Epidermal Inclusion Cyst

Introduction

Background

Several different terms have been used to describe epidermal cysts. Epidermal inclusion cyst refers to those cysts that are the result of the implantation of epidermal elements in the dermis. However, many cysts originate from the infundibular portion of the hair follicle, and the more general term, epidermoid cyst, is favored. Milia merely represent miniature epidermoid cysts. The term wen should be reserved for trichilemmal or pilar cysts. Sebaceous cyst is a misnomer, and the term should not be used at all because these cysts are not of sebaceous origin.

Pathophysiology

Epidermoid cysts result from the proliferation of epidermal cells within a circumscribed space of the dermis. They have been shown to not be of sebaceous origin based on the analysis of their lipid pattern, which demonstrates similarities to the epidermis. In addition, epidermoid cysts express cytokeratins 1 and 10, which are constituents of the suprabasilar layers of the epidermis. The source of this epidermis is often the infundibulum of the hair follicle, as evidenced by the observation that the lining of the 2 structures is identical.

Inflammation is in part mediated by the horny material contained in epidermoid cysts. Extracts of this material have been shown to be chemotactic for polymorphonucleocytes.

The manner in which carcinomas may rarely arise within epidermoid cysts is unknown. In a series of epidermoid cysts with carcinoma, immunohistochemical results for human papillomavirus (HPV) were negative, leading the authors to conclude that HPV is not likely to be the cause of squamous cell carcinomas (SCCs) in these cysts. Some have proposed that repetitive trauma and inflammation may play a role.

Mortality/Morbidity

• Epidermoid cysts grow slowly and usually do not cause symptoms, but they may become inflamed or secondarily infected, resulting in pain and tenderness.
• Rarely, malignancies, including basal cell carcinoma, Bowen disease, SCC, and even mycosis fungoides, have developed in epidermoid cysts.

Sex

In one study, epidermoid cysts were approximately twice as common in men as in women.

Age

Epidermoid cysts may occur at any time in life, but they are most common in the third and fourth decades of life. Gardner syndrome is an exception; the average patient age at onset is 13 years.

Clinical

History

• Discharge of a foul-smelling cheeselike material is a common complaint.
• Less frequently, the cysts can become inflamed or infected, resulting in pain and tenderness.
• In the uncommon event of malignancy, rapid growth, friability, and bleeding have been reported.
• When located orally, the cysts can cause difficulty in breathing, swallowing, or even speaking.
• Lesion of the genitals can be especially painful during intercourse and cause problems with walking or wearing underwear. They can also interfere with urination.
• Subungual lesions have also been associated with pain, as have plantar lesions, causing difficulty with walking or other activities.

Physical

Epidermoid cysts appear as firm, round, mobile, flesh-colored to yellow or white subcutaneous nodules of variable size. A central pore or punctum is an inconsistent finding that may tether the cyst to the overlying epidermis and from which a thick cheesy material can sometimes be expressed. In individuals with dark pigmentation, epidermoid cysts may also be pigmented. In a study of Indian patients with epidermoid cysts, 63% of the cysts contained melanin pigment.

• In one study, epidermoid cysts were most common (in descending order of frequency) on the face, the trunk, the neck, the extremities, and the scalp. While facial involvement is also frequent in Gardner syndrome, the extremities tend to be affected more than the trunk. The Ibos of Nigerian and other cultures who practice female circumcision represent special groups of patients in whom the vulva is the most common site.
• Epidermoid cysts of the genitals are also common in the general population and may appear as a mass in the breast, the vulva, the clitoris, the penis, the scrotum, or the perineum. For one woman, a clitoral cyst present from age 12 years resulted in ambiguous genitalia. The ocular and oral mucosae can also be affected, and cysts have been reported on the palpebral conjunctivae, on the lips, on the buccal mucosa, on and under the tongue, and even on the uvula.
• Epidermoid cysts manifest in various ways on the extremities. When the cysts occur subungually, they can cause changes in the nails, such as onycholysis and subungual hyperkeratosis, which may be mistaken for psoriasis or onychomycosis. Furthermore, epidermoid cysts on the distal portions of the digits may extend into the terminal phalanx. These cysts also produce changes in the nails, such as pincer nails, in addition to erythema, edema, tenderness, and pain. Sometimes, these findings can mimic arthritis. Palmoplantar lesions represent a unique subset of epidermoid cysts.
• The anterior fontanelle, umbilicus, and popliteal fossa are unusual locations where epidermoid cysts have been found.

Causes

Epidermoid cysts likely form by several mechanisms. They may result from the sequestration of epidermal rests during embryonic life, occlusion of the pilosebaceous unit, or traumatic or surgical implantation of epithelial elements. HPV infection and eccrine duct occlusion may be additional factors in the development of palmoplantar epidermoid cysts. HPV has also been identified in nonpalmoplantar epidermoid cysts.

• Congenital epidermoid cysts of the anterior fontanelle or those that are orogenital in location presumably result from sequestration or trapping of epidermal rests along embryonic fusion planes during development. Lip and lingual lesions may be related to aberrant fusion of the branchial arches, and genital lesions could result from improper closure of the genital folds.
• Any benign or malignant process affecting or growing near the pilosebaceous unit may lead to occlusion or impingement of the follicular ostia and subsequent formation of a cyst. Many cysts with an acneiform distribution are probably the result of follicular occlusion. In elderly persons, accumulated sun damage can injure the pilosebaceous unit, thus causing abnormalities, such as comedonal plugging and hypercornification, both of which can eventuate in cyst formation. Alternatively, cases of mycosis fungoides, Bowen disease, molluscum contagiosum, seborrheic keratoses, and nevi have all been reported in association with epidermoid cysts. In each case, the process was growing in and around the hair follicle.
• True epidermal cysts result from the implantation of epithelial elements in the dermis.
  • Injuries, especially of the crushing type, such as the slamming of a car door on a finger, are frequently reported in association with subungual or terminal phalanx epidermoid cysts.
  • As previously mentioned, female circumcision is associated with the formation of epidermoid cysts, perhaps from instruments that are not sharp or from imprecise cutting.
  • Theoretically, any surgical procedure may result in epidermoid cysts, and it is surprising that they are not a more common occurrence. Unusual examples of this mechanism include the formation of multiple epidermoid cysts after rhinoplasty and reduction mammoplasty. The use of dermal grafts, presumably because of the inclusion of epithelial elements, has also resulted in the formation of epidermoid cysts. A similar situation has been observed with the use of myocutaneous flaps where the cutaneous portion is buried. Even seemingly minor procedures, such as needle biopsy of the breast, have reportedly induced epidermoid cysts.
• The origin of palmoplantar cysts is especially controversial, and their etiology may be unique. This idea is based on the discovery of HPV and eccrine structures within these cysts. In addition, the palms and the soles lack the pilosebaceous units present in other parts of the body. Some have also questioned the role of daily minor foot trauma, while others implicate all 3 factors.
  • Numerous reports have documented HPV types 57 and 60 antigens, as well as histologic changes characteristic of wart infection, in epidermoid cysts. These findings have been found more consistently in plantar cysts than in palmar cysts, and HPV type 60 has been identified more frequently than type 57. Although most patients deny a history of trauma, many of these cysts are located over pressure points, and mechanical pressure or minor trauma may be a contributing factor. In one study of 25 plantar epidermoid cysts, all were located on weight-bearing areas. The theory is that trauma introduces wart virus into the epidermis and that mechanical pressure forces the wart and the epidermis to descend into the dermis. Subsequently, the wart induces epithelial proliferation that may result in the formation of cysts. On the other hand, the presence of HPV in epidermoid cysts may merely represent superinfection.
  • Carcinoembryonic antigen–positive ductal structures in conjunction with HPV have been found in plantar epidermoid cysts. Some authors speculate that HPV may preferentially infect acrosyringeal epithelium and then invade dermal eccrine ducts, inducing the formation of cysts. In fact, connections between the eccrine dermal duct and epidermoid cysts have been characterized with 3-dimensional reconstruction analysis. Others dispute the notion that epidermoid cysts (at least palmar ones) are of eccrine origin in light of a study in which palmar epidermoid cysts failed to react with antibodies specific to luminal and secretory cells of lesions in eccrine glands. Instead, immunoreactivity to differentiation-specific cytokeratins (1 and 10) identical to those of the suprabasal layers of the epidermis and follicular infundibulum occurred. The authors of this study concluded that palmar epidermal cysts with HPV infection are not of eccrine origin, but that they are the result of epidermal implantation or trauma. Another explanation that has been proposed, however, is that these findings reflect metaplasia of the eccrine duct epithelium.
• Certain hereditary syndromes have epidermoid cysts as part of their features. Examples include Gardner syndrome, basal cell nevus syndrome, and pachyonychia congenita. In addition, idiopathic scrotal calcinosis may actually represent an end stage of dystrophic calcification of epidermoid cysts in that area of the body.
  • In a study of 39 patients with Gardner syndrome, 13 (33%) had at least 1 epidermoid cyst. The number of lesions varied from 1 to 20, and the average was 4. Of significance, in another study, epidermoid cysts occurred before polyps were detectable in 39 (53%) of 74 patients with Gardner syndrome. Pilomatrical differentiation may be present in portions of the cysts in these patients. A distinct syndrome with colonic polyps and epidermoid cysts has also been described, where patients had malignant brain tumors and lacked the soft-tissue abnormalities seen in Gardner syndrome.
  • An epidermoid cyst may be a feature of pachyonychia congenita. In addition, a syndrome of leukonychia totalis, multiple epidermoid cysts, and renal calculi has been reported.
  • As the name implies, the etiology of idiopathic scrotal calcification is unknown. However, some authors view this condition as an end stage of dystrophic calcification of scrotal epidermoid cysts. This hypothesis is based on the histologic observation of squamous linings surrounding calcified masses. The lining or wall is not always seen because biopsy specimens are often from older lesions where inflammation has destroyed it.