PERSPECTIVE AND PATTERNS OF SPREAD
The eye is a palindrome of three letters, and its oncoanatomy is characterized by being a trilogy anatomically, reflecting it embryonic origin.
PERSPECTIVE AND PATTERNS OF SPREAD
Blindness is a major concern at any age, and any form of tumefaction is a challenge to the preservation of vision. The tissues of the eye in their embryogenic development are derived from neuroectoderm, surface ectoderm, and mesoderm. There are many different tumors that can arise around the orbit and in the eye due to the large variety of tissues that constitute this sensory organ and its anatomic environment (Table 55.1).
The eye is composed of three different layers, each with its unique structures. The neoplasms are different for adults and children. Each structure gives rise to a characteristic tumor that can only occur in that layer; that is, in the retina, retinoblastomas; in the pigmented choroids, the pigmented melanoma; or the sclera and conjunctiva squamous cell cancers. Each tumor spreads in a specific pattern depending on the layers involved however, each can advance and invade into other layers and structures of the eye and orbit (Fig. 55.1; Table 55.2).
An exact understanding of three-dimensional anatomy is essential in radiation oncology, where precision proton beams with sharp and limited Bragg peaks or strategically placed radioisotopic plaques have successfully eradicated choroidal melanomas and preserved vision. In a similar fashion, carefully shaped photon beams with appropriate shielding can save an eye in children with retinoblastomas and embryonal rhabdomyosarcomas.
Preservation of vision with tumor ablation is the essential goal for both the ophthalmologic surgeon and the radiation oncologist. Precise surgical ablative procedures match accurate proton beams and have allowed for high cure rates with eye and vision conservation. Enucleation and exenteration are reserved for very advanced and recurrent sarcomas and cancers.
The patterns of spread are presented to provide an overview of how neoplasms at each site of origin ultimately invade the eye globe from extraocular sites in contrast to intraocular sites. The accompanying SIMLAP tables provide the malignant gradient based on six patterns or vectors of invasion that determine stage advancement.
Figure 55.1 | A. Cancer of the eyelid. Invasion of globe is a late stage. B. Retinoblastoma. Initiates in the eye globe and spreads in an extraocular fashion. C. Orbital sarcomas begin in the orbit soft tissue/muscle and can invade into the eye globe as the tumor advances.
OVERVIEW OF EMBRYOGENESIS
Embryogenesis determines the histogenesis and offers insights into the variety of malignancies that form from birth to infants to children in rapid growth and adults (Table 55.3). Knowing specific normal tissue derivation in the eye provides an understanding of the carcinogenesis to sarcomagenesis (Fig. 55.2). The eye is uniquely designed for perceiving of light and color and distinguishing different forms.
Table 55.3 provides a concise list of the trigermal origin of specific tissues of the eye.
• The optic cup is a neuroectodermal outpouching that forms retina and optic nerve; therefore, primitive retinoblastomas are derived in this layer and spread into the optic nerve and disseminate into the central nervous system.
• Surface ectoderm forms the eyelid epidermis and its epithelial extensions, which become the conjunctival cover inside the eyelid and cover the eye globe. As in skin, epithelial skin cells give rise to basal cell and squamous cell cancers; more rare are melanomas.
• Glandular appendages in the eyelid and the lacrimal gland can give rise to adenocarcinomas, which are ectodermal derivatives.
• Mesoderm forms the connective tissue and mesenchyme of eye and includes the sclera of the eye, the vasculature in retina and choroid, and its arterial and venous drainage. The extraocular muscles can transform into embryonal rhabdomyosarcomas.
The choroid of the eye is the portion of the retina that lies next to the retina and consists of a choriocapillary layer, which consists of branching lamellae that have large, flat melanocyte scattered between connective tissue elements. As in the skin, the melanin protects against the damaging effects of non-ionizing ultraviolet light as it reaches the retina. Melanomas of the iris, uvea, and choroid can be aggressive, and their access to the loose vascular tissue in choroid allows for their metastatic spread. The iris is the anterior part of the vascular coat. The retina is neural ectoderm and can transform into retinoblastomas and invade via the optic nerve into the CNS.
Each source is a derivative of specific structural sites and i turn can lead to tumefactions that are unique.
Figure 55.2 | The eye as seen in a 15-week fetus. All the layers of the eye are established, and the hyaloid artery traverses the vitreous body from the optic disc to the posterior surface of the lens.
OVERVIEW OF HISTOGENESIS OF EYE PRIMARY SITES
• The overview begins with the sagittal section of the eye, which provides a framework for presenting the derivative normal cells and consequential tumors that arise from them (Table 55.4; Fig. 55.3).
• The eyelid forms the external covers of the eye, which are composed of epidermis and dermal glandular appendages that are special and specific to this site. Basal cell cancer are most common, squamous cell cancers are less common, and adenocarcinomas arising from meibomian, sebaceous (Zeis), or apocrine (Moll) glands are rare.
• Squamous cell cancers of the conjunctiva arise from stratified squamous epithelium
• Adenocarcinomas of the lacrimal gland parallel salivary gland neoplasms histopathologically, and both tend to be involved by lymphoma, which can be present in the conjunctiva and/or orbit, often as isolated sites of disease.
• Melanomas can arise from the pigmented uveal or choroid layer of the eye globe, very uncommonly on the iris, and even less so in the conjunctiva.
• The common pediatric tumors arising from the retina are retinoblastomas.
• Embryonal cancers arise from the orbital recti muscles.
• Sarcomas (not cancers).
Figure 55.3 | Sclera/choroid/retina.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
For all intents and purposes, the T category determines the stage. The TNM stage grouping is not used to stage eye malignancies, with the exception of uveal melanomas. Usually, malignancies of the eye are diagnosed and staged when they are millimeters in size rather than centimeters (Table 55.5A). Most often, T1 to T3 in all sites are measured in millimeters, not centimeters, for tumor progression. Careful mapping of tumor depth or height by width is often used. T4 lesions that invade into the orbit soft tissues tend to spread to preauricular, submandibular, and cervical nodes. The globe of the eye is immunologically privileged and without a lymphatic system. N1 is noted, but does not affect stage grouping. M1 is noted, but does not affect or modify stage IV.
The staging of different primary cancers depends on their origin (Fig. 55.4).
A. Eyelid cancers advance by invading the conjunctiva and eye globe.
B. Uvea melanoma of iris and ciliary body invade into canal of Schlemm, cause glaucoma, and extend into choroid and sclera.
C. Retinoblastoma invades globe and optic nerve.
D. Embryonal sarcomas invade orbit and advance, invading eye globe and into the base of the skull.
Stage grouping is new in the seventh edition of AJCC and applies only to eyelid and conjunctiva (Table 55.5B) and Uvea (Table 55.5C).
Figure 55.4 | T columns only. A. Eyelid cancer. B. Uvea melanoma. C. Retinoblastoma. D. Rhabdomyosarcoma. TNM staging criteria are color-coded bars for T advancement: Tis, yellow; T1, green; T2, blue; T3, purple; T4, red.
Orientation of Primary T-oncoanatomy
To appreciate the eye oncoanatomy, one needs to be aware of the trilogy segmentation, beginning with the globe of the eye (Fig. 55.5). A brief description of primary sites follows:
• Globe layers (Fig. 55.5A) are organized in three concentric coats: (i) Outer corneoscleral, (ii) middle vascular uvea/choroid, and (iii) inner photosensitive retina.
• Chambers of the eye (Fig. 55.5B) consist of (i) the anterior chamber, between the cornea and the iris; (ii) the posterior chamber, between the posterior surface of the iris and anterior surface and equator of the lens; and (iii) the vitreous chamber—the space between the lens and retina. The vitreous is filled with a gelatinous substance
From anterior to posterior.
• Eyelid of the eye (Fig. 55.6A) consists of three layers: (i) skin with eyelashes; (ii) meibomian glands, sebaceous glands of Zeis, and apocrine glands of Moll; and (iii) tarsal muscle and conjunctiva cover.
• Lacrimal apparatus (Fig. 55.6B) consists of three parts, as do the tears: (i) the lacrimal gland secretions are watery; the glands of the tarsal plate provide a waxy sebaceous secretion (meibomian) and an oily film (Zeis and Moll) which is collected by (ii) canaliculi at the inner canthus into a lacrimal sac; and (iii) a lacrimal canal that vertically descends into the nares below the inferior turbinate.
• Uvea (Fig. 55.6C) includes the iris, the ciliary body, and choroid.
• Orbit (Fig. 55.6D) contains the globe and consists of three compartments, each of which gives rise to retro-orbital tumors, that is, by adipose tissue in which the recti muscles (medial, lateral, superior, and inferior) and oblique (superior and inferior) muscles are innervated by three cranial nerves (III, IV, and VI), and surrounded by the bony orbit. The bony orbits are like inverted pyramids tipped medially, with four walls, an apex where the optic nerve enters, and the orbital opening surrounded by the eyelids that forms the base. It is approximately 4 cm at its base and 5 cm on its axis. The optic canal is less than 1 cm long. The superior and inferior orbital fissure and foramen allow for nerves arteries, and veins to enter and exit.
Figure 55.5 | Overview of T-oncoanatomy trilogy: Three chambers of the eye, anterior, middle, and posterior. Three layers: sclera, choroid, and retina.
Figure 55.6 | Overview of T-oncoanatomy Tripartite. A. Eyelid: skin, glands, conjunctiva. B. Lacrimal apparatus: gland, sac, duct. C. Uvea: Iris, ciliary body, choroid. D. Orbit: fat, extraocular muscles, optic nerve.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The eye globe is immunologically privileged, in that it is free of lymphatics and is similar to the central nervous system. However, the eyelids and orbital contents can be involved with infiltrations of inflammatory lymphocytes, pseudolymphomas and true lymphomas. A unique feature is the presence of direct lymphatic channels between lacrimal and parotid glands. The orbit and eyelids drain to preauricular or parotid nodes. Lesions at the inner canthus and lacrimal apparatus drain to facial and submandibular nodes (Fig. 55.7A, B; Table 55.6).
Figure 55.7 | N-oncoanatomy. A. Superficial drainage. B. Drainage of the trachea, thyroid gland, larynx, and floor of the mouth
M-ONCOANATOMY
The venous supply is the pathway for metastatic spread of cancers and/or sarcomas that occur with relative frequency in the orbit and the globe of the eye in both children and adults (Fig. 55.7C, D).
• Orbital: Neuroblastoma metastasis in children produces proptosis and ecchymosis (Hutchinson syndrome), whereas lymphomas and pseudolymphomas are more common in adults.
• Global: Metastatic choroidal deposits from the common adult cancers of the lung and the eye cause scotomas.
The venous drainage of the eye and orbit are more the recipient of metastatic cancer than viaducts for dissemination. The eye is relatively avascular, except for the choroidal layer, which has a rich venous network. The optic nerve is surrounded by all of the meningeal layers of the brain; the optic disc is a direct window into the central nervous system. Once the optic nerve is invaded by malignancy, a tumor can disseminate in the central nervous system via the subarachnoid space.
Figure 55.7 | M-oncoanatomy. C. Right ocular fundus, ophthalmoscopic view. Retinal venules (wider) and retinal arterioles (narrower) radiate from the center of the oval optic disc, formed in relation to the entry of the optic nerve into the eyeball. The round, dark area lateral to the disc is the macula; branches of vessels extend to this area, but do not reach its center—the fovea centralis, a depressed spot that is the area of most acute vision. It is avascular but, like the rest of the outermost (cones and rods) layer of the retina, is nourished by the adjacent choriocapillaris. An increase in cerebrospinal fluid pressure slow venous return from the retina, causing edema of the retina (fluid accumulation). The edema is viewed during ophthalmoscopy a swelling of the optic disc, a condition called papilledema. D. Blood supply to the eyeball. The eyeball has three layers: (a) the external, fibrous layer is the sclera and cornea; (b) the middle, vascular layer is the choroid, ciliary bod, and iris; and (c) the internal, neural layer or retina consists of a pigment cell layer and a neural layer. The central artery of the retina—a branch of the ophthalmic artery—is an end artery. Of the eight posterior ciliary arteries, six are short posterior ciliary arteries and supply the choroid, which in turn nourishes the outer, nonvascular layer of the retina. Two long posterior ciliary arteries, one on each side of the eyeball, run between the sclera and choroid to anastomose with the anterior ciliary arteries, which are derived from muscular branches. The choroid is drained by posterior ciliary veins, and four to five vorticose veins drain into the ophthalmic veins. he superior and inferior ophthalmic veins receive the vorticose veins from the eyeball and drain into the cavernous sinus posteriorly and the pterygoid plexus inferiorly. They communicate with the facial and supraorbital veins anteriorly.
Cranial Nerve Oncoanatomy
A diagrammatic presentation of the innovation of the eye: Cranial nerves (CN) II, III, IV, V sensory, and VI (Fig. 55.8A).
• The superior division of the oculomotor nerve (CN III) supplies the superior rectus and levator palpebrae muscles, the optic nerve CNII and optic nerve, chiasm, and tracts (Fig. 55.8B).
• The trochlear nerve (CN IV) lies on the medial side of the superior oblique muscle, and the abducent nerve (CN VI) lies on the medial side of the lateral rectus muscle.
• The lacrimal nerve runs superior to the lateral rectus muscle, supplying sensory fibers to the conjunctiva and skin of th superior eyelid; it receives a communicating branch of the zygomaticotemporal nerve carrying secretory motor fiber from the pterygopalatine ganglion to the lacrimal gland.
• The parasympathetic ciliary ganglion, placed between the lateral rectus muscle and the optic nerve (CN II), gives rise to many short ciliary nerves; the nasociliary nerve gives rise to two long ciliary nerves that anastomose with each other and the short ciliary nerves.
Superficial dissection is shown in Fig. 55.8C.
• The orbital plate of the frontal bone is removed.
• The levator palpebrae superioris muscle lies superficial t the superior rectus muscle.
• The trochlear, frontal, and lacrimal nerves lie immediately inferior to the roof of the orbital cavity.
Figure 55.8D shows deep dissection before (right side) and after (left side) section of the optic nerve (CN II).
• The eyeball occupies the anterior half of the orbital cavity.
• Nerves supplying the four recti (superior, medial, inferior, lateral) enter their ocular surfaces (the superior rectus is not shown).
• The parasympathetic ciliary ganglion lies posteriorly between the lateral rectus muscle and the sheath of the optic nerve.
• The nasociliary nerve (CN V1) sends a branch to the ciliary ganglion and crosses the optic nerve (CN II), where it gives off two long ciliary nerves (sensory to the eyeball and cornea) and the posterior ethmoidal nerve (to the sphenoidal sinus and posterior ethmoidal cells). The nasociliary nerve then divides into the anterior ethmoidal and infratrochlear nerves.
Figure 55.8E is a cross section of the optic nerve with three meningeal surrounding layers.
Figure 55.8 | Cranial nerves (CN) II, III, IV, V, and VI. B. Superior view, Transverse section, Cranial nerve II: optic.
Figure 55.8C–E | C. Orbital cavity, superior view. D. Nerves of the orbit in relation to the orbital fissures and the common tendinous ring. The common tendinous ring is formed by the origin of the four recti and encircles the dural sheath of the optic nerve, CN VI, and the superior and inferior branches of CN III; the nasociliary nerve (CN V1) also passes through this cuff. E. Optic nerve with three meningeal surrounding layers.
STAGING WORKUP
RULES FOR CLASSIFICATION AND STAGING
In general, clinical and pathologic assessment is essential to diagnosis and to staging with surgical resection or biopsy to establish the histopathology of the lesion. Imaging plays an important role in the evaluation.
Clinical Staging
The assessment of the tumor is based on physical examination, including careful inspection and palpation of eyelids and conjunctiva, followed by slit-lamp examination and direct and indirect ophthalmoscopy. Additional imaging techniques, such as ultrasonography, computed tomography (CT), MRI, fluorescein angiography, and isotopic studies may be indicated (Table 55.7). The three planar views of the eye, globe, and orbit are shown in Fig. 55.9. A. CT coronal, B. MRI sagittal, C. MRI transverse.
Pathologic Staging
Resection of primary site and careful assessment of tumor size, extent, and both dimensions—height or depth plus width—is important. Margins of the resected specimen are noted when wedge resection or enucleation of the globe is done. Histopathologic type and tumor grade apply to all sites; R1 is for microscopic and R2 is for macroscopic residual tumor. Venous invasion V1 microscopic and V2 macroscopic also should be noted.
PROGNOSIS AND CANCER SURVIVAL
CANCER STATISTICS AND SURVIVAL
The eye and orbit only account for 2,090 new diagnoses, excluding carcinomas of the eyelids. Deaths attributed to ocular malignancy are less than 10% of the entire group (fewer than 200 patients per year). Some of the most elegant proton and three-dimensional conformal radiation stereotactic techniques allow for cure of choroidal melanomas and retinoblastoma with preservation of vision.
Survival results are impressive. Virtually all eye tumor patients, when properly treated, reach 90% long-term survival.
• Basal cell cancers of the eyelids are greater than 95% curable.
• Radiation isotopic plaque and enucleation were found to be comparable in treating posterior uveal/choroidal melanomas in the Collaborative Ocular Melanoma Study group, consisting of 1,300 patients over 11.5 years. Recurrence rates with radiation range from about 15% to less than 5% with surgery. Cure rates range from 85% to 95%.
• Retinoblastomas are highly curable, with radiation yielding greater than 90% local tumor control, most often with vision conservation. Those patients who relapse can still be cured by enucleation.
• Optic nerve gliomas are extremely curable by stereotactic radiation therapy. The University of Pittsburgh group reports 96%, 90%, and 90% survival at 5, 10, and 15 years, respectively, with 86% retaining vision.
• Orbital and conjunctival lymphomas, when isolated, are 100% locally controlled with chemoradiation, and virtually all patients are long-term survivors.
• Embryonal rhabdomyosarcomas have the highest survivorship compared with all other sites, with up to greater than 90% long-term outcomes.
Figure 55.9 | Orbit, eye globe, and eyelid. A. Coronal view. Note the relationship of the orbit to paranasal sinuses: ethmoid, maxillary, and frontal. E. Ethmoid, CG. Crista Galli, EB. Eyeball, C. Inferior Concha, M. Maxillary Sinus, HP. Hard Palate, OC. Oral Cavity, IM. Inferior Meatus, NS. Nasal Septum, MR. Medial Rectus Muscle, MC. Air cell in middle concha, MM. Middle Meatus, MO. Opening of Maxillary Sinus. B. Sagittal view. Note the relationship of the eye globe and orbit to the cranial cavity and brain and the optic nerve chiasm. 1. Orbicularis oculi, 2. Eyeball, 3. Inferior Oblique Muscle, 4. Extracoronal Fat, 5. Inferior Rectus Muscle, 6. Dural and Arachnoid Sheath, 7. Retrobulbar Fat, 8. Superior Rectus Muscle, M. Maxillary Sinus. C. Axial transverse view. Note the relationship of the extraocular muscles in the orbit. 1. Optic Nerve, 2. The Lateral Rectus Muscle, 3. The Medial Rectus Muscle, 4. The Ethmoid Sinus, 5. Lacrimal Gland.