Pulmonary adenocarcinomas: a single-centre validation study of the clinical and prognostic utility of the WHO/ IASLC subtype classification

Objective: Adenocarcinoma is the most frequently reported histological subtype of lung carcinoma in many series as well as the most histologically variable and heterogeneous form. A WHO/IASLC classification of pulmonary adenocarcinomas was proposed in 2004 suggesting clinical and prognostic implications for the different subtypes. The aim of the present study was to analyze our patient population of resected patients with adenocarcinoma according to the WHO/IASLC classification to evaluate its clinical and prognostic utility Methods: From January 2004 to October 2008 a total of 277 patients received curative resection of primary lung adenocarcinoma at our Institution. There were 191 men (69%) and 86 women (31%) with a mean age of 65 years (range 42-82 years). The tumours were classified according to the 2004 WHO/IASLC classification into: acinar adenocarcinomas (AC), papillary/micropapillary adenocarcinomas (PAP), bronchiolo-alveolar carcinomas (BAC), and solid adenocarcinomas with mucin production (SOL). Adenocarcinomas with mixed subtypes were reclassified according to the most prevalent histotype. Prevalence, correlations and survival analysis both univariate and multivariate using some clinico-pathological variables (age, microscopic vascular invasion, grading, perineural invasion, tumourinfiltrating lymphocytes, T, N status and pathologic Stage) were performed among the different subgroups. Results: There were 41 AC, 82 PAP ( 45 pure papillary and 37 mixed papillary/micropapillary when a >5% micropapillary component was present), 30 BAC, 15 SOL. 10 adenocarcinomas were variant subtypes, including clear cell (4), signet ring (4) and pseudosarcomatous (2) adenocarcinomas. In 99 patients the histological subtype could not be defined. BAC were significantly associated with a less microscopic vascular invasion (p=0.01), a lower grading (G1) (p=0.0001) and a lower N status (p=0.02). Acinar and solid adenocarcinomas showed no significant correlation with any clinico-pathological variable. Papillary/micropapillary adenocarcinomas were associated with a higher grading (G3) (p=0.05). 3-year survival rates for the different subtypes were: BAC, 78%; AC, 75%; SOL, 67% and PAP 62% (pure papillary 68%, mixed papillary/micropapillary 53%). The 99 undefined adenocarcinomas had a 3 year survival rate of 75%. The differences among the groups were not significant (p=0.6). In multivariate analysis, the subgroup classification was not an independent prognostic indicator (HR 1.02, 95%CI 0.84-1.23). Conclusions: In our experience, about one-third of resected pulmonary adenocarcinomas cannot be classified into subtypes using standard histopathologic techniques. The papillary/micropapillary pattern is associated with a higher dedifferentiation, and the micropapillary component confers a survival disadvantage which however was not significant in the present series. Classification of pulmonary adenocarcinomas into subtypes was not an independent prognostic factor in multivariate survival analysis. Although promising, the prognostic utility of the WHO/IASLC adenocarcinoma classification needs to be verified on a larger number of patients.