Syringoma

Background

Syringoma is a benign adnexal neoplasm formed by well-differentiated ductal elements. The name syringoma is derived from the Greek word syrinx, which means reed or pipe.

Based on Friedman and Butler’s classification scheme, 4 variants of syringoma are recognized: (1) a localized form, (2) a form associated with Down syndrome, (3) a generalized form that encompasses multiple and eruptive syringomas, and (4) a familial form.

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Pathophysiology

Syringoma is generally considered a benign neoplasm that differentiates along eccrine lines; very rare malignant variants (syringocarcinoma) are described.

Enzyme immunohistochemical tests demonstrate the presence of eccrine enzymes such as leucine aminopeptidase, succinic dehydrogenase, and phosphorylase. The immunohistochemical pattern of cytokeratin expression indicates differentiation toward both the uppermost part of the dermal duct and the lower intraepidermal duct (ie, sweat duct ridge). However, distinguishing between eccrine and apocrine ducts is sometimes difficult, and many tumors that were traditionally thought to be eccrine have been shown to have apocrine differentiation. Electron microscopy of syringomas demonstrates ductal cells with numerous short microvilli, desmosomes, luminal tonofilaments, and lysosomes.^[1] The histogenesis of syringomas is most likely related to eccrine elements or pluripotential stem cells.

Some investigators have suggested that cases of eruptive syringoma may represent a hyperplastic response of the eccrine duct to an inflammatory reaction rather than a true adnexal neoplasm.^[2] In this setting, the term syringomatous dermatitis may be more appropriate. Likewise, the scalp “syringomas" seen in scarring alopecia represent a reactive proliferation in response to the fibrosis.

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Etiology

Syringomas are usually sporadic, but more than 10 cases of familial syringomas have been reported in the English literature. In the familial setting, syringomas tend to occur in preadolescence or adolescence, most commonly affect the face, and are usually inherited as an autosomal dominant trait.^[3]

Eruptive syringomas (see image below) are more common in African Americans and Asians than in other ethnic groups. One patient presented with extensive eruptive syringomas following liver transplantation, suggesting a potential role for immunosuppression in pathogenesis.^[4]

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Eruptive syringomas.

In Down syndrome, the prevalence of syringoma is reportedly approximately 18-40%, usually located in the periorbital region; however, rare cases of widespread eruptive syringomas associated with Down syndrome have also been reported.^{[5, 6, 7]}  Syringomas associated with Down syndrome have a higher rate of calcification, which may progress to calcinosis cutis.^[8]

Some cases of syringoma are associated with diabetes mellitus; altered glucose metabolism perhaps may lead to the clear-cell phenotype of syringomas in the setting of diabetes.^{[8, 9]}

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Epidemiology

Frequency

Syringomas affect approximately 1% of the population.

Race

A racial or ethnic predilection has not been reported.

Sex

Females are affected by syringomas more often than males.

Age

Syringomas usually first appear at puberty; additional lesions can develop later.

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Prognosis

Syringomas are benign and their significance is largely cosmetic. With treatment, syringomas ideally should be destroyed with minimal scarring and no recurrence. See Surgical Care.

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History

Syringomas usually are asymptomatic. However, rare cases are associated with pruritus, especially in the setting of perspiration or when localized to the vulva.^[3] Uncommonly, the patient may have a family history of similar lesions. Rarely, syringomas may be associated with the Brooke-Spiegler syndrome, an autosomal dominant disease characterized by the development of multiple cylindromas, trichoepitheliomas, and occasional spiradenomas.^[10] Other associations include Nicolau-Balus syndrome, characterized by milia and atrophoderma vermiculatum,^[11] and Costello syndrome, characterized by various other cutaneous manifestations such as hyperkeratosis, hyperpigmentation, papillomas, and deep palmoplantar creases, as well as craniofacial, musculoskeletal, and neurologic abnormalities.^[12] In rare cases, syringoma can be associated with steatocystoma multiplex.^[3] The incidence of syringoma appears notably increased in association with Down syndrome.^{[5, 6, 7]}

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Physical Examination

Appearance

Syringomas are skin-colored or yellowish, generally small, dermal papules (see image below).

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The multiple, small, yellow papules in the lower lid and upper part of the cheek correspond to syringomas. The blue cyst in the inner canthus is an ec....

Sometimes, the lesions may appear translucent or cystic. The surface of syringomas can be rounded or flat. Syringomas are usually smaller than 3 mm in diameter. However, rare cases of giant syringoma have been reported.^[13] Eruptive syringomas typically appear as hyperpigmented papules on the chest, penile shaft, or vulva.

Distribution

Syringomas are usually multiple, sometimes arranged in clusters, and symmetrically distributed. Most commonly, syringomas are limited to the upper parts of the cheeks and lower eyelids.

Other characteristic sites for syringomas include the axillae, chest, abdomen, penis, and vulva. Case reports have described syringomas limited to the dorsa of the hands.^[14] In the variant of eruptive syringoma, multiple lesions appear simultaneously, typically on the chest and lower abdomen. The eruptive variant may involve the penis^[15] and intertriginous areas.^[16] Rarely, syringomas appear as unilateral, linear, nevoid lesions.^[17]

Differential diagnoses and related conditions

In rare instances, scalp syringomas are associated with scarring alopecia.^[18]

Clinically, syringomas on the face must be distinguished from trichoepitheliomas and basal cell carcinomas.

Lesions on the eyelids may be confused with xanthelasmas.

Eruptive syringomas on the trunk can resemble disseminated granuloma annulare.

Microcystic adnexal carcinoma can masquerade as syringoma.^[19] Plaque-type lesions have been described and may be mistaken for microcystic adnexal carcinoma.^[20]

Lesions of Fox-Fordyce disease (multiple pruritic follicular papules) should be differentiated from syringomas.^[21]

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Procedures

An adequately deep biopsy is required to rule out microcystic adnexal carcinoma. Clinical follow-up with consideration of rebiopsy for persistent or recurrent lesions is indicated.

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Histologic Findings

Syringoma is usually located mostly in the superficial dermis and is composed of numerous small ducts embedded in a sclerotic stroma (see image below). Rarely, deep reticular dermal involvement has been reported.^[23]

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Histologic section of syringoma demonstrates numerous small ducts in a sclerotic stroma. Note the tadpole-shaped ducts.

The walls of the ducts are usually lined by two rows of cuboidal-to-flattened epithelial cells and have a lumen containing periodic acid-Schiff–positive, eosinophilic, amorphous debris. Some of the ducts have elongated “tails” of epithelial cells, producing a characteristic comma-shaped or tadpole appearance. Rarely, tumor cells may appear clear as a result of glycogen accumulation (see image below).

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Histologic section of clear-cell syringoma.

In a research context, enzyme immunohistochemical tests in syringoma demonstrate the presence of eccrine-related enzymes such as leucine aminopeptidase, succinic dehydrogenase, and phosphorylase. The immunohistochemical pattern of cytokeratin expression indicates differentiation toward both the uppermost part of the dermal duct and the lower intraepidermal duct (ie, sweat duct ridge).^[24] Distinguishing between eccrine and apocrine ducts may be difficult, however.

The histologic differential diagnosis includes sclerosing (morphealike) basal cell carcinoma and desmoplastic trichoepithelioma. Importantly, syringoma must be distinguished from microcystic adnexal carcinoma, which has similar histologic features but tends to infiltrate the deep dermis and subcutaneous tissue. Therefore, partial superficial biopsies may be problematic in this situation.

Chondroid syringoma is a different benign adnexal tumor with a characteristic myxoid cartilaginous matrix and is analogous to the benign mixed tumor (pleomorphic adenoma) of salivary gland.

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Medical Care

Oral isotretinoin and acitretin and topical tretinoin have been used to treat syringomas, and the application of topical atropine has been used to relieve pruritus.^[25]

Application of topical adelmidrol, a semisynthetic cannabinoid, was beneficial in one case of giant vulvar syringoma; it may act via down-regulation of mast cell activation.^[26]

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Surgical Care

The main reason for treatment is cosmetic; in particular, patients commonly seek treatment for syringomas of the eyelids and cheeks, which may be conspicuous. The goal of therapy for syringomas should be the destruction of the tumor with minimal scarring and no recurrence. However, because syringomas are embedded within the dermis, complete removal is often unsuccessful and recurrence is common.^[25]

No comparative studies and no long-term follow-up studies are available on which to base definitive recommendations for syringoma treatment. Possible treatments include the following:

• Surgical excision with primary suturing
• Scissor excision with secondary intention healing
• Electrocautery^[27]
• Electrodesiccation and curettage
• Carbon dioxide laser using the pinhole method of application or Er:YAG laser ablation^{[28, 29, 30]}
• Fractionated carbon dioxide laser ablation^[31]
• Cryotherapy
• Dermabrasion
• Trichloroacetic acid

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