Utility of PAX-8, CD117 and CD5 in Distinguishing Thymic Carcinoma from Poorly Differentiated Lung Carcinoma
Jaya R Asirvatham, Michael J Esposito, Tawfiqul A Bhuiya. Hofstra North Shore-LIJ School of Medicine, Lake Success, NY
Background: Distinguishing thymic carcinoma from poorly differentiated lung carcinoma in a mediastinal biopsy can be challenging. PAX-8 is a nuclear transcription factor expressed during organogenesis, specific to kidney, ovary and other organs. During neoplastic transformation of the epithelium, the gene is re-expressed. PAX-8 expression has not been documented during thymic organogenesis. However, recent studies comparing PAX-8 expression in malignant and benign tissues, which included only small numbers of thymic carcinomas, reported positivity in 0-80% of thymic carcinomas. Lung carcinomas were largely negative, with positivity in few squamous carcinomas. The aim of this study was to determine if PAX-8 immunostaining can distinguish between thymic carcinoma and poorly differentiated lung carcinoma.
Design: Archived cases of proven thymic carcinoma (n=13) and poorly differentiated lung carcinoma (n=15) were analyzed for the intensity and proportion of expression of PAX-8 (nuclear), CD117 (membranous) and CD5 (membranous) with the interpreters kept blind to the diagnoses. Staining in less than 10% of cells was interpreted as negative.
Results: PAX-8 was positive in 69.2% (9/13) of thymic carcinomas and 6.6% (1/15) of lung carcinomas. The intensity varied from weak to strong granular nuclear staining in 30-100% of cells. A single lung carcinoma positive for PAX-8 had focal squamous differentiation. While CD117 was positive in 84.6% (11/13) of thymic carcinomas, a significant proportion (26.6%) of lung carcinomas was also positive. 53.8% of thymic carcinomas and none of the lung carcinomas were positive for CD5. 46.1%, 53.8% and 69.2% of thymic carcinomas were dual positive for combinations of CD5/PAX-8, CD117/CD5 and CD117/PAX-8, respectively. None of the lung carcinomas were dual positive for any of these combinations. Positivity for any two of the three markers (CD117, CD5 and PAX-8), was seen in 76.9% (10/13) of thymic carcinomas and in none of the lung carcinomas. 53.8% of thymic carcinomas were triple positive, while 15.3% of thymic carcinomas and 66.3% of lung carcinomas were triple negative.
Conclusions: PAX-8 is a sensitive marker for thymic carcinoma and is an important addition to the diagnostic panel for differentiating thymic carcinoma from poorly differentiated lung carcinoma. Adding PAX-8 to CD117 and CD5 increases the diagnostic yield for thymic carcinoma, especially when at least two of three markers are positive. However, triple negativity does not exclude the diagnosis of thymic carcinoma.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 296, Monday Morning