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

C

3.It may be very cellular [i.e., a cellular blue nevus

(Fig. 17.5), which has a low malignant potential].

C.Unless the nevus is the large or giant congenital cellular type, it has no malignant potential.

VI. Congenital oculodermal melanocytosis (nevus of Ota; Fig.

17.6; see also Fig. 17.36D)

A.The condition can be considered a type of blue nevus of the skin around the orbit (in the distribution of the ophthalmic, maxillary, and occasionally mandibular branches of the trigeminal nerve), associated with an ipsilateral blue nevus of the conjunctiva and a di use nevus of the uvea (i.e., ipsilateral congenital ocular melanocytosis).

1.Skin pigmentation is usually prominent, but may be quite subtle.

Approximately 60% of patients have the complete syndrome of skin, conjunctival, and uveal involvement (congenital oculodermal melanocytosis); approximately 34% have only skin involvement (congenital dermal melanocytosis); and approximately 6% have only conjunctival and uveal involvement (congenital ocular melanocytosis).

2.It is quite common in black and Asian patients, but unusual in white patients.

3.Rarely, congenital oculodermal melanocytosis is bilateral.

4.Associated findings in the involved eye include glaucoma (which is common and may develop at any age), uveitis, and cataract.

When congenital oculodermal melanocytosis and nevus flammeus (phakomatosis pigmentovascularis) occur together, especially when each extensively involves the globe, a strong predisposition exists for the development of congenital glaucoma.

B.The di use uveal involvement causes heterochromia iridum (i.e., the involved eye is darker than the uninvolved iris).

Heterochromia iridum (see Table 17.2, p. 694) is a di erence in pigmentation between the two irises, as contrasted to heterochromia iridis, which is an alteration within a single iris (e.g., occasionally, ipsilateral segmental heterochromia is caused by segmental

C.Congenital dermal melanocytosis may occur alone or concurrently with orbital melanocytosis, in which case it is called congenital dermal orbital melanocytosis. It may also occur concurrently with ocular melanocytosis, in which case it is called congenital oculodermal melanocytosis (nevus of Ota).

D.Congenital ocular melanocytosis (see earlier)

E.Congenital oculodermal melanocytosis is potentially malignant only when it occurs in white patients.

Malignant melanomas have been reported in the skin, conjunctiva, uvea (most common), orbit (rarely), and even in the meninges.

The lifetime prevalence of uveal melanomas in white patients who have congenital oculodermal melanocytosis has been estimated to be 1 in 400.

In the United States between 1973 and 1994, an increase in melanoma incidence and mortality rates of approximately 121% and 39%, respectively, occurred.

1.The rising incidence is probably attributable to increased voluntary exposure to sun and the depletion of the ozone layer.

2.An emerging epidemic of melanoma appears to be on the horizon.

B.Melanoma involves the lower lid two-thirds more often than the upper lid.

C.Associated histologic findings include solar elastosis, nevus, and basal cell carcinoma.

Malignant Melanoma

I.General information (Figs 17.7 and 17.8)

A.From the 1960s to the 1980s, the incidence of cutaneous malignant melanoma rose 3.5-fold in men and 4.6- fold in women.

Rarely, a primary choroidal melanoma can occur in a patient who has had a previous cutaneous melanoma.

D.Cuticular melanomas show a nonrandom alteration of chromosome 6.

II.Malignant melanoma may arise from a pre-existing junctional, compound, or, rarely, large or giant congenital mela-

nocytic nevus, or it may arise de novo.

III.Skin melanomas are not classified according to cell type, as are uveal melanomas*

A.Lentigo maligna melanoma

1.The melanoma develops in a preinvasive lesion called lentigo maligna (see p. 668 in this chapter), also called melanotic freckle of Hutchinson or circumscribed precancerous melanosis of Dubreuilh.

2.After a radial growth phase (intraepidermal spread), vertical growth phase (dermal invasion) may occur, elevating the lesion.

B.Superficial spreading malignant melanoma

1.Superficial spreading malignant melanoma has a prolonged radial growth phase before the vertical growth phase.

*On the basis of gross appearance and biologic behavior, melanomas may be divided clinically into lentigo maligna melanoma, superficial spreading melanoma, and nodular melanoma.

2.Clinically, the lesion appears as a nodule or plaque with variable pigmentation and has a “surround component” caused by the intradermal spread.

C.Nodular malignant melanoma

1.This type has only a vertical growth phase, involves the dermis early, and has the worst prognosis.

2.Clinically, the lesion appears as a nodule or plaque without a surround component because no radial growth phase occurs.

D.Acrolentiginous melanoma occurs on the palms, soles, and terminal phalanges.

E.The melanocytic neuroectodermal tumor (retinal anlage tumor, retinal choristoma) of infancy mainly involves the maxilla, but has been reported in many other locations.

F.Mucous membrane malignant melanoma (see discussion of conjunctival melanoma, p. 682 in this chapter).

Rarely,a primary lid melanoma can occur in conjunction with an ipsilateral primary conjunctival melanoma.

G.Miscellaneous—malignant melanoma that arises in a large or giant congenital melanocytic nevus, in the central nervous system, and in the viscera

IV. Histology

A.Normal polarity is lost (i.e., the deep cells are indistinguishable from superficial cells).

B.The overlying epithelium is invaded.

If only epithelial invasion is seen, it is called a superficial spreading or incipient melanoma. Pigmentation may or may not be present. If present, it may vary in different parts of the tumor. If pigmentation is not present, the tumor is called an amelanotic melanoma.

Invasion of the underlying dermis occurs concurrently with (nodular malignant melanoma) or after (superficial spreading malignant melanoma) epithelial invasion.

C.The cells of the neoplasm are atypical.

1.The nuclear-to-cytoplasmic ratio is increased, and large abnormal cells may be seen.

2.Mitotic figures may be present, but frequently are absent.

D.Often, an underlying inflammatory infiltrate of round cells, predominantly lymphocytes, is present.

E.Usually, a combination of the aforementioned criteria rather than any single criterion leads to the diagnosis of malignancy.

Immunohistochemical staining for versican, a major proteoglycan expressed by cutaneous malignant melanomas (CMM), may be helpful in differentiating benign melanocytic nevi (BMN), dysplastic nevi (DN), and CMM. Versican is generally negative in BMN, positive (ranging from weakly to intensively positive) in DN, and intensively positive in CMM. S-100 and NKI/C3 are helpful immunohistologic stains for determining the extent of melanocytic lesions in the conjunctiva. HMB45 immunoreactivity may be helpful in distinguishing benign from malignant melanocytic lesions, particularly those related to primary acquired melanosis (PAM).

F.Radial growth

1.Small clusters and single atypical melanocytes grow throughout the epidermis (pagetoid growth),

E

or at the dermoepidermal junction (lentiginous growth), and may invade the dermis in a platelike fashion.

2.Corium tumor cells tend to be small and of uniform size, similar to tumor cells in the epidermis or dermoepidermal junction.

G.Vertical growth

1.Vertical di ers from radial growth mainly in cytoarchitectural heterogenicity (i.e., at least some of the tumor cells in the dermis have a di erent

appearance than those in the epidermis or at the dermoepidermal junction).

2.Mitotic figures are usually present in the dermal component.

3.Melanomas greater than 1.5 mm in depth carry a distinctly worse survival rate.

V.Prognosis

A.In general, involvement of the lid margin and conjunctiva is associated with a poorer survival rate than localization to the lid skin alone.

B.Superficial, spreading malignant melanoma has a 75% survival rate.

C.Deep malignant melanoma has a 10% to 39% survival rate (variability in survival rates is due to location of tumor and di erent authors’ statistics).

D.The level of expression of at least three integrin subunits has been found to be correlated with melanoma progression.

Breslow thickness is an important prognostic indicator for eyelid skin melanomas.

MELANOTIC TUMORS

OF CONJUNCTIVA

Ephelis (Freckle)

I.An ephelis (freckle) is a brown, patchy, flat lesion with irregular borders.

A.It most often involves the bulbar conjunctiva near the limbus, but it may involve the bulbar or palpebral conjunctiva.

B.The pigmented conjunctiva is movable over the sclera.

C.The lesion is present at birth.

II. Freckles are common in dark races.

III.The histology consists of increased pigmentation in the basal cell layer of the conjunctival epithelium; the number of melanocytes is normal or decreased.

Histologically, the freckle and lentigo are similar, if not identical, to benign acquired melanosis that has no junctional activity.

Lentigo

I. A lentigo is somewhat larger than an ephelis.

II.Histologically, pigmentation of the basal cells of the conjunctival epithelium is increased and melanocytes are increased in number.

Nevus

I.General information (Figs 17.9 to 17.11)

A.A nevus is a hamartomatous, congenital, flat or elevated, well-circumscribed lesion that may not become pigmented until puberty or early adulthood.

1.Conjunctival nevi are usually noted during the first two decades of life.

2.They are almost entirely restricted to the epibulbar surface, the plica, the caruncle (see Fig. 17.11), and the lid margin. The lesion is most commonly found at the nasal or temporal limbus.

3.Nevi are rarely located in the palpebral conjunctiva (1%), fornix (1%) , or cornea (<1%).

4.Over time, a change in color may be seen in

13% of lesions, and the size may change in

8%.

B.Nevi are primarily composed of nevus cells, but may also have epithelial elements (see later discussion of compound nevus).

C.A nevus is the most common conjunctival tumor and consists of five “classic” types:

1.Junctional

2.Subepithelial (analogous to intradermal nevus of skin)

3.Compound

4.Blue

5.Congenital melanocytosis

a.Congenital ocular melanocytosis (melanosis oculi)

b.Congenital oculodermal melanocytosis (nevus of Ota)

6.Unusual types of conjunctival nevi

II.Junctional nevus (Table 17.1; see Fig. 17.9C)

A.Similar in appearance to junctional nevus of the skin.

B.Nevus moves with conjunctiva over sclera.

A junctional nevus (composed of nevocellular cells), not uncommonly, may be associated with a blue nevus (composed of blue nevus cells); the two together are called a combined nevus of the conjunctiva.

C.Histologically, nevus cells appear more “worrisome” than those of skin junctional nevi.

1.Cells tend to be larger and may reach the external surface of the epidermis.

2.The nevus cells are not necessarily limited to the junctional area of the epithelium and subepithelium, but may be found within the epithelial layers, simulating invasion.

3.Histologically, the junctional nevus, when maximally pigmented, is identical in appearance to benign acquired melanosis with junctional activity.

D.Malignant potential is low.

III. Subepithelial nevus (see Table 17.1)

A.Similar to intradermal nevus of the skin; appears flesh-colored to brown depending on the degree of pigmentation.

B.Nevus moves with conjunctiva over sclera.

C.It is not nearly as common as a junctional or compound nevus.

D.Histologically, the cells show normal polarity (i.e., smaller, darker, more spindle-shaped cells present in the deeper layers).

E.It probably has no malignant potential.

IV. Compound nevus (see Table 17.1 and Figs 17.9D and

17.10)

A.Quite similar to compound nevus of the skin; appears brown when pigmented.

B.Nevus moves with conjunctiva over sclera.

C.Histologically, the subepithelial component shows a normal polarity (i.e., cells found closest to the epithelium are plumper, larger, rounder, and paler).

D.The subepithelial hamartomatous component, in addition to containing nevus cells, frequently contains epithelial embryonic rests, which may develop into epithelial cysts (i.e., a cystic nevus; see Fig. 17.10).

1.The epithelial component is present in approximately 50% of conjunctival nevi.

2.Balloon cells, probably representing lipidized melanocytes, are often seen admixed with nevus cells and the epithelial component.

E.Spindle-cell nevus (Spitz nevus; juvenile melanoma)

1.This special form of compound nevus occurs predominantly in children.

2.Histologically, it is similar to “juvenile melanoma” of the skin.

F.Malignant potential is extremely low.

V.Blue nevus

A.Quite similar to blue nevus of the skin; appears di use, blue to slate-gray, and is pigmented from birth.

B.It does not move with the conjunctiva over the sclera.

A junctional nevus (composed of nevocellular cells) not uncommonly may be associated with a blue nevus (composed of blue nevus cells); the two together are called a combined nevus of the conjunctiva.

C.Histologically, nevus cells, mainly deeply pigmented, are seen deep in the subepithelial tissue in interlacing fasciculi.

1.The cells are deeper than the junctional, subepithelial, or compound nevus cells, and are more spindleshaped and elongated, and contain larger branching processes than other types of nevus cells.

2.When very cellular, the nevus is called a cellular blue nevus.

a.It appears as a localized blue nodule.

b.It rarely becomes malignant.

D.A blue nevus may be di cult to di erentiate from other lesions that cause episcleral pigmentation.

E.Only the cellular type is potentially malignant.

VI. Congenital melanocytosis (see Table 17.1)

A.Congenital ocular melanocytosis (melanosis oculi; see Fig. 17.6)

1.Probably it is best considered as a di use blue nevus of the conjunctiva.

It may occur as a cellular blue nevus.

2.The condition is usually unilateral and is mainly present in dark races (blacks and Asians).

3.The lesion is blue or slate-gray from birth, and does not move with the conjunctiva.

4.It is associated with an ipsilateral di use uveal nevus that causes heterochromia, which at times is subtle, especially in brown-eyed people.

Waardenburg’s syndrome consists of heterochromia iridum or iridis (unilateral or bilateral; segmental or diffuse) usually with a similar (congenital hypopigmentation) involvement of the remainder of the uvea; lateral displacement of medial canthi, combined with dystopia of the lacrimal puncta and blepharophimosis; prominent, broad root of the nose; growing together of the eyebrows with hypertrichosis of the medial portions; white forelock, a form of partial albinism (early graying of the hair begins soon after puberty); defective pigmentation in any part of the body; and congenital deafness. The involved eye is the lighter eye. The defect resides on chromosome 2q32.

5.The ocular involvement may be segmental (i.e., limited to a quadrant).

When segmental, the diffuse uveal nevus usually involves the iris, ciliary body, and choroid in the same quadrant (more or less).

6.The condition is potentially malignant when it occurs in white patients; a uveal malignant melanoma results.

Rarely, the conjunctiva or orbit may be the primary site of malignancy.

B.Congenital oculodermal melanocytosis (nevus of Ota; see p. 671 in this chapter).

VII. Unusual types of conjunctival nevi

A.Recurrent nevus—recurrence of an incompletely excised nevus

B.Inflamed nevus—pseudoenlargement of a conjunctival nevus, secondary to inflammation, usually seen between the ages of 15 and 25 years

C.Dysplastic nevus (see p. 669 in this chapter)

D.Spindle-cell nevus (Spitz nevus; juvenile melanoma; see above in this chapter)

E.Balloon cell nevus—probably represents lipidized melanocytes

F.Epithelioid cell nevus—composed entirely of epithelioid melanocytes

Primary Acquired Melanosis

I.PAM (Figs 17.12 and 17.13; see also Table 17.1) A. Clinical characteristics

1.The melanosis consists of a unilateral, di use, brown pigmentation that moves with the conjunctiva over the sclera (analogous to lentigo maligna of the skin).

Rarely, PAM may be amelanotic in both its benign and its malignant forms.

2.The condition has a variable and protracted course.

a.Rarely, it may remain stationary or even recede.

It tends to remain benign, but slowly enlarges over the years.

b.Approximately 17% become malignant, usually

5 to 10 years after onset.

3.The age of onset is approximately 40 to 50 years of age.

4.Rarely, PAM may be associated with malignant melanomas of the nasal cavity and paranasal sinuses.

B.Classification of unilateral PAM*

1.Stage I: Benign acquired melanosis (precancerous melanosis)

a.Stage IA shows minimal melanocytic hyperplasia.

1). Hyperpigmentation of the epithelium may be the only finding (see Fig. 17.12).

2). Some increase in the number of enlarged melanocytes or a few scattered clusters of nevus cells along the basal layer may be seen.

b.Stage IB shows atypical melanocytic hyperplasia.

1). Stage IB1 shows mild to moderately severe atypical melanocytic hyperplasia (see Fig. 17.13C).

a). The lesions show enlarged melanocytes with enlarged nuclei, palisading of

*Zimmerman LE: Criteria for management of melanosis: In correspondence. Arch Ophthalmol 76:307, 1966 (modified in Spencer WH, Zimmerman LE: Conjunctiva. In Ophthalmic Pathology, vol 1. An Atlas and Textbook. Philadelphia, WB Saunders, 1985:201).