Enora Vauléon

Renal cell carcinoma with TFE3 rearrangement at Xp11.2

Renal cell carcinoma with TFE3 (Transcription Factor for immunoglobulin heavy-chain enhancer 3) rearrangement at Xp11.2 is a distinct subtype manifesting an indolent clinical course in children, with recent reports suggesting a more aggressive entity in adults. This subtype is morphologically heterogeneous and can be misclassified as clear cell or papillary renal cell carcinoma (RCC). RCCs with TFE3 rearrangement account for only approximately 1% of adult RCCs and may be clinical aggressive tumor.

Herein, we describe the case of a 17-year-old woman who presented for lumbar and abdominal pain for 3 months. Abdominal CT revealed small liver lesions, retroperitoneal lymphadenopathies, lytic bone lesion L3 confirmed by the PET CT Scan.

A biopsy of a retroperitoneal lymph node revealed a clear/granular cell tumor, with psammoma calcifications with diffuse expression of CD10, focal expression of PAX8 suggesting a renal carcinoma associated with the Xp11.2 translocation/TFE3 rearrangement.

Patient was started on Sunitinib and Denosumab with a good response but one year later we documented a progressive disease so that the patient was included in a clinical trial with a VEGF inhibitor and angiopoïetin II inhibitor. Four cycles later, we documented again a progressive disease with peritoneal carcinomatosis and ascitis. Consequently, a third line therapy with nivolumab was started with good partial response but the treatment was stopped because of nivolumab induced hepatitis. The disease kept on progressing and a fourth line with Cabozantinib was prescribed and PET-FDG showed a mixed response. The patient is still receiving Cabozantinib with dose reduction due to toxicity. The natural history of renal-cell carcinoma associated with TFE3 rearrangement at Xp11.2 is not well described because the tumor type is so rare. The question is whether these patients should be treated the same way as RCCs without molecular alteration.

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