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

A.Xanthelasma is a form of xanthoma [i.e., a tumor containing fat mainly within cells (intracellular)], whereas a lipogranuloma (e.g., a chalazion) is a tumor containing fat mainly outside cells (extracellular).

B.It may occur in primary hypercholesterolemia or with nonfamilial serum cholesterol elevation.

Evidence suggests that xanthelasma may be associated with qualitative and quantitative abnormalities of lipid metabolism (increased levels of serum cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B; and decreased levels of high-density lipoprotein subfraction 2 cholesterol) that may favor lipid deposition in the skin and arterial wall, that xanthelasma is a marker of dyslipidemia, and that patients who have xanthelasma should undergo a full lipid profile to identify those who are at an increased risk for cardiovascular disease.

C.Xanthelasma is associated with other xanthomas or with hyperlipemia syndromes in approximately 5% of patients.

II.After initial surgical excision, the recurrence rate is slightly less than half.

III.Recurrence is more likely if all four lids are involved, if an underlying hyperlipemia syndrome is present, or if there have been previous recurrences.

Lid lesions resembling xanthelasma occur in Erdheim–Chester disease, which is an idiopathic, widespread, multifocal, granulomatous disorder characterized by cholesterol-containing foam cells infiltrating viscera and bones, including the orbit, and sometimes bilateral xanthelasmas. When the orbit is involved, there tends to be bilateral involvement. Histologically, the lesions show broad sheets of lipid-filled xanthoma cells and scattered foci of chronic inflammatory cells, mainly lymphocytes and plasma cells, along with significant fibrosis. Touton giant cells may be found. A localized, adult-onset, periocular xanthogranuloma with severe asthma may be a distinct entity (pseudo Erdheim–Chester disease), or may be a variant of Erdheim–Chester disease or of necrobiotic xanthogranuloma, and needs to be differentiated from other histiocytic proliferations.

IV. Xanthelasmas appear as multiple, soft, yellowish plaques most commonly at the inner aspects of the upper and lower lids.

V.Histologically, lipid-containing foam cells are found in the superficial dermis. The cells cluster around blood vessels and may even involve their walls.

Necrobiotic Xanthogranuloma

I.Necrobiotic xanthogranuloma, an entity of unknown cause, a ects both sexes equally.

A.Cutaneous involvement is universal, with the periorbital region a site of predilection.

B.The typical lesion is an indurated papule, nodule, or plaque that is violaceous to red-orange, often with a central ulceration or atrophy.

II.The most characteristic abnormal laboratory finding is a paraproteinemia.

A.Monoclonal gammopathy associated with IgG is most common, but gammopathy may also be associated with IgA and others.

B.Bone marrow biopsy may show di erent abnormalities,

the most serious of which is multiple myeloma.

III.Systemic findings include hepatomegaly, splenomegaly, lymphadenopathy, arthralgia or arthritis, pulmonary disease, and hypertension.

IV. Histologically, granulomatous masses are separated by broad bands of hyaline necrobiosis. Giant cells are of the foreign-body type and often the Touton type.

The lesions most closely resemble necrobiosis lipoidica diabeticorum, but they may also be confused with juvenile xanthogranuloma, granuloma annulare, erythema induratum, atypical sarcoidosis, Erdheim–Chester disease, Rothman–Makai panniculitis, foreign-body granulomas, various xanthomas, nodular tenosynovitis, and the extra-articular lesions of proliferative synovitis.

Juvenile Xanthogranuloma

Juvenile xanthogranuloma of the eyelid is uncommon; however, it has presented as a large, solitary, pedunculated lesion involving the eyelid in a 31-month-old Japanese girl. Systemic evaluation was unremarkable.

See also p. 343 in Chapter 9.

Amyloidosis

Rarely, nodular cutaneous amyloid tumors of the eyelid may occur in the absence of systemic amyloidosis.

See also p. 238 in Chapter 7.

Malignant Atrophic Papulosis (Degos’ Disease)

I.The syndrome is a rare cutaneovisceral syndrome of unknown cause characterized by the di use eruption of asymptomatic, porcelain-white skin lesions. Death usually occurs within a few months.

II.Ocular lesions include porcelain-white lid lesions; a characteristic white, avascular thickened plaque of the conjunctiva; telangiectasis of conjunctival blood vessels and microaneurysms; strabismus; posterior subcapsular cataract, choroidal lesions such as peripheral choroiditis, small plaques of atrophic choroiditis, gray avascular areas, and discrete loss of choroidal pigment and peripheral retinal pigment epithelium; visual field changes; and intermittent diplopia and papilledema associated with progressive central nervous system involvement.

III.Histologically, capillaries are occluded by endothelial proliferation and swelling; the endarterioles show endothelial proliferation, swelling, and fibrinoid necrosis involving only the intima; arterial involvement is greater than venous; thrombosis may occur secondary to endothelial changes; and no significant inflammatory cellular response is noted.

Calcinosis Cutis

I.Calcinosis cutis has three forms

A.Metastatic calcinosis cutis, or calcium deposition secondary to either hypercalcemia (e.g., with parathyroid neoplasm, hypervitaminosis D, excessive intake of milk and alkali, and extensive destruction of bone by osteomyelitis or metastatic carcinoma) or hyperphosphatemia (e.g., with chronic renal disease and secondary hyperparathyroidism)

B.Dystrophic calcinosis cutis (i.e., deposition in previously damaged tissue)

C.Subepidermal calcified nodule [i.e., a single (rarely two), small, raised, hard nodule, occasionally present at birth]

II.Histologically, forms A and B show large deposits of calcium in the subcutaneous tissue and small, granular deposits in the dermis, whereas form C shows deposits of irregular granules and globules in the upper dermis. The calcium appears as deep blue or purple granules.

Lipoid Proteinosis

I.Lipoid proteinosis (Fig. 6.19) is a rare condition of the lids and mucous membranes that has an autosomal-recessive inheritance pattern. It has been reported to involve siblings. The disorder maps to 1q21, and is caused by mutations in the extracellular matrix protein 1 gene.

II.Multiple, waxy, pearly nodules, 2 to 3 mm in diameter, cover the lid margins linearly along the roots of the cilia. The lesions are said to be pathognomonic for the disorder.

III.Whitish plaques are found on mucous membranes.

IV. Histologically, a papillomatosis of the epidermis occurs along with large dermal collections of an amorphous, eosinophilic, PAS-positive material without inflammation.

Electron microscopy shows large masses of an extracellular, finely granular, amorphous material without a fibrillar structure.

Idiopathic Hemochromatosis

I.Brown pigmentation of the lid margin, conjunctiva, cornea, and around the disc margin has been described (see p. 24

in Chapter 1).

II.Histologically, the brown pigmentation of the lid margin and conjunctiva is caused by an increased melanin content of the epidermis, especially the basal layer.

A.The peripapillary pigmentation may result from small amounts of iron in the peripapillary retinal pigment epithelium.

B.Intraocular deposition of iron is most prominent in the nonpigmented ciliary epithelium but may also be found in the sclera, corneal epithelium, and peripapillary retinal pigment epithelium.

Relapsing Febrile Nodular Nonsuppurative

Panniculitis (Weber–Christian Disease)

Pigmentation

I.Argyrosis

A. Periocular and eyelid skin can be involved in argyrosis,

resulting in the typical grayish discoloration.

1.Chronic use of eyelash tint has been an unusual cause for the disorder.

II.Bimatoprost treatment for glaucoma may result in increased melanin pigmentation of the periocular skin without melanocyte proliferation. The keratinocytes in these patients have abundant mature melanosomes compared to controls.

CYSTS, PSEUDONEOPLASMS,

AND NEOPLASMS

Benign Cystic Lesions

I.The condition, which is of unknown cause, occurs most often in middle-aged and elderly women. It is characterized by malaise and fever and by the appearance of crops of tender nodules and papules in the subcutaneous fat, usually on the trunk and extremities.

II.Ocular findings include necrotic eyelid and subconjunctival nodules and, rarely, ocular proptosis, anterior uveitis, and macular hemorrhage.

III.Histologically, three stages can be seen.

A.An early, rapid phase shows fat necrosis and an acute inflammatory infiltrate of neutrophils, lymphocytes, and histiocytes.

B.A second stage shows a granulomatous inflammation with lipid-filled macrophages, epithelioid cells, and foreign-body giant cells.

C.A third stage of fibrosis may result clinically in depression of the overlying skin.

I.Epidermoid (Fig. 6.20) and dermoid (see Figs 14.12 and 14.13) cysts* are congenital lesions that tend to occur at the outer upper portion of the upper lid.

II.Epidermal inclusion cysts* (see Fig. 6.20) appear identical histologically to congenital epidermoid cysts; the former, however, instead of occurring congenitally, are caused by traumatic dermal implantation of epidermis or are follicular cysts of the hair follicle infundibulum that result from occlusion of its orifice, sometimes the result of trauma.

Milia are identical histologically to epidermal inclusion cysts; they differ only in size, milia being the smaller. They may represent retention cysts, caused by the occlusion of a pilosebaceous follicle

*Rupture of any of these cysts results in a marked granulomatous, foreignbody inflammatory reaction in the adjacent tissue (see Fig. 14.13).

or of sweat pores, may represent benign keratinizing tumors, or they may have a dual origin. Multiple epidermal inclusion cysts, especially of the face and scalp, may occur in Gardner’s syndrome.

Histologically, the cyst is lined by epithelial cells essentially identical to surface epithelium. The cavity contains loose, laminated keratin.

III. Sebaceous (pilar, trichilemmal) cysts* (see footnote on p. 188) are caused by obstruction of the glands of Zeis, of the meibomian glands, or of the isthmus portion of the hair follicle, from which keratinization analogous to the outer root sheath of the hair or trichilemma arises.

Histologically, the cyst is lined by epithelial cells that possess no clearly visible intercellular bridges.

A.The peripheral layer of cells shows a palisade arrangement, and the cells closest to the cavity are swollen without distinct cell borders.

B.The cyst cavity contains an amorphous eosinophilic material.

The epithelial cells lining the sebaceous cyst are different from the typical cells lining an epidermal inclusion cyst, in which the cells are stratified squamous epithelium. The cystic contents of the sebaceous cyst are different from the horny (keratinous) material filling the epidermal inclusion cyst. “Old” sebaceous cysts, however, may show stratified squamous epithelial metaplasia of the lining, resulting in keratinous material filling the cyst and producing a picture identical to an epidermal inclusion cyst, unless a microscopic section accidentally passes through the occluded pore of the sebaceous cyst.

IV. Comedo (blackhead, primary lesion of acne vulgaris) presents clinically as follicular papules and pustules.

A.The comedo occludes the sebaceous glands of the pilosebaceous follicle, which may undergo atrophy.

B.Histologically, the comedo results from intrafollicular orthokeratosis that leads to a cystic collection of sebum and keratin.

C.With rupture of the cyst wall, sebum and keratin are released, causing a foreign-body giant cell granuloma-

tous reaction.

Bacteria, especially Propionibacterium acnes, may be found.

D.Eventually, epithelium grows downward and encapsulates the inflammatory infiltrate.

E.The lesion heals by fibrosis.

V.Steatocystoma

A.Steatocystoma may occur as a solitary cyst (simplex) or as multiple cysts (multiplex), the latter often inherited as an autosomal-dominant trait.

B.The small, firm cysts, which exude an oily or creamy fluid when punctured, are derived from cystic dilatation of the sebaceous duct that empties into the hair follicle.

C.Histologically, a thick, eosinophilic cuticle covers the several layers of epithelial cells lining the cyst wall. Sebaceous lobules are present either within or close to the cyst wall.

VI. Calcifying epithelioma of Malherbe (pilomatricoma; Fig. 6.21)

A.Calcifying epithelioma of Malherbe is a cyst derived from the hair matrix that forms the hair.

B.It can occur at any age, but most appear in the first two decades of life; it presents as a solitary tumor, firm, deep-seated, and covered by normal skin. Nevertheless, it is frequently misdiagnosed when occurring in young adults.

1.If superficial, it produces a blue-red discoloration.

C.Histologically, the tumor is sharply demarcated and composed of basophilic and shadow cells.

1.Basophilic cells closely resemble the basaloid cells of a basal cell carcinoma (dark basophilic nucleus surrounded by scant basophilic cytoplasm).

2.Shadow cells stain faintly eosinophilic, have distinct cell borders, and instead of nuclei show central, unstained regions where the nuclei should be.

a.In older tumors, basophilic cells may have disappeared completely so that only shadow cells remain.

3.The stroma may show areas of keratinization, fibrosis, calcification, foreign-body granuloma, and ossification.

4.Follicular hybrid cyst of the tarsus, which had features of pilomatricoma and steatocystoma, has been reported to perforate the palpebral surface of the conjunctiva.

D.Pilomatrix carcinoma may develop from malignant transformation of a benign pilomatricoma or may arise

de novo.

VII. Hidrocystoma (Figs 6.22 and 6.23)

A.Cysts resulting from occlusion of the eccrine or apocrine duct are referred to as hidrocystomas.

1.Apocrine hidrocystomas usually occur in adults as solitary (sometimes multiple) lesions, often with a blue tint, and are usually located in the skin near the eyes.

2.Eccrine hidrocystomas may be solitary or multiple, and clinically are indistinguishable from apocrine hidrocystomas.

B.Histologically, the apocrine hidrocystoma, which is derived from the apocrine sweat glands of Moll, is an irregularly shaped cyst, and has an outer myoepithelium layer and an inner (luminal) layer of columnar epithelium, showing apical decapitation secretion.

T eheccrine hidrocystoma, which is derived from the eccrine sweat glands, is more rounded and shows a flattened wall that contains one or two layers of cuboidal epithelium and sometimes contains papillary projections into the lumen of the cysts. Mean age at diagnosis is 59 years; 71% of lesions are single; and 87% are located near but not on the eyelid margin.

The apocrine hidrocystoma is more likely to be proliferative than the eccrine hidrocystoma.

A

C

Benign Tumors of the Surface Epithelium

I.Papilloma (Figs 6.24 and 6.25)

A.Papilloma is an upward proliferation of skin resulting in an elevated irregular lesion with an undulating surface.

B.Six conditions show this type of proliferation as a predominant feature: (1) nonspecific papilloma (most common); (2) nevus verrucosus (epidermal cell nevus;

Jadassohn); (3) acanthosis nigricans; (4) verruca vulgaris (see earlier under subsection Viral Diseases); (5)

seborrheic keratosis; and (6) actinic keratosis (see later under section Precancerous Tumors of the Surface Epithelium).

C.Histologically, a papilloma is characterized by fingerlike projections or fronds of papillary dermis covered by epidermis showing a normal polarity but some degree of acanthosis and hyperkeratosis, along with variable parakeratosis and elongation of rete pegs.

1.The dermal component may have a prominent vascular element.

2.Usually, histologic examination of a papillomatous lesion indicates which of the di erent papillomatous conditions is involved.

B

Fig. 6.21 Calcifying epithelioma of Malherbe (pilomatricoma). A, Clinical photo of lesion involving the lateral aspect of the right lower eyelid.

B, Low-magnification photomicrograph demonstration position of lesion relative to the skin surface and light areas of necrosis containing shadow cells and dark basophilic cells. C, High magnification of pale shadow cells on left and dark basophilic cells on right. (A and B, Courtesy of Dr.

Morton Smith; C, courtesy of Armed Forces Institute of Pathology, Washington, DC, accession number 984935.)

D.Nonspecific papilloma (see Fig. 6.25)

1.Nonspecific papilloma, a polyp of the skin, is usually further subdivided into a broad-based and a narrowbased type.

a.The broad-based type is called a sessile papilloma.

b.The narrow-based type is called a pedunculated papilloma, a fibroepithelial papilloma, acrochordon, or simply a skin tag.

2.Histologically, finger-like projections of papillary dermis are covered by normal-thickness epithelium showing elongation of rete ridges and orthokeratosis.

E.Nevus verrucosus (epidermal cell nevus; Jadassohn)

1.Nevus verrucosus consists of a single lesion present at birth or appearing early in life.

2.Histologically, the lesion consists of closely set, papillomatous, orthokeratotic papules, marked acanthosis, and elongation of rete pegs.

F.Acanthosis nigricans

1.Acanthosis nigricans exists in five types, all showing papillomatous and verrucous brownish patches predominantly in the axillae, on the dorsum of fingers, on the neck, or in the genital and submammary regions.

a.Hereditary (benign) type: not associated with an internal adenocarcinoma, other syndromes, or endocrinopathy

b.Benign type: associated with insulin resistance, endocrine disorders, and other disorders such as Crouzon’s disease

c.Pseudoacanthosis nigricans: a reversible condition related to obesity

d.Drug-induced type

e.Adult (malignant) type: associated with an internal adenocarcinoma, most commonly of the stomach

f.Histologically, the first four are identical and show marked orthokeratosis and papillomatosis and mild acanthosis and hyperpigmentation. The fifth has additional malignant cytologic changes.

G.Seborrheic keratosis results from an intraepidermal proliferation of benign basal cells (basal cell acanthoma; see Fig 6.24; Fig. 6.26).

1.Seborrheic keratosis increases in size and number with increasing age and is most common in the elderly.

sk s

A

B

Fig. 6.26 Seborrheic keratosis. A, The “greasy” elevated lesion is present in the middle nasal portion of the left lower lid. Biopsy showed this to be a seborrheic keratosis (sk). The smaller lesion just inferior and nasal to the seborrheic keratosis proved to be a syringoma (s; see Fig. 6.38). Another seborrheic keratosis is present on the side of the nose. B, Histologic section shows a papillomatous lesion that lies above the skin surface and is blue. The lesion contains proliferated basaloid cells and keratin-filled cysts.

2.The lesions tend to be sharply defined, brownish, softly lobulated papules or plaques with a rough, almost warty surface.

3.Histologically, the lesion has a papillomatous configuration and an upward acanthosis so that it sits as a “button” on the surface of the skin and contains

a proliferation of cells closely resembling normal basal cells, called basaloid cells.

The histologic appearance of a seborrheic keratosis is variable. The lesion frequently contains cystic accumulations of horny (keratinous) material. Six subtypes are recognized: acanthotic, hyperkeratotic, reticulated (adenoid), clonal, irritated (IFK; see later), and melanoacanthoma. All show acanthosis, orthokeratosis, and papillomatosis. Some may show an epithelial thickening (acanthotic) or a peculiar adenoid pattern in which the epithelium proliferates in the dermis in narrow, interconnecting cords or tracts (reticulated). It may be deeply pigmented (melanoacan-

thoma) and even confused clinically with a malignant melanoma.

4.IFK (irritated seborrheic keratosis, basosquamous cell epidermal tumor, basosquamous cell acanthoma; Fig. 6.27) resembles a seborrheic keratosis but has an additional squamous element.

a.IFK is a benign epithelial skin lesion found most frequently on the face.

1). Middle-aged or older people are usually a ected.

2). The lesion typically presents as an asymptomatic, pink to flesh-colored, small papule, rarely pigmented.

Rarely, IFK may recur rapidly after excision. Re-exci- sion cures the lesion.

b.It usually shows a papillomatous configuration, exists as a solitary lesion, and may exhibit rapid growth.

c.Most IFKs are identical to irritated seborrheic keratoses, whereas others may be forms of verruca vulgaris or a reactive phenomenon related to pseudoepitheliomatous hyperplasia

(see later).

d.Histologically, IFK is similar to a seborrheic keratosis or verruca vulgaris but with the addition of basaloid cells around whorls of squamous epithelium forming squamous eddies.

II.Pseudoepitheliomatous hyperplasia (invasive acanthosis, invasive acanthoma, carcinomatoid hyperplasia; Fig. 6.28) consists of a benign proliferation of the epidermis simulating an epithelial neoplasm.

A.It is seen frequently at the edge of burns or ulcers, near neoplasms such as basal cell carcinoma, malignant melanoma, or granular cell tumor, around areas of chronic inflammation such as blastomycosis, scrofuloderma, and gumma, or in lesions such as keratoacanthoma and perhaps IFK.

B.Histologically, the usual type of pseudoepitheliomatous hyperplasia, no matter what the associated lesion, if any, has the following characteristics:

1.Irregular invasion of the dermis by squamous cells that may show mitotic figures but do not show dyskeratosis or atypia

2.Frequent infiltration of the squamous proliferations by leukocytes, mainly neutrophils

Although an inflammatory infiltrate is frequently seen under or around a squamous cell carcinoma, the inflammatory cells almost never infiltrate the neoplastic cells directly. If inflammatory cells admixed with squamous cells are seen, especially if the inflammatory cells are neutrophils, a reactive lesion such as pseudoepitheliomatous hyperplasia should be considered.

III.Keratoacanthoma (Fig. 6.29)

A.Keratoacanthoma may be a type of pseudoepitheliomatous hyperplasia, although most dermatopathologists

A

C

now believe it is a type of low-grade squamous cell carcinoma.

B.It consists of a solitary lesion (occasionally grouped lesions) that develops on exposed (usually hairy) areas of skin in middle-aged or elderly people, grows rapidly for 2 to 6 weeks, shows a raised, smooth edge and an umbilicated, crusted center, and then involutes in a few months to a year, leaving a depressed scar.

Rarely, keratoacanthoma can occur on the conjunctiva.

C.Histologically, keratoacanthoma is characterized by its domeor cup-shaped configuration with elevated wall and central keratin mass seen under low magnification, and by acanthosis with normal polarity seen under high magnification.

T ehdeep edges of the tumor appear wide and blunt, rather than infiltrative.

In the past, the tumor has been confused with “aggressive” squamous cell carcinoma. The typical noninvasive, elevated cup shape with a large central keratin core, as seen under lowpower light microscopy, along with the benign cytology and wide and blunt deep edges seen under high-power light microscopy, should lead to the proper diagnosis of keratoacanthoma with no difficulty. If, however, only a small piece of

B

Fig. 6.27 Inverted follicular keratosis. A, Clinical appearance of lesion in the middle of the right lower lid. B, Histologic section shows a papillomatous lesion above the skin surface composed mainly of acanthotic epithelium. C, Increased magnification shows separation or acantholysis of individual squamous cells that surround the characteristic squamous eddies.

tissue (e.g., a partial biopsy) is available for histopathologic examination, it may be difficult or impossible to differentiate a keratoacanthoma from squamous cell carcinoma, and indeed, some keratoacanthomas show areas of undisputed squamous cell carcinoma differentiation. The superficially invasive variant of keratoacanthoma, called invasive keratoacanthoma, may not involute spontaneously and probably represents a form of squamous cell carcinoma.

IV. Warty dyskeratoma

A.It presents primarily on the scalp, face, or neck as an umbilicated, keratotic papule, resembling a keratoacanthoma.

B.Histologically, a cup-shaped invagination is filled with keratin and acantholytic, dyskeratotic cells. Villi of dermal papillae lined by a single layer of basal cells project into the base of the crater.

Corps ronds (i.e., dyskeratotic cells containing pyknotic nuclei, surrounded by a clear halo, present in the granular layer at the entrance to the invagination) are reminiscent of Darier’s disease.

V.Large cell acanthoma

A.Large cell acanthoma appears as a slightly keratotic, solitary lesion, usually smaller than 1 cm, and has a

predilection for the face and neck, followed by the upper extremities.

B.Histologically, it is a benign epidermal lesion showing a moderately acanthotic epidermis that contains sharply circumscribed, uniformly hyperplastic keratinocytes, a

wavy, orthokeratotic, and parakeratotic granular cell layer, and sometimes a papillomatosis.

Dysplastic enlarged keratinocytes and an increased number of Civatte bodies (necrotic keratinocytes) may be found.