Case Report
Long-term Treatment With Sequential Molecular Targeted Therapy for Xp11.2 Translocation Renal Cell Carcinoma: A Case Report and Review of the Literature

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Introduction

Xp11.2 translocation renal cell carcinoma (RCC) is now accepted as a distinctive entity in the 2004 World Health Organization's renal tumor classification. Xp11.2 translocation results in gene fusions involving the transcription factor E3 (TFE3) transcription factor gene. RCC is rare in children, comprising only 2% to 6% of all pediatric primary renal tumors.1 Of these, translocation-associated RCCs account for 20% to 40% of pediatric RCCs.2 Whereas Xp11.2 translocation RCCs are typically considered a pediatric malignancy, its frequency in the adult population is conversely very low (1.6%).3 Meanwhile, adult onset Xp11.2 translocation RCC is associated with a very high malignant aggressiveness, whereas pediatric onset Xp11.2 translocation RCC shows a relatively good clinical course.4 Because of the rarity of Xp11.2 translocation RCCs, the prognosis and outcome in these patients are not fully understood. In addition, for the same reasons, there is currently no standard treatment strategy for this malignancy.

We report a rare case involving an adult patient who achieved a relatively long survival period by means of multimodality treatment, including molecular targeted therapy, for recurrent Xp11.2 translocation RCC. Moreover, we review the literature on previous cases treated with molecular targeted therapy.

Section snippets

Case

We present a case involving a 23-year-old man referred to the Department of Urology from the Pediatric Surgery Department of our hospital because of a resected retroperitoneal lymph node metastasis specimen diagnosed as recurrent RCC associated with Xp11.2 translocations/TFE3 gene fusions, alveolar soft part sarcoma chromosome region, candidate 1/alveolar soft part sarcoma locus (ASPSCR1/ASPL)-TFE3.

At age 9 years, he had been diagnosed with left RCC with hilar lymph node metastases, and the

Discussion

Renal cell carcinoma is a common urological malignancy with a high frequency of invasion and metastasis at the time of diagnosis; however, it is relatively rare in children. Xp11.2 translocation RCC usually occurs in young patients; it accounts for approximately one-third of pediatric RCCs and 15% of RCCs in patients aged younger than 45 years.3 In contrast to conventional RCC, the appropriate treatment strategies for Xp11 translocation RCC remain unclear, because the natural course of this

Conclusion

In the present case, molecular targeted agents were found to be useful and effective therapeutic tools for Xp11.2 translocation RCC. Especially, multimodality therapy, including an mTOR inhibitor, might result in prolonged survival in patients with advanced disease.

Disclosure

The authors have stated that they have no conflicts of interest.

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      Prior reports from the literature suggest that mTOR inhibitors might be effective for Xp11.2 tRCC.11,20 Previous studies had demonstrated enrichment of transcriptional pathways involved in PI3K/ATK/mTOR in some subtypes of Xp11.2 tRCC,19,26 TFE3 gene fusion upregulated the mesenchymal epithelial transition tyrosine kinase receptor, consequently leading to the activation of the mTOR pathways, Moreover, overexpression of phosphorylated S6, a marker of elevated mTOR pathway activation, was reported in cases with long response to mTOR inhibitors.11 However, in our study, all the 5 patients who received everolimus-contained regimens had experienced progress in the 1st 3 month.

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      Therefore, the actual incidence of the late onset Xp11.2 translocation RCC might be higher than reported in the current literature. Because there is a general agreement that Xp11.2 translocation RCC is associated with a high malignant potential and poor prognosis,23 not only pathologists but also surgeons should try to identify more actively and treat more aggressively. This was a retrospective study with the limitations of a relatively small number of cases and short follow-up periods.

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