title: Clinical Relevance of Different Papillary Growth Patterns of Pulmonary Adenocarcinoma.
abstract: Growth patterns of pulmonary adenocarcinoma (ADC) have high prognostic impact and are accepted as a novel classification system for this entity. However, specifically for the papillary pattern, divergent data with respect to prevalence, clinical associations, and prognostic impact have been reported. By evaluating 674 resected pulmonary ADCs containing 308 cases with a papillary component and 101 papillary predominant cases, we documented differences in the morphologic composition of papillary growth patterns and delineated 3 different types. The different types were correlated with pathologic and clinical data including survival. Type 3 papillary cases with any or predominant papillary growth were associated with extensive spread through alveolar spaces, high proliferation, higher stage, low rates of EGFR mutations, and smoking, whereas type 1 papillary tumors showed the opposite associations. The subclassification of papillary growth revealed type-specific associations for overall and disease-free survival (disease-free survival type 1: 67.1 mo, type 2: 56.8 mo, type 3: 49.9 mo, P=0.025). The presence of any papillary type 3 pattern was a predominant pattern independent predictor of worse overall survival (hazard ratio=2.5, P=0.02). For a future grading system of lung ADC, categorization of papillary growth in 1 single category might not be adequate, as this pattern contains a heterogenous mix of tumors with a divergent prognosis. We suggest that papillary pattern types should be separated to further improve the prognostic power of ADC growth pattern analysis.
authors.affiliation: *Institute of Pathology, Heidelberg University †Translational Research Unit ‡Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, Heidelberg §Institute of Pathology, Technical University Munich, Munich, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Alexander
authors.initials: A
authors.lastname: Harms
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor