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

keratinized (Fig. 6.4A; see Fig. 7.17). The keratinizing cells show abundant pink (eosinophilic) cytoplasm and small, normal-appearing nuclei.

In contrast, necrotic keratinocytes have homogeneous pink cytoplasm and nuclear karyolysis and pyknosis.

II.Dyskeratosis is characteristic of benign familial intraepithelial dyskeratosis, Darier’s disease, and Bowen’s disease, and is sometimes seen in actinic keratosis, in squamous cell carcinoma, and after sunburn.

Acantholysis

I.Acantholysis is a separation of epidermal cells that results from a variety of pathologic processes, and causes a dissolution or degeneration of the intercellular connections (see Figs 6.5 and 6.27).

II.Acantholysis is commonly seen in viral vesicles (e.g., herpes simplex), inverted follicular keratosis (IFK), pemphigus, and Darier’s disease.

Bulla

I.A bulla is a fluid-filled space in the epidermis or beneath it (see Fig. 6.5).

Spongiosis is fluid accumulation between keratinocytes (intercellular edema), which may lead to cleft or vesicle formation. It is commonly seen in inflammatory conditions, especially the spectrum of dermatitides. Ballooning is intracellular edema characteristic of virally infected cells.

II.A small bulla is arbitrarily called a vesicle.

Vesicles and bullae may arise from primary cell damage or acantholysis. They may be located under the keratin layer (subcorneal), between the epithelium and dermis (junctional), or in the middle layers of epithelium.

Atrophy

I.Atrophy (see subsection Atrophy later, under Aging, and Fig. 6.8) is: (1) thinning of the epidermis; (2) smoothing

or diminution (e acement) of rete ridges (“pegs”); (3) disorder of epidermal architecture; (4) diminution or loss of epidermal appendages such as hair; and (5) alterations of the collagen and elastic dermal fibers.

II.Atrophy is commonly seen in aging.

It may also be seen in the epidermis overlying a slowgrowing tumor in the corium.

Atypical Cell

I.An atypical cell (see Fig. 6.4B) is one in which the normal

nucleus-to-cytoplasm ratio is altered in favor of the nucleus, which stains darker than normal (hyperchromasia), may show an abnormal configuration (giant form or multinucleated form), may have an abnormal nuclear configuration (e.g., indented, cerebriform, multinucleated), or may

Fig. 6.5 Varieties of bullae encountered in skin.

contain an abnormal mitotic figure (e.g., tripolar metaphase).

If su ciently atypical, according to generally accepted criteria, the cell may be classified as cancerous.

It is the overall pattern of the tissue rather than any one individual cell that aids in the diagnosis of cancer; one dyskeratotic or atypical cell does not necessarily mean the tissue is cancerous.

II.Isolated atypical cells may be found in benign conditions such as actinic keratosis and pseudoepitheliomatous hyperplasia.

Atypical cells may be abundant in malignant conditions such as carcinoma in situ and squamous cell carcinoma.

A.Spatial relationships between cells are also disturbed.

B.Disorganized epithelial architecture is often a better means of diagnosing epithelial malignancy than is individual cell morphology.

CONGENITAL ABNORMALITIES

Dermoid and Epidermoid Cysts

See p. 540 in Chapter 14.

Leukoplakia

I.Leukoplakia (white plaque) is a clinical term (not a histopathologic term) that is usually applied to mucous membrane lesions. The clinical appearance is caused by the orthokeratosis (hyperkeratosis).

II.Clinically, any mucous membrane (conjunctival) lesion that contains orthokeratosis appears as a white plaque (leukoplakia; e.g., orthokeratosis induced by an underlying pinguecula, pterygium, papilloma, or carcinoma in situ).

Polarity

I.Tissue polarity refers to the arrangement of epithelial cells in the epithelium [i.e., in normal polarity an orderly transition exists from basal cells to prickle (acanthocytes), to squamous cells, and so forth].

II.Complete loss of polarity (see Fig. 7.21) has occurred when the cells at the surface are indistinguishable from the cells at the base because of loss of the normal sequence of cell maturation (e.g., in squamous cell carcinoma).

Phakomatous Choristoma

I.Phakomatous choristoma (Fig. 6.6) is a rare, congenital, choristomatous tumor (i.e., a tumor of tissue not normally found in the area) of lenticular anlage, usually involving the inner aspect of the lower lid.

II.Histologically, cells resembling lens epithelial cells and lens “bladder” cells along with patches of a thick, irregular periodic acid–Schi (PAS)-positive membrane closely simulating lens capsule are seen growing irregularly in a dense fibrous tissue matrix.

Positive staining for vimentin, S-100 protein, and numerous antibodies against lens-specific proteins strongly support the lenticular anlage origin.

An unusual complex choristoma of the lateral canthus has been reported to contain elements of hair follicle nevus, bulbar dermoid, epibulbar osseous choristoma, and accessory tragus. It is proposed that the lesion is the result of faulty migration of pluripotential cells during embryogenesis.

Miscellaneous Choristomas and Hamartomas

I. Nevus lipomatosus (pedunculated nevus) has been reported on the eyelid of an 11-year-old boy having an eyelid papule that had been present since birth and was gradually enlarging. Histologically, the lesion was polypoid in shape and consisted of mature adipocytes within the dermis and subconjunctival mucosa consistent with nevus lipomatosus.

II.Juvenile hyaline fibromatosis is characterized by multiple facial nodules, gingival fibromatosis, and osteolytic lesions in the proximal metaphysis of the tibia and humerus symmetrically. It has presented as an eyelid tumor scalloping the superior orbital osseous rim and resulting in blepharoptosis.

III.Neurocutaneous pattern syndromes are a group of disorders characterized by congenital abnormalities involving both the skin and the nervous system for which no identifiable cause has been isolated. Examples are encephalocraniocutaneous lipomatosis, oculocerebrocutaneous syndrome, and linear nevus sebaceous syndrome.

A.Encephalocraniocutaneous lipomatosis is rare and characterized by congenital cutaneous, ocular, and neu-

rologic abnormalities, particularly involving the head and neck. It has been reported in a boy with lipomatous brown pigmented plaques of the top of the skull with accompanying alopecia, ptosis, bulbar conjunctival lipodermoid, microcalcifications, and atrophy of the cerebral parenchyma, and widening of the frontal subarachnoid space and the fissure of Sylvius. There were accompanying intraoral lesions, maxillary compound odontoma, and juvenile extranasopharyngeal angiofibroma of the gingiva.

B.Congenital lipoblastoma of the scalp involving the eyelid has been reported. Histopathologic examination revealed lobular adipose tissue separated by fibrous septa.

Cryptophthalmos (Ablepharon)

I.Cryptophthalmos is a rare condition in which the embryonic lid folds fail to develop.

II.Conjunctiva, cornea, and lid folds are replaced by skin that passes smoothly over the orbital margins. Palpebral structures and eyebrows cannot be identified.

Because the cornea is not formed or is rudimentary, an incision through the skin covering the anterior orbit may enter directly into the inside of the eye.

Microblepharon

Microblepharon is a rare condition in which the lids are usually normally formed but shortened; the shortening results in incomplete lid closure.

Coloboma

I. A coloboma of the lid is a defect that ranges from simple notching at the lid margin to complete absence of a segment of lid.

II.Other ocular and systemic anomalies may be found (see discussion of Goldenhar’s syndrome, p. 265 in Chapter 8).

A.Eyelid colobomas may be seen in the amniotic deformity, adhesion, and mutilation (ADAM) sequence in which a broad spectrum of anomalies having intrinsic causes (germ plasm defect, vascular disruption, and disturbance of threshold boundaries of morphogens during early gastrulation) alternate with extrinsic causes (amniotic band rupture) to explain the condition. In addition to mutilation (reduction) and deformity (ring constriction) of distal extremities there can be acrania, cephalocele, typical or atypical facial clefts, and celosomia in addition to skin evidence of a constriction band.

Epicanthus

I.Epicanthus consists of a rounded, downward-directed fold of skin covering the caruncular area of the eye. It is usually bilateral and is often inherited as an autosomal-dominant trait.

Epicanthus inversus is an upward-directed, rounded fold of skin.

II. Ptosis may be associated with epicanthus.

Ectopic Caruncle

A clinically and histologically normal caruncle may be present in the tarsal area of the lower lid.

Lid Margin Anomalies

I.Congenital entropion—this anomaly may result from an absence of the tarsal plate, or from hypertrophy of the tarsal plate or the marginal (ciliary) portion of the orbicularis muscle.

II.Primary congenital ectropion

A.This is a rare disorder.

B.Most cases are secondary to conditions such as microphthalmos, buphthalmos, or an orbitopalpebral cyst.

C.Congenital entropion and atrichosis of the lower eyelids may be associated with tarsal hypoplasia. It may be an

isolated occurrence or inherited as an autosomaldominant trait.

D.Kabuki (make-up) syndrome includes characteristic facies with long palpebral fissures, everted lower lateral eyelids, and arched eyebrows. Systemic findings include mild to moderate mental retardation, fetal pads, and cleft palate. Additionally, postnatal growth retardation, skeletal and visceral anomalies are present in a large percentage of patients.

E.Oculoauriculofrontonasal syndrome can have features of oculoauriculovertebral spectrum and frontonasal dysplasia sequence. Findings have included preauricular skin tag, hypoplastic pinna lacking an ear canal, everted and hypoplastic eyelid, cleft lip and palate, bifid nasal tip, ocular hypertelorism, micrognathia, hypoplastic mandible, extra cervical rib, hemivertebrae, agenesis of the posterior corpus callosum with midline lipoma, and an extrarenal pelvis.

III.Ankyloblepharon—this defect consists of partial fusion of the lid margins, most commonly the temporal aspects.

Eyelash Anomalies

I.Hypotrichosis (madarosis)

A.Primary hypotrichosis (underdevelopment of the lashes) is rare.

Schopf–Schulz–Passarage syndrome is a rare ectodermal dysplasia characterized by hypodontia, hypotrichosis, nail dystrophy, palmoplantar keratoderma, and periocular and eyelid margin hidrocystomas. Multiple palmoplantar eccrine syringofibroadenomas have also been associated with the syndrome.

B.Most cases are secondary to chronic blepharitis or any condition that causes lid margin scarring or lid neoplasms.

C.Secondary eyelash loss may be associated with hyperthyroidism.

II.Hypertrichosis is an increase in length or number of lashes.

A.Trichomegaly is an increase in the length of the lashes.

Increased eyelash length is associated with allergic diseases.

B.Polytrichia is an increase in the number of lashes.

1.Distichiasis—two rows of cilia

2.Tristichiasis—three rows of cilia

3.Tetrastichiasis—four rows of cilia

Distichiasis is the term used for the congenital presence of an extra row of lashes, whereas trichiasis is the term used for the acquired condition, which is usually secondary to lid scarring. Distichiasis may be associated with late-onset hereditary lymphedema (see section on Congenital Conjunctival Lymphedema in Chapter 7). The syndrome is characterized by lymphedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the meibomian glands. Mutation of the FOXC2 gene (a

member of the forkhead/winged family of transcription factors) has been associated with the lymphedema– distichiasis syndrome. It has been postulated that hereditary distichiasis and lymphedema–distichiasis may not be separate genetic disorders but different phenotypic expressions of the same underlying disorder.

A form of congenital hypertrichosis in the periorbital region, associated with cutaneous hyperpigmentation, may overlie a neurofibroma.

III.Ectopic cilia

A.Ectopic cilia is a rare choristomatous anomaly in which a cluster of lashes grows in a location (lid or conjunctiva) remote from the eyelid margin.

B.A case of complex eyelid choristoma containing ectopic cilia and a functioning lacrimal gland has been reported.

Ptosis

I.Ptosis is a condition in which lid elevation is partially or completely impaired.

A

II.It may be congenital, associated with other anomalies, or caused by trauma, third cranial nerve damage, or many other causes.

III.Histologically, the levator muscle may show atrophy or may appear normal.

Ichthyosis Congenita

I.Ichthyosis (Fig. 6.7) can be divided into four types:

A.Autosomal-dominant ichthyosis vulgaris (onset usually in first year of life)

B.Autosomal-dominant ichthyosis congenita (ichthyosiform erythroderma, onset at birth), with a generalized bullous form and a localized nonbullous form (ichthyosis hystrix)

C.X-linked recessive ichthyosis vulgaris [the rarest type

(Xp22.32), onset at 1 to 3 weeks]

D.Autosomal-recessive ichthyosis congenita with a severe harlequin type and a less severe lamellar type (onset at birth)

B

1.Keratinocyte transglutaminase (TGK) activity mediates the cross-linkage during the formation of the normal cornified cell membrane.

2.Intact cross-linkage of cornified cell envelopes is required for epidermal tissue homeostasis.

3.In lamellar ichthyosis, TGK levels are drastically reduced, causing the keratinocytic defect in the disease.

II.All types have in common dryness of the skin with variable amounts of profuse scaling.

Only in the autosomal-recessive type do ectropion of the lids and conjunctival changes develop.

III.Cicatricial ectropion is a common finding in recessive ichthyosis congenita.

A.Corneal changes such as gray stromal opacities (dystrophica punctiformis profunda) occur in ichthyosis vulgaris and autosomal-recessive ichthyosis congenita.

In X-linked ichthyosis, corneal changes may occur that electron microscopically resemble the changes in lecithin cholesterol acyltransferase disease.

B.Superficial corneal changes (punctate epithelial erosions, gray elevated nodules, and band-shaped keratopathy) also occur.

IV. The di erential diagnosis includes ectodermal dysplasia, poikiloderma congenitale (Rothmund–Thomson syndrome), adult progeria (Werner’s syndrome), keratosis palmaris et plantaris, keratosis follicularis spinulosa decalvans

(Siemens’ disease), epidermolysis bullosa, and the syndrome of ichthyosis follicularis, atrichia, and photophobia (IFAP syndrome, a rare neuroichthyosis that is probably X-linked recessive).

Keratitis–ichthyosis–deafness (KID) syndrome is a rare congenital ectodermal dysplasia characterized by the presence of hyperkeratotic skin lesions, moderate to profound sensorineural hearing loss, and vascularizing keratitis. Genetic mutations in the GJB2 gene coding for connexin 26, which is a component of gap junctions in epithelial cells, have been detected in the disorder. Specific associated ocular and adnexal findings are lid abnormalities, corneal surface instability, limbal stem cell deficiency with resulting corneal complications, and dry eye.

V.Histologically, the epidermis is thickened and covered by a thick, dense, orthokeratotic scale.

In the autosomal-recessive type, the conjunctiva may show a papillary reaction with hyperkeratosis and parakeratosis of the epithelium.

hypersensitivity of the skin to ultraviolet radiation, a deficiency in the repair of damaged DNA, and a resultant high incidence of skin cancers.

Squamous and basal cell carcinomas, fibrosarcoma, and malignant melanoma may all develop on areas of skin exposed to sun. Multiple malignancies of different types may develop in an individual even in children.

II.Skin lesions show three stages: mild, di use erythema associated with scaling and tiny, hyperpigmented macules; atrophy of the skin, mottled pigmentation, and telangiec-

tasis—the picture resembles radiation dermatitis; and development of skin malignancies.

III.Histology

A.Early, the epidermis shows orthokeratotic and atrophic foci associated with epidermal cells and macrophages showing pigment phagocytosis. Subepidermal perivascular infiltrates of lymphocytes and plasma cells are found.

B.Later, the orthokeratosis and pigment deposition become more marked. An associated acanthosis of the epidermis and basophilic degeneration of the collagen are found in the corium.

C.The histopathologic appearance of the malignancies is identical to that in patients who do not have xeroderma pigmentosum.

AGING

Atrophy

See subsection Atrophy, earlier, under Terminology.

I.“Aging”skin appears dry, rough, wrinkled, lax, and unevenly pigmented.

II.Because the collagen of the corium is altered, it stains basophilic instead of eosinophilic with hematoxylin and eosin. The collagen stains positively for elastin; the positivity is not changed if the tissue is pretreated with elastase.

It is the altered staining characteristic of the corium that has led to the use of terms such as basophilic degeneration, actinic changes, and senile elastosis.

III.The elastic tissue is also altered and tremendously increased; it, along with the changed collagen, helps to explain the characteristic wrinkling of senile skin.

Xeroderma Pigmentosum

I.Xeroderma pigmentosum is one of the inherited DNA repair disorders, which also include Cockayne syndrome, trichothiodystrophy, Bloom syndrome, Rothmund– Thomson syndrome, and Werner syndrome. It is inherited as an autosomal-recessive disorder, is characterized by a

Senile Ectropion and Entropion

I.An accentuation of the aging changes may result in an ectropion (turning-out) or an entropion (turning-in) of the lower lid.

II.Histologically, both ectropion and entropion show chronic nongranulomatous inflammation and cicatrization of the skin and conjunctiva.

A.Ectropion exhibits increased orbicularis and Riolan’s muscle ischemia, fragmentation of elastic and collagenous tissues in the orbital septum and tarsus, and hypertrophy of the tarsus. Actinic damage of the anterior eyelid lamella of the lower eyelid has been cited as a contributing factor in patients with involutional eyelid changes, and is most marked in those with ectropion.

B.Entropion shows increased atrophy of the orbital septum and tarsus.

Dermatochalasis

I.Dermatochalasis (Fig. 6.8) is an aging change characterized by lax, redundant skin of the lids. The folds may cover the palpebral fissure, even impairing vision.

Dermatochalasis should not be confused with blepharochalasis, an uncommon condition characterized by permanent changes in the eyelids after recurrent and unpredictable attacks of edema, usually in people younger than 20 years of age. Elastin mRNA expression in cultured fibroblasts from blepharochalasis is not decreased, suggesting that environmental factors or other matrix components of elastic fibers may be involved in the loss of elastic fibers found in the disorder. Also, the Melkersson–Rosenthal syndrome (triad of recurrent labial edema, relapsing facial paralysis, and fissured tongue) can present with eyelid edema of “unknown cause.”

II.Histologically, the epidermis appears thin and smooth with decreased or absent rete ridges.

In the corium, some loss of elastic and collagen tissue occurs along with an increase in capillary vascularity, an often basophilic degeneration of the collagen (actinic elastosis), and a mild lymphocytic inflammatory reaction.

Herniation of Orbital Fat

I.Defects or dehiscences in the orbital septum produced by aging changes, often associated with dermatochalasis, may

result in herniated orbital fat, simulating an orbital lipoma.

II.Histologically, mature fat is found that looks similar to that in a lipoma.

Frequently, the distinction between a primary orbital lipoma and herniated orbital fat is made more readily clinically than histologically.

Floppy-Eyelid Syndrome

A.Upregulation of elastolytic enzymes, probably related to repeated mechanical stress, has been postulated to participate in elastic fiber degradation and subsequent tarsal laxity with eyelash ptosis in floppy-eyelid syndrome.

INFLAMMATION

Terminology

I.Dermatitis (synonymous with eczema, eczematous dermatitis)

A.Dermatitis is a di use inflammation of the skin caused by a variety of cutaneous disorders, some quite specific and others nonspecific.

B.It may be acute (erythema and edema progressing to vesiculation and oozing, then to crusting and scaling), subacute (intermediate between acute and chronic), or chronic (papules, plaques with indistinct borders, less intense erythema, increased skin markings—lichenifi- cation—containing fine scales and firm or indurated to palpation).

Dermatitis of the lids is called blepharitis.

II.Blepharitis

A.Blepharitis is a simple di use inflammation of the lids.

A granulomatous blepharitis, which is part of Melkersson– Rosenthal syndrome (triad of recurrent labial edema, relapsing facial paralysis, and fissured tongue), may present along with lid edema.

B.Seborrheic blepharitis refers to a specific type of chronic blepharitis primarily involving the lid margins and often associated with dandru and greasy scaling of the scalp, eyebrows, central face, chest, and pubic areas.

1.Red, inflamed lid margins and yellow, greasy scales on the lashes are characteristic.

2.Histologically, the epidermis shows spongiosis, a mild, superficial perivascular, predominantly lymphohistiocytic, mononuclear cell infiltrate in the superficial dermis, and even acanthosis, orthokeratosis, or parakeratosis, alone or in combination.

C.Blepharoconjunctivitis refers to a specific type of chronic blepharitis involving the lid margins primarily and the conjunctiva secondarily.

1.Sensitivity to Staphylococcus is the likely cause.

2.The chronic inflammation may result in loss (madarosis) or abnormalities (e.g., trichiasis) of the eyelashes along with secondary phenomena such as hordeolum and chalazion. The lid margins may be thickened and ulcerated with gray, tenacious scales at the base of the remaining lashes.

3.Histologically, a vascularized, chronic, nongranulomatous inflammation, often containing neutrophils, is associated with acanthosis, orthokeratosis, or parakeratosis of the epidermis.

D.Cellulitis refers to a specific type of acute, infectious blepharitis primarily involving the subepithelial tissues.

1.Histologically, polymorphonuclear leukocytes, vascular congestion, and edema predominate.

2.Bacteria, especially Streptococcus, are the usual cause.

Erysipelas is a specific type of acute cellulitis caused by group A hemolytic streptococci that is characterized by a sharply demarcated, red, warm, dermal and subcutaneous facial plaque.

III.Hordeolum (Fig. 6.9)

A.An external hordeolum (stye) results from an acute purulent inflammation of the superficial glands (sweat and sebaceous) and hair follicles of the eyelids.

1.It presents clinically as a discrete, superficial, elevated,erythematous,warm,tender papule or pustule, usually on or near the lid margin.

2.Histologically, polymorphonuclear leukocytes, edema, and vascular congestion are centered primarily around hair follicles and adjacent structures.

A

B

Fig. 6.9 Hordeolum. A, The patient complained of swelling, redness, and pain in the right lower lid over a few days. The inflammation is mainly located in the outer layers of the lid and is called an external hordeolum. Similar inflammation in the inner layers is called an internal hordeolum. B, Histologic section of another case shows a purulent exudate consisting of polymorphonuclear leukocytes and cellular debris.

B.An internal hordeolum results from an acute purulent inflammation of the meibomian glands in the tarsal plate of the eyelids.

It presents clinically as a di use, deep, tender, warm erythematous area involving most of the lid.

Hordeolum can be considered simply as an inflammatory papule or pustule (pimple) of the lid. An external hordeolum is located superficially; an internal hordeolum is deep and points internally.

IV. Chalazion (Fig. 6.10)

A chalazion may result from an internal hordeolum or may start de novo.

A.Chronic inflammation of the meibomian glands (deep chalazion) or Zeis sebaceous glands (superficial chala-

zion) results in a hard, painless nodule in the eyelid called a chalazion or lipogranuloma of the lid.

A lipogranuloma is composed of an extracellular accumulation of fat, as apposed to a xanthoma, which consists of an intracellular accumulation of fat. Lipogranulomatous eyelid inflamma-

tion has resulted from leakage into the eyelid of silicone oil used in vitreoretinal surgery.

B.If the chalazion ruptures through the tarsal conjunctiva, granulation tissue growth (fibroblasts, young capillaries,

lymphocytes, and plasma cells) may result in a rapidly enlarging, painless, polypoid mass (granuloma pyogeni-

cum; Fig. 6.11).

C.Histologically, a zonal lipogranulomatous inflammation is centered around clear spaces previously