Cutaneous cysts

Clinical features

Epidermoid (epidermal, infundibular) cysts, which occur particularly on the face, neck, and upper trunk, are believed to result from damage to the pilosebaceous units. The vulval labia majora and scrotum are also sites of predilection. Rare lesions develop in non-hair-bearing areas like the soles (see below). Young and middle-aged adults are most often affected, and the sexes are involved equally. Epidermoid cysts present as smooth dome-shaped swellings a few millimeters to a few centimeters across ( Fig. 34.1 ). A punctum is usually present ( Fig. 34.2 ).

The presence of multiple lesions may suggest the possibility of Gardner syndrome, which includes polyposis coli, jaw osteomas, and intestinal fibromatoses in addition to cutaneous cysts. Less frequently, patients may manifest lipomas, pilomatrixomas (including epidermoid cysts with pilomatrical lining), and leiomyomas. Multiple lesions also occur in Gorlin-Goltz syndrome (see Chapter 24 ) and may be the first manifestation of the disease. Subconjunctival epidermoid cysts appear to occur exclusively in patients with this syndrome.

Multiple and often large epidermoid cysts are sometimes seen as a complication of ciclosporin therapy in transplantation recipients. Multiple epidermoid cysts have also been described in association with imiquimod and vemurafenib therapy.

Epidermoid inclusion cysts may also complicate penetrating trauma to the skin, such as by a sewing needle, with resultant implantation of squamous epithelium into the dermis ( Fig. 34.3 ). Lesions may rarely develop after genital mutilation, after vaccination (BCG), and after cosmetic surgical procedures including penile girth enhancement therapy and abdominoplasty.

It has been argued that since there is good agreement between the clinical and histologic diagnosis of epidermoid cysts, there is no need to submit these lesions for routine histologic examination. A study found a rate of concordance of about 80% between the clinical and histologic diagnosis, leading the authors to suggest that if the cyst is opened by the surgeon after excision and malodorous cheesy material is obtained, then the lesion can be discarded. This is debatable as malignant changes may exceptionally develop within epidermoid cysts (see below). The incidence of malignancy, mainly squamous cell carcinoma developing in epidermoid cysts, was reported as 0.3% in a retrospective study. However, most cysts developing malignancy become symptomatic, and it has therefore been proposed that excision should be performed only for symptomatic lesions.

Pathogenesis and histologic features

Lesions develop as a result of obstruction of the upper part of the hair follicle or secondary to trauma (inclusion cysts).

Epidermoid cysts are unilocular, spherical, and are lined by an epidermis-like epithelium including a granular cell layer ( Figs 34.4–34.6 ). Exceptional multilocular lesions may occur. The cyst contents of laminated keratin are believed to represent follicular infundibular derivation (the nonimplantation variant). In older lesions, the lining is often somewhat attenuated. Lichenoid inflammation of the wall indistinguishable from lichen planus may be seen. Acute inflammation may result in the subsequent disruption of the cyst wall, with the development of an intense foreign body giant cell reaction ( Fig. 34.7 ). Sometimes this may be so marked that it completely destroys the cyst, and only focal dermal collections of keratin fragments remain ( Fig. 34.8 ). It is not clear whether bacteria play an important role in the development of inflammation in epidermoid cysts. A study from Japan found an increased incidence of anaerobes in inflamed lesions as opposed to those without inflammation. It remains to be established, however, whether this is the result of colonization or a true infection. Occasionally, the cyst lining may show epidermoid and focal trichilemmal keratinization. In the rare hybrid cyst, there is epidermoid keratinization in the superficial half of the cyst and trichilemmal in the lower. Exceptionally, a pigmented variant containing multiple terminal hair shaft fragments may be encountered (pigmented follicular cyst). A case with numerous keratin spherules has been reported.

In patients with Gardner syndrome, the cyst lining occasionally shows focal basaloid cell proliferation with ghost cell change, as seen in pilomatrixoma ( Fig. 34.9 ). Lesions outside this context may occur, including a case in a background of nevus sebaceous. Thus, while highly suggestive, these cannot be considered pathognomonic.

The cysts in Gorlin-Goltz syndrome are usually hybrid with features of epidermoid cyst and steatocytoma.

A case of multiple epidermoid cysts with lesions of angiofibroma in tuberous sclerosis patients associated with obstruction/trauma has been reported.

Epidermoid cysts not uncommonly coexist with melanocytic nevi. This is of particular importance, as the resulting increase in size of the cyst may raise clinical suspicion of melanoma. Most nevi are banal and dermal, but cysts associated with compound nevi, congenital nevi, dysplastic nevi, blue nevi, and spindle cell nevi of Reed have also been documented.

Malignant tumors may rarely develop within the wall of an epidermoid cyst including basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ ( Fig. 34.10 ). There are also rare case reports describing an epidermoid cyst in association with Paget disease and cutaneous neuroendocrine carcinoma (Merkel cell carcinoma). There have been a reported case of melanoma arising in a lesion, an in situ melanoma associated with an adjacent cutaneous melanoma colonizing an epidermoid cyst, and there is a single further report of a melanoma in situ arising in a noncutaneous cerebellopontine angle epidermoid cyst. Pilomatrixoma (in the absence of Gardner syndrome) in conjunction with an epidermoid cyst has also been documented. Because epidermoid cysts with malignant change cannot be clinically reliably distinguished from their extremely common benign counterpoints, histologic examination of all such cysts is recommended.

Epidermoid cysts showing features of a range of cutaneous dermatoses have been described. These include pemphigus, psoriasis, lichen planus, and Darier disease. Changes of epidermolytic hyperkeratosis and involvement by molluscum contagiosum have also been described. Human papillomavirus (HPV) associations are described below (see verrucous cyst and epidermoid cyst of the sole ).

Clinical features

Proliferating epidermoid cyst is rare and poorly documented, with the majority of cases, in fact, describing the pilar/trichilemmal variant. There are, however, very occasional reports of this entity, of which the comprehensive review from the Armed Forces Institute of Pathology is the most informative.

The tumor shows a predilection for males (1.8:1) and, although a wide variety of sites may be affected, the majority appear to present on the pelvic area, scalp, and trunk in descending order of frequency. Most patients are middle aged or elderly (range 21–88 years, mean 54 years). Occasional patients document the presence of a lesion for several decades, giving support to the concept that the resulting tumor has developed within a preexistent benign epidermoid cyst. In this series, proliferating epidermoid cyst was associated with a 20% recurrence rate but metastases were not encountered.

Histologic features

By definition, focal cyst wall lined by stratified squamous epithelium and showing a granular cell layer with epidermoid/infundibular keratinization must be evident. The proliferating component is variable and ranges from well-differentiated squamous epithelium with conspicuous squamous eddies reminiscent of inverted follicular keratosis through to multicystic, keratotic, and verrucous lesions. Rarely, frank invasive carcinoma is encountered.

Clinical features

The verrucous cyst is a variant of epidermoid cyst associated with HPV infection. Adults are affected, and lesions may present at a wide variety of sites although the face, back, and (to a lesser extent) the arms and chest are most often involved. The sexes are affected equally. The cysts show no particular distinguishing clinical features.

Pathogenesis and histologic features

Verrucous cysts are associated with HPV infection as determined by polymerase chain reaction. Thus far, HPV antigens have not been identified with immunohistochemistry. The subtype is unknown in most cases, but a single lesion with the HPV type 59 has been described. HPV16 was demonstrated in a case of invasive squamous cell carcinoma arising from a verrucous cyst. An unusual case of multiple verrucous cysts associated with epidermodysplasia verruciformis-associated HPVs (20, 24, alb-7, and 80) and epidermodysplasia verruciformis-like epidermal lesions in the setting of idiopathic CD4 lymphopenia (immunosuppression) has been described.

Histologically, verrucous cyst shows focal features of a typical epidermoid cyst and rarely features of a trichilemmal cyst. The greater part of the cyst wall, however, is lined by papillomatous, acanthotic squamous epithelium with hyperkeratosis, parakeratosis, and conspicuous hypergranulosis. Keratohyaline granules are enlarged and irregular, and occasionally koilocytes are seen. In some lesions, the epithelium consists of an admixture of basaloid and squamous cells, and squamous eddies are prominent. A lymphohistiocytic infiltrate is sometimes present in the surrounding dermis. A lesion displaying melanocytic and sebaceous differentiation has been described.

Differential diagnosis

Verrucous cyst differs from HPV-associated epidermoid cysts of the sole, which predominantly affect the Japanese and in which the morphology of the wall of the cyst is that of a typical epidermoid cyst.

Clinical features

Epidermoid cyst of the sole has been described mainly in the Japanese. A single case report documents the lesion in a non-Japanese. Involvement of the palm has also been reported. The cyst likely represents an implantation variant. It is of particular interest as it has been shown to be associated with HPV infection in some cases (see below). An exceptional giant lesion extending from the sole into the dorsum of the foot through the interosseous muscles has been described.

Histologic features

Histologically, it is characterized by the presence of eosinophilic intracytoplasmic inclusions in the wall of the cyst and vacuolated cells in the keratin layer. Parakeratosis with absence of the granular cell layer is sometimes noted in the more superficial portion of the cyst. The cyst is filled with orthokeratotic keratin. Immunoperoxidase confirms the presence of viral antigen, and inclusions have been identified ultrastructurally. HPV 57 and 60 have been demonstrated.

Clinical features

Acne, including chloracne (a condition characterized by the development of acneiform lesions in patients following exposure to the halogenated hydrocarbons), is the most common cause of comedone formation. Comedones are follicular retention cysts. When they open directly onto the surface, a blackhead is visible clinically ( Fig. 34.11 ). If the ostial canal is blocked, pigmented keratin is not visible and the medium-sized whitish papule is classified as a closed comedone or whitehead ( Fig. 34.12 ).

Pathogenesis and histologic features

Follicular dilatation and hyperkeratosis (follicular plugging) are common features of facial skin. The development of an acne microcomedone is a further extension of that process. The fully developed blackhead contains abundant laminated keratin and cellular debris ( Fig. 34.13 ). A large sebaceous gland with a small hair may be attached to the widely distended but patent follicle. If the lesion persists, the sebaceous gland and hair commonly atrophy ( Fig. 34.14 ). A histologic section through a closed comedone will often miss the blocked connection with the epidermis, and sometimes a blackhead may appear as an intradermal cyst.

Differential diagnosis

Solar comedones (Favre-Racouchot disease) occur as a clinical triad of cysts, comedones, and elastosis around the orbit and malar areas of elderly patients, and are due to prolonged exposure to sunlight ( Fig. 34.15 ) or very rarely secondary to radiotherapy. Rarely, a plaquelike lesion may be seen. Squamous cell carcinoma may rarely develop within a lesion. Large thin-walled open and closed comedones are present in the upper dermis, accompanied by marked solar elastosis. A small series of cases of what is regarded as a variant of Favre-Racouchot disease and including epidermoid cysts with vellus hairs and solar elastosis and presenting on the ears has been described.

Open and closed comedones are also a feature of the congenital conditions familial comedones and familial dyskeratotic comedones. Both of these have an autosomal dominant mode of inheritance; the former is characterized by a greater number of lesions and an absence of dyskeratosis. . Rarely, late-stage follicular mucinosis and discoid lupus erythematosus may feature large thin-walled comedones as the dominant histologic component.

Clinical features

Milia are common superficial keratinous cysts that present as white or yellow dome-shaped nodules measuring 1–3 mm in diameter. They may represent primary lesions when no cause can be identified or secondary variants usually following skin trauma or other injury.

Primary milia are seen in up to 50% of newborns and present on the face, upper trunk, and extremities. These typically regress spontaneously. Children and adults can also be affected, when lesions are most often apparent on the face (forehead, eyelids, and cheeks) and the external genitalia ( Fig. 34.16 ). Possible association of persistent infantile milia with steatocystoma multiplex and eruptive vellus hair cysts has also been suggested.

Secondary milia may complicate a wide range of conditions including follicular mucinosis, folliculotropic mycosis fungoides, lichen sclerosus, radiotherapy, herpes zoster infection, leishmaniasis, severe burns, dermabrasion, chemical peeling, cutaneous local steroid therapy, adverse drug reactions (e.g., benoxaprofen), contact dermatitis, tattoos, and in a case of generalized granuloma annulare with a photosensitive distribution. Rarely, an association with bullae in systemic AL amyloidosis has been reported. Multiple follicular cysts and milia resulting in cutis verticis gyrate have been described after brain radiotherapy during vemurafenib therapy for melanoma. Lesions have also been described on the face and trunk during treatment with vemurafenib. Milia are also a feature of a number of subepidermal blistering disorders including dystrophic epidermolysis bullosa, epidermolysis bullosa acquisita, porphyria cutanea tarda, pseudoporphyria, and bullous pemphigoid. Milia may exceptionally occur in dominant dystrophic epidermolysis bullosa at sites of intact skin and not in association with scarring, suggesting that it may represent a primary manifestation of the disease. They may also be a feature of a variety of familial dermatoses including Rombo syndrome (facial anetoderma vermiculatum, telangiectasia, milia, hypotrichosis, acral erythema, cyanosis, and tendency to develop trichoepitheliomas and basal cell carcinomata), Bazex-Dupré-Christol syndrome (follicular atrophoderma, congenital hypotrichosis, basal cell carcinomas), familial multiple cylindromas, trichoepitheliomas, milia and spiradenomas (Brooke-Spiegler syndrome), Basan syndrome (diffuse congenital milia, transient neonatal acral bullae, and absence of dermatoglyphics), oral-facial-digital syndrome type 1, atrichia with papular lesions, hereditary vitamin D-dependent rickets type II, basal cell nevus syndrome, generalized basaloid follicular hamartoma syndrome, Nicolas-Balus syndrome (eruptive syringomas, milia, and atrophoderma vermiculata), KID syndrome, and hypotrichosis with light-colored hair and facial milia, and pachyonychia congenital type II. Generalized congenital milia cysts have also been described in an infant with trisomy 13 syndrome. Congenital familial milia with no other associations may also be rarely seen.

Transverse nasal crease is a rare embryologic anomaly that presents at the junction of the middle and lower third of the nose. The clinical presentation varies from a subtle erythematous line to a hypopigmented indentation. It has been suggested that what has been described as transverse nasal milia represents a clinical variant of transverse nasal crease.

Rarely, milia present as a localized plaque variant (milia en plaque). Such lesions are most often described around the ears. A small number of cases involving the eyelids have been documented, and there is one supraclavicular example. One case that developed in a background of pseudoxanthoma elasticum has been described. A further example in association with lupus erythematosus and another one in association with cryotherapy have also been reported. In the small number of documented cases, the sex incidence is equal, and a wide age range has been affected (12–62 years). A congenital case has been described. Bilateral lesions are exceptional. There is no racial predilection. Patients present with an edematous, erythematous plaque studded with numerous milia. Based on a single case with trichoepithelioma-like changes in the background, it has been suggested that this entity represents a variant of follicular hamartoma.

Very occasional examples of eruptive milia have been described including rare cases in children. Recently, these have been classified into spontaneous and autosomal dominant familial variants. They may also represent a component of a genodermatosis.

Pathogenesis and histologic features

Milia consist of miniature epidermoid cysts located in the superficial dermis just underneath the epithelium ( Fig. 34.17 ). Attachment to a vellus hair follicle is often seen in the newborn variant. Secondary lesions may be related to hair follicles or eccrine sweat ducts. The latter are typically seen in milia associated with scarring blistering diseases. Primary lesions may also be associated with the eccrine duct. Milia cysts occurring on palms and soles are likely derived from eccrine sweat ducts.

The etiology of milia en plaque is unknown, although spectacles, earrings, and perfume have been suggested as possible causes. In this variant, a background dense T-cell lymphocytic infiltrate is typically present.

Clinical features

Trichilemmal cysts are found on the scalp in 90% of cases; they are solitary in 30% and multiple in 70% ( Fig. 34.18 ). Unusual sites such as the pulp of a finger have been reported. Proposed criteria for the diagnosis of hereditary trichilemmal cysts include: (1) lesions in at least two first-degree relatives or on three first- or second-degree relatives in two consecutive generations. (2) At least one of the affected persons diagnosed before the age of 45. (3) The presence of multiple or giant (> 5 cm) or unusual histologic features including proliferating cysts or ossification. A case of two female siblings presenting with multiple calcified trichilemmal cysts and alopecia universalis has been described. They present as smooth, yellowish, dome-shaped intradermal swellings and are more common in females ( Fig. 34.19 ). In contrast to epidermoid cysts, they are characteristically devoid of a punctum. It should be noted that the term ‘sebaceous cyst’ favored by many clinicians is a misnomer because such lesions represent either epidermoid or trichilemmal cysts. Typically, the cyst is encapsulated and uncomplicated lesions readily ‘shell out’ at surgery. Acute inflammation is uncommon, and when it does occur it is usually of nonbacterial origin; its presence makes excision more difficult, with an increased likelihood of rupture. Exceptional cases of a lesion presenting with filiform hyperkeratosis, comedo-like lesions, and multiple trichilemmal cysts following Blaschko lines, have been described as trichilemmal cyst nevus (nevus trichilemmocysticus) and regarded as a complex organoid epidermal nevus. A case of multiple giant trichilemmal cysts, one of which displayed transformation to a squamous cell carcinoma, has been reported. Some lesions may be associated with the development of proliferating trichilemmal tumors (see Chapter 31 ).

Histologic features

The cyst is surrounded by a fibrous capsule against which rests a layer(s) of small dark-staining basal cells. These merge with characteristic squamous epithelium composed of pale keratinocytes, which increase in height as they mature and transform abruptly into solid eosinophilic-staining keratin without forming a granular cell layer ( Figs 34.20–34.22 ). Occasionally, small foci of epidermal keratinization (i.e., with a granular cell layer) may also be identified. Calcification occurs in 25% of lesions, regardless of the age or size of the cyst, and cholesterol clefts occur in up to 90% ( Figs 34.23 and 34.24 ). Osseous metaplasia may occur and exceptionally, extramedullary hematopoiesis has been described. Secondary inflammation is manifest as an influx of inflammatory cells into the lumen of the cyst, in contrast to the granulomatous response that may surround an epidermoid cyst. In a small percentage of cases, there is budding of tiny daughter cysts from the parent. Very rarely, sebaceous and apocrine differentiation are found in the cyst wall. Exceptional cases of other neoplasms such as Merkel cell carcinoma colonizing or arising in a trichilemmal cyst have been reported. Carcinoma in situ and squamous cell carcinoma may also rarely develop within trichilemmal cysts.

Clinical features

Vellus hair cysts were originally reported in children and young adults of both sexes. The sex distribution is equal and there is no racial predilection. Patients present with numerous asymptomatic, discrete, soft, flesh-colored or reddish-brown papules, 1–5 mm across, particularly over the parasternal area, although the distribution may be quite widespread. A generalized distribution has been documented. An exceptional case mimicking a nevus of Ota has been described. Lesions may rarely be unilateral. Occasional lesions are umbilicated, and squeezing may express white caseous material. Further cases have expanded the condition to include an inherited (autosomal dominant) variant, which may or may not be manifest at birth and is more likely to occur over the extensor aspects of the limbs. Occurrence in twins has been reported. A facial form, a patient presenting with a periorbital distribution, and a further patient with a single orbital lesion have been described. Spontaneous involution is not uncommon.

Vellus hair cysts have occasionally been associated with renal failure and a number of genodermatoses including pachyonychia congenita, anhidrotic ectodermal dysplasia, hidrotic ectodermal dysplasia, and rarely, Lowe syndrome (oculocerebrorenal syndrome characterized by Fanconi-type renal failure, mental retardation, and ocular abnormalities). Occasionally, solitary lesions are encountered and may be large.

Pathogenesis and histologic features

Eruptive vellus hair cysts most probably develop as a consequence of occlusion of the infundibulum of vellus hairs with resultant cystic dilatation and retention of keratinous debris and vellus hairs. The primary cause of the obstruction is unknown. It has also been proposed that they represent follicular hamartomas. Studies indicate that both eruptive vellus hair cysts and steatocystomas express keratin 17, with the latter also expressing keratin 10. This overlap in keratin expression may help explain the underlying similarities and perhaps overlapping features of these two lesions; however, this opinion is not universal, and their exact relationship remains to be elucidated.

The characteristic histology is that of a mid-dermal cyst containing laminated keratin and many vellus hairs ( Figs 34.25 and 34.26 ). The epithelial lining consists of several layers of squamous epithelium, often with a granular cell layer. Sometimes the cyst is in continuity with the epidermis, an atrophic follicle, or a pilomotor muscle. Vellus hair cysts are more likely to open onto the surface in the congenital variant. Occasionally the cyst ruptures, and there is an associated foreign body giant cell reaction that may be associated with formation of cholesterol clefts.

Differential diagnosis

Eruptive vellus hair cysts show very marked clinical overlap with steatocystoma multiplex and can only be distinguished by histologic analysis. Steatocystoma is characterized by an epidermoid lining without a granular cell layer. The innermost aspect of the cyst wall is covered by an undulating eosinophilic cuticle. Sebaceous glands are present in the wall of the cyst or in the immediate vicinity.

Sometimes, however, patients have both types of cyst simultaneously, and occasionally there are overlapping histologic features sometimes constituting a hybrid cyst.

As noted above, differential keratin expression has been shown to distinguish the two cysts. Thus vellus hair cyst expresses K17 but not K10, whereas steatocystoma expresses K17 and K10. Interestingly, mutations in the KRT17 gene can cause both pachyonychia congenital type 2 and also a condition very similar or identical to steatocystoma multiplex. The relevance of these findings to steatocystoma simplex and vellus hair cysts, if any, remains to be determined.

Clinical features

Dermoid cysts result from the sequestration of cutaneous tissues along embryonal lines of closure. The most common clinical appearance is that of a single nontender small subcutaneous nodule at birth on the lateral aspect of the upper eyelid ( Fig. 34.27 ). Although slow enlargement is the rule, sometimes a sudden increase in size may occur, bringing the lesion to attention at a later age. Other potential sites of dermoid cysts include the midline of the neck, nasal root, nose, forehead, the mastoid area, anterior chest, and scalp. The last is a particularly important site as the lesion may very occasionally show intracranial extension (dumbbell dermoid). Midline occipital lesions are most often affected. Dermoid cysts may also present on mid chest, sacrum, perineum, scrotum, penis, and ear. Dermoid cysts are also encountered in the oral cavity and deeper noncutaneous sites.

Infection of a cranial dermoid cyst is a serious development as it may be complicated by central nervous system involvement. Squamous cell carcinoma very rarely develops in the wall of the cyst. Exceptionally, the development of carcinosarcoma has been described. There are occasional reports of familial dermoid cysts, including one family associated with midline cleft lip.

Pathogenesis and histologic features

The unilocular cysts are usually subcutaneous and may be attached to the periosteum. They are lined by stratified squamous epithelium with associated hair follicles and sebaceous glands ( Fig. 34.28 ). Trichilemmal differentiation is exceptionally seen in the lining of the cyst. Eccrine sweat glands are present in 35% of cases and apocrine glands in 15%. Smooth muscle can be present but – in contrast to benign cystic teratoma – cartilage and bone are not described. Some authors propose an embryological origin for these cysts, particularly in the nasal form.

Antenatal diagnosis has been reported.