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ALK-rearranged renal cell carcinoma with TPM3::ALK gene fusion and review of the literature

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Abstract

ALK-rearranged renal cell carcinoma (ALK-RCC) is a very rare novel molecularly defined entity in the recently published fifth edition of the World Health Organization classification of tumours. We describe a case of ALK-RCC in a 76-year-old female. The tumour was composed of discohesive rhabdoid cells and pleomorphic, multinucleated cells (equivalent to ISUP/WHO grade 4). The tumour showed expression with PAX8, Keratin 7 and alpha methylacyl CoA racemase. ALK (D5F3 clone) was strongly and diffusely positive. ALK-FISH showed significant split signals of ALK, confirming the diagnosis. RNA sequencing showed TPM3::ALK rearrangement. Including the current case, there are 14 reported ALK-RCC cases with the same TPM3 fusion partner gene. Review of these published cases highlights their morphological heterogeneity and stresses the importance of running ALK immunohistochemistry on difficult cases to classify renal tumours. This is important while identification of ALK-RCC has clinical significance due to the availability of targeted therapy with ALK inhibitors.

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Acknowledgements

The authors would also like to thank Dr. Chelsee Hewitt and Mr. David Choong from the Pathology Department at Peter MacCallum Cancer Centre, Victoria, Australia, for their invaluable technical assistance with the molecular studies.

Author information

Authors and Affiliations

  1. Department of Anatomical Pathology, Melbourne Pathology, Sonic Healthcare, Private Bag 5, Collingwood, VIC, 3066, Australia

    Laurence A. Galea

  2. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, VIC, Australia

    Michael S. Hildebrand & Tom Witkowski

  3. Neuroscience Group, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC, Australia

    Michael S. Hildebrand

  4. Department of Cytogenetics, Sullivan Nicolaides Pathology, Sonic Healthcare, Brisbane, QLD, Australia

    Christopher Joy

  5. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Christopher R. McEvoy

  6. Australian Urology Associates, Malvern, Melbourne, VIC, Australia

    Uri Hanegbi

  7. Cabrini Hospital, Melbourne, VIC, Australia

    Uri Hanegbi

  8. Department of Anatomical Pathology, Cabrini Pathology, Sonic Healthcare, Melbourne, VIC, Australia

    Ahmad Aga

Authors
  1. Laurence A. Galea
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  7. Ahmad Aga
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Contributions

LAG: conception and design of the work; analysis and interpretation of the data; writing the manuscript. AA: collection, analysis, and interpretation of the data and revising the manuscript critically for important intellectual content and scientific integrity. MSH, TW, CJ, CRM: analysis and interpretation of the data and revising the manuscript critically for important intellectual content and scientific integrity. UH: collection of data and revising the manuscript critically for important intellectual content and scientific integrity. All of the authors approved the final version of the manuscript.

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Correspondence to Laurence A. Galea.

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Galea, L.A., Hildebrand, M.S., Witkowski, T. et al. ALK-rearranged renal cell carcinoma with TPM3::ALK gene fusion and review of the literature. Virchows Arch 482, 625–633 (2023). https://doi.org/10.1007/s00428-022-03451-z

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  • DOI: https://doi.org/10.1007/s00428-022-03451-z

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