Immunoperoxidase staining of malignant cells in pleural effusions

The indirect immunoperoxidase method was used to detect the presence of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), keratin and alpha-1-antichymotrypsin (alpha 1ACT) in cells of pleural fluid sediments from 30 patients with pleural malignancies (18 mesotheliomas and 12 metastatic carcinomas). CEA was negative in all mesotheliomas and positive in all carcinomas but one (an ovarian serous cystadenocarcinoma); alpha 1ACT was positive in mesotheliomas and negative in carcinomas; EMA and keratin were positive in both types of tumor. These data suggest that the use of immunostaining against CEA and alpha 1ACT seems to improve the cytologic differential diagnosis between malignant mesothelioma and metastatic carcinoma in pleural effusions.     

Immunocytochemistry of malignant mesothelioma: OV632 as a marker of malignant mesothelioma.

In pleural or ascitic effusions the cytomorphological distinction of adenocarcinoma cells, reactive mesothelial cells, and malignant mesothelioma cells often causes a diagnostic dilemma. The value of immunocytochemistry was investigated on cytological smears of 24 well-established cases of malignant mesothelioma, a selected series of 31 metastatic adenocarcinomas, and 20 smears of patients without known malignancy. In these smears we scored the immunoreactivity with a panel of four monoclonal antibodies. In addition to antibodies for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), the monoclonal antibody MOC31 and the ovarian carcinoma specific antibody OV632 were incorporated in the panel. With none of these four antibodies was immunostaining of reactive mesothelial cells found. CEA- and MOC31-positive tumour cells were frequent in metastatic adenocarcinomas, but occurred rarely in malignant mesotheliomas. EMA-positive tumour cells were found in all metastatic adenocarcinomas (100 per cent) and in most malignant mesotheliomas (83 per cent). In addition to the expected reactivity of OV632 with ovarian carcinomas, 22 of 24 malignant mesotheliomas contained immunopositive tumour cells, while only a small proportion of non-ovarian adenocarcinomas reacted with this antibody. This selective staining of malignant mesothelioma cells, but not reactive mesothelial cells, with OV632 now permits the positive identification of malignant mesothelioma cells in male patients.     

Keratin and epithelial membrane antigen immunoreactivity in nonneoplastic fibrous pleural lesions: implications for the diagnosis of desmoplastic mesothelioma

The histologic distinction between desmoplastic mesothelioma and reactive fibrosis and between biphasic desmoplastic mesothelioma and pleural metastases with desmoplasia can be difficult. The presence of such epithelial markers as keratin and epithelial membrane antigen (EMA) within the fibrous areas of a pleural lesion might be construed as evidence in support of the diagnosis of desmoplastic mesothelioma. To test this hypothesis ten desmoplastic mesotheliomas were studied with monoclonal antisera to keratin and EMA and compared with ten hyaline pleural plaques, 11 pleural scars, five benign localized fibrous mesotheliomas, and eight desmoplastic pleural metastases. Although the hyalinized fibrous areas within the desmoplastic mesotheliomas stained with keratin (ten of ten) and EMA (five of ten), the following reactive fibrous pleural lesions were also positive: plaques (four of ten keratin-positive, five of ten EMA-positive); scars (six of 11 keratin-positive, four of 11 EMA-positive); and fibrosis induced by metastases (six of eight keratin-positive, one of eight EMA-positive). Benign localized fibrous mesotheliomas were keratin- and EMA-negative. This study suggests that both benign and malignant fibrous pleural lesions may be of mesothelial origin and demonstrates the need to determine by histologic criteria whether the spindle cell component is benign or malignant before assessing the significance of its keratin or EMA immunoreactivity. The lack of keratin and EMA staining in benign localized fibrous mesotheliomas might be of use in distinguishing benign localized cellular fibrous mesotheliomas from sarcomatous mesotheliomas.     

Unusual intraparenchymal growth patterns of malignant pleural mesothelioma

AIMS: Malignant pleural mesothelioma is known to mimic morphologically a number of diverse reactive and neoplastic conditions. We describe three unusual intraparenchymal growth patterns of malignant mesothelioma seen in a series of 200 malignant pleural mesotheliomas. The diagnostic pitfalls associated with these findings are described and their potential medico-legal implications are highlighted. METHODS AND RESULTS: The study group comprised 200 malignant pleural mesotheliomas. In each case diagnosis was morphologically confirmed with ancillary immunohistochemistry using a broad panel of both mesothelial and epithelial markers. The patterns of intraparenchymal growth were documented and grouped as: direct subpleural; lymphangitic; and other. The 200 malignant pleural mesotheliomas comprised 118 epithelioid, 57 biphasic and 25 sarcomatoid, subtyped according to the WHO classification. Direct subpleural invasion was seen in 42 cases, lymphangitic spread in 27 cases. Other less well-defined intraparenchymal patterns included three sarcomatoid subtype malignant mesotheliomas exhibiting an intra-alveolar growth pattern mimicking epithelioid haemangioendothelioma. One epithelioid subtype malignant mesothelioma contained an intraparenchymal tumour nodule microscopically comprising lepidic spread of neoplastic cells over maintained alveolar structures mimicking bronchioloalveolar carcinoma. One epithelioid subtype malignant mesothelioma morphologically had areas in which alveoli were distended by discohesive epithelioid neoplastic cells with no interstitial invasion. The appearances mimicked desquamative interstitial pneumonia. Immunohistochemistry played an important role in the definitive diagnosis of each unusual parenchymal tumour deposit. In 126 malignant mesotheliomas no invasion of the subjacent lung parenchyma was identified. CONCLUSIONS: An awareness of the unusual parenchymal growth pattern in malignant mesothelioma is important to prevent misdiagnosis of other entities. In the medico-legal setting, the presence of epithelioid haemangioendothelioma or bronchioloalveolar carcinoma (in the absence of asbestosis) may be deemed to impact upon the patient's anticipated life expectancy and thereby would decrease the compensation settlement.     

间皮相关抗体在胸膜恶性间皮瘤和胸膜转移癌鉴别诊断中的作用

目的　探讨calretinin、CK5 / 6、mesothelialcell(MC)、CEA和vimentin在胸膜恶性间皮瘤及胸膜转移性肺腺癌中的表达及其在鉴别诊断中的作用。方法　用免疫组化EnVision二步法检测 13例胸膜恶性间皮瘤和 13例胸膜转移性肺腺癌中的calretinin、CK5 / 6、MC、CEA、vimentin的表达情况。结果　calretinin、CK5 / 6、CEA在恶性间皮瘤与胸膜转移性肺腺癌中表达差异有显著性 (P <0 0 5 )。MC、vimentin在恶性间皮瘤和胸膜转移性肺腺癌中表达差异无显著性 (P >0 0 5 )。结论　间皮相关抗体calretinin、CK5 / 6及癌抗体CEA对鉴别胸膜恶性间皮瘤及胸膜转移性肺腺癌有诊断价值。     

Malignant biphasic pleural mesothelioma metastatic to the liver diagnosed by fine-needle aspiration

As malignant pleural mesotheliomas are most often rapidly fatal, distant metastases are rarely detected. Here, we report a unique case in which the diagnosis of metastatic pleural mesothelioma was made via cytologic examination of a fine-needle aspiration (FNA) of the liver. Recognition of the cytomorphologic features inherent to mesothelioma cells on FNA material may become important for proper patient management. To the best of our knowledge, the diagnosis of malignant pleural mesothelioma metastatic to the liver made by FNA has not been previously documented.     

Cytological differential diagnosis among adenocarcinoma,epithelial mesothelioma,and reactive mesothelial cells in serous effusions by immunocytochemistry

The objective of the study is to estimate the expression of some antibodies in the metastatic adenocarcinomas, malignant epithelial mesotheliomas, and reactive mesothelial cells in serous effusions and to choose effective panel to the differential diagnosis. Totally 113 effusion cytology samples (80 pleural fluid, 30 ascitic, and 3 pericardial fluid) from 60 cases of metastatic adenocarcinoma (ACA), 18 cases of malignant epithelial mesothelioma (MM), and 35 cases of reactive mesothelium (RM) were included in this study. The cytological diagnoses of these cases were confirmed by histopathology or clinical datas. Smears and cell blocks were prepared for each case. Immunocytochemical study was performed on the cell block sections. The sensitivity of E‐cadherin, CEA, MOC‐31, and Ber‐EP4 for adenocarcinoma was 86.7%, 80%, 70%, and 76.4%, respectively. The specificity was 98.1%, 96.2%, 92.5%, and 86.8%, respectively. The sensitivity of calretinin, HBME‐1, and thrombomodulin for RM/MM was 83%, 79.2%, and 47.2% respectively. The specificity was 88.3%, 21.7%, and 70%, respectively. The expression of E‐cadherin, CEA, MOC‐31, Ber‐EP4, calretinin, and thrombomodulin showed significant difference between ACA and RM/MM (P < 0.01). The reactivity of EMA and Des showed significant difference between RM and MM (P < 0.01). In our opinion, the antibody panel that consists of E‐cadherin, CEA, calretinin, and thrombomodulin should be the best for differential diagnosis between metastatic adenocarcinomas and RM/MM in serous effusions. EMA and Des should be used to differentiate malignant epithelial mesothelioma and reactive mesothelial cells. EMA positive and Des negative favor MM, while Des positive and EMA negative favor RM. Diagn. Cytopathol. 2011.     

Malignant mesothelioma: immunohistochemistry and DNA ploidy analysis as methods to differentiate mesothelioma from benign reactive mesothelial cell proliferation and adenocarcinoma in pleural and peritoneal effusions

OBJECTIVE: To determine whether malignant mesotheliomas can be differentiated from adenocarcinomas and benign reactive mesothelial cells in pleural and peritoneal fluids using immunohistochemical analysis in conjunction with DNA ploidy analysis. DESIGN: Sixteen cases of malignant mesothelioma, including epithelial, sarcomatous, and biphasic types, were collected. DNA analysis using flow cytometry and/or image analysis was performed on paraffin-embedded tissue from 15 of the mesothelioma cases, as well as on cytospin cell preparations from samples of pleural and peritoneal fluids from cases with either cytologically proven adenocarcinoma (seven cases) or benign reactive mesothelial cells (seven cases). Immunohistochemical studies were done in 15 mesotheliomas, 5 adenocarcinomas, and 4 benign reactive mesothelial cell effusions. RESULTS: All malignant mesotheliomas tested (100%) stained positively for prekeratin, whereas stains for carcinoembryonic antigen, B72.3, Leu-M1, and Ber-EP4 were negative. Stains vimentin, epithelial membrane antigen, and CA125 were positive in 75%, 75%, and 25% of cases tested, respectively. Benign reactive mesothelial cell cases stained similarly. Adenocarcinomas were more likely to react positively with B72.3, Ber-EP4, and carcinoembryonic antigen, and negatively with vimentin. DNA analysis showed that all benign cases were diploid, while all adenocarcinomas were nondiploid. Fifty-three percent of the malignant mesotheliomas were nondiploid. Sensitivity for detection of nondiploidy was greater for image analysis than for flow cytometry (100% vs 75%). CONCLUSIONS: B72.3, Ber-EP4, carcinoembryonic antigen, and vimentin are useful immunohistochemical markers in differentiating malignant mesotheliomas from adenocarcinomas, whereas immunohistochemistry does not reliably distinguish malignant from benign hyperplastic mesothelial cells. The addition of DNA ploidy studies is useful for differentiating the latter two groups.     

Benign pleural lesions and malignant mesothelioma

Summary In a series of eighteen diffuse malignant mesotheliomas, five cases were encountered in which thoracic surgery with benign nontumorous diagnosis preceded the development of a malignant mesothelioma by several years. The morphological findings in three of these five cases are compared with the morphology of the tumor specimens and an attempt is made to recognize the earliest possible malignant features. Crowding of mesothelial cells, their variability in size and nuclear hyperchromatism are pointed out as warning signs.In relation to these findings, the histogenetic significance of predominantly fibroproliferative versus epithelial-like pleural lesions is discussed. A histogenetic classification, based on the studies of eighteen diffuse malignant mesotheliomas, two benign fibrous mesotheliomas, one pleural fibrosarcoma, and numerous pleural plaques as well as reactive mesothelial lesions, is offered. The therapeutic aspects are mentioned.     

Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas.

Definitive diagnosis of malignant mesothelioma in small specimens can be extremely difficult based on morphology alone. Homozygous deletion of 9p21, the locus harboring the p16 gene, has been reported as the most common genetic alteration in malignant mesotheliomas. Recent studies demonstrated that this alteration may be useful for differentiating benign from malignant mesothelial proliferations in cytology specimens. The aim of this study was to evaluate the diagnostic utility of homozygous deletion of 9p21 assessed by fluorescence in situ hybridization (FISH) in mesothelial proliferations involving serosal surfaces in paraffin-embedded tissue. p16 protein immunoexpression was also explored as a potential diagnostic aid. FISH analysis demonstrated homozygous deletion of the 9p21 locus in 35 of 52 cases (67%) of pleural mesothelioma and in 5 of 20 cases of peritoneal mesothelioma (25%) (P<0.005). None of 40 cases of reactive pleural mesothelial proliferations showed p16 deletion (P<0.005). Loss of immunoexpression of p16 was observed in 71% of the peritoneal mesotheliomas, 40% of the pleural malignant mesotheliomas and 15% of the reactive mesothelial cells. Homozygous deletion did not correlate with p16 protein expression in any of the studied groups. Our study suggests that 9p21 homozygous deletion assessed by FISH on paraffin-embedded tissue may be helpful for differentiating between malignant mesotheliomas and reactive mesothelial proliferations. A discrepancy between p16 protein expression and homozygous deletion suggests that other molecular mechanisms may play a role in p16 protein expression in mesothelial proliferations.     

Immunohistochemical distinction of malignant mesothelioma from pulmonary adenocarcinoma with anti-surfactant apoprotein, anti-Lewisa, and anti-Tn antibodies

Nine cases of malignant mesothelioma of pure epithelial and biphasic types (five pleural, three peritoneal, and one pericardial mesotheliomas), seven cases of benign adenomatoid tumor of the uterus, and 21 cases of peripheral pulmonary adenocarcinoma of non-mucus-producing type were examined immunohistochemically for expression of keratin, vimentin, carcinoembryonic antigen (CEA), surfactant apoprotein, Lewis blood group antigens, and Tn antigen. The majority (78%) of the malignant mesotheliomas expressed keratin, but CEA and surfactant apoprotein were not detected in any mesotheliomas. On the other hand, pulmonary adenocarcinomas expressed not only keratin (100%), but also CEA (62%) and surfactant apoprotein (62%). The expression of Lewisa blood group antigen and Tn antigen was detected in 76% and 62% of the pulmonary adenocarcinomas, respectively, but only one mesothelioma was stained for Lewisa antigen. This study reveals that the majority of malignant mesotheliomas can be distinguished from pulmonary adenocarcinomas by immunohistochemcial staining for CEA, surfactant apoprotein, Lewisa antigen, and Tn antigen. Immunohistochemically, adenomatoid tumors behaved similarly to malignant mesotheliomas.     

Expression of cytokeratin 5/6 in epithelial neoplasms: an immunohistochemical study of 509 cases.

Cytokeratin 5/6 (CK 5/6) immunoreactivity has been observed in the vast majority of cases of malignant mesothelioma but only rarely in pulmonary adenocarcinomas. Thus, CK 5/6 has been used to distinguish malignant mesothelioma from pulmonary adenocarcinoma. However, the utility of CK 5/6 in distinguishing pleural malignant mesothelioma from pleural metastases from nonpulmonary adenocarcinoma, as well as peritoneal malignant mesothelioma from peritoneal metastatic adenocarcinoma, has not yet been adequately addressed because the tissue expression of CK 5/6 in nonpulmonary neoplasms has not been well defined. We have studied the CK 5/6 expression in 509 cases of various epithelial tumors by immunohistochemistry. We found that the vast majority of cases of squamous cell carcinoma, basal cell carcinoma, thymoma, salivary gland tumor, and biphasic malignant mesothelioma were positive for CK 5/6. In addition, CK 5/6 immunoreactivity was detected in 15 of 24 cases (62%) of transitional cell carcinoma, in 5 of 10 cases (50%) of endometrial adenocarcinoma, in about one third of cases of pancreatic adenocarcinoma (38%) and breast adenocarcinoma (31%), and in one quarter of cases of ovarian adenocarcinomas (25%). Our study confirms the diagnostic utility of CK 5/6 immunohistochemistry in distinguishing biphasic mesothelioma from pulmonary adenocarcinoma but raises caution about its use for the differential diagnosis of pleural or peritoneal malignant mesothelioma versus pleural or peritoneal metastatic nonpulmonary adenocarcinoma, because many types of nonpulmonary adenocarcinomas may be positive for CK 5/6.     

Assessment of cell cycle state may facilitate the histopathological diagnosis of malignant mesothelioma

AIMS: The differentiation of benign pleural conditions from malignant mesothelioma may be difficult, especially with a small biopsy. We have tested the hypothesis that assessment of the cell cycle status is of value in the histopathological diagnosis of such biopsies, by comparing 33 malignant mesotheliomas with 36 cases of reactive mesothelial hyperplasia and reactive pleural fibrosis. METHODS AND RESULTS: Biopsies were investigated for proliferative status by immunostaining for a novel antibody, MCM2, all of which showed nuclear expression of MCM2 at higher frequency than Ki67 (P < 0.0001). Counts in areas of maximum tumour staining showed significantly higher labelling indices (LIMax) in epithelioid and sarcomatoid mesotheliomas compared with reactive mesothelial hyperplasia and reactive pleural fibrosis (P < 0.0001 for both). Average counts (LIAve) revealed a significant increase in epithelioid mesothelioma compared with reactive mesothelial hyperplasia (P < 0.0001). CONCLUSION: We consider MCM2 to be a useful adjunct in the differential diagnosis of malignant mesothelioma.     

Differences in lectin binding of malignant pleural mesothelioma and adenocarcinoma of the lung.

In order to differentiate between malignant pleural mesothelioma and adenocarcinoma of the lung, the glycoconjugate profiles of 6 reactive mesothelial lesions, 23 mesotheliomas (17 epithelial, 1 desmoplastic, 2 biphasic, and 3 fibrous types), and 28 well-differentiated pulmonary adenocarcinomas were evaluated with the use of 8 lectins in addition to anti-carcinoembryonic, anti-keratin and anti-epithelial membrane antigen. Formalin-fixed, paraffin-embedded tissues were stained with the avidin-biotin peroxidase complex method. Reactions of wheat germ (WGA) and peanut (PNA) agglutinin with neuraminidase treatment lectins were positive in 5 of 6 (83%) and 3 of 6 (50%) cases, respectively, in reactive mesothelial lesions. Thirteen of 23 (57%) malignant mesotheliomas of the pleura showed a positive reaction for WGA and PNA with neuraminidase treatment; other lectins were low-positive, below 9%. In contrast, pulmonary adenocarcinomas showed positive reactions in 27 of 28 cases (96%) for PNA, 26 of 28 (93%) for Ricinus communis (RCA-I), 25 of 28 (89%) for WGA, and 22 of 28 (79%) for succinylated WGA (SucWGA). The findings suggest that malignant pleural mesothelioma and pulmonary adenocarcinoma have consistent and distinct glycoconjugate profiles, and that stains for RCA-I and SucWGA may be useful for differential diagnosis.     

The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas

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.     

CD44H expression in reactive mesothelium, pleural mesothelioma and pulmonary adenocarcinoma

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.     

Immunocytochemical typification of mesothelial cells in effusions: In vivo and in vitro models

We have performed immunocytochemical, immunoelectron microscopy. Western blot, and culture techniques using monoclonal antibodies against cytokeratin, vimentin, and desmin on 17 benign and 20 malignant effusions of pleural and ascitic origin. Triple coexpression of these three antigens was observed in benign reactive mesothelial cells as well as in one case of mesothelioma. All metastatic adenocarcinoma cells were consistently negative to desmin and positive to cytokeratin and vimentin. Present results were helpful to distinguish reactive and malignant mesothelioma from metastatic carcinoma cells in effusions. © 1994 Wiley-Liss, Inc.     

Immunohistological study of malignant diffuse mesotheliomas of the pleura

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.     

HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of pleura.

AIMS: To determine the usefulness of antibodies HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of the pleura. METHODS: Using microwave antigen retrieval and streptavidin-biotin complex horseradish peroxidase immunohistochemistry the above antibodies were used to stain sections of 57 malignant mesotheliomas, 17 reactive pleural hyperplasias, 23 cases of carcinoma metastatic in pleura, 20 primary ovarian cell carcinomas, and 20 primary renal cell carcinomas. RESULTS: Eighty six per cent of mesotheliomas and 82% of reactive mesothelial hyperplasias stained strongly with HBME-1. However, 48% of carcinomas metastatic to pleura also stained, as did all serous ovarian carcinomas. Seventy two per cent of mesotheliomas and 24% of reactive mesothelial hyperplasias stained strongly with the antithrombomodulin antibody; 86% and 88%, respectively, of these cases showed staining of any type. While 26% of metastatic carcinomas showed some staining with antithrombomodulin, only one third of these (9%) showed strong, yet focal, staining. Of 40 ovarian and renal carcinomas only two (5%) showed any staining with antithrombomodulin. CONCLUSIONS: HBME-1, although a sensitive mesothelial marker, is not sufficiently specific to be useful diagnostically, as almost half of carcinomas metastatic to pleura also stained positive. Antithrombomodulin is also a sensitive mesothelial marker and is sufficiently specific to be a useful discriminator, positively identifying, in appropriate circumstances, the mesothelial nature of a cell population.