Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion

Abstract

The World Health Organization 2016 edition assigned anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) as an emerging renal tumor entity. Identifying ALK-RCC is important because ALK inhibitors have been shown to be effective in treatment. Here, we report the case of a 14-year-old young man with ALK-RCC. Computed tomography revealed a well-demarcated 5.3-cm enhancing mass at the upper pole of the left kidney. There was no further history or symptoms of the sickle-cell trait. The patient underwent left radical nephrectomy. Pathologically, the mass was diagnosed as an unclassified RCC. Targeted next-generation sequencing identified a TPM3-ALK fusion gene. The present report and literature review demonstrate that TPM3-ALK RCC may be associated with distinct clinicopathological features. Microscopically, the tumors showed diffuse growth and tubulocystic changes with inflammatory cell infiltration. Tumor cells were dis-cohesive and epithelioid with abundant eosinophilic cytoplasm and cytoplasmic vacuoles. If morphological features and TFE3 expression are present in adolescent and young patients, molecular tests for ALK translocation should be performed. This awareness is critically important, because ALK rearrangement confers sensitivity to ALK inhibitors.

ALK-rearranged Renal Cell Carcinoma (RCC): A Report of 2 Cases and Review of the Literature Emphasizing the Distinction Between VCL-ALK and Non-VCL-ALK RCC

“…Since then, 3 additional VCL-ALK cases have been reported. [3][4][5] In addition, there have been multiple case reports and small case series describing ALK-rearranged RCCs with fusion partners besides VCL, including TPM3, EML4, STRN, etc [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ; these RCCs occurred mostly in adults without sickle cell trait. Herein, we present 2 previously unreported cases of ALK-rearranged RCC-1 with a VCL-ALK fusion and the other with an EML4-ALK fusion-which further support the distinctive clinicopathologic features of the VCL-ALK RCCs.…”

Anaplastic Lymphoma Kinase (ALK) Translocation Re-arrangement Renal Cell Carcinomas: A Review and Update of the Literature

“…It has been iterated that ALK re-arrangement is oncogenic which does activate cellular signalling pathways by dimerization through the specific structures of fusion partners [2]. It has been stated that genetic alterations within ALK has been found in various tumours [3]. The World Health Organization (WHO) 2016 edition assigned anaplastic lymphoma kinase (ALK) re-arrangement-associated renal cell carcinoma (ALK-RCC) as an emerging kidney tumour entity [3].…”

“…It has been stated that genetic alterations within ALK has been found in various tumours [3]. The World Health Organization (WHO) 2016 edition assigned anaplastic lymphoma kinase (ALK) re-arrangement-associated renal cell carcinoma (ALK-RCC) as an emerging kidney tumour entity [3]. It has been iterated that the identification of ALK-RCC is important or pertinent in that ALK inhibitors have been demonstrated to be effective with regard to treatment of ALK re-arrangement renal cell carcinoma.…”

“…It has been iterated that the identification of ALK-RCC is important or pertinent in that ALK inhibitors have been demonstrated to be effective with regard to treatment of ALK re-arrangement renal cell carcinoma. [3]. It had been iterated that up to March 2020, 28 cases of ALK-RCC had been reported and six partner genes had been confirmed within the tumour [3], [4] [5] [6] [7].…”

“…[3]. It had been iterated that up to March 2020, 28 cases of ALK-RCC had been reported and six partner genes had been confirmed within the tumour [3], [4] [5] [6] [7]. It has been iterated that the recognition of ALK alterations within neoplasms is important in view of the potential benefit of ALK inhibitors.…”