Pathologic review of the Mayo Lung Project

Abstract

BACKGROUNDIn the Mayo Lung Project Screening Trial, there were more carcinomas identified in the screened group compared with the control group. The screened group had better survival, but there was no difference in lung carcinoma mortality between the screened group and the control group. The purpose of this study was to review all available original pathology from the trial to determine whether overdiagnosis (carcinomas that do not result in the death of the patient) or misdiagnosis of lung carcinoma may explain this discrepancy.METHODSAll available lung pathology slides from patients who underwent surgery at the Mayo Clinic were reviewed independently by three blinded lung pathologists. Tumors were classified according to the 1999 World Health Organization criteria. In addition, agreement among the pathologists was assessed.RESULTSAmong 106 patients who underwent surgery at the Mayo Clinic, slides were available for review from 105 patients, including 77 slides from the screened group and 28 slides from the control group. The original diagnosis of carcinoma was confirmed in all patients. In 7 patients (6.7%), there was unanimous agreement that the lesion was preinvasive (carcinoma in situ), and these lesions all were from the screened group. In 90 patients (85.5%), there was unanimous agreement that the tumors were invasive. In 8 patients (7.8%), there was some disagreement between the observers about whether lesions were invasive or preinvasive; 7 of these 8 lesions were from the screened group. The level of agreement among pathologists for invasive carcinomas was > 94% for all comparisons, and the κ statistic ranged from 0.67 (substantial agreement) to 0.84 (almost perfect agreement). There was good agreement among the pathologists about tumor cell type with the κ statistic ≥ 0.65.CONCLUSIONSThe histologic diagnosis of carcinoma was confirmed for all 105 slides that were reviewed. The results of this study indicate that misdiagnosis does not explain the increased numbers of carcinomas identified in the screened group. The increased numbers of in situ carcinomas in the screened group resulted in increased numbers of squamous carcinomas in the screened group compared with the control group and may have contributed to the better survival. It is possible that carcinoma in situ accounted for some instances of overdiagnosis. Cancer 2002;95:2361–5. © 2002 American Cancer Society.DOI 10.1002/cncr.10930

Validation of Interobserver Agreement in Lung Cancer Assessment: Hematoxylin-Eosin Diagnostic Reproducibility for Non–Small Cell Lung Cancer: The 2004 World Health Organization Classification and Therapeutically Relevant Subsets

“…The low κ for 44DC is not surprising because many of these diagnoses would not be made in practice without ancillary stains. Our 10DC IOR results appear similar in magnitude to studies of prior versions of the classification, 12,13,15,16,18–22,24 but direct comparison to historic studies is limited because the most methodologically similar study 12,13 used bronchial biopsies rather than resection specimens. Additionally, other studies used glass slides and simplified the classification system into major diagnostic categories rather than using the comprehensive diagnostic listings.…”

“…Other IOR studies 14,15,18,19,22 are not directly comparable to the current study because they mix H&E-only diagnoses with diagnoses using both H&E and mucin stains. Employing the 1999 WHO classification, Colby et al 16 found dominant cell–type agreement in 74% to 82% of NSCLC/small cell lung cancer cases, with an overall κ of 0.65 to 0.74. No published IOR studies were found with the 2004-WHO classifications.…”

Early Detection of Lung Cancer

“…A pathology review of all cases diagnosed by the Mayo Lung Project (MLP) with the aim of assessing the relevance of overdiagnosis proved that carcinoma in situ only accounted for 7–15% of all lung cancers, and was generally due to sputum cytology examination [68]. The high prevalence of well-differentiated adenocarcinomas in early detection studies using spiral CT, compared to standard clinical series or registry data, is another argument believed to support overdiagnosis.…”

Modeling excess lung cancer risk among screened arm participants in the Mayo Lung Project

“…Overdiagnosis occurs in the event that, through early detection, a disease state is identified, which does not shorten the patient’s life expectancy. However, a pathologic review of cases detected in the MLP confirmed the histologic diagnosis of cancer in all cases it studied although a higher rate of carcinoma in situ detected in the screening arm was noted9. Other studies indicate that the power of the MLP may have been lower than initially planned, and that the initial findings of the MLP were not inconsistent with a model of moderately aggressive tumor progression and a modest mortality benefit10,11.…”