Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution

e15078 Background: Translocation renal cell carcinomas (tRCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. These neoplasms are only recently recognised and outcome data are premature. We report 2 cases of tRCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: : Approximately 70 new cases of RCC are referred to our centre annually. Recently, 2 renal cell carcinomas were suspected to be tRCCs on morphology and immunohistochemical(IHC) features (RCC+/CK7-/EMA-). Using IHC we tested for expression of TFE3 and TFEB. Results: : Both tumours were tRCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 RCC with mixed clear cell and papillary architecture. IHC for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She relapsed 9 months later with local recurrence, retroperitoneal adenopathy and lung metastases. She commenced sunitinib and response assessment is pending. The 2nd case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen. Staging CT revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. IHC for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 9 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and will also report 3 further cases suspected to be tRCCs based on morphology and IHC. Confirmatory TFE3/TFEB IHC is awaited.

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Translocation renal cell carcinomas: An evolving entity.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.472 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 472-472

Author(s):

Richard Martin Bambury ◽

Claire Brady ◽

Aoife McCarthy ◽

Stewart Fleming ◽

Nicholas J. Mayer ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Transcription Factor ◽

Cell Carcinoma ◽

Metastatic Disease ◽

Renal Cell ◽

Renal Mass ◽

Renal Cell Carcinomas ◽

Fuhrman Grade ◽

Post Surgery ◽

Disease Free

472 Background: Translocation renal cell carcinomas (RCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. As these neoplasms are only recently recognised, outcome data are premature. We report 2 cases of translocation RCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: In our recent practice, 2 renal cell carcinomas were suspected to be translocation tumours based on morphology and immunohistochemical features (RCC+/CK7-/EMA-). Using immunohistochemistry we tested for expression of TFE3 and TFEB. Results: Both tumours were translocation RCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 renal cell carcinoma with papillary architecture and eosinophillic hyaline nodules within many of the papillae. Staining for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She remains disease free 6 months post surgery. The second case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen performed after a new diagnosis of haemochromatosis. Staging CT imaging revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. Staining for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 5 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and identification of new cases to determine the clinical behaviour of these rare cancers in the Irish setting.

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