An Update on Molecular Diagnostics of Squamous and Salivary Gland Tumors of the Head and Neck

Abstract Context.—Molecular testing in anatomic pathology is becoming standardized and can contribute valuable diagnostic, therapeutic, and prognostic information for the clinical management of patients. In head and neck pathology, recent advances in molecular testing have provided important targets in several different diagnostic areas, with particular emerging clinical applications in squamous and salivary gland pathology. In squamous mucosal-derived lesions, human papilloma virus has emerged as an important pathogenic etiology in a subset of oropharyngeal squamous cell carcinomas. Within the category of salivary gland tumors, 3 tumors have recently been recognized that contain oncogenic translocations. Objective.—To describe the current state of information about the molecular alterations in squamous lesions and in salivary gland tumors of the head and neck. Data Sources.—Published literature on squamous and salivary gland tumors of the head and neck. Conclusions.—The different approaches to identification of viral-associated tumors include assays using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Most mucoepidermoid carcinomas harbor MECT1-MAML2 gene rearrangement. The MYB-NFIB translocations have recently been identified in adenoid cystic carcinomas. Finally, a newly described tumor of salivary gland, mammary analogue secretory carcinoma, harbors the ETV6-NTRK3 translocation. Although these translocations are just emerging as diagnostic targets, future roles may evolve as potential therapeutic targets.

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Genetics of Head and Neck Cancer: Advances in Molecular Research

Otolaryngology ◽

10.1016/s0194-5998(05)80248-7 ◽

1995 ◽

Vol 112 (5) ◽

pp. P101-P102

Author(s):

Michael S. Benninger ◽

Daniel Van Dyke ◽

Carol Bradford ◽

Thomas Carey

Keyword(s):

Polymerase Chain Reaction ◽

Head And Neck ◽

Molecular Data ◽

Microsatellite Repeat ◽

Chain Reaction ◽

Papilloma Virus ◽

Molecular Assessment ◽

Polymerase Chain

Educational objectives: To be familiar with cytogenetic and molecular data on early, advanced, recurrent metastatic head and neck cancers, and to understand common methodologies for genetic and molecular assessment including fluorescence in situ hybridization, microsatellite repeat polymorphisms, and polymerase chain reaction, as well as the role of human papilloma virus in squamous cell carcinoma (SCC).

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New Developments in Salivary Gland Pathology: Clinically Useful Ancillary Testing and New Potentially Targetable Molecular Alterations

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0259-sa ◽

2017 ◽

Vol 141 (3) ◽

pp. 381-395 ◽

Cited By ~ 27

Author(s):

Christopher C. Griffith ◽

Alessandra C. Schmitt ◽

James L. Little ◽

Kelly R. Magliocca

Keyword(s):

Salivary Gland ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Salivary Gland Tumor ◽

Molecular Techniques ◽

Salivary Gland Tumors ◽

Gland Tumor ◽

Molecular Alterations ◽

Tumor Pathology

Accurate diagnosis of salivary gland tumors can be challenging because of the many diagnostic entities, the sometimes extensive morphologic overlap, and the rarity of most tumor types. Ancillary testing is beginning to ameliorate some of these challenges through access to newer immunohistochemical stains and fluorescence in situ hybridization probes, which can limit differential diagnostic considerations in some cases. These ancillary testing strategies are especially useful in small biopsy samples, including aspiration cytology. Molecular techniques are also expanding our understanding of salivary gland tumor pathology and are helping to identify potential targets that may improve treatment for some of these tumors. Here, we summarize the clinical use of new immunohistochemical markers in our practice and review the current understanding of chromosomal rearrangements in salivary gland tumor pathology, emphasizing the prospects for exploiting molecular alterations in salivary gland tumors for diagnosis and targeted therapy. We find that immunohistochemistry and fluorescence in situ hybridization are powerful tools toward the diagnosis of salivary gland tumors, especially when used in a systematic manner based on morphologic differential-diagnostic considerations. As new targeted therapies emerge, it will become increasingly vital to incorporate appropriate molecular testing into the pathologic evaluation of salivary gland cancers.

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Human papilloma virus detection in liquid cytology, in situ hybridization and polymerase chain reaction

Virchows Archiv ◽

10.1007/s00428-004-1158-2 ◽

2005 ◽

Vol 446 (2) ◽

pp. 202-203 ◽

Cited By ~ 1

Author(s):

F. Alameda ◽

L. Pijuan ◽

L. Ferrer ◽

M. L. Mari�oso ◽

M. Muset ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

In Situ Hybridization ◽

Human Papilloma Virus ◽

Virus Detection ◽

Chain Reaction ◽

Papilloma Virus ◽

Polymerase Chain

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Gene Expression Profiling of Head and Neck Tumors Identifies FOXP1 and SOX10 Expression as Useful for Distinguishing Ameloblastoma From Basaloid Salivary Gland Tumors

The American Journal of Surgical Pathology ◽

10.1097/pas.0000000000001421 ◽

2020 ◽

Vol 44 (5) ◽

pp. 665-672

Author(s):

Yen Chen Kevin Ko ◽

Sushama Varma ◽

Chun Fang Zhu ◽

Shirley Xiaolei Zhu ◽

Sujay Vennam ◽

...

Keyword(s):

Gene Expression ◽

Salivary Gland ◽

Head And Neck ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Salivary Gland Tumors ◽

Head And Neck Tumors ◽

Neck Tumors ◽

Sox10 Expression

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High-Risk Human Papillomavirus (HPV) in Parotid Lesions

The International Journal of Biological Markers ◽

10.1177/172460080702200401 ◽

2007 ◽

Vol 22 (4) ◽

pp. 239-244 ◽

Cited By ~ 14

Author(s):

D. Vageli ◽

G. Sourvinos ◽

M. Ioannou ◽

G.K. Koukoulis ◽

D.A. Spandidos

Keyword(s):

Salivary Gland ◽

Viral Load ◽

High Risk ◽

Salivary Gland Tumors ◽

Specific Primers ◽

In Situ Pcr ◽

Hpv Genotypes ◽

Pleomorphic Adenomas ◽

High Risk Hpv

Although several studies have reported that oropharyngeal infection with HPV may predispose to tumorigenesis, little is known about the etiological factors of salivary gland tumors and the presence of HPV We studied 9 parotid lesions for HPV infection including an oncocytoma, an acinic cell carcinoma, a high-grade adenocarcinoma, a low-grade polymorphous adenocarcinoma, a Warthin's tumor and 2 pleomorphic adenomas, a lymphoepithelial cyst and a lipoma of the parotid gland. DNA was extracted from formalin-fixed and paraffin-embedded tissue sections. Solution PCR for HPV detection was performed using the GP5+/GP6+ primers, while HPV typing was carried out by multiplex PCR for HPV6, 11, 16, 18, and 33; positive samples were recorfirmed by PCR with specific primers for each type. Quantitative real-time PCR for the high-risk HPV genotypes 16, 18, 31, 33, 35, 52, 58 and 67 was also performed to quantitate the viral load. Finally, in situ PCR was employed with HPV16-specific primers by direct-detection method. Seven of the 9 parotid lesions were HPV positive while 6 of these 7 had been infected by HPV16 and/or HPV18 oncogenic types. High viral load of high-risk genotypes of HPV was found in the oncocytoma, in one of the pleomorphic adenomas, and in the Warthin's tumor. Finally, in situ PCR indicated that HPV16 amplification occurred in the salivary gland tumors. This is the first time that high-risk HPV genotypes are detected in these histological types of parotid lesions, suggesting the possible involvement of the virus in the disease.

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Precision oncology for the treatment of salivary gland tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17577 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17577-e17577

Author(s):

Damian Tobias Rieke ◽

Mario Lamping ◽

Serge Leyvraz ◽

Theo Daniel Kim ◽

Lutz Brinkmann ◽

...

Keyword(s):

Salivary Gland ◽

Rna Sequencing ◽

Salivary Gland Tumors ◽

Tumor Board ◽

Molecular Testing ◽

Precision Oncology ◽

Rna Seq ◽

Mixed Response ◽

Antiandrogen Therapy ◽

Panel Sequencing

e17577 Background: Salivary gland tumors (SGT) represent a rare and heterogeneous group of malignancies. No standard treatment exists in the advanced situation and the prognosis is poor. We here report characteristics and clinical outcomes of patients with SGT discussed at the Charité molecular tumor board (MTB). Methods: Patients with advanced cancer and no curative treatment option were discussed at the Charité MTB. Eligible patients underwent fresh tissue sampling and subsequent whole exome (WES) and RNA sequencing (RNA-seq) and immunohistochemical analyses (EGFR, HER2, AR as well as validation tests) or panel sequencing. Results from molecular testing were discussed at the MTB and patients were followed-up after recommendations were made. Results: 24 patients (median age 56 years, 13 male, 11 female) with advanced SGT were presented at the MTB between 2016 and 2019 (9 adenoidcystic carcinomas, 5 adenocarcinomas, 3 mucoepidermoid, 2 carcinosarcoma, 5 miscellaneous). WES/RNA sequencing was performed on tumor tissue from 16 patients. 2 patients were not included in the sequencing program and WES/RNA-Seq was ongoing for another 4 patients at the time of analysis. For another 2 patients, panel sequencing and IHC analysis, respectively was done. Results from analyses were discussed and a median of 2 recommendations, ranked by priority according to prespecified evidence levels, were made for 17 patients, each. Most commonly proposed treatment options by the MTB were FGFR inhibitors in 6 patients, mTOR or PARP inhibitors in 5 each, EGFR, HDAC inhibitors or antiandrogen therapy in 4, each. Treatments following MTB recommendations were initiated in 8 patients, 1 of which received a second recommended therapy after progression (antiandrogen therapy in 4, EGFR inhibitor in 2, a PDGFR, mTOR and PARP inhibitor in 1, each). A clinical benefit (CR = 1; Mixed Response = 1, SD = 3) was achieved in 5 patients, including a complete response in a patient with a metastatic adenocarcinoma of the parotid gland, treated with antiandrogen therapy. Conclusions: Precision oncology represents a feasible treatment strategy in patients with advanced SGT and shows early evidence of activity in a subset of patients. These results suggest further exploration of personalized therapy in these hard-to-treat tumors.

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