Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

4.Histologically, CHRPE consists of hypertrophy of RPE cells, and an increase in size (macromelanosomes) and number of their melanin granules.

Although RPE hypertrophy (increase in size of cells) is the predominant component, RPE hyperplasia (increase in number of cells) is also present in many lesions.

a.The surrounding halo is due to atrophy or loss of pigment from the adjacent RPE, or both.

b.Degeneration of the overlying neural retinal photoreceptor cells may be found.

The histology of CHRPE is almost identical to that of grouped pigmentation (bear tracks—see p. 396 in Chapter 11). Both can be considered variants of the same process. The former is a larger focal lesion, and the latter are smaller multifocal lesions.

5.Congenital hypertrophy of the RPE can give rise to adenocarcinoma.

Acquired Neoplasms

I. Fuchs’ adenoma (proliferation rather than neoplasm; see

Fig. 9.17)

II.Adenoma (epithelioma; Fig. 17.21)

A.Adenomas may arise from the ciliary epithelium or RPE.

B.Clinically, they tend to be darker and their margins more abruptly elevated than in ciliary body melanomas.

Adenoma of the ciliary body nonpigmented epithelium has been reported with concomitant neovascularization of the optic disc (NVD) and cystoid macular edema (CME). It was postulated that elevated vascular endothelial growth factors in intraocular fluids, which were determined in both aqueous and vitreous obtained at surgery, may have played a role the development of NVD and CME.

C.Benign adenoma of the ciliary body pigment epithelium may exhibit progressive growth and undergo

malignant change. These lesions may invade the ante- rior-chamber angle or cause pigment dispersion. Cataract, vitreous hemorrhage, and neovascular glaucoma have also been reported in association with these lesions.

D.Histologically, the epithelial cells appear polyhedral and have variable pigmentation.

1.They may show a tubular (papillary) pattern, a vacuolated (solid) pattern, or a mixture of both; the tumors may become cystic.

2.The heavily pigmented cells are frequently vacuolated.

The vacuoles contain a sialomucin that can be digested with neuraminidase (sialidase).

3.Nuclear atypia is common, but mitotic figures are rare.

4.Immunohistochemically, they show positivity for vimentin, S-100 protein, and low-molecular-weight cytokeratins. They are negative for vimentin.

5.In contrast to tumorlike hyperplastic lesions of the RPE, the RPE adenoma is sporadic melan-A-positive.

6.Histologically, adenoma may be di cult to di erentiate from reactive proliferations of the PE.

a.The cells of the adenoma are variably pigmented and are packed together tightly with little or no stroma, whereas the individual cells in pseudoadenomatous hyperplasia tend to be separated by an amorphous basement membrane-like material, and show little atypia and no mitotic

figures.

7.Transmission electron microscopy reveals tight junctions between cells.

III.Adenocarcinoma

A.Like adenomas, pleomorphic adenocarcinomas may have a vacuolated (solid) or tubular (papillary) pattern, or a mixture of both.

B.When the PE becomes malignant, it forms an incidentally pigmented adenocarcinoma, not a malignant melanoma.

Clinically, the tumors are locally invasive, but it is questionable whether they have the biologic ability to metastasize or even to undergo extrascleral extension.

C.Adenocarcinoma is a histologic diagnosis based on cellular atypia.

1.In addition to hyaluronic acid secretion, immunohistochemical staining shows strong positivity for vimentin, focal positivity for epithelial basement membrane antigen and S-100 protein, and weak positivity for neuron-specific enolase.

2.Adenocarcinoma of the nonpigmented ciliary epithelium has been reported to be immunohistochemically positive for AE1 and epithelial membrane antigen.

An imbalance of chromosome 6 has been found by comparative genomic hybridization in a patient with pleomorphic adenocarcinoma of the ciliary epithelium.

IV. Leiomyoepithelioma of iris PE

V.Melanotic neuroectodermal (retinal anlage) tumor of infancy

MELANOTIC TUMORS OF THE UVEA

Iris

I.Ephelis (freckle; Fig. 17.22)

A.A freckle shows increased pigmentation of anterior border layer melanocytes without increased number of melanocytes.

B.There is no discrete mass or nodule.

II.Nevus (see Fig. 17.22)

A.A nevus shows an increased number of atypical, benignappearing melanocytes (i.e., nevus cells) with variable pigmentation.

B.A discrete mass or nodule is present, often on the iris anterior surface (i.e., within the anterior border layer of the iris).

C.An increased incidence of iris nevi occurs in people who have neurofibromatosis (see Fig. 2.4), but probably not in those who have ciliary body or choroidal malignant melanomas.

D.A di use (or rarely segmental) nevus of the iris (and the rest of the uvea) is present in congenital ocular or oculodermal melanocytosis.

Rarely, a diffuse nevus of the iris can cause glaucoma by direct involvement of the drainage area, or by synechiae and secondary closed-angle glaucoma.

E.An acquired, di use nevus of the iris may be associated with the iris nevus syndrome, part of the iridocorneal endothelial (ICE) syndrome (see p. 639 in Chapter 16).

Melanocytoma (magnocellular nevus; see p. 721 in this chapter) of the iris may occur. Necrosis of a melanocytoma may mislead the clinician to a diagnosis of malignant melanoma. Another unusual type of iris nevus is called the benign epithelioid cell nevus. A rare case of probable autosomal-dominant, “aggressive” iris nevus in childhood has been reported.

F.Malignant change is rare.

III. Heterochromia (Table 17.2)

IV. Malignant melanoma (Figs 17.23 and 17.24; see also Fig. 16.18)

A.Iris malignant melanomas have no sex predilection; the average age of involvement is 47 years.

B.They are the most common primary neoplasm of the iris and constitute approximately 5% to 8% of all uveal melanomas.

1.They usually arise from the anterior border layer tissue of the iris (as do iris nevi).

A

C

TABLE 17.2 Differential Diagnosis of Heterochromia

B

Fig. 17.22 Iris freckle and nevus. A, Clinical appearance of one iris nevus at 4 o’clock and numerous iris freckles. B, An iris freckle results from increased pigmentation of melanocytes of the anterior border layer without an increase of mass. C, An iris nevus is composed of nevus cells that result in increased mass—in this instance two nevi, one located near the pupillary border and the other slightly more peripheral.

2.Most, if not all, iris malignant melanomas arise from pre-existing nevi of the iris.

3.The geographic sector distribution of iris malignant melanoma is, in descending frequency, pupillary zone, entire sector, pupillary and midzone, midzone, periphery, periphery and midzone.

4.The geographic quadrant distribution of iris malignant melanomas is, in descending frequency inferior, temporal, nasal, superior.

C.Clinically, an iris melanoma may present as a discrete mass, a di use mass, heterochromia (see Table 17.2), glaucoma, chronic uveitis, or spontaneous hyphema. The glaucoma is caused by direct invasion of the aqueous drainage area, synechiae and secondary angle closure glaucoma, or induction of neovascularization or melanomalytic glaucoma.

Diffuse iris melanomas most often present with unilateral glaucoma and heterochromia. Metastasis occurs in about 13% of cases.

D.The tumors may be deeply pigmented, partially pigmented, or nonpigmented, and frequently show increased vascularity and distortion of the pupil toward the iris quadrant of involvement.

E.Most iris malignant melanomas are composed of spindle cells and, therefore, are relatively benign.

A spindle-A cell iris melanoma has no capacity to metastasize and can be considered a spindle cell nevus.

1.Only those tumors that have spindle-B or epithelioid cells, or involve the iris root or angle, have the ability to metastasize, and then they do so less than

10% of the time.

Because most iris “melanomas” are spindle-cell nevi, the Callender classification is best applied to ciliary body and choroidal melanomas.

2.The mortality rate is 4% to 5%.

On re-examination, 70% to 80% of previously diagnosed iris melanomas proved to be iris spindle-cell nevi, not melanomas.

F. Di erential diagnosis

1.Anterior staphyloma

2.Exudative mass in anterior chamber

a.Pigmented macrophages

b.Phacoanaphylactic endophthalmitis

c.Juvenile xanthogranuloma

3.Ocular penetration with uveal prolapse

4.“Postoperative confusion”

a.Posterioror anterior-chamber epithelial cyst

Anterior-chamber cysts may also occur spontaneously without surgery. The postoperative and the spontaneous cysts have been confused with iris malignant melanomas.

b.Iridencleisis (unplanned)

5.Miscellaneous

a.Nodular iris thickening and scarring

b.Foreign body in iris

c.Ectropion uveae

d.Segmental congenital ocular melanocytosis

e.Intrairis hemorrhage

f.Other iris tumors [e.g., nevus, ICE syndrome, leiomyoma, metastatic tumors (Fig. 17.25),

rhabdomyosarcoma (Fig. 17.26), and ciliary body malignant melanoma]

1.Angioleiomyoma

a.Tumor is composed of spindle cells with abundant cytoplasm

b.Contains many blood vessels

c.Immunohistochemical stains positive for smooth-muscle actin, and desmin, and negative for S-100 and HMB-45.

d.Granulomatous inflammation with Busacca and Koeppe nodules

e.Iris varix

Ciliary Body and Choroid

I.Nevus (Figs 17.27 to 17.29; see also Fig. 17.21B)

A. Incidence

1.Nevi of the ciliary body and choroid are found in at least 30% of people.

At least one discrete, focal, pigmented nevus, 0.5 disc diameter (DD) or greater, is present in one eye in 30% of patients. Approximately 3% to 4% of patients have one or more nevi in both eyes, and 7% of patients have multiple nevi in the same eye. Approximately 55% of patients with choroidal nevi have iris freckles or nevi in the same eye, but only 20% of patients without choroidal nevi have iris freckles or nevi.

2.The nevi have no sex predilection.

Fig. 17.27 Choroidal nevus. Distribution of 102 nevi in choroid and ciliary body. (From Naumann G et al.: Arch Ophthalmol 76:784, 1966. © American Medical Association. All rights reserved.)

3.The incidence in children is extremely low.

The low incidence in children may be caused by delayed pigmentation of pre-existing nevi.

The incidence then increases progressively during the second, third, and fourth decades and levels o at approximately 35%.

B.Location (see Fig. 17.27)

1.The overwhelming majority (91%) occur in the posterior half of the eye; most (59%) occur in the posterior third.

2.An almost equal incidence occurs in the anterior third of the choroid and the ciliary body.

C.Size and shape (see Fig. 17.28)

1.Nevi range in diameter from 0.5 to 11.0 mm (i.e.,

0.33 to 7 DD). Over 95% are 3 mm (2 DD) or less.

2.The lesions usually occupy the entire thickness of the choroid except for the choriocapillaris.

3.Typically, nevi are flat, discoid lesions, but 67% exceed the thickness of the adjacent choroid.

A

C

E

4.Nevi tend to be relatively avascular.

The relative avascularity helps to explain their fluorescein fundus picture, which is one of decreased fluorescence. An amelanotic nevus may be inadvertently detected when a fluorescein angiogram is being examined and shows a region of persistent choroidal hypofluorescence

B

D

Fig. 17.28 Choroidal nevus. Choroidal nevi may be flat and deeply pigmented (A), show overlying drusen (B), demonstrate orange pigment (C), or be multiple (D). E, Fluorescein appearance of choroidal nevus above optic disc in D (second nevus at 8 o’clock not seen).

without the presence of a corresponding pigmented fundus. Melanomas, on the other hand, are highly vascular with abnormal vessels that readily leak fluorescein. Rarely, however, nevi leak fluorescein and melanomas do not.

D.Cytology and pigmentation (Figs 17.30 and 17.31; see also Figs 17.28 and 17.29)