Orbit and Lacrimal Drainage System
Highlights
Nonspecific orbital inflammation comprises a heterogeneous group of
noninfectious inflammatory processes that can affect any part of the orbit.
Lymphoproliferative lesions are among the more common infiltrative processes
in the orbit and can occur within the lacrimal gland or elsewhere in the orbit.
🔥 HIGH-YIELD: Rhabdomyosarcoma is the most common malignant orbital
tumor in children. Urgent action is required to establish a diagnosis and prevent
loss of orbital and ocular function when suspected.
Topography
Bony Orbit and Soft Tissues
Seven bones form the boundaries of the orbit:
ethmoid
frontal
lacrimal
maxillary
palatine
sphenoid
zygomatic bones.
The orbital cavity contains:
globe
lacrimal gland
muscles
tendons
fat
fasciae
vessels
nerves
ciliary ganglion
cartilaginous trochlea.
Inflammatory and neoplastic processes increasing orbital volume lead to:
proptosis (protrusion)
displacement (dystopia) of the globe.
Degree and direction of ocular displacement help localize mass position.
Lacrimal Gland
Situated anteriorly in the superotemporal quadrant of the orbit.
Divided into orbital and palpebral lobes by the lateral portion of the aponeurosis
of the levator palpebrae superioris muscle.
Eccrine gland; acini are round, composed of cuboidal epithelium.
Nucleus located toward the outer edge of the acinus.
Ducts within fibrovascular stroma are lined by 2 layers:
inner low cuboidal epithelium
outer layer of low, flat myoepithelial cells.
Histologic appearance very similar to salivary glands.
Developmental Anomalies
Cysts
Orbital cysts may arise from various ocular surface or orbital tissues.
Types include:
conjunctival/eyelid epithelium cysts
teratomatous cysts
neural cysts
secondary cysts (mucoceles)
inflammatory cysts (parasitic)
solid lesions with a cystic component.
Can be developmental or acquired.
Dermoid cyst
Most common type of orbital cyst; a developmental lesion.
Believed to form when surface ectodermal nests become entrapped in bony
sutures during embryogenesis.
Most manifest in childhood as a unilateral mass in the lateral brow.
Histology:
Lined by keratinized stratified squamous epithelium.
Contains keratin, sebum, and hair.
Walls contain dermal appendages: sebaceous glands, hair follicles, and
sweat glands.
Simple epithelial (epidermoid) cyst: If the cyst wall lacks adnexal structures.
May also be lined by respiratory, conjunctival, or apocrine epithelium.
Rupture of a dermoid cyst may cause a marked granulomatous reaction due to
sebum in the cyst lumen.
Intact excision is preferable.
Inflammation
Orbital inflammation can be idiopathic or secondary to:
Systemic inflammatory process (e.g., granulomatosis with polyangiitis).
Retained foreign body.
Infectious disease.
Can be diffuse (e.g., sclerosing orbititis, diffuse anterior inflammation) or
localized (e.g., orbital myositis, optic perineuritis).
Conditions masquerading as orbital inflammation include developmental orbital
mass lesions and neoplastic disease (e.g., orbital lymphoma,
rhabdomyosarcoma).
Noninfectious Inflammation
Thyroid eye disease (TED)
Also known as Graves disease, thyroid ophthalmopathy, and thyroid-associated
orbitopathy.
Related to thyroid dysfunction.
Most common cause of unilateral and bilateral proptosis (exophthalmos) in
adults.
Signs and symptoms related to:
Inflammation of orbital connective tissue.
Alterations in extracellular matrix of extraocular muscles.
Inflammation and fibrosis of extraocular muscles.
Adipogenesis.
Muscles appear firm and white; tendons usually not involved.
Early stages:
Cellular infiltrate of mononuclear inflammatory cells (lymphocytes, plasma
cells, mast cells) and fibroblasts permeates interstitial tissues of extraocular
muscles.
Most commonly affects inferior and medial rectus muscles.
Fibroblasts synthesize hyaluronic acid (hyaluronan) and other
glycosaminoglycans, leading to muscle enlargement.
Clinical Pearl: Thyroid function test results may be normal in patients with TED.
Orbital fibrocytes (precursor cells of fibroblasts) are derived from neural crest and
are pluripotent; enhanced cell signaling promotes adipocyte differentiation and
adipogenesis.
Increased bulk within the orbit can compromise the optic nerve at the orbital
apex, potentially causing optic nerve head swelling.
Late stages: Associated with progressive fibrosis, resulting in restriction of ocular
movement and severe eyelid retraction with resultant exposure keratitis.
Immunoglobulin G4–related disease (IgG4-RD)
Inflammatory condition characterized by:
Tumefactive lesions in 1 or more organs.
Lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells.
Variable degrees of fibrosis, often in a storiform pattern (whorls of cells).
Obliterative phlebitis.
Elevated serum IgG4 levels.
Orbital and ocular adnexal involvement (IgG4-related ophthalmic disease)
initially described as bilateral and symmetric, with persistent swelling of lacrimal
glands and infiltration of IgG4 plasma cells.
Can manifest in lacrimal glands, extraocular muscles, orbital nerves, sclerae, and
eyelids.
Proposed criteria for IgG4-related ophthalmic disease:
Imaging studies showing lacrimal gland enlargement or a mass lesion
involving the lacrimal gland, trigeminal nerve, or various other ophthalmic
tissues.
Histologic examination showing lymphoplasmacytic infiltration with
associated fibrosis, and with a ratio of IgG4-positive to IgG-positive plasma
cells ≥40% or >50 IgG4-positive plasma cells per high-power field (40×
objective).
Serum IgG4 level ≥135 mg/dL.
Diagnostic criteria and clinical implications continue to evolve.
Occasionally, extranodal marginal zone lymphoma (EMZL) of mucosa-associated
lymphoid tissue (MALT) has been documented to arise in patients with
preexisting IgG4-RD.
Nonspecific orbital inflammation (NSOI)
Also known as orbital pseudotumor or idiopathic orbital inflammatory syndrome.
Space-occupying inflammatory disorder that simulates a neoplasm but has no
recognizable cause.
Accounts for approximately 5% of orbital lesions; affects children and adults.
Clinically, onset is often abrupt, and patients usually report pain.
Inflammatory response may be diffuse or compartmentalized.
Orbital myositis: Localized to an extraocular muscle.
Dacryoadenitis: Localized to the lacrimal gland.
Early stages:
Inflammation predominates.
Mixed inflammatory response (eosinophils, neutrophils, plasma cells,
lymphocytes, histiocytes [macrophages]).
Often perivascular and frequently infiltrates muscle and fat, causing fat
necrosis.
Later stages:
Fibrosis is the predominant feature, often with interspersed lymphoid
follicles with germinal centers.
Fibrosis may replace orbital fat and encase extraocular muscles and the
optic nerve, restricting their function.
"Sclerosing" variant: Some cases show significant fibrosis and collagen
deposition early, lacking typical inflammatory clinical signs. Its classification as a
separate entity or variant of NSOI is controversial.
Differential diagnosis: Lymphoproliferative processes such as lymphoma.
Differentiation from lymphoid tumors: Immunophenotypic and molecular
genetic analyses can differentiate NSOI (polyclonal infiltrate of lymphocytes)
from lymphoma (monoclonal).
IgG4-positive lymphoplasmacytic infiltrates are a marker for IgG4-related
sclerosing disease.
Infectious Inflammation
Bacterial infections of the orbit (orbital cellulitis)
Can occur through:
Direct inoculation (trauma, surgery).
Opportunistic infection (necrotizing fasciitis, mucormycosis).
Spread from infection of adjacent structures (sinusitis) - most common
cause.
Spread from a distant focus (bacteremia).
Common organisms:
Haemophilus influenzae
Streptococcus
Staphylococcus
Clostridium
Bacteroides
Klebsiella
Proteus species.
Organism most commonly involved differs with patient age.
Histology: Acute inflammation, necrosis, and abscess formation may be present.
Tuberculosis: Rarely involves the orbit, produces a necrotizing granulomatous
reaction.
Fungal and parasitic infections of the orbit
Fungal infections generally produce severe, insidious orbital inflammation.
Rhinocerebral or rhino-orbito-cerebral mucormycosis
Usually occurs in patients with:
poorly controlled diabetes (especially with ketoacidosis)
solid malignant neoplasms
extensive burns
corticosteroid treatment
severe neutropenia.
Resurgence during COVID-19 pandemic in those recovering from moderate to
severe SARS-CoV-2 infection.
Typically represents spread from an adjacent sinus infection.
Specific fungal genus involved: Usually Mucor or Rhizopus.
Histologic examination: Inflammation (acute and chronic) in a background of
necrosis, often granulomatous.
Broad, nonseptate hyphae may be identified with hematoxylin and eosin,
periodic acid–Schiff (PAS), and Gomori methenamine silver (GMS) stains.
These fungi can invade blood vessel walls and cause a thrombotic vasculitis,
resulting in ischemic necrosis.
Potential for hematogenous spread to the central nervous system (CNS), leading
to stroke and death.
Diagnosis made by biopsy, often of necrotic-appearing tissues (eschar).
Aspergillus infection of the orbit
Can occur in immunocompromised and otherwise healthy individuals.
Slowly progressive and insidious symptoms often lead to unrecognized sino-
orbital aspergillosis, resulting in a sclerosing granulomatous reaction.
Difficult to culture, but may be observed in biopsied tissue as septate hyphae
with 45° angle branching.
Orbital infections can be fatal if extension into the brain occurs, even with
aggressive surgical therapy and adjunct antifungal agents.
Parasitic infections of the orbit
Rare, especially in high-income countries.
May be caused by:
Echinococcus species (orbital hydatid cyst)
Taenia solium (cysticercosis)
Loa loa (ocular filariasis [loiasis]).
Seen mostly in patients from, or who have traveled to, endemic areas.
Serologic studies for specific parasites may aid diagnosis.
Infections of the lacrimal drainage system
Infections can occur in various parts of the lacrimal drainage system; may be
acute or chronic.
Most commonly affected areas:
canaliculus (canaliculitis)
lacrimal sac (dacryocystitis).
Predisposing factors:
obstruction
presence of foreign material (e.g., dacryolith, punctal plug).
Bacteria, fungi, and viruses can all cause infection.
🔥 HIGH-YIELD: Actinomyces israelii (filamentous gram-positive bacterium) is
the most common causative organism in cases of canaliculitis.
This organism may form a bacterial aggregate (dacryolith) with a characteristic
yellow color, known as a “sulfur granule.”
Degenerations
Amyloid
Amyloid deposition in the orbit can be localized or occur as a manifestation of
systemic amyloidosis.
When amyloid deposition involves the extraocular muscles and nerves, it can
cause ophthalmoplegia and ptosis.
Neoplasia
Neoplasms of the orbit may be primary or secondary (extensions from adjacent
structures or metastatic disease).
Secondary tumors are slightly more common than primary tumors.
Orbital tumors in children vs. adults
Children:
Developmental tumors are most often encountered.
Approximately 90% of orbital tumors are benign.
Benign cystic lesions (dermoid or simple epithelial cysts) represent 50% of
orbital lesions.
🔥 HIGH-YIELD: Rhabdomyosarcoma is the most common primary orbital
malignant tumor in children (3% of all orbital masses).
Orbit may also be involved secondarily in cases of retinoblastoma,
neuroblastoma, and leukemia/lymphoma.
Adults: Vascular and lymphoid tumors are most often seen.
Lacrimal Gland Neoplasia
Lacrimal gland is a modified salivary gland.
Epithelial lacrimal gland tumors are categorized by the WHO epithelial salivary
gland tumor classification system.
Most common types of epithelial lacrimal gland tumors:
Pleomorphic adenoma.
Adenocarcinoma arising from pleomorphic adenoma (carcinoma ex
pleomorphic adenoma).
Adenoid cystic carcinoma.
Pleomorphic adenoma
Also known as benign mixed tumor.
Most common epithelial tumor of the lacrimal gland.
Usually presents in the fourth or fifth decade of life with an indolent painless
proptosis.
Characteristics:
Pseudoencapsulated.
Progressive expansive growth pattern.
Results in smooth bony scalloping without bone destruction.
Tumor growth stimulates the periosteum to deposit a thin layer of new
bone (cortication).
Histology:
Composed of cells of varying morphologies: epithelial, myoepithelial, and
stromal cells.
Has a fibrous pseudocapsule.
Comprises a mixture of duct-derived epithelial and stromal elements, all
arising from the lacrimal glandular epithelium.
Epithelial component may form nests or tubules lined by 2 layers of cells,
with the outermost layer blending imperceptibly with the stroma.
Stroma may appear myxoid and may contain heterologous elements,
including cartilage and bone.
Malignant transformation:
May occur in a long-standing or incompletely excised pleomorphic
adenoma, forming adenocarcinoma (carcinoma ex pleomorphic adenoma).
Characterized by relatively rapid growth after a period of relative
quiescence.
Malignancies (including adenocarcinoma and adenoid cystic carcinoma)
may also develop in pleomorphic adenomas that recur in the orbit.
Treatment: Complete excision with a margin of normal tissue.
Incomplete excision may enable late tumor recurrence.
Clinical Pearl: Incisional biopsy or fine-needle aspiration biopsy should be
avoided to prevent disruption of the pseudocapsule and tumor spillage.
Adenoid Cystic Carcinoma
Clinical Presentation:
Typically presents in the 40–60 year age range.
Unilateral.
Located in the orbital lobe of the lacrimal gland.
Often associated with pain, with or without paresthesia.
Orbital Imaging:
Infiltrative mass with bone destruction.
Perineural invasion is common.
Diffuse contrast enhancement.
Treatment:
Complete excision followed by radiotherapy.
Orbital exenteration versus intra-arterial chemotherapy in advanced cases.
Prognosis: Poor.
Ocular Adnexal Lymphoproliferative Lesions (LPL)
Clinical Presentation:
Typically presents in the 60–70 year age range.
Unilateral or bilateral.
Located in intraconal and extraconal spaces.
No pain.
Orbital Imaging:
Poorly circumscribed homogeneous mass that molds around the globe and
adjacent ocular structures without bony erosion.
Treatment:
Radiotherapy, chemotherapy, or immunotherapy, depending on subtype.
Attempts to perform complete excision may cause damage to adjacent
structures.
Prognosis: Good for EMZL (Extranodal Marginal Zone Lymphoma); poor for LPL
and MCL (Mantle Cell Lymphoma).
Adenoid cystic carcinoma (ACC)
Can develop in an individual with pleomorphic adenoma or, more commonly,
arise de novo.
Slightly more common in women.
Median age at presentation is 40–60 years.
Clinical Presentation:
Rapidly progressive proptosis.
Pain is a prominent symptom, often out of proportion to the size of the
mass.
Perineural invasion is common, leading to paresthesia or numbness in the
distribution of affected nerves.
Histology:
Characterized by basaloid cells arranged in cribriform (sieve-like) patterns,
solid nests, or tubular structures.
Often contains mucinous or hyaline material within the spaces.
Infiltrative growth pattern, often with perineural invasion.
Prognosis: Poor, with high rates of local recurrence and distant metastasis.
Treatment: Aggressive surgical excision, often followed by radiation therapy.
Orbital exenteration may be necessary.
Lymphoproliferative Lesions
Ocular adnexal (conjunctival, orbit, and eyelid) lymphoproliferative lesions are a
diverse group of lymphoid neoplasms that can affect various parts of the ocular
adnexa.
They range from benign reactive lymphoid hyperplasias to malignant
lymphomas.
Classification: Based on the World Health Organization (WHO) classification of
lymphoid neoplasms.
Most common type: Extranodal marginal zone lymphoma (EMZL) of mucosa-
associated lymphoid tissue (MALT lymphoma).
Clinical Presentation:
Often presents as a painless, slowly growing mass.
May cause proptosis, eyelid swelling, or conjunctival mass.
Can be unilateral or bilateral.
Histology:
Dense lymphoid infiltrate composed of small to medium-sized
lymphocytes.
May show plasmacytic differentiation.
Lymphoepithelial lesions (infiltration of glandular epithelium by
lymphocytes) are characteristic of MALT lymphoma.
Immunophenotype:
B-cell lymphomas typically express CD20.
T-cell lymphomas express CD3.
Molecular Genetics:
Translocation t(11;18)(q21;q21) is common in MALT lymphoma and is
associated with resistance to Helicobacter pylori eradication therapy (if
gastric MALT).
Treatment:
Localized disease: Radiation therapy.
Systemic disease: Chemotherapy or immunotherapy.
Watch and wait approach may be considered for indolent cases.
Prognosis: Generally good for MALT lymphoma, but can vary depending on
subtype and stage.
a diverse group of lymphoid neoplasms that can affect various parts of the ocular
adnexa.
They range from benign reactive lymphoid hyperplasias to malignant
lymphomas.
Classification: Based on the World Health Organization (WHO) classification of
lymphoid neoplasms.
Most common type: Extranodal marginal zone lymphoma (EMZL) of mucosa-
associated lymphoid tissue (MALT lymphoma).
Clinical Presentation:
Often presents as a painless, slowly growing mass.
May cause proptosis, eyelid swelling, or conjunctival mass.
Can be unilateral or bilateral.
Histology:
Dense lymphoid infiltrate composed of small to medium-sized
lymphocytes.
May show plasmacytic differentiation.
Lymphoepithelial lesions (infiltration of glandular epithelium by
lymphocytes) are characteristic of MALT lymphoma.
Immunophenotype:
B-cell lymphomas typically express CD20.
T-cell lymphomas express CD3.
Molecular Genetics:
Translocation t(11;18)(q21;q21) is common in MALT lymphoma and is
associated with resistance to Helicobacter pylori eradication therapy (if
gastric MALT).
Treatment:
Localized disease: Radiation therapy.
Systemic disease: Chemotherapy or immunotherapy.
Watch and wait approach may be considered for indolent cases.
Prognosis: Generally good for MALT lymphoma, but can vary depending on
subtype and stage.
a diverse group of lymphoid neoplasms that can affect various parts of the ocular
adnexa.
They range from benign reactive lymphoid hyperplasias to malignant
lymphomas.
Classification: Based on the World Health Organization (WHO) classification of
lymphoid neoplasms.
Most common type: Extranodal marginal zone lymphoma (EMZL) of mucosa-
associated lymphoid tissue (MALT lymphoma).
Clinical Presentation:
Often presents as a painless, slowly growing mass.
May cause proptosis, eyelid swelling, or conjunctival mass.
Can be unilateral or bilateral.
Histology:
Dense lymphoid infiltrate composed of small to medium-sized
lymphocytes.
May show plasmacytic differentiation.
Lymphoepithelial lesions (infiltration of glandular epithelium by
lymphocytes) are characteristic of MALT lymphoma.
Immunophenotype:
B-cell lymphomas typically express CD20.
T-cell lymphomas express CD3.
Molecular Genetics:
Translocation t(11;18)(q21;q21) is common in MALT lymphoma and is
associated with resistance to Helicobacter pylori eradication therapy (if
gastric MALT).
Treatment:
Localized disease: Radiation therapy.
Systemic disease: Chemotherapy or immunotherapy.
Watch and wait approach may be considered for indolent cases.
Prognosis: Generally good for MALT lymphoma, but can vary depending on
subtype and stage.
a diverse group of lymphoid neoplasms that can affect various parts of the ocular
adnexa. * They range from benign reactive lymphoid hyperplasias to malignant
lymphomas. * Classification: Based on the World Health Organization (WHO)
classification of lymphoid neoplasms. * Most common type: Extranodal marginal zone
lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT lymphoma). * Clinical
Presentation: * Often presents as a painless, slowly growing mass. * May cause
proptosis, eyelid swelling, or conjunctival mass. * Can be unilateral or bilateral. *
Histology: * Dense lymphoid infiltrate composed of small to medium-sized
lymphocytes. * May show plasmacytic differentiation. * Lymphoepithelial lesions
(infiltration of glandular epithelium by lymphocytes) are characteristic of MALT
lymphoma. * Immunophenotype: * B-cell lymphomas typically express CD20. * T-cell
lymphomas express CD3. * Molecular Genetics: * Translocation t(11;18)(q21;q21) is
common in MALT lymphoma and is associated with resistance to Helicobacter pylori
eradication therapy (if gastric MALT). * Treatment: * Localized disease: Radiation
therapy. * Systemic disease: Chemotherapy or immunotherapy. * Watch and wait
approach may be considered for indolent cases. * Prognosis: Generally good for MALT
lymphoma, but can vary depending on subtype and stage.
ise from a diverse group of lymphoid neoplasms that can affect various parts of the
ocular adnexa. They range from benign reactive lymphoid hyperplasias to malignant
lymphomas. The most common type is extranodal marginal zone lymphoma (EMZL) of
mucosa-associated lymphoid tissue (MALT lymphoma). Clinical presentation often
includes a painless, slowly growing mass, which may cause proptosis, eyelid swelling,
or conjunctival mass, and can be unilateral or bilateral. Histologically, these lesions
show a dense lymphoid infiltrate composed of small to medium-sized lymphocytes,
sometimes with plasmacytic differentiation. Lymphoepithelial lesions, characterized
by the infiltration of glandular epithelium by lymphocytes, are typical of MALT
lymphoma. Immunophenotypically, B-cell lymphomas typically express CD20, while T-
cell lymphomas express CD3. Molecular genetic analysis often reveals a translocation
t(11;18)(q21;q21) in MALT lymphoma, which is associated with resistance to
Helicobacter pylori eradication therapy (if gastric MALT). Treatment for localized
disease usually involves radiation therapy, while systemic disease may require
chemotherapy or immunotherapy. A watch and wait approach can be considered for
indolent cases. The prognosis for MALT lymphoma is generally good, but it can vary
depending on the specific subtype and stage of the disease.
ise from a diverse group of lymphoid neoplasms that can affect various parts of the
ocular adnexa. They range from benign reactive lymphoid hyperplasias to malignant
lymphomas. The most common type is extranodal marginal zone lymphoma (EMZL) of
mucosa-associated lymphoid tissue (MALT lymphoma). Clinical presentation often
includes a painless, slowly growing mass, which may cause proptosis, eyelid swelling,
or conjunctival mass, and can be unilateral or bilateral. Histologically, these lesions
show a dense lymphoid infiltrate composed of small to medium-sized lymphocytes,
sometimes with plasmacytic differentiation. Lymphoepithelial lesions, characterized
by the infiltration of glandular epithelium by lymphocytes, are typical of MALT
lymphoma. Immunophenotypically, B-cell lymphomas typically express CD20, while T-
cell lymphomas express CD3. Molecular genetic analysis often reveals a translocation
t(11;18)(q21;21) in MALT lymphoma, which is associated with resistance to
Helicobacter pylori eradication therapy (if gastric MALT). Treatment for localized
disease usually involves radiation therapy, while systemic disease may require
chemotherapy or immunotherapy. A watch and wait approach can be considered for
indolent cases. The prognosis for MALT lymphoma is generally good, but it can vary
depending on the specific subtype and stage of the disease.
