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

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Fig. 9.15 Central areolar choroidal sclerosis. A, Clinical appearance (left eye) of fundus in patient who had bilateral symmetric macular lesions. B, Histologic section of another case shows that the retinal pigment epithelium (RPE) and neural retina, which are relatively normal on the far left, show an abrupt transition to a chorioretinal abnormality that involves the outer neural retinal layers, RPE, and choroid. C, Increased magnification of the transition zone shows an intact Bruch’s membrane but loss of photoreceptors and RPE and obliteration of the choriocapillaris; no blood-containing vessels seen in remainder of choroid (r, neural retina; rpe, retinal pigment epithelium; ee, end of retinal pigment epithelium; er, end of retinal receptors). (A, Courtesy of Dr. WE Benson; B and C, modified from Ferry AP et al.: Arch Ophthalmol 88:39, 1972. © American Medical Association. All rights reserved.)

C

Clinically, the condition may be indistinguishable from geographic RPE atrophy of age-related macular degeneration.

c.Histologically, the area of involvement shows an incomplete or complete loss or degeneration of the choriocapillaris, the RPE, and the outer retinal layers.

2.Involvement of the peripapillary area—peripapil- lary choroidal sclerosis

a.The area of involvement, mainly the posterior one-third of the globe surrounding the optic nerve, shows a sharply demarcated atrophic area and easily seen, large choroidal vessels.

b.Histologically, the area of involvement shows absence of choriocapillaris, RPE, and photoreceptors and a decrease in choroidal arteries and veins.

Bruch’s membrane is intact except for some breaks in the immediate peripapillary region.

Angioid streaks may also be found.

3.Involvement of the paramacular area—also called circinate choroidal sclerosis

a.Total choroidal vascular atrophy involving the posterior eye grounds

Histologically, the choriocapillaris, the RPE, and the outer neural retinal layers are degenerated and sharply demarcated from adjacent normal chorioretinal areas. Diffuse and focal areas of round cell inflammation (mainly lymphocytes) may be found.

Involvement of the macula alone or throughout most of the posterior eyegrounds—also termed serpiginous choroiditis, serpiginous choroidopathy, serpiginous degeneration of the choroid, geographic helicoid peripapillary choroidopathy, geographic choroiditis, choroidal vascular abiotrophy, and central gyrate atrophy

Tuberculous choroiditis may mimic serpiginous choroiditis.

b.The dystrophy is characterized by well-defined gray lesions seen initially at the level of the pigment epithelium, usually contiguous with or very close to the optic nerve.

1). Each new lesion does not change its size or shape.

2). With healing, degeneration of the pigment epithelium, geographic atrophy of the choroid, or even subretinal neovascularization and subretinal scar formation (disciform macular degeneration) may occur.

B.The disease progress is away from the optic disc, with new attacks occurring in areas previously uninvolved.

1.Visual acuity is only a ected if the central fovea is involved in an attack.

Rarely, the initial lesion, or the only lesion, may be in the macula.

2.Involvement with nasal and temporal foci—also called progressive bifocal chorioretinal atrophy

(PBCRA)

The gene for PBCRA has been linked to chromosome 6q near the genomic assignment for North Carolina macular dystrophy. The phenotype of PBCRA, although similar to North Carolina macular dystrophy, is quite distinct.

3.Involvement of the disc—also called choroiditis areata, circumpapillary dysgenesis of the pigment epithelium, and chorioretinitis striata

4.Malignant myopia (see p. 423 in Chapter 11)

II.Di use choroidal dystrophies

A.Di use choriocapillaris atrophy—also called generalized choroidal angiosclerosis, di use choroidal sclerosis, and generalized choroidal sclerosis

Histologically, the choriocapillaris, the RPE, and the outer neural retinal layers are degenerated.

B.Di use total choroidal vascular atrophy

1.Autosomal-recessive inheritance (carried on chromosome 10q26)—also called gyrate atrophy of the choroid

a.Gyrate atrophy of the choroid is characterized by the development of atrophic chorioretinal patches in the periphery (often with glistening crystals scattered at the equator), progressing more centrally than peripherally, and partially fusing.

b.Other ocular findings include posterior subcapsular cataracts and myopia, cystoid macular edema, and, rarely, retinitis pigmentosa.

A peripapillary atrophy may develop simultaneously. In the final stage, all of the fundi except the macula may be involved so that the condition may resemble choroideremia.

c.Patients have hyperornithinemia (10to 20-fold increased ornithine concentration in plasma and

other body fluids), caused by a deficiency of the mitochondrial matrix enzyme ornithine-δ-

aminotransferase (OAT). They may also show subjective sensory symptoms of peripheral neuropathy.

1). OAT catalyzes the major catabolic pathway of ornithine, which involves the interconversion of ornithine, glutamate, and proline through the intermediate pyrroline-5- carboxylate and requires pyridoxal phosphate

(vitamin B6) as coenzyme.

2). The OAT gene maps to chromosome 10q26, and OAT-related sequences have also been mapped to chromosome Xp11.3–p11.23 and

Xp11.22–p11.21.

d.The condition becomes manifest in the second or third decade of life and slowly progresses, causing a concentric reduction of the visual field, leading to tunnel vision, and ultimately to blindness in the fourth to seventh decade of life. Decreasing vision and night blindness are prominent symptoms, along with electrophysiologic dysfunction.

e.An arginine-restricted diet slows the progress of the condition, whereas creatine supplementation appears to have no e ect.

f.Histologically, the iris, corneal endothelium, nonpigmented ciliary epithelium, and, to a lesser extent, photoreceptors show abnormal mitochondria.

An abrupt transition occurs between the normal and the involved chorioretinal area; the latter shows near-total atrophy of the neural retina, RPE, and choroid.

2.X-linked inheritance—also called choroideremia, progressive tapetochoroidal dystrophy, and progressive chorioretinal degeneration (Fig. 9.16)

a.This condition is characterized by almost complete degeneration of the retina and choroid

(except in the macula) in a ected men. It becomes manifest in childhood and progresses slowly until complete at approximately 50 years of age.

The fundus picture in carrier women resembles that seen in the early stages in affected men, namely, degeneration of the peripheral RPE giving a salt-and- pepper appearance. Mutations can cause severe visual loss in female carriers.

b.It is unclear whether the earliest changes are in the choroid or the RPE, or both.

c.Component A (but not B) of Rab geranylgeranyl transferase appears to be deficient in choroideremia.

Transfer of the Rab geranylgeranyl depends on the participation of Rab escort proteins (REP). REP-1 is produced by a gene on the X chromosome, which is defective in patients who have choroideremia.

d.Histologically, the choroid and RPE are absent or markedly atrophic, and the overlying outer neural retinal layers are atrophic. Uveal vascular endothelial cell and RPE abnormalities may be found where uveal vessels still persist.

III.All of the aforementioned choroidal entities, although usually called atrophies, should more properly be called dystrophies with secondary retinal changes; it is likely that the primary dystrophic abnormality resides in the choroidal vasculature or the RPE.

TUMORS

Epithelial

I.Hyperplasias (see p. 22 in Chapter 1 and section Melanotic Tumors of Pigment Epithelium of Iris, Ciliary Body, and

Retina in Chapter 17)

Occasionally, pseudoadenomatous hyperplasias may become extreme and produce masses that are noted clinically, either localized to the posterior chamber or, rarely, proliferated into the anterior chamber.

II.Benign adenoma of Fuchs (Fuchs’ reactive hyperplasia, coronal adenoma, Fuchs’ epithelioma, benign ciliary epithelioma; Fig. 9.17)

A.The small, age-related tumor is present in over 25% of older people, is located in the pars plicata of the ciliary body, is benign, and is usually found incidentally when an enucleated globe is being examined microscopically.

B.It may rarely cause localized occlusion of the anteriorchamber angle.

C.The tumor is proliferative rather than neoplastic, i.e, a

hyperplasia not an adenoma.

D. Histologically, it is a benign proliferation of cords of the nonpigmented ciliary epithelium interspersed

with abundant, amorphous, eosinophilic, acellular basement membrane material (type IV collagen and laminin are found immunohistochemically), acid mucopolysaccharides (mainly hyaluronic acid), and glycoproteins.

III. Medulloepithelioma (see p. 686 in Chapter 17)

Muscular

I.Leiomyomas—benign smooth-muscle tumors—may rarely occur in the iris, ciliary body, or choroid.

A.Leiomyomas have a predilection for women.

B.The tumors tend to a ect the ciliary body and anterior choroid, unlike melanomas, which favor the posterior choroid.

C.It is di cult to di erentiate a leiomyoma from an amelanotic spindle cell nevus and low-grade melanoma without the use of electron microscopy and immunohistochemical studies.

Many cases previously diagnosed as leiomyoma are probably melanocytic, rather than smooth-muscle, lesions.

D.Electron microscopic criteria for smooth-muscle cells include an investing thin basement membrane, plasmalemmal vesicles, plasmalemma-associated densities, and myriad longitudinally aligned, intracytoplasmic filaments with scattered associated densities, characteristics that allow for identification of the cells in less than optimally fixed tissue. In addition, immunohistochemical stains for muscle-specific antigen, smooth-muscle actin, and vimentin are positive in leiomyomas.

E.Mesectodermal leiomyoma (see p. 555 in Chapter 14)

1.This rare variant of leiomyoma, which microscopically resembles a neurogenic tumor more than a myogenic tumor, presumably originates from the neural crest.

2.Histologically (Fig. 9.18), widely spaced tumor cell nuclei are set in a fibrillar cytoplasmic matrix and may show immunoexpression of neural markers.

The tumors resemble ganglionic, astrocytic, and peripheral nerve tumors. The presence of a reticulum differentiates mesectodermal leiomyoma from astrocytic tumors, where the fiber is absent. Immunohistochemistry and electron microscopy are needed to differentiate the tumor from peripheral nerve tumors. If the characteristic immunohistochemical and ultrastructural features of smoothmuscle cells are found, the diagnosis is clear.

F.Leiomyosarcoma has been reported as a rare iris neoplasm.

II.A rhabdomyosarcoma is an extremely rare tumor of the iris and is probably atavistic.

Vascular

I.True hemangiomas of the iris and ciliary body are extremely rare.

A.Presumed iris hemangioma has been reported in association with multiple central nervous system (CNS) cavernous hemangiomas and may represent a distinct

form of phakomatosis.

II.Hemangioma of the choroid (Fig. 9.19)

A.Hemangioma of the choroid occurs in two types, circumscibed and di use

1.Circumscribed is usually solitary and not associated with any systemic process.

2.Di use may rarely occur as an isolated finding but mostly it is part of the Sturge–Weber syndrome (see

Fig. 2.2).

B.Over long intervals of observation, choroidal hemangiomas may show slight enlargement.

C.Clinically, it presents as a circumscribed, orange-red mass that shows early fluorescence with fluorecein

and indocyanine green. Subretinal fluid is quite common

D.Histologically the choroidal tumor shows large, dilated, blood-filled spaces lined by endothelium and sharply demarcated from the normal, surrounding choroid.

III.Hemangiopericytoma

A.Hemangiopericytomas are much more common in the orbit (see p. 546 in Chapter 14) than intraocularly.

B.Histologically, well-vascularized spindle cell proliferation is present in the uvea in a sinusoidal pattern.

IV. AV malformation of the iris

A.AV iris malformation, also called racemose hemangioma, is rare

B.It consists of a unilateral continuity between an artery and a vein without an intervening capillary bed.

C.The lesion is benign and stationary.

Osseous

I.Choroidal osteoma (osseous choristoma of the choroid; Fig. 9.20)

A.This benign, ossifying lesion is found mainly in women in their second or third decade of life and is bilateral in approximately 25% of patients.

Bilateral osseous choristoma of the choroid has been reported in an 8-month-old girl.

1.Growth may be seen in approximately 51% of cases with long-term follow-up.

2.An associated subretinal fluid, neovascularization, or hemorrhage may be present. Over 10 years about 56% of all patients will have decreased vision to 20/200 or worse.

Choroidal osteomas may follow ocular inflammation, be associated with systemic illness, or be familial. Rarely, they may undergo growth or spontaneous involution.

B.The characteristic clinical findings include:

1.A slightly irregularly elevated, yellow-white, juxtapapillary choroidal tumor with well-defined geographic borders

2.Di use, mottled depigmentation of the overlying pigment epithelium

3.Multiple small vascular networks on the tumor surface

C.The tumor is dense ultrasonically; tissues behind the tumor are silent.

Decalcification occurs over time in almost 50% of patients.

D.Histologically, mature bone with interconnecting marrow spaces is seen sharply demarcated from the surrounding choroid.

Melanomatous

See Chapter 17.

A

Leukemic and Lymphomatous

I.Acute granulocytic (myelogenous; Fig. 9.21) and lymphocytic leukemias not infrequently have uveal, usually posterior choroidal, infiltrates as part of the generalized disease.

Esterases are enzymes that hydrolyze aliphatic and aromatic esters. Nonspecific esterase activity, as determined by using α-naphthyl acetate as a substrate, is not detectable in granulocytic cells. Specific esterase activity, however, as determined by using naphthol ASD-chloroacetate, is present exclusively in granulocytic cells. By demonstrating specific esterase activity on histologic sections (cytochemical method), acute granulocytic (myelogenous) leukemia can be differentiated from acute lymphocytic leukemia. Demonstrating specific esterase activity histologically is especially helpful in diagnosing leukemic infiltrates [called myeloid (granulocytic) sarcoma], particularly in the orbit, where granulocytic leukemic infiltrates may appear greenish clinically because of the presence of the pigment myeloperoxidase, and then are called chloromas. In addition, the combined use of the cytochemical

B

method with immunology (positive for CD43, CD45, antilysozyme, Lader stain) and morphologic study gives the best yield in differentiating the acute blastic leukemias.

A.Approximately 30% of autopsy eyes from fatal leukemic cases show ocular involvement, mainly leukemic infiltrates in the choroid. Also, 42% of newly diagnosed cases of acute leukemia show ocular findings, especially intraretinal hemorrhages, white-centered hemorrhages, and cotton-wool spots.

Rarely, the first sign of granulocytic leukemia relapse is ocular adnexal involvement.

B.Retinal hemorrhages are most likely to occur in patients who have both anemia and thrombocytopenia com-

bined; and when the two are severe (hemoglobin

<8 g/100 ml and platelets <100 000/mm), retinal hemorrhages may occur in 70% of patients.

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II.Malignant lymphomas (see p. 574 in Chapter 14)— non-Hodgkin’s lymphoma of the CNS (NHL-CNS) and systemic non-Hodgkin’s lymphoma rarely involve the eye, but do so much more often than Hodgkin’s lymphoma.

A.NHL-CNS—old terms—reticulum cell sarcoma, histiocytic lymphoma, microgliomatosis

1.NHL-CNS (Fig. 9.22), usually a large B-cell lymphoma, may be associated with similar multifocal neoplastic infiltrates in the vitreous, presenting clinically as uveitis.

Occasionally, NHL-CNS may involve the eye primarily and simulate a chronic uveitis, often with a vitreitis. Concentrations of interleukin-10 from vitreous aspirates may be helpful in making the diagnosis.

a.The retina and choroid may also be involved (oculocerebral non-Hodgkin’s lymphoma).

b.The neoplasm probably arises in the brain and eye as a result of multicentric origin rather than by metastasis.

NHL-CNS is composed completely of B lymphocytes 70% of the time, T lymphocytes, 20%, and true histiocytes, less than 10%. When the neoplasm arises multicentrically in subretinal pigment epithelial space, it produces multiple, large, solid detachments of RPE that are characteristic.

2.Systemic spread outside the CNS and eyes is found in only 7.5% of autopsies.

B.Systemic non-Hodgkin’s lymphoma

1.Systemic non-Hodgkin’s lymphoma almost always arises outside the CNS.

2.Ocular involvement occurs through invasion of choroidal circulation and spreads to the choroid.

3.Patients who have systemic non-Hodgkin’s lymphoma (as well as Hodgkin’s lymphoma) often have concurrent signs and symptoms of a systemic lymphoma at the time of ocular involvement and pose less of a diagnostic dilemma than

NHL-CNS.

4.Rarely, adult T-cell lymphoma/leukemia (caused by human T-lymphotropic virus type 1 infection) presents as an intraocular lymphoma.

III.Occasionally, benign lymphoid infiltration (lymphoid tumor), containing lymphocytes, plasma cells, and reticulum cells, may be seen in the uveal tract.

A.The infiltrates are usually unilateral but may be bilateral.

The infiltrates may appear as multifocal, confluent and nonconfluent, creamy choroidal patches that collect

fluorescein without leakage into the subneural retinal or subretinal pigment epithelial spaces.

B.They resemble the inflammatory pseudotumors, especially reactive lymphoid hyperplasia (see p. 574 in

Chapter 14), seen in the orbit.

Probably, uveal lymphoid infiltration (benign lymphoid hyperplasia of the uvea) is a low-grade B-cell lymphoma, which can be associated with episcleral conjunctival nodules.

B.Malignant melanoma of conjunctiva

C.Retinoblastoma

D.Malignant melanoma of uvea (e.g., ciliary body melanoma extending into choroid or iris)

E.Embryonal and adult medulloepitheliomas

F.Glioma of optic nerve

G.Meningioma of optic nerve sheaths

It is extremely rare for an orbital neoplasm to invade through the sclera into the uvea or through the meninges into the optic nerve.

II.Metastatic—most common adult intraocular neoplasm (Fig. 9.23)

Although metastatic neoplasms are often considered to be the second most common intraocular neoplasm (second to primary uveal malignant melanomas), clinical and autopsy evidence suggests that metastatic cancer is the most common intraocular neoplasm.

A.Lung: most common metastatic lesion in men (usually occurs early in the course of the disease and may be the initial finding).

With increased smoking among women, their frequency of lung carcinoma continues to rise rapidly and now equals the frequency in men.

B.Breast: most common metastatic lesion in women

(usually occurs late in the course of the disease and breast surgery was usually performed previously).

C.All other primary sites are relatively uncommon as sources of intraocular metastases.

D.Metastatic intraocular neoplasms are more common in women and are bilateral in approximately 20% to 25% of cases.

Although metastatic choroidal tumors tend to be oval-shaped clinically, rarely they may be mushroom-shaped and simulate a choroidal melanoma

Other Tumors

I.Neural

A.Neurofibromas of the uvea occur as part of di use neurofibromatosis (see p. 31 in Chapter 2).

B.Neurilemmomas (see p. 558 in Chapter 14) and glioneuromas (see p. 689 in Chapter 17) are exceedingly rare tumors of the uveal tract.

II.Benign fibrous tumor is exceedingly rare.

Secondary Neoplasms

I.By direct extension:

A.Squamous (or rarely basal) cell carcinoma of conjunctiva

UVEAL EDEMA (UVEAL DETACHMENT; UVEAL HYDROPS)

Types

I.Uveal e usion syndrome—uveal e usion with choroidal and ciliary body detachment (spontaneous serous detachments)

A.Uveal e usion is characterized by a slowly progressive, often bilateral neural retinal detachment that shows shifting fluid and is mainly found in middle-aged, otherwise healthy men. Also noted are dilated episcleral vessels, vitreous cells, characteristic “leopard-spot” RPE

changes, and abnormal ultrasonographic and angiographic findings.

Elevation of cerebrospinal fluid protein occurs in approximately 50% of cases. Although considered idiopathic, it may be caused by a congenital anomaly of the sclera and, in some cases, the vortex veins. The syndrome may also be found in nanophthalmic eyes and in patients who have primary pulmonary hypertension and vomiting.

B.Choroidal e usion is presumably the underlying cause and results from the thickened sclera and vortex vein anomalies.

Signs of uveitis are minimal or absent.

C.Scleral abnormalities, secondary to proteoglycan deposition in the matrix, impede transscleral fluid outflow.

D.The neural retinal detachment may reattach after months or even years, although it may remain permanently detached.

II.Posttrauma—either surgical or nonsurgical trauma

A.Hypotony and vasodilatation after penetration of the globe combine to produce transudation of fluid through uveal vessels, leading to uveal edema.

Clinically, this appears as a combined detachment of uveal tract and retina.

B.Uveal hemorrhage may occur secondary to the trauma and result in uveal detachment.

III.Vascular—malignant hypertension, eclampsia, nephritis, and other conditions that a ect the ciliary vessels can lead

to uveal edema.

IV. Inflammatory—any type of ocular inflammation (i.e., acute, nongranulomatous, or granulomatous, e.g., Harada’s disease) can induce uveal edema.

V.Associated with malignant choroidal tumors

Choroidal detachment can occur in association with metastatic choroidal tumors or choroidal melanomas.

VI. Sequelae—in atrophic eyes with or without shrinkage, secondary to any cause, traction bands and organized scar tissue may induce uveal detachment.