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

200 TUMORS OF THE EYE AND OCULAR ADNEXA

Figure 9–2. Anterior iris stromal cysts with destruction of the iris surface.

25 reported cases.19 In one report, 8 of 9 children had obstruction of the visual axis, and 7 required multiple treatments.20 Overall, that group noted that only 3 percent of primary cysts of the iris epithelium were in a central location.21 While some clinicians have tried trichloroacetic acid, complete surgical removal is the treatment of choice.17,19,22,23 Rarely, there can be spontaneous collapse of a primary stromal cyst.24

Iris Nevi

Typical iris nevi are flat lesions that usually do not involve either the pupil or trabecular meshwork; these tumors are < 4 mm in diameter and generally

Figure 9–3. Posterior iris pigmentary cyst involving the pupil.

do not produce glaucoma (Figure 9–5). Occasionally, a large, flat nevoid proliferation can involve substantially greater iris area, and some of these require biopsy. Among dark-skinned patients, a presumably autosomal-dominant pattern of bilateral diffuse nodular nevi has been described in 30 patients.25 A benign, histologically confirmed,

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Figures 9–4. A to C, Three cases of posterior pigment iris cysts shown on high-frequency ultrasonography.

growing iris lesion is shown in Figure 9–6. Unfortunately, 5 years later, the tumor grew further and subsequent sections revealed an area of malignant transformation. In children, a nevoid process, sector melanosis of the iris (Figure 9–7), can occur. We have never observed malignant degeneration in that group of patients. There have been 16 reported cases of familial intraocular melanoma.26 In one pedigree, two generations of patients with aggressive iris nevi (with apparent extention onto the limbus in one case) were reported.26 Similarly, melanocytoma, a magnocellular nevus, can also involve the iris or ciliary body. Usually, they are darkly pigmented, but often, they can present an identical clinical and imaging pattern of a melanoma (Figure 9–8 and 9–9).27–32 Rarely, these can undergo malignant degeneration.

Much less often, a leiomyoepithelioma or adenoma of the iris pigmented epithelium can present as a jet black mass.23 Unfortunately, our experience has shown that we are unable, even with high-frequency ultrasonography, to differentiate a very small histologically documented iris melanoma from an atypical iris nevus (unpublished observations).

Anterior Uveal Melanoma

(Ciliary Body and Iris)

Iris and ciliary body melanomas together account for approximately 20 percent of uveal melanomas. Iris color is a risk factor for the development of iris melanocytic lesions. Two studies have demonstrated a statistically significant association between light-

Figure 9–9. Ciliary body melanocytoma that grew and was excised.

colored irides and the development of both melanomas and nevi of the iris.33 The ratio of iris to ciliary body and choroidal melanomas is estimated to be between 1:6 and 1:20.34 There have been approximately 10 cases of uveal melanoma in association with neurofibramatosis type-1 (NF1). In one recent report, the patient had involvement of the iris and cornea by a melanoma.35 The peak incidence of iris melanomas occurs in patients 10 to 20 years younger than patients with choroidal melanomas. Iris tumors are often detected either as an incidental finding or because of cosmetic change. Patients may have decreased vision due to a sector lens opacity (Figure 9–10) or as a result of astigmatism induced by an irisciliary body melanoma pressing against the lens.36

Iris melanomas often have prominent intrinsic vessels (Figure 9–11), ectropion iridis (Figure 9–12),

Figure 9–11. Prominent intrinsic vessels in an iris melanoma.

secondary cataract, variable pigmentation, and, occasionally, increased intraocular pressure. Sentinel vessels can occur with both iris and ciliary body melanomas (Figure 9–13). Most commonly, melanomas involve the inferior iris.

A diffuse or ring melanoma is a variant of iris melanoma that is extremely difficult to diagnose and manage; it can present as a subtle 360° ring of tumor or can have a focal lesion with a subclinical tumor involving the rest of the angle circumference (Figure 9–14).37 Usually, the first type of ring melanoma is initially misdiagnosed as a glaucoma of uncertain etiology. Rarely, other tumors, such as lymphomas, can simulate this problem.38

Tapioca melanoma is another variant of iris melanoma (Figure 9–15).39 This tumor is usually a large, irregular, multinodular, lightly pigmented lesion.

The histologic classification of iris melanoma is in flux. Jakobiec reviewed 189 “iris melanoma”

diagnoses and reclassified 87 percent as nevi.40 Histologically confirmed iris nevi can grow, involve the angle, and produce ectropion iridis. The clinical overlap between benign and malignant iris tumors makes diagnosis sometimes difficult.

All patients with pigmented iris lesions are examined with slit-lamp biomicroscopy and bilateral evaluation with a three-mirror contact lens; fundus examination with 360° scleral depression is also used to ascertain whether the ciliary body or anterior choroid is involved. The presence or absence and the degree of angle-ciliary body involvement (optimally assessed with high-frequency ultrasonography) are noted; it is important to determine angle pigmentation contiguous to and away from the tumor in the involved eye and

whether it is or is not present in the contralateral eye. Neither radioactive phosphorus tests nor standard ultrasonography is useful in the evaluation of iris tumors that do not involve the ciliary body. In the past immersion B-scans of iris-ciliary body melanomas did not accurately delineate the ciliary body involvement by the tumor. Fortunately, the development of high frequency ultrasonography has allowed us to demonstrate iris tumors with involvement of the ciliary body quite well (Figure 9–16). These ultrasound probes with 20 to 100 MHz transducers have approximately 10-fold better resolution in the anterior segment than standard echography; however, the diagnostic accuracy of this newer technique and its utility in the management of iris tumors is still uncertain.41

Figure 9–14. Presumed focal melanoma that histologically had 360° angle involvement (ring melanoma).

Figure 9–16. High-frequency ultrasonography of an iris-ciliary body melanoma with mass against the posterior cornea. This type of ultrasonography does not demonstrate posterior involvement as well as the standard scan can.

204 TUMORS OF THE EYE AND OCULAR ADNEXA

The two signs that are most reliable in the diagnosis of iris melanoma are demonstrable tumor growth, and the presence of an intensely vascular tumor (see Figure 9–11). Figure 9–17 demonstrates a very small melanoma that had documented growth; histologically, it was the mixed-cell type. Ring melanomas are the most difficult to diagnose, if no focal tumor is present.

Anterior segment fluorescein angiography has been advocated by some investigators.42–45 While obvious iris melanomas often have diffuse confluent fluorescence from ill-defined vascular foci, in indeterminate lesions, angiography has not been helpful. Figure 9–18 shows a fluorescein angiogram of a histologically confirmed iris melanoma with typical leakage. In a series of 26 iris-ciliary body melanomas that underwent iridocyclectomy, we could not differentiate the two benign melanocytic proliferations from the malignant melanomas on the basis of fluorescein angiographic criteria.45 We were also unable to distinguish spindle cell from either mixed cell or epithelioid melanomas on fluorescein angiographic criteria.45

As discussed under management, fine-needle aspiration biopsy (FNAB) can be quite useful in two settings. We have most often used this technique on patients with an apparently focal pigmented tumor and increased intraocular pressure. An FNAB positive for melanoma that is performed 180° away from the main mass is diagnostic for ring melanoma. Rarely, in cases that are suspected of being nonmelanoma malignancies of the iris, this diagnostic assay is also useful.46

Figure 9–18. Diffuse leakage on fluorescein angiogram of a histologically confirmed iris melanoma.

Other Iris Lesions

Patients with either Cogan-Reese syndrome or the essential iris atrophy spectrum of iridocorneal endothelial syndrome are often referred for evaluation of a suspected iris melanoma.5 Almost all these patients have peripheral anterior synechiae and corneal endothelial changes, and some have glaucoma; the first two features are not common in melanoma. Patients with essential iris atrophy have a distorted pupil and enlarging areas of iris atrophy; a typical example of this entity is shown in Figure 9–19. The syndrome is more common in females. Probably, there is a viral etiology for these diseases.47 Cogan-Reese syndrome often has some associated iris atrophy and areas of iris nodules; usually, these nodules are multiple, as shown in Figure 9–20.

Tumors metastatic to the iris, unlike those which involve the choroid, often are detected after the pri-

mary tumor has been discovered. Almost all are amelanotic, and many diffusely involve the iris (Figure 9–21). They are much less frequent than posterior uveal metastases; approximately 10 percent of ocular metastases involve the iris.48 The most common sites of primary carcinomas are the breast, lung, kidney, and gastrointestinal tract.49 Less commonly, cutaneous melanoma, thyroid carcinoma, and lymphomas can present in this part of the eye as the initial manifestation of the neoplasm.38,50–53 Neonatal hepatoblastoma, endometrial carcinoma, Ewing’s sarcoma, and renal cell carcinoma have also been described.36,54–56 As discussed in Chapter 5, many patients with endodermally derived malignancies will have elevated levels (> 10 ng/mL) of plasma carcinoembryonic antigen (CEA); patients with uveal melanomas consistently have lower values.57 Some of these metastases are solitary as shown in Figures 9–22, 9–23, and 9–24.

Lymphomas or leukemias may produce iris infiltration; this may be the first sign of disease reactivation although it almost never is the first presentation of the malignancy.2,38,58 In anterior segment lymphoma, a malignant hypopyon is usually present (Figure 9–25). Rarely, other malignancies can produce a pseudohypyon (see Chapter 10).59 A metastatic cutaneous melanoma may present as a black hypopyon without an obvious mass (Figure 9–26).53 A presumed breast metastasis presented with bilateral pseudohypopyons (Figure 9–27).

Iris nodules can also occur either with neurofibromatosis or sarcoidosis (Figure 9–28); neither is likely to be confused with a melanoma.59 Rarely, other diseases, including Cushing’s disease, can have Lisch nodules.60 Other clinical systemic and ocular findings associated with both these conditions allow easy differentiation from a malignant melanoma.

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Figures 9–24. A, Solitary metastatic cutaneous melanoma in a patient with widespread metastases. B, Progression of the iris lesion (that mirrored systemic tumor growth.)

Juvenile xanthogranuloma (JXG) is usually a childhood tumor, occurring rarely in adults.10–12,61 The lesions are most commonly gray or yellow and have associated heterochromia, hyphema, and glaucoma. While typical skin changes are helpful to establish this diagnosis, they are found in only about

Figure 9–26. Cutaneous melanoma metastatic to the anterior segment, presenting as a black hypopyon.

one-third of patients with eye lesions.14,62 Intraocular tumor growth is usually quite rapid. These tumors respond rapidly to either corticosteroids or to as little as 2 Gray (Gy) of photon radiation, although most clinicians have used a slightly higher dose.

A number of less common primary iris tumors have been reported. Often, establishing the correct diagnosis, even with conventional light microscopy, has been difficult. Two recent reports emphasize this problem. Kluppel and colleagues reported a 2-month-old girl with a highly vascular 2-clock-hour tumor which was a lacrimal gland choristoma.63 At the other end of the age spectrum, Spraul reported an 81-year-old with an adeno-carcinoma of the iris epithelium.64 An especially perplexing group of

reported lesions have been iris leiomyomas and leiomyosarcomas. Foss and co-workers showed that 24 cases that had been classified as iris tumors of muscle origin were all melanocytic neoplasms, when studied with appropriate stains and antibodies.65 Other rare tumors that have been reported to involve the iris include lacrimal choristomas and primary rhabdomyosarcoma.66,67

We have very rarely observed some pigmented tumors that enlarged on serial examinations and were shown to be benign when examined after iridocyclectomy. These tumefactions include atypical melanocytic proliferations, adenomas of the ciliary epithelium, and melanocytoma. In an enlarging irisciliary body pigment adenoma, we suspected the correct diagnosis on FNAB (Figure 9–29) but performed an iridocyclectomy to be certain. The cytopathology demonstrated benign pigmented cells and large pigment granules. We have also seen a case (see Figure 9–6) in which a substantial iridectomy (approximately 25% of the total iris) showed only benign cells, yet 5 years later, when the eye was blind and painful from medically intractable glaucoma, the enucleated specimen demonstrated melanoma.

MANAGEMENT OF IRIS LESIONS

Iris Melanoma

Iris melanoma management options include observation, iridectomy, iridocyclectomy, and enucleation. The tumor-related mortality associated with iris melanomas has been reported to be extremely small.6,68 Metastases occur predominantly in three clinical situations: (1) when a partial resection was inadvertently performed, usually during a glau- coma-filtering procedure because the cause of glaucoma was not recognized; (2) when the iris is involved as part of a diffuse uveal melanoma (Figure 9–30) (see Chapter 5); and (3) in tumors with a significant ciliary body component and some iris invasion (Figure 9–31). Less commonly, some investigators have reported a few iris melanomas which have metastasized but do not fit into the above groups. A review of the world’s literature found that only 31 of 1,043 (3%) reported iris melanomas developed metastases.6

Figure 9–28. Sarcoid granuloma in the angle. The patient had other stigmata of sarcoid, including uveitis, and both a positive gallium scan and an elevated serum ACE.

Shields and colleagues have pointed out that the low death rate which has been reported in retrospective analyses of histologic studies of iris melanomas could be an artifact. Many of the cases that Geisse and Robertson, as well as others, have included in their reports probably would have been reclassified as benign pigmented tumors.6,40 It is therefore likely that there is a higher metastatic rate with larger tumors, especially those with more malignant cell types or those that recur. In one series, Sunba had noted approximately a 10 percent incidence of metastatic disease associated with iris melanomas.69

All elevated iris pigmented tumors are sequentially observed, unless the lesion is highly vascular or glaucoma is present. Figure 9–32 shows an indeterminate pigmented iris tumor followed up for over 10 years, without change. Most possible iris melanomas with normal intraocular pressure are followed up until growth is documented. Figure 9–33 shows a very large iris melanoma in a one-eyed patient who retained 20/30 vision in the affected eye; there had been no growth over a 10-year interval.

In patients with highly vascular lesions that are most consistent with iris melanoma, intervention is indicated. The clinical patterns of iris tumors shown in Figure 9–11 have almost always been associated with melanoma on histologic evaluation, and it has been our clinical impression that the tumor type is

more likely to have a more malignant (mixed or epithelioid) cytologic pattern. If the lesion can be adequately excised, a conventional iridectomy is performed. If the angle is involved, an iridocyclectomy is done (see “management of ciliary body melanoma”). Iridectomy is performed through a limbus-based incision. The pupil may be spared if it is not involved. It is crucial to lay the tumor specimen on a piece of sterile filter paper and orient it properly. If the material is just haphazardly placed into a specimen jar, it is virtually impossible to retrospectively ascertain either the margins or the orientation of the specimen.

If glaucoma is present, it is important to determine the cause of the increased intraocular pressure. It may be due to coincident primary glaucoma, malignant cells invading the filtration angle, an iris melanoma with neovascular glaucoma, or tumor pigment (alone or in macrophages) clogging the trabecular mesh- work.70–72 Often, it is impossible to precisely determine the etiology of increased intraocular pressure in a given patient. Clinically undetectable tumor can invade the trabecular meshwork. An FNAB may be useful in such situations (see “invasive diagnostic modalities” in Chapters 8 and 15). The eye in Figure 9–34 had a pressure of 50 mm Hg on maximum

Figure 9–30. Iris melanoma as a component of a diffuse uveal melanoma with extraocular extension.

Figure 9–31. Higher mortality is noted in iris-ciliary body melanomas than with pure iris lesions. Tumor-related mortality is further increased with localized extrascleral extension.

Figure 9–32. Presumed iris melanoma monitored photographically, without change from 1965 to 1986.

medical therapy. There was a focal iris tumor and 360° of angle pigmentation. An FNAB of the angle 180° away from the tumor was used to determine whether pigment-bearing macrophages or tumor cells were present. Only pigmented macrophages were present, and the tumor was removed with an iridocyclectomy. If tumor cells had been noted in the angle 180° from the main mass, enucleation would have been indicated, since a ring melanoma cannot be surgically removed with retention of the eye.73 A second indication for FNAB in iris tumors is to evaluate a large, growing atypical lesion. In some of these lesions, biopsy has demonstrated malignant cells and thus mandated therapy. Figure 9–35A illustrates an unusual ring iris-ciliary body melanoma; a transcorneal 25-gauge FNAB documented the melanoma (Figure 9–35B). A similar finding was noted in this young woman who had a filtering operation, with no mass noted by the referring doctor

Figure 9–33. Large iris melanoma with corneal touch in a oneeyed patient showing no growth over a 10-year interval, with visual acuity remaining 20/25.

Figure 9–34. Pigmented iris lesion with 4+ anterior segment cells and an intraocular pressure of 50 mm Hg on maximum medical therapy.

and continued increased intraocular pressure (Figure 9–36). FNAB demonstrated the ring melanoma.

Glaucoma management in eyes with possible iris melanomas or atypical iris nevi is difficult. Since tumor-related deaths with iris melanoma can occur after filtering operations inadvertently transect the lesion, we are unwilling to filter these patients. We have only treated the glaucoma medically. If maximum medical therapy does not control the pressure, we allow the glaucoma to progress.74

We have not used radiation to treat isolated iris melanomas. Irradiation of the entire anterior segment with either conventional photons or charged particles in sufficient dosage to control the melanoma often destroys the eye. In 14 patients, with very short followup, Shields and colleagues have used brachytherapy in tumors that involved < 7 clock hours. Longer fol- low-up is necessary to determine the efficacy and complications with this approach.75

Lesions < 5 clock hours (150° of angle) can be surgically excised. Figure 9–37 shows a patient 5 years after resection of a growing iris melanoma with a large iridectomy; the patient has retained 20/20 vision. There are now five different contact lens companies that make cosmetic lenses to camouflage a sector defect. The role of Lasik or other procedures to correct astigmia as a result of an iridectomy or more commonly after an iridocyclectomy is unclear.