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

Less common causes of flat choroidal pigmentation include multiple choroidal nevi, which occur as a normal variant, or proliferations of uveal melanocytes that are rarely observed as a form of a paraneoplastic syndrome in patients with widespread metastases.2,3 In the latter syndrome of bilateral diffuse melanocytic proliferations in association with carcinoma, most patients develop ocular symptoms prior to the detection of the primary neoplasms.2–5 Exudative detachments and cataracts develop rapidly in this paraneoplastic process.

Finally, as discussed under choroidal melanocytomas, diffuse, benign, flat choroidal pigmented lesions can occur. More extensive evaluation of presumptive nevi is indicated if any of the following is present:

1.Visual symptoms, such as decreased acuity or an absolute scotoma

2.An elevated lesion (Figure 6–6), or one with a diameter > 6 mm

3.Overlying orange pigmentation (Figure 6–7)

Figure 6–7. Orange pigmentation over a nevus, which has been monitored for over 10 years, with a change.

4. Overlying subretinal fluid. (Figure 6–8)

Orange pigmentation, visible because of the contrast between lipofuscin and melanin, is most commonly observed over melanomas.6 Nevi with orange pigment are more likely to progress to melanomas; however, the patient with the lesion in Figure 6–7 has been followed up for over 20 years without change. As previously mentioned, it is almost impossible to differentiate atypical nevi from small

melanomas of this size. The majority of small pigmented tumors that sometimes progress into small uveal melanomas (< 3 mm thick and < 10 mm in diameter), are initially asymptomatic, do not have subretinal fluid, and can be safely watched until growth is documented (see Chapter 7).7 Fluorescein angiography is usually not useful in differentiating small melanomas from nevi; in a study we performed several years ago, the overall accuracy of fluorescein angiography in all sizes of uveal melanoma was approximately 50 percent.8,9

Fluorescein angiography may be helpful in diagnosing a few conditions including choroidal hemangiomas and subretinal hemorrhages, disciform degenerations, and arterial macroaneurysms.9 Figure 6–9 shows an arterial macroaneurysm with secondary hemorrhage, a condition that clinically simulates a small uveal melanoma. The corresponding fluorescein angiogram nicely delineates the correct diagnosis with closure of the vessel, hemorrhage obscuring underlying detail, and exudate (Figure 6–10).

Indocyanine green angiography data have been reported in various tumors. The author has not been impressed that it has been a useful diagnostic adjuvant.10,11 As discussed under uveal melanoma prognosis, it is possible that confocal indocyanine green laser scanning ophthalmoscopy may be useful, if it can reliably demonstrate the uveal melanoma microvascular

Figure 6–8. A nevus with secondary exudative detachment. On quantitative echography, the lesion measured < 1.5 mm thick.

Figure 6–9. An arterial macroaneurysm clinically simulating a uveal melanoma, with what appears to be overlying orange pigment. Closer examination shows subretinal hemorrhage around the base of the lesion and an occluded arteriole distal to the macroaneurysm.

102 TUMORS OF THE EYE AND OCULAR ADNEXA

Figure 6–10. Fluorescein angiogram of an arterial macroaneurysm with hemorrhage obscuring underlying detail.

patterns.12,13 At present the use of optical coherence tomography is of limited value in choroidal tumor diagnosis.14

The accuracy of ultrasonography in the differentiation of atypical uveal nevi from melanoma is unclear. I have not been willing to diagnose a melanoma on the basis of ultrasonographic criteria alone unless it is > 3 mm in thickness. We have serially examined some of these indeterminate pigmented lesions, that have many A- and B-scan melanoma characteristics (see section on choroidal

melanoma), for as long as 20 years without evidence of growth. Figure 6–11 demonstrates the ultrasonographic pattern of an indeterminate pigmented uveal mass (see Figure 6–7). On B-scan, there is some choroidal excavation (Figure 6–11A). The absence of orbital shadowing and an acoustic quiet zone (findings characteristic of larger uveal melanomas) probably does not represent a significant difference in internal architecture from larger melanomas but, rather, reflects the fact that the mass is too thin for these ultrasound features to have developed. Similarly, the A-scan pattern is not classic for a melanoma; the area of low-medium reflectivity is minimal, and the lesion often has medium to high reflectivity (Figure 6–11B). We recently examined a patient we had diagnosed as a nonpigmented nevoma (indeterminant pigmented lesion) approximately 10 years ago. The patient had 20/20 vision and no symptoms until recently. The correct nature of the enlarged lesion could now be ascertained both clinically and on ultrasonography. It was an obvious hemangioma; however, neither the initial clinical ultrasound pattern nor the fluorescein angiogram was diagnostic when it was 2.0 mm thick.

There have been a few modifications in the ultrasound technique that may be helpful in monitoring in unusual settings. Several investigators have attempted to use new ultrasound contrast agents to differentiate

lesions of varying vascular nature. While not helpful diagnostically, three-dimentional ultrasonography may be useful for the post-treatment serial evaluation of tumors.15,16

Positron emission tomography (PET) scanning can be used to visualize some larger uveal melanomas.17 Our experience, and that of most investigators, has been that choroidal tumors < 7 mm in diameter and 5 mm thick are poorly evaluated with this technique, and yet that is the size in which many diagnostic difficulties occur (unpublished observations). Use of magnetic resonance imaging (MRI) is discussed in Chapter 7. It is an expensive technique, and does not appear to increase intraocular diagnostic accuracy; MRI is mainly used to detect localized extrascleral extension of a uveal melanoma.18–20

In indeterminate pigmented choroidal lesions, there are a few signs that suggest a melanoma. Obviously, growth, while not an absolute criterion of a small melanoma, is such a finding. Other factors suggesting malignancy are visual symptoms, orange pigmentation, and subretinal fluid. As discussed under management, we do not treat most patients with asymptomatic, indeterminate pigmented lesions, since no diagnostic modality accurately differentiates these nevomas into nevi and melanomas, and we have observed no tumor related-mortality in lesions that have not grown. As discussed in Chapter 8, we have been able to accurately delineate those nevomas at very high risk for growth; we intervene especially in those cases with tumors distant from the nerve and fovea.

RETINAL PIGMENT EPITHELIAL LESIONS

RPE lesions can occasionally be confused with melanomas. Most RPE proliferations are almost always flat. Congenital RPE hypertrophies often have a halo, scalloped margins, and lacunae and usually have areas that are much more darkly pigmented than either melanomas or nevi (Figures 6–12 and 6–13). Occasionally, as patients age, these lesions may become entirely amelanotic. The RPE hypertrophy lesions that are associated with Gardner’s syndrome (familial polyposis) are much smaller in area than lesions that could be confused with an uveal melanoma.24 The pattern of these

Figure 6–12. Retinal pigment hypertrophy with characteristic scalloped margins and lacunae.

small RPE proliferations generally at the posterior pole is helpful, especially to identify family members at risk for Gardner’s syndrome.25,26

RPE hyperplasia is a reactive process that occurs as a result of infection, trauma, or uveitis; these lesions are typified by flat, black pigmentation with ragged margins (Figure 6–14).27 Occasionally, these lesions can have an atypical appearance.28

Occasionally, RPE proliferations can be very difficult to diagnose correctly. In the case of lesions in the periphery, it is often difficult to determine tumor

Figure 6–13. Grouped pigmentation, a forme fruste of RPE hypertrophy.

104 TUMORS OF THE EYE AND OCULAR ADNEXA

Figure 6–14. Retinal pigment epithelial hyperplasia with typically ragged margins. The nature of the margins and absence of lacunae help differentiate this acquired lesion from congenital RPE hypertrophy.

thickness. The patient shown in Figure 6–15 was referred for a melanoma because the flat nature of this RPE hypertrophy was not appreciated. In one case, even with a fine-needle aspiration biopsy (FNAB), the diagnosis was not established until after enucleation.29

Shields and colleagues, on the basis of some cases in which histologic data became available, have noted a typical feature of a prominant feeder vessel in elevated RPE adenomas. Figures 6–16 and 6–17 demonstrate such cases that we have followed up for many years, with lesions that almost look like small, black, mini-collar buttons with a feeder vessel.30–32 These tumors are, presumably, RPE adenomas.

Adenocarcinomas of the RPE have been described, although they are quite rare and, fortunately, do not metastasize. An ultrasound may have a pattern different from a uveal melanoma.32,33

CHOROIDAL METASTASES

Differentiation of a uveal metastasis from a primary uveal melanoma can be difficult. Approximately 6 to 10 percent of patients with documented uveal melanomas have had another systemic malignancy treated previously.34,35 We have not found an excess of systemic malignancies in uveal melanoma patients.36 The finding of a past history of systemic malignancy on review of systems in a patient with a uveal tumor can present problems. We have managed several patients with uveal melanoma who were initially treated elsewhere with insufficient radiation because of their past medical history and an incorrect diagnosis of a presumed metastatic choroidal mass prior to

Figure 6–17. Another RPE adenoma similar to one shown in Figure 6–16.

their referral. In one patient with a history of localized breast carcinoma, 50 gray (Gy) of photon radiation plus combination chemotherapy was given for a choroidal nevus (Figure 6–18). Conversely, some patients have been treated for uveal melanomas but who have had obvious metastatic choroidal tumors.

Metastatic deposits in the uveal tract may be the first sign of a systemic malignancy in as many as 50 percent of patients.37 The most common primary tumors that secondarily involve the choroid are breast, lung, kidney, gastrointestinal tract, and genitourinary tumors. In over 80 percent of patients with lung and renal tumor metastases, the eye lesion is the first manifestation of malignancy. In contrast, over 90 percent

of patients with breast metastases to the uvea have a history of primary tumor treatment. In different series, the incidence of primary sites has varied.38

Metastatic choroidal tumors are amelanotic, usually involve the posterior pole, especially the macula, and are associated with subretinal fluid. In approximately one-fourth of cases, metastases to the uveal tract are bilateral and/or multifocal (Figure 6–19). Metastatic deposits are much less frequent in the optic nerve, retina, iris, ciliary body, or vitreous.39,40 In a recent report from Philadelphia, the iris was involved in 9 percent, the ciliary body in 2 percent, and the choroid in 88 percent of uveal metastases.41

The mushroom shape or collar-button configuration associated with a uveal melanoma is almost never associated with a metastatic choroidal tumor. In one such case with a mini-collar button, the patient was diagnosed elsewhere with a presumed choroidal metastasis on the basis of a known primary. This patient was referred to the author after she failed to respond to 40 Gy of photon radiation. Cytology confirmed that the correct diagnosis was a uveal melanoma. There is no intrinsic tumor pigmentation in uveal metastases; however, overlying RPE alteration may produce hyperplastic RPE pigmentation. The clinical pattern of different histologic types of metastatic tumors is not diagnostic. Breast carcinomas metastatic to the uveal tract often have a peau d’orange pattern of pigmentary alteration (Figure 6–20). Metastatic foci can be quite large, as the tumor shown in Figure 6–21 demonstrates.

(CEA) level is elevated above 10 ng/mL in approximately 50 percent of these cases versus almost no uveal melanoma patients.45

In some cases, the clinical and ultrasonographic pattern in metastatic uveal tumors is not clear cut (Figures 6–22A to C).46,47 As described below, FNAB has been a very important adjunct in cases with atypical choroidal metastases.39,48–52

The reason for the relative incidence of choroidal metastases as compared with other ocular sites is uncertain. The choroid has, perhaps, the highest blood flow of any body site.53 In approximately, 3 to 4 percent of metastatic carcinoma patients, a primary malignancy is not identifiable; in referral centers, this incidence is approximately 10 percent.54

Rarely, metastases to the choroid can occur many years after the primary tumor has been treated or removed.55 This can be especially true with carcinoid tumors and renal cell carcinoma, and in one case, ocular metastases were discovered 9 years after resection of the primary lesion.56 The pattern of metastases

is partially predicated on the vascular endothelial differences as well as surface antigens of the tumors.57 The treatment of metastatic choroidal tumors is discussed in Chapter 8. Depending on the systemic status of the patient, this can include chemotherapy, conventional teletherapy, laser, or brachytherapy.

CHOROIDAL HEMANGIOMA

Choroidal hemangiomas may occur as solitary, focal lesions or as a diffuse process, often in association with Sturge-Weber syndrome.58–60 The focal lesions have a typical clinical pattern; they are moderately elevated (2 to 5 mm) pinkish-orange lesions, often with overlying subretinal fluid (Figure 6–23). The fluorescein angiographic pattern is believed by some to be diagnostic; however, we have seen two patients with typical patterns, in whom we histologically confirmed the diagnosis of a melanoma.59,60 On fluorescein angiography, the lesion is usually characterized by early lobular filling of the choroidal ves-

Figure 6–23. Solitary choroidal hemangiomas.

sels in the area of the tumor prior to filling of the retinal vessels (Figures 6–24A and B). The ultrasonographic pattern is diagnostic. The B-scan appearance is similar in some respects to a metastasis; a choroidal hemangioma appears solid without choroidal excavation, acoustic quiet zone, or orbital shadowing (Figure 6–25A). On A-scan, the lesion has uniform high reflectivity (Figure 6–25B).

These tumors have rarely been demonstrated to grow. In one report, Medlock and colleagues noted 5 patients who showed an enlargement, with a mean interval of 52 months.61 We have recently examined

A

B

Figure 6–24. A, Clinical photograph of a choroidal hemangioma with a typical orangish-pink coloration. B, Early lobular fluorescence prior to the filling of retinal vessels, typical for a choroidal hemangioma. (Fluorescein angiogram of Figure 6–24A: early lobular fluorescence).

markedly asymmetric disease, or if the lesion occurs outside the anatomic macula (Figures 6–28 and 6–29). It is important to evaluate the contralateral macula in any patient suspected of harboring a foveal uveal melanoma, since the finding of macular degeneration in the contralateral eye helps to determine the true nature of the lesion (Figures 6–30A and B).

Hemorrhage, as seen in Figures 6–28 and 6–29, would be very unusual in a uveal melanoma this thin; melanomas generally only produce a vitreous hemorrhage when an overlying retinal vessel is torn as the tumor breaks through Bruch’s membrane. Lipid exudation is also common in a disciform process but relatively rare in an untreated melanoma. The ultra-