Lacrimal Gland Tumors

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Background

The lacrimal gland is a bilobed eccrine secretory gland, which is situated in the superotemporal orbit. The 2 lobes of the lacrimal gland, the orbital lobe and the much smaller palpebral lobe, are separated anatomically by the lateral horn of the levator aponeurosis. Only the palpebral lobe can be visualized in the superior fornix on lid eversion. Thus, disease processes that solely affect the orbital lobe may not manifest until later in the course of the illness.

Mass lesions of the lacrimal gland can be classified broadly into inflammatory and neoplastic subtypes. Inflammatory etiologies, while not uncommon, include dacryoadenitis, sarcoidosis, and orbital inflammatory pseudotumor. For the purposes of this discussion, the focus will be on neoplastic lesions of the lacrimal gland. Most of the neoplastic lesions in the lacrimal gland are epithelial in origin, with approximately 50% classified as benign and 50% as malignant.

Benign lesions include pleomorphic adenomas (benign mixed cell tumors), benign reactive lymphoid hyperplasia, and oncocytomas. These lesions are slowly growing masses more commonly found in adults in their forth to fifth decades of life. Malignant tumors of the lacrimal gland include adenoid cystic carcinoma, adenocarcinoma, squamous cell carcinoma, mucoepidermoid carcinoma, and malignant lymphomas.

Adenoid cystic carcinoma is the most common malignant lacrimal gland tumor, comprising 50% of malignant tumors of lacrimal gland and 25% of all lacrimal gland tumors. Most cases are seen in the third decade of life with a second bimodal peak in the teenage years.

Epidemiology

Frequency

United States

Data about the prevalence of lacrimal gland tumors is quite sparse in the literature as this condition is quite rare. Malignant epithelial neoplasms of the lacrimal gland account for approximately 2% of all orbital neoplasms. Similarly, epithelial neoplasms account for only 4% of all lacrimal gland lesions.

Mortality/Morbidity

Patients with lacrimal gland tumors, especially malignant ones, need to be observed long term before successful treatment can be claimed. The approximate 15-year mortality rate approaches 75%.

Age

Lacrimal gland tumors are seen more frequently in the third decade of life, and the second bimodal peak is in the teenage years.

History

The presentation of lacrimal gland tumors varies from patients who are asymptomatic but have a slight fullness in the temporal upper lid to those who present with frank proptosis, diplopia, and an encroaching mass lesion.

The history of a long-standing (>1-2 y), noninfiltrating lacrimal gland lesion suggests a benign tumor, such as a pleomorphic adenoma.

A shorter history suggests either an inflammatory or a malignant process.

Pain most commonly is seen with inflammatory lesions of the lacrimal gland, but adenoid cystic carcinomas and other malignancies also can present with pain secondary to perineural or bony involvement.

Malignant lesions characteristically present with a subacute course of proptosis and temporal sensory loss in the distribution of the lacrimal nerve in one third of patients.

Diplopia and diminished visual acuity can be seen with rapidly progressive lesions.

Benign lesions commonly present with painless inferonasal globe displacement and fullness of the superotemporal lid and orbit.

Physical

Examination may reveal clues in delineating the type of lacrimal gland tumor.

Displacement of the globe with or without proptosis is the most common presentation of malignant lesions (seen in 75% of these tumors). It characteristically is nonaxial with inferomedial globe displacement.

An S-shaped contour to the upper lid also is common with lacrimal gland lesions, but relatively nonspecific to the type of tumor.

Similarly, a mass may or may not be palpable in the lacrimal fossa. A firm, rubbery, nontender mass can be seen with either benign or lymphoproliferative lesions. A decreased Schirmer test suggests an inflammatory lesion.

Less common findings include motility restriction, elevated intraocular pressure (IOP), and chorioretinal folds.

Nonocular findings include preauricular lymphadenopathy from regional metastasis in malignant lesions.

Causes

See Background.

Imaging Studies

Neuroimaging studies can be of great assistance in making the correct diagnosis.

Computed tomography (CT) scan of benign epithelial lesions, such as pleomorphic adenomas, reveals a well-circumscribed, pseudoencapsulated lesion in the superotemporal fossa.

Characteristic bony changes include expansion and remodeling in the lacrimal fossa without evidence of bony invasion or erosion.

In contrast, malignant epithelial lesions, such as adenoid cystic carcinoma, usually present as an irregular mass, producing bony erosion (70%) and occasional calcification (20%).

Lymphoproliferative lesions usually are eccentric in shape with significant contrast enhancement.

Other Tests

Immunohistochemistry may be helpful in distinguishing between inflammatory, benign, and malignant lymphoproliferative lesions. Immunohistochemistry is a laboratory modality that uses special markers to demonstrate the presence of specific antigens in target tissues.

Benign inflammatory lesions (pseudotumor) have a polyclonal morphology, whereas the lymphoid lesions tend to be monoclonal.

Histologic Findings

Histologic examination of pleomorphic adenomas reveals evidence of both epithelial and mesenchymal differentiation. Proliferation of benign epithelial cells usually is arranged in a double layer to form lumens. Stromal differentiation can be seen in the formation of bone and cartilage.

Adenoid cystic carcinomas are derived from duct cells, and they form spaces into which basement membranelike material is deposited. This confers a cribriform or "Swiss cheese" appearance to the tissue, although growth in tubules and nests also are recognized. Five histologic patterns have been observed in these lesions, as follows: (1) cribriform (the most common subtype), (2) sclerosing, (3) basaloid, (4) comedo, and (5) ductal. The basaloid type has the worst prognosis.

Medical Care

Radiation therapy is the mainstay of treatment for lymphoid lesions, ranging from 2000-3000 cGy of total radiation. Antineoplastic agents, administered under the direction of an oncologist, usually are required for systemic disease.

Surgical Care

The treatment of lacrimal gland tumors can be divided largely into 2 categories based on the duration of symptoms, clinical evaluation, and radiographic features of the lesion.

Patients with a long-standing, painless, slowly growing mass with a well-circumscribed appearance on imaging studies are presumed to have a pleomorphic adenoma.

Treatment is extirpation, consisting of a lateral orbitotomy with intracapsular removal of all lesional tissue with careful attention to prevent violation of the pseudocapsule.

Incisional biopsy of these lesions is contraindicated because, although histologically benign, incomplete excision often leads to repeated recurrences (as high as 30% in some studies) and malignant transformation.

Small, fingerlike protuberances outside the main tumor bulk with subsequent seeding of the residual tumor are believed to be responsible for this phenomenon.

Painful lesions of short duration (>4-8 wk), especially with concomitant bony involvement, require an incisional biopsy of the lacrimal gland lesion and careful histopathologic evaluation to rule out a malignant neoplasm.

If pathologic evaluation of the permanent sections of the lesion reveals adenoid cystic carcinoma, prognosis for survival is poor.

Treatment modalities are difficult to evaluate prospectively because of the low incidence and the tendency for long-term recurrences.

The classic treatment consists of radical exenteration with frontal bone excision, maxillectomy, and temporalis fossa excision as an attempt at a curative modality in these patients (because of the diffusely infiltrative nature of these lesions and the tendency for perineural spread).

If a malignant lesion is suspected preoperatively, complete extirpation as the initial procedure (as per a pleomorphic adenoma) and follow-up radiotherapy of 6400-6800 cGy may produce a long-term survival no worse than radical exenteration with significantly less morbidity.

According to one study, when intra-arterial chemotherapy is used as an adjunct to radiation treatment and/or surgery, there is some benefit to overall disease-free survival.[1]

Mortality is increased, if bony involvement is present.

Consultations

Appropriate hematology and oncology consultations are indicated to exclude systemic involvement, if a diagnosis of lymphoma is confirmed.

Coordinated treatment with a radiation oncologist often is used for malignant and lymphoid lesions.

Further Inpatient Care

Most patients who undergo lumpectomy without bone removal can be discharged the same day. Hospitalization is usually required for more extensive surgery and/or if treatment with chemotherapeutic agents is necessary.

Prognosis

For pleomorphic adenomas, long-term studies reveal an increased incidence of malignant transformation (10% at 20 y and 20% at 30 y) associated with multiple recurrences for lesions that had frequent incisional biopsies and incomplete removal of the primary tumor.

Annual follow-up care is suggested to monitor the effects of treatment and to observe for recurrence or systemic involvement.

Systemic lymphoma develops in 20-30% of patients with malignant lymphoma of the lacrimal gland. Incidence is much higher if the initial presentation is with bilateral lacrimal gland involvement. Rasmussen et al discovered that malignant lymphoma of the lacrimal gland is fairly rare and is mostly found in elderly women; most lacrimal gland lymphomas are low grade, and the prognosis is relatively good.[2]

Adenoid cystic carcinomas carry a poorer prognosis because of bony extension and perineural infiltration. These patients have a 50% at 5-year and 75% at 15-year mortality rate. Death commonly is due to intracranial spread and pulmonary metastasis. Histologic pattern also is of prognostic significance with a cribriform pattern having a 70% at 5-year survival compared to a 20% at 5-year survival with a basaloid pattern. A recent paper that reviewed 53 patients with adenoid cystic carcinoma suggested that worse disease at time of diagnosis correlates with a poorer overall prognosis.[3]

Author

Dan D DeAngelis, MD, FRCSC, Assistant Professor of Ophthalmic Plastic and Reconstructive Surgery, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Ophthalmologist, Department of Ophthalmology and Vision Sciences, Hospital for Sick Children

Disclosure: Nothing to disclose.

Coauthor(s)

Noelene K Pang, MD, Ophthalmic Plastic and Reconstructive Surgery

Disclosure: Nothing to disclose.

Specialty Editors

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Jeff Hurwitz, MD, FRCS(C) Director of Ophthalmic Plastic Surgery, Ophthalmologist-in-Chief, Mount Sinai Hospital; Chairman, Professor, Department of Ophthalmology, University of Toronto, Canada

Disclosure: Nothing to disclose.

References

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