Is D2-40 a useful marker for distinguishing malignant mesothelioma from pulmonary adenocarcinoma and benign mesothelial proliferations?

Since pulmonary adenocarcinomas, malignant mesotheliomas (MM), and sometimes benign mesothelial proliferations show a great histomorphological resemblance to each other, an immunohistochemical panel is usually necessary for differential diagnosis. D2-40 is an available monoclonal antibody, which is already in use as a lymphatic endothelial marker. It has also been suggested to be useful in identifying the mesothelial differentiation. The aim of this study is to compare D2-40 immunostaining in MM, pulmonary adenocarcinoma, and benign mesothelial proliferations. In this retrospective study, D2-40 immunostaining was investigated in 37 cases of MM, 36 cases of pulmonary adenocarcinoma, and 31 cases of benign mesothelial proliferation. The diagnosis of MM had previously been confirmed by a panel including calretinin, CK5/6, and CEA. Predominantly membranous immunoreactivity was observed in 51% of MMs and in 55% of benign mesothelial proliferations. All the 36 pulmonary adenocarcinomas were negative. These results were statistically significant (p<0.001). We believe that D2-40 may be helpful in the differential diagnosis of MM from pleural involvement of pulmonary adenocarcinoma.     

Sarcomatous Type of Malignant Mesothelioma

Thirteen malignant mesotheliomas of a sarcomatous type were studied by light microscopy and ten were studied by electron microscopy. The histologic patterns varied from tumor to tumor, often resembling other soft tissue sarcomas. Electron microscopic observation showed most of the tumors to be composed of primitive cells. Despite their mesenchymal character, many tumors contained foci of rudimentary epithelial differentiation. It is concluded that both histologic types of malignant mesothelioma, the epithelial as well as the sarcomatous, originate from the same precursor cell at various points of its differentiation and reflect the range of maturation from the mesenchymal reserve cell to the epithelial mesothelial cell.     

Sarcomatous Type of Malignant Mesothelioma

Thirteen malignant mesotheliomas of a sarcomatous type were studied by light microscopy and ten were studied by electron microscopy. The histologic patterns varied from tumor to tumor, often resembling other soft tissue sarcomas. Electron microscopic observation showed most of the tumors to be composed of primitive cells. Despite their mesenchymal character, many tumors contained foci of rudimentary epithelial differentiation. It is concluded that both histologic types of malignant mesothelioma, the epithelial as well as the sarcomatous, originate from the same precursor cell at various points of its differentiation and reflect the range of maturation from the mesenchymal reserve cell to the epithelial mesothelial cell.     

A morphometrically-based classification rule for the diagnosis of primary mesothelial lesions

A computer-aided morphometrical study was performed on histological specimens of reactive hyperplastic (n = 10) and malignant (n = 17) mesothelium. For each cell, seven nuclear features were measured and 13 parameters computed. Using stepwise variable selection, discriminant analysis chose the nuclear contour index, the standard deviation of the nuclear area, and the mean of the nuclear perimeter as discriminating features between hyperplastic and malignant mesothelium. The coefficients of these variables were included in a discriminant function which gave perfect discrimination between the two groups of lesions. When the function was assessed on a test set of hyperplastic (n = 10) and malignant (n = 17) mesothelial lesions treated as 'unknown', complete separation between these two diagnostic categories was achieved. This classification rule may help to increase the level of confidence with which a histological diagnosis of mesothelioma can be established.     

Cytologic diagnosis of malignant mesothelioma,with particular emphasis on the epithelial noncohesive cell type

The effusion cytologies from 21 cases of malignant mesothelioma (MM) (15 pleural, 6 peritoneal) diagnosed at the Indiana University Medical Center during 1990–1997 were reviewed. Using the classification of Tao (Acta Cytol 1979;23:209–213), 13 cases of MM were of the epithelial cohesive cell type and 8 were of the epithelial noncohesive cell type. While the epithelial cohesive cell type has been discussed in the literature, the epithelial noncohesive cell type has not. The cytomorphologic features for both types are presented with particular emphasis on the noncohesive cell type. The differential diagnosis and use of ancillary confirmatory laboratory tests are briefly discussed. Because of its resemblance to florid reactive mesothelial hyperplasia and the general lack of awareness of the existence of the single‐cell pattern of mesothelioma, this diagnosis can often be missed. Diagn. Cytopathol. 1999;20:57–62. © 1999 Wiley‐Liss, Inc.     

Anti-cytokeratin 5/6: a positive marker for epithelioid mesothelioma

Aims : Previous studies using frozen material have suggested that cytokeratin 5 is expressed by pleural mesothelioma but not by adenocarcinoma. In the present study, reactions for cytokeratins 5 and 6 were investigated in 33 pleural mesotheliomas and 27 secondary adenocarcinomas of the pleura using formalin-fixed, paraffin-embedded material and a commercially available antibody (anti-cytokeratin 5/6). Methods and results : All of the adenocarcinomas originated in the peripheral lung. The epithelioid component of the mesotheliomas gave a strongly positive reaction; the reaction in sarcomatoid or desmoplastic areas was absent or weak. Twenty-two of the adenocarcinomas were negative, in four there was a weak, equivocal reaction, and in one there was patchy positivity. Conclusions : We conclude that this antibody is potentially a useful positive marker for the identification of the epithelioid variant of mesothelioma in formalin-fixed and paraffin-embedded material.     

Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression

Histological diagnosis of malignant mesothelioma and differentiation from adenocarcinoma is often difficult. Definitive pathological confirmation of malignant mesothelioma requires demonstration of an appropriate immunohistochemical phenotype. Selection of an optimum panel of immunohistochemical antibodies for the reliable identification of malignant mesothelioma is hindered by the absence of a specific immunohistochemical label for mesothelioma cells. Recently, we have found that the ovarian carcinoma cell antibody CA125 labels malignant mesothelioma cells, and the antibody HBME-1 has been developed as a sensitive mesothelial cell marker. We have compared the immunohistochemical staining patterns achieved with CA125 and HBME-1 to those obtained using a panel of eight further antibodies in 17 malignant mesotheliomas and 14 primary and secondary adenocarcinomas within lung and pleura. CA125 labelled malignant mesothelioma cells in 15 of 17 cases (88%), and adenocarcinoma cells in seven of 14 cases (50%). HBME-1 labelled mesothelioma cells in all 17 cases (100%) but also labelled adenocarcinoma cells in 10 of 14 cases (71%). BerEP4 positively labelled one malignant mesothelioma but was negative in the remaining 16 cases and positively labelled nine of 14 adenocarcinomas (64%). Monoclonal anti-CEA, AUA-1, CA19.9 and LeuM1 labelled no malignant mesotheliomas and were positive in 10 (71%), nine (64%), eight (57%) and six (43%) of 14 cases of adenocarcinoma, respectively. Diastase-PAS staining detected neutral mucin in none of the malignant mesotheliomas but in 10 (71%) of the 14 adenocarcinomas. We conclude that CA125 and HBME-1 do not label mesothelial cells with sufficient specificity to be useful for differentiating malignant mesothelioma from adenocarcinoma, although negative staining with HBME-1 makes a diagnosis of malignant mesothelioma unlikely. As there remains an absence of a specific positive mesothelial cell marker this distinction is still most reliably made using a panel of antibodies including at least two of the following: anti-CEA, AUA-1, BerEP4, LeuM1 and CA19.9, in combination with histochemical assessment of neutral mucin production.     

Immunohistochemical evidence for mesothelial origin of paratesticular adenomatoid tumour

AIMS: To investigate the histogenesis of paratesticular adenomatoid tumour by use of immunohistochemical markers for a variety of carcinomas and mesothelioma. METHODS AND RESULTS: Immunohistochemical staining of sections from 12 cases of paratesticular adenomatoid tumour was undertaken using primary antibodies to antigens expressed by benign epithelial cells and carcinoma (cytokeratin AE1/AE3, cytokeratin 34ssE12, epithelial membrane antigen, MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1), stromal and vascular markers (vimentin, CD34, factor VIII), and mesothelioma-associated antigens (thrombomodulin, HBME-1, OC 125) and p53 protein. There was absence of immunohistochemical expression of epithelial/carcinoma markers MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1 and to factor VIII and CD34. All tumours expressed cytokeratin AE1/AE3, epithelial membrane antigen and vimentin, with weak expression of cytokeratin 34ssE12 in 25% of tumours. Each tumour showed expression of thrombomodulin, HBME-1 and OC 125 in a membranous distribution. p53 protein expression was not detected. CONCLUSIONS: The immunohistochemical profile of paratesticular adenomatoid tumour is strongly supportive of a mesothelial cell origin.     

HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma

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.     

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.