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

filled with lipid but dissolved out during tissue processing.

1.Polymorphonuclear leukocytes, plasma cells, and lymphocytes may also be found in abundance.

2.Not infrequently, multinucleated giant cells (resembling foreign-body giant cells or Langhans’ giant cells) and even asteroid and Schaumann’s bodies— all nonspecific findings—may be seen.

Recurrent giant chalazia may be found in the hyperimmunoglobulin E (Job) syndrome. The syndrome is a rare immunodeficiency and multisystem disorder characterized by recurrent skin and pulmonary abscesses, connective tissue abnormalities, and elevated levels of serum immunoglobulin E (IgE).

V.Acne rosacea

A.Acne rosacea a ects mainly the skin of the middle face, nose, cheeks, forehead, and chin, and presents in three types, which may occur separately or together: (1) an erythematous telangiectatic type with erythema, telangiectasis, follicular pustules, and occasional abscesses;

(2)a glandular hyperplastic type with enlargement of the nose (rhinophyma); and (3) a papular type with numerous, moderately firm, slightly raised papules 1 to

2 mm in diameter and associated with di use erythema.

Many dermatologists believe that some cases of acne rosacea are caused by large numbers of Demodex (see subsection

Demodicosis, later).

B.Ocular involvement is commonly found and consists of blepharitis, chalazion, conjunctival and lid granulomas, episcleritis, hyperemic conjunctivitis, internal hordeolum, keratitis, lid margin telangiectasis, meibomianitis, squamous metaplasia of the meibomian duct, and superficial punctate keratopathy.

C.Histology

1.Type 1 shows dilated blood vessels and a nonspecific, dermal, chronic nongranulomatous inflammatory infiltrate often associated with pustules (i.e., intrafollicular accumulations of neutrophils).

2.Type 2 shows hyperplasia of sebaceous glands along with the findings seen in type 1.

3.Type 3 shows papules composed of either a chronic nongranulomatous inflammatory infiltrate or, fre-

quently, a granulomatous inflammatory infiltrate

simulating tuberculosis (formerly called rosacea-like, tuberculid, or lupoid rosacea).

VI. Relapsing febrile nodular nonsuppurative panniculitis (Weber–Christian disease)—see p. 188 in this chapter.

Viral Diseases

I.Molluscum contagiosum (Fig. 6.12)

A.Clinically, a dome-shaped, small (1 to 3 mm), discrete, waxy papule, often multiple, is seen with a characteristic umbilicated center (central dell).

Blepharoconjunctivitis associated with molluscum contagiosum may occur in the Wiskott–Aldrich syndrome (WAS), which is characterized by atopic dermatitis, thrombocytopenic purpura, normal-appearing megakaryocytes but small, defective platelets, and increased susceptibility to infections. The syndrome represents an immunologically deficient state (decreased levels of serum IgM and increased levels of IgA and IgE) and is transmitted as an X-linked recessive trait (abnormal gene on Xp11–11.3 chromosome). WASp, the protein made by the gene that is defective in WAS, is impaired. Another condition, acquired immunodeficiency syndrome (AIDS; see p. 21 in Chapter 1), may show multiple eyelid lesions of molluscum or present initially with molluscum eyelid lesions. In addition, multiple epibulbar molluscum lesions have been reported in association with atopic dermatitis.

B.The large pox virus replicates in the cytoplasm and is seen histologically as large, homogeneous, purple, intracytoplasmic inclusion bodies (molluscum bodies) in a markedly acanthotic epidermis.

1.In the deeper layers of the epidermis, near the basal layer, viruses are present as tiny, eosinophilic, intracytoplasmic inclusions. As the bodies extend toward

the surface, they grow so enormous that they exceed the size of the invaded cells.

2. At the level of the epidermal granular layer, the large bodies change from eosinophilic to basophilic.

II.Verruca (wart; Fig. 6.13)

A.Verruca vulgaris (anywhere on the skin), verruca plana

(mainly on face and dorsa of hands), verruca plantaris

(soles of feet), and condyloma acuminatum (glans penis, mucosa of female genitalia, and around anus) are all caused by a variety of the papillomaviruses.

B.Verruca vulgaris appears as a small papule containing a digitated surface or an elongated, filiform wart around the eyelids, usually at or near the lid margin.

C.Histologically, massive papillomatosis, marked by acanthosis, parakeratosis, and orthokeratosis, and containing collections of serum in the stratum corneum at the tips of the digitations, is seen.

1.Characteristically, in early lesions, cells in the upper part of the squamous layer and in the granular layer are vacuolated.

2.In the vacuolated keratocytes, condensation and clumping of dark-staining keratohyaline granules and occasional intranuclear eosinophilic inclusion bodies, which represent virus inclusions, are noted.

III.Viral vesicular lesions

A.Infections with the viruses of variola (smallpox), vaccinia (cowpox), varicella (chickenpox), herpes zoster (shingles), and primary and recurrent herpes simplex all produce similar erythematous–vesicular–pustular and crusted papular eruptions.

B.Histologically, an intraepidermal vesicle characterizes all five diseases (see Fig. 6.5).

1.Marked interepidermal spongiosis involves the deep epidermis and results in swollen epidermal cells that lose their intercellular bridges, causing acantholysis and intraepidermal vesicle formation.

2.Reticular degeneration and necrosis and massive ballooning degeneration involve the superficial and peripheral epidermis and result in enormous swelling of the squamous cells (intracellular edema), causing them to burst so that only the resistant parts of cell walls remain as septa forming a multilocular vesicle.

Ballooning degeneration is specific for viral vesicles, whereas reticular degeneration is seen in acute dermatitis (e.g., poison ivy).

3.Multinucleated epithelial giant cells, often with steel-gray nuclei showing peripheral margination of clumped chromatin, may be seen with herpes simplex and herpes zoster.

4.A dense, superficial, dermal, perivascular lymphohistiocytic inflammation, often with neutrophils infiltrating the epidermis, is seen.

5. Eosinophilic inclusion bodies are found in all five diseases, mainly in the cytoplasm in variola and in vaccinia (Guarnieri bodies). They are occasionally found in the nucleus in variola, but exclusively in the nucleus (usually surrounded by a halo or clear zone) in varicella, herpes zoster, and herpes simplex.

IV. Trachoma and lymphogranuloma venereum (see pp. 231 and 232 in Chapter 7).

Bacterial Diseases

I.Impetigo

A.Impetigo may be caused by staphylococci or streptococci (less common), both of which cause a bullous eruption.

B.Histologically, a superficial bulla directly under the keratin layer is filled with polymorphonuclear leukocytes; cocci are found in neutrophils or free in the bulla.

A

C

II.Staphylococcus—see under Impetigo (previous entry) and

Blepharoconjunctivitis (p. 174 in this chapter).

III.Parinaud’s oculoglandular syndrome (see p. 232 in Chapter 7).

Fungal and Parasitic Diseases

See subsections on fungal and parasitic nontraumatic infections,

pp.85–93 in Chapter 4.

I. Demodicosis (Fig. 6.14)

A.The parasitic mite, Demodex folliculorum, lives in the

hair follicles in humans and certain other mammals, especially around the nose and eyelashes. D. brevis lives in eyelash and small hair sebaceous glands, and in lobules of meibomian glands.

B.Although present in almost all middle-aged and elderly people, and in a significant percentage of younger people, the mites seem relatively innocuous and only rarely produce any symptoms.

Many dermatologists believe that some cases of acne rosacea and folliculitis are caused by large numbers of Demodex, especially in immunosuppressed patients.

C.Histologically, the mite is often seen as an incidental

finding in a hair follicle in skin sections.

B

Fig. 6.13 Verruca vulgaris. A, Clinical appearance of a typical “warty” lesion near the lid margin. B, Histologic section demonstrates papillomatous lesion with marked orthokeratosis (hyperkeratosis) and elongated rete ridges characteristically bent inward (i.e., radiating toward central focus). C, High magnification shows acanthosis, orthokeratosis (hyperkeratosis), intracellular dark-staining keratohyaline granules, and occasional intranuclear eosinophilic inclusion bodies, which represent virus inclusions. Most vacuolated cells contain smaller eosinophilic particles, probably representing degenerative products.

D.No inflammatory reaction is associated with the mite.

II.Phthirus pubis (Fig. 6.15)

A.Infestation of the eyelashes and brow by P. pubis, the crab louse, is called phthiriasis palpebrarum.

B.Transmission from the primary site of infestation, the pubic hair, is usually by hand.

1.The louse, or several lice, grips the bottom of the lash with its claw.

2.The ova (nits) are often present in considerable numbers, adhering to the lashes.

3.A secondary blepharoconjunctivitis may be present.

LID MANIFESTATIONS OF SYSTEMIC DERMATOSES OR DISEASE

Ichthyosis Congenita

See section Congenital Abnormalities earlier in this chapter.

Xeroderma Pigmentosum

See section Congenital Abnormalities earlier in this chapter.

Pemphigus

See p. 229 in Chapter 7.

Ocular involvement in pemphigus vulgaris occurs rarely, and is usually limited to the conjunctiva and/or the eyelids. In contrast, pemphigus foliaceus involves the skin of the eyelid and not the conjunctiva.

Ehlers–Danlos Syndrome (“India-Rubber Man”)

I.Ehlers–Danlos (ED) syndrome consists of a rare, heterogeneous group of disorders characterized by loose-jointed-

ness, hyperextensibility, fragile and bruisable skin with “cigarette paper” scarring, generalized friability of tissues, vascular abnormalities with rupture of great vessels, hernias, gastrointestinal diverticula, and friability of the bowel and lungs.

Most cases are inherited as autosomal-dominant traits, and the others show an X-linked recessive or autosomal-reces- sive pattern (including one probably distinct “ocular” form, i.e. type VI).

The skin in ED syndrome is hyperextensible but not lax. When it is pulled, it stretches; when let go, it quickly springs to the original

position. The skin in cutis laxa (see subsection Cutis Laxa, later), on the other hand, tends to return slowly after it is pulled.

II.The basic problem appears to be an abnormal organization of collagen bundles into an intermeshing network; a defect in the collagen interferes with cross-linking.

Most patients with ED syndrome type VI (ocular type) lack lysyl hydroxylase, an enzyme that catalyzes the hydroxylation of lysine to hydroxylysine. In hydroxylysine deficiency, the structural integrity of collagen is thought to be diminished because hydroxylysine is an important source of cross-links in collagen. A few cases of ED syndrome type VI, however, show normal activity of the enzyme lysyl hydroxylase. Therefore, two variants of ED syndrome type VI may exist.

III.Ocular findings include epicanthus (the most common

finding), hypertelorism, poliosis, strabismus, blue sclera, microcornea, megalocornea, myopia, keratoconus, ectopia lentis, intraocular hemorrhage, neural retinal abnormalities, and angioid streaks.

A

IV. Histologically, conjunctival biopsies studied by light and electron microscopy showed no abnormalities.

T e pathologic lesions in ED syndrome are controversial.

Cutis Laxa

I.In cutis laxa (Fig. 6.16), the extensible skin hangs in loose folds over all parts of the body, especially in those areas where it is normally loose (e.g., around the eyes).

A.The lungs may be involved with emphysema.

B.Cor pulmonale may result in early death.

C.Both autosomal-dominant and recessive forms have been reported.

D.It may also be an acquired condition.

1.Rarely, it is found to involve only the face without a preceding inflammatory condition or systemic

involvement.

II.The basic defect seems to be in the elastic fibers, which are reduced in number, shortened, and show granular

degeneration.

III.Ocular findings include hypertelorism, blepharochalasis, ectropion, and corneal opacities.

B

IV. Histologically, the skin shows fragmentation and granular degeneration of the dermal elastic tissue, along with an increase in the amount of dermal ground substance.

Pseudoxanthoma Elasticum

I.Pseudoxanthoma elasticum is mostly inherited in an autosomal-recessive manner, but also in an autosomaldominant pattern, and mainly involves the skin, the eyes, and the cardiovascular system.

Linkage analysis and mutation detection techniques have shown mutations in the ABCC6 gene.

A.The skin of the face, neck, axillary folds, cubital areas, inguinal folds, and periumbilical area (often with an umbilical hernia) becomes thickened and grooved, with the areas between the grooves diamond-shaped, rectangular, polygonal, elevated, and yellowish (resembling chicken skin).

1.The skin in the involved areas becomes lax, redundant, and relatively inelastic.

2.The skin changes are often not noted until the second decade of life or later.

B.The eyes show angioid streaks (see Fig. 11.38), often with subretinal neovascularization.

1.Examination of the fundus may show a background pattern, called peau d’orange, in the posterior aspect of the eyes, caused by multiple breaks in Bruch’s membrane.

2.The optic nerve may contain drusen.

Drusen of the optic nerve occurs 20 to 50 times more often in pseudoxanthoma elasticum than in the general, healthy population.

C.The cardiovascular system manifestations include weak or absent peripheral pulses, intermittent claudication, angina pectoris, and internal hemorrhages.

II.The basic defect seems to be related to a dystrophy of elastic fibers, but some think collagen fibers are at fault.

III.Histologically, the skin shows elastin abnormalities only in the midepidermis, with elastin band swelling, granular degeneration, and fragmentation. Angioid streaks consist of breaks in Bruch’s membrane.

Erythema Multiforme

I.Erythema multiforme, an acute, self-limited dermatosis, is a common-pathway, cutaneous reaction to drugs, viral or bacterial infections, or unknown causes.

II.Erythema multiforme shows multiform lesions of macules, papules (most common lesion), vesicles, and bullae.

Characteristic “target” lesions are noted as round to oval erythematous plaques that contain central darkening and marginal erythema.

III.A severe form of erythema multiforme, starting suddenly with high fever and prostration and showing predomi-

nantly a bullous eruption of the skin and mucous membranes, including conjunctiva, is Stevens–Johnson syndrome.

The systemic syndrome may lead to death.

IV. Another severe variant of erythema multiforme is toxic epidermal necrolysis (see later).

V.Histologic findings

A.In the skin of Stevens–Johnson syndrome, a dense lymphohistiocytic inflammation obscures the dermoepidermal junction and is associated with progressive necrosis of keratinocytes from the basilar to the uppermost portions of the epidermis.

B.In the conjunctiva, epithelial goblet cells and openings of the accessory lacrimal glands may be destroyed, leading to marked drying of the conjunctiva and epidermidalization.

Both intraepidermal and subepidermal vesiculation may lead to severe scarring, including symblepharon and entropion.

C.The cellular infiltrate consists largely of lymphocytes, mainly T4+ (helper) cells in the dermis and T8+ (cytotoxic) cells in the epidermis.

Toxic Epidermal Necrolysis

I.Toxic epidermal necrolysis (Lyell’s disease; epidermolysis necroticans combustiformis; acute epidermal necrolysis;

scalded-skin syndrome) really consists of two di erent diseases, Lyell’s disease (subepidermal type or true toxic epi-

dermal necrolysis—probably a variant of severe erythema multiforme), and Ritter’s disease (subcorneal type or staphylococcal scalded-skin syndrome—not related to toxic epidermal necrolysis).

A.Toxic epidermal necrolysis (Lyell’s disease) is probably a variant of severe erythema multiforme, frequently occurs as a drug allergy, often overlaps with Stevens–

Johnson syndrome, and histologically resembles the epidermal type of erythema multiforme.

B.Staphylococcal scalded-skin syndrome (Ritter’s disease) is not related to erythema multiforme, occurs largely in the newborn and in children younger than 5 years, and occurs as an acute disease.

1.Its onset begins abruptly with di use erythema accompanied by severe malaise and high fever.

2.Large areas of epidermis form clear fluid-filled, flaccid bullae, which exfoliate almost immediately, so that the denuded areas resemble scalded skin.

Phage group II staphylococci are absent from the bullae but are present at a distant site (e.g., purulent conjunctivitis, rhinitis, or pharyngitis). The bullae are caused by a staphylococcal toxin called exfoliatin.

3.The disease runs an acute course and is fatal in fewer than 4% of cases.

It rarely occurs in adults, but when it does, it may have a mortality rate of over 50%.

II.Histologically, most cases of toxic epidermal necrolysis show a severe degeneration and necrosis of epidermal cells resulting in detachment of the entire epidermis (flaccid bullae).

Epidermolysis Bullosa

I.Epidermolysis bullosa hereditaria (mechanobullous diseases) includes a group of rare, inherited, noninflammatory, nonimmunologic diseases characterized by the susceptibility of the skin to blister after even mild trauma.

An unrelated acquired form is thought to be an autoimmune disease.

II.Ocular complications (especially in recessive epidermolysis bullosa) include loss of eyelashes, obstruction of the lacrimal ducts, and epiphora. Late complications include cicatricial ectropion, exposure keratitis, recurrent corneal erosions and ulcers, and even corneal perforation.

III.Histologically, according to the di erent types, blisters can form in the epidermis, at the lamina lucida, or below the lamina lucida.

Underlying the plasma membrane of the basal epithelial cells is a comparatively electron-lucent zone, the lamina lucida, which separates the trilaminar plasma membrane (approximately 8 nm wide) from the medium-dense basement membrane (lamina densa).

Contact Dermatitis

I.An allergenic or irritating substance applied to the skin may result in contact dermatitis, which is a type IV immunologic reaction requiring a primary exposure, sensitization, and re-exposure to an allergen, and then an immunologic delay before clinical expression of the dermatitis.

A.Contact dermatitis is one of the most common abnormal conditions a ecting the lids.

B.Agents such as cosmetics and locally applied atropine and epinephrine may produce a contact dermatitis.

C.Contact dermatitis may be present in three forms:

1.An acute form with di use erythema, edema, oozing, vesicles, bullae, and crusting

2.A chronic form with erythema, scaling, and thick, hard, leathery skin (lichenification)

3.A subacute form showing characteristics of acute and chronic forms

Anterior subcapsular cataracts (usual form) and posterior subcapsular cataracts (rare form) seem to occur with increased frequency in patients who have a history of atopia.

II.Histology

A.In the acute stage, epidermal (intraepidermal vesicles) and dermal edema predominate along with a lymphocytic infiltrate.

Spongiosis or intercellular edema between squamous cells contributes to the formation of vesicles (unilocular bullae). Intracellular edema, however, results in reticular degeneration and the formation of multilocular bullae.

B.In the chronic stage, there is acanthosis, orthokeratosis, and some parakeratosis together with elongation of rete pegs.

1.Mild spongiosis is present, but vesicle formation does not occur.

2.In the dermis, perivascular lymphocytes, eosinophils, histiocytes, and fibroblasts are found.

Histologically, a distinction cannot be made between a primary allergic contact dermatitis and an irritant-induced or toxic dermatitis, except possibly in the early stage. Atopic dermatitis, which is a chronic, severely pruritic dermatitis associated with a personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis), does not show vesicles, although it does show lichenified and scaling erythematous areas, which when active may show oozing and crusting, but no vesicles.

Collagen Diseases

I. Dermatomyositis (see p. 540 in Chapter 14).

II.Periarteritis (polyarteritis) nodosa

A.Periarteritis nodosa is a disease of unknown cause characterized by a panarteritis of smalland medium-sized, muscular-type arteries of kidney, muscle, heart, gastrointestinal tract, and pancreas, but not of the central nervous system or lungs, and rarely of the skin.

A benign cutaneous form of periarteritis nodosa exists as a chronic disease limited to the skin and subcutaneous tissue.

B.Histologically, four stages may be seen:

1.The degenerative or necrotic stage: foci of necrosis

(fibrinoid necrosis) involve the coats of the artery and may result in localized dehiscences or aneurysms.

2.The inflammatory stage: inflammatory cells, predominantly neutrophils but also eosinophils and lymphocytes, infiltrate the necrotic areas.

3.The granulation stage: healing occurs with the formation of granulation tissue, which may occlude the vascular lumens.

4.The fibrotic stage: healing ends with scar formation.

III.Lupus erythematosus can be subdivided into three types:

1.Chronic discoid, which is limited to the skin

a.Discoid lupus erythematosus involving the eyelids is rare. It may present as madarosis.

b.Periorbital edema and erythema are rare cutaneous manifestations of discoid lupus erythematosus.

2.Intermediate or subacute, which has systemic symptoms in addition to skin lesions

3.Systemic, which is dominated by visceral lesions

Transition from the chronic discoid type to the systemic type occurs infrequently.

A.Histology shows five main characteristics (when they involve the skin, the three types of lupus erythematosus di er only in degree of involvement; the systemic form is the most severe).

B.All five histologic characteristics are not necessarily present in each case.

1.Orthokeratosis with keratotic plugging found mainly in the follicular openings but also found elsewhere

2.Atrophy of the squamous layer of epidermis and of rete pegs

3.Liquefaction degeneration of basal cells (i.e., vacuolation and dissolution of basal cells—most significant finding)

4.Focal lymphocytic dermal infiltrates mainly around dermal appendages

5.Edema, vasodilatation, and extravasation of erythrocytes in the upper dermis

IV. Scleroderma (Fig. 6.17) exists in two forms: (1) a benign circumscribed (morphea) form, which almost never pro-

gresses or transforms to the systemic form; and (2) a systemic form (progressive systemic sclerosis), which may prove fatal.

A.The characteristic lesion is a sclerotic plaque with an ivory-colored center and appearing bound-down when palpated.

B.Ocular findings include pseudoptosis secondary to swollen lids, hyposecretion of tears with trophic changes in the cornea and conjunctiva (Sjögren’s syndrome), ocular muscle palsies, temporal arteritis, unilateral glaucoma,exophthalmos,neural retinal cotton-wool patches, signs of hypertensive retinopathy, defects of the retinal pigment epithelium near the macula, central serous choroidopathy, and fluorescein leaks of thickened retinal capillaries.

C.Histologically, the morphea and the systemic forms are similar, if not identical.

1.Early, the dermal collagen bundles appear swollen and homogeneous and are separated by edema.

Round inflammatory cells, mainly lymphocytes, are found around edematous blood vessel walls and between collagen bundles (panniculitis).

2.In the intermediate stages, the subcutaneous tissue is infiltrated by round inflammatory cells, dermal collagen becomes further thickened, and dermal adnexa are involved in the process.

Blood vessel walls show edema with intimal proliferation and narrowing of their lumina.

3.In the late stages, the dermis is thickened by the addition of new collagen at the expense of subcutaneous tissue.

a.The subcutaneous fat is replaced by collagen and blood vessels are fibrotic.

b.The thickened dermis contains hyalinized, hypertrophic, closely packed collagen bundles, atrophic sweat glands trapped in the midst of collagen bundles, decreased fibrocytes, and few or no sebaceous glands or hair structures.

c.Inflammation is minor or absent.

4.The overlying epidermal structure, including rete ridges, is rather well preserved except in the late stages of the systemic form, when atrophy occurs.

5.The underlying muscle, especially in the systemic form, may be involved and shows early degeneration, swelling, and inflammation, followed by late

fibrosis.

Granulomatous Vasculitis

I.Wegener’s granulomatosis

A.The classic form of Wegener’s granulomatosis is characterized by generalized small-vessel vasculitis, necrotizing granulomas,focal necrotizing glomerulonephritis, and vasculitis of the upper and lower respiratory tract.

1.Typical presentation is a persistent inflammatory nasal and sinus disease associated with systemic symptoms of fever, malaise, and migratory arthritis.

2.Serum antineutrophilic cytoplasmic antibodies

(ANCAs) are a sensitive and rather specific marker for Wegener’s granulomatosis.

3.A limited form of Wegener’s granulomatosis lacks renal involvement (see Fig. 8.59).

4.In both the classic and limited forms, most of the ocular findings can occur.

5.Ocular involvement, most commonly orbital, occurs in up to 50%, and neurologic involvement in up to

54% of cases.

B.Ocular findings include dry eyes, nasolacrimal obstruction, blepharitis, conjunctivitis, scleritis or episcleritis, corneoscleral ulceration, uveitis, retinal vein occlusion, retinal pigmentary changes, acute retinal necrosis, choroidal folds, optic neuritis, and exophthalmos secondary to orbital involvement. It has presented as cicatricial conjunctival inflammation with trichiasis.

C.Histologically, the classic triad of necrotizing vasculitis (granulomatous and disseminated small-vessel), tissue necrosis, and granulomatous inflammation are characteristic.

T ehvasculitis can be seen in three forms:

1.Microvasculitis or capillaritis—infiltration and destruction of capillaries, venules, and arterioles by neutrophils

2.Granulomatous vasculitis (most characteristic)— granulomatous vasculitis involving small or medium-sized arteries and veins

3.Necrotizing vasculitis involving small or mediumsized arteries and veins but not associated with granulomatous inflammation

II.Allergic granulomatosis (allergic vasculitis, Churg–Strauss syndrome) involves the same-size arteries as periarteritis but di ers in having respiratory symptoms, pulmonary infiltrates, systemic and local eosinophilia, intravascular and extravascular granulomatous lesions, and often cutaneous and subcutaneous nodules and petechial lesions.

III. Temporal arteritis (see p. 507 in Chapter 13)

Vasculitis-LikeDisordersandLeukemia/Lymphoma

I.Natural killer (NK) T-cell lymphoma (polymorphic reticulosis or angiocentric T-cell lymphoma)

A.NK cells are a distinct non-T, non-B lineage of lymphocytes that mediate major histocompatibility complex-unrestricted cytotoxicity.

B.NK/T-cell malignancies are uncommon and were previously known as polymorphic reticulosis or angiocentric T-cell lymphomas.The World Health Organization further divides these lesions into NK/T-cell lymphoma

(nasal and extranasal) type and aggressive NK-cell leukemia.

1.Its lymphoma cells are CD2+, CD56+, and CD3epsilon+.

C.Relatively common in Asia,Mexico,and South America, but extremely rare in most western countries.

D.Lethal midline granuloma form of NK/T-cell lymphoma.

1.Rare entity that usually arises in the nasal cavity.

2.It has a male preponderance, and a wide age range.

3.It is extremely aggressive, and has approximately a

20% 5-year survival.

E.Apoptosis, necrosis, and angioinvasion are typical features of the lymphoma.

F.Invasion and blockage of blood vessels by lymphoma cells result in marked ischemic necrosis of normal and neoplastic tissues.

G.The leukemic form tends to a ect younger patients, who often present with advanced disease and multiple organ involvement.

1.Survival is particularly brief.

H.Gamma-delta T-cell receptor clonality is the most common T-cell receptor rearrangement in several T- cell lymphomas, including NK/T-cell lymphoma.

I.Characteristic patterns of genomic alteration typify aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma, nasal type.

J.Epstein–Barr virus (EBV) can encode multiple genes that drive cell proliferation and confer resistance to cell death, including two viral proteins that mimic the e ects of activated cellular signaling proteins.

1.Infection with the virus is associated with a variety of lymphomas and lymphoproliferative disorders, including Burkitt’s lymphoma; NK/T-cell lymphoma, lymphoma and lymphoproliferative dis-

eases in immunocompromised individuals, and

Hodgkin’s lymphoma.

2.The presence of EBV-infected cells in the aqueous humor originating from nasal NK/T-cell lymphoma has been reported.

K.The majority of ocular adnexal lymphomas are marginal zone B-cell (mucosal-associated lymphoid tissue: MALT) lymphomas.

L.In one Korean study, only 2/68 cases were NK/T cell lesions.

M.NK/T-cell lymphoma has occasionally involved the eye.

N.Extranodal nasal type NK/T-cell lymphoma has involved the posterior orbit, lungs, uterus, adrenal gland, pericardium, and meninges in a 41-year-old woman with a rapidly fatal clinical course.

O.Lethal midline granuloma in NK/T-cell lymphoma has presented as conjunctival swelling of the left upper eyelid. The tumor was exceptional because this patient was Caucasian and was not immunosuppressed.

P.Other rare T-cell lymphomas involving the eyelids have been reported.

A

II.Symmetrical leukemia cutis of the eyelids accompanied by B-cell chronic lymphocytic leukemia has been reported.

The di erential diagnosis for a cause of such eyelid swell-

ing includes other tumors, hyperthyroidism, nephrotic syndrome, and hypoalbuminemia. Additionally, metastasis from the histiocytoid form of breast carcinoma may produce eyelid swelling.

III.Primary di use large B-cell lymphoma has presented as an ulcerating lesion of the eyelid tarsal surface. Positivity of monoclonal antibodies for CD20 and CD79a, and polyclonal antibodies for lambda chains, confirmed the

diagnosis.

IV. Mycosis fungoides, which is a cutaneous T-cell lymphoma, has presented as a severe, progressive, full-thickness, lowereyelid ulceration in a 72-year-old man.

Xanthelasma

I.Xanthelasma (Fig. 6.18) most commonly occurs in middleaged or elderly people who usually, but not always, have normal serum cholesterol levels.

B