The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct
- PDF / 2,464,465 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 64 Downloads / 183 Views
ORIGINAL PAPER
The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra‑spinal paraganglioma Biswarathan Ramani1 · Rohit Gupta1 · Jasper Wu1 · Jairo Barreto1 · Andrew W. Bollen1 · Tarik Tihan1 · Praveen V. Mummaneni2 · Christopher Ames2 · Aaron Clark2 · Nancy Ann Oberheim Bush3 · Nicholas Butowski3 · Daniel Phillips4 · Bruce E. King5 · Susan M. Bator5 · Elizabeth C. Treynor6 · Viktor Zherebitskiy7 · Paula S. Quinn8 · Jeffrey B. Walker9 · Melike Pekmezci1 · Daniel V. Sullivan1 · Jeffrey W. Hofmann1 · Emily A. Sloan1 · Susan M. Chang3 · Mitchel S. Berger2 · David A. Solomon1 · Arie Perry1,2 Received: 27 July 2020 / Revised: 28 August 2020 / Accepted: 29 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated 17 CEPs from 11 male and 6 female patients with a median age of 38 years (range 21–82), none with a family history of neuroendocrine neoplasia. Six of the 17 tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all 17 CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on 12 of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors. Keywords Cauda equina paraganglioma · Filum terminale · Neuroendocrine tumor · Molecular neuropathology · Succinate dehydrogenase · DNA methylation profiling
Introduction
Biswarathan Ramani and Rohit Gupta equally contributed to this study. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00401-020-02221-y) contains supplementary material, which
Data Loading...
