Chapter 118. Benign Epithelial Tumors, Hamartomas, and Hyperplasias

Benign epithelial tumors, hamartomas, and hyperplasias comprise a large and disparate group of tumors and no single classification system unifies them, as their cells of origin and clinical presentation can vary substantially. In this chapter, the clinical entities are grouped by clinical or histologic features to better present them from a practical diagnostic and treatment perspective (Table 118-1).

Seborrheic keratoses (SKs) are the most common benign epidermal tumor of the skin and a frequent focus of patient concern because of their variable appearance. These lesions are common in middle-aged individuals and can arise as early as adolescence.1 Although there are many clinical variants of the lesions, these lesions usually begin as well-circumscribed, dull, flat, tan, or brown patches. As they grow, they become more papular, taking on a waxy, verrucous, or stuck-on appearance (Figs. 118-1 and 118-2). Many lesions display distinctive pseudohorn cysts that likely represent plugged follicular orifices. SKs may arise on any nonmucosal surface, and multiple lesions may be distributed in a Christmas tree pattern along skin folds or in Blaschko's lines.2 The color of these lesions ranges from pale white to black. At times, distinguishing these lesions from a nevus or melanoma can be clinically challenging. Because melanoma, basal cell carcinoma, and other cutaneous malignancies have been reported to arise in SKs, care must be taken to critically evaluate rapidly growing, symptomatic, or unusual lesions.3,4

The name seborrheic comes from the Greek word for sebum, and is a misnomer for these common growths. While the precise etiology of SKs is unknown, it is a tumor of keratinocytic origin. Genetics, sun exposure, and infection have all been implicated as possible factors. Many individuals with SKs have a positive family history for the condition. SKs demonstrate irregularities in the expression of the apoptosis markers p53 and Bcl-2, though no genetic locus or chromosomal imbalance has been detected to date.5,6 The higher prevalence of SKs on sun-exposed skin implies a possible causative role.7

Viral infection has also been considered a possible cause of SKs based on occasional clinical similarities to warts. Although no human papillomavirus (HPV) DNA was detected in a study of 40 genital SK biopsies, nongenital skin yielded different results. Epidermodysplasia verruciformis-associated HPV DNA has been demonstrated in 42 of 55 (76%) nongenital SK biopsies compared to only 13 of 48 (27%) healthy controls (p < 0.005).8 These findings indicate the possible role of viral infection in the development of SKs in nongenital skin.

Although the etiology of SKs remains unknown, the monoclonal nature of these neoplasms has been established in 2001.9 By tracking polymorphisms in a human androgen receptor, researchers found that more than half of the 38 SKs sampled, regardless of subtype, were clonal in nature.9 The development of SKs has also been associated with circulating epidermal growth factors and melanocyte-derived growth factors in addition to the local increased expression of tumor necrosis factor-α and endothelin-converting enzyme.10 The latter two are associated with an increased expression of the keratinocyte melanogen, endothelin-1, resulting in hyperpigmentation within SKs.

There are many clinicopathologic variants of SKs, and while distinction is usually unnecessary, the commonplace nature of SKs makes these variants relevant.

Common Seborrheic Keratosis

A common SK is classically described as a stuck-on, verrucous plaque (Figs. 118-1 and 118-2) with pseudohorn cysts (Fig. 118-3). Hyperkeratosis, acanthosis, and papillomatosis are hallmark pathologic findings. An increased number of melanocytes may also be present, giving lesions a tan or dark brown color. SKs are usually asymptomatic but may itch. Common SKs spare the palms, soles, and mucosa.

Reticulated Seborrheic Keratosis

Reticulated SKs are also known as adenoid SKs. Some believe a solar lentigo usually precedes this often pigmented patch or papule. Histologically, there are small horn cysts suspended among interwoven strands of basophilic cells (Fig. 118-4).11

Stucco Keratosis

Stucco keratoses are also described as verrucous, serrated, hyperkeratotic, and digitate. These lesions are commonly 1- to 3-mm, flat-topped, white to tan papules that adhere tightly to the skin on the lower legs (eFig. 118-4.1). Histologically, no keratinocytic vacuolar changes or viral cytopathic changes are observed, thus distinguishing them from verruca plana.

Melanoacanthoma

Melanoacanthoma is also known as pigmented SK. This benign, slow-growing SK resembles melanoma clinically, and is often located on the trunk, head, or neck of older individuals. The term melanoacanthoma was introduced in 1960 to describe a pigmented lesion composed of nested melanocytes and keratinocytes.12

Dermatosis Papulosa Nigra

Dermatosis papulosa nigra are small dark brown to black papules that are commonly found on the face of individuals of Fitzpatrick skin phototype IV or greater. They are histologically identical to SKs (Fig. 118-5).

Skin Tags

While often felt to be a distinct entity, some skin tags share clinical and histologic overlap with some SKs. These rough, 1- to 2-mm pedunculated papules are commonly located in areas of friction. The axilla, inframammary area, and neck are common locations where these papules commonly appear. Spontaneous regression can occur.

Histologic Variants

Clonal Seborrheic Keratoses

Clonal SK is a histologic term used to describe intraepithelial nests of basophilic keratinocytes of varying sizes with admixed melanocytes (Fig. 118-6). As previously stated, in one study, more than half of the 38 SKs sampled, regardless of subtype, were clonal in nature.9

Irritated Seborrheic Keratosis

Irritated SKs represent SKs that have been mechanically or chemically irritated or are involved in immunologic responses. Although inciting trauma is occasionally associated with irritated SKs, spontaneous inflammation is common (Fig. 118-7). Histologically, the dermis underlying these lesions is filled with a dense inflammatory infiltrate predominantly of lymphocytes. This inflammation is occasionally lichenoid or neutrophil rich. Swirled collections of eosinophilic keratinocytes can be seen in the epidermis.13 Eczematous changes in or around the lesion, also known as Meyerson phenomenon, can also be seen.14

Association with Skin Cancers

Varying degrees of squamous atypia can be seen in SKs. Bowenoid transformation of benign SKs into squamous cell carcinoma in situ has been documented but the development of basal or squamous cell carcinoma in a SK is rare.15 Lesions demonstrating the histology of both SKs and malignancies have been reported.16,17 Although it is likely that most of these lesions represent collision tumors, malignant transformation of SKs into basal cell carcinomas, squamous cell carcinomas, and melanomas can occur. In a retrospective study of 813 lesions histologically diagnosed as SKs, 5.3% were associated with nonmelanoma skin cancer. In this study, the most common malignancy was squamous cell carcinoma in situ, followed by basal cell carcinomas and invasive squamous cell carcinomas; no melanomas were observed.17 Clinically atypical or rapidly growing SKs should be biopsied to rule out the possibility of malignancy.

Leser–TréLat Sign

In the context of internal malignancy, individuals can develop multiple, eruptive SKs also known as the Leser–Trélat sign. Adenocarcinoma of the stomach is the most commonly associated malignancy,18,19 though adenocarcinoma of the lung and colon have also been linked. Other diseases reported to occur with eruptive SKs are leukemia, lymphoma, lepromatous leprosy, human immunodeficiency virus infection, erythrodermic eczema, and melanoma.20–23 Inflammation of eruptive SKs during chemotherapy, especially cytarabine, is known to occur (Fig. 118-7).24 The presentation of eruptive SKs with acanthosis nigricans led many to speculate a common reactive mechanism.25 Abnormal immune responses may also play a role in the development of this clinical sign.

Treatment

Rapid growth, atypical morphologic features, unusual lesion location, or symptoms should all be considered when evaluating SKs, and care should be taken not to destroy a lesion that begs further pathologic examination. For any lesion with a possibility of malignancy, removal must be performed in a fashion that yields tissue for evaluation.

For clearly benign, yet symptomatic or cosmetically undesirable lesions, destruction with cryotherapy, electrodesiccation followed by curettage, curettage followed by desiccation, or laser ablation have all been shown to be effective. Reports of giant SKs measuring many centimeters have been treated successfully with either dermabrasion or topical fluorouracil.26,27 Surgical excision is also an accepted treatment approach, especially if the lesion is pedunculated and can be transected at its base. Common complications of these destructive measures include scarring, pigmentary alteration, incomplete removal, or recurrence. Recurrence of the lesions may occur, and it is not uncommon to require multiple treatments to ensure the complete destruction of the initial lesion. It is preferable to ensure that the method of removal minimizes the risk of scarring.

Epidermal nevus is a generalized term for hamartomatous proliferations of epithelium. The subtypes of this tumor differ according to the distribution of the lesions or the predominant histologic cell type: keratinocyte (verrucous epidermal nevus), sebaceous gland (nevus sebaceous), pilosebaceous unit (nevus comedonicus), eccrine gland (eccrine nevus), or apocrine gland (apocrine nevus). eTable 118-1.1 provides a classification of one framework to discuss this large and diverse entity. Currently, there are six different epidermal nevus syndromes described: (1) Proteus, (2) congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome, (3) phakomatosis pigmentokeratotica, (4) sebaceous nevus, (5) Becker's nevus, and (6) nevus comedonicus.28

Epidemiology

Epidermal nevi occur in 1 in 1,000 live births.29 Eighty percent of lesions appear within the first year of life, with the majority of lesions appearing by age 14 years. There are rare reports of adult onset of epidermal nevi, with the oldest patient being a 60-year-old woman.30 Such late-developing epidermal nevi probably represent lesions that have always been present subclinically, but recent growth resulted in clinical recognition.31 There is an equal male–female prevalence, and most cases are sporadic. However, some familial cases have been documented.32

Verrucous Epidermal Nevus

Verrucous epidermal nevus is also known as linear verrucous epidermal nevus or linear epidermal nevus.

Clinical Features

Verrucous epidermal nevi are characterized by localized or diffuse, closely set, skin-colored, brown, or gray–brown verrucous papules, which may coalesce to form well-demarcated papillomatous plaques (Fig. 118-8). Linear configurations are common on the limbs as is distribution in Blaschko's lines or in relaxed skin tension lines (Fig. 118-9).

Extensive distribution of a verrucous epidermal nevus is termed systemized epidermal nevus. Variants of this type of nevus include nevus unius lateris (Fig. 118-10), epidermal nevi distributed on one-half of the body; and ichthyosis hystrix, epidermal nevi distributed bilaterally. Commonly, systematized nevi take on a transverse configuration on the trunk and linear configuration on the limbs.

An epidermal nevus presenting with pruritus, erythema, and scaling is likely a variant of the epidermal nevus termed an inflammatory linear verrucous epidermal nevus (ILVEN) (Fig. 118-11). These lesions are found most commonly on the buttocks and lower extremities.

Course and Complications

Linear epidermal nevi tend to appear between birth and adolescence. Although congenital lesions tend not to expand significantly, lesions that present after birth may expand during childhood, stabilizing in size at or around puberty.33 Although intertriginous lesions may become macerated and secondarily infected, the majority of epidermal nevi remain quiescent after adolescence. Rare cases of basal cell carcinoma and squamous cell carcinoma arising within epidermal nevi have been reported. This malignant transformation is most common in middle-aged or elderly individuals, though the youngest reported case occurred in a 17-year-old woman.34

Epidermal nevi may present in conjunction with other epidermal lesions such as café-au-lait macules, congenital hypopigmented macules, and congenital nevocellular nevi and may be associated with abnormalities in other systems.33 (See Section “Epidermal Nevus Syndrome”).

Rarely, patients with epidermal nevi have offspring with epidermolytic hyperkeratosis (EHK), a condition resulting from a mutation in keratin 10 (K10). Paller et al35 investigated three families with this occurrence. The analysis of skin samples of parents and offspring with EHK demonstrated a parental mutation in one of the two K10 alleles within the epidermal nevus; nonlesional skin showed no mutation. Offspring showed the same K10 mutation as their parents.35 The presence of two genetically distinct cell lines in the parents, also known as mosaicism, is a result of postzygotic mutation during embryogenesis.36 If histopathologic evaluation of an epidermal nevus reveals findings consistent with EHK, the patient is at risk of having a child with EHK. Prenatal counseling may be very important for these patients.

Pathology

There are ten histologic variants of the epidermal nevus, with over 60% of lesions displaying acanthosis, papillomatosis, and hyperkeratosis (Fig. 118-12).37 Rare variants may have features similar to SKs, with thin, elongated rete ridges; or EHK, with compact orthokeratosis, vacuolization of the granular layer of the epidermis, and large keratohyalin granules within or outside cells.38 Epidermal hyperkeratosis may be a more common finding in ichthyosis hystrix. ILVEN is a histologically distinct variant of the epidermal nevus that displays a chronic dermal inflammatory infiltrate, psoriasiform epidermal hyperplasia, and alternating bands of ortho- and parakeratosis. In this variant, the granular layer is absent underlying the areas of parakeratosis.39

Differential Diagnosis

(See Box 118-1).

Lichen striatus, linear Darier disease, linear porokeratosis, linear lichen planus, linear psoriasis, and the verrucous stage of incontinentia pigmenti may all have similar clinical presentations as the linear verrucous epidermal nevus. Lichen striatus may mimic ILVEN clinically, but is self-limited as compared with epidermal nevi. Histology may be useful in differentiating these entities. Linear Darier disease and linear porokeratosis can be differentiated pathologically with linear Darier disease having the distinct pathologic findings of acantholytic dyskeratosis, and linear porokeratosis having coronoid lamellae. Although some consider linear lichen planus and linear psoriasis to be variants of the ILVEN, the genetics and the immunology has yet to be fully characterized.40–42 Incontinentia pigmenti can be distinguished clinically based on the transient nature of this phase and the preceding verrucous phase. Histologically, this entity can be distinguished by its dyskeratosis, pigment incontinence, eosinophilic exocytosis, and basal layer vacuolization.

Treatment

Complete excision of an epidermal nevus to the level of the deep dermis is necessary to prevent recurrences. However, based on the size and distribution of the lesion, excision may not be an appropriate treatment option. Multiple other surgical and medical treatments are available to treat or destroy these lesions. Laser ablation, electrofulguration, cryotherapy, and medium to full-depth chemical peels may offer partial or full destruction of lesions. Although topical retinoids and calcipotriene offer little relief, these medications can be used as an adjunctive therapy to increase the efficacy of the surgical intervention. Systemic retinoids and antipsoriatic agents may offer some clinical improvement. There are reports of successful treatment of ILVEN with etanercept.43 If malignant transformation is confirmed within an epidermal nevus, the lesion should be completely excised.

Nevus Sebaceous

Nevus sebaceous is also known as nevus sebaceous of Jadassohn and organoid nevus.

Clinical Features

Nevus sebaceous presents as a linear, hairless, yellow, waxy, and verrucous plaque (Fig. 118-13). It can be flat at birth, becoming plaque-like under the hormonal influences of puberty. These nevi are common in the scalp, but there are reports of lesions on the face, chest, and in oral mucosa. Tumors can arise within nevus sebaceous. The most common benign tumors are syringocystadenoma papilliferum and trichoblastoma.44 Other benign tumors reported to arise in a nevus sebaceous are the leiomyoma, syringoma, spiradenoma, hidradenoma, and keratoacanthoma.45 It was once believed that individuals with this tumor were at increased risk of basal cell carcinomas, but a retrospective review of 596 cases by Cribier et al revealed that most lesions initially diagnosed as basal cell carcinoma were actually trichoblastomas.46 A second retrospective study of 757 tumors confirmed this finding.47 This does not exclude the possibility of the development of basal cell carcinoma in these lesions. Rarely, malignant tumors such as apocrine carcinoma, squamous cell carcinoma, and malignant eccrine poromas may arise within nevus sebaceous.48

Nevus sebaceous syndrome is the very rare association of an extensive, congenital nevus sebaceous with ocular abnormalities and cerebral defects such as mental retardation or seizures. This syndrome is also known as Schimmelpenning-Feuerstein-Mims syndrome or organoid-nevus syndrome.49,50

Pathology

Immature sebaceous glands located high in the dermis and malformed pilosebaceous units are features of nevus sebaceous (Fig. 118-14). Vellus hairs are more common than terminal hairs in these lesions. Epidermal acanthosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia can also be seen.

Differential Diagnosis

Epidermal nevi and aplasia cutis may be clinically similar to nevus sebaceous but biopsy can easily distinguish between these entities.

Treatment

Excision of nevus sebaceous was common when these lesions were thought to carry an increased risk of basal cell carcinoma. Rapidly growing papules or nodules demand pathologic evaluation to evaluate for rare malignancies, but excision should be considered on a case-by-case manner.48

Nevus Comedonicus

Nevus comedonicus is also known as comedo nevus, nevus follicularis keratosis, nevus acneiformis unilateralis, and nevus zoniforme.51 Nevus comedonicus is a rare hamartoma of the pilosebaceous unit.52,53 Clinically, comedo-like dilated pores with keratinaceous plugs present in a linear, nevoid, bilateral, or zosteriform pattern (Fig. 118-15).52 An inflammatory variant also exists, with suppurative cysts and acne-like lesions. These lesions appear on the face, chest, or upper arms at birth or during childhood.28 Nevus comedonicus syndrome is the association of nevus comedonicus with noncutaneous findings such as skeletal defects, cerebral abnormalities, and cataracts.54

Course and Complications

Nevus comedonicus lesions follow a noninflammatory or inflammatory course and do not resolve spontaneously. The inflammatory course may result in scarring. Nevus comedonicus syndrome results in developmental, cerebral, skeletal, or ocular defects that present by the age 15 years.55

Pathology

The hallmark findings in nevus comedonicus are keratin-filled epidermal invaginations associated with atrophic sebaceous glands or follicles. EHK may be seen.56

Differential Diagnosis

The differential diagnosis of this lesion includes acne vulgaris, milia, acne neonatorum, nevus sebaceous, and linear Darier disease.

Treatment

The noninflammatory variant of nevus comedonicus is usually asymptomatic, with treatment based on the cosmetic concerns of the patient. The inflammatory variant can result in significant suppuration and pain, requiring medical or surgical intervention. Inflammation may be controlled with tazarotene cream or other retinoids, tacrolimus ointment, calcipotriene cream, and intralesional steroids.57 Keratolytics may be of some help. Systemic antibiotics may help to control infection or inflammation. Surgical interventions, such as extraction, excision, dermabrasion, or laser resurfacing, may result in good clinical results.58,59

Eccrine Nevus

An eccrine nevus, the simplest form of eccrine hamartoma, is characterized by an increase in the number or size of eccrine coils.60–63 Fewer than 20 cases of eccrine nevi have been described in the literature. Distributed on the trunk, arms, or legs, these lesions occur equally in men and women. Although there seems to be a childhood predominance, the onset ranges from birth to the eighth decade.64 The morphology of eccrine nevi may vary, appearing clinically as tan papules or normal skin.65–66 These lesions do not always display hyperhidrosis, however, when they do, treatment is targeted at the control of that symptom. Agents such as aluminum chloride solution, anticholinergics, antidepressants with anticholinergic activity, botulinum toxin, iontophoresis, or sympathectomy have been reported to help control the hyperhidrosis. Surgical excision of the lesion is also an acceptable treatment.67,68

Apocrine Nevus

Apocrine nevi are hamartomatous proliferations of mature apocrine glands often found within a nevus sebaceous. Clinical presentation varies, but they can be found as soft nodules or papules in the axilla or on the upper chest. Histologically, the apocrine glands extend from the epidermis to the fat. These lesions can be surgically excised if desired.69

Epidermal Nevus Syndrome59

Epidermal nevus syndrome is also known as Schimmelpenning syndrome, Feuerstein–Mims syndrome, and Solomon syndrome. Epidermal nevus syndrome is the association of any type of epidermal nevus with various cutaneous, ocular, neurologic, skeletal, cardiovascular, or urogenital developmental abnormalities. Historically, there have been six epidermal nevus syndromes described: (1) Proteus syndrome, (2) congenital hemidysplasia with ichthyosiform nevus and limb defects, (3) phakomatosis pigmentokeratotica, (4) sebaceous nevus, (5) Becker's nevus, and (6) nevus comedonicus. Some authors argue that epidermal nevus syndrome is a collection of many different distinct clinical syndromes.

Happle70 proposed that the epidermal nevus syndrome is not a single entity but consists of at least six distinct diseases that differ in genetic origin and share the common feature of mosaicism. The entities include Schimmelpenning syndrome; nevus comedonicus syndrome; pigmented hairy epidermal nevus syndrome; Proteus syndrome; congenital hemidysplasia, ichthyosiform dermatitis, and limb defects syndrome; and phacomatosis pigmentokeratotica.

Epidemiology

Epidermal nevus syndrome affects men and women equally and presents within the first 40 years of life. Inheritance is sporadic, although anecdotal reports of familial transmission have been reported.70 Although the exact incidence of epidermal nevus syndrome is unknown, a study of 119 cases of epidermal nevi showed that 33% of patients showed one or more extracutaneous abnormalities, 16% showed two or more abnormalities, 10% showed three or more abnormalities, and 5% showed five or more abnormalities.

Clinical Features

Solomon and Esterly provided a detailed account of the spectrum of epidermal nevi seen in the epidermal nevus syndrome.29 They described seven types of lesions. The majority of patients had nevus unius lateris; 20% of patients had ichthyosis hystrix; and another 20% had what the authors termed the acanthotic form of epidermal nevus. These lesions presented as large, unilateral, brown, slightly scaly patches. About 10% of patients had linear nevus sebaceous involving the scalp and face. Localized linear verrucous nevus and a velvety epidermal nevus in the axilla similar to acanthosis nigricans were seen in a minority of cases. Some patients had a mixture of several types of lesions.

Table 118-2 lists the mucocutaneous changes other than epidermal nevus that may be seen in patients with epidermal nevus syndrome.71 Hemangiomas and pigmentary changes are found in 10%–20% of patients. Less common findings are hair abnormalities, dental abnormalities in association with mucosal epidermal nevi, and dermatomegaly. This last condition involves an increase in skin thickness, warmth, and hairiness. As discussed earlier, various cutaneous tumors may develop within the epidermal nevus.

A wide range of skeletal abnormalities has been reported (eTable 118-2.1).70–72 The incidence of skeletal changes has ranged from 15% to 70%.

Neurologic abnormalities occur in 15%–50% of cases (eTable 118-2.2).

From 9% to 30% of patients with epidermal nevus syndrome have ocular abnormalities (eTable 118-2.3).73

As in isolated epidermal nevi, malignant transformation may occur within the epidermal nevi in patients with epidermal nevus syndrome. This occurrence is most common in those with nevus sebaceous. Perhaps less well known is the association of visceral malignancies with the epidermal nevus syndrome. The following tumors are reported to occur at a higher frequency and at an earlier age in patients with epidermal nevus syndrome: tumors of the genitourinary system (Wilms’ tumor, nephroblastoma, metastatic transitional cell carcinoma of the bladder, and rhabdomyosarcoma of the bladder); tumors of the gastrointestinal tract (hepatic adenoma, salivary gland adenocarcinoma, and carcinoma of the esophagus and stomach); and tumors of the central nervous system (astrocytoma, mixed glioma, and meningioma). Breast carcinoma, mandibular ameloblastoma, chondroma, odontoma, and endometrioma are other tumors associated with epidermal nevus syndrome.41 However, these associations have not been confirmed by case-controlled studies.

Management

Patients with extensive epidermal nevi or those with epidermal nevi and systemic abnormalities should be suspected of having the epidermal nevus syndrome. Evaluation and management of patients with epidermal nevus syndrome requires a multidisciplinary team approach involving the dermatologist, pediatrician, ophthalmologist, neurologist, plastic surgeon, and orthopedic services. These patients require a careful history with particular attention given to developmental history, attainment of milestones, history of seizures, and abnormalities of the bones, eyes, and urinary tract. Thorough mucocutaneous, neurologic, ophthalmologic, and orthopedic examinations are necessary. Most cases of Proteus syndrome are caused by a mosaic activating mutation in AKT1. (N Engl J Med 365:611-619, 2011). A regular follow-up program should be planned for the patient.

Lichen striatus is a rare, idiopathic, linear, papular eruption that usually resolves in 1–2 years.

Etiology and Epidemiology

Lichen striatus, which is also known as Blaschko linear acquired inflammatory skin eruption, most commonly affects individuals from 4 months to 15 years of age.74 The etiology is unknown. This self-limited dermatosis occurs most commonly on the limbs in females. However, distribution on the face and trunk has been reported.75 Nail changes are uncommon.76 Most cases are distributed in Blaschko's lines, though axial distributions have been reported. A retrospective analysis of 155 cases of children with lichen striatus revealed an association with atopic dermatitis in 70 of the cases.77

Clinical Features78

Lichen striatus is an eruption characterized by the sudden onset of flat-topped, 1–3 mm, pink, tan, or hypopigmented papules in a linear configuration or Blaschkoid distribution (Fig. 118-16). Bilateral eruptions have been reported, though unilateral lesions are the norm. These flat-topped papules may have an associated scale. Longitudinal ridging and nail plate thinning can be seen. This eruption is usually self-limited, lasting from a few months to 2 years before spontaneously regressing.

Pathology

Lichen striatus is characterized by a lichenoid, lymphocytic infiltrate involving three to four adjacent dermal papillae with overlying epidermal acanthosis, dyskeratosis, hyperkeratosis, and occasional parakeratosis.78,79 Intraepidermal vesicles containing Langerhans cells can be seen in half of the cases.80

Differential Diagnosis

Lichen planus, psoriasis, linear porokeratosis, lichen nitidus, Darier disease, and ILVEN can have similar morphology and distribution to lichen striatus. These clinical entities can usually be separated based on histopathology. ILVEN can be distinguished clinically because of its earlier onset and lack of spontaneous regression.80

Treatment

Symptomatic control of pruritus with topical steroids may be necessary. Otherwise, treatment is generally not necessary for this self-limited condition.

Clear cell acanthoma is most commonly found equally in men and women ages in the sixth to eighth decade.

Etiology

The etiology of clear cell acanthoma, also known as Degos acanthoma and pale cell acanthoma, is unknown. When initially described by Degos et al in 1962, the lesion was thought to be benign tumor of epithelial origin.81 Although initially thought to be of follicular or sweat-gland origin, the expression of involucrin and epithelial membrane antigen by clear cell acanthomas indicates an epithelial origin.82–84 The cytokeratin staining patterns, interestingly, reveal staining patterns commonly found in inflammatory dermatoses such as lichen planus, psoriasis, and discoid lupus.85 The presence of clear cell acanthomas on psoriatic plaques has led many to question the role of inflammation in the development of these lesions.86

Clinical Features

Clear cell acanthoma is commonly a solitary, shiny, erythematous to brown, well-demarcated papule or nodule that blanches almost fully with pressure (Fig. 118-17). Surrounding the lesion is a collarette of scale. These lesions range from 5 mm to 2 cm, although the giant clear cell acanthoma can measure greater than 5 cm.87 The lesions are usually found on the legs but can be located on the trunk and face. Although commonly solitary, multiple lesions have been reported. The dermatoscopic findings of the clear cell acanthoma are similar to that seen in psoriasis, with vascular puncta prominent in the lesion.88 These lesions bleed with trauma.

Pathology

Sharply demarcated, pale-staining keratinocytes within a background of epidermal psoriasiform hyperplasia is characteristic in a clear cell acanthoma (Fig. 118-17). The glycogen-rich keratinocytes in the epidermis stain distinctively with periodic acid-Schiff, which then can be washed out by diastase that digests the glycogen.89 Other epidermal findings include suprapapillary plate thinning, neutrophils, and sparing of adnexal epidermis. A mixed inflammatory infiltrate, papillary dermal edema, and enlarged vessels can be seen in the dermis.

Treatment

Cryotherapy, curettage and electrodesiccation, laser ablation, or surgical excision, have been used to successfully treat this lesion.90

See reference 91.

Etiology and Pathogenesis

Clinical Features

Pathology

Treatment

Clinical Features

Pathology

Differential Diagnosis

Treatment, Course, and Prognosis

Also called clavus helicis, chondrodermatitis nodularis helicis (CNH) is a chronic, solitary, tender, ulcerated nodule on the helix of the ear, first described in 1915.97

Etiology and Pathogenesis

Many etiologic factors have been suggested for CNH. It is thought to be a disease of degenerated collagen that undergoes transepithelial elimination.98 Vascular insufficiency, pressure, injury to the cartilage, sun-exposure, and low temperature have all been implicated in inciting cartilage damage. Recently, Magro et al described 24 patients with early-onset CNH who had concomitant microvascular disease, strengthening the argument for the role of ischemia in the development of this process.99 Reports of CNH in association with the pressure from cell phone use has also been documented.100 The finding of solar elastosis histologically at the periphery of many lesions along with the prevalence of CNH in lightly pigmented populations raise the possible link between sun-exposure and CNH.101

Clinical Features

This disorder is found overwhelmingly in adult men over the age of 50, with the male–female prevalence being greater than 2:1.102 Two cases of CNH in children have been reported.103,104 Patients present with a history of a suddenly appearing, skin-colored to pink papule or nodule on the ear that grew rapidly and subsequently remained quiescent. These lesions tend to be on the right helix, measure less than 1 cm, and are associated with pain (Fig. 118-18). The pain can be paroxysmal or associated with changes in ambient temperature. The lesion may have a central ulceration with an adherent hemorrhagic or scale crust. Spontaneous resolution of CNH is unlikely. A possible subset of CNH may be seen in elderly women who have a history of prior trauma. For these women, spontaneous regression is not uncommon.

Differential Diagnosis

Basal cell carcinoma, keratoacanthoma, warts, rheumatoid nodules, squamous cell carcinoma, clavus, and tophus are all within the differential of CNH.

Pathology105

In the epidermis, there is commonly hyperkeratosis and parakeratosis; ulceration may be present. Occasionally, degenerated collagen is seen in the epidermis, indicating a transepidermal elimination process. A brisk, predominantly lymphocytic infiltrate is noted in the dermis with admixed histiocytes and few neutrophils. Telangiectasias and solar elastosis are often noted in the adjacent dermis. The perichondrium shows inflammation and fibrous thickening. The cartilage may show hyalinization, necrosis, and, at times, ossification.

Treatment

Conservative treatment includes pressure-relieving pillows with a doughnut shape that are commercially available. In a recent study examining the role of such pressure-relieving devices, 13 of 15 patients (87%) were healed at follow-up after 1 month of conservative treatment.106 High-potency steroids, intralesional steroids, and laser ablation may also be used to induce symptom control or regression of the lesion.107 Excision of CNH nodules using a shave or excisional technique through and around the affected cartilage is also an accepted treatment option, though recurrences may occur at the edge of the lesion.108

Epidermoid Cyst

An epidermoid cyst, also known as a follicular cyst-infundibular type, keratin cyst, epidermal cyst, epidermal inclusion cyst, or an epithelial cyst, is a keratin-filled epithelial-lined cyst. The term sebaceous cyst is a misnomer and should be avoided, as these cysts do not involve sebaceous glands, nor do they contain sebum.

Epidemiology

Epidermoid cysts are found most commonly in adult men and women. Genetic disorders, such as Gorlin syndrome (nevoid basal cell carcinoma syndrome), pachyonychia congenita type 2 (Jackson–Lawler type), and Gardner syndrome, may predispose individuals to having this type of cyst.

Etiology and Pathogenesis

Epidermal cysts are most commonly the result of plugged pilosebaceous units. These cysts express the same cytokeratin profile as the follicular infundibulum.109 Epidermal cysts can also be caused by the traumatic implantation of epidermal cells into deeper tissues or by the proliferation of viable epidermal remnants along embryonic fusion planes.110,111 Epidermoid cysts can be located anywhere on the body and are characterized by their distinctive pathology. Recently, HPV type 57 and 60 DNA has been detected in palmoplantar epidermoid cysts.112,113

Clinical Presentation

Epidermoid cysts are classically dermal or subcutaneous mobile nodules with a central punctum (Fig. 118-19). Lesions not associated with trauma are commonly located on the upper chest, upper back, neck, or head. Traumatic lesions are more common on the palms, soles, or buttocks. The punctum, when present, represents the plugged pilosebaceous unit from which foul smelling cheesy debris may be expressed. These lesions can be skin-colored, yellow, or white. Cysts are usually slow growing and asymptomatic, though rupture is common.

Complications

A brisk, foreign-body giant cell reaction is possible if epidermoid cysts rupture into surrounding tissue. This foreign-body reaction may mimic that of secondary bacterial infection. However, polymicrobial infection of a cyst with aerobic or anaerobic organisms may occur. Common aerobes include Staphylococcus aureus, group A Streptococcus, and Escherichia coli, while common aerobes include Peptostreptococcus species and Bacteroides species. Polymicrobial infection is most common. Although the clinical course of epidermoid cysts is benign, basal cell carcinoma, squamous cell carcinoma, epithelioid carcinoma, and other malignancies have been reported to occur in conjunction with these cysts, though malignant transformation is rare.114–116

Pathology

An epidermoid cyst has a stratified, squamous lining with an intact granular layer (Fig. 118-20). These cysts contain central, eosinophilic, keratinaceous debris that can incite a foreign-body reaction of multinucleated giant cells and histiocytes when released into the dermis and surrounding tissue.

Differential Diagnosis

Steatocystoma multiplex, pilar cysts, and lipomas can all mimic epidermoid cysts. However, clinically, steatocystoma multiplex usually express a liquid rather than a cheesy material, pilar cysts are most commonly on the scalp, and lipomas are softer, deeper, and without a punctum. Pathology also distinguishes between these lesions.

Treatment

Complete excision or destruction of the cyst lining is the definitive treatment, and is required to prevent cyst recurrence. Intralesional steroids at a concentration of 5 mg/mL can be used to control small, inflamed, symptomatic lesions. If the cyst becomes inflamed, painful, or purulent, infection must be considered. Incision and drainage with oral antibiotic therapy to treat S. aureus should be initiated. Wound cultures with directed therapy may be indicated, based on the clinical presentation of the lesion. If the cyst has ruptured or has become infected, excision of the lesion should be deferred until the inflammation has decreased which will decrease the likelihood of wound dehiscence.

Trichilemmal Cyst (Pilar Cyst)

Trichilemmal cysts are keratin-filled, epithelial-lined cysts usually on the scalp that arise from the outer root sheath of the hair follicle.

Epidemiology

Trichilemmal cysts can be found in 5%–10% of the population, most commonly in middle-aged women.

Etiology and Pathogenesis

Pilar cysts arise from the epithelium located between the orifice of the sebaceous gland and the arrector pili muscle. This squamous epithelium undergoes rapid keratinization resulting in a cyst wall without a granular layer.

Clinical Features

Pilar cysts are mobile, firm, well-circumscribed nodules located overwhelmingly in the scalp (Fig. 118-21). These lesions can also be found on the face, head, and neck. Most patients have more than one lesion, with 10% of people having more than 10 lesions. Rapid growth is abnormal and can be a sign of infection or malignant transformation.117

Complications

Although these lesions largely remain asymptomatic, rupture and infection can occur. Proliferating trichilemmal tumors are a variant of this benign lesion and are commonly found on the scalp of elderly women. This lesion can destroy adjacent lesions and ulcerate, mimicking skin cancer. Malignant degeneration of pilar cysts into malignant proliferating trichilemmal cysts can occasionally occur.

Pathology

The hallmark finding of these cysts is the absence of a granular layer within the cyst wall (Fig. 118-22). The cyst content is usually eosinophilic keratin, but basophilic areas of calcification may occur in the lumen of these lesions. If lobules of squamous epithelium are seen in the walls of the lesion, it is most likely a proliferating trichilemmal cyst. Invasion of the cyst lining into the surrounding tumor indicates malignancy.

Differential Diagnosis

See Section “Differential Diagnosis” under “Epidermoid Cyst.”

Treatment

The treatment is the same as with epidermoid cysts. Because the cyst wall of these tumors is clinically more firm than that of epidermoid cysts, it is possible to extract the lesion through a small incision made with a dermal punch trephine.

Milium

Milia are minute epidermoid cysts, lined with epidermis and filled with keratin.

Epidemiology

Milia are common congenital and acquired lesions in both infants and adults. Men and women are affected equally.

Etiology and Pathogenesis

Milia are thought to result from pilosebaceous or eccrine sweat duct plugging. These superficial lesions can be primary or secondary, with the latter resulting from injury to the basement membrane of the skin. Secondary lesions are common in subepidermal blistering diseases such as epidermolysis bullosa and porphyria cutanea tarda, burns, after dermabrasion or ablative laser resurfacing, or in conjunction with topical therapy such as glucocorticoid therapy or 5-fluorouracil treatment.118–121

Clinical Features

Milia are 1- to 2-mm, white, domed papules commonly located on the cheeks and eyelids of adults (Fig. 118-23). In infants, milia are common on the face and the mucosa. Epstein's pearls are milia on the palate. Eruptive milia have been reported, though this is a rare occurrence.121 Milia en plaque is a plaque-type, inflammatory variant of milia that is commonly located on the ear.122 Acquired milia (eFig. 118-23.1) can be located anywhere the predisposing trauma or other factors have occurred.

Pathology

The pathology of a milium is similar to that of an epidermoid cyst, but the small size and occasional connection to eccrine ducts or vellus hair follicles distinguish these two entities. Bacteria are not usually seen in milia.

Treatment

Congenital milia tend to spontaneously resolve. Acquired milia can resolve spontaneously as well, but can also be removed by disrupting the overlying epidermis with light electro-desiccation or incision, usually with an 11-blade and expressing the keratin contents.

Steatocystoma Multiplex

Steatocystoma multiplex are numerous, epithelial-lined, sebum-filled dermal cysts with characteristic sebaceous glands in the cyst walls.

Etiology and Pathogenesis

Steatocystoma multiplex, (sebocystomatosis, epidermal polycystic disease) can be a sporadic or autosomal-dominant disorder. These lesions can also be found in syndromes such as Alagille syndrome and pachyonychia congenita type II. In the latter, lesions are associated with mutations in K17. Sporadic solitary lesions are termed steatocystoma simplex.

Clinical Features

These lesions present as asymptomatic, yellow or skin-colored dermal papules or cysts located most commonly on the trunk, upper arms, scrotum, or chest (Fig. 118-24). Oily material can be expressed from these lesions when incised. These lesions can become infected and suppurate, resulting in sinus formation and scarring.

Pathology

The cyst walls of steatocystoma multiplex are composed of stratified, squamous epithelium with an absent granular layer. Sebaceous glands are located in the cyst wall (eFig. 118-24.1). There is an eosinophilic cuticle on the luminal side of this wall with keratin, oil, and hairs in the lumen.

Differential Diagnosis

Eruptive vellus hair cysts can mimic steatocystoma multiplex clinically. They may have a tuft of hairs protruding from the cyst centrally, with findings of vellus hairs in the lumen with follicles in the wall. Epidermal inclusion cysts also have to be excluded. The pathogenesis of steatocystoma, epidermal inclusion cysts, and eruptive vellus hair cysts may be similar.123

Treatment

At times, simple excision or drainage with manual removal of the cyst wall results in the clinical resolution of lesions.124,125 Inflamed lesions have been reported to respond to intralesional steroids, carbon dioxide laser, oral retinoids, or cryotherapy.126

Dermoid Cyst

Dermoid cysts are epithelial-lined cysts containing various appendageal structures resulting from retained epithelium along embryonic fusion planes. These cysts are either congenital or develop in childhood. The prevalence is equal in men and women.

Clinical Features

Dermoid cysts are smooth, occur in the midline, and commonly possess a deep sinus tract that connects to the epidermis. They can measure between 1 cm and 4 cm, and are most commonly located on the forehead, lateral eye, or neck.127,128 A superficial dermoid cyst located on the dorsal nose is referred to as fistula of the dorsum of the nose and is characterized by a central tuft of hair or communication intracranially. Dermoid cysts can be located deep in the subcutaneous tissue, intracranially, or intraorbitally.129

Complications

Infections, rupture, and abscess formation from the manipulation of these cysts are possible serious complications.

Pathology

Stratified squamous epithelium with a variety of adnexal structures may be present in the walls of dermoid cysts. Smooth muscle, pilosebaceous units, apocrine or eccrine glands, or goblet cells may also be present in the cyst walls. These cysts contain keratin and hairs.

Differential Diagnosis

The differential diagnosis of dermoid cysts includes gliomas, encephaloceles, hemangiomas, soft tissue sarcomas, and other epidermal cysts such as branchial cleft cysts and thyroglossal duct cysts.

Treatment

Imaging studies that help to characterize the extent of the tumor are necessary before excision is undertaken. Consultation with neurosurgery, otolaryngology, or plastic surgery may be indicated.

Branchial Cyst (Branchial Cleft Cyst)

Sequestration of first or second branchial cleft membranes results in these cysts, sinuses, or tags.

Epidemiology

Branchial cleft cysts are largely sporadic, but autosomal dominant cases have been reported. There is no gender predominance. Ten percent of lesions are bilateral.

Etiology and Pathogenesis

These cysts result from the occlusion of branchial cleft sinuses.

Clinical Features

These asymptomatic lesions are often located along the angle of the mandible if arising from the first branchial cleft and the middle to lower third of the anterior border of the sternocleidomastoid in cases arising from the second branchial cleft. They may present after an upper respiratory infection as a painful mass. These lesions tend to drain internally, but communication with the epidermis can occur. Branchial cysts may become complicated by infection.

Pathology

Branchial cleft cysts are lined with epithelium containing lymphoid follicles, mucous glands, or smooth muscle. A dense lymphocytic infiltrate may also be seen. The cyst contents contain mucin.

Treatment

Excision is the treatment of choice. Infected cysts may require incision and drainage or antibiotic therapy.

Preauricular Cyst and Sinus (Congenital Auricular Fistula, Ear Pits)

Preauricular cysts or sinuses are epithelial invaginations located in the preauricular area.