Lacrimal gland ductal carcinomas: Clinical, Morphological and Genetic characterization and implications for targeted treatment

Purpose Ductal carcinomas ( DC s) of the lacrimal gland are very rare but aggressive malignancies. We investigated DC of the lacrimal gland for potentially clinically actionable targets in the search for new therapeutic options. Methods Case 1: A 77‐year‐old man, presented with diplopia and xerophtalmia; case 2: A 53‐year‐old man, presented with headache, proptosis and chemosis and case 3: A 73‐year‐old man, presenting with chemosis and a corneal abscess. All three cases were characterized morphologically including immunohistochemistry and genetically with fluorescence in situ hybridization ( FISH ) and one case with next‐generation sequencing ( NGS ) of cancer relevant genes. Results 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 CK 7, CK 19, EMA , p53 and HER 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 PTEN were identified in case 1, whereas HER 2 amplification was found in cases 2 and 3. Conclusion This study identified a spectrum of genetic events and pattern of protein expression in DC 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 HER 2 signalling pathway could alleviate the effect of HER 2‐directed therapy illustrating an inadequacy of isolated HER 2 testing.