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We investigated <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content> of the lacrimal gland for potentially clinically actionable targets in the search for new therapeutic options.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Case 1: A 77\u2010year\u2010old man, presented with diplopia and xerophtalmia; case 2: A 53\u2010year\u2010old man, presented with headache, proptosis and chemosis and case 3: A 73\u2010year\u2010old man, presenting with chemosis and a corneal abscess. All three cases were characterized morphologically including immunohistochemistry and genetically with fluorescence in\u00a0situ hybridization (<jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>) and one case with next\u2010generation sequencing (<jats:styled-content style=\"fixed-case\">NGS<\/jats:styled-content>) of cancer relevant genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cases 1 and 3 were composed of large, rounded, irregular cystic nodules of carcinoma cells with prominent central comedonecrosis, whereas case 2 had a scirrhous morphology. High expression of <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>7, <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>19, <jats:styled-content style=\"fixed-case\">EMA<\/jats:styled-content>, p53 and <jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2 was characteristic for all three tumours. Androgen receptor was intensely positive in case 1, in scattered cells in case 2 and negative in case 3, whereas oestrogen and progesterone receptor were consistently negative. Genetically, a hemizygous deletion and a point mutation in <jats:italic><jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content><\/jats:italic> were identified in case 1, whereas <jats:italic><jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2<\/jats:italic> amplification was found in cases 2 and 3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identified a spectrum of genetic events and pattern of protein expression in <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content> of the lacrimal gland similar to a subset of carcinomas of the breast and ductal carcinomas of the salivary glands. For therapeutic purposes, aberrations in several components of especially the <jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2 signalling pathway could alleviate the effect of <jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2\u2010directed therapy illustrating an inadequacy of isolated <jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2 testing.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.13310","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T09:10:48Z","timestamp":1478164248000},"page":"299-306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Lacrimal gland ductal carcinomas: Clinical, Morphological and Genetic characterization and implications for targeted 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