AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common intra-oral salivary gland malignancy. The vast majority of PLGAs harbour a PRKD1 E710D hot-spot somatic mutation or somatic rearrangements of PRKD1, PRKD2 or PRKD3. Given the kinase domain homology among PRKD1, PRKD2 and PRKD3, we sought to define whether PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements would be driven by somatic mutations affecting the kinase domains of PRKD2 or PRKD3. METHODS AND RESULTS: DNA was extracted from eight microdissected PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements. Samples were thoroughly centrally reviewed, microdissected and subjected to Sanger sequencing of the kinase domains of the PRKD2 and PRKD3 genes. None of the PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements harboured somatic mutations in the kinase domains of the PRKD2 or PRKD3 genes. CONCLUSION: PLGAs lacking PRKD1 somatic mutations or PRKD gene family rearrangements are unlikely to harbour somatic mutations in the kinase domains of PRKD2 or PRKD3. Further studies are warranted to define the driver genetic events in this subgroup of PLGAs.

Department of Pathology Medical Faculty of Charles University Plzen Czech Republic

Department of Pathology Memorial Sloan Kettering Cancer Center New York NY USA

Department of Pathology Robert J Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic Cleveland OH USA

Department of Pathology University Health Network Toronto Ontario Canada

Division of Pathology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Instituto Português de Oncologia Oporto Portugal

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Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005.

Foschini MP, Eusebi V. Rare (new) entities of the breast and medullary carcinoma. Pathology. 2009;41:48–56. PubMed

Olusanya AA, Akadiri OA, Akinmoladun VI, Adeyemi BF. Polymorphous low grade adenocarcinoma: Literature review and report of lower lip lesion with suspected lung metastasis. J Maxillofac Oral Surg. 2011;10:60–63. PubMed PMC

Lee VK, McCaughan BC, Scolyer RA. Polymorphous low-grade adenocarcinoma in the lung: A case report. Int J Surg Pathol. 2004;12:287–292. PubMed

Tanaka F, Wada H, Inui K, et al. Pulmonary metastasis of polymorphous low-grade adenocarcinoma of the minor salivary gland. Thorac Cardiovasc Surg. 1995;43:178–180. PubMed

Simpson RH, Pereira EM, Ribeiro AC, Abdulkadir A, Reis-Filho JS. Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma. Histopathology. 2002;41:250–259. PubMed

Evans HL, Luna MA. Polymorphous low-grade adenocarcinoma: A study of 40 cases with long-term follow up and an evaluation of the importance of papillary areas. Am J Surg Pathol. 2000;24:1319–1328. PubMed

Perez-Ordonez B, Linkov I, Huvos AG. Polymorphous low-grade adenocarcinoma of minor salivary glands: A study of 17 cases with emphasis on cell differentiation. Histopathology. 1998;32:521–529. PubMed

Marchio C, Weigelt B, Reis-Filho JS. Adenoid cystic carcinomas of the breast and salivary glands (or ‘the strange case of dr jekyll and mr hyde’ of exocrine gland carcinomas) J Clin Pathol. 2010;63:220–228. PubMed

Weinreb I, Piscuoglio S, Martelotto LG, et al. Hotspot activating prkd1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat Genet. 2014;46:1166–1169. PubMed PMC

Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cbioportal. Sci Signal. 2013;6:pl1. PubMed PMC

Rozengurt E, Rey O, Waldron RT. Protein kinase d signaling. J Biol Chem. 2005;280:13205–13208. PubMed

Weigelt B, Ghajar CM, Bissell MJ. The need for complex 3d culture models to unravel novel pathways and identify accurate biomarkers in breast cancer. Adv Drug Deliv Rev. 2014;69–70:42–51. PubMed PMC

Rykx A, De Kimpe L, Mikhalap S, et al. Protein kinase d: A family affair. FEBS Lett. 2003;546:81–86. PubMed

Weinreb I, Zhang L, Tirunagari LM, et al. Novel prkd gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosomes Cancer. 2014;53:845–856. PubMed

Marchio C, Iravani M, Natrajan R, et al. Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. J Pathol. 2008;215:398–410. PubMed

Guerini-Rocco E, Hodi Z, Piscuoglio S, et al. The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: An exploratory, hypothesis-generating study. J Pathol. 2015;237:166–178. PubMed PMC

Natrajan R, Wilkerson PM, Marchio C, et al. Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. J Pathol. 2014;232:553–565. PubMed PMC

Ng CK, Martelotto LG, Gauthier A, et al. Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification. Genome Biol. 2015;16:107. PubMed PMC

Barnes L. Surgical pathology of the head and neck. third. Taylor & Francis; 2008.

Sreeja C, Shahela T, Aesha S, Satish MK. Taxonomy of salivary gland neoplasm. J Clin Diagn Res. 2014;8:291–293. PubMed PMC

Ashworth A, Lord CJ, Reis-Filho JS. Genetic interactions in cancer progression and treatment. Cell. 2011;145:30–38. PubMed

Weigelt B, Reis-Filho JS. Epistatic interactions and drug response. J Pathol. 2014;232:255–263. PubMed

Sundram V, Chauhan SC, Jaggi M. Emerging roles of protein kinase d1 in cancer. Mol Cancer Res. 2011;9:985–996. PubMed PMC

McHugh JB, Visscher DW, Barnes EL. Update on selected salivary gland neoplasms. Arch Pathol Lab Med. 2009;133:1763–1774. PubMed

Simpson RH, Desai S, Di Palma S. Salivary duct carcinoma in situ of the parotid gland. Histopathology. 2008;53:416–425. PubMed

Valverde AM, Sinnett-Smith J, Van Lint J, Rozengurt E. Molecular cloning and characterization of protein kinase d: A target for diacylglycerol and phorbol esters with a distinctive catalytic domain. Proc Natl Acad Sci U S A. 1994;91:8572–8576. PubMed PMC

Newly described salivary gland tumors