Cutaneous Adnexal Cysts Revisited: What We Know and What We Think We Know.

Cutaneous cysts have been classified by dermatopathologists in many different ways. Here, we propose a novel classification of cutaneous adnexal cysts according to their origin in the folliculosebaceous unit and the sweat glands. By examining the lining of the cystic structure, its origin can be easily identified. Epidermal cysts have an epithelial wall containing a granular layer with lamellar keratinization, indicating an infundibular origin. Tricholemmal cysts have an undulating epithelial wall with no granular layer and a compact keratinization, showing an isthmic origin. In steatocystoma, dermoid cyst, and folliculosebaceous hamartoma, the epithelial lining shows a crenulated appearance which is seen in the sebaceous duct. Hidrocystoma shows the characteristic cuboidal epithelial lining of sweat glands with decapitation secretion in its apocrine forms. The hair matrix cyst wall is composed of basaloid cells maturing to squamoid cells, as seen in the normal hair matrix and shadow cells in the lumen. Metabolizing acquired dioxin-induced skin hamartoma (MADISH) is a cystic lesion with lamellar keratinization, and no sebaceous glands. The classification proposed here aims to simplify the complexity of cutaneous adnexal cysts, and to facilitate a better understanding of the origin of cystic lesions of the skin.

Historical Classification

Cutaneous cysts have been classified differently by various authors in major dermatopathology textbooks (Tables 1, 2, 3 4). Weedon [1] classifies them as appendageal, developmental, miscellaneous, or lymphatic (Table 1). The classification by McKee [2] includes follicular and glandular cysts (Table 2). Rapini [3] did not make a subclassification of cutaneous cysts (Table 3). Barnhill [4] is the only author cited here who classifies cutaneous cysts according to the types of cells in their wall lining (Table 4).

Table 1

Classification of cutaneous cysts according to Weedon [1]

Appendageal cysts Epidermal (infundibular) cyst HPV-related epidermal cysts Proliferating epidermal cyst Tricholemmal (sebaceous, isthmus-catagen) cyst Proliferating and malignant tricholemmal cyst Onycholemmal cyst Malignant onycholemmal cyst Hybrid cyst Hair matrix cyst Cystic panfolliculoma Pigmented follicular cyst Cutaneous keratocyst Vellus hair cyst Steatocytoma multiplex Milium Comedo/comedonal cyst Eccrine hidrocystoma Apocrine hidrocystoma

This classification is taken from chapter 16: “Cysts, Sinuses and Pits” [1].

Table 2

Classification of cutaneous cysts according to McKee [2]

Follicular Epidermoid cyst Proliferating epidermoid cyst Hybrid cyst Verrucous cyst Epidermoid cyst of the sole Comedonal cyst Milia Trichilemmal cyst Vellus hair cysts Dermoid cysts Cutaneous mature cystic teratoma

Glandular Bronchogenic cysts Thyroglossal duct cyst Brachial cyst Cervical thymic cyst Cutaneous ciliated cyst Median raphe cyst

This classification is taken from chapter 30: “Cutaneous Cysts” [2].

Table 3

Classification of skin cysts according to Rapini [3]

Epidermoid cystPilar cystDermoid cystVellus hair cystSteatocystomaCervical thymic cystCutaneous ciliated cystThyroglossal duct cystBranchial cleft cystBronchogenic cystHidrocystomaMedian raphe cyst of the penisAuricular pseudocyst

This classification is taken from chapter 19: “Cysts” [3].

Table 4

Classification of cutaneous cysts according to Barnhill [4]

Epithelial-lined cystsStratified squamous Epidermoid (infundibular) cyst Pilar (tricholemmal) cyst Vellus hair cyst Milia Follicular hybrid cyst Pigmented follicular cystStratified squamous with components in cyst wall Steatocystoma (simplex and multiplex) Dermoid cyst Thymic cystCuboidal Eccrine hidrocystoma Apocrine hidrocystomaMixed squamous and nonsquamous ciliated Bronchogenic cyst Brachial cleft cyst Thyroglossal duct cyst Cutaneous ciliated cyst Ciliated cyst of vulva Omphalomesenteric cystPseudostratified columnar Median raphe cyst

Cysts not lined by an epitheliumDigital mucous cystMucoceleMetaplastic synovial cystPilonidal cystPseudocyst of auricle

New entitiesProliferating epithelial cyst

This classification is taken from chapter 25: “Cutaneous Cysts and Related Lesions (Table 25-1: Classification of cutaneous cysts)” [4].

We propose a novel classification of cutaneous adnexal cysts according to their origin in the folliculosebaceous unit and sweat glands (Table 5; Fig. 1). This classification is in accordance with the cytokeratin expression profile of these cysts (Table 6).

Table 5

Our proposed novel classification of cutaneous adnexal cysts

Cysts with infundibular epithelial wall Epidermal (infundibular) cyst Comedon Milia Vellus hair cyst

Cysts with isthmic epithelial wall Tricholemmal cyst

Cysts with sebaceous duct epithelial wall Steatocystoma Cutaneous keratocyst

Cysts with glandular epithelial wall Eccrine/apocrine hidrocystoma

Cysts with hair matrix epithelial wall Hair matrix (pilomatrical) cyst

Hamartomatous cysts Dermoid cyst Folliculosebaceous hamartoma MADISH (metabolizing acquired dioxin-induced skin hamartoma)

Fig. 1.

Proposed novel classification of cutaneous adnexal cysts according to their origin in the folliculosebaceous unit and sweat glands.

Table 6

Cytokeratin expression of different cutaneous adnexal cysts (see Table 5)

	CK1	CK5	CK7	CK8	CK10	CK14	CK15	CK16	CK17	CK18	CK19
Epidermal cyst					+
Vellus hair cyst	+				+				+
Tricholemmal cyst					+				+
Steatocystoma					+				+
Hidrocystoma eccrine	+	+			+	+
Hidrocystoma apocrine			+	+						+	+
Dermoid cyst	+				+	+			+
Folliculosebaceous hamartoma	+				+		+	+	+
MADISH							+

Discussion

Cutaneous cysts have been classified by many prominent dermatopathologists in different ways as explained above. Here, we have proposed a novel classification of cutaneous adnexal cysts according to their origin in the folliculosebaceous unit and sweat glands. By examining the lining of the cystic structure, its origin can be easily identified. Epidermal cysts have an epithelial wall containing a granular layer, and the keratinization through the lumen is lamellar, indicating an infundibular origin (Fig. 2a, b). Tricholemmal cysts have an undulating epithelial wall with no granular layer and a compact keratinization, showing an isthmic origin (Fig. 2c, d). In steatocystoma, dermoid cyst, and folliculosebaceous hamartoma, the epithelial lining shows a crenulated appearance which is seen in the sebaceous duct (Fig. 2e, f, k, l, m, n). Hidrocystoma shows the characteristic cuboidal epithelial lining of sweat glands with decapitation secretion in its apocrine form (Fig. 2g, h). The hair matrix cyst wall is composed of basaloid cells maturing to squamoid cells, as seen in the normal hair matrix and shadow cells in the lumen (Fig. 2i, j). Metabolizing acquired dioxin-induced skin hamartoma (MADISH) is a cystic lesion with no sebaceous glands, and shows lamellar keratinization [5, 6] (Fig. 2o, p).

Fig. 2.

Epidermal cyst (a), tricholemmal cyst (c), steatocystoma (e), hidrocystoma (g), hair matrix cyst (i), dermoid cyst (k), folliculosebaceous hamartoma (m), and MADISH (o). ×1. Close-up of sections shows the epithelial lining with a granular layer and lamellar keratinization (b, p), undulation and tricholemmal keratinization with no granular layer (d), crenulation with sebaceous-duct-type keratinization (f, l, n), cuboidal cells with apocrine-type secretion (h), and basaloid cells with maturation to squamoid cells (j). ×40.

The cytokeratin expression pattern is also consistent with the origin of the cyst. For example, the sebaceous-duct keratin, CK17, is expressed in steatocystoma, dermoid cyst, and folliculosebaceous hamartoma. Epidermal cysts express CK10 as do tricholemmal cysts, which also express CK17. Eccrine and apocrine hidrocystomas show broader expression of cytokeratins (CK1, CK5, CK7, CK8, CK10, CK14, CK18, and CK19). CK16 is only expressed by folliculosebaceous hamartoma [7, 8, 9]. In MADISH, as in folliculosebaceous hamartoma, CK15 is expressed (Table 6). The hair matrix cyst, often diagnosed as a part of a follicular hybrid cyst (e.g., epidermal and/or tricholemmal cyst) does not express any cytokeratins [10]; how ever, the wall of the cyst shows a strong positivity for β-catenin [11].

The follicular stem cell marker Lrig1 is expressed at the isthmic region of the human folliculosebaceous unit [12], and the activation of β-catenin in Lrig1-positive stem cells gives rise to cystic proliferations that are reminiscent of MADISH in mice [13].

Trichoblastic infundibular cyst, cystic trichoblastoma, cystic panfolliculoma, dermoid cyst with basaloid proliferations, folliculosebaceous cystic hamartoma, and BCC occurring in infundibular cysts have also been classified differentially [14]. Recently, cutaneous keratocyst and steatocystoma, unified as sebaceous-duct cyst, have been proposed to be a hamartoma resembling the sebaceous duct [15, 16].

The classification proposed here aims to simplify the complexity of cutaneous adnexal cysts and facilitate a better understanding of the origin of the cystic lesions of the skin.

Disclosure Statement

The authors have no conflict of interest to declare.