Comment on the paper ‘Boffetta et al. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy. Ann Oncol 2018; 29(2): 484–489’
Authors: D. Consonni, C. Mensi
Journal: Annals of Oncology (2018)

In a recent paper on diagnostic evaluation of 127 deaths from pleural or peritoneal cancers (or malignant mesotheliomas, MM) among workers in an asbestos textile factory in Piedmont, Italy, sensitivity and specificity of the Regional Mesothelioma Registry of Piedmont (RMRP) were calculated [1.Boffetta P. Righi L. Ciocan C. et al.Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.Ann Oncol. 2018; 29: 484-489Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. We argue that those calculations are incorrect. For 35 cases, pathology samples were retrieved and MM diagnosis confirmed by morphological and immuno-histological (IHC) revision. A total of 76 cases were also listed in the RMRP (56 certain, 19 probable/possible and 1 non-MM). The RMRP, established in 1993, is part of a national mesothelioma registry (ReNaM, Registro Nazionale Mesoteliomi) organized as a network of regional registries which follow the same procedures for classifying the available diagnostic evidence [2.Marinaccio A. Binazzi A. Bonafede M. et al.Il Registro Nazionale dei Mesoteliomi. Quinto rapporto. INAIL, Rome2015Google Scholar, 3.Marinaccio A. Binazzi A. Bonafede M. et al.Epidemiology of malignant mesothelioma in Italy: surveillance systems, territorial clusters and occupations involved.J Thorac Dis. 2018; 10: S221-S227Crossref PubMed Scopus (11) Google Scholar]. The authors crossed RMRP information with their revised diagnoses, and stated: ‘If we consider our diagnostic validation as gold standard, the sensitivity of the classification of the Registry (certain confirmed mesothelioma versus other) was 83% and the specificity 34% (results not shown in detail)’ [1.Boffetta P. Righi L. Ciocan C. et al.Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.Ann Oncol. 2018; 29: 484-489Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar, p. 486]. The latter finding, if true, would be of major concern, implying 66% of false positives in the RMRP. Based on figures in the paper [1.Boffetta P. Righi L. Ciocan C. et al.Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.Ann Oncol. 2018; 29: 484-489Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar, p. 486], we reconstructed Table 1, which compares revised and RMRP diagnoses. Considering all MM, including probable and possible MM (main ReNaM statistics are based on all cases), sensitivity is (29 + 6)/35 = 100%. The two central columns are not informative, because no diagnostic validation was performed; considering all those cases as ‘non-MM’, considering that RMRP classified 40 (= 27 + 13) as MM, is an evident mistake [1.Boffetta P. Righi L. Ciocan C. et al.Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.Ann Oncol. 2018; 29: 484-489Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. Strictly speaking, also the fourth column cannot be used in calculating specificity (the five non-MM cases did not undergo diagnostic revision). However, given that three were epithelial cancers, one was a non-neoplastic disease, and one had been classified as non-MM by the RMRP, it is plausible that IHC would have confirmed them as ‘true non-MM’. In this case, specificity would be (1 + 4)/5 = 100%. The four cases missing in the RMRP must be counted as non-MM, because they are not the target of MM registries (although some of them may be recorded because suspected diagnoses were scrutinized). Reasons for the high number of missing cases in the RMRP are: (i) death before 1993 (31 cases), (ii) MM diagnosed in workers emigrated outside Piedmont (no information available) and (iii) diagnosis of non-MM (no information available except for the four cases noted above).Table 1Comparison of revised and Regional Mesothelioma Registry of Piedmont (RMRP) diagnoses, 1963–2013Revised diagnosesRMRP diagnosesIHC- MMRecord- based MMDCO- MMNon- MMTotalCertain MM29(27)056Probable/possible MM6(13)019Non-MM00011Missing0(47)451Total3533545127Number in parenthesis refer either to the Record-based MM or to the DCO-MM column. DCO, death certificate only; IHC-MM, immunohistochemistry-confirmed malignant mesothelioma cases; MM, malignant mesothelioma. Open table in a new tab Number in parenthesis refer either to the Record-based MM or to the DCO-MM column. DCO, death certificate only; IHC-MM, immunohistochemistry-confirmed malignant mesothelioma cases; MM, malignant mesothelioma. In conclusion, contrarily to what stated in the paper [1.Boffetta P. Righi L. Ciocan C. et al.Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.Ann Oncol. 2018; 29: 484-489Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar], a high quality of the RMRP emerges from the available data. Finally, we note that the authors of the paper (on mesothelioma) have declared no conflict of interests [1.Boffetta P. Righi L. Ciocan C. et al.Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.Ann Oncol. 2018; 29: 484-489Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. This is odd, given that two of the authors in a recent paper (on mesothelioma) reported ‘consulting or advisory roles’ for four large companies and one author declared ‘other relationships’ with law offices [4.Boffetta P. Malvezzi M. Pira E. et al.International analysis of age-specific mortality rates from mesothelioma on the basis of the International Classification of Diseases, 10th Revision.J Glob Oncol. 2018; : 1-15PubMed Google Scholar]. These companies and law offices are currently involved in litigations regarding asbestos-related diseases. None declared.