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Lacrimal gland ductal carcinomas: Clinical, Morphological and Genetic characterization and implications for targeted treatment
Author(s) -
Andreasen Simon,
Grauslund Morten,
Heegaard Steffen
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.13310
Subject(s) - lacrimal gland , pathology , pten , immunohistochemistry , ductal carcinoma , salivary gland , biology , medicine , breast cancer , cancer , cancer research , genetics , apoptosis , pi3k/akt/mtor pathway
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.