The lacrimal gland receives its blood supply from the lacrimal artery, which arises from the ophthalmic artery lateral to the optic nerve and proceeds along the upper border of the lateral rectus muscle together with the lacrimal nerve. Venous drainage is through the lacrimal vein, which drains to the superior ophthalmic vein. Chemotherapy may be administered directly into the lacrimal artery or systemically through the intravenous route; lacrimal gland carcinomas may seed elsewhere through the lacrimal vein.
The lacrimal nerve provides sensory innervation for the lateral upper forehead and is a frequent conduit for perineural spread of lacrimal epithelial malignancies into the posterior orbit and cranium.
The reflex tearing pathway consists of both an afferent and efferent pathway. The afferent pathway consists of sensory fibers from the corneal surface (carried with the long posterior ciliary nerves) and sensory and olfactory nerves from the nasal cavity. The efferent pathway arises in the lacrimal nucleus in the ventral pons: parasympathetic fibers are carried with the seventh nerve to the greater petrosal nerve and synapse within the sphenopalatine ganglion within the pterygopalatine fossa. Postganglionic fibers enter the orbit through the inferior fissure, form a plexus with sympathetic fibers behind the globe, and mediate lacrimal secretion (Fig. 17.2).
Epidemiology
The true incidence of specific lacrimal gland lesions is difficult to ascertain because of methodology biases. For example, some series are based on general clinical populations while others are drawn from tertiary referral centers.1–12 Furthermore, some series include all lacrimal fossa lesions while others include only biopsy-proven diagnoses.
An oft-quoted 1956 study found that half of lacrimal fossa lesions were epithelial tumors; among those, one-half were malignant.3 Two later studies found that only one-third of lacrimal fossa lesions were of epithelial origin and that the incidence of epithelial malignancies was low. A more recent series that included only biopsy-proven lacrimal gland lesions found 60% epithelial tumors, 30% inflammation, and 10% lymphoproliferative disease (Table 17.2).1 This is obviously not representative of the general population of patients who present with lacrimal gland masses. Despite these disparate statistics, inflammatory lesions constitute the most common lacrimal fossa lesion followed by lymphoproliferative disease and epithelial tumors.1,5,6,18
Table 17.2
Epithelial Tumors of the Lacrimal Gland*
| BENIGN | |
| Pleomorphic adenoma (benign mixed tumor) | 48% |
| Other benign tumors | 1% |
| MALIGNANT | |
| Adenoid cystic carcinoma | 30% |
| Pleomorphic adenocarcinoma (malignant mixed tumor, carcinoma ex pleomorphic adenoma) | 9% |
| Mucoepidermoid carcinoma | 2% |
| Adenocarcinoma | 4% |
| Undifferentiated carcinoma | 3% |
| Other malignant tumors | 3% |
The age distribution varies among these various conditions. Infection of the lacrimal gland is more common in children, whereas noninfectious inflammations occur frequently in young and middle-aged populations.25 Lymphoma is frequent in the sixth decade of life but may occur at all ages. Epithelial tumors may also occur in patients of all ages but are primarily a disease of middle-aged adults. PA, the most common primary lacrimal gland solid tumor, presents at a mean age of 40 years, with a range from 8 to 80 years.26 Adenoid cystic carcinoma (ACC), the most common lacrimal gland epithelial malignancy, has a bimodal age distribution, with most patients diagnosed in their 40s and a smaller peak in the teenage years.27 Carcinoma ex PA, adenocarcinoma, and MEC all have a mean age at presentation of approximately 50 to 52 years.8,9,28 MEC is diagnosed slightly more often in women (female/male ratio 3 : 2) and adenocarcinoma more commonly in men, whereas there is no apparent gender predilection for PA, ACC, or carcinoma ex PA.29,30 No racial predilection has been reported for any of the lacrimal gland epithelial tumors.5,8,28,31
Bilateral involvement of the lacrimal glands suggests either an inflammatory or lymphoproliferative process. Bilateral involvement is rare in epithelial lesions.
Inflammatory Lesions
Dacryoadenitis can result from infection or autoimmune disease. Acute cases are more commonly nonspecific idiopathic or related to infection, whereas chronic cases are frequently caused by a granulocytic or fibrotic processes of autoimmune origin. Lacrimal gland inflammation is also discussed in Chapters 10 and 11.
Infectious Dacryoadenitis
Infectious dacryoadenitis is thought to be caused by ascension of an inciting agent from the conjunctiva through the lacrimal ductules into the lacrimal gland or from direct hematogenous spread.32 It can be caused by viral, bacterial, or fungal infection. Infectious dacryoadenitis may involve either lobe of the lacrimal gland separately or both at the same time; 50% of the cases are bilateral.
Clinical Features
Presenting symptoms include pain, epiphora, chemosis, conjunctival injection, mucous discharge, and fullness of the superior sulcus and of the eyelid, which may become erythematous and edematous, assuming an S-shaped configuration. In children, the subcutaneous edema often may extend into the temple and cheek in association with enlarged preauricular lymph nodes. Involvement of the orbital portion of the gland is often associated with proptosis and painful eye movements (Fig. 17.3).
Infectious dacryoadenitis may be found in children with mumps, measles, influenza, scarlet fever, or erysipelas. In adulthood, it tends to occur with diabetes and other immune deficiency states.
Management
Acute dacryoadenitis is usually self-limited. In the acute phase, cold compresses, steroid ointment, and oral antipyretic drugs may offer some relief. If bacterial infection is suspected (mucopurulent discharge, history of trauma, or systemic bacterial infection), systemic antibiotics should be administered.33 One common regimen would be amoxicillin/clavulanate 875 mg by mouth every 12 hours for 7 days. A response to appropriate antibiotic therapy should be apparent within the first 48 to 72 hours, with complete resolution of the disease in approximately 1 week. An inadequate response should prompt diagnostic biopsy. Ultrasonography, CT, and MRI may help refine the diagnosis, but their use depends on patient age. Biopsy-proven chronic infectious dacryoadenitis should be treated with antibiotics, as guided by culture sensitivities and infectious disease consultation.
Autoimmune Dacryoadenitis
Inflammation resulting from autoimmune disease can arise in the setting of named disorders or may be entirely nonspecific. The former group traditionally includes sarcoidosis, Sjögren syndrome, Churg-Strauss syndrome, and granulomatosis with polyangiitis (GPA, Wegener disease).34–38 A number of cases previously described as idiopathic orbital inflammation probably represent a newly recognized entity, IG4-related disease (IG4-RD). Hence, the reports of sclerosing or fibrotic dacryoadenitis caused by this specific inflammation are increasing (Fig. 17.4).
Clinical Features
Noninfectious dacryoadenitis shares similar clinical features to infectious disease, with the exception of the sclerosing variant.16 In contrast, sclerosing disease progresses gradually over 1 month to 1 year into a firm mass; this may result in diplopia, proptosis, impairment of vision, and persistent pain and, over time, become very difficult to treat. In the majority of reported cases the involvement is bilateral,36,37 but unilateral presentation has been reported.35
Management
For typical acute dacryoadenitis, a short course of oral corticosteroid (prednisolone 1 mg/kg/day) may be administered to control the inflammatory symptoms, to minimize the recurrence, and to confirm the diagnosis. If adequate response occurs within the first 72 hours, the initial high dose may be maintained for 1 week and then tapered over 6 weeks. Most cases of acute idiopathic inflammations will respond to several weeks of oral corticosteroids; however, refractory diseases such as GPA, sclerosing inflammations, and IgG4-RD may require several months of low-dose corticosteroids, often in combination with other immunosuppressives under the co-management of a rheumatologist.
Controversy: A notable response to corticosteroids within 48 to 72 hours confirms the diagnosis of inflammatory dacryoadenitis.25 Atypical presentation, recurrent disease, or inadequate response to medical treatment requires surgical biopsy. Other authorities recommend biopsy in advance of anti-inflammatory treatment to avoid diminishing the value of the biopsy specimen. Specific inflammatory diseases such as GPA, sarcoidosis, or Churg-Strauss syndrome require specific, individual treatment protocols (see Chapter 11).6,34,38 The sclerosing variant of the idiopathic orbital inflammation (IgG4-RD) constitutes a peculiar subgroup with a tendency to progress despite immunosuppressive treatment.41 In selected cases, surgical debulking of the fibrotic mass may be helpful.
Lymphoproliferative Disorders
Lymphoproliferative lesions include benign reactive lymphoid hyperplasia, atypical lymphoproliferative process, and malignant lymphomas.42 This spectrum of diseases is fully covered in Chapter 15.
Epidemiology
Primary orbital lymphoma represents 1% of all non-Hodgkin lymphoma (NHL) and 8% of extranodal NHL.41 Although the rate of lacrimal gland lymphoma is disputed,5,18 the most recent review1 on orbital expanding lesions showed that NHL accounted for 7% of lesions of lacrimal gland and for 3% of all lesions in the superotemporal orbital quadrant. Hodgkin disease involving the lacrimal gland has not been reported. Lymphomas are increasing in incidence worldwide.
Pathogenesis
The orbit lacks a native population of lymphocytes and native lymphatic channels and is therefore considered an extranodal site. Mucosal organs contain a specific part of the immune system, termed mucosa-associated lymphoid tissue (MALT).41 The association between infections such as with Epstein-Barr virus or Chlamydia psittaci and NHL has been postulated and observed in Italy, the United States, and Japan.43 However, this issue remains controversial because of the findings from other studies. The variable worldwide prevalence of those infections, together with different environmental and genetic factors, could explain these conflicting results.
Clinical Features
Most patients with lacrimal gland lymphomas are over 65 years of age at the time of diagnosis. The most common manifestation of the disease is a slowly progressive, nontender, unilateral, or bilateral enlargement of the lacrimal gland causing inferior globe displacement, proptosis, and an S-shaped deformity of the lid. Bilateral involvement occurs in 10% to 15% of cases of primary orbital lymphoma.41
Pathology
The most frequent histology of primary orbital lymphoma is extranodal marginal zone B-cell lymphoma of MALT. Diffuse large-cell lymphoma, follicular lymphoma, and marginal cell lymphoma also occur in the lacrimal gland. In one of the largest cohort studies46 on lymphoma of the ocular adnexa, 61% of orbital MALT lymphomas involved the lacrimal glands, and follicular lymphomas were the second most common. Mantle cell lymphoma, chronic lymphocytic leukemia, and lymphoplasmacytic lymphomas of the orbit are rare.
Management
Surgery alone is generally not recommended unless a discrete mass is encountered because of the high rate of local relapses. In patients diagnosed with lymphoma, systemic evaluation is necessary to stage the disease and determine appropriate therapy. Localized disease may be controlled in over 90% of cases by using low-dose radiotherapy (20–36 Gy).41 Systemic disease is usually treated with combination chemotherapy,47,48 depending on stage and histopathologic grade (see Chapter 15).
Epithelial Tumors
Epithelial tumors are the third most common lacrimal gland masses and include both benign and malignant tumors.
Pleomorphic Adenoma (Benign Mixed Tumor)
Epidemiology
PA is the most frequent neoplasm of the lacrimal gland in all series and accounts for approximately 50% of all lacrimal gland epithelial tumors.1,5 The highest incidence occurs in the fourth and fifth decades.49
Clinical Features
The typical clinical presentation of PA is an insidious onset of painless proptosis with inferonasal displacement of the globe and lateral upper lid fullness (Fig. 17.6A). Atypical presentations may also occur.13–15,42,49 Duration of symptoms may range from 1 month to more than 5 years. The orbital lobe of the lacrimal gland is generally affected; PA arising from the palpebral lobe is rare.
Investigations
On CT or MRI, lacrimal gland PA presents as a round to oval, well-circumscribed lesion. PA may have variable attenuation because of disparate composition and cellularity within an individual tumor (Fig. 17.6B). Highly cellular regions are homogeneous, whereas less cellular areas tend to show nonhomogeneous attenuation as a result of mesenchymal stroma, cystic degeneration, necrosis, or serous or mucus collection. Calcifications and anterior extension of the mass beyond the orbital rim are rare. The same features are found on MRI, since small tumors with a compact epithelial component appear as relatively homogeneous lesions of intermediate signal intensity on T1-weighted images and appear as high signal intensity on T2-weighted images, whereas large tumors with abundant mesenchymal component, hemorrhage, or necrosis exhibit heterogeneous signal intensity on T1- and T2-weighted images.40,44,45
Pathology
PA is characterized by a proliferation of both epithelial and mesenchymal components in varying proportions. The epithelial cells form characteristic ductal structures with surrounding myoepithelial cells, which blend gradually into myxomatous mesenchyme.50,51
The epithelial component is usually a mixture of well-formed ductal structures with closely associated nonductal cells that include spindle, round, stellate, plasmacytoid, oncocytoid, polygonal, and clear forms. Squamous metaplasia occurs rarely. The mesenchymal component demonstrates varying degrees of myxoid, hyaline, cartilagenous, or osseous differentiation. Multifocal and multinodular growth patterns have an increased risk of recurrence51 (Fig. 17.6D and E).
Management
Surgical removal is the mainstay of treatment for patients with lacrimal gland PA. En bloc removal is always recommended in suspected cases (Fig. 17.6C).49 Preservation of the palpebral lobe during surgery, when possible, may help to mitigate loss of reflex or emotional tearing. When the tumor is large and extends posteriorly, a lateral orbitotomy facilitates en bloc excision, including the overlying periorbita.
The prognosis of PA depends on its risk for recurrence or malignant transformation. The 5-year recurrence rate is negligible for completely excised lesions but is reported to be as high as 30% for incompletely excised tumors. The likelihood of malignant transformation of PA appears to be related to tumor stage, with a 10% incidence of malignant transformation of recurrent adenomas by 20 years after treatment and 20% by 30 years.28 However, in a recent large multicenter study on lacrimal gland epithelial tumors, no transformation of recurrent cases was found even with long follow-up.19 The higher rates reported earlier probably represent cases with incomplete excision or biopsy alone.
Controversy: Incompletely excised PA carries a risk of recurrence or malignant transformation at a rate of approximately 1% per year. Classic teaching, therefore, recommends en bloc resection for solid round tumors of the lacrimal gland suspicious for PA. However, this policy will occasionally lead to unnecessary excision of lacrimal glands with lesions such as lymphoproliferations mistaken for PA that otherwise be adequately treated with corticosteroids or immunosuppressives.13 Some surgeons have shown excellent diagnostic benefit from fine-needle aspiration biopsy (FNAB) with minimal risk of seeding even with PA. Others feel that sampling with FNAB is insufficient for these mixed tumors, as malignant regions have been found on sectioning in some cases. Generally, large-bore needle and core sampling are felt to increase risk of tumor seeding and are not recommended.51
Rare Benign Epithelial Tumors of the Lacrimal Gland
Myoepithelioma is a benign neoplasm primarily composed of myoepithelial cells that can successfully be treated with complete excision. Oncocytoma comprises epithelial cells characterized histologically as having abundant eosinophilic cytoplasm full of mitochondria. In the ocular adnexa, they are most commonly found in the caruncle, but there are rare reports of involvement of the lacrimal gland. Excision is curative. Although frequent in the salivary glands, Wharthin tumor of the lacrimal gland is extremely rare, with only one case reported in the literature.47
Adenoid Cystic Carcinoma
Epidemiology
ACC represents 18% of lacrimal gland lesions and 2% of all orbital lesions.1 It is the most common malignant epithelial tumor of the lacrimal gland.5,48,52
Clinical Features
ACC generally presents earlier compared with PA, with a mean age of 40 years; it can occur as early as age 10 years.53 Females are affected more frequently than males, with a ratio of 2 : 1. Patients typically present within a few months complaining of pain. The pain results from early sensory nerve invasion26,52 and is an important feature distinguishing ACC from PA and other lesions.52 Neural invasion may also cause frontotemporal hypesthesia. Given the superotemporal location of the lacrimal gland in the orbit, patients often present with proptosis with inferior and nasal deviation of the globe, “S-shaped” blepharoptosis, diplopia, and ocular motility deficits (Fig. 17.7A).
Investigations
On radiologic imaging, ACC appears as a solid nodular mass with irregular margins, infiltrating adjacent tissue and causing bone destruction.54 Typical CT features include irregular margins, osteolysis, and calcification. On MRI, ACC shows moderate signal intensity after contrast injection, and the tumor is isointense to muscle on both T1- and T2-weighted MRI. However, these features may vary, depending on the prevalent histologic pattern. Solid patterns tend to be more hypointense on T2 compared with the cribriform pattern, which can show hyperintense areas40 (Fig. 17.7B and C, Box 17.1).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
