Neoplasms of the orbit may be primary or secondary (extensions from adjacent structures or metastatic disease). Secondary tumors are slightly more common than primary tumors (see the section Secondary Tumors at the end of this chapter). The types of orbital tumors that occur in children differ from those that occur in adults. Developmental tumors are the primary orbital lesions most often encountered in children, whereas vascular and lymphoid tumors are the primary orbital lesions most often seen in adults.
In children, approximately 90% of orbital tumors are benign. Benign cystic lesions (dermoid or simple epithelial cysts) represent 50% of orbital lesions in childhood. Rhabdomyosarcoma is the most common primary orbital malignant tumor in childhood and represents 3% of all orbital masses. The orbit may be involved secondarily in cases of retinoblastoma, neuroblastoma, and leukemia/lymphoma.
Lacrimal Gland Neoplasia
Because the lacrimal gland is very similar to the salivary gland, epithelial lacrimal gland tumors are categorized according to the World Health Organization (WHO) epithelial salivary gland classification system. The most common types of epithelial lacrimal gland tumors are pleomorphic adenoma, adenocarcinoma arising from pleomorphic adenoma (carcinoma ex pleomorphic adenoma), and adenoid cystic carcinoma.
The most common epithelial tumor of the lacrimal gland is pleomorphic adenoma (also known as benign mixed tumor). Pleomorphic adenoma is slightly more common in men than in women and usually presents in the fourth or fifth decade of life. The tumor is pseudoencapsulated and grows slowly by expansion. This progressive expansive growth may excavate the bone of the lacrimal fossa. Tumor growth stimulates the periosteum to deposit a thin layer of new bone (ie, cortication). The adjacent orbital bone is not eroded. Typically, the patient experiences no pain.
Histologically, pleomorphic adenoma has a fibrous pseudocapsule and comprises a mixture of duct-derived epithelial and stromal elements, all arising from the lacrimal glandular epithelium. The epithelial component may form nests or tubules lined by 2 layers of cells, the outermost layer blending imperceptibly with the stroma (Fig 14-7). The stroma may appear myxoid and may contain heterologous elements, including cartilage and bone. Results of immunohistochemistry (IHC) reflect the epithelial and myoepithelial components, both derived from epithelium. The tumor cells are usually positive with IHC for keratin and epithelial membrane antigen in the ductal areas and positive with IHC for keratin, actin, myosin, fibronectin, and S-100 protein in the myoepithelial areas. Microscopic foci of carcinoma in situ may be identified in these lesions but are not a significant feature.
Malignant transformation may take place in a long-standing or incompletely excised pleomorphic adenoma in the form of adenocarcinoma (carcinoma ex pleomorphic adenoma), with relatively rapid growth after a period of relative quiescence. Malignancies, including adenocarcinoma (carcinoma ex pleomorphic adenoma) and adenoid cystic carcinoma, may also develop in pleomorphic adenomas that recur in the orbit.
Adenoid cystic carcinoma
As mentioned previously, adenoid cystic carcinoma (ACC) can develop in a pleomorphic adenoma or, more commonly, arise de novo in the lacrimal gland. The tumor is slightly more common in women than in men, and the median age at presentation is about 40 years.
Unlike pleomorphic adenoma, ACC has no pseudocapsule; it tends to erode bone and invade orbital nerves, accounting for the pain that is frequently reported by patients on presentation. The gross appearance is grayish white, firm, and nodular. Histologically, the tumor cells may grow in a variety of patterns: cribriform (“Swiss cheese”), which is the most common; basaloid (solid nests); comedo; sclerosing; and tubular (ductal) (Fig 14-8). Presence of the basaloid pattern has been associated with a worse prognosis (5-year survival rate of 20%) when compared with absence of a basaloid component (5-year survival rate of 70%). IHC staining for S-100 protein, keratin, and actin is typically positive within areas of myoepithelial differentiation. There is a correlation between expression of bcl-2 and BAX proteins and a more favorable prognosis. Expression of p53 is associated with a poor prognosis. Orbital exenteration is one of the currently accepted treatments for this tumor, but some advocate globe-sparing intra-arterial chemotherapy.
Figure 14-7 Pleomorphic adenoma (benign mixed tumor) of the lacrimal gland. A, Clinical photograph. A superotemporal orbital mass is present, causing proptosis and downward displacement of the left globe. B, CT scan (coronal view) demonstrates the left orbit tumor. C, Low-magnification photomicrograph shows the circumscribed nature of this pleomorphic adenoma. D, Note both the neoplastic epithelial elements (arrow) and the fibromyxoid stroma (asterisk).E, Frequent well-differentiated glandular structures with lumina (asterisk) are seen. The outer myoepithelial layer can become metaplastic and form other mesenchymal tissue (eg, bone, cartilage [arrow]).
(Parts A and B courtesy of Sander Dubovy, MD; parts C–E courtesy of Heather Potter, MD.)
Figure 14-8 Adenoid cystic carcinoma of the lacrimal gland. A, Low-magnification photomicrograph shows numerous invasive tumor lobules. B, Note the characteristic cribriform (“Swiss cheese”) pattern of growth. C, The solid lobules of tumor represent the basaloid pattern, which is associated with a less favorable prognosis. D, Perineural invasion of tumor. Blue tumor invades the perineurium and surrounds a peripheral nerve (asterisk).
(Part A courtesy of Heather Potter, MD; parts B–D courtesy of Nasreen A. Syed, MD.)
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(6):1210–1215.
von Holstein SL, Coupland SE, Briscoe D, Le Tourneau C, Heegaard S. Epithelial tumours of the lacrimal gland: a clinical, histopathological, surgical and oncological survey. Acta Ophthalmol. 2013;91(3):195–206.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.