Cutaneous cysts in the periorbital region can originate from dermal adnexal elements such as sweat glands or hair follicles. Cutaneous keratinous cysts are one type of skin cysts that derive from the folliculosebaceous apparatus, with different epithelial segments giving rise to distinct histologically defined types of cyst.

The hair follicle and associated structures are divided into four general regions.¹ The infundibulum is the most superficial, located at the epidermis-dermis junction immediately beneath the opening pore and extending to the level of the emptying duct of the associated sebaceous gland. The isthmus is located between the sebaceous gland duct and the hair bulge situated midway along the follicle. When present, the arrector pili muscle attaches to the bulge. The suprabulbar segment begins at the hair bulge and extends inferiorly and terminates at the matrical cells and the hair bulb. Each region of the follicle can be the etiology of a cyst, the lining of which resembles the characteristics of the keratinocytes lining that segment of the follicle.²

Cysts that are surrounded by an epithelial cell lining, either stratified squamous epithelium or nonstratified squamous epithelium, are generally called true cysts.³ Over the years, and even currently, the names applied to true cysts have been inconsistent, and certain terms have been applied interchangeably and often erroneously to different lesions. This had led to significant confusion in the medical literature. The term sebaceous cyst has been the most widely used terminology. It was introduced by Rudolf Virchow, who considered all epithelium-lined cysts of the skin with semisolid or fluid contents to be formed from sebaceous glands.⁴ Since then, this term has been used to describe most cystic lesions of the skin and has become so inclusive that it has lost all significant meaning.⁵

In 1930, Broders and Wilson⁶ classified these cystic lesions of the skin based on histology and their contents into “keratomas” and “true sebaceous cysts.” Later, Warvi and Gates⁵ used the term epidermal cyst for Broders and Wilson’s keratoma, defining these as congenital or acquired keratin-filled cysts. In addition, they recognized a category of “epidermal cysts of traumatic origin,” basically equivalent to epidermal inclusion cysts (EICs) of modern terminology. They also accepted the rare occurrence of a true “sebaceous cyst,” defined as a retention cyst of sebaceous glands with sebaceous secreting elements in the cyst walls.

While each of the keratinous cyst types arising from the folliculosebaceous unit is well defined on histopathologic criteria, clinically they are all nearly identical and usually cannot be distinguished without a biopsy. The most important of these cysts are the epidermoid cyst (EC), epithelial inclusion cyst, and trichilemmal cyst. In this chapter, we include all three under the term “cutaneous keratinous cysts.” True sebaceous cysts, or more appropriately sebaceous duct cysts, are discussed in a separate chapter (Chapter 114).

Within the group of cutaneous keratinous cysts, ECs are the most common and can occur anywhere in the body. About 7% of them occur in the head and neck. They are defined as a simple cyst lined with stratified squamous epithelium and a lumen filled with laminated keratin produced by the epithelial lining, and they contain no other specialized
adnexal structures.⁷ They can occur at any age from birth to old age, but often become apparent in patients between 15 and 35 years and are seen most often in the third and fourth decades.⁸ ECs are usually solitary, although multiple cysts can occur, and males are more frequently affected than females. An EC is formed by the proliferation of infundibular epithelial cells within a confined dermal space, with retention of keratinous debris, and can be either congenital or acquired.⁹,¹⁰ The center of ECs contains keratin with a cheesy appearance and not sebum.

Most ECs are sporadic occurrences, but familial inheritance is known, especially in individuals with multiple lesions.³,¹¹ ECs are also seen in patients with Gardner syndrome, particularly on the face and scalp. Gardner syndrome is an autosomal dominant disease characterized by colorectal polyps with a high risk for the development of malignancy and associated with the early onset of multiple ECs in atypical localizations such as the limbs. ECs are also seen in basal cell nevus (Gorlin) syndrome¹²,¹³ and pachyonychia congenita.¹⁴,¹⁵ In Favre-Racouchot syndrome (nodular elastosis with cysts and comedones), ECs may result from chronic sun-damaged skin in elderly patients.¹⁶

Approximately 1% of ECs may have a malignant potential, transforming to squamous cell and basal cell carcinoma.¹³,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³ How carcinomas arise within ECs is unclear. Immunohistochemistry for HPV is typically negative, suggesting that HPV is not likely to play a role. Chronic irritation or repetitive trauma to the epithelial lining of the cyst has been suggested to play a role, but this relationship has not been conclusively established.²⁴

EIC is a subset of EC. Numerous synonyms for this lesion have included EC, epidermal cyst, infundibular cyst, inclusion cyst, and keratin cyst. However, unlike ECs, EICs result from the implantation and multiplication of surface epithelial cells in the dermis or subcutaneous tissues as a result of trauma or previous surgery.²⁵ They can occur anywhere on the body and usually present as a nodule in or directly beneath the skin. Like the more general EC, EICs are freely moveable and can range in size from several millimeters to several centimeters in diameter. They may gradually enlarge over time, and occasionally can become inflamed and infected, becoming erythematous, fluctuant, and even painful.

Trichilemmal cysts, also known as pilar cysts or wen, account for about 10% to 20% of cutaneous keratinous cysts.²⁶ Based on anatomy, histology, histochemistry, and method of keratinization, McGavran and Binninglon²⁶ concluded that these cysts derive from the pilary apparatus of the dermal follicular unit. Several years later, Pinkus²⁷ showed that the epithelial lining of these cysts keratinizes like that of the outer root sheath of the hair follicle at the isthmus and trichilemmal sac around the catagen hair,²⁸ the phase after anagen where the outer root sheath shrinks and detaches from the dermal papilla. He concluded that the pilar cysts are trichilemmal cysts. The cyst cavity contains amorphous eosinophilic keratin.

Trichilemmal cysts are more common in areas with dense hair follicle concentrations such as the scalp but have also been described on the eyelids.²⁹,³⁰,³¹,³² Unlike ECs, an overlying punctum is normally not present, but otherwise, they are indistinguishable clinically from the more common ECs. In about 2% of trichilemmal cysts, single or multiple foci of proliferating cells give rise to proliferating tumors, often called proliferating trichilemmal cysts or tumors.³³ These occur mainly in women older than 60 years and are seen most often on the scalp³⁴ and rarely on the eyelids.³⁵ These lesions have been classified as benign, low-grade malignant, or high-grade malignant depending on the presence of local infiltration and cytologic grade³³,³⁶ and can metastasize in about 25% cases.³³,³⁷,³⁸,³⁹,⁴⁰