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Adam J. Cohen, MD · Michael Mercandetti, MD, MBA, FACS · David A. Weinberg, MD, FACS
The lacrimal gland is an exocrine gland, nestled within the lacrimal gland fossa of the frontal bone in the superotemporal orbit. The gland is subdivided anatomically, by the lateral horn of the levator aponeurosis, into a smaller palpebral and larger orbital lobe, consisting of epithelial cells, acini of secretory cells, and ductules.
The palpebral lobe can be discerned on examination to reveal gross abnormalities, while the orbital lobe usually escapes the clinician's scrutiny and can harbor pathology that perhaps eludes detection until more fulminant stages.
Lacrimal gland masses have been reported to represent up to 13% of all biopsied orbital space-occupying lesions and arise most commonly from the orbital lobe, with 17% of lesions originating from the palpebral lobe.1 These lesions can essentially be viewed as stemming from either inflammatory or neoplastic lineages. Although inflammatory processes weigh heavily in the differential of lacrimal gland masses, the thrust of this discussion will review lacrimal gland neoplasms of noninflammatory origins.
Most past literature is in agreement with Reese's 1956 treatise2 on lacrimal tumors, supporting the notion of an equal distribution between tumefaction originating from lacrimal epithelial constituents and a nonepithelial ancestry. Traditional delineation is depicted in the flow chart below. More recent literature buttresses the notion of lower incidence of epithelial lesions, ranging in occurrence from 22% to 47%.3
Lacrimal gland neoplasms can manifest with a broad range of symptoms. Patients can present with minimal complaints, such as temporal upper eyelid swelling, or more prominent disturbances, such as pain, epiphora, diplopia, paresthesias, proptosis, and palpation of a mass. In some cases, the patient may describe no symptomatology related to the lesion.
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Rapid onset of symptoms with pain, tenderness, and upper lid edema is usually suggestive of an inflammatory process, although enlarging malignancies, such as adenoid cystic carcinoma, can cause similar symptoms related to perineural spread and osteolytic activity. Duration of symptoms longer than 6 months can be thought to be the result of a slow-growing benign tumefaction.
Signs stemming from malignant lacrimal neoplasm most commonly include globe displacement in an inferomedial vector and can be accompanied by proptosis. Preauricular adenopathy may be present as a result of metastases from the lacrimal gland or distant sites. Pain and tenderness are more commonly found with malignant lesions, but this cannot be relied upon when differentiating between benign and malignant tumefactions. This can lead one to reason that sole dependence on symptoms can lead to misdiagnosis and mismanagement of lacrimal lesions.4 A discussion of common lacrimal neoplasms follows.
Pleomorphic adenomas (benign mixed tumors) have the highest incidence of all epithelial tumors and are found primarily in the orbital lobe of the lacrimal gland. A large number of these lesions manifest in the fifth decade of life, but occurrence has been described in a patient as young as 7 years of age.5 Classically, these are unilateral, slow growing, and painless lesions, which can result in inferomedial globe displacement and proptosis.
Computerized tomography (CT scan) classically finds a well-circumscribed heterogeneous lesion without bony destruction, although lacrimal fossa remodeling may be present with long-standing lesions.6 Gross examination will find a well-encapsulated, multilobulated tumefaction with extension beyond its capsule. Histologically, two main cell lineages are observed: ductal epithelial cells and mesenchymal tissue composed of adipose, cartilage, and fibrous components.6 Complete extirpation of the lesion is usually accomplished via a superolateral orbitotomy. It is paramount to remove the entire lesion with its capsule intact because of the potential for malignant transformation of these neoplasms.
Adenoid cystic carcinoma is the most common nonlymphoproliferative and aggressive malignancy of the lacrimal gland, comprising 1.6% of all orbital tumors with a 5-year survival rate cited at 21%.5 Interestingly, Font and colleagues reported two patients with survival periods of greater than 10 years following early orbital exenteration and excision of recurrences,7 while other sources have reported dismal outcomes similar to the rate noted above. Font and colleagues reported a mean age of onset of 40 years,7 although occurrence in patients as young as 6 years of age has been described.8
Patients afflicted with this neoplasm typically have a short duration of symptoms, including pain secondary to its propensity for perineural invasion and bony destruction. Imaging may divulge a well-defined mass, masquerading as a pleomorphic adenoma or, more frequently, diffuse orbital involvement with bony destruction, calcification, and intracranial spread.6 Light microscopy uncovers epithelial cells that can be arranged in a cribiform (Swiss cheese), basaloid (solid), sclerosing, tubular (ductal), or comedocarcinoma pattern,3 with cribiform reportedly having a longer survival rate and basaloid having the shortest.9 Obtaining tissue for histopathologic study can be achieved via fine needle aspiration10 or open biopsy technique. A transeptal approach has been advocated with the thought that violation of the periosteum increases the chance of seeding of malignant cells.3
Treatment entails exenteration of the orbit with removal of any bones suspected of having involvement. Rootman and colleagues tout a more aggressive approach, including orbitectomy - anterior temporalis muscle resection including the zygomaticofrontal and zygomaticotemporal nerves.11 Despite radical surgical extirpation and adjunctive therapies, such as radiotherapy, chemotherapy, and local brachytherapy, the outlook for most of these patients remains dismal.
Primary adenocarcinoma of the lacrimal gland is an extremely uncommon entity. Heaps and colleagues reported a series of 13 patients and found the average age of diagnosis was 50 years of age, with a superotemporal palpable mass being described as the most common presenting symptom,12 although approximately 40% of patients complained of pain, lacrimation, and signs of inflammation.12 Exenteration coupled with radiation therapy has been reported with some success, but definitive and optimal treatment regimens remain to be standardized, as a result of this neoplasm's small prevalence. Heaps and colleagues reported that four of seven patients who underwent exenteration coupled with radiotherapy had disease-free survival ranging from 2 to 16 years.12 Metastases occur early via lymphatic channels, and a thorough head and neck examination for adenopathy is paramount at the time of initial evaluation. In addition, a subtype of primary adenocarcinoma, the basal cell variant, has rarely been reported.13
Mucoepidermoid carcinoma, although common in the major salivary glands, is quite a rare tumefaction of the lacrimal gland. Eviatar and colleagues reviewed 25 cases and found the average age of onset to be 49 years with a female predominance.14 CT scan findings are similar to those of adenoid cystic carcinoma, except for its marked enhancement with contrast and its high signal intensity on T1-weighted magnetic resonance images.6 Histologic grading of this malignancy correlates with patient survival, with grade 1 or well-differentiated tumors having the best prognosis and grade 3 having the worst prognosis. Eviatar reported seven of eight patients with well-differentiated lesions surviving after excision with or without radiotherapy, while only one of eight survived without recurrence after exenteration and radiotherapy at 4 years for a less differentiated lesion.14
Rare tumefactions such as a solitary fibrous tumor of the lacrimal fossa,15 spindle cell carcinoma,16 and oncocytic tumors17 of the lacrimal gland have been described in the case reports in the literature.
Lymphoproliferative tumefactions encompass a wide range of disease processes, spanning from idiopathic benign lymphoid hyperplasia or arising from more ominous malignant lymphomas, including the mucosa-associated lymphoid tissue (MALT) variant of lymphoma. These lymphocytic proliferations are usually found in older adults, being atypical in children, and have a unilateral predilection. Shields and colleagues reported 71 of 645 orbital biopsies were found to be of lymphocytic or plasmacytic origin, with 12 of 71 found within the lacrimal gland.18 Rootman found that lymphoma without systemic origin was the most common nonepithelial lacrimal gland tumor.11
Patients may describe a gradually enlarging, painless superotemporal orbital lesion. Displacement of the globe, proptosis, and a palpable mass are noted in 50% of patients.19 CT imaging finds a globular, compacted lesion that follows the contour of surrounding structures and at times smooth erosion of the lateral orbital wall or lacrimal fossa. MRI is inferior to CT scanning with regards to evaluation of surrounding bony anatomy, reducing its ability to differentiate between benign and malignant processes. Grossly, lymphomas typically produce a smooth, homogenous, nonencapsulated enlargement of the lacrimal gland, with anterior extension and palpebral lobe involvement. In most instances, surrounding bone is not disturbed, but one finds gross distortion of the gland's structure, which can sometimes result in small external protuberances. It is extremely difficult to differentiate benign from malignant neoplastic processes on gross examination alone.
Establishing an accurate diagnosis requires multiple biopsies of the mass. Microscopic studies find atypical sheets of monomorphic cells that lack germinal centers; whereas benign lymphoid hyperplasia possesses abundant germinal centers and a polymorphic cell population.19 Immunohistochemical staining finds monoclonal B-cell lymphocytes consistent with a non-Hodgkin's lymphoma in an overwhelmingly disproportionate number of cases. Interestingly, benign lymphoid hyperplasia is found to express T-cell lymphocytes in the majority of cases.19
Jakobiec and colleagues reported an overall 35% incidence of systemic disease with orbital lymphoid processes and a 46% incidence with high-grade lymphoma.20 It is therefore salutary that all patients found to have malignant lymphoma or benign lymphoid hyperplasia of the lacrimal gland undergo a thorough systemic evaluation and, if negative, be monitored closely by the appropriate specialist.
Total tumor extirpation is usually not undertaken secondary to its excellent response to radiotherapy. Once the diagnosis is established and systemic evaluation is devoid of lymphoproliferation, delivery of orbital radiation may begin with shielding of the globe. Both benign and malignant lesions can be treated with this modality, with the former receiving roughly 2000 cGy and the latter up to 3500 cGy of radiation. If systemic involvement is found, chemotherapeutic agents should be employed and the patient followed for optic nerve compression or other sight-threatening mass effects.
HIV-associated lymphoma is usually high-grade, large-cell immunoblastic non-Hodgkin's and Burkitt's type.5 It is exceedingly aggressive and carries a poor prognosis.