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28.01.2020 | Brief Report | Ausgabe 6/2020

Virchows Archiv 6/2020

ALK-rearranged renal cell carcinoma with a novel PLEKHA7-ALK translocation and metanephric adenoma-like morphology

Zeitschrift:
Virchows Archiv > Ausgabe 6/2020
Autoren:
Jen-Fan Hang, Hsiao-Jen Chung, Chin-Chen Pan
Wichtige Hinweise
A comment to this article is available online at https://​doi.​org/​10.​1007/​s00428-020-02766-z.

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Abstract

ALK-rearranged renal cell carcinoma is a provisional entity in the 2016 WHO Classification of Tumors of the Urinary System and Male Genital Organs. The reported fusion partners included VCL, TPM3, EML4, STRN, and HOOK1. Herein, we present a peculiar renal cell carcinoma morphologically resembling metanephric adenoma and harboring a novel PLEKHA7-ALK fusion. Microscopically, the tumor is composed of bland epithelial cells with scant to moderate amount of amphophilic cytoplasm, round and uniform nuclei, delicate chromatin, and inconspicuous nucleoli, arranged in tightly packed small acini and angulated tubules. Papillary formation, intraluminal glomeruloid tufts, microcysts, and solid nests were focally observed. Psammomatous calcifications were evident. The tumor cells were diffusely reactive for CK7, AMACR, PAX8, and ALK, while non-reactive for WT1, BRAF V600E, CD57, carbonic anhydrase IX, TFE3, and cathepsin K. Fluorescence in situ hybridization showed breaking apart of ALK. A novel PLEKHA7exon18-ALKexon20 fusion was detected using ArcherDX FusionPlex next-generation sequencing panel and was further confirmed with reverse-transcriptase PCR. Our case demonstrates that in contrast to prior cases showing high-grade tumor cells, ALK-rearranged renal cell carcinoma may also present as a low-grade renal tumor mimicking metanephric adenoma. Immunohistochemistry and molecular testing are helpful to identify this tumor, which may be eligible for ALK inhibitor-targeted therapy.

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