2 Malignant Tumors

INTRODUCTION

Eyelid malignancies are common enough to be of concern to all physicians dealing with eyes and the skin of the face. The most common eyelid cancer is basal cell carcinoma. In the western hemisphere it accounts for more than 85% of all eyelid malignancies. However, in China the incidence seems to be closer to 50% of eyelid malignancies. Squamous cell carcinoma and sebaceous gland carcinoma combine to make up most of the other 50%: whereas, in the western countries, these two tumors make up less than 10% of all eyelid malignancies.

Two other tumors, lymphoma and malignant melanoma, occur on the eyelids with much less frequency but must be considered because of their serious potential. There are some other very rare tumors that will be mentioned in this chapter.

All of these tumors can be lethal but cure rates are high if the cancers are recognized and treated early enough to prevent spread beyond the eyelids. Basal cell carcinoma is the easiest to cure because it grows slowly and causes damage by direct extension and very rarely metastasizes. Squamous cell carcinoma metastasizes on occasion. Sebaceous cell carcinoma and malignant melanoma have a high rate of metastasis; therefore, early treatment is essential in these cases. Lymphoma may present in the ocular area and proper treatment may prevent spread to the rest of the body.

BASAL CELL CARCINOMA

Basal cell carcinoma is the most common malignancy of the eyelids. It occurs most frequently on the lower eyelid and the medial canthus, depending on which study is reviewed.1–5 Most authors agree that the lateral canthus is the area of least involvement. Since basal cell carcinomas often involves an upper or lower lid in association with part of the medial or lateral canthus, these statistical distributions are somewhat arbitrary. In one study, the tumor distribution was as follows: lower lid, 53%; medial canthus, 27%; upper lid, 1.2%; and lateral canthus, 8%.1 Another study had these statistics: lower lid, 66%; upper lid, 16%; medial canthus, 13%; lateral canthus, 3%.3

The tumor is most often found in the sixth, seventh, and eighth decades of life, but 15% of patients in one study1 and close to 5% of patients in another study3 were between the ages of 20 and 40 years.

The major etiological association appears to be with extended sun exposure in a fair-skinned person. This concept is based on the very extensive literature of basal cell carcinoma appearing in Europe, Australia, and North America.6 However, basal cell carcinoma is seen in the East,

including Japan, Korea, and India.7, 8 There is no sex predilection. In an article from Sweden, the authors conclude that ultraviolet light only partially explains the etiology of periocular basal cell carcinoma.9

Although basal cell carcinomas exhibit various clinical presentations, the physical characteristics and behavior patterns of these tumors can be correlated with their different histological presentations. The most common type is an indurated, firm, nodular tumor, often with fine telangiectasia. This tumor usually has no associated discomfort, and for that reason, patients often allow the tumors to get quite large before seeking medical assistance. Histologically, the nodular type of basal cell carcinoma shows the tumor cells growing in nests with peripheral palisading. The nodular type of tumor tends to be the least aggressive and rarely has subcutaneous extensions which are not clinically visible (36–38).

Some authors further subdivide the nodular pattern into an ulcerative pattern and a multicentric pattern.10 In the ulcerative pattern, there is a true ulcer crater within a raised, pearly margin. This type of clinical presentation has given rise to the term rodent ulcer which, in the past, has been synonymous with basal cell carcinoma. The ulcerative type of basal cell carcinoma usually shows a deeper more infiltrative dermal component to the tumor (39–42). The multicentric pattern shows numerous lobules of tumor at the base of the epithelium or in the superficial chorion.

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36–38 Examples of nodular basal cell carcinomas. 36: A pearly nodule typical of a basal cell carcinoma which is raised above the skin.The edges are well defined, round and smooth.This is clinically a nodular type and the margins would not be expected to extend beyond the visible tumor.

The margin of this lesion is often beyond the area of suspected clinical involvement (43, 44).

The other subclassification of basal cell carcinoma is the morpheaform or sclerosing basal cell carcinoma. Clinically, this pattern is that of a flat, indurated plaque. It may be on the lid margin or just below the lashes. It often simulates a localized blepharitis. If this pattern occurs away from the lid margin, it appears as a firm subcutaneous lesion (45). There may be inflammation associated with the lesion. The borders are usually quite indistinct. In some cases, there is extensive subcutaneous involvement which is not visible clinically. A retrospective study showed that the defect left after Mohs micrographic surgery was 6.1 times the size of the original clinical tumor for morpheaform carcinoma, compared to 4.4 times for the nodular or basosquamous types.6 The morpheaform basal cell carcinoma is usually the most aggressive. However, authors of a study carried out at the Armed Forces Institute of Pathology in Washington, D.C. concluded that a mixed type basal cell carcinoma may be as aggressive as the morphea type.11

Histologically, these tumors consist of cells growing in thin strands or cords with an extensive connective tissue component. The morpheaform type of tumor may give vague discomfort, but often they are asymptomatic (46, 47). A rare variant is the clear-cell basal cell carcinoma which does not often present on the eyelids.12

Patients can present with discomfort in the area of the

lid margin and no obvious tumor. Skin biopsies sometimes appear negative for tumor. However, in one study fullthickness lid margin biopsies revealed the presence of morpheaform tumors that were much more extensive than clinical evidence had indicated (48).13

Although basal cell carcinomas are the most common malignant eyelid tumors, diagnosis is missed in a significant number of patients (43, 44, 52, 53). Pigmented basal cell carcinomas, although rare, are commonly missed prior to biopsy (21). One study showed eight out of nine pigmented basal cell carcinomas to have incorrect clinical diagnoses, whereas a correct diagnosis prior to biopsy was made in 80% of nonpigmented basal cell carcinomas.14 Another study showed only 60% of all basal cell carcinomas to be properly diagnosed prior to biopsy.10

In a prospective study, tumors were clinically diagnosed. All tumors were biopsied and the histological results were compared with the clinical diagnoses. In most cases, the clinical diagnoses were correct. A few tumors which were thought to be malignant showed benign histology when biopsied. In these patients, re-biopsy was performed because of the high clinical suspicion of malignancy. In fact, these tumors were malignant. The authors concluded that clinical diagnosis, although not perfect, is pretty good and a second biopsy should be performed if there is a high clinical suspicion of malignancy. They also concluded that all tumors which are excised should be sent for histological confirmation.15

18 Malignant Tumors

Basal cell carcinomas tend to grow slowly, and many patients present with a history of having noticed a tumor several months to several years prior to seeking medical attention. The most dangerous are untreated basal cell carcinomas in the medial canthus since posterior extension can progress into the sinuses (49–53).4 For all practical purposes, basal cell carcinomas do not metastasize, and, therefore, elimination of the localized lesion should result in a high cure rate. However, there are exceptions.13 Some authors feel that the basosquamous cell carcinoma may have a tendency to metastasize.6

TREATMENT

There are three techniques that can yield satisfactory results in the majority of patients with basal cell carcinoma. These are: surgery using microscopic evaluation of the margins, cryotherapy, and radiation therapy.

Two separate studies have reported zero recurrence rates after excision of eyelid basal cell carcinomas using frozen section control.1, 16 The follow-up period in these studies ranged from several months to 18 years. Surgeons using the Mohs technique have reported recurrence rates of 6% or less.2, 17, 18 In a study in which microscopic control was not used during surgical excision of eyelid basal cell carcinomas, 50% were reported to be incompletely excised when histological examination was performed. There was a recurrence rate of 23.4% (11 of 47 tumors) among the incompletely excised carcinomas.19 A study from Iceland demonstrated about a 30% recurrence rate with incompletely excised lesions.5

Treatment of basal cell carcinomas using cryotherapy has become an acceptable treatment with a high cure rate. For lesions less than 10 mm (0.4 in) in diameter, nodular basal cell carcinomas had a 97% cure rate with cryotherapy, and infiltrated morpheaform basal cell carcinomas had a 94% cure rate. However, with lesions larger than 10 mm diameter, the cure rate dropped to 85% for nodular basal cell tumors and 82% for infiltrative lesions. These statistics are based on a five-year follow-up.20 In a prospective study, 222 eyelid tumors were followed for up to 10 years. Ninetytwo were studied for five years. There were no recurrences in this group of patients.21 Another study had a 92% nonrecurrence rate with a mean follow-up of five years.22

Chemotherapy using cisplatin and doxorubicin was used in recurrent invasive basal cell carcinoma of the medial canthus and orbit. Complete remission was still evident after five years.23

Radiation therapy is an excellent way to control basal cell carcinoma. The pros and cons of radiation versus surgery have been expressed in the medical literature.24 In one study, treatment of eyelid basal cell carcinoma using radiation therapy resulted in a tumor control rate of 96%.25

Electrodessication and curettage, and topical treatment with antineoplastic medications have a recurrence rate which is significantly higher than surgery, radiation therapy, or cryotherapy. For this reason, those methods receive no further attention in this text.

COMMENT

Several patients each year present to the author with a history of a benign tumor based on biopsy. If clinical suspicion for malignancy is high, the area will be re-biopsied, or the whole tumor may be removed. In the vast majority of these cases, malignancy is found. In these cases it is possible that the first biopsy was not aggressive enough because of fear of causing an eyelid defect from the biopsy. To diagnose and treat eyelid tumors, the surgeon must be comfortable with surgery of the eyelid margin and tear drainage system.

Surgical excision with microscopic evaluation of the margins is the best method for eliminating basal cell carcinoma. In most cases, reconstruction should be done shortly after the tumor has been removed. Occasionally, spontaneous granulation can be used with good results. The tumor excision may be done by the same surgeon who is performing the repair, or it may be done by someone else, such as a dermatologist trained in the Mohs technique. Consideration regarding length of time needed for excision and repair, as well as logistical problems, may help in the decision as to which surgical technique is best in a particular situation.

This book is devoted to the surgical removal of periocular tumors and methods of repair – other methods of treatment will not be discussed extensively. Readers are encouraged to examine the medical literature to become familiar with the other forms of treatment of eyelid tumors.

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49–53 Basal cell carcinomas causing extensive destruction. 49: Destructive basal cell carcinoma in an elderly male. 50: A

70-year-old female with extensive destruction by basal cell carcinoma, histologically reported as solid and cystic in type. 51: 60-year-old female who ignored the basal cell carcinoma growing on her face for several years. 52: 65-year-old female who had an eyelid basal cell carcinoma surgically removed and postoperative radiation therapy. She was followed by her physicians for several years as the eyelids began to ‘scar’. She was eventually sent to me for eyelid reconstruction to open her eyes. 53: Same patient as 52 two months postexenteration for extensive basal cell carcinoma involving both eyelids, globe and extension into the orbit. Her surgeon and radiologist mistook an enlarging basal cell carcinoma for radiation changes.

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