Skin and Lacrimal Drainage System

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Skin and Lacrimal Drainage System

Skin

Normal Anatomy (Figs. 6.1 and 6.2)

Epidermis

Lid skin is quite thin.

I. The epidermis is composed of a few layers of squamous cells (keratinocytes) and a basal layer; large rete pegs are absent.

II. Admixed with the epithelial cells are dendritic melanocytes and Langerhans’ cells (dendritic-appearing cells expressing class II antigen).

III. Expression of immunohistochemical markers for cytokeratins, mucin, and stem cells varies considerably among the various epithelia at the mucocutaneous junction of the eyelid.

A. At the mucocutaneous junction, CK7, -15, and -19 are absent; however, the epithelium reacts positively for CK1, -4, -8, -10, -13, and -14.

B. Reactivity also is found for MUC1 and MUC4 but not for MUC5AC.

C. No reactivity is determined for K15, BCRP/ABCG2, and integrin β₁ in the area of the mucocutaneous epithelium, but a strong reactivity is present for N-cadherin.

Fig. 6.2 Normal anatomy. A, Cross-section of the eyelid shows the inner white tarsal plate, the middle layers of muscle fibers, and the surface epithelium. Note the cilia coming out of the lid margin inferiorly. B, Histologic section shows the inner tarsal plate (p) containing the meibomian glands, the middle muscular bundles (m), and the surface epithelium (e). The cilia exit from the middle portion of the lid margin inferiorly. Apocrine sweat glands, eccrine sweat glands, sebaceous glands of Zeis, and hair follicles of the surface lanugo hairs are also seen in the lids (see also Figs. 1.27C and 7.1) (g, accessory lacrimal glands). (A, Courtesy of Dr. RC Eagle, Jr.)

Dermis

The dermis is sparse, composed of delicate collagen fibrils, and contains the vasculature and epidermal appendages, sebaceous glands, apocrine and eccrine sweat glands, and hair complexes.

Subcutaneous Tissue

The subcutaneous layer is mostly composed of adipose tissue.

Terminology

Orthokeratosis and Parakeratosis

I. The stratum corneum (keratin layer) is thickened.

Hyperkeratosis means “increased scale” and includes both orthokeratosis and parakeratosis. In orthokeratosis, a thick granular layer is found because the epidermal cells slowly migrate upward; when the migration upward is rapid, no granular cells are seen and parakeratosis results. Orthokeratosis is hyperkeratosis composed of cells that have complete keratinization and no nuclear remnants, whereas parakeratosis is hyperkeratosis that shows incomplete keratinization in which nuclei are retained in the cells of the stratum corneum. Orthokeratosis and parakeratosis often exist in the same lesion (Fig. 6.3A).

Fig. 6.3 Orthokeratosis, parakeratosis, and acanthosis. A, In this actinic keratosis, orthokeratosis (hyperkeratosis) is present (right half of picture) where the granular cell layer is prominent. Parakeratosis is present (left half of picture) where nuclei are retained in cells of keratin layer; granular cell layer is not prominent. B, In this squamous papilloma, acanthosis is present, especially on right side, evidenced by thickening of prickle-cell (squamous) layer. The granular cell layer is also thickened, and orthokeratosis is present.

II. Orthokeratosis commonly is seen in verruca and the scaly lesions such as actinic and seborrheic keratoses.

III. Parakeratosis is characteristic of psoriasis and other inflammatory conditions (e.g., seborrheic keratosis).

Acanthosis

I. The stratum spinosum (squamous or prickle-cell layer) of the epidermis shows increased thickness (see Fig. 6.3B).

II. It is commonly seen in many proliferative epithelial lesions (e.g., papilloma, actinic keratosis, squamous cell carcinomas, and pseudoepitheliomatous hyperplasia).

Dyskeratosis

I. Dyskeratosis is keratinization of individual cells within the stratum spinosum, where the cells are not normally keratinized (Fig. 6.4A; see Fig. 7.18). 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.

Fig. 6.4 Dyskeratosis and atypical cells. A, In this case of hereditary benign intraepithelial dyskeratosis, keratinization of individual cells is present in the stratum spinosum (squamous or prickle-cell layer)—see also Fig. 7.18B. B, In this sebaceous gland carcinoma, many atypical cells are seen, including a tripolar mitotic figure.

II. Dyskeratosis is characteristic of benign familial intraepithelial dyskeratosis, Darier’s disease, and Bowen’s disease, and it 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 6.28).

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 or beneath the epidermis (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 (effacement) 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 slow-growing 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 contain an abnormal mitotic figure (e.g., tripolar metaphase). If sufficiently 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.

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. 7.22) has occurred when the cells at the surface are indistinguishable from the cells at the base (e.g., in squamous cell carcinoma or malignant melanoma).

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 Chapter 14.

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–Schiff (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 supports the lenticular anlage origin.

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.

Miscellaneous Choristomas and Hamartomas

I. Nevus lipomatosus (pedunculated nevus) is a gradually enlarging congenital eyelid papule. Histologically, the lesion is polypoid in shape and consists 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 may present 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 neurologic 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 and eyelid is very rare. Histopathologic examination shows lobular adipose tissue separated by fibrous septa.

IV. Caliber persistent artery refers to a large-caliber artery that is present adjacent to an epithelial or mucosal surface.

A. On the head and neck, the lesion most commonly is found on the lower lip, but it has been documented on the eyelid.

B. It is of significance because of the possibility of confusion with a subcutaneous mass lesion and because of its propensity to bleed profusely on attempted biopsy.

C. Histopathologic examination demonstrates a large-caliber artery within the dermis extending at almost right angles to the skin surface.

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 in Chapter 8).

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 (rare)

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

B. Congenital entropion and atrichosis of the lower eyelids may be associated with tarsal hypoplasia. It may be an isolated occurrence or inherited as an autosomal-dominant trait.

C. Kabuki (makeup) 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. In addition, postnatal growth retardation and skeletal and visceral anomalies are present in a large percentage of patients.

D. 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—for example, sebaceous gland carcinoma.

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 may be 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; and (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, rather, different phenotypic expressions of the same underlying disorder. Continue small print. 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.

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 1–3 weeks]

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

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.

Fig. 6.7 Ichthyosis congenita. A, Child has severe ichthyosis congenita. B and C, Right and left eyes show thickened, scaly skin and keratinization (white-gray plaques) of palpebral conjunctiva. D, Thickened epidermis and very prominent granular cell and keratin layers are seen (conjunctiva also showed papillary reaction with keratinization). (D, Modified from Katowitz JA, Yolles EA, Yanoff M: Ichthyosis congenita. Arch Ophthalmol 91:208, with permission. © American Medical Association 1974. All rights reserved.)

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 differential 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.