Surfactant protein A compared to thyroid transcription factor-1 in identifying metastatic tumors of lung origin in cytopathology

IntroductionDifferentiating primary tumors and metastases of lung origin from other neoplasms often cannot be done on cytomorphology alone. Immunocytochemistry using markers such as thyroid transcription factor-1 (TTF-1) is employed for this purpose. Surfactant protein A (SPA) is a glycoprotein with multiple functions in the lung. There have been limited immunohistochemical studies investigating the diagnostic role of SPA. This study aimed to determine the diagnostic utility of SPA compared with that of TTF-1 in identifying tumors of lung origin in cytology samples.Materials and methodsA total of 155 consecutive cytology specimens procured outside of the lung were analyzed, in which SPA immunohistochemistry was reported. Cases were reviewed to document final diagnoses, immunostain results (including TTF-1), and histopathology follow-up when available.ResultsCytoplasmic SPA immunoreactivity was identified primarily in metastatic lung adenocarcinomas (ADC). SPA was also positive in 3 carcinomas of gynecologic/breast origin. SPA and TTF-1 specificity and positive predictive value were high (>90%) with relatively low sensitivity and negative predictive value for identifying metastatic ADC of lung origin. A panel of SPA and TTF-1 correctly identified most (79.7%) lung metastatic adenocarcinomas.ConclusionsSPA is a useful cytoplasmic marker to confirm lung origin in metastatic nonmucinous ADC. However, SPA is limited by having low sensitivity and being negative in up to 35% of metastatic ADCs of lung origin, whereas TTF-1 exhibited better sensitivity. SPA may rarely demonstrate false immunoreactivity in a subset of gynecologic/breast carcinomas. Employing a panel of SPA and TTF-1 has better diagnostic utility than either stain alone.