A Review of Cytology of Salivary Gland Lesions: Old, Updated and New

Jihong Sun, Xiu Yang


Fine needle aspiration (FNA) biopsy plays a critical role in the diagnosis of salivary gland lesion.  Compared to excisional biopsy, FNA is safer, faster and less tumor seeding spread. The sensitivity and specificity of FNA for diagnosing neoplasm is very high. In this review, we will discuss the cytological findings of a wide spectrum of non-neoplastic and neoplastic diseases in salivary glands. We will further discuss the differentiation diagnosis for each entity.  The new molecular findings in salivary gland tumors will be addressed. 


Salivary gland, cytology, fine needle aspiration, immunohistochemistry, gene translocation

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Majewski J, Schwartzentruber J, Lalonde E, Montpetit A, Jabado N. What can exome sequencing do for you? J Med Genet. 2011;48(9):580-589.

Service RF. Gene sequencing. The race for the $1000 genome. Science. 2006;311(5767):1544-1546.

KA. W. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP). www.genome.gov/sequencingcosts. Jan 1, 2015.

Taber JKA, Dickinson BD, Wilson M. The promise and challenges of next-generation genome sequencing for clinical care. JAMA Intern Med. 2014;174(2):275-280.

van El CG, Cornel MC, Borry P, et al. Whole-genome sequencing in health care: recommendations of the European Society of Human Genetics. Eur J Hum Genet. 2013;21(6):580-584.

Glass DA II, Nuara AA. Whole exome sequencing. Dermatitis. 2013;24(1):33-34.

Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014;59(1):5-15.

Ng SB, Turner EH, Robertson PD, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):272-276.

Ng SB, Buckingham KJ, Lee C, et al. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010;42(1):30-35.

Bamshad MJ, Shendure JA, Valle D, et al. The Centers for Mendelian Genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions. Am J Med Genet A. 2012;158A(7):1523-1525.

Pediatric Cardiac Genomics Consortium, Gelb B, Brueckner M, et al. The Congenital Heart Disease Genetic Network Study: rationale, design, and early results. Circ Res. 2013;112(4):698-706.

Zaidi S, Choi M, Wakimoto H, et al. De novo mutations in histone-modifying genes in congenital heart disease. Nature. 2013;498(7453):220-223.

The Deciphering Developmental Disorders (DDD) study. http://www.ddduk.org/. Accessed 25/08/2014.

Firth HV, Wright CF, Study DDD. The Deciphering Developmental Disorders (DDD) study. Dev Med Child Neurol. 2011;53(8):702-703.

Mendelian Exome Sequencing Project (Mendelian Exome). https://www.nhlbi.nih.gov/research/resources/genetics-genomics/mendelian.htm. Accessed 25/08/2014.

Gahl WA, Markello TC, Toro C, et al. The National Institutes of Health Undiagnosed Diseases Program: insights into rare diseases. Genet Med. 2012;14(1):51-59.

Gahl WA, Tifft CJ. The NIH Undiagnosed Diseases Program: lessons learned. JAMA. 2011;305(18):1904-1905.

The UK10K project. http://www.uk10k.org/. Accessed 25/08/2014.

Ding LE, Burnett L, Chesher D. The impact of reporting incidental findings from exome and whole-genome sequencing: predicted frequencies based on modeling. Genet Med. 2014.

Rabbani B, Mahdieh N, Hosomichi K, Nakaoka H, Inoue I. Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. J Hum Genet. 2012;57(10):621-632.

Beaulieu CL, Majewski J, Schwartzentruber J, et al. FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene-discovery project. Am J Hum Genet. 2014;94(6):809-817.

de Ligt J, Willemsen MH, van Bon BW, et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012;367(20):1921-1929.

Rauch A, Wieczorek D, Graf E, et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet. 2012;380(9854):1674-1682.

Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013;369(16):1502-1511.

Kuehn BM. NIH's Undiagnosed Diseases Program expands: 6 new sites offer potential answers to more patients. JAMA. 2014;312(6):587.

Backenroth D, Homsy J, Murillo LR, et al. CANOES: detecting rare copy number variants from whole exome sequencing data. Nucleic Acids Res. 2014;42(12):e97.

Shi Y, Majewski J. FishingCNV: a graphical software package for detecting rare copy number variations in exome-sequencing data. Bioinformatics. 2013;29(11):1461-1462.

Mao H, Yang W, Lee PP, et al. Exome sequencing identifies novel compound heterozygous mutations of IL-10 receptor 1 in neonatal-onset Crohn's disease. Genes Immun. 2012;13(5):437-442.

Glocker EO, Kotlarz D, Boztug K, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009;361(21):2033-2045.

Li M, Pang SY, Song Y, Kung MH, Ho SL, Sham PC. Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family. Clin Genet. 2013;83(3):269-273.

Wang JL, Yang X, Xia K, et al. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain. 2010;133(Pt 12):3510-3518.

Lee PP, Mao H, Yang W, et al. Penicillium marneffei infection and impaired IFN-gamma immunity in humans with autosomal-dominant gain-of-phosphorylation STAT1 mutations. J Allergy Clin Immunol. 2014;133(3):894-896 e895.

Luo R, Wong YL, Law WC, et al. BALSA: integrated secondary analysis for whole-genome and whole-exome sequencing, accelerated by GPU. PeerJ. 2014;2:e421.

Zhang L, Zhang J, Yang J, Ying D, Lau YL, Yang W. PriVar: a toolkit for prioritizing SNVs and indels from next-generation sequencing data. Bioinformatics. 2013;29(1):124-125.

Zeng S, Yang J, Chung BH, Lau YL, Yang W. EFIN: predicting the functional impact of nonsynonymous single nucleotide polymorphisms in human genome. BMC Genomics. 2014;15:455.

Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86(5):749-764.

Jamal SM, Yu JH, Chong JX, et al. Practices and policies of clinical exome sequencing providers: analysis and implications. Am J Med Genet A. 2013;161A(5):935-950.

Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754-1760.

Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248-249.

Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073-1081.

Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164.

Schuurs-Hoeijmakers JH, Oh EC, Vissers LE, et al. Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome. Am J Hum Genet. 2012;91(6):1122-1127.

Abecasis GR, Altshuler D, Auton A, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319): 1061-1073.

Kaname T, Yanagi K, Naritomi K. A commentary on the promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014;59(3):117-118.

Kuehn BM. 1000 Genomes Project promises closer look at variation in human genome. JAMA. 2008;300(23):2715.

Genome of the Netherlands C, Genome of the Netherlands C. Whole-genome sequence variation, population structure and demographic history of the Dutch population. Nat Genet. 2014;46(8):818-825.

Ground-breaking ceremony for Hong Kong Children's Hospital. http://www.info.gov.hk/gia/general/201402/25/P201402250508.htm. Accessed 29/08/2014.

Moskaluk CA. Adenoid Cystic Carcinoma: Clinical and Molecular Features. Head Neck Pathol. 2013;7:17-22.

Persson M, Andrén Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci U S A. 2009;106:18740-18744.

Skálová A, Vanecek T, Sima R, et al. Mammary Analogue Secretory Carcinoma of Salivary Glands, Containing the ETV6-NTRK3 Fusion Gene: A Hitherto Undescribed Salivary Gland Tumor Entity. Am J Surg Pathol. 2010;34:599-608.

Skalova A. Mammary Analogue Secretory Carcinoma of Salivary Gland Origin: An Update and Expanded Morphologic and Immunohistochemical Spectrum of Recently Described Entity. Head Neck Pathol. 2013;7(Suppl 1):30-36.

Bishop JA, Yonescu R, Batista DA, Westra WH, Ali SZ. Cytopathologic features of mammary analogue secretory carcinoma. Cancer Cytopathol. 2013;121:228-233.

Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61:387-394.

Yang X, Cole A, Oktay M, Smith R, Cajigas A, Khader S. Fine needle aspiration of an unusual malignant mixed tumor in the parotid gland. Lab Med. 2014;45:141-146.


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