Angiokeratoma of the Scrotum

Background

In 1896, John Addison Fordyce first described angiokeratomas of Fordyce on the scrotum of a 60-year-old man.^[1] Angiokeratomas are typically asymptomatic, 2- to 5-mm, blue-to-red papules with a scaly surface located on the scrotum, shaft of penis, labia majora, inner thigh, or lower abdomen. Histologically, they are composed of ectatic thin-walled vessels in the superficial dermis with overlying epidermal hyperplasia.^{[2, 3, 4, 5]}

"Angiokeratoma" is a broad term that encompassing various asymptomatic hyperkeratotic vascular disorders accompanied by a histologic combination of hyperkeratosis and superficial dermal vascular ectasia.^[6] More specifically, angiokeratomas can be categorized into localized and systemic forms.

There are four major localized forms with different presentations. First, solitary papular angiokeratomas typically occurs on the legs. Second, Fordyce-type angiokeratomas are usually localized to the scrotum and vulva. Third, angiokeratoma circumscriptum naviforme is the congenital form that presents as multiple, hyperkeratotic, papular, and plaquelike lesions, usually unilaterally on the lower leg, foot, thigh, buttock, and occasionally elsewhere. Finally, bilateral angiokeratomas, also known as the Mibelli type, occur on the dorsa of the fingers and toes.

The generalized systemic form, angiokeratoma corporis diffusum, is usually associated with metabolic disorders, the most common being Fabry disease or fucosidosis. Although Fabry disease is associated with the generalized presentation, a case report in 2010 recommends considering Fabry disease in all male patients with angiokeratomas, even if localized to the scrotum.^[7] Although the pathogenesis and clinical presentation vary, the histologic features are similar for all forms.^{[2, 8, 9]}

Precise epidemiological data are lacking, although estimations have been made. The principal morbidity comes from bleeding, anxiety, and overtreatment due to misdiagnosis by physicians. Usually, these lesions do not require treatment. If treatment is needed, locally destructive methods including electrocoagulation, excision, cryotherapy, or laser therapy may be used.^{[2, 10]}

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Pathophysiology

The pathophysiology of angiokeratomas remains unknown, although some authors believe increased venous pressure may contribute to their formation.^[11] Many reports describe angiokeratomas occurring in the presence of a varicocele or other conditions of increased venous pressure (eg, hernias, epididymal tumors, urinary system tumors, trauma, and thrombophlebitis).^[10] One series reports that up to half of patients with angiokeratomas have associated venous pressure conditions.^[12] One report describes treatment of the varicocele followed by resolution of the angiokeratomas,^[10] although another report describes varicocele treatment followed by no improvement in the angiokeratomas.^[13] Other proposed causative factors include acute or chronic trauma and nevoid or vascular malformations.^[14]

However, some authors contend that the coexistence of varicoceles and angiokeratomas is coincidental, as many cases have been described in which no cause for increased venous pressure was found.^[13] In a study of 435 military recruits aged 18-19 years, 10% (n = 46) were found to have varicoceles, but no angiokeratomas. They also surveyed 30 soldiers aged 45-55 years with varicoceles but again found no angiokeratomas.^[13] Similarly, a study of 1552 Japanese males found no history of any venous obstructive disorders.^[15]

The literature notes several associated predisposing factors with this disease. In a study of vulval angiokeratomas, 54% of patients were noted to have a predisposing factor (eg, pregnancy, vulval varicosity, post partum, post hysterectomy), while the rest had none.^[12] There is also a report of this condition occurring in conjunction with chronic infection with human papillomavirus in a 25-year-old woman.^[16] In addition, there may be iatrogenic predisposing factors as well. Several reports detail that radiation therapy for treatment of genitourinary malignancy may be associated with the formation of angiokeratomas of the penis and the vulva.^[17] Another case report describes a man with a recurrent penile angiokeratoma after surgery.^[18]

Angiokeratomas of Fordyce have also been reported in association with nevus lipomatosus,^[19] oral mucosal angiokeratomas,^{[8, 20]} and papular xanthoma.^[21]

Interestingly, a case of a 16-year-old boy with congenital lymphangiectasia-lymphedema born to consanguineous parents was found to have angiokeratoma of the scrotum and the penis at an early age.^[22]

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Epidemiology

Frequency

The precise incidence of angiokeratomas of Fordyce is unknown, but they are considered common, especially with increasing age.^{[2, 3, 4]}

Race

Most reports on the disease include large case series of angiokeratomas from the United States and Japan, which may at first paint a picture of disease predominantly in whites and in Japanese populations. However, cases in patients of other ethnicities exist but may be underreported.

Sex

There are more reports describing males more often than females, although direct figures of comparison do not exist. Some suggest that incidence in females is just as common as in males, but cases are grossly underreported and underrepresented in the literature.^[23]

Age

Cases have been reported ranging from children born with lesions to patients in their sixth decade who develop lesions.^[24] One publication on vulval angiokeratomas confirmed by pathology reports showed that 68% of lesions occurred in women aged 20-40 years.^[5] A study of 1552 Japanese males found that angiokeratomas occurred at all ages but were most prevalent among people older than 40 years.^[15] Prevalence according to this report was as follows^[25] :

• Age 16-20 years - 0.6%
• Age 21-30 years - 1.5%
• Age 31-40 years - 6.2%
• Age 41-50 years - 13.1%
• Age 51-60 years - 13.4%
• Age 61-70 years - 15.9%
• Age 70 years or older - 16.6%

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Prognosis

No fatalities have been reported from this condition. The most significant morbidity comes from bleeding.^[5] The papules can bleed spontaneously if traumatized or during intercourse. Many of the reports describe patient concern that the lesions represent a sexually transmitted disease.^[26]

Spontaneous resolution of angiokeratomas has not been observed in the literature; these lesions persist unless treated. Patients with multiple angiokeratomas are more likely to have recurrences after treatment than those with few or solitary angiokeratomas.

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Patient Education

In most cases of angiokeratoma, the patient, and when appropriate the partner, should be reassured that the condition is common, benign, and does not represent any form of sexually transmitted disease. More lesions may develop with increasing age.

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History

Patients usually give a history of many years of a progressive appearance of asymptomatic papules on the scrotum. The patient may not be aware of the lesions, and bleeding (spontaneous, after intercourse or scratching) may be the first presentation causing the patient to seek medical help.^{[2, 10]}

Many cases are reported in which help was sought to rule out a sexually transmitted disease or to rule out malignancy.^{[5, 27, 26]}

Bleeding from vulval lesions may occur spontaneously, during pregnancy, or after intercourse.^[5]

Most authors report that lesions are asymptomatic; however, a few describe pain or itching.^[28]

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Physical Examination

Fordyce angiokeratomas appear as black, blue, or dark red, dome-shaped papules ranging from 1-6 mm in diameter, with a mean of 3 mm. The overlying surface may show slight scales (hyperkeratosis).^[29]

Reports suggest that in younger patients, the lesions tend to be smaller, more erythematous, and less hyperkeratotic. Older patients have larger, darker lesions (blue/black) with overlying scales.^[5]

The lesions can present as singular or multiple. In a study of 25 women with vulval lesions, 50% of the cases had solitary lesions.^[5]

Lesions have been reported on the labia majora, shaft of the penis, corona of the glans penis, inner thigh, and lower abdomen. The scrotum is the most common site.^{[30, 31]}

See the images below.

View Image

Image courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

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Close-up of the eruption. Image courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

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Causes

The role of coexistent venous hypertension, varicocele, or status post radiotherapy remains uncertain and warrants further investigation.

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Complications

As mentioned previously, bleeding is the only major complication.

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Imaging Studies

Imaging studies are not warranted in the evaluation of angiokeratomas.

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Procedures

Dermoscopy can assist with the diagnosis. Angiokeratoma is characterized by large, well-demarcated, round-to-oval, and red-to-black areas, which are lacunar. In addition, a white surrounding veil corresponds to the acanthotic and hyperkeratotic epidermis.^[17]

If the diagnosis is in doubt, then a skin biopsy is recommended.

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Histologic Findings

Numerous dilated, thin-walled vessels are positioned in the papillary dermis or superficial submucosa, with an intimate relationship to the overlying acanthotic epidermis with overlying parakeratosis.^[18] In addition to elongation of the rete ridges, the epithelium is usually hyperkeratotic. Thrombosis of the vascular spaces is common, and, frequently, recanalization of occluded vascular spaces occurs, creating the pathologic pattern known as papillary endothelial hyperplasia (Masson lesion).^[17]

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Medical Care

The importance of these lesions was well summarized by Bean, "These varicules should be known so that we can allay the fears of old men, many of whom have worries enough already." If the lesions are an incidental finding or are asymptomatic, the patient can be reassured about the lesions’ benign nature. If concern exists regarding bleeding or cosmetic appearance, then several surgical treatment options are available.

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Surgical Care

Excision

This is not practical if more than a few lesions exist. However, excision can be performed with the patient under local anesthesia, with a good cosmetic result.^{[2, 3, 4, 25, 33, 34]} Obtaining negative margins has been recommended by authors who have treated recurrent angiokeratomas of the scrotum.^[18]

Cryotherapy

Application of liquid nitrogen has been used with resolution of diffuse patterns, but with residual hypopigmentation and scarring.

Electrocautery

Light electrocoagulation has been used with or without local anesthesia to produce effective resolution of diffuse lesions.^{[2, 3, 4, 25, 33, 34]}

Laser

Successful resolution has been reported with single treatments using both the 578-nm copper laser^[33] and the argon laser,^[34] resulting in minimal scarring.

A 2004 study showed benefit using a 532-nm potassium-titanyl-phosphate (KTP) laser.^[25] Another study in 2006 evaluated the efficacy of pulsed-dye laser in 12 patients with scrotal angiokeratomas.^[35] The results demonstrated good-to-excellent response in all patients, with transient purpura and minimal procedural bleeding as the only adverse effects.

In 2009, a study has shown long pulse 1-64 Nd:YAG laser to be effective, with at least 65-100% improvement in 10 patients and only 1 who had had a long-term adverse effect of an atrophic scar.^[36]

A second study published in 2009 also using long-pulse 1064-nm Nd:YAG laser described 2 cases (one of the scrotum, one of the vulva) treated successfully with no recurrence in a 2-year and 6-month follow-up, respectively.^[37]

More recently, 595-nm variable-pulse pulsed dye laser treatment has proven to be safe and efficient in removing angiokeratomas within 1-7 sessions. Of 24 treated patients, only 4 reported recurrence, with no serious adverse effects reported.^[38]

In addition, ablative lasers such as carbon dioxide and erbium-doped yttrium aluminum garnet lasers have been used to remove the hyperkeratotic epidermis before treatment with a vascular laser.^{[39, 40]}

Sclerotherapy

A 2010 article reported 3 cases treated successfully with repeated local injections of 0.5% ethanolamine oleate or 0.25% sodium tetradecyl sulfate. Both therapies had minimal and temporary adverse effects, including mild pain and epithelial sloughing with no scarring.^[41]

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Consultations

Consult a dermatologist if the diagnosis is in doubt; alternatively, a biopsy can be performed on the lesions and can be submitted to a dermatopathology laboratory for microscopic diagnosis.

Consult a urologist if a varicocele is suspected.

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Long-Term Monitoring

If a surgical procedure is performed, follow-up care at 3 months post treatment is indicated to assess the cosmetic result and to look for recurrences.

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Medication Summary

Angiokeratomas of Fordyce are a benign neoplasms and are not amenable to drug therapy.^{[2, 3, 25, 33, 34]}

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