[Bronchiolar-alveolar carcinoma: From concept to innovative therapeutic strategies]

Bronchioloalveolar carcinoma (BAC) is a primary pulmonary adenocarcinoma (ADC) developped from the terminal respiratory unit. Its restrictive definition adopted by the 1999 WHO pathological classification needs a complete tumor resection to exclude any signs of histological invasion. Although IIIB-IV tumors were excluded from the strict WHO definition of BAC, the first international workshop on BAC in 2004 had focussed on the need to include in the same spectrum of disease pure BAC and ADC with BAC feature (ADC-WBF). BAC and ADC-WBF affect more frequently women, non-smokers and Asian people than other non-small cell carcinoma. Their predominant lepidic and aerogenous tumor progression results in a frequent pneumonic, multifocal or diffuse presentation and explains why death is more frequently related to bilateral pulmonary involvement than extrathoracic metastasis. Natural history is slower and prognosis better than for other ADC. Within this entity, there are different cytological subtypes: mucinous, non-mucinous and mixed and according to them different clinical and biological phenotypes, with different sensitivity to therapeutic agents. At present, the diagnosis, the staging and the therapeutic strategy does not differ from that of non-small lung carcinoma cells. In localized forms, surgical resection remains the best therapeutic option for localized tumors. In diffuse forms, high frequency of epidermal growth factor receptor (EGFR) expression on tumor cells and its gene amplification and/or mutation as well as a particular sensitivity of this entity to EGFR tyrosine kinase inhibitors offer new strategy of therapeutical management in patients with non-resectable tumor. However, the place of chemotherapy has recently been revisited in this entity known until now as chemoresistant tumors. The results are being evaluated. It is necessary to continue therapeutic trials to determine criteria for choosing a first-line TKI or conventional chemotherapy in that entity. Cytological subtype will probably have an important role to play in this choice.