[1485] PAX8 as an Immunohistochemical Marker To Distinguish Metastatic Renal Cell Carcinoma from Hemangioblastoma

NT Beaubier, CE Keller, D Hamele-Bena, GX Tong. Columbia University Medical Center, New York, NY; Montefiore Medical Center, New York, NY

Background: Renal cell carcinoma (RCC) has a predilection for distant metastasis. Metastatic RCC (mRCC) to the brain, especially clear cell type, can be a diagnostic challenge because of the overlapping histologic features with hemangioblastoma, and the coexistence of both entities in von Hippel-Lindau syndrome. Immunohistochemistry (IHC) is often needed to make the differentiation. However, most markers currently used have variable sensitivity and specificity. PAX8 is a transcription factor expressed in both fetal and adult renal epithelial cells and is required for the early development of renal lineage cells. PAX8 has been detected in renal epithelial tumors and is postulated to be a marker for tumors of renal origin. In this study, we investigate the diagnostic utility of IHC with PAX8 in the differential diagnosis of mRCC and hemangioblastoma in the brain.
Design: Twenty mRCCs and 18 hemangioblastomas were retrieved from archived material. IHC with PAX8 was performed on paraffin embedded tissue sections with the avidin-biotin peroxidase method after antigen retrieval. Distinct nuclear staining (intensity graded from 0 to 3) is considered specific. Cases with a score of 0 or 1 are considered negative and 2 or 3 positive.
Results: All mRCCs have a confirmed history of primary RCC. The mRCCs consist of 17 clear cell variants with Fuhrman nuclear grade 2 to 3, 2 with sarcomatoid features, and 1 with rhabdoid areas. Strong, diffuse PAX8 staining was detected in all 17 clear cell variants. Although no PAX8 was detected in the sarcomatoid or rhabdoid areas of the other three mRCCs, moderate to strong PAX8 staining was noted in the clear cell areas of these cases and they were considered to be positive. Of the 18 cases of hemangioblastoma, 17 were devoid of any PAX8 staining. In one case, a few scattered cells stained weakly for PAX8 in the tumor areas; the nature of these cells is under investigation. Purkinje cells and lymphocytes were noted to be positive for PAX8. Overall, PAX8 was found to have a sensitivity of 100% and a specificity of 94.4% in detection of mRCC when compared to hemangioblastoma.
Conclusions: We find that PAX8 is expressed in mRCCs in the brain and is a highly sensitive and specific marker to distinguish RCC from hemangioblastoma with similar clear cell morphology. We suggest that PAX8 should be included in the panel of differential markers for the diagnosis of mRCC in the brain.
Category: Neuropathology

Tuesday, March 10, 2009 9:30 AM

Poster Session III # 200, Tuesday Morning