Lacrimal gland ductal carcinomas: Clinical, Morphological and Genetic characterization and implications for targeted treatment.
OBJECTIVE
Ductal carcinomas (DCs) 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 CK7, CK19, EMA, p53 and HER2 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 HER2 amplification was found in cases 2 and 3.


CONCLUSIONS
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 HER2 signalling pathway could alleviate the effect of HER2-directed therapy illustrating an inadequacy of isolated HER2 testing.
Department of Otorhinolaryngology Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Otorhinolaryngology and Maxillofacial Surgery, Zealand University Hospital, Køge, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Simon
http://orcid.org/0000-0002-1528-4988
S
Andreasen
Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Morten
M
Grauslund
Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Ophthalmology, Rigshospitalet-Glostrup, Copenhagen University Hospital, Copenhagen, Denmark.
Steffen
S
Heegaard
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D000368:Aged; D001706:Biopsy; D044584:Carcinoma, Ductal / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005134:Eye Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D017809:Fatal Outcome; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000473:pathology* / Q000601:surgery; D007766:Lacrimal Apparatus Diseases / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D013508:Ophthalmologic Surgical Procedures; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins
D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
HER2; PTEN; androgen receptor; ductal adenocarcinoma; ductal carcinoma; genetics; lacrimal gland