Yonsei Med J.  2020 Mar;61(3):262-266. 10.3349/ymj.2020.61.3.262.

Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion

• Woo CG
• Yun SJ
• Son SM
• Lim YH
• Lee OJ

• KMID: 2470924
• DOI: http://doi.org/10.3349/ymj.2020.61.3.262

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.

Keyword

Anaplastic lymphoma kinase; TPM3 protein; gene rearrangement; renal cell carcinoma; ALK inhibitors

MeSH Terms

Adolescent
Carcinoma, Renal Cell*
Cytoplasm
Eosinophils
Gene Rearrangement
Humans
Kidney
Lymphoma
Nephrectomy
Phosphotransferases
Vacuoles
World Health Organization
Phosphotransferases

Figure

• 

  Fig. 1 Gross findings of ALK rearrangement-associated renal cell carcinoma. (A) A well-demarcated, solid cystic mass (arrow) at the upper pole of the left kidney is observed on abdominal computed tomography. (B) The mass (arrow) is yellow-to-grey, involving the renal medulla and cortex.

• 

  Fig. 2 Microscopic findings of ALK rearrangement-associated renal cell carcinoma. (A) The tumor cells are dis-cohesive and epithelioid with abundant eosinophilic cytoplasm, cytoplasmic vacuoles, and intracytoplasmic mucin. Some tumor cells have extreme nuclear pleomorphism and multinucleated giant cells (H&E, ×400). (B) The tumor shows diffuse growth and focal tubulocystic changes (H&E, ×200). (C) Membranous and cytoplasmic ALK expression was confirmed by immunohistochemistry (×200).

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