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

  • Lester D. R. ThompsonEmail author
  • Kelly R. Magliocca
  • Simon Andreasen
  • Katlin Kiss
  • Lisa Rooper
  • Edward Stelow
  • Bruce M. Wenig
  • Justin A. Bishop
Original Paper


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.


Endolymphatic sac tumor Immunohistochemistry CAIX pax-8 Von Hippel-Lindau syndrome Renal cell carcinoma Differential diagnosis 



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

Compliance with Ethical Standards

Conflict of interest

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.

Ethical Approval

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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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply  2018

Authors and Affiliations

  • Lester D. R. Thompson
    • 1
    • 9
    Email author
  • Kelly R. Magliocca
    • 2
  • Simon Andreasen
    • 3
  • Katlin Kiss
    • 4
  • Lisa Rooper
    • 5
  • Edward Stelow
    • 6
  • Bruce M. Wenig
    • 7
  • Justin A. Bishop
    • 8
  1. 1.Southern California Permanente Medical GroupWoodland HillsUSA
  2. 2.Emory Pathology and Laboratory MedicineAtlantaUSA
  3. 3.Department of Otorhinolaryngology Head and Neck Surgery and Audiology & Department of PathologyRigshospitaletCopenhagenDenmark
  4. 4.Department of PathologyRigshospitaletCopenhagenDenmark
  5. 5.Johns Hopkins HospitalBaltimoreUSA
  6. 6.University of VirginiaCharlottesvilleUSA
  7. 7.Moffitt Cancer CenterTampaUSA
  8. 8.University of Texas, Southwestern Medical CenterDallasUSA
  9. 9.Department of Pathology, Woodland Hills Medical CenterSouthern California Permanente Medical GroupWoodland HillsUSA

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