title: Diagnostic use of PAX8, CAIX, TTF-1, and TGB in metastatic renal cell carcinoma of the thyroid.
abstract: 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.
authors: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors: Ashley
authors: A
authors: Cimino-Mathews
authors: Rajni
authors: R
authors: Sharma
authors: George J
authors: GJ
authors: Netto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002256:Carbonic Anhydrases / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis; D012680:Sensitivity and Specificity; D013954:Thyroglobulin / Q000032:analysis; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000556:secondary*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013954:Thyroglobulin; D002256:Carbonic Anhydrases