ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients

Abstract

Background: Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases.

Methods: We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases.

Results: One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin.

Conclusions: We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.

Keywords: ALK; Carcinoma, renal cell; Immunohistochemistry; In situ hybridization, fluorescence.

Fig. 1

Anaplastic lymphoma kinase (ALK) immunohistochemistry and fluorescence in situ hybridization. (A) Tumor cells show diffuse strong positivity for ALK in immunohistochemistry. (B) FISH analysis using dual color ALK break-apart probe shows one red, one green, and one fused signal indicating one rearranged ALK gene and one intact ALK gene.

Fig. 2

Pathologic features of renal cell carcinoma showing anaplastic lymphoma kinase (ALK) rearrangement. (A) Grossly, the tumor is a well-circumscribed, partially cystic mass. Microscopically, the tumor shows a papillary (B), tubular or solid pattern (C) with occasional foam cell collections (D).

Fig. 3

Immunohistochemical findings of renal cell carcinoma showing anaplastic lymphoma kinase (ALK) rearrangement. The tumor cells are positive for cytokeratin 7 (A), PAX-2 (B), and focal positive for CD10 (C) and negative for alpha-methylacyl-CoA racemase (D).