Lacrimal gland duct obstruction and dacryops: Unravelling its pathogenesis with proteomics and cellular profiling

<h4>Purpose</h4>To understand the pathogenesis of the main lacrimal gland dacryops (ductular cyst) using proteomics and cellular profiling.<h4>Methods</h4>Four patients (mean age, 42.2 ± 18.4 years) with dacryops underwent cyst excision following the aspiration of the cyst contents. Cyst contents were processed using mass spectrometry and compared with eight healthy tear samples. The cyst wall was processed for histology (H&E, Masson trichrome), epithelial (Aquaporin 5, CK15, CK19), stromal (Vimentin), neural (beta-III tubulin, NCAM), and immune cell markers (CD3, CD20, CD138, myeloperoxidase, CD68).<h4>Results</h4>The cyst lining was cuboidal to squamous in three cases (CK19+, ductal origin), and exhibited goblet cell metaplasia in one case. Compared to normal ducts, the dacryops cyst wall lacked expression of AQP5 and beta-III tubulin. Subepithelial fibrosis and strong vimentin positivity were observed in all specimens, along with mild to moderate inflammation. Infiltrating immune cells were CD20⁺ and CD138+, with a few macrophages and neutrophils noted perivascularly. The visible few lacrimal gland acini within the cyst wall showed inflammation, IgA-positive plasma cells, and focal acinar atrophy. The cyst fluid and tear samples were widely separated on the PCA plot, with 190 proteins upregulated and 52 downregulated. The upregulated proteins were involved in immunoglobulin-mediated immune responses, complement activation, apolipoproteins, extracellular matrix components (including matrix metalloproteinases 7 and 10), and glycosaminoglycan binding.<h4>Conclusion</h4>Dacryops involves reactive ductular ectasia secondary to inflammation, resulting in increased MMPs, fibrosis, and loss of the periductal neural network. The cyst fluid is rich in apolipoproteins, immunoglobulins, and complement factors. Future research could focus on the lipidomics of the cyst fluid.