Eruptive Vellus Hair Cysts: Report of a New Case with Immunohistochemical Study and Literature ReviewZaharia D. · Kanitakis J.
Department of Dermatology and Laboratory of Dermatopathology, Edouard Herriot Hospital Group, Lyon, France Corresponding Author
Eruptive vellus hair cysts (EVHC) are rather uncommon lesions, of which 222 cases have been published in the literature. Their etiopathogenesis is poorly known. We report herein a new typical case of EVHC that was studied immunohistochemically. A 15-year-old male presented with a 4-year history of progressively developing small brown-gray papules on the trunk and extremities. Microscopically the lesions consisted of small epidermoid cysts containing vellus hairs. Immunohistochemically, the lesions expressed keratin 1/10, calretinin and p63 but no epithelial membrane antigen, filaggrin or androgen receptors. A review of the relevant literature shows that EVHC may be inherited or acquired and may be associated to other genodermatoses, namely sebocystomatosis. They could be due to hamartomatous follicular growth, to a trouble in infundibular keratinization leading to vellus hair follicle occlusion, or represent an example of acquired hamartoma. Although benign, this condition is difficult to treat.
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Eruptive vellus hair cysts (EVHC) are uncommon lesions first described in 1977 . They manifest clinically with multiple, small papules with a smooth or centrally umbilicated surface and consist pathologically of epidermoid cysts containing vellus hairs. Up till now 222 cases of EVHC have been published in the literature . We report herein a new case of this uncommon condition studied immunohistochemically in a male adolescent suffering also from juvenile acne. A review of the relevant literature is presented with emphasis on the pathogenesis and the pathological differential diagnosis of this condition.
A 15-year-old North African adolescent (skin type IV) presented with multiple, moderately pruritic lesions that had been noticed 4 years before and were progressively increasing in number. Except for mild juvenile acne, the patient’s past personal and family medical history was unremarkable. Physical examination revealed about 30 skin-colored or brown/blue papulonodules measuring 3–6 mm with a smooth surface. They were present on the chest and neck, the flexor face of arms and forearms, upper thighs, shoulders and both axillae (fig. 1). Histological examination of a representative lesion from the forearm showed in the mid-dermis a small roundish cyst lined by a multilayered epidermal-type epithelium lacking a visible granular layer; it contained laminated keratin and small hair shafts (fig. 2), some of which showed birefringence under polarized light. The adjacent dermis contained a mild lymphocytic infiltrate but no sebaceous glands. The association of these clinicopathologic findings was diagnostic of EVHC. Immunohistochemically, keratinocytes of the cyst wall showed strong cytoplasmic expression of the suprabasal keratins 1/10 and calretinin, and nuclear expression of p63. The proliferation-associated antigen Ki67 was expressed by approximately 10% of basal keratinocytes (fig. 3). No expression of the following antigens was seen: keratins 7, 15 and 20, epithelial membrane antigen, filaggrin and androgen receptors.
|Fig. 1. Clinical appearance of EVHC. Brown-grey papules are seen on the neck and chest (a) and the axilla (b). c Close-up view of a lesion of the inner face of the arm.|
|Fig. 2. Microscopically, an EVHC is present in the dermis, surrounded by a mild infiltrate (a). It is lined by an epidermal-type epithelium devoid of granular layer and contains several sections of vellus hairs (b). HES staining.|
|Fig. 3. Immunohistochemically, the cyst wall shows strong cytoplasmic expression of calretinin (a) and keratins 1/10 (b), and nuclear expression of p63 (c); expression of Ki67 is much lower (d). Immunoperoxidase revealed with diaminobenzidine, counterstained with Mayer’s hematoxylin.|
EVHC were first described in two children presenting with follicular papules on the chest and flexor extremities . Subsequent reports showed that the condition is usually acquired, appearing mostly during the first three decades of life (mean age at diagnosis 24 years) , although it may be present at birth [1,2,3]. The development of lesions is usually progressive, but not necessarily eruptive, contrary to what their name suggests. There is a slight female predominance (1.3:1). Most reported patients were Caucasians, but EVHC also affect Asian and Black people . Typically, EVHC manifest as multiple (2–400) smooth, uniform, grouped or scattered papules or nodules measuring 1–7 mm, occurring symmetrically on the mid-chest, the neck, the extensor or flexor extremities and the axilla. Rare patients with a single lesion or with generalized ones exist . Facial lesions occur ; they were the unique localization in ten cases  and were unilateral in one of them . Unusual sites include the back, labium major , the buttocks and groin . The lesions are usually flesh-colored, but may be brown, red, white, bluish-grey (especially in Asian people) or yellowish [2,6] and may have an umbilicated or crusted surface . Umbilication probably reflects opening of the cysts to the epidermis , whereby extrusion of the cyst contents may occur, possibly leading to spontaneous resolution . They are usually asymptomatic; very rarely are they painful  or pruritic , as in our patient.
Histologically, EVHC belong to the spectrum of hair follicle-related cysts, of which several distinct varieties exist (table 1). Typical EVHC consist of small follicular cysts containing laminated keratinous material and numerous transversely and obliquely sectioned birefringent vellus hair shafts. The cyst wall consists of several layers of keratinocytes showing infundibular and isthmic-type keratinization . Absence of the granular layer does not rule out the diagnosis of EVHC since this may be absent from the cyst wall ; this was the case in our patient, in whom negative immunostaining for filaggrin confirmed the absence of keratohyalin granules, characteristic of the granular cell layer. Our immunohistochemical study showed that the cyst wall expresses several antigens of the normal hair follicle infundibulum, including keratins 1/10, calretinin (expressed specifically by the companion cell layer of the outer root sheath)  and p63, expressed by most basal and suprabasal epidermal and hair follicle keratinocytes. The expression of Ki67 was reduced, suggesting that the proliferation rate of the lesions is low, at least within a clinically stable lesion. Sebaceous glands have been rarely found within or near the cyst wall , raising the problem of differential diagnosis with steatocystomas (see below). In our case the cyst was not associated with sebaceous glands, as was also confirmed by the non-expression of sebocyte-associated antigens, including epithelial membrane antigen and androgen receptors (although these were expressed by normal sebaceous glands present in the surrounding dermis).
|Table 1. Various types of hair follicle-related cutaneous cysts [20,25,26,27]|
Clinically, EVHC must be differentiated from adnexal tumors, keratosis pilaris, perforating disorders, dermoid cysts, juvenile acne and acneiform eruptions, folliculitis, molluscum contagiosum, syringomas, milia and steatocystoma multiplex (SCM). Microscopically, the diagnosis of cutaneous epithelial cysts is based on the characteristics of the cyst wall, the type of keratinization and the content of the cavity . Whereas most clinical simulators of EVHC can be differentiated histologically, the distinction from SCM may be delicate. The relationship between the two conditions has been debated as they share similarities regarding age of onset, localization, clinical appearance and mode of inheritance , so that some authors regard them as variants of one entity . However, typical EVHC and SCM usually display different clinicopathological and immunohistochemical features . SCM lesions are as a rule larger and their incision discharges an oily fluid . Pathologically, typical SCM cysts are optically empty following loss of the sebaceous content during tissue processing; their wall is made of a thin stratified epithelium with a crenulated appearance devoid of granular layer, lined by a homogeneous hyaline cuticle similar to that of the sebaceous duct . Sebaceous glands (occasionally atrophic) are consistently present adjacent to, or within, the cyst wall. Occasionally, fragmented vellus hair shafts may be seen within the cyst. However, cases with overlapping pathological features between SCM and EVHC exist  and are often referred to as ‘hybrid cysts’ ; in addition, some patients reportedly have lesions of both SCM and EVHC . It has therefore been proposed that EVHC and SCM are variants of one disorder originating in the pilosebaceous duct . EVHC seem to originate from, or differentiate toward, the infundibulum (or isthmus) of hair follicles, as suggested by the expression of keratin 17 in the squamous epithelium. SCM could arise from the sebaceous duct as the squamous epithelium expresses keratins 10 and 17 . However, another study found that SCM are keratin 10–/14+, supporting their origin from sebaceous ducts . Overlapping features between EVHC and SCM might result from a cystic evolution at the junction of the pilosebaceous duct. It has even been proposed that SCM and EVHC, together with milia, multiple pigmented follicular cysts and hybrid cysts, should be referred to as ‘multiple pilosebaceous cysts’ .
The pathogenesis of EVHC is poorly known. Nineteen families with EVHC have been reported, showing an autosomal dominant transmission; they have an earlier onset compared with acquired cases (8.7 years) . Most EVHC are acquired and sporadic, appearing in the absence of triggering factors such as trauma or irritation [1,2,3]. They are occasionally associated with other genodermatoses, such as SCM (14 cases) , pachyonychia congenita , ectodermal dysplasia , oculo-cerebro-renal (Lowe) syndrome , and with chronic renal failure . Esterly et al.  hypothesized that a particular developmental abnormality of the vellus hair follicle predisposes it to infundibular occlusion, resulting in retention of vellus hairs and keratin into the newly formed cavity. Others regard EVHC as benign follicular hamartomas differentiating towards vellus hairs; this theory would account for the numerous vellus hairs typically seen in EVHC . Acquired EVHC could result from increased proliferation or differentiation of follicular keratinocytes, following stimulation by local or systemic factors. Such infundibular keratinization trigger factors could include advanced glycation end product in chronic renal failure , and lysosomal enzymes in Lowe syndrome . Advanced glycation end product might activate follicular keratinocytes, thereby favoring the development of cystic lesions following minor trauma or scratching . In Lowe syndrome, the deficiency in phosphatase leads to the extracellular deposition of lysosomal enzymes, so that the cysts could result from a localized attempt to wall off these enzymes . UV light could act as an additional triggering factor, as three patients developed vellus hair-containing follicular cysts associated with solar elastosis. Acquired or developmental defects of the hair follicle might be responsible for the occlusion of both infundibular or vellus cyst formation in this setting . EVHC could represent an example of ‘acquired hamartomas’, such as those that reportedly occur after dioxin exposure, formerly known as ‘chloracne’ and more recently termed ‘MADISH’ (metabolizing acquired dioxin-induced skin hamartomas) by Saurat and Sorg . The key features of hamartomas are a combination of ‘structure loss’ and ‘structure gain’, with preservation of other normal skin structures. In the case of EVHC, the ‘structure gain’ corresponds to the appearance of cystic lesions with epithelial walls showing epidermal-like differentiation with the expected expression of epidermal/pilar differentiation markers, such as keratins 1 and 10, calretinin and the nuclear protein p63. The ‘structure loss’ corresponds to the usual absence of sebaceous glands from EVHC; the cases where such glands were observed could correspond to early stages of EVHC formation, before the total disappearance of sebaceous glands. Considering this, MADISH could be added to the (pathological) differential diagnosis of EVHC; however, patients with EVHC do not report past exposure to dioxin (or to some other environmental toxic substance) .
EVHC run a chronic course. About 25% of cases resolve spontaneously, possibly through transepidermal elimination . No standard treatment exists for this benign condition that may nevertheless cause cosmetic concern. If treatment is requested, topical 12% lactic acid, retinoic acid, adapalene or calcipotriene can be tried, but the results are modest . Tazarotene 0.1% cream reportedly achieves better results than erbium:YAG laser or incision . Encouraging results with erbium:YAG laser followed by manual cyst extraction were recently reported . Neither oral isotretinoin (1 mg/kg for 20 weeks) nor vitamin A therapy proved successful [5,23]. Individual lesions may be extracted with dissecting forceps after puncturing the skin under local anesthesia or destroyed with dermabrasion, incision and drainage, curettage and cauterization . CO2 laser vaporization and erbium:YAG laser proved effective for treating some lesions [4,5]; recurrences are however possible and the risk of scar formation should be considered.
We thank Dr. B. Balme for her contribution to the pathological study.
The authors have no conflicts of interest to declare.
Department of Dermatology and Laboratory of Dermatopathology
Edouard Herriot Hospital Group
5 place d’Arsonval, FR–69437 Lyon Cedex 03 (France)
Tel. +33 472 110 301, E-Mail firstname.lastname@example.org
Received: November 29, 2011
Accepted after revision: January 31, 2012
Published online: March 28, 2012
Number of Print Pages : 5
Number of Figures : 3, Number of Tables : 1, Number of References : 27
Vol. 224, No. 1, Year 2012 (Cover Date: May 2012)
Journal Editor: Saurat J.-H. (Geneva)
ISSN: 1018-8665 (Print), eISSN: 1421-9832 (Online)
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