10 Eyelid and Periocular Tumors
“Eyelid and Periocular Tumors” discusses these lesions, which are very common in patients referred to ophthalmologists. The main goal in the evaluation of these lesions is to differentiate malignant from benign lesions and to recognize the relevance of some lesions as markers of the potential for systemic malignancies, such as Muir-Torre syndrome (MTS): a combination of neoplasms of the skin and a visceral malignancy. A number of subtle features can help to differentiate malignant from benign eyelid tumors, but it can be extremely difficult to make the correct diagnosis of an eyelid lesion without a biopsy. Some malignant lesions may appear relatively innocuous; conversely, some benign lesions may appear extremely sinister. Alternatively, the clinical pattern of some malignant eyelid tumors can simulate other tumor types. Early diagnosis can significantly reduce morbidity and mortality associated with malignant eyelid tumors, but only if a high degree of clinical suspicion is applied when examining all eyelid lesions. The appropriate management of malignant eyelid tumors requires a thorough understanding of their clinical characteristics and their pathologic behavior.
Eyelid and periocular skin lesions are very common in patients referred to ophthalmologists. The main goal in the evaluation of these lesions is to differentiate malignant from benign lesions and to recognize the relevance of some lesions as markers of the potential for systemic malignancies, such as Muir-Torre syndrome (MTS)—a combination of neoplasms of the skin (usually sebaceous adenoma, sebaceous epithelioma, or sebaceous carcinoma but also keratoacanthoma) and a visceral malignancy (usually colorectal, endometrial, small intestine, and urothelial).
In general, the majority of malignant tumors affecting the eyelids and periocular area are slowly enlarging, destructive lesions that distort or frankly destroy eyelid anatomy. There are a number of subtle features that can help to differentiate malignant from benign eyelid tumors (Box 10.1). It can, however, be extremely difficult to make the correct diagnosis of an eyelid lesion without a biopsy. Some malignant lesions may appear relatively innocuous (Fig. 10‑1a). Conversely, some benign lesions may appear extremely sinister (Fig. 10‑1b).
Box 10.1 Clinical Signs Suggestive of Malignancy
A localized loss of lashes
Obliteration of the eyelid margin
Pearly telangiectatic change
A new enlarging pigmented lesion
An area of diffuse induration
A scirrhous retracted area
Alternatively, the clinical pattern of some malignant eyelid tumors can simulate other tumor types; for example, pigmented eyelid tumors are much more commonly basal cell carcinomas (BCC) than melanomas (Fig. 10‑2).
Early diagnosis can significantly reduce morbidity and indeed mortality associated with malignant eyelid tumors. However, malignant eyelid tumors are diagnosed early only if a high degree of clinical suspicion is applied when examining all eyelid lesions. The appropriate management of malignant eyelid tumors requires a thorough understanding of their clinical characteristics and their pathologic behavior.
Slit lamp examination can highlight these various features that help to differentiate benign from malignant tumors (Fig. 10‑3). Most benign eyelid tumors can be readily diagnosed on the basis of their typical clinical appearance and behavior. In some cases, however, the diagnosis can only be made with the aid of a biopsy. Changes in the appearance of an eyelid lesion previously believed to be benign, such as an increase in size, ulceration, or bleeding, are indications for a biopsy.
Malignant eyelid tumors are diagnosed early only if a high degree of clinical suspicion is applied when examining all eyelid lesions. A classification of benign and malignant eyelid tumors is provided in Table 10‑1.
10.2 Benign Eyelid And Periocular Tumors
The eyelids have many different components from which a multitude of benign tumors may arise. Most benign eyelid tumors arise from structures that compose the eyelid skin: the epidermis, the dermis, the adnexa (pilosebaceous units, eccrine, and apocrine sweat glands), and pigment cells.
Examples of a number of common and less common benign eyelid tumors are presented.
10.2.1 Benign Lesions of the Epidermis
The term papilloma is used to describe any lesion that exhibits a papillomatous growth pattern (i.e., a smooth, rounded or pedunculated elevation). The term squamous papilloma is used to describe any papilloma that has a nonviral cause. This is the most common benign eyelid lesion and occurs most in patients older than 30 years. Eyelid papillomata present as single or multiple small flesh-colored sessile (Fig. 10‑4) or pedunculated growths with a central vascular core that bleeds readily on removal of the lesion.
The lesion may also develop on the palpebral or bulbar conjunctiva. Occasionally a malignant lesion can resemble a papilloma (Fig. 10‑5).
The lesions can be removed surgically. A broad-based lesion affecting the eyelid margin can be shaved and the base cauterized to avoid disruption to the eyelid margin.
A seborrheic keratosis is the most common benign eyelid tumor. It is most common in middle-aged and elderly individuals of Western European descent. It is an epithelial tumor that can occur anywhere on the body. On the eyelids the lesion typically presents with a greasy appearance and may be sessile, lobulated, papillary, or pedunculated. The surface of the lesion has friable excrescences (Fig. 10‑6). The lesions should not usually present difficulties in clinical diagnosis, but they can be confused with verruca vulgaris, actinic keratosis, pigmented BCC, and eyelid melanoma.
These lesions are easily removed by simple shave excision, leaving a flat surface that re-epithelializes.
Inverted Follicular Keratosis
Inverted follicular keratosis is a benign lesion that occurs in older patients and more commonly affects males (Fig. 10‑7). It presents as a small hyperkeratotic or warty mass that may show scaling. It is often mistaken for a malignant lesion, particularly when it is associated with the development of a cutaneous horn.
Inverted follicular keratosis is treated by complete surgical excision to prevent recurrence.
Cutaneous horn is the term used to describe a protuberant projection of packed keratin that resembles a horn seen in animals (Fig. 10‑8). It is more common in elderly patients. The horn can be associated with a number of benign, premalignant, and malignant lesions at its base, and the underlying diagnosis may be masked. Any such horn should raise the suspicion that the underlying lesion may be a squamous cell carcinoma (SCC). A cutaneous horn may also be associated with verruca vulgaris, actinic keratosis, seborrheic keratosis, inverted follicular keratosis, tricholemmoma, and BCC.
In most patients the diagnosis is uncertain until the lesion has been removed and submitted for histopathological examination.
Because the cutaneous horn may overlie a malignant lesion, a complete surgical excision biopsy should be performed.
An epidermoid cyst (epidermal inclusion cyst) is a very common lesion that arises from entrapment of surface epithelium. This can occur after surgery or spontaneously. The lesion presents as a slowly growing round, firm, whitish or yellowish lump, which is usually solitary and mobile (Fig. 10‑9). A central pore may be seen. Rupture of the cyst wall can result in an inflammatory foreign body reaction or a secondary infection.
The lesion should be completely removed. Incomplete removal results in recurrence of the lesion.
A dermoid cyst is a choristoma that results from the sequestration of skin during embryonic development. Continued secretion by sebaceous and sweat glands contained within the lesion causes a gradual increase in the size of the cyst. The cyst also contains hairs. The cyst is present at birth but may not become evident until adulthood. The cyst may lie outside the orbit but may have an extension into the orbit. A “dumb-bell” dermoid cyst has an orbital extension and an extraorbital extension, usually positioned over the lateral orbital wall. Rupture of the cyst releases secretions that are highly irritant and cause an acute inflammatory reaction.
Most dermoid cysts are discovered in childhood and are located over the frontozygomatic suture (Fig. 10‑10). They can occur in the superomedial aspect of the eyelid or orbit, where they must be differentiated from a meningocele or meningoencephalocele by means of computed tomography (CT). Any dermoid cyst with suspected intraorbital extension should be scanned before surgical intervention.
Treatment of a dermoid cyst consists of complete surgical excision. Most lesions can be removed via an upper lid skin crease incision, avoiding a visible scar (Fig. 10‑11a,b). Care should be taken to ensure that the cyst is removed completely and without rupturing the cyst wall. The (off-label) intralesional injection of Tisseel can greatly assist the removal of such lesions. Such an injection results in a solidification of the cyst, making the dissection easier to perform and avoiding the risk of rupture with spillage of cyst contents. It is important to inform the histopathologist that this has been used. Great care should also be taken to avoid intraoperative damage to the trochlea when removing a medial canthal dermoid cyst.
A suspected dermoid cyst located in the superomedial aspect of the eyelid or orbit must be differentiated from a meningocele or meningoencephalocele by CT. Any dermoid cyst with suspected intraorbital extension should be scanned before surgical intervention. Great care should be taken to avoid intraoperative damage to the trochlea when removing a medial canthal dermoid cyst.
Phakomatous choristoma is a rare congenital lesion that results from surface ectodermal cells destined to form the lens plate and lens vesicle in the embryo, remaining outside the optic vesicle during closure of the embryonic fissure. These cells multiply and form the lesion in the anteroinferior aspect of the lower eyelid (Fig. 10‑12). The eye is usually free from any associated developmental anomalies.
The lesion is managed by surgical excision.
Milia are small, raised, round, white, well-circumscribed, superficial keratin cysts (Fig. 10‑13). They are caused by occlusion of pilosebaceous units. These commonly occur in the eyelids. They are particularly common in newborn babies. They may occur spontaneously or can occur after trauma or treatments such as chemical peeling. As in the previous example, milia may be seen in young patients with Gorlin’s syndrome (basal cell nevus syndrome).
The lesions can be removed for cosmetic reasons by incising them with the cutting edge of a sterile needle.
The skin lesions of molluscum contagiosum are usually multiple, dome-shaped, and umbilicated papules (Fig. 10‑14). They are self-limiting in immunocompetent patients. An associated follicular conjunctivitis may occur. Severe and aggressive involvement of the periocular region may occur in patients with acquired immunodeficiency syndrome (AIDS) or who are otherwise severely immunocompromised.
The lesions can be treated by incision and curettage, surgical excision, electrodessication, or cryotherapy.
A verruca vulgaris is a papilloma caused by the human papillomavirus (Fig. 10‑15). The lesion may appear as a filiform or flat wart. The lesion begins as a small brown papule that slowly enlarges and develops an elevated irregular hyperkeratotic, papillomatous surface. The filiform type is the most common variety seen on the eyelids. Lesions that involve the eyelid margin may be associated with a papillary conjunctivitis from the shedding of viral particles into the conjunctival sac.
Although the lesion can be treated in a variety of ways, including cryotherapy, chemical cautery, and electrodessication, complete surgical excision is preferable.
10.2.2 Benign Lesions of the Dermis
A capillary hemangioma represents the most common benign periocular tumor of infancy. It is thought to be a vascular hamartoma. These benign vascular tumors are usually not apparent at birth but appear soon after in the first few weeks of life. They are generally associated with a growth phase characterized by rapid enlargement and reach 80% of their full size by approximately 5 months of age. This is followed by a period of slowed growth, which is then followed by a regression stage, resulting in a gradual decrease in the size of the lesion. Involution generally occurs at a rate of 10% per year, with approximately 50% of lesions completely resolved by 5 years of age. Ninety percent of lesions regress completely by 9 to 10 years of age. Overall, approximately 85% of these lesions regress without the need for any active intervention.
The clinical appearance varies with the depth of the lesion. The lesion may present as a superficial cutaneous lesion (a strawberry hemangioma), a subcutaneous lesion, an orbital lesion, or a combination of all three (Fig. 10‑16a). Initially the hemangioma typically presents as a flat red lesion with overlying telangiectases and then grows into a red, elevated soft painless compressible mass. A subcutaneous hemangioma presents as a bluish-purple mass. The extent of the lesion may need to be determined by imaging using CT, magnetic resonance imaging (MRI), or ultrasound scanning. Great care should be taken to differentiate such lesions from other more sinister mimicking lesions (Fig. 10‑16b).
Large facial hemangiomas can be associated with PHACES syndrome ( P osterior fossa malformations, H emangioma, A rterial anomalies, C ardiac defects, E ye abnormalities, S ternal clefting). Lower face and neck hemangiomas have been associated with concomitant airway hemangiomas that may cause significant bleeding during anesthesia.
PHACES syndrome should be suspected when a hemangioma is segmental and larger than 5 cm in size. The patient should undergo an echocardiogram to exclude any contraindications to the use of systemic propranolol and an MRI or magnetic resonance angiogram of the head and neck. Children with PHACES syndrome are more likely to develop migraine headaches, seizures, developmental delays, speech delays and, very rarely, ischemic strokes. The Dandy-Walker malformation is the most common developmental abnormality of the brain and is seen in approximately one-third of PHACES patients. They may also have cardiac anomalies such as coarctation of the aorta, other aortic arch abnormalities, and vascular anomalies. Aneurysms, anomalous branches of the internal carotid artery, and arterial stenosis are common associations. Children with PHACES also have a significant risk of permanent cosmetic deformity, because their hemangiomas are often very extensive.
Ocular abnormalities that have been reported with PHACES syndrome include the following:
Ipsilateral Horner’s syndrome.
Retinal vascular dilation and tortuosity.
Iris vessel hypertrophy.
Optic nerve hypoplasia.
Congenital oculomotor nerve palsy.
Periorbital and orbital hemangiomas can be associated with visual morbidity for a number of reasons:
Eyelid lesions can cause a mechanical blepharoptosis and occlusive amblyopia and may also be associated with induced astigmatism, causing refractive amblyopia that may not resolve with treatment of the hemangioma.
Orbital hemangiomas are associated with proptosis and secondary exposure keratopathy, ocular motility restrictions, and optic nerve compromise if the posterior orbit is involved.
Treatment of periocular capillary hemangiomas is indicated to prevent loss of visual function and to prevent pain and disfigurement. Observation alone is a very reasonable option for lesions that do not interfere with vision or cause any significant deformity or dysfunction.
There are several treatment options:
For many years both intralesional steroid injections and oral steroids have been considered the mainstay of treatment in cases in which active intervention is considered appropriate, taking into consideration the risks of such treatment. Orally administered steroids in infants are associated with significant risks, however: adrenal suppression, growth retardation, immunosuppression, cataracts, and glaucoma. Intralesional steroid injections are also associated with risks: localized fat atrophy, cutaneous pigmentary changes, and, very rarely, devastating visual loss from emboli affecting the arterial blood flow to the retina and occlusion of the central retinal artery from the effects of a retrobulbar hemorrhage.
It is imperative that an infant is very closely monitored by both a pediatrician and an ophthalmologist throughout the course of treatment.
Pulsed-dye laser treatment has been used for capillary hemangiomas with some improvement. Generally this has been recommended during the early proliferative or the late regression phases when the lesion is flatter.
Surgical debulking or a complete surgical excision may be required for well-defined localized lesions that fail to respond to medical management (Fig. 10‑17). Because these are vascular tumors, intraoperative bleeding is a risk factor that must be considered. Surgical excision in the late involuted phases can be indicated to remove unsightly residual lesions.
Propranolol is a nonselective beta blocker that inhibits the action of epinephrine and norepinephrine on β1 and β2 receptors. It has been used in children for the management of hypertension, tachycardia, migraine headaches, tremors, and performance anxiety. It has had a good safety and tolerance record.
In 2008 Dr. Christine Leaute-Labreze and colleagues described two pediatric patients who showed resolution of capillary hemangiomas when they were treated with oral propranolol for the management of cardiac disease. They subsequently treated nine additional children who had capillary hemangiomas but who did not have cardiac disease using oral propranolol. All these patients showed changes in their hemangiomas within 24 hours of commencing the oral propranolol, and each had resolution of the lesions after a course of treatment without significant systemic side effects.
The mode of action of propranolol on capillary hemangiomas is not entirely clear but may include vasoconstriction of the intralesional blood vessels, downregulation of growth factors including vascular endothelial growth factor (VEGF) and fibroblast growth factor, and triggering apoptosis.
There have been many subsequent reports using oral propranolol as a primary treatment of capillary hemangiomas with excellent results, although the treatment is not effective for all patients. Some lesions show recurrence after treatment, whereas some lesions continue to progress with no response at all. Side effects associated with treatment with oral propranolol must be considered and include bradycardia, hypotension, hypoglycemia, allergic reaction to the medication, and gastrointestinal upset.
Treatment using oral propranolol should be undertaken by a pediatrician.
Timolol maleate is a nonselective beta blocker that is similar to Propranolol and had been used for many years to treat glaucoma. Several authors have shown a regression response in some periocular capillary hemangiomas treated with topical timolol maleate gel. They reported no adverse ocular or systemic side effects associated with this treatment.
A cavernous hemangioma is rarely seen as an isolated eyelid lesion. It represents a hamartoma and is much more common in the orbit, where it occurs as the most benign orbital tumor in adults. In contrast to the lesion seen in the orbit, an eyelid cavernous hemangioma is not encapsulated and tends to be adherent to the overlying dermis. A subtype termed sinusoidal cavernous hemangioma involves the eyelid and adjacent brow or cheek and has a more aggressive growth pattern (Fig. 10‑18). It is dark blue in appearance through the overlying thinned skin and compressible. Because the lesion rarely appears before middle childhood, it seldom causes amblyopia.
Although the lesion can be treated with intralesional sclerosing agents or cryotherapy, surgical excision is usually preferred.
Plexiform neurofibromas are pathognomonic for type 1 neurofibromatosis (NF-1). The tumor arises from and grows along peripheral nerves. The lesions typically present during the first decade of childhood and may be responsible for occlusion amblyopia. The lesions typically present with a diffuse infiltration of the eyelid and orbit. Palpation of the lesions gives a sensation that has been likened to that of feeling a “bag of worms.” The findings at surgery explain the reasons for this. The upper eyelid is involved in approximately 95% of cases. The lower eyelid is involved in approximately 50% of cases and the brow in approximately 15 to 20% of cases. The upper lid becomes ptotic and gradually assumes an S-shape as it thickens and develops horizontal laxity. The lesions are quite vascular and widely and diffusely infiltrative.
Systemic associations may include the following:
Central nervous system hamartomas.
Medullary thyroid carcinoma.
Ocular associations may include the following:
Iris nodules (Lisch nodules).
Retinal astrocytic hamartoma.
Optic nerve glioma.
Optic nerve meningioma.
Pulsating exophthalmos related to sphenoid wing maldevelopment (Fig. 10‑19).
Plexiform neurofibromas are extremely difficult to manage because of their infiltrative growth pattern and vascularity. Surgical debulking may improve the patient’s visual function and cosmetic appearance, but this usually has to be repeated at regular intervals. The surgery can be very difficult. The surgeon should be prepared to manage a significant secondary soft tissue volume deficit, because the external appearances can belie the full extent of the lesion (Fig. 10‑20). The surgeon should obtain consent in advance for the use of primary fat grafting.