Etiology

• Typically develops from malignant transformation of a pleomorphic adenoma ("benign mixed tumor") of the lacrimal gland
• Most commonly arises after incomplete resection of a pleomorphic adenoma
• Can occur after degeneration of a chronic lacrimal gland lesion (ie, long-standing tumor with acute change
• De novo development has been reported.
• Also termed "carcinoma ex pleomorphic adenoma" and "carcinoma in pleomorphic adenoma"

Epidemiology

• Generally, occurs 15–20 years after excision of pleomorphic adenoma
• Represents 4–15% of epithelial neoplasms of the lacrimal gland (Shields 2009)
• Median age of 43 years in one series (Von Holstein 2014)
• Sixth or seventh decade in another report (Shields 2004)

History

• Enlarging mass in the lacrimal gland fossa
• Inferior or inferomedial displacement of globe
• Can be associated with discomfort, edema, and diplopia
• Duration of lesion and history of previous surgical interventions.

Clinical features

• Progressive inferior and inferolateral displacement of the globe
• Axial proptosis
• Long-standing symptoms
• Palpable mass, choroidal striae, increased resistance to retropulsion

Testing and evaluation for establishing the diagnosis

• Computed tomographic (CT) imaging will show both enlargement of the lacrimal gland fossa, of the pleomorphic adenoma, and bony destruction suggesting malignant transformation.
• Compare to previous studies when available.
• Histopathology
• Observing malignant elements within a pleomorphic adenoma makes diagnosis.
• Can be malignant elements in what appears similar to a pleomorphic adenoma
• Atypia, necrosis, mitotic figures

Testing for staging, fundamental impairment

• The sixth or seventh edition of the American Joint Committee on Cancer (AJCC) TNM definitions for carcinoma of the lacrimal gland can be used (see outline on Adenoid Cystic Carcinoma), but has not been validated for malignant mixed tumor.
• Histopathologic classifications might have prognostic value.
• Noninvasive (i.e., in situ disease) within the encapsulated tumor
• Minimally invasive (involvement < 1.5 mm distal from the capsule)
• Invasive (involvement > 1.5 mm from the capsule)

Primary risk factor is a history of pleomorphic adenoma with incomplete excision.

• Benign mixed tumor (pleomorphic adenoma)
• Adenoid cystic carcinoma
• Adenocarcinoma
• Squamous cell carcinoma
• Mucoepidermoid carcinoma
• Lymphoproliferative lesion of the lacrimal gland
• Specific inflammatory process/rheumatologic disease/dacryoadenitis
• Nonspecific or idiopathic orbital inflammation
• Less common lacrimal gland lesions
• Oncocytoma
• Acinic cell carcinoma
• Myoepithelioma
• Solitary fibrous tumor
• Cystadenocarcinoma

Natural history

• Can behave like adenoid cystic carcinoma with intracranial and perineural invasion
• Can have tumor-related death when intervention is delayed.
• Usually identified relatively early in tumor progression because of the harbinger pleomorphic adenoma.

Medical therapy

There is no known effective chemotherapeutic or immunobiologic regimen for this tumor.

Radiation

• No studies have assessed the impact of radiation therapy on lacrimal gland malignant mixed tumor.
• For invasive parotid malignant mixed tumor, adjunctive radiation has been shown to improve local recurrence rates (Chen 2007).

Surgery

• There has been no large case series.
• Outcomes are good for noninvasive and minimally invasive disease after surgery, even without adjuvant radiation (Bernardini 2008).

Common treatment responses, follow-up strategies

• With minimally invasive and in situ disease surgical cure can be achieved with wide excision.
• Early perineural invasion and bony involvement are not seen; this differs from adenoid cystic carcinoma.
• Local and distant spread can be seen with continued tumor progression beyond the encapsulated mass.

• Radiation-related toxicity
• Dry eye syndrome/ocular surface disease
• Radiation dermatitis
• Radiation retinopathy
• Radiation optic neuropathy

• Local recurrence can be managed with exenteration and/or radiotherapy.
• Regional lymph node metastasis can be managed with nodal dissection and/or radiotherapy.
• Distant metastasis has no known treatment.