but was seen in eight of 12 pure epithelial-type mesotheliomas of the pleura and in all four papillary epithelial peritoneal mesotheliomas. For pure epithelial mesotheliomas thrombomodulin was 75% sensitive. Only two of 32 pulmonary adenocarcinomas were immunoreactive yielding a 94% specificity for thrombomodulin. In comparison, OV 632 and HBME-1 showed 67% and 62% antibody sensitivity, respectively, for malignant mesothelioma but this was accompanied by low specificity (OV 632, 37%; HBME-1, 28%). Both OV 632 and HBME-1 are considered unsuitable for use in differentiating between mesotheliomas and pulmonary adenocarcinomas. We advocate the use of thrombomodulin as a mesothelioma-binding antibody in the standard panel of antibodies used in the evaluation of malignant mesothelioma.
Multilocular peritoneal inclusion cyst (multicystic mesothelioma) with hyaline globules. J. Lamovec, J. Sinkovec. 1996;28(5):466-9. Case report PubMed · Publisher
Solitary fibrous tumour of the orbit. R. Sciot, J. Goffin, E. Fossion, et al. 1996;28(2):188-91. Case report PubMed · Publisher
A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm-Horsfall protein and thrombomodulin. R.L. Attanoos, H. Goddard, N.D. Thomas, et al. 1995;27(4):361-6. PubMed · Publisher

Abstract

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesothelioma. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulo-papillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thrombomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours.
Smooth muscle tumours of the pleura. A.R. Gibbs. 1995;27(3):295-6. Review PubMed · Publisher

Summary

This commentary discussed a report by Moran and colleagues, published in the same issue of Histopathology, of five cases they considered primary smooth muscle tumours of the pleura. The author noted that primary pleural neoplasms are uncommon and nearly all have been described as localized (solitary) fibrous tumours or diffuse malignant mesotheliomas. The author also described evidence that submesothelial cells proliferate after injury, show myofibroblastoid features, and are capable of diverse differentiation. In Moran's series, all cases labelled for smooth muscle actin and vimentin and four for desmin. Four tumours were localized: two were classified as being of undetermined malignant potential and two as leiomyosarcomas. One tumour was diffuse. The author compared these cases with published localized fibrous tumours and found many similarities in clinical presentation, gross and microscopic appearance, and desmin and actin labelling. The diffuse case resembled malignant mesothelioma in its growth pattern. A previous study had found desmin and smooth muscle actin, with cytokeratin, in 2 of 45 malignant mesotheliomas. The author concluded that it is debatable whether the cases should strictly be classified as smooth muscle tumours. They may instead represent benign and malignant localized fibrous tumours and a leiomyoid diffuse mesothelioma. The author stated that asbestos exposure is strongly associated with diffuse malignant mesothelioma but not with localized fibrous tumours. None of Moran's subjects were exposed, and the author said exposure history should not be used to establish either diagnosis.

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 histopathological diagnosis of malignant mesothelioma v. pulmonary adenocarcinoma: reproducibility of the histopathological diagnosis. B.G. Skov, A.F. Lauritzen, F. Hirsch, et al. 1994;24(6):553-7. PubMed · Publisher

Abstract

In a randomized design we examined the interobserver variation in the histopathological diagnosis of adenocarcinoma of the lung and malignant mesothelioma. In three rounds, three pathologists assessed slides from 42 tumours originally diagnosed as adenocarcinomas, malignant mesotheliomas or benign lesions in the pleura. In the first round the assessments were made on haematoxylin and eosin (H & E) stained sections; in the second, on H & E sections plus sections stained with histochemical mucin stains; and in the final round, the diagnoses were made on H & E sections and sections stained with a panel of antibodies against various antigens (cytokeratin, EMA, CEA, Ber-EP4, B72.3, Leu-M1, vimentin and S-100 protein) said to be of value in the differential diagnosis. The overall interobserver agreements for the three rounds were 0.659, 0.802 and 0.817; the kappa values were 0.461, 0.681 and 0.690. It is concluded that differentiation between adenocarcinoma of the lung and malignant mesothelioma should be made on sections stained with H & E and mucin and/or immunohistochemical staining reactions, including antibodies against B72.3, Ber-EP4 and CEA.
Expression of p53 in reactive mesothelium. S. Dowell, N. Derias, P.O. Wilson, et al. 1993;22(1):96-7. Letter PubMed · Publisher

Summary

This letter reported preliminary observations on p53 protein staining in reactive (non-cancerous) mesothelial cells. The authors were from Guy's and St Thomas's, London, and the CRC Laboratories, University of Dundee. They noted that immunostaining is widely used to look for abnormalities of the p53 tumour suppressor gene, but that the staining has become harder to interpret. In their earlier work on formalin-fixed, wax-embedded tissue, p53 immunoreactivity was present in 14 of 20 cases of malignant mesothelioma and in none of 20 reactive mesothelial proliferations. This suggested that p53 staining might help with diagnosis. In an ongoing prospective study of p53 in cytological material, more than 75 examples of reactive mesothelial proliferation had been examined by September 1992. The samples were acetone-methanol fixed and stained with the monoclonal antibody Do-1 and the polyclonal reagent CM-1. Nuclear p53 immunoreactivity was seen in 11 cases (14.7%) of reactive proliferations, both pleural and peritoneal. Results were similar with both antibodies and with both indirect and ABC detection systems. The authors said the biological basis of this staining was uncertain. They stood by their findings in tissue sections but advised caution in using p53 staining on mesothelial proliferations until its biology is better understood. They suggested the difference between cytological and histological material might reflect cells' response to mechanical contact as opposed to existing in suspension.

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.
Leiomyoid mesotheliomas. H. Battifora. 1993;22(6):601; author reply 602. Comment · Letter PubMed · Publisher
The frequency of p53 immunostaining in asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas. F.G. Mayall, H. Goddard, A.R. Gibbs. 1993;22(4):383-6. PubMed · Publisher

Abstract

It has been suggested that asbestos might have an important role in the development of p53 mutations in mesotheliomas. The objective of this study was to examine asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas to establish whether the frequency of p53 immunostaining and, by implication, p53 gene mutation is related to asbestos exposure. Immunopositivity for p53 was found in seven (44%) of the 16 mesotheliomas examined. The frequency was approximately the same in both the asbestos-associated mesotheliomas and the non-asbestos-associated mesotheliomas. It is concluded that the frequency of p53 immunostaining in mesotheliomas and, by implication, the frequency of p53 gene mutation is probably not related to asbestos exposure.
Adenomatoid tumours: a mucin histochemical and immunohistochemical study. M.J. Goddard, J.W. Grant. 1992;20(1):57-61. PubMed · Publisher

Abstract

We have examined 16 cases of adenomatoid tumour using a panel of monoclonal and polyclonal antibodies and also stained them for the presence of hyaluronidase-sensitive alcianophilic material. Fourteen cases expressed cytokeratins and a proportion of these also expressed S-100 protein, neuron-specific enolase, vimentin, and human milk fat globule protein 2. The same 14 cases also showed hyaluronidase-sensitive staining with alcian blue. No expression of factor VIII-related antigen was seen in these cases. We conclude that this provides further evidence of a mesothelial origin of these tumours. The remaining two cases did not express cytokeratins and no hyaluronidase-sensitive staining with alcian blue was seen. They did however express factor VIII-related antigen. Although they were morphologically indistinguishable from the other 14 cases, we suggest that they should be more properly regarded as angiomas.
An assessment of involucrin as a diagnostically useful immunohistochemical marker in lung tumours. F.G. Mayall, H. Goddard, A.R. Gibbs. 1992;20(1):53-5. PubMed · Publisher

Abstract

A previous report has described involucrin as a specific immunohistochemical marker of squamous differentiation in lung carcinomas. The aim of our study was to examine the expression of this antigen in a wide variety of lung tumours, with particular attention to its potential value in the typing of biopsy specimens. We found that immunostaining for involucrin was common in squamous carcinomas but was also found in adenocarcinomas, adenosquamous carcinomas, large cell carcinomas and carcinosarcomas. Small cell carcinomas, carcinoid tumours and mesotheliomas were negative. Contrary to previous claims, this marker appears to have little diagnostic utility in the typing of lung tumours.
Intermediate filament expression in mesotheliomas: leiomyoid mesotheliomas are not uncommon. F.G. Mayall, H. Goddard, A.R. Gibbs. 1992;21(5):453-7. PubMed · Publisher

Abstract

In this study we examined intermediate filament expression in 45 formalin-fixed mesotheliomas. Immunostaining for cytokeratin was found in 86%, for vimentin in 71%, and for desmin in 4%; none stained for glial fibrillary acidic protein or neurofilament. The two biphasic mesotheliomas which expressed desmin also expressed smooth muscle actin but were negative for myoglobin. This, together with the ultrastructural findings, was taken as unequivocal evidence of a leiomyoid form of mesothelioma which might easily be confused with leiomyosarcoma. Both of these tumours co-expressed cytokeratin, exemplifying the value of cytokeratin immunostaining in the distinction between mesothelioma and sarcoma. Consistent non-expression of glial fibrillary acidic protein in mesotheliomas may help to distinguish them from nerve sheath tumours.
p53 expression is common in malignant mesothelioma. G. Kafiri, D.M. Thomas, N.A. Shepherd, et al. 1992;21(4):331-4. PubMed · Publisher

Abstract

The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p53 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia.
A new insight into the histogenesis of 'mesodermomas'--malignant mesotheliomas. A. Donna, P.G. Betta, V. Bianchi, et al. 1991;19(3):239-44. PubMed · Publisher

Abstract

A myogenic phenotype was induced in cultures of human mesothelial cells treated for 72 h with atrazine, a triazine derivative. Immunoreactivity for both myosin and myoglobin was detected in a large number of these cells, irrespective of their polygonal or spindle morphology, whereas no expression of desmin was observed. These findings support the embryological identity of mesothelium and mesoderm, the former being, in the post-embryonic stage, potentially capable of differentiation along the same lineages which the latter normally displays during embryogenesis. In the light of this concept it can be assumed that primary malignancies arising from the mesothelium have the competence to express the pluripotent nature of embryonic mesoderm, and hence the term mesodermoma is appropriate for this group of tumours, including mesotheliomas in a classical sense. A postulated mechanism for the phenotypic change of mesothelial cells is also outlined, involving atrazine conversion to 5-aza-chloro-cytidine, a probable DNA hypomethylating and gene activating agent, like its analogue 5-azacytidine.
Malignant peritoneal mesothelioma giving rise to multiple intestinal polyps. F.G. Mayall, A.R. Gibbs. 1991;18(5):480-2. Case report PubMed · Publisher
Congenital juvenile granulosa cell tumour of the testis: report of a case showing extensive degenerative changes. J.K. Chan, V.S. Chan, K.L. Mak. 1990;17(1):75-80. Case report PubMed · Publisher

Abstract

Juvenile granulosa cell tumour is a rare neoplasm of the testis which occurs predominantly in infancy and which may be associated with sex chromosomal abnormalities. We report an unusual case with deceptive histological features resulting from extensive degenerative changes. In the pedunculated intra-abdominal mass resected from a 1-month-old male baby with 45,X/46,X,iso(Yq) mosaicism, there were multiple large cystic spaces devoid of cellular lining or lined by flat nondescript cells, mimicking various cystic lesions such as multicystic mesothelioma, cystic lymphangioma and cystic dysplasia. The cysts were separated by a highly vascularized fibrous stroma. Only in very rare cysts and the smaller cysts in the region of the pedicle were granulosa cells identified, permitting a diagnosis of juvenile granulosa cell tumour to be made.

1980s

Adenomatoid tumour of the uterus. N. Marcussen, A. Donna. 1988;13(5):582-3. Case report PubMed · Publisher

Abstract

Two adenomatoid tumours of the uterus were examined immunohistochemically using antibodies to keratin, Factor VIII related antigen, EMA, CEA and a specific protein isolated from mesothelioma cells. The tumour cells gave positive staining for keratin and for the specific mesothelial marker. The results strongly support a mesothelial origin for adenomatoid tumours and this panel of antibodies may be used to solve diagnostic problems.
Giant cystic adenomatoid tumour (mesothelioma) of the uterus. D.L. Bisset, J.A. Morris, H. Fox. 1988;12(5):555-8. Case report PubMed · Publisher
Synovial sarcoma of the heart arising from a so-called mesothelioma of the atrio-ventricular node. E.A. Sheffield, B. Corrin, B.J. Addis, et al. 1988;12(2):191-201. Case report PubMed · Publisher

Abstract

A primary tumour of the right atrium with morphological, ultrastructural and immunohistochemical features of a synovial sarcoma is described. This appeared to have arisen from a benign so-called mesothelioma of the atrio-ventricular node and had metastasized to the lungs. The histogenesis and relationship of these two tumours are discussed.
Paraplegia due to massive asbestos-related pleural and mediastinal fibrosis. C.J. O'Brien, A.J. Franks. 1987;11(5):541-8. Case report PubMed · Publisher

Abstract

A case of massive pleural and mediastinal fibrosis related to occupational exposure to asbestos is presented. The terminal illness was marked by the acute onset of paraplegia. Autopsy revealed occlusive lesions of upper intercostal arteries within sheets of dense fibrous tissue and an ischaemic myelopathy. The presence of vascular lesions suggests a relationship with idiopathic mediastinal fibrosis.
Secretory component in pulmonary adenocarcinoma and mesothelioma. A. Kondi-Paphitis, B.J. Addis. 1986;10(12):1279-87. PubMed · Publisher

Abstract

The distribution of secretory component was examined by an immunoperoxidase method in 40 pulmonary adenocarcinomas, 11 malignant pleural mesotheliomas and areas of normal lung adjacent to the tumours. Secretory component was demonstrated in tumour cells in 25 (67%) adenocarcinomas. Its presence correlated with the degree of differentiation but was not related to tumour pattern. In the normal lung secretory component can be demonstrated in bronchial ciliated cells, bronchial gland serous cells, bronchiolar epithelium and hyperplastic alveolar epithelium. Although not usually detectable in normal mucous cells it was frequently present in mucin-producing tumours. None of the mesotheliomas examined contained secretory component and this may be an additional useful feature in the differential diagnosis between mesothelioma and adenocarcinoma.
Solitary (localized) fibrous mesothelioma: evidence against mesothelial cell origin. P.A. Dervan, B. Tobin, M. O'Connor. 1986;10(8):867-75. PubMed · Publisher

Abstract

Five cases of solitary (localized) fibrous mesothelioma were studied immunohistochemically, utilizing monoclonal antibodies against high and low molecular weight cytokeratin, vimentin, carcinoembryonic antigen, epithelial membrane antigen and factor VIII related antigen. In contrast to normal mesothelium and contrary to previous reports from malignant mesotheliomas all the tumours were negative for keratin. They were strongly positive for vimentin. Two cases were studied electron microscopically; no ultrastructural evidence of mesothelial cell differentiation was identified. Our immunohistochemical and ultrastructural findings argue against a mesothelial cell origin, whereas the presence of vimentin suggests a mesenchymal histogenesis. It is postulated that these tumours arise from sub-mesothelial mesenchymal connective tissue.
Application of markers in the diagnosis of soft tissue tumours. P.J. Roholl, A.S. De Jong, F.C. Ramaekers. 1985;9(10):1019-35. PubMed · Publisher

Abstract

In this review we describe the application of markers which are useful for the diagnosis of soft tissue tumours in paraffin sections. Detection of intermediate filament proteins appears to be most useful for first screening of these neoplasms because all, except neuroblastomas, express vimentin; cytokeratin is expressed in synovial sarcomas, epithelioid sarcomas and mesotheliomas; desmin in myogenic tumours and glial fibrillary acidic protein in astrocytomas and gliomas. Tissue-specific markers are: factor VIII--related antigen-endothelial cells; myoglobulin and skeletal muscle myosin--skeletal muscle cells; neuron specific enolase--neurons and cells of the APUD systems; and leukocyte-associated antigen--leukocytes. Markers which are present in a variety of cell types and therefore do not serve as tissue-specific markers are; S-100 proteins, alpha-1-antichymotrypsin, creatine kinase M and actin. The S-100 antigens have been detected in melanomas, granular cell tumours, chondrosarcomas and in some schwannomas and liposarcomas. Alpha-1-antichymotrypsin has been found in fibrohistiocytic and 'true' histiocytic tumours and creatine kinase M and actin in myogenic tumours. No specific markers have, as yet, been described for fibrosarcomas, Ewing's sarcomas and hemangiopericytomas.
Benign localized mesothelioma of the pleura. J.P. Janssen, S.S. Wagenaar, J.M. van den Bosch, et al. 1985;9(3):309-13. PubMed · Publisher

Abstract

Eleven cases of benign localized mesotheliomas of the pleura are described. Ten patients were asymptomatic and discovered by routine X-rays. In eight cases the tumour was localized in the visceral pleura and all tumours showed only a benign mesenchymal component. Non-neoplastic epithelial structures can become entrapped within the tumour. A benign clinical behaviour and an excellent prognosis could be expected after surgical resection.
Factor VIII-related antigen in malignant mesotheliomas. A.J. Balaton. 1985;9(6):673-4. Letter PubMed · Publisher
Immunohistological study of malignant diffuse mesotheliomas of the pleura. H. Loosli, J. Hurlimann. 1984;8(5):793-803. PubMed · Publisher

Abstract

Paraffin sections from fifteen cases of malignant diffuse mesothelioma of the pleura and five cases of bronchial adenocarcinoma infiltrating the pleura were examined with an antiserum specific for factor VIII related antigen and with antisera against various epithelial markers: keratin, carcinoembryonic antigen (CEA), fat globule membrane antigen and secretory component. In all adenocarcinomas all the epithelial markers were present whereas the factor VIII related antigen was absent. The distribution of the fat globule membrane antigens, keratin, secretory component and factor VIII related antigen varied from one mesothelioma to another. The mesotheliomas were generally negative for CEA. The three mesotheliomas which were positive for CEA were also positive for alcian blue after hyaluronidase treatment. Amongst the markers used, CEA seems the most useful for the differential diagnosis between carcinoma and mesothelioma. However, the simultaneous detection of several markers allows the characterization of various phenotypes. Some of them are close to the phenotypes of true adenocarcinoma. A relation between a given phenotype and the biological behaviour of the tumour has still to be demonstrated.
Papillary mesothelioma of ovary. B.J. Addis, H. Fox. 1983;7(2):287-98. Case report PubMed · Publisher

Abstract

A case of primary papillary mesothelioma of the ovary is reported and its microscopic and ultrastructural features described. This tumour was an incidental surgical finding and was accompanied by multiple, partially cystic, peritoneal lesions with similar microscopic features. The histological pattern was predominantly papillary with well-differentiated mesothelial cells and a prominent stromal infiltrate that included large numbers of lymphocytes and lipid-filled macrophages. A comparison is made with adenomatoid tumours and with other tumours of ovarian epithelium and it is suggested that this tumour may represent the benign counterpart of one form of clear cell carcinoma of the ovary. The presence of multiple peritoneal lesions may indicate limited malignant potential comparable to some other papillary epithelial neoplasms of the ovary.
Scanning electron microscopy. K.E. Carr, P.G. Toner, K.M. Saleh. 1982;6(1):3-24. Review PubMed · Publisher

Abstract

The technology of scanning electron microscopy (SEM) is described in brief. Its application to the study of cell and tissue structure is demonstrated and the evolution of the concept of "topographical histology" is discussed. Some current literature on the application of SEM is reviewed under the headings of experimental pathology and human pathology. While SEM has become an indispensable technique for the experimental morphologist, its application to diagnostic pathology and cytology is still at an early exploratory stage.
Benign papillary mesothelioma of peritoneum: a histological, histochemical and ultrastructural study of six cases. J.R. Goepel. 1981;5(1):21-30. PubMed · Publisher

Abstract

Six cases of localized benign papillary mesothelioma of peritoneum were retrieved from laboratory files over a 20-year period. One presented because of pain following torsion and the remaining five were incidental findings at operation. Light microscopy showed a delicate papillary stroma covered by a single layer of mesothelial cells. The mesothelial cells often showed punctate periodic acid-Schiff staining of cytoplasm. The brush border and stroma showed alcian blue positive staining which was abrogated by prior incubation with hyaluronidase. Electron microscopy revealed typical features of mesothelial cells with long microvilli, rough endoplasmic reticulum in relation to mitochondria, bundles of microfilaments, and tight junctions. Between cells there was a series of intercommunicating channels containing occasional lymphocytes and debris. These features are compared with nodular mesothelial hyperplasia, malignant mesothelioma and adenomatoid tumours of the genital tract. The necessity to distinguish benign papillary mesothelioma from metastatic carcinoma is stressed and relies on the recognition of their mesothelial origin.
Mesodermomas: a new embryological approach to primary tumours of coelomic surfaces. A. Donna, P.G. Betta. 1981;5(1):31-44. PubMed · Publisher

Abstract

It appears that the so-called mesothelium lining the serous cavities is in fact mesoderm, with an epithelial-like arrangement which persists in the post-embryological stage. Cellular variability of primary tumours of serous surfaces can be explained on this developmental evidence. The term mesodermoma seems to be justified to define neoplasms arising from undifferentiated and multipotential mesoderm which, in neoplastic disease, exhibits a wide range of differential activity and gives rise to tumours with prevailing myoblastic, angioblastic, lymphoblastic, chondroblastic, osteoblastic, fibroblastic or epithelial-like features.

1970s

Metastatic tumours in the testis. A.J. Tiltman. 1979;3(1):31-7. PubMed · Publisher

Abstract

In a prospective autopsy study of male subjects with solic malignant neoplasms, six were shown to have metastatic deposits within the testis (2.5%). These were metastases from carcinoma of the prostate (two cases), melanoma (two cases), bronchial carcinoma (one case) and pleural mesothelioma (one case). In addition, four of 29 leukaemic patients and six of 28 with non-Hodgkin's lymphoma showed testicular involvement. The metastases from the solid tumours presented in solitary nodules, as multiple nodules or as a diffuse involvement. Microscopically, these were represented by tumour cells within the interstitial tissue without involvement of the seminiferous tubules; interstitial tissue and tubular involvement, and tumour confined to the seminiferous tubules respectively.

Browse every journal in the library or the library by type of article, or return to medical research.

This page is provided for general informational purposes and does not constitute legal advice. Every asbestos case turns on its own facts, exposure history, diagnosis, deadlines, available evidence, and applicable law. Reviewing this page does not create an attorney-client relationship. For advice about your specific situation, call 833-4-ASBESTOS for a free case review.

Asbestos

Exposure

Look it up

By location

Cell types

Treatment & help

Cancers

Lung disease

Not sure

Trust claims

Lawsuits

Benefits

Guides & deadlines

Look up

History

Read & watch

The firm

Reach us