The lacrimal gland can be involved in a wide spectrum of orbital pathology.1 As lacrimal gland lesions can be difficult to accurately diagnose, this overview can help avoid pitfalls and aid in the differential and management.
To diagnose lacrimal lesions, a brief anatomy review is useful. The lacrimal gland has the size and shape of an almond and is located on the superolateral aspect of the orbit. Two lobes are recognized: the palpebral and the orbital lobe that are separated by the lateral horn of the levator aponeurosis.
Key examination findings in patients with lacrimal gland lesions can include globe displacement (generally inferiorly) and fullness in the superior-temporal orbit. Other signs and symptoms to look for include: change in facial sensation; altered motility; ptosis; erythema or thickness of overlying skin; and conjunctival changes. For example, the acute onset of a painful, erythematous, indurated eyelid may suggest inflammation, whereas an insidious and painless mass in a slightly older population may correspond to a lymphoproliferative lesion. A complete review of systems should also be taken; duration of symptoms, rapidity of onset, and any previous trauma or cancer history are important to elicit from the patient. From a practical standpoint, these patients generally require some imaging. CT is the most commonly used and provides important information about any possible changes to the adjacent bone.
Tumors of the lacrimal gland represent 10 percent of all mass occupying lesions in the orbit1 and are broadly classified as epithelial and non-epithelial lesions (See Table 1). Traditionally, it has been said that 50 percent of the lacrimal masses are epithelial and 50 percent are non-epithelial. However, more recent data indicate that non-epithelial tumors account for 80 percent of the total of the lacrimal gland tumors (this includes inflammatory and lymphoid lesions).1
Of all orbital lesions, lacrimal epithelial tumors comprise from 5 to 8 percent, with half of these being benign mixed tumors and the other half carcinomas.1-15
The most common epithelial benign lesion of the lacrimal gland is the benign mixed tumor, which generally presents as a painless mass without signs of inflammation for more than 12 months. On the other hand, malignant epithelial lesions most commonly present with painful swelling of the upper eyelid that develops within one year.
Because the lacrimal and salivary glands share similar characteristics, the American Joint Committee on Cancer classification (AJCC) has aligned the classification with those of the salivary gland.5 Recently, Jack Rootman, MD, and Valerie A. White, MD, published an update of this classification, and adjusted the size of the lacrimal gland to the TNM classification of the salivary tumors.6,7 Details on this classification are beyond the scope of this article, but an overview can be found in Table 2.
CT and MRI are utilized to differentiate between different types of masses and determine the extent of lesions involving the lacrimal gland and the bony fossa.
It is frequently very difficult to diagnose specific disease on the basis of imaging characteristics alone (See Figure 1). Benign epithelial tumors are commonly seen with a well-defined benign appearance, whereas malignant carcinomas appear with an invasive malignant appearance. However, some malignant tumors, such as a malignant myoepithelioma, may appear non-invasive and could be mistaken as benign on imaging alone. Lymphomatous lesions of the lacrimal gland, ranging from reactive hyperplasia to malignant lymphoma, can be difficult to differentiate both radiologically and pathologically.
For these reasons, imaging, pathologic verification and systemic evaluation are often needed in the diagnosis of a lacrimal gland tumor.
• Dacryocele (dacryops) is a retention cyst of a gland ductule. It generally presents in young adults with signs and symptoms of inflammation in the superotemporal conjunctival fornix. Diagnosis is made based on clinical appearance (See Figure 2) and imaging is not required. In cases of large and persistent cysts, microsurgical drainage of the affected ductule is indicated, taking care not to damage the normal lacrimal gland, which can cause a postoperative dry eye.8
• Pleomorphic adenomas account for 3 to 5 percent of all orbital tumors and 50 percent of all epithelial tumors of the lacrimal gland. These lesions become evident during the fourth and fifth decades as a slow onset and painless proptosis with inferonasal displacement of the globe.1,8 The orbital lobe of the lacrimal gland is generally affected. The tumor is soft and oval with frequent expansion of the lacrimal gland fossa and flattening of the globe. Calcifications and anterior extension of the mass beyond the orbital rim are rare. In contrast, when these lesions present in younger patients, the symptom duration is shorter, the palpebral lobe is affected, and a hard mobile mass can be palpated superolaterally.10 On CT scan, the gland may look normal with an enlarged rounded anterior surface extending outside the orbital rim (See Figure 3).
Suspicion of a pleomorphic adenoma based on clinical history and radiological signs is key to avoid an incisional biopsy. Because recurrent pleomorphic adenomas can undergo malignant changes, adequate management requires a complete excision of the lesion through a lateral orbitotomy to avoid a rupture or breach of the pseudocapsule. The five-year recurrence rate is 3 percent for completely excised lesions and 32 percent for incompletely excised tumors. Previous studies reported a 10 percent incidence of malignant transformation of recurrent adenomas by 20 years after treatment, and 20 percent by 30 years.4
Some advocate the use of fine-needle aspiration biopsy, however, in my opinion there is no reason for undertaking this in the presence of a clinically and radiologically characteristic disease. Preservation of the palpebral lobe during the surgery, when possible, may help to prevent dry-eye syndrome.
Adenoid Cystic Carcinoma
Adenoid cystic carcinoma is the most common malignant epithelial tumor of the lacrimal gland. It accounts for about 1.6 percent of all orbital tumors and 3.8 percent of all primary orbital tumors.2-4 There is no sex-predilection. Age of presentation is about 40 years old, with a range of 6.5 to 80 years. This wide range of presentation may confuse clinicians when a unilateral mass in the upper temporal quadrant is present in children and teenagers, and ACCs can be mistaken for dermoids. Thus, a high clinical suspicion is indicated.
Patients with an ACC present with rapid onset (usually under one year) of a temporal mass.2-4,8-13 Symptoms are globe displacement, swelling, diplopia, visual change, ptosis and lacrimation (See Figure 4). Because this tumor invades perineurally and into the adjacent bone, patients may have pain (35 to 40 percent of cases)2-4,8-14 or, more rarely, numbness.
On CT scans, ACC appears as a round or ovoid tumor with irregular borders within the lateral wall of the orbit. The lacrimal fossa is usually enlarged with bone invasion (See Figure 4d). Bita Esmaeli, MD, and colleagues have recently shown that 50 percent of their patients with ACC had bone involvement.11 For this reason it is recommended to ask for bone window images and contrast enhancement if intracranial or extradural extension is suspected. In their series, John E. Wright, MD, and colleagues showed 75 percent bone erosion, 34 percent bone destruction and 22 percent soft tissue calcification.13 Invasion of the tumor into the cavernous sinus, brain or bone marrow is best evaluated with an MRI with enhancement.
The best treatment for an adenoid cystic carcinoma is still controversial. Surgical techniques include local resection, en bloc removal and exenteration. The tumor is difficult to dissect, and radical exenteration, with removal of the frontal bone, the lateral wall of the orbit and the temporal muscle, has been recommended. However, even with this radical approach, the mean survival is five years, with a 20-percent survival at 10 years. Mortality is associated with intracranial invasion and lung metastasis.1-4,7-14 Radiotherapy in the dose of 50 to 60 Gy after local resection has been demonstrated to prolong survival and reduce recurrences.
Recently, a new and promising treatment option was published by David T. Tse, MD, and colleagues on the use of intra-arterial cytoreductive chemotherapy (IAAC) as an adjunct to exenteration and standard radiotherapy.4,15 The authors found a significant reduction of recurrences and mortality related to the tumor with this treatment when compared with patients treated with conventional therapies.4,13-15
The difficulty of achieving a cure for this disease is attributable to the complex orbital anatomy and the aggressive biological behavior of the tumor with its demonstrated infiltrative growth pattern, propensity for perineural infiltration with retrograde intracranial extension, and hematogenous and lymphatic invasion.5 Intracranial extension and metastatic disease are the principal causes for death.12
Macroscopically, an adenoid cystic carcinoma appears as a white-grayish solid and circumscribed tumor. Microscopically, five histologic patterns are identified, and in order of frequency, they are: cribiform (Swiss cheese); solid (basaloid); sclerosing; comedocarcinomatous; and tubular.1-4,10 The basaloid pattern most commonly occurs in patients older than 40 years and is associated with a worse prognosis and shorter survival, in contrast to the cribiform pattern.
Malignant Mixed Tumor
Malignant mixed tumor is also called carcinoma ex pleomorphic adenoma, pleomorphic carcinoma or carcinoma in pleomorphic adenoma,1-4,7-13 and represents a pleomorphic adenoma that has undergone malignant degeneration. These account for 4 to 15 percent of the epithelial tumors of the lacrimal gland. Typically, it occurs one decade later than pleomorphic adenoma.
Malignant mixed tumors can present in one of three clinical patterns.8 First, and most common, is a patient who initially had a benign mixed tumor resected incompletely and had a recurrence years later. Second is a patient with a long-standing, indolent lacrimal gland tumor who suddenly experienced an acute expansion with pain and swelling of the upper eyelid. And third, a patient who presents with rapid onset of symptoms, including pain, and aggressive bone destruction is found. The latter presentation is considered to be de novo.8
Radiologic features of malignant mixed tumors show an enlarged lacrimal fossa surrounded by bone destruction, signs that are suggestive of malignancy. However, sometimes this tumor may show as a smooth tumor without bone destruction. As with all bone evaluation, inspection for bone changes on CT is best identified with a bone window. In cases of dural or intracranial extension, contrast enhancement is useful. On CT, it is not possible to differentiate a malignant mixed tumor from other types of carcinoma (See Figure 5).
Histologically, to fit in the diagnosis, benign and malignant components of the lesion need to be identified.2,3,8 A mixed tumor shows features of a benign mixed tumor with areas of malignant transformation. If the benign component is not present, then the diagnosis is pleomorphic carcinoma. In most cases these elements are poorly differentiated adenocarcinomas, but squamous cell carcinoma, adenoid cystic carcinoma or even a sarcoma can be found.
Malignant mixed tumors are also subclassified in non-invasive (intracapsular or carcinoma in situ), minimally invasive and invasive. The first two have an excellent prognosis even without adjunctive radiotherapy, when they are totally resected without breach of the capsule.
Adenocarcinoma comprises 7 percent of the epithelial tumors of the lacrimal gland.1-3 It affects older patients (18 to 80, mean 58 years) and is more common in the male population. Clinical presentation is that of a rapidly growing and palpable mass that causes proptosis, globe displacement, diplopia, ptosis, visual loss and pain.7 This tumor has a more aggressive behavior and a shorter patient survival time than adenoid cystic carcinoma (1.5 years). Mortality is associated with an early lymphatic dissemination of the tumor cells to lymph nodes and lungs.4,6 Aggressive treatment is warranted, including a monobloc craniofacial orbitotectomy, exenteration, lymph node dissection and subsequent radiotherapy.8-15 Patients under this protocol have shown a better survival rate and fewer recurrences.
Other Less Common Tumors
• Hemangioma. Vascular lesions such as cavernous hemangioma, epithelioid hemangioma and hemangioendothelioma can grow within the lacrimal gland.7 If these lesions are confined to the lacrimal gland, the treatment is simple excision.
• Oncocytoma. Oncocytomas are rare neoplasias that may occur in the caruncle, lacrimal sac, conjunctiva and lacrimal glands. These lesions are more common in the elderly. Benign and malignant oncocytomas have been reported in the lacrimal gland.16 Malignant lesions may show intracranial extension.
• Acinic cell carcinoma. Although acinic cell carcinoma comprises 2 to 4 percent of the parotid glands primary tumors, only a few cases are reported in the lacrimal gland. Females in the sixth decade appear to be more affected.17 This is usually a slow-growing and painless mass but can develop intracranial extension.
• Sebaceous cell carcinoma. A sebaceous cell carcinoma of the lacrimal gland is very rare but very aggressive.18 It may occur from heterotopic sebaceous tissue. Differential diagnosis should include metastatic spread or orbital invasion of an eyelid tumor. Exenteration, lymph node dissection and postoperative radiotherapy are indicated.
• Spindle cell myoepithelioma. This is a benign and monomorphic adenoma composed of myoepithelial cells.19 It presents as a well-circumscribed solid lesion that if removed completely through a lateral orbitotomy has a benign behavior similar to that of pleomorphic adenoma (See Figure 6).
• Solitary fibrous tumor. This rare spindle cell neoplasm frequently arises in the pleura. The clinical behavior (slow progressive and painless mass with unilateral proptosis) and tomographic findings (mild bony remodeling without calcifications) are similar to that of pleomorphic adenoma (See Figure 7). Treatment is with en bloc excision. Recurrences are common and malignant transformation even several years after surgery has been documented.1,4,16 Thus, careful follow-up is needed.
• Primary cystadenocarcinoma. This rare and just recently described entity follows the clinical course of a similar lesion in the salivary glands.20 When the lesion is completely excised, it has an indolent behavior and there is no need for additional radiotherapy.
Recently, a better knowledge and understanding of the counterpart major salivary glands has revised the classification of lacrimal gland tumors. Increased understanding has brought evolution to the nomenclature and new diagnostic and theraputic modalities are following. CT and MRI are very valuable to assess lacrimal gland lesions. A high index of suspicion and knowledge of the radiologic findings and clinical behavior of the different lesions is imperative when dealing with lacrimal tumors. Complete resection of the lacrimal gland may prevent recurrences and later malignant transformation of some previously benign lesions. Management of malignant tumors is still controversial and may require a more aggressive treatment including exenteration, en-bloc craniofacial orbitotomy, with bone removal, radiotherapy and chemotherapy. A new promising and recent option is the IV administration of chemotherapy agents. Further studies are needed to standarize the best treatment option for the different tumors that can affect the lacrimal gland. REVIEW
Dr. Tovilla-Canales is director of, and Drs. Ball and Olvera practice in the orbit and oculoplastics department of the Institute of Ophthalmology, “Fundación Conde de Valenciana,” Universidad Nacional Autónoma de México. Dr. Martin is in the radiology department at the same institution. Contact Dr. Tovilla-Canales at Departmento de Cirugìa de Orbita y Oculoplastica, Instituto de Oftalmologia “Fundación Conde de Valenciana.” Enrique Sada Muguerza #1. Cto Centro Comercial Satelite. CP 53110. Edo de Mexico, México.
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