Interobserver variability in histopathologic subtyping and grading of pulmonary adenocarcinoma

The classification of lung tumors by the World Health Organization (WHO 1981) describes subtyping of adenocarcinoma of the lung (ACL) into acinar adenocarcinoma and papillary adenocarcinoma, bronchioloalveolar carcinoma, and solid carcinoma with mucus formation. Acinar and papillary adenocarcinoma may be graded as well-, moderately, or poorly differentiated. This study evaluated the interobserver variability in the subtyping and grading of ACL according to the WHO classification.

Histologic specimens from 211 patients with disease of Stages IIIa-IV were classified in a blind manner by three panelists. All available paraffin-embedded tissue blocks, including metastatic tumors, were sampled, and new slides were made for the study.

Twenty-two ACL tumors could not be assigned a subtype by Panelist 1, which left 189 tumors as the basis for additional evaluation. Overall agreement for the three panelists regarding subtypes was 41%. Nonchance agreement was evaluated by kappa statistics, which may vary between -1 in the event of agreement that is less than that expected by chance and /1 in the event of full agreement. The kappa value regarding subtypes was 0.18 (95% confidence limits, 0.14-0.23). Overall observed agreement regarding degree of differentiation was 43%, with a kappa value of 0.12 (95% confidence limits, 0.06-0.17). Histologic material was obtained by thoracotomy in a subgroup of 53 patients, and in this patient group unanimity among two or more panelists was 88% for subtyping and 100% for degree of differentiation.

The degree of agreement in subtying and grading of ACL in Stages IIIa-IV is low, suggesting that more objective criteria is needed before a prognostic impact of such variables can be assessed. The quality and quantity of material available for subtyping obviously influence the results, which is reflected in a better agreement when histologic material is obtained by thoracotomy.