Ординатура / Офтальмология / Английские материалы / Tumors of the Eye and Ocular Adnexa_Char_2001

MALIGNANT MELANOMA

Melanomas account for approximately 1 percent of eyelid tumors.116 As discussed above, pigmented basal cell carcinoma is almost 10 times more common than melanoma as a cause of a pigmented lid neoplasm. Several studies have shown that the annual incidence of melanoma has at least tripled in the last four decades in all age groups.116,117

Probably the majority of melanomas arise from malignant degeneration of pre-existing nevi.118 There

Figure 1–20. The direct coronal MR image from the patient shown in Figure 1–19 demonstrates perineural invasion into the superior orbit.

1–23. Occasionally, the eyelid may be secondarily involved by a conjunctival melanoma (Figure 1–24).

Early diagnosis of melanomas, when the tumor is relatively thin, has resulted in improved prognosis. While other factors, including gender, age, site, ulceration, regression, and mitotic index are correlated with prognosis, tumor thickness remains the most important predictor of prognosis. In melanomas of < 0.85 mm thickness, there is < 1 percent tumor-related mortality, while lesions > 3.65 mm thick have 8-year survival rates of < 38 percent.125 Further, for cutaneous melanomas, the average time to metastasize varies according to tumor thickness. In thin melanomas, tumor-related mortality peaked at 6 years, while thicker tumors had a mortality peak at approximately 40 months.126 The reason for the better prognosis in women is uncertain; hypotheses advanced include a difference in

anatomic sites, differences in tumor thickness, and hormonal factors.123

Unlike uveal melanomas, in which it is not uncommon to develop metastases more than 10 years after diagnosis, late onset of widespread disease is rare with cutaneous melanomas, and over 80 percent of late metastases have occurred with uveal melanomas.127–131

There have been several staging systems for cutaneous melanoma since one of the earliest in 1947 by Ackerman and Del Regato.

Table 1–4 shows a truncated revision of the 1997 Joint Committee on the cancer staging system for melanoma. It is very rare to see melanomas of the lid present with nodal involvement. “Level” in Table 1–4 refers to the earlier Clark classification, while “thickness” is derived from the work of Breslow.132 In a large retrospective study by Volmer, he noted that in

12 TUMORS OF THE EYE AND OCULAR ADNEXA

Table 1–4. TRUNCATED REVISION OF THE 1997 JOINT COMMITTEE ON CANCER STAGING SYSTEM FOR MELANOMA

a vast majority of cases, thickness is a more important prognostic parameter than level.133 In cases where there appears to be a difference in the level and thickness criteria, the recommendation has been to use the finding with the worst prognostic significance to stage the tumor. In patients with lid tumors < 1 mm thick, it is probably not cost effective to do a metastatic work-up, unless they are symptomatic.133

TUMORS METASTATIC TO THE LIDS

Tumors metastatic to the lids are very rare. In a review of 1,502 lid biopsies, Foos and colleagues noted only one such lesion.134 Similarly, < 1 percent of 892 consecutive lid biopsies were metastatic in Aurora and Blodi’s series.3 Approximately 60 cases have been reported, some with both lid and orbital involvement. The vast majority have other known metastases at the time of presentation.135–143 As is the case for uveal metastases, lung and breast carcinomas account for approximately 80 percent of lesions that metastasize to the lid; however, rare malignancies, such as carcinoid and Merkel cell carcinomas, have also been reported.134,144,145

Figure 1–25. Cutaneous melanoma metastatic to lid.

Figure 1–26. Metastatic breast carcinoma diffusely involving the lower eye lid.

The clinical pattern of lid metastases is not pathognomonic. Usually, these lesions occur as a nodular or diffuse indurated area. The former presentation, as shown in Figure 1–25, is typical for a metastatic cutaneous melanoma, although occasional lid metastases can simulate a chalazion.120,136 Figure 1–26 shows metastasis of a diffuse breast carcinoma to the left lower eye lid, which responded completely to chemotherapy. In most cases, other evidence of metastasis are present at the time the lid lesion is diagnosed. As with uveal metastases, once the lid metastases are noted, survival is usually < 1 year.

KAPOSI’S SARCOMA

KS was first described in l872, although prior to l981, most of the cases of KS occurred in elderly Italian or Jewish males or African children.146,147 This vascular sarcoma had an indolent disease course and usually involved the extremities. KS, prior to the outbreak of acquired immunodeficiency disease syndrome (AIDS), was rarely noted to involve the periocular structures. Only 30 cases in the lids or conjunctiva were described prior to 1982.147–151 KS is now a less common manifestation of AIDS, since the use of multiple protease inhibitors. Lid KS or, more commonly, lid and conjunctival KS can develop in homosexual males known to have AIDS. Usually, these lesions are violaceous in color (Figure 1–27), and often, the conjunctival involvement is diffuse and can simulate inflammation (see Chapter 4, Figure 4–36).

Figure 1–27. Kaposi’s sarcoma in a patient with AIDS.

Unfortunately, while local control is easily achieved with low-dose radiation therapy, the systemic disease process has been rapidly fatal.102 As mentioned above, with the newer generation of drugs, KS is much less common, and it is uncertain if this statement regarding mortality is still relevant.

RARE LID MALIGNANCIES

There are a number of rare lid malignant tumors that are only diagnosed on histologic examination. As discussed above, these tumors, like other malignant lesions, show growth, inflammation, or other signs of invasive behavior; but none have a pathognomonic appearance.152–161 An adnexal malignancy is shown in Figure 1–28; as in a basal cell carcinoma, there is loss of lashes, but the author has not observed ulceration with these lesions.

Figure 1–28. Adnexal malignant tumor with loss of lashes.

Merkel cell carcinomas are derived from neuroendocrine cells that are present in the basal layer of the epidermis and outer root sheath of hair follicles, and function as mechanoreceptors. These neoplasms typically involve the upper lid and are usually violaceous and have overlying telangiectasia;120,162–165 rarely, these lesions can be multiple.166 They occur more commonly in females, and often express both cytokeratin-20 and neurofilament protein.167 They often have a typical pattern; in the one Merkel cell tumor that this author managed, the diagnosis was not made prior to biopsy.168,169 Some of the rarer lid malignancies are listed in Table 1–2.170 Several case reports document such rare lesions as mucinous eccrine carcinomas, signet ring carcinomas of the eccrine gland, syringomatous carcinomas, and procarcinoma, all simulating more common tumors.171–177

In contrast to most lymphoid lesions that more commonly involve either the conjunctiva or the orbit, mycosis fungoides, an uncommon T-cell lymphoma, has a predilection for the eyelids when it involves the ocular structures.164–179 More commonly, T-cell lymphomas, when they involve the eye, produce other findings. In a large Mayo Clinic series, a cicatricial ectropion was the most common finding in 17 of 42 (40 percent) patients.180

PEDIATRIC LID TUMORS

Infantile Hemangioma

Capillary hemangiomas that involve the lid, conjunctiva, orbit, or a combination of these sites, most commonly present either at birth or in the first few months of life and are the most frequent ophthalmic neoplasm of infancy. There has been recent investigation in the molecular pathogenesis of this entity, although it currently does not have clinical application.5

A number of different terms have been used to describe this tumor, including juvenile hemangioma, cellular hemangioma, and benign hemangioendothelioma. These lesions usually present as a swelling of the eyelid, often involving the contiguous conjunctiva and the orbit (Figure 1–29). The mass is easily compressible and often has a reddish tint, although it may be bluish when the child cries (Figures 1–29 and 1–30). Figure 1–31 shows a parasagittal T1-weighted

Figure 1–29. Capillary hemangioma involves the lid, conjunctiva, and anterior orbit.

magnetic resonance imaging (MRI) scan of such a lesion. In contradiction to nonvascular tumors, capillary hemangiomas are dark on T1 -weighted images and hyperintense to brain on T2-weighted images (Figures 1–32 and 1–33). On the T2-weighted image, this mass is hyperintense to brain. Ninety-five percent of capillary hemangiomas are evident before age 6 months, and occasionally, they are noted in the first week of life. Usually, the growth in the first year is rapid, and then slow regression occurs.181 An example is shown in Figures 1–34 and 1–35. Figure 1–34 is a child the day after birth; the same child 1 year later is shown in Figure 1–35. Involution is usually complete by 5 years. Initial clinical findings of involution are a central loss of the bright color of the mass.182 Most series have noted more females than males, often in a 3:1 ratio. Similarly, it appears that women who have undergone chorionic villus sampling have over a 10-fold increased chance of developing this problem.183

Figure 1–30. Typical color of lid hemangioma.

Figure 1–31. T1-weighted parasagittal MR image of a capillary hemangioma. On T2–weighted scans the lesion is hyperintense to brain.

The clinical course of these lesions is extremely variable. Often, they will show growth in the first 3 to 9 months of life, remain stationary, and then slowly resolve. Stigmar and colleagues noted that approximately 60 percent of cases resolved by age 4 years and 75 percent by age 7 years.184

Unfortunately, a number of major complications can occur; most commonly, these include strabismus,

Figure 1–32. T1-weighted axial MR images. The tumor is hypointense in respect to brain.

Figure 1–33. T2-weighted MR image. The capillary hemangioma is hyperintense with respect to brain.

anisometropic amblyopia, proptosis, and compression of the optic nerve. Haik and colleagues reviewed 101 cases of capillary hemangioma and found an 80 percent complication rate, with 60 percent of patients having amblyopia.185 In a study of 51 cases, Stigmar and associates noted that 27 developed amblyopia, and 17 had strabismus.123 Robb found that 46 percent of 37 patients had refractive errors, with both myopia and astigmatism.186 Amblyopia occurred most commonly when the eyelid occluded the pupil.

The author conservatively monitors most infants with capillary hemangiomas, unless a biopsy is needed to exclude the diagnosis of a possible malignant tumor or, more commonly, enlargement of the mass makes the development of amblyopia likely.

Figure 1–35. Patient shown in Figure 1-34 at age 1 year.

Generally, if the visual axis is not occluded, the author has opted for serial observation, since these children are at much less risk for developing amblyopia, although pressure of the tumor may alter the refractive status of the globe. If the mass grows and the visual axis is obstructed, then intervention is mandated.

There have been a number of therapeutic options, including injection of sclerosing agents, radiotherapy, systemic steroids, local steroid injection, diathermy, and surgical excision.187 Most clinicians have abandoned the use of radiation, diathermy, or sclerosing agents. Certainly, the use of radon seeds is no longer advisable, given the public health safety problems with that particular isotope. In some of the experimental models, therapy with angiogenesis inhibitors has shown some promise.188

Intralesional steroid injection has been used in a number of infantile hemangiomas. Fost and Esterly

first described this technique in nonophthalmic cases in 1968.189 Hiles and Plichard first described its use in the management of ophthalmic cases, and Kushner popularized this technique.190,191 Kushner described good resolution in most patients with intralesional steroids.191,192 In growing lesions or in those that occlude the peripapillary axis on initial examination, approximately 1.0 cc of 40 mg/mL of methylprednisolone sodium succinate (Solu-Medrol) is injected into multiple sites of the lesion. Usually, there is blanching of the vascular pattern with rapid regression of tumor size within 48 hours after injection. In lesions that respond, involution is quite rapid over the first 2 weeks but may continue over a 2-month period. Some lesions have not responded to steroid injection, and if no response occurs in the first 2 weeks, a sec-

Figure 1–38. Resections of capillary hemangioma after failure to respond to intralesional corticosteroids.

ond injection is given. The author has never seen a patient who has not responded to two injections respond to further steroids. Figures 1–36 and 1–37 demonstrate a patient with a growing capillary hemangioma of the lid prior to and 3 days after intralesional steroids. Two injections of intralesional steroids have

A

B

Figure 1–40. A, Clinical photograph of a large plexiform neurofibroma. B, T1-weighted axial MR scan of the NF-1 patient shown in 1–40A.

Figure 1–41. One day after excision of neurofibroma shown in Figure 1–40.

little systemic morbidity, but there have been isolated reports of other complications. Sutula and Glover noted eyelid necrosis after steroid injection in a young female.193 Other case reports have noted other corticosteroid complications, such as linear fat atrophy, pigmentation, subcutaneous atrophy, adrenal suppression, and occlusion of the central retinal artery.194–196 Neither Kushner nor this author have had these complications occur.192 Oral steroids (oral prednisone) are also used, generally in a dose of 3 to 5 mg/kg daily. Most investigators have noted about a 30 percent complete resolution rate, 30 percent stabilization, and 40 percent failure rate with this technique.197 Many pediatric ophthalmologists prefer this approach. This author has generally found intralesional injection more efficacious; however, the opposite response has been noted in a few cases. There have been a few reports of interferon use in this tumor; however, inter- feron-associated retinopathy has also been described; therefore, the relative safety and efficacy of that approach are uncertain.198,199

If these approaches are not effective, the author has debulked tumors that produce significant ocular morbidity (Figure 1–38). Care is taken to avoid damage to the levator and extraocular muscles, since these capillary hemangiomas are quite diffuse. In this author’s experience, surprisingly, there have not been problems with hemostasis, although in a couple of cases, the author used the CO2 laser to debulk a lesion, with hemostasis. Two series of 5 and 12 cases have used a similar approach, as we have, with good results.196,200 Rarely, a similar process can develop in an adult.200,201

Lid Neurofibromas

Plexiform neurofibromas are often observed on the lid of patients with neurofibromatosis. The systemic disease and newer molecular genetics are discussed under “Pediatric Orbital Tumors.” A typical lid neurofibroma is shown in Figure 1–39.167 Often, there is congenital localized hypertrichosis.202 The management of these lesions is difficult. Usually, in large tumors, only incomplete excision is possible, and over time, other eyelid and orbital neurofibromas become clinically detectable. Figures 1–40 and 1–41 show a patient with a large tumor prior to and 1 day after a partial excision.

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