Bronchioloalveolar carcinoma: diagnostic pitfalls and immunocytochemical contribution

Because bronchioloalveolar carcinoma (BAC) commonly displays bland cytologic appearance, there is a good potential for misinterpretation. The aim of this study was twofold: one was to identify the most reproducible cytomorphologic features to distinguish BAC from conventional lung adenocarcinoma (CLA) on fine-needle aspiration (FNA), and the other was to investigate the staining characteristics of these two variants of lung carcinoma with P53 tumor suppressor gene immunostain and their potential value in the distinction between the two entities. Cytology records of 13 histologically documented BACs was retrieved: 7 FNA, 3 bronchial washing/bronchial brushing (BW/ BB), and 3 scraping smears of surgical specimens. Two cases had both FNA and BW/BB material. Immunostains for P53 protein, carcinoembryonic antigen (CEA), and Ki67(MIB-1) monoclonal antibodies were performed on 13 BACs (FNA cell blocks and tissue) and on 11 FNA cell blocks of CLA. Cytologically, BAC showed uniform cells with abundant, lacy cytoplasm, and bland, folded nuclei arranged singly, in papillary clusters, and sheets. Immunocytochemically, one BAC and one CLA were technically unacceptable. Of the 12 remaining BAC cases, 10 were reactive with CEA, 9 reactive with Ki67 (> 5%), and 4 reactive with P53. Of the 10 remaining CLAs, 9 were positive with CEA, 9 were reactive with Ki67 (> 5%), and 8 were reactive with P53. We conclude that BAC demonstrates distinctive cytologic features, but difficulty may be encountered with well-differentiated CLA, metastatic adenocarcinoma, and other lesions. Immunocytochemically, CEA and Ki67 do not appear to be discriminate, but P53 may be of value in distinguishing BAC from CLA. Attention to subtle nuclear changes, characteristic grouping, cellular arrangement, and P53 reactivity could enable cytopathologists to accurately diagnose BAC.