Lesions of Oil Gland Origin
Chalazia and hordeola are common eyelid lesions; they may present as obvious inflammations, or, if noninflamed, may be mistaken for cutaneous or subcutaneous neoplasms. At times, the reverse may be true, as malignant lesions may simulate benign processes.
These growths (Figure 7) occur due to obstruction of the orifices of the oil-producing meibomian glands. Subsequently, the sebaceous contents of these glands are forced into the tarsus and surrounding soft tissues of the eyelid, leading to a chronic localized inflammatory response. Risk factors for chalazia are chronic blepharitis, rosacea, and chronic occupational exposure to fine particulate debris. The typical clinical findings are a tender, erythematous eyelid nodule overlying the tarsus, sometimes accompanied by secondary acute bacterial infection. Some patients may present with the sudden onset of multiple simultaneous chalazia involving several eyelids, suggesting hormonal or exogenous predisposing factors. The classic histopathologic finding in chalazia is chronic lipogranulomatous inflammation.
In the early inflammatory phase, conservative treatment with warm compresses and eyelid scrubs are helpful. Topical antibiotic or anti-inflammatory ocular drops or ointments offer minimal, if any, benefit. Acutely infected chalazia with localized abscess or cellulitis may benefit from oral antibiotics directed toward Gram-positive bacteria such as Staphylococcus aureus. In some cases in which a large painful abscess develops, early surgical drainage of the abscess is beneficial. Systemic doxycycline (40 to 100 mg daily or twice a day) provides long-term suppression of meibomian gland inflammation associated with chronic blepharitis and ocular rosacea and may accelerate the resolution of chalazia. Tetracycline in a maintenance dose of 250 mg twice a day is better tolerated than doxycycline in some patients, due to the decreased incidence of gastrointestinal side effects. This suppressive treatment may need to be continued for at least 2 months.
Eventually, most chalazia become chronic and cyst-like, and the larger ones often require surgical management. Simple incision and curettage of the chalazion is often adequate for permanent resolution. If the greatest inflammatory response is on the posterior eyelid margin, an incision through tarsus and conjunctiva is appropriate for drainage. Sharp dissection and excision of all lipogranulomatous contents, as well as the posterior cyst wall, is indicated. This results in a posterior marsupialization of the chalazion. Extreme care is needed when removing inflammatory tissue at the eyelid margin or adjacent to the punctum. In the cases in which the greatest inflammatory response is anterior, incision through the skin and orbicularis muscle with appropriate removal of granulomatous tissue is recommended. Because of the possibility of mistaking malignant lesions for chalazia, histopathologic examination is appropriate for any suspicious or atypical chalazion and for all recurrent chalazia. Local injection of corticosteroids in chalazia can be beneficial for small chalazia, but this may cause depigmentation of the overlying skin and is not as effective as surgical treatment.
A hordeolum (Figure 8) is an acute bacterial infection within the glands of Zeis (external hordeolum, or stye). The infection often appears to surround an eyelash follicle, and the lash can be removed to promote drainage. Spontaneous resolution usually occurs with small hordeola. If symptoms persist, application of hot compresses and topical antibiotic ointment is usually successful in resolving the lesion. Larger painful hordeola with abscess development or cellulitis can be treated with oral antibiotics, and sometimes also require incision and drainage.
Sebaceous gland hyperplasia manifests as multiple small yellow papules, often with central umbilication, on the forehead and cheeks. They often occur in patients over the age of 40. These lesions may appear to be similar to basal cell carcinomas, because of central umbilication and fine telangiectasias. However, they have a yellow coloration and are usually not as indurated as basal cell carcinoma. They may arise following chronic dermatitis and are sometimes associated with rosacea. When sebaceous hyperplasia involves the meibomian glands, the eyelids may become thickened and develop ectropion and may often exhibit co-existing chronic blepharitis. With this constellation of findings, sebaceous gland carcinoma must be considered as a possible diagnosis and biopsy is warranted.
This type of tumor presents as a yellowish papule on the face, scalp, or trunk. It is rare and may have an appearance similar to basal cell carcinoma or seborrheic keratosis. Patients with a history of multiple sebaceous gland adenomas, multifocal adenomatoid sebaceous hyperplasia, or basal cell carcinomas with sebaceous differentiation may have Muir-Torre syndrome. These patients have an increased risk of visceral malignancy and should undergo a thorough systemic evaluation. Treatment options for sebaceous adenomas include complete excision, cryotherapy, or ablation with carbon dioxide laser.
These yellowish plaques typically present in the medial aspect of the upper and lower eyelids and often extend into the medial canthus (Figure 9). They contain lipid-laden macrophages within the superficial dermis, but the contents may extend deeply into underlying orbicularis muscle. Although xanthelasmas usually occur in patients with normal serum cholesterol levels, in some cases they may be associated with hereditary hypertriglyceridemia or hypercholesterolemia. Conservative surgical excision is the preferred method of treatment of xanthelasmas, taking care to avoid the removal of too much eyelid skin, which could lead to cicatricial ectropion. Following surgery, xanthelasmas may recur near the original excision site, sometimes requiring repeated excisions. Other treatment options for more superficial xanthelasmas include CO2 laser ablation or topical 100% trichloroacetic acid (TCA).
Tumors of Melanocytic Origin
Benign melanocytic lesions of the skin may develop from 3 sources: nevus cells, dermal melanocytes, and epidermal melanocytes. Nearly any benign or malignant lesion may contain pigmentation, and conversely, lesions of melanocytic origin do not always have visible pigmentation. Although seborrheic keratoses and basal cell carcinomas are sometimes pigmented, dermal nevi typically have no pigmentation in Caucasian patients. Melanocytes are typically located at the dermal-epidermal junction of the skin. Nevus cells are similar to melanocytes, but are arranged in clusters and have ultrastructural differences. Melanocytes as well as nevus cells may develop into a number of benign melanocytic lesions. Aside from the discrete melanocytic lesions described below, diffuse eyelid skin hyperpigmentation called melasma, or chloasma, may occur in women who are pregnant or using oral contraceptives. This also presents as a hereditary condition in families with an autosomal dominant trait and in patients with chronic inflammatory dermatoses, including atopic eczema and rosacea.
Nevi are the third most common benign skin lesions found in the periocular region. They arise from nevus cells, which are incompletely differentiated melanocytes, and form clusters within the epidermis, dermis, or in the junction zone between the epidermis and dermis. Nevi are not typically visible at birth; they appear during childhood and often exhibit a more rapid increase in pigmentation about the time of puberty.
All nevi evolve in location and appearance during life through 3 stages. The junctional stage is located in the basal layer of the epidermis at the dermal-epidermal junction, the compound stage extends from the junctional zone up into the epidermis and down into the dermis, and the intradermal stage is caused by involution of the epidermal component and persistence of the dermal component of the compound nevus. In children, nevi usually start as junctional nevi, which are typically flat, pigmented macules. After the second decade, most nevi develop into compound nevi, at which stage they appear as elevated pigmented papules. Later in adult life, the epidermal component and its pigmentation are lost and the compound nevus becomes an intradermal nevus. It is still elevated but has evolved into a minimally pigmented or amelanotic lesion (Figure 12). By age 70 virtually all nevi will be dermal nevi and will have lost most of their pigmentation.
Nevi are common on the eyelid margin, and the posterior surface typically has been molded by the ocular surface. Benign nevi require no treatment, but malignant transformation of a junctional or compound nevus can very rarely occur. If there are no suspicious features to suggest malignant transformation, smaller nevi can be managed by simple excision or by shaving at the dermal-epidermal junction. Although they may recur following this, they rarely re-grow to attain their original dimensions. Large lid margin nevi that are symptomatic or cosmetically bothersome to the patient may be completely excised using a full-thickness wedge resection technique.
Simple lentigines are flat, evenly pigmented macules that are slightly larger than ephelides (freckles). Simple lentigines occur throughout life; they are not considered to be related to ultraviolet radiation or sun exposure. This type of lentigo contains more epidermal melanocytes than a freckle, and melanin is found in adjacent basal keratinocytes in lentigines, but not in freckles. Multiple eyelid lentigines may be associated with Peutz-Jeghers syndrome. No treatment is necessary for lentigo simplex. Melanin-bleaching topical medications may be used to achieve cosmetic improvement.
Solar Lentigo (Lentigo Senilis)
Multiple solar lentigines are often encountered in older individuals and are often incorrectly referred to as liver spots. These pigmented macules contain an increased number of melanocytes and present as multiple, dark-brown flat lesions, some with irregular borders. Solar lentigines are typically more pigmented and larger than simple lentigines. These lesions arise following chronic sun exposure, and the dorsum of the hands and the forehead are the most commonly involved areas. No treatment is usually necessary, but sun protection is recommended. Melanin-bleaching topical medications or cryotherapy may help diminish the hyperpigmentation.
A blue nevus is a dark bluish-gray, dome-shaped, slightly elevated papule that may be congenital and present at birth or may develop during childhood. It arises from dermal melanocytes and is usually 10 mm or less in diameter. Although the malignant potential is extremely low, these lesions are frequently excised.
Also known as nevus of Ota, this diffuse, periocular congenital blue nevus most often affects female individuals of African, Hispanic, or Asian descent. The eyelid and periocular skin is blue or brown, due to diffuse proliferation of dermal melanocytes in the distribution of the first and second divisions of cranial nerve V. The vast majority of cases are unilateral with only about 5% of cases being bilateral. When the periocular hyperpigmentation is associated with patchy slate-gray pigmentation on the episclera and uvea, as occurs in two-thirds of patients, the condition is known as oculodermal melanocytosis. Approximately 1 in 400 patients with oculodermal melanocytosis will develop a uveal malignant melanoma from malignant transformation, which is more likely in white patients. There is no treatment or intervention that will prevent malignant transformation.
Premalignant Epidermal Lesions
Actinic keratosis is the most common precancerous skin lesion and usually affects elderly individuals with a fair complexion and a history of repeated sun exposure over many years. These lesions are typically irregular, round, scaly, keratotic plaques, which have a roughened texture on palpation. They are most often observed on the face, head, neck, dorsum of the hands, and forearms. These lesions are constantly changing and evolving, and often worsen and enlarge in response to increased sunlight exposure. As many as 25% of actinic keratoses will resolve spontaneously over a 12-month period, although new lesions will continue to develop. The risk of malignant transformation of an individual actinic keratosis is only 0.24% per year, but over many years, a patient with multiple actinic keratoses has a 12% to 16% incidence of developing squamous cell carcinoma. However, squamous cell carcinomas evolving from actinic keratoses are believed to be less aggressive than those arising de novo.
For lesions arising in the periocular region, biopsy is recommended to establish a definitive diagnosis and identify early malignancies. Treatment of these lesions with complete excision or cryoablation is recommended. Alternative dermatologic therapies have included 5-fluorouracil or imiquimod cream.
This disease represents squamous cell carcinoma in situ involving the skin. Growths present as nonhealing elevated erythematous lesions, with scaling, crusting, or pigmented keratotic plaques. On histopathologic examination, the lesions demonstrate full-thickness epidermal atypia with no dermal invasion. Five percent of patients with Bowen disease may progress to vertically invasive squamous cell carcinoma. Therefore, complete surgical excision is strongly recommended. Along the eyelid margin, an incorrect diagnosis of “Bowen disease” may actually represent the pagetoid spread of sebaceous carcinoma. In some of these cases, the pagetoid spread may precede the clinical findings of invasive sebaceous cell carcinoma within the deeper tissues of the eyelid.
Although it was previously regarded to be a benign stable lesion, many dermatopathology authors now consider keratoacanthoma to represent a low-grade squamous cell carcinoma. Keratoacanthoma usually begins as a flesh-colored papule on the lower lid that evolves quickly into a dome-shaped nodule with a central keratin-filled crater and rolled, elevated margins (Figure 13). These lesions are most often observed in middle-aged, elderly, or immunosuppressed patients. A common clinical course is gradual spontaneous involution over 3 to 6 months. The abundant keratin material in the central crater may induce an inflammatory immune response, which may play a significant role in spontaneous resolution. The treatment of choice is complete surgical excision.
Premalignant Melanocytic Lesions
Also known as Hutchinson’s melanotic freckle or precancerous melanosis, lentigo maligna (Figure 14) is a slowly enlarging, flat, irregular, unevenly pigmented lesion that often involves the malar regions. Features that differentiate lentigo maligna from senile or solar lentigo are irregular borders, significant pigmentary variation, and slow, progressive enlargement. This continued enlargement represents a radial, intraepidermal uncontrolled growth phase of melanocytes that may last for decades and eventually may progress to nodules of vertically invasive melanoma (lentigo malignant melanoma).
Examination of the involved area under ultraviolet illumination with a “Woods light” may reveal that the area of active disease often extends beyond the visible pigmented borders of the lesion. Cutaneous lentigo maligna of the eyelid may extend onto the conjunctival surface, where it appears identical to primary acquired melanosis (PAM). Historically, complete wide excision with frozen and permanent sections for monitoring the surgical margins has been recommended to reduce the incidence of invasive melanoma. This approach has been debated because of the large size of these lesions, the potentially disfiguring nature of aggressive surgical resection, the occurrence in very elderly patients, and the uncertain and sometimes stable natural history of these lesions. Estimates of the risk of developing invasive lentigo malignant melanoma vary from 10% to 30%, and malignant transformation sometimes does not occur for 1 or 2 decades or longer. Frequent repeated examinations, irradiation, or cryoablation have been advocated as alternatives to wide excision for extensive lesions. However, if nodules of invasive melanoma develop, then complete surgical excision with permanent section histopathologic monitoring of margins is still the treatment of choice. Frequent postoperative observation for development of recurrence is necessary.