Syringoma
Synonyms and keywords: Clear cell syringoma

# Overview
Syringomas are eccrine sweat duct tumors, typically found clustered on eyelids. However, they may also be found in the axilla, abdomen, chest, neck, scalp or groin area. Syringomas are symmetrically distributed, usually multiple, and sometimes arranged in clusters. Syringoma is a benign adnexal neoplasm which is formed by well-differentiated ductal elements.

# Historical Perspective
The name syringoma is derived from the Greek word syrinx, which means pipe or tube.

# Classification
Syringoma may be classified according to Friedman and Butler's classification into four subtypes:
- A localized form
- A form associated with Down syndrome
- A generalized form that encompasses multiple and eruptive syringomas
- A familial form

## Location
The majority of syringomas are located on the upper parts of the cheeks and lower eyelids. Other common sites for syringomas include:
- Axilla
- Chest
- Abdomen
- Penis
- Vulva
Syringomas limited to the dorsa of the hands have also been described. In the variant of eruptive syringoma, multiple lesions appear simultaneously on the chest and lower abdomen. However, rarely syringomas may appear as unilateral, linear, or nevoid lesions. The eruptive variant may involve the intertriginous areas and penis.

# Pathophysiology

## Pathogenesis
The pathophysiology of syringomas is largely unknown. However, it is hypothesized that syringomas are benign hyperplastic growths that arise from the intraepidermal portion of eccrine ducts in response to an inflammatory reaction rather than a true adnexal neoplasm. It has also been suggested that a hamartoma of pluripotent stem cells could precede the pathological process of eruptive syringomas. Additionally, syringomas may be under hormonal influence, which may explain its female predominance. An alternate hypothesis suggests that phosphorylase deficiency, resulting from hyperglycemia seen in diabetes leads to an accumulation of glycogen in the skin and within the clear cells of syringomas.

## Genetics
A mutation in chromosome 16q22 has been associated with the development of familial autosomal dominant syringoma.

## Gross Pathology
On gross pathology, syringoma may have the following appearance:
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## Microscopic Pathology
- On immunohistochemical tests, the presence of eccrine enzymes such as leucine aminopeptidase, succinic dehydrogenase, and phosphorylase and the immunohistochemical pattern of cytokeratin expression which indicates differentiation toward both the uppermost part of the dermal duct and the lower intraepidermal duct are characteristic findings of syringoma.
- On microscopic histopathological analysis, the histogenesis of syringomas is most likely related to eccrine or pluripotential stem cells.
- On electron microscopy, ductal cells with numerous short microvilli, desmosomes, luminal tonofilaments, and lysosomes are characteristic findings of syringoma.

## Associated Conditions
Syringomas may be found in association with other disorders such as:
- Hailey-Hailey disease also known as chronicfamilial benign pemphigus
- Diabetes mellitus
- Down syndrome
- Brooke-Spiegler
- Nicolau-Balus

# Causes
- Syringoma may be caused by either sporadic mutation or occur in the setting of certain genetic disorders.
- A mutation in chromosome 16q22 has been associated with the development of familial autosomal dominant syringoma..
- Usually, syringomas are sporadic. Familial syringomas are usually inherited as an autosomal dominant trait, tend to occur in adolescence or preadolescence, and most commonly affect the face.
- If the syringoma is associated with Down syndrome, it is usually located in the periorbital region. However, some rare cases of eruptive syringomas associated withDown syndrome have also been reported. Clear-cell syringoma may be associated with diabetes mellitus.

# Differentiating Syringoma from other Diseases
- Syringoma must be differentiated from other diseases such as:
- Acne Vulgaris
- Apocrine Hydrocystoma
- Basal Cell Carcinoma
- Colloid Milium
- Cowden Disease (Multiple hamartoma syndrome)
- Favre-Racouchot syndrome (Nodular Elastosis With Cysts and Comedones)
- Granuloma annulare
- Microcystic Adnexal Carcinoma
- Milia
- Sebaceous hyperplasia
- Steatocystoma multiplex
- Trichoepithelioma
- Tuberculosis
- Xanthelasma

# Epidemiology and Demographics
Syringomas affect approximately 1% of the population.

## Age
Syringomas are more commonly observed at puberty. However, patients of all ages may be affected by syringomas.

## Gender
Females are more commonly affected with syringoma than males.

## Race
There is no racial predilection for syringoma.

# Risk Factors
There are no established risk factors for syringoma.

# Natural History, Complications and Prognosis
The majority of patients with syringomas remain asymptomatic and suffer no sequelae or complications. Prognosis is generally excellent and with treatment, syringomas usually resolve with minimal scarring and no recurrence.

# Diagnosis

## History
A positive family history of syringoma may be present.

## Symptoms
Syringomas are most commonly asymptomatic. In some cases, patients with syringoma may present with pruritis.

## Physical Examination
Physical examination may be remarkable for:
- Skin-colored or yellowish, small dermal papules
- Eruptive syringomas appear as hyperpigmented papules on the chest, penile shaft, or vulva
- Lesions may appear translucent or cystic
- Syringomas are commonly smaller than 3mm in diameter

## Laboratory Findings
There are no specific laboratory findings associated with syringoma.

## Imaging Findings
There are no imaging findings associated with syringoma.

## Other Diagnostic Studies
- Syringoma may be diagnosed by skin biopsy.
- An adequate deep biopsy is usually required to rule out microcystic adnexal carcinoma.
- Consideration of rebiopsy for persistent or recurrent lesions is indicated.

# Treatment

## Medical Therapy
The mainstay of medical therapy for syringoma is oral isotretinoin, topical atropine, topical tretinoin, and oral tranilast.

## Surgery
Surgery is the mainstay of therapy for syringomas. The main reason for treatment is cosmetic; patients commonly seek treatment for syringomas of the cheeks and eyelids. The goal of surgical therapy for syringomas should be the destruction of the tumor with minimal scarring and no recurrence. However, complete removal of syringomas is often unsuccessful and recurrence is common because syringomas are embedded within the dermis. Possible surgical treatment options available for syringomas include:
- Surgical excision with primary suturing
- Scissor excision with secondary intention healing
- Electrocautery
- Electrodesiccation and curettage
- Carbon dioxide laser using the pinhole method of application or Er:YAG laser ablation
- Fractionated carbon dioxide laser ablation
- Cryotherapy
- Dermabrasion
- Trichloroacetic acid

## Prevention
There are no primary preventive measures available for syringoma. However, clinical follow-up with consideration of repeat biopsy for persistent or recurrent lesions is indicated.