Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls

Rachel Jester, Iya Znoyko, Maria Garnovskaya, Joseph N. Rozier, Ryan Kegl, Sunil Patel, Tuan Tran, Malak Abedalthagafi, Craig M. Horbinski, Mary Richardson, Daynna J. Wolff, Razvan Lapadat, William Moore, Fausto J. Rodriguez, Jason Mull, Adriana Olar

Research output: Contribution to journalArticle

Abstract

Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease. Onset is usually in the 3rd to 5th decade with hearing loss and an indolent course. ELSTs present as locally destructive lesions with characteristic computed tomography imaging features. Histologically, they show papillary, cystic or glandular architectures. Immunohistochemically, they express keratin, EMA, and variably S100 and GFAP. Currently it is recommended that, given its rarity, ELST needs to be differentiated from other entities with similar morphologic patterns, particularly other VHL-associated neoplasms such as metastatic clear cell renal cell carcinoma (ccRCC). Nineteen ELST cases were studied. Immunohistochemistry (18/19) and single nucleotide polymorphism microarray testing was performed (12/19). Comparison with the immunophenotype and copy number profile in RCC is discussed. Patients presented with characteristic bone destructive lesions in the petrous temporal bones. Pathology of tumors showed characteristic ELST morphology with immunoexpression of CK7, GFAP, S100, PAX-8, PAX-2, CA-9 in the tumor cells. Immunostaines for RCC, CD10, CK20, chromogranin A, synaptophysin, TTF-1, thyroglobulin, and transthyretin were negative in the tumor cells. Molecular testing showed loss of 3p and 9q in 66% (8/12) and 58% (7/12) cases, respectively. Immunoreactivity for renal markers in ELST is an important diagnostic caveat and has not been previously reported. In fact, renal markers are currently recommended in order to rule out metastatic RCC although PAX gene complex and CA-9 have been implicated in the development of the inner ear. Importantly copy number assessment of ELST has not been previously reported. Loss of 3p (including the VHL locus) in ELST suggests similar mechanistic origins as ccRCC.

Original languageEnglish (US)
Number of pages1
JournalActa neuropathologica communications
Volume6
Issue number1
DOIs
StatePublished - Oct 19 2018

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Endolymphatic Sac
Renal Cell Carcinoma
Kidney
Neoplasms
von Hippel-Lindau Disease
Petrous Bone
Chromogranin A
Synaptophysin
Prealbumin
Thyroglobulin
Temporal Bone
Inner Ear
Temporal Lobe
Keratins
Hearing Loss

Keywords

  • CA-9
  • Copy number profiles
  • Endolymphatic sac tumor
  • PAX-2
  • PAX-8
  • Renal cell carcinoma
  • VHL

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls. / Jester, Rachel; Znoyko, Iya; Garnovskaya, Maria; Rozier, Joseph N.; Kegl, Ryan; Patel, Sunil; Tran, Tuan; Abedalthagafi, Malak; Horbinski, Craig M.; Richardson, Mary; Wolff, Daynna J.; Lapadat, Razvan; Moore, William; Rodriguez, Fausto J.; Mull, Jason; Olar, Adriana.

In: Acta neuropathologica communications, Vol. 6, No. 1, 19.10.2018.

Research output: Contribution to journalArticle

Jester, R, Znoyko, I, Garnovskaya, M, Rozier, JN, Kegl, R, Patel, S, Tran, T, Abedalthagafi, M, Horbinski, CM, Richardson, M, Wolff, DJ, Lapadat, R, Moore, W, Rodriguez, FJ, Mull, J & Olar, A 2018, 'Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls', Acta neuropathologica communications, vol. 6, no. 1. https://doi.org/10.1186/s40478-018-0607-0
Jester, Rachel ; Znoyko, Iya ; Garnovskaya, Maria ; Rozier, Joseph N. ; Kegl, Ryan ; Patel, Sunil ; Tran, Tuan ; Abedalthagafi, Malak ; Horbinski, Craig M. ; Richardson, Mary ; Wolff, Daynna J. ; Lapadat, Razvan ; Moore, William ; Rodriguez, Fausto J. ; Mull, Jason ; Olar, Adriana. / Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls. In: Acta neuropathologica communications. 2018 ; Vol. 6, No. 1.
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AU - Jester, Rachel

AU - Znoyko, Iya

AU - Garnovskaya, Maria

AU - Rozier, Joseph N.

AU - Kegl, Ryan

AU - Patel, Sunil

AU - Tran, Tuan

AU - Abedalthagafi, Malak

AU - Horbinski, Craig M.

AU - Richardson, Mary

AU - Wolff, Daynna J.

AU - Lapadat, Razvan

AU - Moore, William

AU - Rodriguez, Fausto J.

AU - Mull, Jason

AU - Olar, Adriana

PY - 2018/10/19

Y1 - 2018/10/19

N2 - Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease. Onset is usually in the 3rd to 5th decade with hearing loss and an indolent course. ELSTs present as locally destructive lesions with characteristic computed tomography imaging features. Histologically, they show papillary, cystic or glandular architectures. Immunohistochemically, they express keratin, EMA, and variably S100 and GFAP. Currently it is recommended that, given its rarity, ELST needs to be differentiated from other entities with similar morphologic patterns, particularly other VHL-associated neoplasms such as metastatic clear cell renal cell carcinoma (ccRCC). Nineteen ELST cases were studied. Immunohistochemistry (18/19) and single nucleotide polymorphism microarray testing was performed (12/19). Comparison with the immunophenotype and copy number profile in RCC is discussed. Patients presented with characteristic bone destructive lesions in the petrous temporal bones. Pathology of tumors showed characteristic ELST morphology with immunoexpression of CK7, GFAP, S100, PAX-8, PAX-2, CA-9 in the tumor cells. Immunostaines for RCC, CD10, CK20, chromogranin A, synaptophysin, TTF-1, thyroglobulin, and transthyretin were negative in the tumor cells. Molecular testing showed loss of 3p and 9q in 66% (8/12) and 58% (7/12) cases, respectively. Immunoreactivity for renal markers in ELST is an important diagnostic caveat and has not been previously reported. In fact, renal markers are currently recommended in order to rule out metastatic RCC although PAX gene complex and CA-9 have been implicated in the development of the inner ear. Importantly copy number assessment of ELST has not been previously reported. Loss of 3p (including the VHL locus) in ELST suggests similar mechanistic origins as ccRCC.

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