Translocation renal cell carcinomas in adults: a single-institution experience

Abstract

Translocation renal cell carcinoma is a newly recognized subtype of renal cell carcinoma (RCC) with chromosomal translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21). Xp11 translocation RCC was originally described as a pediatric neoplasm representing 20% to 40% of pediatric RCCs, with a much lower frequency in the adult population. TFEB translocation RCC is very rare, with approximately 10 cases reported in the literature. Here, we describe the clinicopathologic features of adult translocation RCC from a single institution. Using tissue microarray, immunohistochemistry, cytogenetic examination, and fluorescence in situ hybridization, we identified 6 (∼5%) cases of TFE3 translocation RCC and 1 (<1%) case of TFEB translocation RCC in 121 consecutive adult RCC cases between 2001 and 2009. Our results suggest that weak TFE3 staining of a significant proportion of RCC cases may be because of expression of the full-length TFE3 protein rather than the chimeric fusion protein resulting from chromosomal translocation.

Figure 1

Gross pictures, H&Es and IHC of Xp11 translocation RCC. (A), (B) Gross pictures from case #4 and #1, respectively. (C), (D) H&E from case #3 showed typical clear cells with papillary architecture. (E), (F) H&E from case #1 showed polygonal cells with large cytoplasmic vacuoles and eccentric nuclei (signet ring-like) with a microcystic growth pattern. (G), (H) H&E from case #5 showed a solid/syncytial growth pattern and grade 4 nuclear atypia. IHC (I) for CD10, (J) for AE1/3, (K) for Melan-A, (L) for HMB 45, and (M) for TFE3.

Figure 2

Biological meaning of weak TFE3 nuclear staining. (A), (B) an example of Strong TFE3 nuclear staining at low and high power, respectively. (C), (D) an example of weak nuclear TFE3 staining at low and high power, respectively. (E) RT-PCR results from a weak nuclear TFE3 staining case using primers for wild-type (non-translocation) and all 5 known translocation types. Only wild-type (non-translocation) TFE3 transcript was detected. (F) RT-PCR Beta-actin control results from the same sample. (G) Example of FISH results from weak TFE3 nuclear staining cases. There was no evidence of TFE3 gene rearrangement in these cases.

Figure 3

H&E and IHC of TFEB translocation RCC. (A)& (B), showing tubular and papillary architecture.. (C)&(D), showing solid growth pattern. IHC (E) for AE1/3, (F) for CD10, Please note that trapped tubule serve as internal positive control and tumor cells were completely negative for these 2 staining. (G) for Melan-A, (H) for HMB45, (I) for Vimentin and (J) for TFEB.