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Lacrimal gland ductal carcinomas: Clinical, Morphological and Genetic characterization and implications for targeted
Simon Andreasen1,2,3, Morten Grauslund4, Steffen Heegaard4,5
1Department of Otorhinolaryngology Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Purpose:
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.
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 HER2 signalling pathway could alleviate the effect of HER2-directed therapy illustrating an inadequacy of isolated HER2 testing.
Insights
Ductal carcinomas of the lacrimal gland are rare, aggressive tumors. Genetic analysis revealed PTEN mutations and HER2 amplification, suggesting targeted therapies may be beneficial.
Area of Science:
- Ophthalmology
- Oncology
- Pathology
Background:
- Ductal carcinomas (DCs) of the lacrimal gland are rare and aggressive malignancies.
- Investigating actionable targets for new therapeutic options is crucial for these rare cancers.
Observation:
- Three cases of lacrimal gland DC were analyzed morphologically, immunohistochemically, and genetically.
- Morphological analysis revealed cystic nodules with comedonecrosis and scirrhous patterns.
- Immunohistochemistry showed high expression of CK7, CK19, EMA, p53, and HER2 in all tumors.
Findings:
- Genetic analysis identified PTEN mutations in one case and HER2 amplification in two cases.
- Androgen receptor expression varied, while estrogen and progesterone receptors were negative.
- The protein and genetic profiles showed similarities to subsets of breast and salivary gland ductal carcinomas.
Implications:
- Aberrations in the HER2 signaling pathway suggest potential efficacy of HER2-directed therapies.
- Isolated HER2 testing may be insufficient, highlighting the need for broader pathway analysis.
- Understanding these molecular alterations can guide personalized treatment strategies for lacrimal gland DC.
