From the Section of Ophthalmology, Department of Head and Neck Surgery (FMG, RS, AMS, BE), the Department of Pathology (DB), the Department of Plastic Surgery (JMS), and the Department of Neurosurgery (NBL), The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Roman Shinder, MD, Section of Ophthalmology, Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1445, Houston, TX 77030.
The most common primary epithelial malignancies of the lacrimal gland are adenoid cystic carcinoma (60%), malignant mixed tumor (20%), and de novo adenocarcinoma (10%).1,2 We report the clinical and pathologic features in a teenage patient with spontaneous malignant mixed tumor (carcinoma ex-pleomorphic adenoma) of the lacrimal gland. To our knowledge, this may be the first reported case of carcinoma ex-pleomorphic adenoma of the lacrimal gland in the pediatric age group.
A 17-year-old boy with a 6-month history of a painless, enlarging right orbital mass was referred to our institution. He noted deterioration of vision in his right eye during the previous 2 months. Ophthalmic examination yielded a best-corrected visual acuity of 20/25 in the right eye. Gross examination showed right periorbital fullness, with proptosis and inferonasal dystopia of the right eye (Fig. 1). There was 7 mm of proptosis and restriction of motility on the right side. There was also elevation of the superior choroid on fundus examination.
Figure 1. Patient at Presentation with Proptosis and Inferonasal Dystopia of the Right Globe.
Orbital imaging showed a right lacrimal gland mass with invasion of the lateral orbital wall into the temporalis muscle (Fig. 2). After negative findings on a metastatic work-up, the patient underwent a right anterior orbitotomy with lacrimal gland biopsy, which revealed poorly differentiated carcinoma with perineural invasion (Fig. 3A).
Figure 2. (A) Axial Computed Tomography and (B) Coronal T-2 Weighted Magnetic Resonance Imaging Demonstrate a Right Lacrimal Gland Mass with Contiguous Invasion Through the Lateral Orbital Wall Invading the Temporalis Muscle.
Figure 3. Histopathologic Findings. (A) The Large Part of the Mass Consisted of an Infiltrative Carcinoma with Scant Peripheral Residual Lacrimal Gland Parenchyma (hematoxylin–Eosin, Original Magnification ×4). (B) Interface Between the Hyalinized Areas of Pleomorphic Adenoma (arrow) and Regions with Large and Pleomorphic Carcinomatous Cells (Hematoxylin–Eosin, Original Magnification ×4). (C) Perineural Invasion Was Present (hematoxylin–Eosin, Original Magnification ×10).
The patient underwent a craniotomy and an extended right orbital exenteration with removal of the superior and lateral orbital walls and temporalis muscle. Microscopically, the tumor comprised two components: expanding round cellular nodules with necrotic centers and smaller, more irregular cords and ducts within a sclerotic background (Fig. 3B). Perineural invasion was noted (Fig. 3C). The mitotic rate was high, and tumor necrosis was prominent. A minute peripheral remnant of lacrimal gland and residual hyalinized pleomorphic adenoma were noted (Fig. 3B). The histologic findings were most consistent with high-grade malignant mixed tumor ex-pleomorphic adenoma invading bone with perineural and vascular invasion.
The patient underwent external beam radiotherapy with a total dose of 60 Gy. The patient is currently 6 months post exenteration and has no clinical or radiographic evidence of recurrence. The patient is scheduled to begin adjuvant systemic chemotherapy consisting of carboplatin, paclitaxel, and Herceptin (Genentech, South San Francisco, CA) in the near future.
Malignant mixed tumor is the second most common epithelial lacrimal gland malignancy after adenoid cystic carcinoma. In a recent 30-year survey of 1,264 patients with orbital tumors and pseudotumors, Shields et al. found 4 cases of malignant mixed tumor.2 This represented less than 1% of all orbital lesions, but 24% of primary malignant epithelial lacrimal gland tumors.2 It is known to evolve in three possible ways: it can occur years after incomplete excision or incisional biopsy of a pleomorphic adenoma (most common); evolve from a previously unrecognized pleomorphic adenoma with a short course of lacrimal gland enlargement (5 months or less); or gradually transform from a pleomorphic adenoma over the course of decades.3,4 This tumor most commonly occurs in the sixth or seventh decade of life.5
The lacrimal gland is histologically similar to other salivary glands and, as such, pathologic diagnoses in the lacrimal gland are often comparable to those found in the salivary glands. In this case, malignant mixed tumor ex-pleomorphic adenoma would be synonymous with spontaneous salivary duct carcinoma. Malignant mixed tumor is histologically similar to a pleomorphic adenoma but has areas of malignant poorly differentiated carcinoma,6 as were seen in our patient. Computed tomography is the imaging modality of choice to investigate for bony involvement, and biopsy is necessary to establish the diagnosis and determine treatment options.
The major predictors of survival are pathologic stage, histologic grade, proliferation index, ratio of carcinoma to benign components, and invasion.7 The 5-year survival rate for patients with carcinoma ex-pleomorphic adenoma of the salivary gland was 30% in 66 patients treated at the Mayo Clinic.7
Given the locally aggressive nature of this tumor, orbital exenteration and removal of involved structures including the bony lacrimal gland fossa and adjuvant radiotherapy has been advocated.6 Metastasis is rare.8
In our patient, the tumor most likely developed spontaneously from a previously unrecognized pleomorphic adenoma because there was no prior surgical intervention and the duration of symptoms was only a few months. Although other primary malignant epithelial lacrimal gland tumors including adenoid cystic carcinoma were in the differential diagnosis in this case, the histopathologic findings were consistent with a malignant mixed tumor, especially given the presence of the pleomorphic adenoma tissue (Fig. 3B). We found no other reports in the literature of malignant mixed tumor of the lacrimal gland in the pediatric age group. This rare entity should be considered in the differential diagnosis of any patient with an enlarging lacrimal gland mass, regardless of age. Additionally, clinicians must keep in mind that this rare entity may arise spontaneously in patients without a known history of pleomorphic adenoma.
- Shields JA, Shields CL, Epstein JA, Scartozzi R, Eagle RC Jr, . Review: primary epithelial malignancies of the lacrimal gland: the 2003 Ramon L. Font lecture. Ophthal Plast Reconstr Surg. 2004;20:10–21. doi:10.1097/01.IOP.0000103003.87842.BB [CrossRef]
- Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery Lecture, part 1. Ophthalmology. 2004;111:997–1008. doi:10.1016/j.ophtha.2003.01.002 [CrossRef]
- Garrity J, Henderson J, Cameron JD. Primary epithelial neoplasms. In: Garrity JA, Henderson JW, eds. Henderson’s Orbital Tumors, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2007:281–288.
- Shields JA, Shields CL. Malignant transformation of presumed pleomorphic adenoma of lacrimal gland after 60 years. Arch Ophthalmol. 1987;105:1403–1405.
- Bernardini FP, Devoto MH, Croxatto JO. Epithelial tumors of the lacrimal gland: an update. Curr Opin Ophthalmol. 2008;19:409–413. doi:10.1097/ICU.0b013e32830b13e1 [CrossRef]
- Kuroishikawa M, Kiyosawa M, Akashi T, Mochizuki M. Case of lacrimal gland carcinoma ex adenoma. Jpn J Ophthalmol. 2004;48:181–182. doi:10.1007/s10384-003-0025-z [CrossRef]
- Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001;32:596–604. doi:10.1053/hupa.2001.25000 [CrossRef]
- Chang CJ, Lin TK, Wei LC, et al. Carcinoma ex pleomorphic adenoma of the lacrimal gland: a case report. Ann Ophthalmol (Skokie). 2006;38:141–144. doi:10.1385/AO:38:2:141 [CrossRef]