What are the possible causes of lacrimal gland enlargement?

Causes of Enlarged Lacrimal Glands

Lacrimal gland enlargement results from inflammatory infiltration, infectious processes, or neoplastic replacement of glandular tissue, with the most common causes being Sjögren's syndrome, sarcoidosis, IgG4-related disease, lymphoma, and viral infections.

Autoimmune and Inflammatory Causes

Sjögren's Syndrome

• Inflammatory cellular infiltration of the lacrimal gland leads to gland enlargement and tear production deficiency 1
• Approximately 10% of patients with clinically significant aqueous deficient dry eye have underlying primary Sjögren's syndrome 1
• Primary Sjögren's syndrome carries a 5% risk of lymphoid malignancy, with an incidence rate of 18.9% among rheumatic diseases 1
• Histopathology shows inflammatory cellular infiltration of exocrine glands 2

IgG4-Related Dacryoadenitis

• Presents with bilateral lacrimal gland swelling in 50% of cases, often with extensive inflammation beyond the gland itself 3
• Associated ophthalmologic symptoms include diplopia, ptosis, visual field disturbance, eye pain, and decreased visual acuity 3
• Frequently associated with other IgG4-related diseases including sialadenitis (42%), autoimmune pancreatitis (33%), and lymphadenopathy (67%) 3
• Serum IgG4 levels are markedly elevated, particularly in patients with concurrent systemic IgG4-related disease (1070 ± 813 mg/dl) 3
• Responds to steroid therapy but may relapse in patients with markedly elevated IgG4 levels 3

Sarcoidosis

• Results in infiltration of the lacrimal gland with replacement of secretory acini 1
• Lacrimal glands may be enlarged bilaterally on imaging 1
• Histopathology shows non-caseating granulomas composed of epithelioid cells, giant cells, and CD4+ T cells 1
• Sarcoidal reaction was identified in 12% of biopsied lacrimal gland inflammation cases 2

Granulomatosis with Polyangiitis (GPA)

• Accounts for 10% of specific lacrimal gland inflammation cases requiring biopsy 2
• Presents with inflammatory features including erythema, edema, and tenderness 2

Sclerosing Inflammation

• Represents a distinct inflammatory subtype identified in approximately 3% of biopsied cases 2

Infectious Causes

Viral Infections

• Epstein-Barr virus causes lacrimal gland swelling, dry eye, and can be associated with Sjögren's syndrome 1
• Human T-cell lymphotropic virus type 1 and HIV can cause lacrimal gland involvement 1
• Diffuse infiltrative lymphadenopathy syndrome occurs in HIV-infected patients, predominantly children 1
• Hepatitis C infection leads to decreased tear secretion and reduced lactoferrin concentrations 1
• SARS-CoV-2 can cause chronic bilateral dacryoadenitis, responsive to oral prednisone 4

Bacterial Infections

• Infectious dacryoadenitis represents a small proportion of cases but requires specific antimicrobial therapy 2

Neoplastic Causes

Lymphoma

• Infiltration of the lacrimal gland with replacement of secretory acini occurs in lymphoma 1
• Accounts for 8% of specific lacrimal gland inflammation cases requiring biopsy 2
• Dacryoadenitis can be a presenting sign of undiagnosed lymphoma, making tissue diagnosis critical 5
• Sjögren's syndrome patients have increased lymphoma risk (5% develop lymphoid malignancy) 1

Epithelial Malignancies

• Myoepithelial carcinoma can present as lacrimal gland enlargement 2
• Pleomorphic adenoma requires complete in-toto removal to prevent recurrence or malignant transformation 6

Infiltrative Systemic Diseases

Hemochromatosis and Amyloidosis

• Result in infiltration of the lacrimal gland with replacement of secretory acini 1

Graft-Versus-Host Disease (GVHD)

• In chronic GVHD, infiltration and fibrosis of the lacrimal glands occurs as a result of T-cell interaction with fibroblasts 1
• Severe dry eye develops in hematopoietic stem cell transplant recipients with or without GVHD 1

Other Specific Causes

• Xanthogranuloma, eosinophilic angiocentric fibrosis, and eosinophilic allergic granulomatous nodules are rare causes 2

Diagnostic Approach

When to Biopsy

• In patients with lacrimal gland inflammation (erythema, edema, tenderness) where specific diagnosis cannot be made clinically or on imaging, biopsy is warranted 2
• 61.7% of biopsied cases have specific identifiable histopathology 2
• 38% of patients with lacrimal gland inflammation have associated systemic diseases 2
• Tissue diagnosis is vital because dacryoadenitis can be the presenting sign of undiagnosed systemic disease and can mimic lymphoma 5

Clinical Pitfall

• Nonspecific inflammation accounts for 38.3% of biopsied cases, but empirical corticosteroid treatment without tissue diagnosis risks missing specific treatable causes or malignancy 2, 5
• Allergic histories and elevated serum IgE levels are present in 50% of IgG4-related dacryoadenitis cases 3