Masses of the Lacrimal Gland: Evaluation and Treatment

Abstract

Lacrimal gland lesions account for approximately 9 to 10% of all biopsied orbital masses. Potential causes include nongranulomatous and granulomatous inflammation, autoimmune disease, lymphoproliferative disorders, benign epithelial proliferation, malignant neoplasia, and metastatic disease. Inflammatory lesions and lymphoproliferative disorders are the most common and may be unilateral or bilateral; they may also be localized to the orbit or associated with systemic disease. Both benign and malignant epithelial lacrimal gland masses tend to be unilateral and involve the orbital lobe, but a more rapid onset of symptoms and periorbital pain strongly suggest malignant disease. On orbital imaging, both inflammatory and lymphoproliferative lesions conform to the globe and surrounding structures, without changes in adjacent bone, whereas epithelial lacrimal gland masses often show scalloping of the lacrimal gland fossa. Malignant epithelial lacrimal gland tumors can also have radiographic evidence of bony invasion and destruction. Masses of the lacrimal gland may be due to a broad range of pathologies, and a good working knowledge of common clinical characteristics and radiographic imaging findings is essential for diagnosis and treatment. All patients with inflammatory, lymphoproliferative, and epithelial neoplastic lesions involving the lacrimal gland require long-term surveillance for disease recurrence and progression.

Keywords

adenoid cystic carcinoma - dacryoadenitis - carcinoma ex pleomorphic adenoma - lacrimal gland mass - orbital lymphoma - orbital pseudotumor - pleomorphic adenoma - surgical debulking of lacrimal gland

Introduction

Masses of the lacrimal gland are relatively uncommon, with an incidence of approximately 1.3 per 1 million people per year.[1] Lacrimal gland lesions account for approximately 9 to 10% of all biopsied orbital masses and can be caused by inflammation, lymphoproliferative disorders, primary epithelial neoplasms (benign or malignant), or metastatic disease.[2] [3] These lesions may be difficult to differentiate based on clinical and radiographic findings alone, and a tissue biopsy is often required for definitive histopathologic diagnosis. We review the most common etiologies of lacrimal gland enlargement and their clinical characteristics, imaging findings, indications for biopsy, medical and surgical treatment options, and prognosis, with a focus on the surgeon's approach to each condition.

General Diagnostic Considerations

The clinical presentation, including history and physical examination, provides the initial clues toward the diagnosis of a lacrimal gland mass. A palpable mass in the lateral upper eyelid, inferonasal globe displacement, proptosis, ptosis, diplopia, extraocular motility deficits, and vision loss are all possible signs and symptoms of lacrimal gland enlargement. Generally, an acute presentation is most likely due to either an infectious or an inflammatory etiology. Both present acutely or subacutely with periocular pain and tenderness, upper eyelid edema and erythema, and conjunctival injection, but a subacute presentation is more likely to be inflammatory. A more rapid presentation with regional lymphadenopathy, purulent discharge, and/or abscess formation suggests an infection. Slower onset, known history or concurrent manifestations of autoimmune disease, and/or lack of response to systemic antibiotics point toward a noninfectious inflammatory disease. Inflammatory signs and symptoms are typically absent in lacrimal gland neoplasia, which usually present subacutely or chronically with proptosis, inferonasal globe displacement, upper eyelid swelling or palpable mass, diplopia, and/or vision loss. Periorbital pain may also be present with neoplastic lesions, particularly if malignant.

Inflammatory Lesions of the Lacrimal Gland

Dacryoadenitis, or inflammation of the lacrimal gland, is the most common etiology of lacrimal gland enlargement and may be unilateral or bilateral.[1] This can be secondary to a viral or bacterial infection, autoimmune disease, or idiopathic inflammation.

Infectious Dacryoadenitis

Viral dacryoadenitis is rare, but more commonly occurs in children and young adults. An acute presentation with upper eyelid swelling, erythema, and pain or discomfort in the superotemporal orbit accompanied by conjunctival injection, chemosis, preauricular/cervical adenopathy, and/or constitutional symptoms raises the possibility of an infectious etiology.[4] This is most frequently associated with Epstein–Barr virus, but can also be due to adenovirus, mumps rubella virus, herpes simplex viruses, varicella zoster virus, and cytomegalovirus.[5] [6] Lacrimal gland swelling related to a viral infection is typically self-limited and resolves within 4 to 6 weeks of symptom onset.

A bacterial infection of the lacrimal gland occurs even less commonly and may be secondary to Staphylococcus aureus (including methicillin-resistant strains), Streptococcus pneumoniae, and Haemophilus influenzae.[6] [7] Sources include an overlying skin infection, adjacent sinusitis, or hematogenous spread.[6] There is typically suppurative discharge from the lacrimal ducts, which should be sent for Gram stain and culture to guide antibiotic selection. Treatment includes systemic antibiotics, with incision and drainage of any abscess. Bacterial dacryoadenitis is often diagnosed clinically and does not require orbital imaging or lacrimal gland biopsy unless the patient's presentation is atypical (e.g., older patient), there is disease recurrence, or there is persistence of lacrimal gland enlargement and/or symptoms despite seemingly appropriate treatment.[8]

Idiopathic and Autoimmune Dacryoadenitis

Dacryoadenitis is part of a spectrum of orbital inflammatory disorders that may also involve inflammation of the sclera, extraocular muscles, orbital fat, and/or optic nerve sheath. Presenting symptoms classically include unilateral upper eyelid swelling, erythema, pain or discomfort in the superotemporal orbit, conjunctival injection, and chemosis ([Fig. 1a]), but may also be bilateral (either simultaneous or sequential) in approximately 16% of patients.[9] Dacryoadenitis may be the sole presenting symptom of systemic autoimmune disease (e.g., sarcoidosis, granulomatosis with polyangiitis [GPA, formerly known as Wegener's granulomatosis], Graves' disease, Sjögren's syndrome, and IgG4-related disease) but can also be idiopathic and isolated to the orbit.[6] Some patients can also experience dry eye symptoms, whereas others may develop this over time, especially if associated with systemic autoimmune disease. Nonspecific or idiopathic orbital inflammation (NSOI) is a diagnosis of exclusion and requires a negative workup for autoimmune disease.

Fig. 1 Nonspecific orbital inflammation (NSOI) involving the lacrimal gland. (a) A 36-year-old woman with chronic left-sided proptosis and recurrent bouts of inflammation of the lacrimal gland and surrounding structures. Systemic workup was negative for underlying autoimmune disease, and lacrimal gland biopsy confirmed the diagnosis of NSOI. (b) T1-weighted contrast-enhanced magnetic resonance imaging of the orbits showed marked and diffuse enhancement of the lacrimal gland, superior rectus muscle, and adjacent connective tissues on the left.

In general, initial, mild, and/or unilateral presentations may be observed or treated with nonsteroidal anti-inflammatory drugs (NSAIDs). However, bilateral, recurrent, or more severe presentations should be thoroughly worked up and treated more aggressively. Systemic workup includes complete blood count (CBC), complete metabolic panel (CMP), angiotensin-converting enzyme (ACE), antineutrophil cytoplasmic antibodies (ANCA), anti-Sjögren syndrome related antigen A (anti-SSA/Ro) antibodies, anti-Sjögren syndrome related antigen B (anti-SSB/La) antibodies, antinuclear antibodies (ANAs), rheumatoid factor (RF), chest radiograph, and orbital imaging.[6] On both computed tomography (CT) and magnetic resonance imaging (MRI), the lacrimal gland is typically diffusely enlarged and brightly enhances with intravenous contrast ([Fig. 1b]).[10] [11] The gland also characteristically molds to surrounding structures, without any changes in the overlying bony architecture. Depending on the extent of involvement, diffuse enhancement of sclera, extraocular muscles, orbital fat, and/or the optic nerve sheath may also be observed. Other findings (e.g., sinus and midline disease in GPA, ipsilateral sinus disease in IgG4-related disease) may also be seen on neuroimaging.[6]

Treatment often requires systemic corticosteroids (e.g., oral prednisone dosed at 1 mg/kg/d) with slow taper over weeks to months.[11] In severe, vision-threatening orbital inflammation, admission for high-dose intravenous corticosteroids is indicated. Most patients respond well to systemic corticosteroids, but up to 74% of patients have recurrence of symptoms when attempting to taper or discontinue steroids.[12] Over a quarter of patients also ultimately develop steroid dependence and may require steroid-sparing therapy (e.g., methotrexate, azathioprine, mycophenolate mofetil), orbital radiation, or biologics (e.g., rituximab) to achieve remission.[12] [13] Intra- or perilesional corticosteroid injection may also be considered, and sustained results have been reported.[14] If autoimmune disease is present, systemic therapy is often required. Unlike other autoimmune conditions, GPA should always be initially treated with high-dose systemic corticosteroids and cytotoxic agents (e.g., cyclophosphamide); even if the disease is localized to the lacrimal gland, any patient with suspected GPA should be co-managed with a rheumatologist.[6]

Lacrimal gland biopsy is not absolutely necessary to diagnose inflammatory dacryoadenitis because clinical response to treatment with NSAIDs and/or systemic corticosteroids is typically sufficient.[6] However, lacrimal gland biopsy is indicated in recalcitrant cases or in those with suspected systemic inflammatory conditions. This is performed on the orbital lobe of the gland, via a lid crease incision, in order to protect the lacrimal ductules passing through the smaller palpebral lobe. Surgical debulking or complete excision of the orbital lobe may be considered for both diagnostic and therapeutic purposes.[12] For this procedure, any firm, white, abnormal-appearing tissue is excised for diagnostic biopsy and therapeutic debulking. A large sample of tissue is required and should be sent fresh in transport media in case flow cytometry is indicated. If a well-delineated mass is present, the orbital lobe can be removed in its entirety, with the palpebral lobe left intact. In a two-center study of 46 patients with idiopathic dacryoadenitis, surgical debulking or complete excision of the orbital lobe of the lacrimal gland, with or without concurrent local and/or systemic steroid, was effective in achieving clinical remission in 80% of patients, with 8% recurrence.[12] Complete cure was achieved in 74% of all patients, some of whom previously exhibited steroid dependence. Interestingly, surgical debulking did not lead to new or worsening dry eye symptoms.

Lymphoproliferative Disorders

Lymphoproliferative tumors account for 14 to 38% of lacrimal gland biopsies, with increasing incidence over the last 30 years.[1] [2] [15] [16] [17] [18] The most common presenting sign is painless unilateral enlargement of the lacrimal gland. Bilateral lacrimal gland enlargement occurs less frequently and is associated with disseminated disease ([Fig. 2]).[19] [20]

Fig. 2 Lymphoma. (a) A 73-year-old man with a history of hypothyroidism presented with significant enlargement of right greater than left lacrimal glands. On examination, both lacrimal glands were firm, immobile, and nontender. (b) Computed tomography of the orbits showed enlarged, homogeneous, moderately enhancing lacrimal glands. Positron emission tomography revealed diffuse visceral disease. The patient is currently being monitored without treatment for indolent disease by his hematologist-oncologist.

Once the patient is diagnosed with malignant lymphoma of the lacrimal gland, the patient should be referred to a hematologist-oncologist for staging (most often with positron emission tomography [PET]) and treatment. Approximately 17 to 25% of patients have concurrent systemic lymphoma at the time of diagnosis of the orbital mass.[19] [21] [22]

Current therapeutic options for malignant lacrimal gland lymphomas include radiation (typically 28–36 Gy), chemotherapy, immunotherapy, and surgical excision.[23] The prognosis for most lacrimal gland lymphomas is good, with disease-specific survival of 76% at 5 years and 56% at 10 years.[19] All patients require long-term surveillance for disease recurrence and progression, regardless of tumor grade.

Epithelial Masses of the Lacrimal Gland

Pleomorphic Adenoma (Benign Mixed Tumor)

Pleomorphic adenomas are the most common epithelial tumors of the lacrimal gland and usually present as slowly progressive, painless, unilateral proptosis in middle-aged adults.[15] [24] Symptoms are typically present for more than 12 months and may gradually result in inferonasal displacement of the ipsilateral globe with limitation of extraocular motility. The tumor nearly always involves the orbital lobe ([Fig. 3a,b]).[24] Pain and sensory loss are not classically seen with pleomorphic adenomas and, if present, suggest malignancy.[24]

Fig. 3 Pleomorphic adenoma (benign mixed tumor). (a) A 32-year-old woman with no prior medical history presented with symptoms of progressive proptosis, diplopia, and decreased vision on the right for over 5 years. (b) There was marked limitation of upgaze on the right. (c) T1-weighted magnetic resonance imaging of the orbits showed a large, round, heterogeneously enhancing mass of the orbital lobe of the lacrimal gland, with inferonasal globe displacement. The mass was removed en bloc by lateral orbitotomy.

On orbital imaging, the tumor appears as a well-defined, unilateral, homogeneous, round or oval mass in the anterolateral orbit that moderately enhances on both CT and MRI ([Fig. 3c]).[25] Depending on tumor cellularity and composition, larger masses may have heterogeneous attenuation, but calcification is rare.[24] [26] Smooth, shallow scalloping, or pressure-related expansion of the lacrimal gland fossa, is frequently seen on CT, but no true bone breakdown is seen.

Some authors propose that fine-needle aspiration biopsy (FNAB) or incisional biopsy should be considered for all epithelial tumors of the lacrimal gland because definitive histopathologic diagnosis can guide subsequent therapeutic decision-making without increased risk of recurrence or malignant change.[27] [28] If preoperative incisional biopsy is performed, then a transcutaneous approach through the lateral upper eyelid and septum is strongly recommended. Later surgical resection should then excise the entire biopsy tract to ensure complete tumor removal because residual tumor cells have the potential to proliferate and may undergo malignant transformation, with patients presenting with recurrent disease years later.[29] If complete excision with an intact pseudocapsule is achieved, the 5-year recurrence rate can be as low as 3%, compared to 32% among cases where there was history of prior biopsy or incomplete excision.[24]

In cases of recurrence, a local resection can again be performed if the recurrent mass is well circumscribed. However, if there is histopathologic evidence of orbital invasion or there is concern for multifocal recurrence, then orbital exenteration with removal of any involved bone is recommended. It is possible for the tumor to invade the apex of the orbit and surrounding bone to the point where surgical resection is no longer a viable option. In such cases, orbital radiation can be offered as palliative therapy, but pleomorphic adenomas are considered to be fairly radioresistant.[30] [31]

Pleomorphic Adenocarcinoma (Carcinoma Ex Pleomorphic Adenoma or Malignant Mixed Tumor)

Carcinoma ex pleomorphic adenoma arises from the malignant transformation of pleomorphic adenoma and comprises approximately 8% of all epithelial lacrimal gland tumors.[1] [2] Adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma, carcinosarcoma, squamous cell carcinoma, and sebaceous cell carcinoma have all been previously described as histologic subtypes of carcinoma ex pleomorphic adenoma, although poorly differentiated adenocarcinomas are the most common.[32] [33] [34] [35] [36] Generally, patients have a known history of pleomorphic adenoma that was either biopsied or incompletely excised years or decades previously, though carcinoma may also arise de novo from a primary pleomorphic adenoma with no prior surgical history.[29] [37] Classic symptoms and signs include recent rapid progression of lateral upper eyelid swelling and/or proptosis, the presence of pain, and evidence of bony erosion on orbital imaging.[33] Malignant mixed tumors also typically have ill-defined margins and are more likely to be heterogeneous, have calcifications, and show evidence of orbital spread with or without bony invasion than pleomorphic adenomas on CT.[38]

A transcutaneous biopsy is generally recommended to confirm the diagnosis of malignant mixed tumor. Once a histopathologic diagnosis is obtained, operability is determined. Occasionally, a malignant mixed tumor may be well circumscribed and noninvasive, for which local resection may be sufficient.[28] [33] [36] [39] In more infiltrative cases, however, orbital exenteration with or without bone removal should be performed, if possible.[33] [40] Regional and cervical lymph node dissection should also be considered because there can be early lymphatic dissemination.[33] Adjuvant radiotherapy may also be useful, but it will not improve outcomes if surgical resection is incomplete.[31] Approximately 4 to 6 months after exenteration, the patient can be fitted for an orbital prosthesis ([Fig. 4]).

Fig. 4 An orbital prosthesis, as seen on the patient's left, can be attached to the exenterated socket by adhesives, magnets, or osseointegrated implants. Broad-rimmed spectacles can help conceal the edges of the orbital prosthesis.

Despite aggressive surgical resection, prognosis is poor in patients whose histology reveals poorly differentiated, invasive carcinoma.[28] Intracranial spread and metastasis to the lung, chest, and bones have all been reported.[32] [33] Of note, patients with carcinoma ex pleomorphic adenoma and known history of pleomorphic adenoma may live longer (median: 12.0 years) than those whose tumor arose de novo (median: 3.5 years).[41]

Adenoid Cystic Carcinoma

ACC is the most common primary epithelial malignant tumor of the lacrimal gland.[1] [2] Patients typically present with a less than 12-month history of symptoms and signs similar to those with benign lacrimal gland masses, and also classically have periorbital pain associated with paresthesias, suggesting perineural invasion.[39] [42]

On orbital imaging, ACC is typically heterogeneous, is isodense or isointense to extraocular muscle, and moderately enhances, but can either be well circumscribed or ill defined with infiltration of adjacent tissues.[25] [38] Bony invasion and intralesional calcification may also be seen. A “tail” or “wedge” sign (extension of lacrimal gland tissue in the shape of a triangle between the neighboring superior or lateral rectus muscle and respective orbital wall, without evidence of intraconal involvement) is indicative of posterior extension and strongly suggests a malignant rather than a benign tumor ([Fig. 5]).[38] [43] Contrast-enhanced MRI is most useful in detecting perineural invasion, intracranial extension, cavernous sinus involvement, and/or bone marrow replacement in ACC.[25] [39]

Fig. 5 Adenoid cystic carcinoma. An axial view on T1-weighted magnetic resonance imaging of the orbits shows a large, enhancing superolateral mass causing 5 mm of proptosis and displacing the globe downward, with a positive tail sign (arrowhead). The patient underwent exenteration alone, but developed a pulmonary nodule a year later, for which she was treated with carboplatin and paclitaxel. Approximately 7.5 years after diagnosis, she is alive with stable pulmonary nodules.

When there is high clinical suspicion for ACC, a direct transcutaneous biopsy should be performed. Once a histopathologic diagnosis is obtained, staging by the American Joint Committee on Cancer (AJCC) classification system is recommended to assess the extent of disease and determine treatment options.[44] [45] Often, there is already evidence of local and perineural spread; a majority of patients have ≥T3 tumors on presentation.[44] [46]

Traditionally, orbital exenteration with or without bony removal, followed by adjuvant radiotherapy, is recommended to achieve locoregional control, but recent studies have shown that globe-preserving surgery with or without bony removal, followed by postoperative radiotherapy, may be appropriate for patients with <T3 disease.[44] [47] [48] However, if the tumor is >2.5 cm in its greatest dimension or there is radiographic evidence of posterior extension, then orbital exenteration should be performed, with removal of all radiologically and/or clinically involved bone.[44] Adjuvant radiotherapy is recommended for nearly all patients, given the propensity for early perineural invasion.[44] [49] Postoperative chemotherapy may also be considered in certain patients.[50]

In recent years, a treatment protocol consisting of neoadjuvant intra-arterial cytoreductive chemotherapy (IACC), followed by orbital exenteration, postoperative chemoradiation, and adjuvant chemotherapy, has been proposed to achieve locoregional control and improve disease-specific survival in patients with ACC.[51] However, strict adherence to protocol and an intact lacrimal artery, without significant prior tissue manipulation (other than transcutaneous biopsy for histopathologic diagnosis), are required for success of this treatment plan. Although reported results have been promising, prospective randomized multicenter clinical trials with long-term follow-up have been very difficult to carry out.[52]

Despite aggressive treatment, prognosis is very poor for patients with ACC. According to a review of patients with ACC in the Surveillance, Epidemiology, and End Results (SEER) Registry, those with localized tumors at the time of diagnosis have nearly 89% disease-specific survival at 5 years, 59% at 10 years, 52% at 15 years, and 45% at 20 and 25 years.[46] Although 5-year disease-specific survival is similar at 85% for patients with regional spread at diagnosis, only 37% are living at 10 years, and few live after 15 years.[46] Long-term surveillance is required for all patients with ACC, as late relapse, intracranial spread, and distant metastasis are not uncommon.

Metastasis to the Lacrimal Gland

There are several reports of tumors metastasizing to the lacrimal gland in the literature. Metastatic tumors to the lacrimal gland are most commonly breast carcinomas.[1] [53] [54] [55] [56] Neuroendocrine or carcinoid tumors,[57] gestational choriocarcinoma,[58] esophageal carcinoma,[59] hepatocellular carcinoma,[60] renal cell carcinoma,[61] gastrointestinal stromal tumors,[62] osteosarcoma,[63] and pleural mesothelioma[64] have all been reported. Biopsy yields a histopathologic diagnosis, with subsequent systemic evaluation performed for staging. Treatment depends on tumor type, grade, and stage, and is directed by either a surgical or medical oncologist.

Conclusion

Masses of the lacrimal gland encompass a broad range of pathologies, and a good working knowledge of common clinical characteristics and radiographic imaging findings is essential in differentiating between inflammatory lesions, benign and malignant lacrimal gland neoplasms, and metastatic disease. Inflammatory lesions are the most common causes of lacrimal gland enlargement, followed by lymphoproliferative disorders. Epithelial lacrimal gland masses tend to be unilateral and involve the orbital lobe. Periorbital pain and rapid symptom onset (i.e., <10 months) are strongly suggestive of malignancy. A histopathologic specimen is often required for diagnosis. Depending on the suspected diagnosis, an anterior transcutaneous tissue biopsy or FNAB may be advised in order to preserve normal tissue barriers, such as the periosteum.

Once a diagnosis is obtained, treatment often involves multidisciplinary care, with involvement of rheumatology and oncology in addition to the skull base team. All patients with history of an epithelial lacrimal gland tumor (i.e., benign or malignant) or lymphoproliferative disease involving the lacrimal gland require long-term surveillance for disease recurrence and progression, regardless of tumor grade, given the propensity for late locoregional recurrence and systemic disease.

Conflict of Interest

None declared.

• References

• 1 von Holstein SL, Therkildsen MH, Prause JU, Stenman G, Siersma VD, Heegaard S. Lacrimal gland lesions in Denmark between 1974 and 2007. Acta Ophthalmol 2013; 91 (04) 349-354
• 2 Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery Lecture, part 1. Ophthalmology 2004; 111 (05) 997-1008
• 3 Bonavolontà G, Strianese D, Grassi P. et al. An analysis of 2,480 space-occupying lesions of the orbit from 1976 to 2011. Ophthal Plast Reconstr Surg 2013; 29 (02) 79-86
• 4 Gao Y, Moonis G, Cunnane ME, Eisenberg RL. Lacrimal gland masses. AJR Am J Roentgenol 2013; 201 (03) W371-W381
• 5 Rhem MN, Wilhelmus KR, Jones DB. Epstein-Barr virus dacryoadenitis. Am J Ophthalmol 2000; 129 (03) 372-375
• 6 Mombaerts I. The many facets of dacryoadenitis. Curr Opin Ophthalmol 2015; 26 (05) 399-407
• 7 Goold LA, Madge SN, Au A. et al. Acute suppurative bacterial dacryoadenitis: a case series. Br J Ophthalmol 2013; 97 (06) 735-738
• 8 Snebold NG. Noninfectious orbital inflammations and vasculitis. In: Albert DM, Jakobiec FA. eds. Principles and Practice of Ophthalmology. Philadelphia, PA: W.B. Saunders; 1994: 1923-1942
• 9 Andrew NH, Kearney D, Sladden N. et al. Idiopathic dacryoadenitis: clinical features, histopathology, and treatment outcomes. Am J Ophthalmol 2016; 163: 148-153.e1
• 10 Ding ZX, Lip G, Chong V. Idiopathic orbital pseudotumour. Clin Radiol 2011; 66 (09) 886-892
• 11 Gündüz AK, Yeşiltaş YS, Shields CL. Overview of benign and malignant lacrimal gland tumors. Curr Opin Ophthalmol 2018; 29 (05) 458-468
• 12 Mombaerts I, Cameron JD, Chanlalit W, Garrity JA. Surgical debulking for idiopathic dacryoadenitis: a diagnosis and a cure. Ophthalmology 2014; 121 (02) 603-609
• 13 Swamy BN, McCluskey P, Nemet A. et al. Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes. Br J Ophthalmol 2007; 91 (12) 1667-1670
• 14 Leibovitch I, Prabhakaran VC, Davis G, Selva D. Intraorbital injection of triamcinolone acetonide in patients with idiopathic orbital inflammation. Arch Ophthalmol 2007; 125 (12) 1647-1651
• 15 Shields CL, Shields JA, Eagle RC, Rathmell JP. Clinicopathologic review of 142 cases of lacrimal gland lesions. Ophthalmology 1989; 96 (04) 431-435
• 16 Lacrimal Gland Tumor Study Group. An epidemiological survey of lacrimal fossa lesions in Japan: number of patients and their sex ratio by pathological diagnosis. Jpn J Ophthalmol 2005; 49 (05) 343-348
• 17 Teo L, Seah LL, Choo CT, Chee SP, Chee E, Looi A. A survey of the histopathology of lacrimal gland lesions in a tertiary referral centre. Orbit 2013; 32 (01) 1-7
• 18 Andreoli MT, Aakalu V, Setabutr P. Epidemiological trends in malignant lacrimal gland tumors. Otolaryngol Head Neck Surg 2015; 152 (02) 279-283
• 19 Jenkins C, Rose GE, Bunce C. et al. Clinical features associated with survival of patients with lymphoma of the ocular adnexa. Eye (Lond) 2003; 17 (07) 809-820
• 20 Demirci H, Shields CL, Karatza EC, Shields JA. Orbital lymphoproliferative tumors: analysis of clinical features and systemic involvement in 160 cases. Ophthalmology 2008; 115: 1626-1631 , 1631.e1–1631.e3
• 21 Rasmussen P, Ralfkiaer E, Prause JU, Sjö LD, Siersma VD, Heegaard S. Malignant lymphoma of the lacrimal gland: a nation-based study. Arch Ophthalmol 2011; 129 (10) 1275-1280
• 22 Sullivan TJ, Whitehead K, Williamson R. et al. Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study with statistical analysis of 69 patients. Ophthal Plast Reconstr Surg 2005; 21 (03) 177-188
• 23 Aronow ME. Ocular adnexal lymphoma: evidence-based treatment approach. Int Ophthalmol Clin 2015; 55 (01) 97-109
• 24 Rose GE, Wright JE. Pleomorphic adenoma of the lacrimal gland. Br J Ophthalmol 1992; 76 (07) 395-400
• 25 Vaidhyanath R, Kirke R, Brown L, Sampath R. Lacrimal fossa lesions: pictorial review of CT and MRI features. Orbit 2008; 27 (06) 410-418
• 26 Jung WS, Ahn KJ, Park MR. et al. The radiological spectrum of orbital pathologies that involve the lacrimal gland and the lacrimal fossa. Korean J Radiol 2007; 8 (04) 336-342
• 27 Lai T, Prabhakaran VC, Malhotra R, Selva D. Pleomorphic adenoma of the lacrimal gland: is there a role for biopsy?. Eye (Lond) 2009; 23 (01) 2-6
• 28 von Holstein SL, Fehr A, Persson M. et al. Lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma: genomic profiles, gene fusions, and clinical characteristics. Ophthalmology 2014; 121 (05) 1125-1133
• 29 Currie ZI, Rose GE. Long-term risk of recurrence after intact excision of pleomorphic adenomas of the lacrimal gland. Arch Ophthalmol 2007; 125 (12) 1643-1646
• 30 Wright JE, Stewart WB, Krohel GB. Clinical presentation and management of lacrimal gland tumours. Br J Ophthalmol 1979; 63 (09) 600-606
• 31 Brada M, Henk JM. Radiotherapy for lacrimal gland tumours. Radiother Oncol 1987; 9 (03) 175-183
• 32 Perzin KH, Jakobiec FA, Livolsi VA, Desjardins L. Lacrimal gland malignant mixed tumors (carcinomas arising in benign mixed tumors): a clinico-pathologic study. Cancer 1980; 45 (10) 2593-2606
• 33 Henderson JW, Farrow GM. Primary malignant mixed tumors of the lacrimal gland. Report of 10 cases. Ophthalmology 1980; 87 (06) 466-475
• 34 Witschel H, Zimmerman LE. Malignant mixed tumor of the lacrimal gland. A clinicopathologic report of two unusual cases. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1981; 216 (04) 327-337
• 35 Kamei I, Yoshida N, Yukawa S. et al. Malignant transformation of benign mixed tumor of lacrimal gland to squamous cell carcinoma 19 years after initial surgery: report of a case. No Shinkei Geka 1992; 20 (01) 79-83
• 36 Weis E, Rootman J, Joly TJ. et al. Epithelial lacrimal gland tumors: pathologic classification and current understanding. Arch Ophthalmol 2009; 127 (08) 1016-1028
• 37 Shields JA, Shields CL. Malignant transformation of presumed pleomorphic adenoma of lacrimal gland after 60 years. Arch Ophthalmol 1987; 105 (10) 1403-1405
• 38 Young SM, Kim YD, Shin HJ, Imagawa Y, Lang SS, Woo KI. Lacrimal gland pleomorphic adenoma and malignant epithelial tumours: clinical and imaging differences. Br J Ophthalmol 2019; 103 (02) 264-268
• 39 Rootman J, White VA, Al-Katan H. Neoplasia. In: Rootman J. ed. Diseases of the Orbit: A Multidisciplinary Approach. Philadelphia, PA: Lippincott Williams & Wilkins; 2002: 213-284
• 40 Shields JA, Shields CL, Demirci H, Honavar SG, Singh AD. Experience with eyelid-sparing orbital exenteration: the 2000 Tullos O. Coston Lecture. Ophthal Plast Reconstr Surg 2001; 17 (05) 355-361
• 41 Font RL, Gamel JW. Epithelial tumors of the lacrimal gland, an analysis of 265 cases. In: Jakobiec FA. ed. Ocular and Adnexal Tumors. Birmingham, AL: Aesculapius Publishing Co.; 1978: 787-805
• 42 Wright JE, Rose GE, Garner A. Primary malignant neoplasms of the lacrimal gland. Br J Ophthalmol 1992; 76 (07) 401-407
• 43 Lorenzano D, Rose GE. The “wedge sign”: an imaging sign for aggressive lacrimal gland disease. Ophthalmology 2017; 124 (07) 1081-1083
• 44 Ahmad SM, Esmaeli B, Williams M. et al. American Joint Committee on Cancer classification predicts outcome of patients with lacrimal gland adenoid cystic carcinoma. Ophthalmology 2009; 116 (06) 1210-1215
• 45 Lacrimal Gland Carcinoma. In: Amin MB, Edge S, Greene F. eds. AJCC Cancer Staging Manual. 8th ed.. New York, NY: Springer; 2017: 841-848
• 46 Li N, Xu L, Zhao H, El-Naggar AK, Sturgis EM. A comparison of the demographics, clinical features, and survival of patients with adenoid cystic carcinoma of major and minor salivary glands versus less common sites within the Surveillance, Epidemiology, and End Results registry. Cancer 2012; 118 (16) 3945-3953
• 47 Noh JM, Lee E, Ahn YC. et al. Clinical significance of post-surgical residual tumor burden and radiation therapy in treating patients with lacrimal adenoid cystic carcinoma. Oncotarget 2016; 7 (37) 60639-60646
• 48 Han J, Kim YD, Woo KI, Sobti D. Long-term outcomes of eye-sparing surgery for adenoid cystic carcinoma of lacrimal gland. Ophthal Plast Reconstr Surg 2018; 34 (01) 74-78
• 49 Woo KI, Kim YD, Sa HS, Esmaeli B. Current treatment of lacrimal gland carcinoma. Curr Opin Ophthalmol 2016; 27 (05) 449-456
• 50 Esmaeli B, Yin VT, Hanna EY. et al. Eye-sparing multidisciplinary approach for the management of lacrimal gland carcinoma. Head Neck 2016; 38 (08) 1258-1262
• 51 Tse DT, Kossler AL, Feuer WJ, Benedetto PW. Long-term outcomes of neoadjuvant intra-arterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma. Ophthalmology 2013; 120 (07) 1313-1323
• 52 Bradley EA, Bradley DJ. Adenoid cystic carcinoma of the lacrimal gland: rare … lethal … cured?. Ophthalmology 2013; 120 (07) 1311-1312
• 53 Font RL, Smith SL, Bryan RG. Malignant epithelial tumors of the lacrimal gland: a clinicopathologic study of 21 cases. Arch Ophthalmol 1998; 116 (05) 613-616
• 54 Rao RC, Elner VM, Demirci H. A red and swollen eyelid. Breast carcinoma metastasis to left lacrimal gland. JAMA Oncol 2015; 1 (04) 537-538
• 55 Nickelsen MN, VON Holstein S, Hansen AB, Prause JU, Heegaard S. Breast carcinoma metastasis to the lacrimal gland: Two case reports. Oncol Lett 2015; 10 (02) 1031-1035
• 56 Laforga JB. Lacrimal gland metastasis from invasive lobular carcinoma (ER⁺, PR⁻, Her-2⁺) as the first manifestation of disseminated breast cancer. Breast J 2020; 26 (04) 762-763
• 57 Harris DC, Clark CV, Bartholomew RS. Carcinoid tumour in the lacrimal gland. Doc Ophthalmol 1989; 73 (01) 43-51
• 58 Ahamed NA, Sait K, Anfnan N, Farwan K, Nizamuddin SH, Baeesa SS. Gestational choriocarcinoma presenting with lacrimal gland metastasis: a first reported case. Case Rep Obstet Gynecol 2015; 2015: 879538
• 59 Oworu O, Kyle P, Morton R. Metastatic oesophageal carcinoma presenting as a lacrimal gland tumour. Br J Ophthalmol 2004; 88 (07) 972-973
• 60 Chen H, Li J, Wang L. et al. Hepatocellular carcinoma metastasis to the lacrimal gland: A case report. Oncol Lett 2014; 8 (02) 911-913
• 61 Shields JA, Shields CL, Eagle Jr RC, Singh AD, Armstrong T. Metastatic renal cell carcinoma to the palpebral lobe of the lacrimal gland. Ophthal Plast Reconstr Surg 2001; 17 (03) 191-194
• 62 Yu Y, Ji X, Li W, Wu C. Orbital metastasis from a gastrointestinal stromal tumor: a case report. Am J Ophthalmol Case Rep 2019; 16: 100528
• 63 Shambhu SK, Rambhatla S, Chandak A. Metastatic osteosarcoma of lacrimal gland. Del J Ophthalmol 2017; 27: 197-198
• 64 Hanafi H, Verdijk RM, Paridaens D. Malignant pleural mesothelioma with lacrimal gland metastasis. Acta Ophthalmol 2016; 94 (08) 836-838

Publication History

Article published online:
18 February 2021