SalvGlandDx – a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

Sandra N. Freiberger; Muriel Brada; Christine Fritz; Sylvia Höller; Alexander Vogetseder; Milo Horcic; Michel Bihl; Michal Michal; Martin Lanzer; Martin Wartenberg; Urs Borner; Peter K. Bode; Martina A. Broglie; Tamara Rordorf; Grégoire B. Morand; Niels J. Rupp

Neoplasia: An International Journal for Oncology Research (May 2021)

SalvGlandDx – a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

Sandra N. Freiberger,
Muriel Brada,
Christine Fritz,
Sylvia Höller,
Alexander Vogetseder,
Milo Horcic,
Michel Bihl,
Michal Michal,
Martin Lanzer,
Martin Wartenberg,
Urs Borner,
Peter K. Bode,
Martina A. Broglie,
Tamara Rordorf,
Grégoire B. Morand,
Niels J. Rupp

Affiliations

Sandra N. Freiberger: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Muriel Brada: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Christine Fritz: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Sylvia Höller: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Alexander Vogetseder: Department of Pathology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
Milo Horcic: Institute for Histological and Cytological Diagnostics AG, Aarau, Switzerland
Michel Bihl: Department of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland
Michal Michal: Sikl's Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic; Bioptical Laboratory, Pilsen, Czech Republic
Martin Lanzer: Department of Oral and Maxillofacial Surgery, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Martin Wartenberg: Institute of Pathology, University of Bern, Bern, Switzerland
Urs Borner: Department of Otorhinolaryngology, Head and Neck Surgery, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
Peter K. Bode: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Martina A. Broglie: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Tamara Rordorf: Department of Medical Oncology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
Grégoire B. Morand: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland; Department of Otolaryngology-Head and Neck Surgery, Sir Mortimer B. Davis- Jewish General Hospital, McGill University, Montreal, Quebec, Canada; University of Zurich, Zurich, Switzerland
Niels J. Rupp: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland; Corresponding author: Niels J. Rupp, MD, Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland, Tel. +41 44 255 50 91, Fax. +41 44 255 44 40

Journal volume & issue: Vol. 23, no. 5
pp. 473 – 487

Abstract

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Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the “SalvGlandDx” panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

Published in Neoplasia: An International Journal for Oncology Research

ISSN: 1522-8002 (Print); 1476-5586 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/neoplasia/

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