Benign tumors and cysts of the epidermis

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Chapter 2

Benign tumors and cysts of the epidermis

Dirk M. Elston

A clinical image atlas for entities throughout the text can be found in the on-line content for this book.

Benign acanthomas

Acanthomas are benign cutaneous neoplasms characterized by an expansion of the epidermis. The acanthoma may be composed of clones of cells that displace or compress the preexisting epidermis. In contrast to the reactive acanthosis seen in inflammatory disorders, the rete ridge pattern is commonly ablated by the neoplastic tissue of an acanthoma.

Seborrheic keratoses

Seborrheic keratoses are acanthomas composed of small polygonal keratinocytes about the size of acrosyringeal keratinocytes (the cells that make up the intraepidermal portion of the eccrine duct). The cells are typically smaller than the cells of the surrounding epidermis, and they are commonly pigmented. Architectural subtypes of seborrheic keratoses include acanthotic, hyperkeratotic, reticulated, and clonal. Any of these subtypes may be pigmented, irritated (spindling of cells and squamous eddy formation), or inflamed (usually lymphoid inflammation). Melanoacanthoma is a distinct subtype of seborrheic keratosis composed of small keratinocytes and dendritic melanocytes.

Seborrheic keratoses produce a characteristic loose lamellar “shredded-wheat” stratum corneum. Exceptions include irritated or inflamed seborrheic keratosis. Instead of the characteristic loose lamellar horn, irritated or inflamed seborrheic keratoses produce a compact brightly eosinophilic parakeratotic stratum corneum. Adjacent unaffected areas of the seborrheic keratosis still produce the characteristic loose lamellar stratum corneum, and it is common to see remnants of loose stratum corneum above areas of compact stratum corneum. Melanoacanthomas produce a deeply eosinophilic compact parakeratotic stratum corneum, even when they are not irritated or inflamed.

Seborrheic keratoses may express BCL-2, a marker associated with resistance to programmed cell death (apoptosis). Activating point mutations in the gene encoding fibroblast growth factor receptor 3, a tyrosine kinase receptor, are also common in seborrheic keratoses.

Acanthotic seborrheic keratosis

Key features

• Broad sheets of small polygonal keratinocytes with intervening horn cysts

• Loose lamellar “shredded-wheat” or “onion-skin” keratin

• Commonly pigmented

Fig 2-1 Acanthotic seborrheic keratosis

Acanthotic seborrheic keratoses are composed of broad sheets of cells with intervening horn cysts or pseudohorn cysts. Horn cysts are completely encased within the acanthoma, whereas pseudohorn cysts open to the surface. Like other seborrheic keratoses, they may become irritated or inflamed.

Fig 2-2 Pigmented acanthotic seborrheic keratosis

Fig 2-3 Irritated acanthotic seborrheic keratosis

Fig 2-4 Inflamed acanthotic seborrheic keratosis

Fig 2-5 Hyperkeratotic seborrheic keratosis

Hyperkeratotic seborrheic keratosis

Key features

• Tall stacks of loose lamellar “shredded-wheat” keratin

• Papillomatosis – hills and dales that may produce a “church-spire” appearance

Fig 2-6 Inflamed hyperkeratotic seborrheic keratosis

The tall stacked stratum corneum is typically much thicker than the epidermis. As in other forms of seborrheic keratosis, the keratin has a loose lamellar “shredded-wheat” appearance unless the lesion has become irritated or inflamed. Papillomatosis is characteristic, but variable in degree. Horn cysts are inconspicuous or absent.

Clonal seborrheic keratosis is characterized by islands of small keratinocytes with uniform bland nuclei. The nests are embedded within the epidermis. Sometimes, the nests are large enough that the normal epidermis is reduced to thin strands separating the large nests. Horn cysts are usually absent. The nests may demonstrate pigment. There may be squamous eddies (irritated seborrheic keratosis), lymphocytes (inflamed seborrheic keratosis), or both. In contrast to Bowen’s disease, the cells are uniform and atypia is absent. In contrast to hidroacanthoma simplex, no ducts are present within the clones.

Differential Diagnosis

Hidroacanthoma simplex

Key features

• Clonal islands of small keratinocytes similar in appearance to those of clonal seborrheic keratosis

• Ducts present focally within the clonal islands

Fig 2-14 Hidroacanthoma simplex

Bowen’s disease

Key features

• Clonal islands of atypical keratinocytes within the epidermis

• Cells may be anaplastic or glassy and eosinophilic

• Buckshot scatter of cells may be present focally

• Apoptotic keratinocytes commonly scattered within nests

• Overlying stratum corneum becomes compact and parakeratotic where clones touch surface

• More typical Bowen’s disease may be present in the adjacent skin

Fig 2-15 Clonal Bowen’s disease

Pigmented seborrheic keratosis

Key features

• Pigment within keratinocytes

• May be acanthotic, hyperkeratotic, reticulated, or clonal

• When clonal, the pigment is restricted to the clonal islands

Fig 2-16 Pigmented seborrheic keratosis

Irritated seborrheic keratosis

Key features

• Squamous eddies

• Spindled keratinocytes

• Horn cysts common

• Keratin commonly becomes compact, eosinophilic, and parakeratotic

• Keratin often retains a loose lamellar pattern in some areas

Irritated seborrheic keratosis is characterized by the formation of squamous eddies within the epidermis and the presence of spindled keratinocytes. Some areas of the tumor typically still produce a loose lamellar “shredded-wheat” pattern of keratin, and horn cysts composed of loose lamellar keratin are often present. In areas, the keratin becomes compact, eosinophilic, and parakeratotic. A zone of loose lamellar keratin may be seen above the dense eosinophilic keratin. This was produced before the lesion became irritated. It has since been pushed upward.

Fig 2-17 Irritated seborrheic keratosis with prominent squamous eddies

Fig 2-18 Irritated seborrheic keratosis with prominent spindling of keratinocytes

Inflamed seborrheic keratosis

Key features

• Lymphocytes and spongiosis

• In areas, the stratum corneum becomes compact, eosinophilic, and parakeratotic

• Loose lamellar keratin is commonly retained in other areas

• Horn cysts are common

• Lichenoid interface dermatitis may be present

• An overlying crust may be present

Fig 2-19 Inflamed seborrheic keratosis with lymphocytes and spongiosis

Inflamed seborrheic keratosis is characterized by lymphocytes and spongiosis within the epidermis or the presence of lichenoid interface dermatitis. Some areas of the tumor typically still produce a loose lamellar “shredded-wheat” pattern of keratin, and horn cysts composed of loose lamellar keratin are often present. As in irritated seborrheic keratoses, a zone of loose lamellar keratin may sometimes be seen above a zone of dense eosinophilic keratin. When clonal, the spongiosis and lymphoid infiltrate are typically restricted to the clonal islands.

Fig 2-20 Inflamed seborrheic keratosis with lichenoid interface dermatitis

Melanoacanthoma

Key features

• Acanthoma composed of both small keratinocytes and pigmented dendritic melanocytes

• Most pigment is within dendrites

• Overlying stratum corneum is almost always compact eosinophilic and parakeratotic

Fig 2-21 Melanoacanthoma

Cutaneous melanoacanthomas are a type of seborrheic keratosis, composed of both small cuboidal keratinocytes and pigmented dendritic melanocytes. Most melanin pigment is contained within the melanocytic dendrites with little visible pigment within the keratinocytes. Unlike most seborrheic keratoses, horn cysts and loose lamellar horn are typically absent. Instead, the overlying stratum corneum is almost always compact, eosinophilic, and parakeratotic. Cutaneous melanoacanthomas may be clonal. Oral melanoacanthomas are reactive proliferations unrelated to seborrheic keratosis.

Clear cell acanthoma (pale cell acanthoma)

Key features

• Discrete acanthoma with overlying parakeratosis

• Distinct transition between the normal epidermis and the clearer/paler cells in the stratum spinosum

• Peppered with neutrophils

Fig 2-22 Clear cell acanthoma

Clear cell acanthomas are recognizable as a clearly defined acanthotic area of the epidermis with ample clear or pale cytoplasm. A thin overlying parakeratotic scale crust is present, and there is a distinct transition between surrounding normal stratum corneum and the parakeratotic stratum corneum as well as between the normal epidermis and the paler cells comprising the acanthoma. Neutrophils are scattered throughout the lesion. The cells of the acanthoma are deficient in phosphorylase, resulting in an accumulation of glycogen.

Large cell acanthoma

Key features

• Discrete acanthoma composed of cells with large nuclei

• Overlying lamellar hyperkeratosis is common

• May be pigmented

Fig 2-23 Large cell acanthoma

The rete ridges may be bulbous or there may be a solid plate-like acanthosis. The cells composing the acanthoma have large nuclei, typically twice the size of the nuclei in the surrounding epidermis.

Large cell acanthomas represent a heterogeneous group of lesions. The most common type presents as a slightly hyperkeratotic pigmented patch, resembling a solar lentigo. Other lesions are erythematous. Many appear to represent a histologic variant of solar lentigo, others of Bowen’s disease. The cells of some lesions have been shown to be aneuploid, and no histologic features predict which lesions demonstrate aneuploid populations. Because of this, many clinicians prefer to destroy any remaining lesion by means of cryotherapy.

Inverted follicular keratosis (IFK)

Key features

• Endophytic lesion resembling an expanded hair follicle

• Squamous eddies

Fig 2-24 Inverted follicular keratosis

The outline of the epithelial column is smooth, with no evidence of jagged invasive growth.

True inverted follicular keratoses are benign follicular proliferations unrelated to human papillomavirus infection. Multiple lesions may be associated with Cowden’s syndrome. Follicular warts may sometimes have squamous eddies and resemble IFK.

Warty dyskeratoma

Key features

• Endophytic growth

• Acantholytic dyskeratosis

• Overlying parakeratotic crust may be present

Fig 2-25 Warty dyskeratoma

Two types of dyskeratotic cells are noted. Corps ronds are round dyskeratotic cells that stain pale pink to red, and may have a wide clear halo surrounding the nucleus. Grains are flattened basophilic dyskeratotic cells. Either or both may be present. Some lesions are crateriform; others resemble expanded hair follicles.

Acantholytic acanthoma

Key features

• Acanthoma composed of bland keratinocytes

• Acantholysis

Fig 2-26 Acantholytic acanthoma

The appearance resembles the “dilapidated brick wall” of Hailey–Hailey disease.

Epidermolytic acanthoma

Key features

• Often crateriform

• Epidermolytic hyperkeratosis

Fig 2-27 Epidermolytic acanthoma

Epidermolytic acanthomas are characterized by epidermolytic hyperkeratosis. The granular layer is thick and contains irregularly shaped keratohyalin granules and cytoplasmic borders are indistinct. Clinically, the lesions are solitary discrete acanthomas resembling seborrheic keratoses.

Epidermal nevi

Key features

• Discrete acanthomas or hyperkeratotic lesions

Epidermal nevi are typically present at or near birth. Linear epidermal nevi follow Blaschko’s lines and may represent mosaicism, via post-zygotic somatic mutation, lyonization of X chromosomes, or loss of heterozygosity. Patients with multiple epidermal nevi may have associated eye, central nervous, and musculoskeletal abnormalities.

Common epidermal nevus

Key features

• Resembles seborrheic keratosis

Inflammatory linear verrucous epidermal nevus (ILVEN)

Key features

• Variable acanthosis

• Stratum corneum with alternating orthokeratosis and parakeratosis

• Parakeratotic areas have no granular layer

• Orthokeratotic areas have a granular layer

Fig 2-28 ILVEN

The name “inflammatory” linear verrucous epidermal nevus relates to the erythematous clinical appearance of the lesions. Orthokeratosis and parakeratosis alternate from right to left.

Widely separated lesions involving different parts of the body suggest that the mutation occurred in the embryo prior to gastrulation. In this case, the affected cell line is more likely to contribute to many organ tissues, including the gonads.

Cysts

Epidermoid cyst (epidermal inclusion cyst, infundibular cyst)

Key features

• Lining resembles the surface epidermis, but with no adnexal structures

• Loose lamellar “onion-skin” keratin within the cyst

Fig 2-29 Epidermoid cyst

Epidermoid cysts often connect to the surface with a visible punctum. This connection may be visible histologically. In a young cyst, a rete ridge pattern may be present. As tension increases within the cyst, the lining is stretched and the rete pattern disappears. Ruptured cysts demonstrate a neutrophilic infiltrate, histiocytes, and foreign-body giant cells. Flat bits of keratin are noted within giant cells.

Fig 2-30 Ruptured and inflamed epidermoid cyst

Epidermoid cyst with pilomatrical differentiation

Key features

• Areas of ghost cell keratinization as in a pilomatricoma

• Associated with Gardner’s syndrome

Fig 2-31 Epidermoid cyst with pilomatrical differentiation

Vellus hair cyst

Key features

• Wall resembles that of an epidermoid cyst

• Many small vellus hairs within the cyst

• Frequently arise in an eruptive fashion

Fig 2-32 Vellus hair cyst

Eruptive vellus hair cysts may coexist with steatocystomas, and individual cysts may have features of both. Eruptive vellus hair cysts have been reported in association with renal failure and Lowe syndrome (Fanconi-type renal failure, mental retardation, and eye abnormalities).

Dermoid cyst

Key features

• Wall commonly resembles that of an epidermoid cyst

• Adnexal structures within cyst wall

Fig 2-33 Dermoid cyst

Adnexal structures within the cyst wall may include terminal hair follicles, sebaceous glands, eccrine glands, and apocrine glands. Terminal hair shafts are commonly noted within the cyst contents. Lamellar keratin is typically present, although some dermoid cysts demonstrate a bright red “shark-tooth” lining similar to that of a steatocystoma. Dermoid cysts occur in embryonic fusion planes and may be associated with underlying skull defects.

Pilar cyst (trichilemmal cyst, isthmus catagen cyst)

Key features

• Abrupt keratinization without a granular layer

• Deeply eosinophilic dense keratin

• Focal calcification of contents common

• Typically on scalp

• Often multiple

Fig 2-34 Pilar cyst

The abrupt keratinization of pilar cysts resembles that of the outer root sheath (the trichilemma).

Proliferating pilar cyst

Key features

• Rolls and scrolls

• May form small new cysts within the confines of the mother cyst

• Trichilemmal keratinization

Fig 2-35 Proliferating pilar cyst

As the epithelium proliferates, the wall buckles inward, rolling on itself and producing a trabecular or scroll-like appearance (“rolls and scrolls”). A diagnosis of trichilemmal carcinoma should be suspected in tumors with a location other than scalp, recent rapid growth, size greater than 5 cm, infiltrative growth, significant cytologic atypia, and mitotic activity.

Differential Diagnosis

Pilomatricoma

Key features

• Rolls and scrolls

• Ghost cell keratinization, see page 73

Fig 2-36 Pilomatricoma

Branchial cleft cyst

Key features

• Epidermoid or pseudostratified columnar epithelium

• Lymphoid tissue with germinal centers surrounding the cyst

• Cyst usually appears empty

Fig 2-37 Branchial cleft cyst

Branchial cleft cysts are generally found on the lateral part of the neck, anterior to the sternocleidomastoid muscle. They may occur as a result of failure of obliteration of the second branchial cleft in embryonic development. Phylogenetically, the branchial apparatus may be related to gill slits. This analogy is helpful in remembering the typical location on the lateral neck. They are the most common cause of a congenital neck mass, and 2–3% of cases are bilateral.

Although the classic teaching has been that branchial cleft cysts and bronchogenic cysts are embryologically distinct, cases with overlap in distribution and histology occur. In general, branchial cleft cysts are far more likely to occur on the side of the neck, and to demonstrate lymphoid follicles and stratified squamous epithelium. Although smooth muscle may occur, it is rare.

Bronchogenic cyst

Key features

• Ciliated pseudostratified columnar epithelium

• Goblet cells

• May have circumferential smooth muscle around cyst

• May have cartilage

Fig 2-38 Bronchogenic cyst

Bronchogenic cysts are typically midline lesions, located in the suprasternal notch. Bronchogenic cysts are thought to result from remnants of the primitive foregut. Although bronchogenic cysts occur predominantly within the chest, cutaneous lesions generally present as neck lesions in children.

As compared with branchial cleft cysts, bronchogenic cysts typically lack lymphoid follicles. They typically demonstrate pseudostratified respiratory-type ciliated epithelium, goblet cells, concentric smooth muscle, and cartilage.

Steatocystoma (simple sebaceous duct cyst)

Key features

• Wavy, eosinophilic “shark’s-tooth” cuticle

• Sebaceous glands in cyst wall

• Oily contents, frequently containing vellus hairs

Fig 2-39 Steatocystoma

Steatocystomas are commonly inherited, with multiple lesions on the chest. The appearance resembles nodulocystic acne. Solitary lesions are common, and sporadic in occurrence. The cyst lining resembles that of the sebaceous duct. Sebaceous glands are common within the cyst wall, but may not be prominent. Some sections lack visible sebaceous glands, but the cyst can still be identified by the characteristic wavy eosinophilic cuticle.

While dermoid cysts may occasionally demonstrate an identical wavy cuticle, they also commonly demonstrate terminal hair follicles, and may have eccrine or apocrine glands within the cyst wall. Grossly, steatocystomas tend to drain oil and collapse when sectioned, while dermoid cysts tend to remain rigid because they contain keratin.

Median raphe cyst

Key features

• Midline along anogenital raphe

• Debris-filled cyst

• Lining variable

• Surrounding skin has characteristics of genital skin

Fig 2-40 Median raphe cyst

Median raphe cysts occur in men in a characteristic ventral location from the meatus to the anus. The cyst may first become apparent after intercourse. Median raphe cysts may result from incomplete embryonic fusion of the urethral folds, from ectopic periurethral glands of Littre, or sequestration of urethral epithelium after closure of the median raphe.

Typically, the cyst is filled with amorphous debris, and the surrounding genital skin is readily identified by the presence of delicate collagen, randomly arranged smooth muscle, many small nerves, and prominent vascularity. Unlike the circumferential smooth muscle of a bronchogenic cyst, the smooth muscle in genital skin has a random, haphazard arrangement throughout the surrounding skin. The cyst wall itself has a highly variable lining. Some areas may appear ciliated, some cuboidal, and some areas may suggest decapitation secretion.

Cutaneous ciliated cyst

Key features

• Similar to median raphe cysts

• Much less likely to occur on genital skin

Fig 2-41 Cutaneous ciliated cyst

Although ciliated cysts typically occur on the legs of women, and are thought to relate to Müllerian duct remnants, they are occasionally noted in men. Ciliated cysts are commonly filled with debris, and the appearance of the cyst itself can be indistinguishable from that of a median raphe cyst. Helpful differentiating features are the location, sex of the patient, and characteristics of the surrounding skin. As ciliated cysts commonly occur on the legs, the skin lacks the typical appearance of genital skin.