Pathology Committee - International Association for the Study of Lung Cancer

IASLC Pathology Committee

Mission Statement:

To advance clinical management, education and research for the IASLC, in relation to the pathology of thoracic cancers, the functions of the IASLC Pathology Committee include:

Developing new ideas on improving the pathological classification of thoracic malignancies.
Conducting studies and developing criteria that lead to greater accuracy of tumor diagnosis by pathologists worldwide.
Developing standards and reference materials for molecular testing that are becoming necessary for personalizing patient treatment with new targeted therapies in lung cancer.

IASLC Pathology Committee 2018

Current Projects:

Adenocarcinoma grading project (A. Moreira): The purpose of this project is to create an objective system for adenocarcinoma, based on histological features. The IASLC classification of adenocarcinoma is based on the predominant pattern of growth that has been shown to be associated with prognosis. However, many other histological features of the tumors (modifiers) have also been suggested to be of prognostic value (secondary patterns of growth, nuclear grade, mitotic counts, STAS, etc.) For this project, all proposed prognostic features will be evaluated in a multicentric database contributed by members of the Pathology Committee. The parameters and/or combinations that are relevant to prognostication will serve as the basis for the grading system. The grading scheme will be tested and validated in additional datasets.

Drs. A. Moreira and P. Russell lead a working group to drive this project on histological grading. About 500 cases with outcomes were collected and evaluated for grading. The predominant pattern plus the second most predominant were best in the training and validation set, followed very closely by predominant plus worse pattern. The group tested modifiers (nuclear grade, STAS, mitotic count, cytology grade) with the two most predominant plus worse case. Results demonstrate that modifiers have no impact on the grading system. Statistical results indicate that the difference between the two most predominant plus worse case is insignificant. The group is currently working on a reproducibility study and expects to publish results around the third quarter of 2019.

Assessment of Immune-Related Biomarkers (M. Mino-Kenudson and S. Lantuejoul): The purpose of this project is to 1)understand global PD-L1 practices and identify associated issues, 2) update the recommendations on PD-L1 testing practice, 3) improve the selection of patients for treatment with PD-1/PD-L1 therapy, and 4) improve the prediction of response to anti-PD-1/PD-L1 therapy and other immunotherapies. To achieve these goals, the group is 1) collecting data from a Global Survey on Immune Biomarkers in Lung Cancer, 2) writing a white paper on PD-L1 Testing for publication around the end of 2019, 3) conducting a study for PD-L1 LDT standardization and 4) conducting a study on other predictive immune markers.

Cytology (L. Bubendorf and P. Russell): The cytology group is working on three projects. 1) Review paper on predictive ICC marker testing: The group is summarizing the current situation and challenges of IHC predictive biomarkers with an emphasis on ALK, ROS1 and PD-L1, which will be submitted for publication in February 2019. 2) Cytological criteria for subclassification of NSCLC: The goals of this project include defining specific cytological criteria to accurately determine the AC, SCC, and NSCC-NOS subtypes of NSCLC (in cell blocks and non-cell block cytology), and to evaluate the accuracy and interobserver variability among cytopathologists. Study participants are evaluating 100 cases and comparing histological and cytological features. Once results are collected (around August 2019), the group will draft a manuscript. 3) Harmonize diagnostic IHC in ethanol-fixed cytological lung cancer specimens: The goal of this project is to harmonize IHC protocols on ethanol fixed cytological specimens. This project will start after the manuscript on cytological criteria for NSCLC subtyping is drafted. The group will develop protocols for different immunostainer platforms and focus on TTF1 and p40. The group plans to complete this study around the third quarter of 2020.

Diagnostic IHC recommendations (Y. Yatabe): Immunohistochemistry (IHC) is routinely used in diagnosing lung cancer, particularly with small biopsy/cytology specimens and poorly-differentiated tumors. Currently, TTF1 and p40 staining efficiently separates adenocarcinoma and squamous cell carcinoma, respectively, even in the case of poorly-differentiated NSCLC with small biopsies and cytologic specimens. However, there are disadvantages to selecting an antibody panel, antibody clones, and interpreting the staining. The purpose of this project is to address these challenges to benefit the practicing community.

To provide some answers in response to these difficult situations, the Pathology Committee published a consensus report and web page on diagnostic IHC (please click here). The committee plans to create an atlas, diagnostic workflow recommendation cards and webinars.

Invasion and micro-staging reproducibility study on small size adenocarcinoma (E. Thunnissen, M. Noguchi): The current WHO classification of adenocarcinoma has strength, but also some weaknesses. Determination of invasion has led to variation of interpretation in daily practice. Not surprisingly, the measurement of invasion also leads to a large variation. This may partly be explained by the two-dimensional terminology of the adenocarcinoma classification. This project aims at modifying the current classification in order to obtain a better world-wide application standard.

Drs. E. Thunnissen and M. Noguchi lead a working group to perform a deeper study based on preliminary data.

Major Pathological Response to Neoadjuvant Therapies (W. Travis and S. Dacic) The purpose of this project is to a) establish recommendations for pathological processing and analysis of neoadjuvant-treated lung cancer specimens (both primary tumors and lymph node metastasis); b) standardize assessments of pathological response in primary tumors and lymph node metastasis on both IMT and chemotherapy in the context of clinical trials and standard of care practice; c) perform interobserver studies; and, d) apply image analysis approaches for response assessment. There is consideration to also include in this study immune cell infiltration analysis in lung cancer tissue specimens.

Staging of Multiple Nodules Using Molecular Tools (S. Dacic. And Teh-Ying): The purpose of this project is to 1) provide insight on the value of molecular testing for staging multiple primary tumor nodules, 2) compare diagnostic performance of different molecular testing platforms, 3) develop molecular panels to differentiate between second primaries and metastasis, 4) and compare morphologic and molecular staging in respect to patient outcomes.

Staging R Factors Working Group (A. Nicholson): Dr. Nicholson will follow up with Dr. Borczuk to coordinate future activities. The chair and committee members are discussing the possibility of starting a project on applying molecular assays for better determination of primary vs. metastasis (in cases of multiple tumors in lung cancer).