Clear-cell renal cell carcinoma (ccRCC) may present with metastatic lesions in patients with a concurrent undiagnosed primary or a remote history of ccRCC. The thyroid is not uncommonly involved by metastatic ccRCC, in which a metastasis could be misinterpreted as a clear-cell change in adenomatoid nodules, follicular adenomas, or parathyroid glands. PAX8 is a transcription factor expressed by thyroid and renal-lineage cells. No previous study has evaluated the diagnostic use of PAX8 and ccRCC marker carbonic anhydrase IX (CAIX) in this setting. Cases of metastatic ccRCC in the thyroid (n=12), parathyroid glands and adenomas with clear-cell change (n=6), papillary thyroid carcinoma (n=6), thyroid follicular adenomas (n=5), and adenomatoid nodules with clear-cell change (n=5) were studied. Cases were assessed by standard immunohistochemistry for thyroid transcription factor-1 (TTF-1), thyroglobulin (TGB), PAX8, and CAIX. The extent and intensity of nuclear or cytoplasmic immunoexpression were assessed, with any labeling considered as a positive result. All metastatic ccRCCs were positive for PAX8 (moderate-to-strong, patchy-to-diffuse) and CAIX (strong, diffuse), and were negative for TTF-1 and TGB. All primary thyroid lesions labeled strongly and diffusely for TTF-1, TGB, and PAX8, and were negative for CAIX. Parathyroid tissues were negative for TTF-1, TGB, PAX8, and CAIX. An immunoprofile of “TTF1(−)/TGB(−)/CAIX(+)” was 100% sensitive and specific for metastatic ccRCC of the thyroid. The reverse profile “TTF1(+)/TGB(+)/CAIX(−)” supported a primary thyroid lesion. PAX8 was not useful in distinguishing metastatic ccRCC from thyroid lesions.
Departments of *Pathology
‡Oncology, The Johns Hopkins Hospital, Baltimore, MD
Funding Sources: Brady Urologic Institute at the Johns Hopkins Hospital, Patana Gift Fund.
Presented in part at the United States and Canadian Academy of Pathology (USCAP) Annual meeting, San Antonio, March 2, 2011.
Correspondence: George J. Netto, MD, Department of Pathology, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287 (e-mail: firstname.lastname@example.org).