Pulmonary
mucin-producing
adenocarcinomas may be indistinguishable on conventional histology from a
metastasis, as thyroid transcription factor-1 (TTF-1) expression often is lacking and KRAS mutations are widely present even in extrapulmonary sites. Few data have been reported on the diagnostic role of napsin-A and
epidermal growth factor receptor (EGFR) and
anaplastic lymphoma kinase (ALK) gene alterations in this challenging differential diagnosis. Seventy-seven surgically resected cases, including 53 primary and 24 metastatic
tumors from different sites, were evaluated for napsin-A, TTF-1, and ALK by immunohistochemistry and for EGFR mutations by direct sequencing. Overall, napsin-A expression in primary lung
mucin-producing
adenocarcinomas was 36% (8% mucinous, 17%
colloid, 87.5% solid, and 100% signet ring cell) and TTF-1 expression reached an overall figure of 42% (12.5% mucinous, 33%
colloid, 87.5% solid, and 100% signet ring cell). Metastatic
mucinous adenocarcinomas did not react with napsin-A or with TTF-1. All primary and metastatic
tumors lacked EGFR mutations, while a single case of signet ring cell
lung adenocarcinoma showed ALK expression and rearrangement at fluorescent in situ hybridization analysis. Napsin-A has a lower sensitivity compared with TTF-1 in primary
mucin-producing
adenocarcinomas of the lung. However, both
antibodies have an absolute specificity, being always negative in metastatic
mucinous adenocarcinomas. EGFR mutations and ALK translocation or expression are exceedingly rare in
mucin-producing
adenocarcinomas of the lung, resulting unnecessary as diagnostic tool in this setting.