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CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients

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Abstract

Endolymphatic sac tumors (ELSTs) are rare, slowly growing temporal bone neoplasms which show a high association with von Hippel-Lindau (VHL) syndrome. The immunohistochemistry evaluation of these papillary-cystic neoplasms frequently raises the differential diagnosis with renal cell carcinoma, among other metastatic neoplasms, whether in VHL patients or not. A cohort of 26 patients with ELSTs were evaluated for histologic features, immunohistochemistry findings, and association with VHL. Standard immunohistochemistry evaluation was performed. Sixteen females and 10 males ranging in age from 10 to 69 years (mean 44; VHL mean: 32) at initial presentation, comprised the cohort of patients. Most (86%) experienced hearing changes or inner ear symptoms (vertigo, dizziness), with an average duration of symptoms for 39 months (range 2–240 months). The tumors were an average of 2.9 cm (range 0.4–8 cm), with 14 left, 11 right sided and one bilateral tumor. Nine patients had documented VHL, with 3 patients having a concurrent or subsequent clear cell renal cell carcinoma. Patients were followed an average of 6.2 years (available in 24 patients): 19 alive without disease, 7.5 years; 2 dead without disease, 1.2 years; and 3 alive with disease, 3.1 years. The neoplastic cells show the following immunohistochemistry findings: AE1/AE3, EMA, CK7, CAIX, GLUT1, VEGF: 100% of cases tested were positive; pax-8: 85% of cases positive; CD10 and RCC: 0% of cases reactive. Based on this cohort of 26 patients with ELST, 9 of whom had VHL, the strong pax-8 and CAIX should be used in conjunction with negative CD10 and RCC to help exclude a metastatic renal cell carcinoma. As CAIX is an enzyme overexpressed in hypoxia and hypoxia inducible factor is what VHL protein regulates, this is an expected, although previously unreported finding. Whether part of VHL or not, VHL mutations may be a somatic rather than germline finding in the tumors, a possible further explanation for the CAIX reaction.

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Acknowledgements

Presented at the 106th Annual Meeting of the United States and Canadian Academy of Pathology, Vancouver, British Columbia, Canada, March, 2018.

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Authors and Affiliations

  1. Southern California Permanente Medical Group, Woodland Hills, CA, USA

    Lester D. R. Thompson

  2. Emory Pathology and Laboratory Medicine, Atlanta, GA, USA

    Kelly R. Magliocca

  3. Department of Otorhinolaryngology Head and Neck Surgery and Audiology & Department of Pathology, Rigshospitalet, Copenhagen, Denmark

    Simon Andreasen

  4. Department of Pathology, Rigshospitalet, Copenhagen, Denmark

    Katlin Kiss

  5. Johns Hopkins Hospital, Baltimore, MD, USA

    Lisa Rooper

  6. University of Virginia, Charlottesville, VA, USA

    Edward Stelow

  7. Moffitt Cancer Center, Tampa, FL, USA

    Bruce M. Wenig

  8. University of Texas, Southwestern Medical Center, Dallas, TX, USA

    Justin A. Bishop

  9. Department of Pathology, Woodland Hills Medical Center, Southern California Permanente Medical Group, 5601 De Soto Avenue, Woodland Hills, CA, 91365, USA

    Lester D. R. Thompson

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  1. Lester D. R. Thompson
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Correspondence to Lester D. R. Thompson.

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All authors declare that they have no conflict of interest as it relates to this research project. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of Southern California Permanente Medical Group.

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All procedures performed in this retrospective data analysis involving human participants were in accordance with the ethical standards of the institutional review board (IRB #5968), which did not require informed consent.

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Thompson, L.D.R., Magliocca, K.R., Andreasen, S. et al. CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients. Head and Neck Pathol 13, 355–363 (2019). https://doi.org/10.1007/s12105-018-0973-8

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