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K. Torkko



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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-010 - Pilot Internet Survey of Interobserver Variability in Pathology Diagnoses of Multiple Tumor Nodules (ID 2851)

      09:30 - 09:30  |  Author(s): K. Torkko

      • Abstract
      • Slides

      Background:
      The distinction between separate primary lung cancers (SPLC) or intrapulmonary metastases (IM) is of great clinical importance because of the substantial staging and prognostic implications. With the broad implementation of CT screening for lung cancer, the recognition of multiple tumor nodules is increasingly common. Currently, similarities and differences in histology between two tumors provide the most definitive distinction between SPT and IM. However, the level of agreement among pathologists regarding this question has not been tested. The IASLC Pathology Committee and the Multidisciplinary SPT Working Group has addressed this issue through a pilot online survey. This study assesses the feasibility and reports preliminary results of a web-based survey to determine interobserver variation in distinguishing SPT and IM.

      Methods:
      A pilot study was conducted to test whether multiple observers could assess a collection of 50 cases of multiple tumors through a digital web-based system. Five pairs of resected nodules were assembled from the University of Colorado and scanned into an image database using an Aperio AT2 slide scanner (Leica Biosystems) with a 40X objective. Reviewers were asked to review slide images, to provide a histological diagnosis according to WHO criteria, to answer questions regarding specific histological details related to each nodule and to determine whether the multiple nodules were SPT and IM. Combined results were evaluated for level of concordance on the central question of primary or metastatic status. Results were also correlated with EGFR, KRAS, ALK and TP53 mutational status.

      Results:
      A total 21 pulmonary pathology subspecialists completed the survey, evaluating 10 nodules from 5 patients. Ten of the reviewers were from the US, 3 from Japan, 2 from the UK, and one each from Canada, France, Germany, the Netherlands, Korea and Sweden. On the question of SPLC vs IM, 10 reviewers agreed on all cases and these determinations were regarded the histological consensus. There was 85% overall concordance with the consensus diagnosis. Most of dissenting opinions related to a single case. In all but one instance, tumors from the same individual with different histological diagnoses were designated SPLC. However, in 30% of the cases, tumors from the same individual with identical histological diagnoses were determined to be SPLC. The histological attributes regardless of WHO diagnostic category that significantly (each p>0.0001) contributed to this conclusion included lepidic growth, cell size, nuclear pleomorphism and nucleolar prominence. The mutational status of these cases was in complete agreement with the histological consensus. Mutations that distinguished SPT included KRAS, EGFR or TP53 mutation in only one member of a tumor pair or different EGFR mutations in each member of a pair. In IM, identical KRAS mutation was found in both members of a tumor pair.

      Conclusion:
      In this pilot study a high level of consensus was achieved in separating SPLC vs or IM. A large minority (30%) of tumor pairs with identical histological diagnoses were determined to be SPLC suggesting that histological features beyond those used for WHO classification are taken into account when determining SPT status.

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