A distinctive cytomorphological feature of interstitial pneumonia-related lung adenocarcinoma: The potential issues and solutions in practical diagnosis

Background: The cytological features of interstitial pneumonia (IP)-related lung adenocarcinoma (LADC) have not been clearly described. This study aimed to describe its cytomorphological features, uncover potential problems in practical cytological diagnosis, and provide possible solutions. Methods: Bronchial brushing cytology samples from 40 IP-related LADC cases (the IP group) and 110 control cases (LADC unrelated to IP; the non-IP group) were analyzed. All patients underwent surgery after brushing cytology, and their histopathological subtypes were determined. The authors reviewed the cytological features and focused particularly on cytoplasmic mucin production. Results: In the IP group, neoplastic cells with cytoplasmic mucin were detected at a significantly higher frequency (44.4% [8 of 18] vs. 6.3% [4 of 64]), and most of them were invasive mucinous adenocarcinomas (IMAs). Twenty-two of the 40 LADC cases in the IP group failed to be judged as "malignant/positive " (thus, they were judged to be "equivocal and/or negative "). The frequency of equivocal and/or negative judgments was 55.0% (22 of 40) in the IP group and 41.8% (46 of 110) in the non-IP group. The cytological diagnosis of IMA was difficult because it showed only slight nuclear atypia. Therefore, the authors examined the immunocytochemical expression of hepatocyte nuclear factor 4 alpha (HNF4 alpha), a diagnostic marker for IMA. As a result, four of the six cases that were judged to be equivocal in the IP group showed positive signals and could be retrospectively judged as malignant/positive. Conclusions: The cytological diagnosis of IP-related LADC may be more difficult because of the larger proportion of IMA. Immunocytochemistry for HNF4 alpha can be used to improve diagnostic confidence in IP-related LADC.