Allen R. Gibbs

Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms.

Aims

Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma

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.

Primary malignant gonadal mesotheliomas and asbestos

Aims:u2003

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.

Three decades of experience in the surgical multi-modality management of pleural mesothelioma

BACKGROUNDnOptimal management of diffuse malignant pleural mesothelioma (DMPM) remains unclear. We report our 30-year surgical experience with DMPM with emphasis on surgical procedure and post-operative adjuvant therapy.nnnMETHODSnDuring the period of the study, 217 patients with DMPM were referred for surgical opinion. Patients who only had pleural biopsies were excluded (n=78). Consecutive patients who underwent surgical treatment were included (n=139). Surgical options were extra-pleural pneumonectomy (EPP) for Butchart stage I disease in clinically fit patients (n=49) or pleurectomy/decortication in patients who were either not fit for EPP or had advanced disease (Butchart stage II and III) or both (n=90). Post-operative adjuvant therapy included either chemotherapy, radiotherapy, both or none.nnnRESULTSnThe median follow-up was 10.0 months. The longest survival (median 26.0 months, IQR: 11.14-40.9 months) occurred in the pleurectomy/decortication group who received both post-operative chemotherapy and radiotherapy (n=24) (p<0.001). EPP whether or not combined with adjuvant therapy provided no significant survival advantage in comparison to pleurectomy/decortication (overall median survival 10.3 months vs 10.1 months, p=0.09). On univariate analysis, pleurectomy/decortication combined with chemotherapy and radiotherapy was the strongest predictor of prolonged survival (Hazard Ratio=3.6). Multivariate analysis with the inclusion of histological type, surgical procedure and type of adjuvant therapy, EPP without adjuvant therapy was an independent risk-factor for decreased survival (Hazard Ratio=9.2).nnnCONCLUSIONSnIn this series, cytoreductive surgery combined with post-operative adjuvant therapy provided better survival despite either advanced disease or surgically less fit patients. Thus, pleurectomy/decortication may be the procedure of choice, given that neither surgical procedure (EPP or PD) is not curative.

A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu‐M1, Ber EP4, Tamm‐Horsfall protein and thrombomodulin

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 mesotheliomas. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulopapillary 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, thromobomodulin 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.

A Rare Case of Primary Pleomorphic Adenoma in Main Bronchus

Primary pleomorphic adenoma of the lung is a rare occurrence. Clinical suspicion is normally low due to its rarity. We describe a case of a primary pleomorphic adenoma arising from the origin of the right main bronchus and include our management strategy.

Usual interstitial pneumonia in asbestos‐exposed cohorts – concurrent idiopathic pulmonary fibrosis or atypical asbestosis?

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