Atypical Skin Lesions

Epidermoid Cysts (Keratin Cysts)

These common cysts enlarge subcutaneously but maintain a connection to the overlying skin at their punctum. Lined by squamous epithelium, they produce soft keratin that fills the cyst with a waxy/cheesy material. Although often called sebaceous cysts, this is a misnomer as they do not contain sebum. True sebaceous cysts are uncommon, arising from the sebaceous glands. There are two types of epidermoid cyst. Epidermal inclusion cysts result from the inoculation of squamous epithelium into the dermis during trauma (e.g., body piercing). Infundibular cysts specifically arise at the infundibular portion of the hair follicle, but are otherwise clinically the same.

Management depends upon the state of the cyst at presentation. Patients typically present with cysts either as non-tender lumps attached to the undersurface of the skin or when they become infected. Surgical excision in quiescence is ideal, but must include excision of the attachment to the overlying skin (the punctum) ( Fig. 10.1 ). Significant compression can cause a release of keratin through the punctum, but this also increases the risk of infection. In infection, decompression of the cyst abscess, removal of the cyst material, and curettage of the cyst lining allows resolution of the infection and often reduces the size of the lesion down to a small scar. Curettage is associated with a significant risk of recurrence because of its inability to ensure complete removal of the lining of the cyst. Once the scar has settled appropriately, the scar, remaining cyst, and its punctum can be removed to stop recurrence. Uncommonly, they spontaneously resolve by becoming marsupialized and discharging.

Tricholemmal (Pilar) Cysts

Tricholemmal cysts are similar to epidermoid cysts except that they specifically arise from the outer root sheath of hair follicles. For this reason, they are sometimes referred to as isthmus-catagen cysts and are mobile and filled with keratin. They typically arise in the scalp as this has the highest density of hair follicles. They are usually multiple and the tendency to form tricholemmal cysts runs in families. Surgical excision is the treatment of choice and when excised with the overlying hair follicle, recurrence is unlikely. On histology, they can demonstrate areas of nuclear atypia, mitotic figures, and dyskeratosis and therefore be confused with squamous cell carcinoma, but it is rare for them to undergo malignant transformation.

Dermoid Cysts

Dermoid cysts are hamartomas, often containing multiple epithelial derivatives (skin, hair etc.) and occasionally other tissues including fat, cartilage or bone/teeth. They are found in numerous organs and regions of the body. In the skin they are often near the midline or in the head and neck along tissue fusion planes. They can have intracranial, intraspinal, and other deep connections, including down to bone. As they are developmental in their origin and are present at birth, those with a superficial position and/or in the head and neck usually present at an early age, whereas dermoid cysts in other areas are more likely to be incidental findings or found following slow enlargement at any time in life. The key factors in their management are recognition of their potential to involve deeper structures (e.g., nasal dermoid with intracranial extension) and their potential to be associated with other conditions. Excision of the cyst with any communications to underlying structures is effective to prevent recurrence.

Acrochorda

Acrochorda ( acrochordon = singular) or skin tags are fibroepithelial polyps that appear as raised, smooth or irregular-surfaced pieces of skin on a small stalk called the peduncle. Nearly half of the adult population has at least one near skin creases in the neck, axilla, groin, breasts and eyelids. Shear forces of skin on skin are thought to be their underlying cause and therefore they are common in obesity. Female gender, human papilloma virus 6 and 11 and familial tendency are all thought to predispose to them. They may be symptomatic due to irritation from clothing or jewelry or when they bleed because of tractional injury. Acrochorda are usually small (2–5 mm) but occasionally larger. They are composed of a fibrovascular core and adipose tissue covered by normal skin. Numerous treatment modalities are available from ligation to cryotherapy and simple surgical removal, but the patient must be aware of the risk of further lesions.

Warts

Warts are focal (verrucous) keratinized lesions caused by human papilloma virus (HPV). The virus replicates in the stratum granulosum, inducing underlying basal keratinocytes to proliferate, causing a hyperkeratotic response. They may appear raised, flat, filiform, cauliflower or ingrown (e.g., plantar warts) and can also occur under or around the nails. Over 150 different types of HPVs have been characterized but, typically, only 1–2 strains cause each normal variant (verruca vulgaris HPV 2 and 4, cauliflower/Butcher’s warts HPV 7, palmoplantar warts/myrmecia HPV 1, flat warts HPV 3 and 10). These are distinct from the HPV strains associated with genital warts (HPV 6 and 8) and those producing an increased risk of intraepithelial neoplasia or invasive tumors affecting the vulva, penis, cervix or oral cavity (HPV 16 and 18). Warts may be singular or multiple, with a predilection for the hands due to contact transfer. Wart infections are self-limiting and resolve once the host mounts an immune response to the virus. Surgical excision produces some release of HP virions, but topical therapies are a less invasive approach to induce an immune response.

Therapy is largely divided into management of the hyperkeratosis and induction of a suitable immune response. Hyperkeratosis management can be undertaken by multiple means, including use of salicylic acid (3%–60%, daily or twice/day), occlusive dressings, cryotherapy, and shaving by scalpel or sharp curette.

Topical therapies to promote an immune response include podophyllin (resin or toxin), formalin (3% solution), imiquimod (Aldara), retinoids such as tretinoin and 5-fluorouracil (5-FU). Podophyllin is available over the counter in most countries and can be applied without specific training. Other approaches that have been used include laser therapy, intralesional agents (bleomycin and interferon-alpha) and topical allergens or caustic agents. While usually successful, they have significant potential side effects not found with the mainstream therapies above. Patient education usually helps to avoid surgical intervention and scarring. Histologically warts demonstrate koilocytes (vacuolated cells with viral infection) and hypergranulosis with columns of parakeratosis and compact orthokeratosis. Typically, the marked hyperkeratosis and papillomatosis are associated with elongated rete ridges sloping inwards to the center of the lesion.

Malignant transformation is sometimes seen in long-standing immune suppression, but it is unclear to what degree HPV infection contributes because the patients already have increased risk of skin cancers. Epidermodysplasia verruciformis (Lewandowsky-Lutz dysplasia) is a rare autosomal recessive skin disorder that increases the susceptibility to HPV infections. These patients have a very high risk of skin cancer due to the increased risk of malignant transformation of their lesions.

Pilomatrixoma

This benign appendageal tumor typically occurs in the head and neck region and demonstrates differentiation towards hair (follicular) cells. While considered tumors of children, they can occur in adults. They are associated with a mutation in the CTNNB1 gene and while familial cases have been observed, the mode of inheritance has not yet been established. In addition to sporadic cases, they may be associated with Gardner syndrome (familial colorectal polyposis), myotonic dystrophy (especially if multiple lesions), and sarcoidosis. Pilomatrixomas present as firm nodules that are usually solitary and asymptomatic, but are occasionally associated with local pain if infected or inflamed. Usually slow-growing, they can be confused with other skin lesions, including nodular basal cell carcinoma, despite their deep position in the lower dermis or underlying adipose tissue. Lesions often contain calcium deposits that are visible on medical imaging. Pilomatrix carcinoma is well documented but very rare.

Histology demonstrates irregular islands of epithelial cells surrounded by a connective tissue capsule that produces a diffuse lesion in most cases. The epithelial cells are divided into basophilic (germinal) cells around the periphery and shadow cells (anucleated) centrally in keeping with a hair-like process. Chronic lesions have fewer basophilic cells and calcium deposits can be visualized through the use of special stains (von Kossa). The diffuse nature of most lesions leads to a greater risk of local recurrence unless a wide local excision is performed (1 cm or greater). Mohs micrographic surgery (MMS) has been trialed to minimize resection of uninvolved tissue, but its effectiveness remains unclear relative to standard surgical excision.

Trichoepithelioma

Trichoepithelioma is a tumor of the hair follicle and adnexae that is often confused with basal cell carcinoma (BCC). They typically arise as single or multiple small (<1 cm), firm round lesions on the face before or after puberty that may display pearling. The lesions form a basic hair follicle but no hair shafts and may have a different surface color depending on their site of origin. Solitary lesions are typically sporadic, but a familial (multiple) form of trichoepithelioma has been associated with mutations on chromosome16q21 (Brooke–Speigler syndrome). Trichoepitheliomas are composed of nests of basophilic cells often arranged like a hair follicle but they do not display the surrounding myxoid stroma or perinest-clefting found in BCC. A desmoplastic variant commonly forms an annular shape that can be confused with BCC and has a marked desmoplastic surrounding response on histology ( Fig. 10.2 ). Simple surgical excision of all forms without a significant margin is usually effective in preventing recurrence.

Trichofolliculoma

Trichofolliculomas arise directly from hair follicle tissue. They are uncommon small solitary nodules found around the face of adults. A central pore may express sebum and/or hair. They are thought to arise from hamartomatous rests of stem cells that show incomplete differentiation towards hair follicles as supported by the prominence of Merkel cells within the follicular epithelium in these lesions. Their central follicle may have secondary or tertiary follicles and hair shafts may be present within the follicle lumen on histology, helping to distinguish them from trichoepitheliomas along with a prominent surrounding stroma. There is a sebaceous variant where the central follicle has well-differentiated sebaceous lobules emptying into it. They are considered benign with only a single case of perineural invasion ever reported.

Tricholemmoma (Trichilemmoma)

Tricholemmoma is an uncommon benign tumor arising from the outer root sheath of hair follicles. It appears as a warty or smooth papule on the face and neck region, and when multiple lesions are present it is diagnostic of Cowden’s syndrome (hamartomatous intestinal polyposis with multiple tricholemmoma lesions). Cowden’s syndrome demonstrates autosomal dominant germline inheritance associated with mutations of the tumor suppressor gene PTEN (phosphatase and tensin homolog) located on chromosome 10q23.3 but other mutations are occasionally found (e.g., BMPR1A ). PTEN is negative in sporadic tricholemmomas, but often positive in Cowden’s syndrome, presumably due to a loss of function mutation. On histology it appears as lobular downward growths of epidermis and is often surrounded by a hyaline band or thickened basement membrane. Clear cells or cells with prominent vacuoles are typically present (glycogen) and the lobules demonstrate peripheral palisading.