Syringomas are cutaneous appendages benign tumors originated from the ducts of the eccrine sweat glands. The clinical varieties classified by Friedman and Bulter are the generalized form that includes the multiple and eruptive syringomas and the localized form, in which the vulvar syringomas are included.

We present 5 cases of vulvar syringomas, which were submitted to immunohistochemistry to determine estrogen and progesterone receptors. The immunohistochemical analysis showed positivity in four of the 5 cases for progesterone receptors, and negativity in the 5 cases for the estrogen receptors.

Keywords: Vulvar syringoma, Immunohistochemistry, Estrogen and progesterone

INTRODUCTION

Syringomas are cutaneous appendages benign tumors originated from the ducts of the eccrine sweat glands. [1,2].

In 1872, Kaposi and Biesiadeki first described the syringoma and called it Lymphangioma Tuberosum Multiplex [3]. Later, immunohistochemical and electron microscopy studies demonstrated its origin in the eccrine sweat glands [4].

The most frequent location is on the lower eyelids, but they also occur in other areas less frequently such as the forehead, neck, perilabial area, axillar region or limbs, and vulva, this last topography being very rare [1,5-10] and first reported by Carreiro in 1972 [11].

The clinical varieties classified by Friedman and Bulter are the generalized form that includes the multiple and eruptive syringomas, the familiar form, the associated to Down syndrome, and the localized form [12,13] in which the vulvar syringomas are included [12].

Clinically syringomas are recognized as multiple papular-appearing lesions from yellow-brown to skin-color, with smooth surface and firm consistency, with a bilateral, symmetrical linear distribution, 1-3 mm in diameter, and located more frequently in the labia majora ( Figure 1A,1B) [1,13,14].

The histological features are proliferation of eccrine ducts in the superficial dermis, covered by a double layer of cuboidal cells of eosinophilic cytoplasm, as well as microcystic dilations of eosinophilic PAS-positive content, which simulate a Paisley tie pattern (Figure 2A,2B) [1,10,12,14].

Some authors suggest that vulvar syringomas have a hormonal influence, justifying this hypothesis by its presentation in young women, their presence after puberty, growth during puberty and pregnancy, as well as exacerbation of pruritus during menstruation and pregnancy [6,12,15,16].

The presence and absence of progesterone receptors in vulvar stromal tissue [17], normal eccrine glands and keratinocytes suggesting a probable correlation in the evolution of syringomas with prolonged exposure to a hormonal environment with progesterone has been contradictorily reported [1,6,15,16,18-20]. The biological behavior of vulvar stromal cells and keratinocytes has not been demonstrated in relation to the hormonal stimulation of progesterone, although their association seems to be evident because they are more frequent in women, their evolution indicates that its appearance is at puberty, it grows in gestational stages and with the use of contraceptives, and they stay during the premenopausal period [15,16].

The presence of progesterone receptors in syringomas has been documented by immunohistochemistry in a study by Wallace and Smoller, who demonstrated positive immunostaining of progesterone receptor expression in eight of nine cases of extragenital syringomas; [15] Yorganci et al. also demonstrated positivity for progesterone receptors in a specific case of vulvar syringoma [16]. There is still controversy due to other studies with conflicting findings. Trager et al. did not detect positivity with estrogen or progesterone immunostaining in a case of syringomas in the neck and vulva in an 8 year-old girl [21]. Huang et al. also demonstrated negativity of both receptors in 15 cases of vulvar syringomas [6].

Due to this discordant information, the objective of our work was to identify the presence of estrogen and progesterone receptors in five cases of syringomas located in the genital area of women who came to consultation for this condition.

MATERIALS AND METHODS

A complete search was made in the histopathological results database of the Section of Dermatopathology of the ‘Dr. Manuel Gea González’ General Hospital with the words ‘syringoma’ and ‘vulvar syringoma’; we found 5 cases with these diagnoses in a search of the files reported from January 1995 to September 2017. An ambispective and cross-sectional study was carried out, the study universe was every case reported with histopathological diagnosis of vulvar syringomas and complemented by the immunohistochemical study for hormonal receptors of estrogen and progesterone.

The paraffin blocks were obtained, the histological diagnosis of syringomas was confirmed, and the standard immunohistochemistry technique was performed with an adequate control.

RESULTS

We found 5 cases of vulvar syringomas that were submitted to immunohistochemistry analysis. The age of the 5 patients varied from 18 to 55 years-old (mean 36 years-old).

The data can be found in Table 1.

DISCUSSION

From the premise that the intraepidermal portion of the eccrine ducts marks positivity for progesterone receptors, the anatomical structure that gives rise to the tumor, we expect that syringomas will also be positive for progesterone receptors [15]. The roll of these receptors in the etiology of syringomas is unknown; despite this we consider that hormonal influence exists since it is well documented that syringomas are more frequent in women, proliferate at puberty and grow during pregnancy and the premenstrual period [16].

We found nuclear positivity for progesterone receptors in 4 out of 5 cases, and negativity for estrogen receptors in the 5 cases.

The results obtained in our study agree with that of Wallace and Yorganci [15,16] that supports the proposal that there is a specific hormonal influence of progesterone for the development of syringomas of vulvar localization; however, the study of Garau et al. concluded that there is a variable expression of estrogen and progesterone receptors in normal vulvar epithelial tissue, which explains the discrepancy of data in the aforementioned studies [20].

We also detected that there is uptake of progesterone in other sites of the epithelium, not only in the eccrine ducts, but also in keratinocytes of the basal layer and in sebaceous glands, agreeing with the authors who have referred positivity in these locations [15].

In our sample, the presence of mild pruritus was reported in two cases, with the other 3 cases being asymptomatic; however, the most relevant personal concern of the patients was the aesthetic discomfort, It is important to identify vulvar syringomas to avoid confusion with their differential diagnoses, particularly with epidermal cyst, multiple steatocystomas, lichen simplex chronicus, angiokeratomas, Fox-Fordyce disease, senile angioma, condyloma acuminata and candidiasis [10].

No interventional treatment was indicated in any of the cases, explanations and measures of genital hygiene were advised.

CONCLUSION

We conclude and agree with the previously reported studies of the hormonal influence for the development of vulvar syringomas.

Since it is a poorly visible condition and the definitive diagnosis depends directly on the histopathological study, we consider it to be an underdiagnosed condition.

First-contact physicians, as well as gynecologists and dermatologists, should be aware of these benign tumors and their differential diagnoses for a proper channeling to the next level of care, and to avoid inappropriate diagnoses and unnecessary treatments.