Ophthalmology – Lacrimal Gland Tumors

Basics

Description

Lacrimal gland tumors and masses comprise a broad group of disorders involving the lacrimal gland in the superotemporal orbit. They may be:

• Epithelial or nonepithelial
• Benign or malignant
• Inflammatory or neoplastic
• Primary or metastatic

Only a minority of orbital lesions arise from the lacrimal gland, and most lacrimal gland enlargements are nonepithelial, particularly inflammatory or lymphoid disorders.

Important categories include:

• Inflammatory dacryoadenitis
• Idiopathic orbital inflammatory disease
• Sarcoidosis
• Lymphoid tumors
• Dacryops
• Pleomorphic adenoma
• Adenoid cystic carcinoma
• Other epithelial malignancies
• Metastatic disease

The clinical behavior varies widely, so the tempo of growth, presence of pain, globe displacement, imaging characteristics, and bone involvement are particularly important.

Epidemiology

Approximately 10% of orbital lesions involve the lacrimal gland.

Most lacrimal gland lesions are nonepithelial. Important nonepithelial causes include:

• Inflammatory disease
• Lymphoma
• Reactive lymphoid hyperplasia
• Sarcoidosis

Among epithelial tumors, benign lesions include pleomorphic adenoma and ductal cysts such as dacryops, while adenoid cystic carcinoma is one of the most important malignant epithelial tumors.

Adenoid Cystic Carcinoma

Adenoid cystic carcinoma can occur at almost any age but most often presents in adulthood.

It is notable for:

• Relatively rapid progression
• Pain
• Bone destruction
• Perineural invasion
• Local recurrence
• Potential intracranial and systemic spread

Pain is an especially important warning sign because perineural invasion is characteristic.

Dacryops

A dacryops is a ductal cyst involving the lacrimal gland, often the palpebral lobe.

It is usually:

• Benign
• Slowly growing
• Painless
• Occasionally visible beneath the superior temporal conjunctiva

Many require no treatment unless they become symptomatic or enlarge.

Lymphoid Lesions

Lymphoid disease of the lacrimal gland includes:

• Reactive lymphoid hyperplasia
• Atypical lymphoid hyperplasia
• Non-Hodgkin lymphoma

Orbital lymphoma is more common in older adults and often presents as a painless, slowly enlarging lacrimal gland mass.

Idiopathic Orbital Inflammation

Idiopathic orbital inflammatory disease may involve the lacrimal gland and present as inflammatory dacryoadenitis.

It commonly produces:

• Acute pain
• Swelling of the lateral upper eyelid
• Tenderness
• Conjunctival injection
• Diplopia
• Proptosis

A rapid response to corticosteroids may occur, but corticosteroid responsiveness does not by itself establish the diagnosis.

Sarcoidosis

The lacrimal gland is one of the most commonly affected orbital structures in sarcoidosis.

Lacrimal gland involvement may be:

• Bilateral
• Painless or mildly uncomfortable
• Associated with dry eye
• Associated with systemic pulmonary, skin, or lymph node disease

Sarcoidosis is particularly important in younger and middle-aged adults.

Risk Factors

Risk factors depend on the underlying pathology.

Malignant Epithelial Tumors

Important concerns include:

• Previous incomplete excision of a lacrimal gland epithelial tumor
• Recurrent pleomorphic adenoma
• Longstanding lesion with recent acceleration in growth

Incomplete excision of pleomorphic adenoma can lead to recurrence and, rarely, malignant transformation.

Lymphoma

Sjögren syndrome and other chronic autoimmune conditions may increase the risk of ocular adnexal lymphoma.

Inflammatory Disease

Immune-mediated disease and systemic inflammatory disorders may predispose to lacrimal gland inflammation.

Genetics

Genetic abnormalities vary according to tumor type.

Certain lymphomas have characteristic chromosomal translocations and molecular abnormalities.

Sarcoidosis has complex genetic susceptibility with HLA and other immune-related associations.

Most benign epithelial lacrimal gland tumors do not have a simple inherited pattern.

General Prevention

There is no reliable strategy to prevent most lacrimal gland tumors.

The most important preventive principle is appropriate management of a suspected pleomorphic adenoma, because incomplete biopsy or piecemeal excision can increase the risk of recurrence.

Etiology

Epithelial Lesions

Important epithelial lesions include:

• Dacryops
• Pleomorphic adenoma
• Adenoid cystic carcinoma
• Carcinoma ex pleomorphic adenoma
• Mucoepidermoid carcinoma
• Other adenocarcinomas

Nonepithelial Lesions

These include:

• Idiopathic inflammatory dacryoadenitis
• Lymphoma
• Reactive lymphoid hyperplasia
• Sarcoidosis
• Leukemia
• Granulomatosis with polyangiitis
• Metastatic disease
• Plasmacytoma
• Dermoid lesions
• Infectious dacryoadenitis

Commonly Associated Conditions

Lymphoma

A pink, fleshy salmon-patch conjunctival lesion may accompany ocular adnexal lymphoma.

Sjögren syndrome is associated with increased lymphoma risk.

Sarcoidosis

Associated systemic findings include:

• Pulmonary disease
• Bilateral hilar lymphadenopathy
• Uveitis
• Skin disease
• Parotid enlargement
• Cranial neuropathies

Heerfordt Syndrome

This may include:

• Parotid enlargement
• Uveitis
• Facial nerve palsy
• Fever

Löfgren Syndrome

This includes:

• Erythema nodosum
• Bilateral hilar lymphadenopathy
• Arthritis or arthralgia

Diagnosis

History

The history should focus on:

• Duration of the mass
• Rate of enlargement
• Pain
• Diplopia
• Visual decline
• Previous orbital surgery
• Previous lacrimal gland biopsy
• Previous malignancy
• Autoimmune disease
• Constitutional symptoms
• Respiratory symptoms

The pattern of symptoms often provides clues to the underlying pathology.

Clinical Patterns

Benign Epithelial Tumor

A benign epithelial tumor such as pleomorphic adenoma typically causes:

• Slow, painless progression
• Proptosis
• Inferonasal globe displacement
• Upper eyelid fullness

The course may extend over months to years.

Malignant Epithelial Tumor

Features concerning for malignancy include:

• Relatively rapid growth
• Significant pain
• Sensory disturbance
• Diplopia
• Ptosis
• Bone destruction
• Perineural symptoms
• Reduced vision

Adenoid cystic carcinoma is especially associated with pain from perineural invasion.

Inflammatory Dacryoadenitis

Inflammatory disease tends to present more abruptly with:

• Pain
• Tender upper eyelid swelling
• Redness
• Conjunctival chemosis
• Tearing
• Diplopia

The lateral upper eyelid may develop an S-shaped contour.

Lymphoma

Lymphoma often presents as:

• Painless
• Slowly progressive
• Firm lacrimal gland enlargement
• Proptosis
• Globe displacement

Bilateral disease is possible.

Physical Examination

A complete ophthalmic and orbital examination should include:

• Visual acuity
• Pupillary examination
• Color vision
• Visual fields
• Intraocular pressure
• Extraocular movements
• Eyelid position
• Proptosis measurement
• Cranial nerve examination
• Slit-lamp examination
• Dilated fundus examination

Globe Displacement

Lacrimal gland masses characteristically displace the globe inferonasally because the gland lies in the superotemporal orbit.

The degree and direction of displacement provide useful localization information.

Optic Nerve Assessment

Large or posterior lesions can compress the optic nerve.

Signs of compressive optic neuropathy include:

• Reduced visual acuity
• Dyschromatopsia
• Relative afferent pupillary defect
• Visual field loss
• Optic disc edema or pallor

Any evidence of optic nerve compromise requires urgent evaluation.

Anterior Segment Findings

Depending on the underlying disorder, slit-lamp examination may demonstrate:

• Conjunctival masses
• Conjunctival inflammation
• Episcleritis
• Scleritis
• Dry eye
• Keratic precipitates
• Anterior chamber cells and flare
• Synechiae

These findings may point toward inflammatory or systemic disease such as sarcoidosis.

Posterior Segment Findings

Possible findings include:

• Retinal vasculitis
• Peripheral vascular sheathing
• Intermediate uveitis
• Optic disc swelling

These are more suggestive of systemic inflammatory conditions than isolated epithelial tumors.

Systemic Examination

When systemic inflammatory or malignant disease is suspected, examination should look for:

• Lymphadenopathy
• Skin lesions
• Erythema nodosum
• Arthritis
• Hepatosplenomegaly
• Pulmonary signs

Diagnostic Tests and Interpretation

Laboratory Evaluation

Laboratory testing should be guided by the clinical differential rather than performed indiscriminately.

Possible tests include:

• CBC with differential
• ESR and CRP
• Serum protein electrophoresis
• ACE and other sarcoid-directed testing
• ANCA when granulomatosis with polyangiitis is suspected
• ANA when autoimmune disease is suspected
• Syphilis serology
• Tuberculosis testing

Modern sarcoidosis workup generally relies more heavily on the overall clinical picture and tissue confirmation than on ACE alone.

Orbital Imaging

CT

Orbital CT is useful for evaluating:

• Tumor location
• Bone remodeling
• Bone erosion or destruction
• Calcification
• Extension into adjacent structures

Bone destruction strongly increases concern for malignancy or aggressive inflammation.

MRI

MRI provides superior soft-tissue characterization and is useful for assessing:

• Perineural spread
• Intracranial extension
• Cavernous sinus involvement
• Orbital apex extension
• Relationship to surrounding muscles and nerves

Contrast-enhanced MRI is especially valuable when malignant disease is suspected.

Chest Imaging

Chest radiography or CT may be indicated if considering:

• Sarcoidosis
• Tuberculosis
• Metastatic disease
• Primary thoracic malignancy

Biopsy Principles

Biopsy strategy depends strongly on the suspected diagnosis.

Important Principle – Pleomorphic Adenoma

A lesion strongly suspected to be a pleomorphic adenoma should generally not undergo incisional biopsy, because violating the pseudocapsule can seed tumor cells and increase the risk of recurrence.

The preferred approach is complete intact excision when technically appropriate.

Inflammatory or Lymphoid Lesions

Biopsy is often appropriate when:

• The diagnosis is uncertain
• Lymphoma is suspected
• The lesion is atypical
• Steroid response is incomplete
• The disease recurs
• Malignancy is possible

Preferred Biopsy Site

When lacrimal gland biopsy is required, the orbital lobe is often preferred when feasible to reduce damage to the ductules of the palpebral lobe and thereby reduce postoperative dry eye.

Sarcoidosis Biopsy

Tissue may be obtained from:

• Lacrimal gland
• Conjunctiva
• Skin lesion
• Lymph node
• Pulmonary tissue

Histology demonstrates noncaseating granulomas, but infectious causes of granulomatous inflammation must be excluded.

Special stains and microbiologic testing may be necessary for:

• Mycobacteria
• Fungal organisms

Pathological Findings

Adenoid Cystic Carcinoma

Histologic patterns include:

• Cribriform
• Tubular
• Basaloid
• Solid
• Other mixed patterns

Perineural invasion is a characteristic and clinically important feature.

Pleomorphic Adenoma

Pleomorphic adenoma contains a mixture of:

• Epithelial elements
• Myoepithelial elements
• Myxoid or chondroid stroma

Sarcoidosis

Typical pathology shows noncaseating granulomas after exclusion of infection.

Idiopathic Orbital Inflammation

Pathology may show a mixed inflammatory infiltrate with:

• Lymphocytes
• Plasma cells
• Macrophages
• Variable eosinophils
• Fibrosis
• Tissue edema

Differential Diagnosis

Important differential diagnoses include:

• Pleomorphic adenoma
• Adenoid cystic carcinoma
• Lymphoma
• Reactive lymphoid hyperplasia
• Idiopathic orbital inflammation
• Sarcoidosis
• Granulomatosis with polyangiitis
• Metastatic tumor
• Leukemia
• Dermoid cyst
• Prolapsed orbital fat
• Infectious dacryoadenitis
• Perilacrimal orbital tumors

Prolapsed orbital fat can mimic lacrimal gland enlargement, particularly in older adults.

Treatment

Treatment depends entirely on the underlying diagnosis.

Pleomorphic Adenoma

The preferred treatment is complete surgical excision with the capsule intact.

Incomplete excision should be avoided because it increases the risk of:

• Recurrence
• Multifocal seeding
• Malignant transformation

Dacryops

Asymptomatic lesions may be observed.

Symptomatic or enlarging lesions may undergo:

• Marsupialization
• Complete excision

depending on location and anatomy.

Adenoid Cystic Carcinoma

Management usually requires multidisciplinary orbital oncology care.

Treatment may involve combinations of:

• Complete surgical resection when feasible
• Radiation therapy
• Systemic therapy in selected cases

The historical use of routine orbital exenteration has evolved, and modern treatment is individualized according to tumor extent, margins, perineural spread, and available eye-sparing oncologic approaches.

Lymphoma

Treatment begins with tissue diagnosis and staging.

Management may include:

• Local radiation for localized disease
• Systemic immunotherapy
• Chemotherapy
• Combined approaches

Treatment depends on lymphoma subtype and systemic involvement.

Sarcoidosis

Treatment depends on severity.

Possible approaches include:

• Observation for mild disease
• Systemic corticosteroids
• Steroid-sparing immunomodulatory therapy

Surgery is generally limited to diagnostic biopsy or selected cases requiring decompression.

Idiopathic Orbital Inflammation

Corticosteroids are commonly used when the diagnosis is sufficiently secure.

A prompt clinical response is expected in many cases.

However, lack of response, recurrence, or atypical imaging should prompt reconsideration of the diagnosis and often biopsy.

Steroid-resistant disease may require:

• Immunomodulatory therapy
• Radiation therapy
• Alternative diagnosis workup

Infectious Dacryoadenitis

Infectious causes require organism-directed treatment.

Bacterial disease may require:

• Systemic antibiotics
• Drainage if abscess develops

Steroids should not be given as stand-alone treatment if infection remains possible.

Referral

Referral may include:

• Oculoplastic/orbital surgeon
• Ocular oncologist
• Hematology/oncology
• Rheumatology
• Pulmonology
• Neurology or neurosurgery
• Infectious disease

depending on the suspected pathology.

Inpatient Considerations

Admission may be required for:

• Compressive optic neuropathy
• Rapidly progressive orbital inflammation
• Severe infection
• Intravenous corticosteroid treatment
• Orbital surgery
• Significant neurologic extension

Optic nerve dysfunction from a lacrimal gland mass requires urgent management.

Follow-Up

Follow-up depends on etiology.

Inflammatory disease may require close review during active treatment, often within days to weeks.

Malignant tumors require long-term surveillance for:

• Local recurrence
• Perineural spread
• Distant metastasis

Benign lesions that have been completely excised generally require less intensive monitoring but still need assessment for recurrence when clinically indicated.

Monitoring During Corticosteroid Therapy

Patients receiving prolonged corticosteroids should be monitored for:

• Elevated IOP
• Cataract
• Hyperglycemia
• Hypertension
• Bone loss
• Other systemic adverse effects

Coordination with primary care or relevant medical specialists is important.

Prognosis

Prognosis varies dramatically with the underlying diagnosis.

Benign Lesions

Completely excised benign epithelial tumors generally have an excellent prognosis.

Inflammatory Disease

Idiopathic inflammation and sarcoidosis often respond well to treatment but can recur.

Lymphoma

Prognosis depends on histologic subtype and systemic stage.

Adenoid Cystic Carcinoma

Adenoid cystic carcinoma has a more guarded prognosis because of:

• Perineural invasion
• Local recurrence
• Intracranial extension
• Distant metastasis

Long-term surveillance is essential.

Complications

Potential complications include:

• Proptosis
• Diplopia
• Ptosis
• Exposure keratopathy
• Dry eye after lacrimal gland surgery
• Optic neuropathy
• Vision loss
• Tumor recurrence
• Intracranial extension
• Metastatic disease

The key clinical pearl is: a slowly enlarging painless superotemporal orbital mass suggests a benign epithelial or lymphoid lesion, whereas rapid growth, pain, sensory symptoms, bone destruction, or perineural involvement should raise strong suspicion for lacrimal gland malignancy, particularly adenoid cystic carcinoma.