MALIGNANT MELANOMA

Cutaneous malignant melanoma is the leading cause of death from all primary skin tumors. Melanoma rarely arises on the lid, constituting approximately 1% of all eyelid malignancies. The incidence of cutaneous melanoma has risen greatly in past decades, for reasons that are not altogether clear. When on the eyelids they most commonly affect the lower lid. The largest reported series of eyelid melanomas consists of only 32 tumors.8

Cutaneous melanoma arises from epidermal melanocytes and is histologically classified into four different types of tumors: lentigo maligna melanoma, superficial spreading melanoma, nodular malignant melanoma, and acral lentiginous melanoma. The first three types can occur on the eyelid, the fourth (acral lentiginous) only occurs on distal extremities and will not be covered here.

The histopathology of cutaneous malignant melanoma varies by type. Common features include atypical melanocytes showing many dysplastic features, such as nuclear atypia, pleomorphism, and mitotic figures (166). Differences in growth patterns between the different histologic subtypes of melanoma can be summarized as follows:

•Lentigo maligna displays diffuse hyperplasia of malignant melanocytes along the basal cell layer of the epidermis. Lentigo may surround pilosebaceous structures, and occasionally sends fascicles of spindle-shaped cells into the deep dermis.

•Superficial spreading melanoma exhibits pagetoid features, in that groups or nests of malignant melanocytes can be found in a diffuse area, without continuity. These melanocytes are found in all layers of the epidermis. The vertical growth phase of this type of tumor can show spindle or epithelioid cell types.

•Nodular melanoma shows rapid vertical growth, probably not preceded by any significant horizontal phase. Epithelioid cells are seen, occasionally in an adenoid pattern. This type of melanoma carries the worst prognosis.

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Two systems are used to determine prognosis in the histopathologic examination of cutaneous malignant melanoma. The first, named for WH Clark, classifies tumors based on their level of invasion, where level 1 tumors are confined to the epidermis, and level 5 tumors extend into the subcutaneous tissue.9 The second system, described by Breslow, uses depth measurements (in millimeters) to determine prognosis.10 Tumors <0.76 mm 0.03 in) thick have a 100% five-year survival rate, whereas tumors >1.5 mm (0.06 in) thick have less than a 50% fiveyear survival rate.

REFERENCES

1.Doxanas MT, Green WR, Iliff CE (1981). Factors in the successful surgical management of basal cell carcinoma of the eyelid. Am J Ophthalmol., 91: 726–736.

2.Kass LG, Hornblass A (1989). Sebaceous carcinoma of the ocular adnexa. Surv. Ophthalmol., 33: 477–490.

3.Reifler DM, Hornblass A (1986). Squamous cell carcinoma of the eyelid. Surv. Ophthalmol., 30: 349–365.

4.Yanoff M, Fine BS (1996). Skin and lacrimal drainage system. In: Ocular Pathology, 4th edn. M. Yanoff, BS Fine (eds). Chicago, Mosby-Wolfe, pp. 190–191.

5.Graham JH, Helwig EB (1972). Premalignant cutaneous and mucocutaneous diseases. In: Dermal Pathology. JH Graham, WC Johnson, EB Helwig (eds). Hagerstown, MD, Harper and Row, p. 561.

6.Doxanas MT, Iliff WJ, Iliff NT, Green WR (1987). Squamous cell carcinoma of the eyelids. Ophthalmology, 94: 538–541.

7.Riley FC (1970). Metastatic tumors of the eyelids. Am. J. Ophthalmol., 69: 259–264.

8.Grossniklaus HE, McLean IW (1991). Cutaneous melanoma of the eyelid: Clinicopathologic features.

Ophthalmology, 98: 1867–1873.

9.Clark WH Jr, From Bernardino EA, et al. (1969). The histogenesis and biologic behavior of primary human malignant melanoma of the skin. Cancer Res., 29: 705.

10.Breslow A (1970). Thickness, cross-sectional areas and depths of invasion in the prognosis of cutaneous melanoma. Ann. Surg., 172: 902–908.

BIOPSY TECHNIQUES

Although clinical acumen is very valuable in the diagnosis of eyelid tumors, a biopsy is necessary for confirmation. For small tumors that appear to be benign, an excisional biopsy can be performed. A preoperative photograph should be taken. If the diagnosis turns out to be malignant and the pathology report shows that the tumor has not been completely excised, then further excision and possible reconstruction will be necessary. If there has been a time lapse of several weeks from the time of the initial biopsy to the time of the second surgical procedure, the area of the original biopsy might have healed to a significant degree making it difficult to decide where to do the further surgical excision. The preoperative photo will be most helpful in these cases.

If the tumor is thought to be malignant, it is preferable to do an incisional biopsy for the purpose of making a diagnosis and leaving a sufficient amount of tumor so that when a final excision is done there will be enough tumor present in the specimen for the pathologist to evaluate the margins (167, 168). In situations where excisional biopsy shows a malignant tumor, the patient may be left with either no scar, or only a slight scar. In these cases, a subsequent relatively wide excision would have to be performed, in order to remove the small amount of residual tumor that might be present after the original biopsy showed incomplete resection of the tumor.

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TREATMENT

There are essentially three acceptable methods for the treatment of eyelid tumors: surgery, cryotherapy, and radiation therapy. While all three methods are currently accepted modalities for the treatment of most eyelid tumors, not all tumors can be best treated by all methods.

SURGERY

Mohs technique

Two techniques, which are similar in theory, are currently accepted methods for the surgical removal of eyelid malignancies. These are Mohs fresh tissue technique and frozen section control using microscopic evaluation of the margins. The original Mohs technique consisted of fixing the cancerous tissues with a zinc chloride paste, and then excising the tumor by layers and examining each section microscopically to see the extent of the tumor. Deeper sections were taken until all of the tumor was removed. The advantage of the technique is to follow the tumor extensions in any direction until all of the cancer is eradicated.1

For tumors around the eyelid, a fresh tissue technique was developed because the zinc chloride paste caused ocular irritation.2 In the fresh tissue technique, local anesthetic is used, and the tumor is then excised by layers just as in the original chemosurgical technique. The sections are stained and numbered so that the tumor can be followed to its depth and all extensions beyond the clinically apparent tumor can be completely removed. Cure rates vary from 94% using the fresh tissue technique in the periorbital area,3 to 99.3% for skin basal cell carcinomas in all areas using the fixed tissue method.4

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As this technique is currently used, a surgeon trained in Mohs chemosurgery will remove the tumor, and either allow the area to heal by spontaneous granulation or refer the patient to a reconstructive surgeon for eyelid repair. The advantage of this method is a high cure rate combined with conservation of tissue that, in the eyelid area, may well be important.

One of the potential disadvantages of the Mohs technique is that the surgeon performing the chemosurgery does not usually perform the reconstruction. Hence, repair of the eyelid may not commence immediately after the chemosurgery has been completed. The ideal situation would be for the reconstructive surgeon to continue with the patient as soon as the chemosurgeon is finished.

Frozen section control

In contrast to the Mohs technique, an attempt is made to remove the entire tumor at once. The tumor is evaluated clinically and an incision is made to include the tumor and 2–3 mm (0.1 in) of normal appearing tissue around the tumor. If microscopic tumor is seen at any of the margins, more sections are taken.

The tumor can also be removed with the Ellman Surgitron (see Chapter 7: General Principals of Eyelid Reconstruction and Radiosurgery), using the A-10 needle on ‘cut’. This gives so little lateral heat that the edges of the specimen are not distorted and the pathologist can give an accurate reading. In some cases, a small tumor may only involve the lid margin and not extend deep into the tarsus. The A-10 is so thin that splitting the tarsus horizontally is easily done. This will allow preservation of tarsus for reconstruction.

The traditional method of performing frozen sections

for eyelid tumors has been to make one or two crosssectional cuts through the tumor to see if it extended to the edges of these cuts. This method does not allow for evaluation of tributaries of tumor that may extend past the surgical margins in a plane not evaluated by the crosssectional cuts.

A currently acceptable method of frozen section control is to remove the tumor with 2–3 mm (0.1 in) of apparently normal tissue, and then take thin slices of all borders and examine these sections in their entirety as flat preparations (168). This method will evaluate all of the margins of the specimen, and will also find any tumor that might be extending into the tissues in an area that was not appreciated clinically. In this regard, the method is similar to the Mohs technique for finding tumor extension no matter in which direction it may be headed.5, 6

This approach requires that the pathologist works closely with the surgeon. The pathologist must completely understand the tumor orientation since frozen section analysis will be used to evaluate the extent of the tumor. Some surgeons prefer to take slices themselves from the tumor margin for microscopic evaluation, while others leave the pathologist to make all of the sections in order to understand the orientation of the tumor. If there is extension to any of the margins, further dissection is done only in that area, until the margins are completely clear of tumor. This method is also similar to the Mohs fresh tissue technique, in that further tissue is removed only where tumor extension is found.

To assure proper orientation by the pathologist, the tumor can be sent to the laboratory on a properly labeled drawing. In some cases, the pathologist may be present when the tumor is removed and/or the surgeon may leave the operating suite and work together with the pathologist while the frozen sections are taken. Both the surgeon and the pathologist can then examine the microscopic specimen to assure that further dissection will only be done where tumor is present. Reconstruction is usually begun after all of the tumor has been removed. However, in some cases, flaps or grafts that may be needed in the reconstruction can be fashioned while the pathologist is reviewing the microscopic slides.

RADIATION THERAPY

Radiation therapy is an effective method of treating eyelid carcinomas. Cure rates of 99%,7 95% for basal cell carcinoma,8 and 97% for squamous cell carcinoma8 have been reported. For eyelid lymphomas, radiation therapy is the treatment of choice. Sebaceous cell carcinoma does not respond well to radiation therapy which should only be reserved for situations in which surgery is contraindicated.

Most authors report acceptable cosmetic results and a low incidence of side-effects with radiation therapy.7–9 Prior to the emergence of outpatient surgical facilities, one advantage of radiation therapy was elimination of hospitalization. However, since most eyelid tumor surgery is performed in an outpatient setting, this particular advantage of radiation therapy over surgical therapy has been diminished.

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Disadvantages of radiation therapy include permanent alopecia, radiation dermatitis, conjunctivitis, and lacrimal duct stenosis.7, 9 A significant drawback to radiation therapy becomes apparent if the malignancy recurs since additional X-ray treatment is usually contraindicated and secondary surgery becomes more difficult and less effective in areas where radiation therapy has already been performed.10

CRYOTHERAPY

Cryotherapy is an effective treatment for many benign eyelid lesions,11 as well as for basal cell carcinoma of the eyelids. Studies have shown a 97% cure rate for nodular basal cell carcinoma, and a 97% cure rate for infiltrative basal cell carcinoma in the eyelid region if the lesions were <10 mm(0.4 in) in diameter.12 The cure rate dropped to 85% and 82% respectively, for lesions >10 mm in diameter.

In order to kill tumor cells, a temperature of –25°C (–13°F) to –30°C (–22°F) must be reached. Liquid nitrogen has been shown to be the best substance available to obtain this temperature at the tumor depth.10 In order to be sure that the temperature at the tumor is ideal, a thermocouple must be used. After injecting a local anesthetic, the thermocouple needle is inserted to the depth of the tumor. Liquid nitrogen is applied to the surface of the tumor by using a spray, or by a probe through which a stream of nitrogen vapor is passed. If the tumor is near the eyelid, the globe should be protected. Liquid nitrogen is applied until a temperature of –30°C is obtained. The area is then allowed to thaw spontaneously to 0°C (32°F). Liquid nitrogen is reapplied until the thermocouple reaches –30°C again. The area is again allowed to thaw spontaneously to 0°C.

Advantages of cryotherapy include economy of time for the patient and the surgeon, and decreased costs compared to other methods of treatment of eyelid carcinoma. Complications include depigmentation of the skin and alopecia of the treated area.

COMMENT

Since basal cell carcinoma and squamous cell carcinoma can be locally destructive or even lethal in some cases, the best method of treatment is surgical removal with microscopic control followed by appropriate reconstruction immediately or shortly after the tumor has been removed. If surgery is not appropriate for various reasons, cryotherapy or radiation therapy must then be considered. The author has seen a patient with an eyelid sebaceous cell carcinoma that was completely removed as indicated by frozen section analysis. Metastases occurred and she was tumor free 5 years after initiation of chemotherapy.

For small benign lesions, surgical removal has the advantage of obtaining microscopic diagnosis and a good cosmetic result. Cryotherapy can also give a good cosmetic result but lacks the advantage of obtaining a tissue diagnosis. Once a tissue diagnosis has been made, radiation therapy is the treatment of choice for lymphomatous lesions.