Xp11.2 Translocation Renal Cell Carcinoma With TFE3 Rearrangement: Distinct Morphological Features and Prognosis With Different Fusion Partners

BackgroundRenal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion is a rare and new subtype of RCC and was classified by the WHO in 2004. Since then, multiple 5′ fusion partners for TFE3 have been reported; however, the impact of individual fusion variant on specific clinicopathologic features of Xp11.2 RCCs has not been well defined.MethodsFour Xp11.2 translocation RCCs were identified by morphological, immunostaining, and fluorescence in situ hybridization (FISH) assays from 200 patients who attended Guangdong General Hospital between January 2017 and January 2020. All these four cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. The clinicopathologic features, including clinical manifestations, pathological findings, treatment strategies, clinical outcomes, and follow-up information on Xp11.2 translocation RCCs, were recorded and evaluated.ResultsThese four cases affected one male and three females. The median age was 13 years at the time of diagnosis (range = 4–20 years). All the examined tumors were unilateral and unifocal. The largest diameter of these tumors ranged from 2.0 to 10.0 cm, and the average was 5.55 cm. Regional lymph node or distant metastasis developed in two patients. Three cases demonstrated known fusions: ASPCR1–TFE3 (two cases) and PRCC–TFE3 (one case). However, one case showed an unreported VCP–TFE3 fusion gene in Xp11.2 translocation RCCs. Immunohistochemistry results revealed tumor cells diffusely positive for TFE3, but have no consistency in other markers. Moreover, there were different clinical prognoses among the different variant TFE3 rearrangements; RCC patients with VCP–TFE3 translocation had worse prognosis compared to those with other fusion types. Follow-up were available for all the patients and ranged from 3 to 36 months. Three patients were without evidence of disease progression, while that with VCP–TFE3 fusion died of the disease 3 months after the diagnosis.ConclusionIn conclusion, our data expand the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11.2 RCCs with specific TFE3 gene fusions. We identified a novel VCP–TFE3 fusion in Xp11.2 translocation RCCs for the first time, which has unique morphology and worse prognosis than those with other variant TFE3 rearrangements. Integration of morphological, immunohistochemical, and molecular methods is often necessary for the precise diagnosis and optimal clinical management of malignant tumors.

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Postoperative recurrence of adult renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion

Journal of International Medical Research ◽

10.1177/0300060517711358 ◽

2017 ◽

Vol 45 (4) ◽

pp. 1287-1296 ◽

Cited By ~ 1

Author(s):

Zhen Wang ◽

Ning Liu ◽

Weidong Gan ◽

Xiaogong Li ◽

Gutian Zhang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Gene Fusion ◽

Tnm Classification ◽

Vena Cava ◽

Postoperative Recurrence ◽

Study Cohort ◽

Xp11.2 Translocation

Objective To analyze the postoperative recurrence of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 tRCC). Methods This retrospective study was approved by the institutional review board and performed in accordance with the ethical standards established by the institution. Demographic, clinical, pathological, and follow-up data were compiled for the study cohort. Results During a mean follow-up of 41.3 months (range, 3–104 months), 8 of 34 patients with Xp11.2 tRCC were confirmed to have recurrence. Three of these patients died with poor outcomes due to a vena cava tumor embolus, and one died of distant metastasis 48 months after the initial nephrectomy during which lymph node metastasis was found. Three patients survived after cytoreduction surgery. One patient was diagnosed with lung metastasis 11 months postoperatively. Conclusions The TNM classification provides significant prognostic information for Xp11.2 tRCC. A relatively active surveillance algorithm is recommended, and cytoreduction surgery is an effective approach for recurrent Xp11.2 tRCC. Larger studies are required to more extensively investigate the recurrence of these potentially aggressive tumors.

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Renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion: an adult case report and literature review

Journal of International Medical Research ◽

10.1177/0300060520942095 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052094209

Author(s):

Yuxiong Wang ◽

Yuantao Wang ◽

Mingliang Feng ◽

Xin Lian ◽

Yongsheng Lei ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Transcription Factor ◽

Cell Carcinoma ◽

Renal Cell ◽

Gene Fusion ◽

Relevant Literature ◽

Clinical Manifestations ◽

Adult Case ◽

Xp11.2 Translocation

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/transcription factor E3 ( TFE3) gene fusion is a rare and independent subtype of RCC included in the classification of MiT (microphthalmia-associated transcriptional factor) family translocation RCC. Herein, we report an adult case of Xp11.2 translocation RCC, and review the relevant literature to improve our understanding of the pathogenesis, epidemiology, clinical manifestations, diagnosis, differential diagnosis, treatment, and other aspects of the disease.

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Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients

European Radiology ◽

10.1007/s00330-016-4421-4 ◽

2016 ◽

Vol 27 (2) ◽

pp. 543-552 ◽

Cited By ~ 7

Author(s):

Xiao Chen ◽

Qingqiang Zhu ◽

Baoxin Li ◽

Wenjing Cui ◽

Hao Zhou ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Gene Fusion ◽

Fusion Imaging ◽

Imaging Findings ◽

Xp11.2 Translocation

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MDCT Findings of Renal Cell Carcinoma Associated With Xp11.2 Translocation and TFE3 Gene Fusion and Papillary Renal Cell Carcinoma

American Journal of Roentgenology ◽

10.2214/ajr.14.12950 ◽

2015 ◽

Vol 204 (3) ◽

pp. 542-549 ◽

Cited By ~ 12

Author(s):

Sungmin Woo ◽

Sang Youn Kim ◽

Myoung Seok Lee ◽

Kyung Chul Moon ◽

See Hyung Kim ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Gene Fusion ◽

Papillary Renal Cell Carcinoma ◽

Xp11.2 Translocation

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Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: a case report and review of literature

Rare Tumors ◽

10.4081/rt.2009.e53 ◽

2009 ◽

Vol 1 (2) ◽

pp. 164-166

Author(s):

Jigarkumar Parikh ◽

Teresa Coleman ◽

Nidia Messias ◽

James Brown

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathways ◽

Renal Cell ◽

Gene Fusion ◽

Mammalian Target Of Rapamycin ◽

World Health ◽

Target Of Rapamycin ◽

Tyrosine Kinase Receptor ◽

Xp11.2 Translocation

Xp11.2 translocation renal cell carcinomas (TRCCs) are a rare family of tumors newly recognized by the World Health Organization (WHO) in 2004. These tumors result in the fusion of partner genes to the TFE3 gene located on Xp11.2. They are most common in the pediatric population, but have been recently implicated in adult renal cell carcinoma (RCC) presenting at an early age. TFE3-mediated direct transcriptional upregulation of the Met tyrosine kinase receptor triggers dramatic activation of downstream signaling pathways including the protein kinase B (Akt)/phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways. Temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR) kinase, a component of intracellular signaling pathways involved in the growth and proliferation of malignant cells. Here we present a case of a 22-year old female who has been treated with temsirolimus for her Xp11.2/ TFE3 gene fusion RCC.

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Adult-onset renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion

Medicine ◽

10.1097/md.0000000000011023 ◽

2018 ◽

Vol 97 (24) ◽

pp. e11023 ◽

Cited By ~ 1

Author(s):

Pengfeng Gong ◽

Qianfeng Zhuang ◽

Kun Wang ◽

Renfang Xu ◽

Yiming Chen ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Gene Fusion ◽

Adult Onset ◽

Xp11.2 Translocation

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Contrast-enhanced ultrasound findings of adult renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma

Cancer Imaging ◽

10.1186/s40644-019-0268-7 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Shuping Wei ◽

Fuli Tian ◽

Qiuyuan Xia ◽

Pengfei Huang ◽

Yidan Zhang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Gene Fusion ◽

Clear Cell ◽

Contrast Enhanced Ultrasound ◽

Peak Enhancement ◽

Contrast Enhanced ◽

Cystic Component ◽

Xp11.2 Translocation

Abstract Background To investigate the contrast-enhanced ultrasound (CEUS) findings of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2/TFE3) in adult patients by comparison with those of clear cell RCC (ccRCC) and papillary RCC (pRCC). Methods In total, 110 patients (110 renal masses) who underwent CEUS examinations were enrolled in this study. The cases included 18 Xp11.2/TFE3 RCCs, 60 ccRCCs and 32 pRCCs. All masses were confirmed by operative pathology. The CEUS imaging data of these patients were retrospectively analysed by two readers. The conventional US and CEUS features of Xp11.2/TFE3 RCC were compared with those of ccRCC and pRCC. Results The age of the patients with Xp11.2/TFE3 RCC ranged from 20 to 68 years, with a mean age of 38.3 ± 16.3 years and a slight female predominance. The weighted kappa value that interprets the concordance between the interobserver agreement of the US and CEUS features ranged from 0.61 to 0.89. On conventional US and CEUS imaging of Xp11.2/TFE3 RCCs, the tumours were hypoechoic (6/18, 33.3%), isoechoic (8/18, 44.4%), and hyperechoic (4/18, 22.2%). The cystic component was present in 5 cases (27.8%), calcification was present in 9 cases (50.0%), and colour flow signal was present in 7 cases (38.9%). Most cases showed simultaneous wash-in (11/18, 61.1%); the peak enhancement showed hypoenhancement (6/18, 33.3%), isoenhancement (10/18, 55.6%), and hyperenhancement (2/18, 11.1%); most cases exhibited heterogeneous enhancement (12/18, 66.7%) and fast- or simultaneous-out (16/18, 88.9%); and a pseudocapsule was present in 6 cases (33.3%). In the multivariate logistic regression analysis, calcification and lower peak enhancement were more likely to be present in Xp11.2/TFE3 RCC than in ccRCC (P < 0.05), and younger age and relatively high peak enhancement were more likely to be present in Xp11.2/TFE3 RCC than in pRCC (P < 0.05). The calcification combined peak enhancement model differentiated Xp11.2/TFE3 RCC from ccRCC, and the age combined peak enhancement model differentiated Xp11.2/TFE3 RCC from pRCC with an AUC, a sensitivity and a specificity of 0.896, 94.4% and 73.3% and 0.786, 50.0% and 100.0%, respectively. Conclusions The specific CEUS features combined with demographic information and clinical symptoms may be helpful for differentiating Xp11.2/TFE3 RCC from ccRCC and pRCC.

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Recurrence and survival following preoperative sorafenib for advanced renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.384 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 384-384

Author(s):

K. Rathmell ◽

C. L. Cowey ◽

G. Grigson ◽

C. Watkins ◽

E. Wallen ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Stage Iv ◽

Preoperative Therapy ◽

Advanced Renal Cell Carcinoma ◽

Prolonged Treatment ◽

Stage Iv Disease ◽

The Impact

384 Background: The impact of neoadjuvant or preoperative therapy in the setting of advanced renal cell carcinoma on recurrence-free or survival outcomes is not known. Methods: 28 patients with renal cell carcinoma were treated with preoperative sorafenib in a prospective pilot study (LCCC 0603). Patient files were reviewed a median of 885 days (2.42 years) following nephrectomy. Records were evaluated for 13 patients with nonmetastatic disease for development of recurrence, and for 15 patients with stage IV disease for survival. Results: For the nonmetastatic patients, only 2 patients had developed recurrent disease, one underwent metastectomy and remains in surveillance and the other is on second line systemic targeted therapy. A median recurrence-free survival has not been met after a median 2.5 years. For stage IV disease patients at a median follow up of 2.3 years, a median survival has also not been reached. Four patients are deceased, one patient is lost to follow up, and 10 remain alive. Treatments for metastatic disease included continued sorafenib, high dose interleukin-2, sunitinib, pazopanib, temsirolimus, and everolimus. Some stage IV patients have also enjoyed prolonged treatment-free intervals ranging from six months to over two years, with biopsy confirmed, but indolent disease. Conclusions: Although these data are descriptive, these observations are suggestive that preoperative therapy with sorafenib is unlikely to accelerate the growth of grossly metastatic or micrometastatic disease. Further studies are needed to determine whether preoperative therapy is valuable in improving recurrence-free or overall survival endpoints. [Table: see text]

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