Utility of PAX8 in the Diagnosis of Anaplastic Thyroid Carcinoma.
Justin A Bishop, William H Westra. The Johns Hopkins Medical Institutions, Baltimore, MD
Background: Anaplastic thyroid carcinoma (ATC) can be difficult to diagnose as these tumors do not show evidence of thyroid differentiation morphologically or immunohistochemically. Depending on the histologic variant, ATC may be confused with high grade sarcoma or poorly differentiated squamous cell carcinoma. Paired box gene 8 (PAX8) is a transcription factor expressed in the nuclei of thyroid follicular epithelium. Expression of PAX8 is retained in thyroid cancers including some ATCs. Moreover, the restricted expression of PAX8 to the thyroid and only a few tissues outside of the thyroid (e.g. kidney and female genital tract) suggests that PAX8 staining could be diagnostically useful when dealing with sarcomatoid or squamoid tumors of the neck. The purpose of this study was to determine the frequency of PAX8 staining in ATC, and to evaluate PAX8 immunohistochemistry as a means of distinguishing the squamoid variant of ATC from squamous cell carcinoma of the head neck (HNSCC).
Design: PAX8 immunohistochemistry was performed on 26 ATCs and 101 HNSCCs. Staining results of the ATCs were correlated with histologic features and status of the BRAF gene.
Results: The dominant histologic patterns of the ATCs were squamoid (n=15), giant cell/pleomorphic (n=6) and spindled (n=5). Overall, PAX8 staining was present in 21 (81%) of the ATCs. By histologic variant, PAX8 was positive in 15 of 15 (100%) squamoid ATCs, 3 of 6 (50%) giant cell/pleomorphic ATCs, and 3 of 5 (60%) spindled ATCs. ATCs arising in association with papillary carcinomas were not more likely to express PAX8 than those arising in association with follicular carcinomas (88% vs 100%, p = 1). There was no correlation between PAX8 staining and activating mutations of the BRAF gene. All 101 HNSCCs were PAX8-negative.
Conclusions: PAX8 expression is retained in the majority of ATCs including the squamoid variant, but PAX8 is not expressed in HNSCC of mucosal origin. In effect, PAX8 staining is an excellent marker for carcinomas of follicular epithelial origin, including those carcinomas that are undifferentiated in most other respects. The tissue specificity of PAX8 expression may be useful in resolving the differential diagnosis of ATC such as in the distinction between the squamoid variant of ATC and HNSCC.
Monday, February 28, 2011 8:15 AM
Platform Session: Section H 1, Monday Morning