Angiokeratoma of the Scrotum 

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]}

Precise data on their frequency and distribution are lacking, although estimations have been made. The principal morbidity comes from bleeding, anxiety, and overtreatment due to misdiagnosis by physicians. Usually, they do not require treatment. If treatment is needed, then locally destructive methods including laser, electrocoagulation, excision, cryotherapy, or laser therapy may be used.^{[2, 6]}

Angiokeratoma is a broad term that describes various conditions of asymptomatic hyperkeratotic vascular disorders with a histologic combination of hyperkeratosis and superficial dermal vascular ectasia.^[7] More specifically, angiokeratomas can be categorized into localized and systemic forms.

The localized forms include (1) solitary papular angiokeratoma, which typically occurs on the legs; (2) localized angiokeratoma of the scrotum and vulva (Fordyce type); (3) the congenital form, angiokeratoma circumscriptum naviforme, which presents as multiple, hyperkeratotic, papular and plaquelike lesions, usually unilaterally on the lower leg, foot, thigh, buttock, and occasionally elsewhere; and (4) bilateral angiokeratomas that occur on the dorsa of the fingers and toes (Mibelli type).

The generalized systemic form, angiokeratoma corporis diffusum, is usually associated with a metabolic disorder, the most common being Fabry disease or fucosidosis. Even though 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.^[8] Although the pathogenesis and clinical presentation vary, the histologic features are similar for all forms.^{[2, 9, 10]}

The pathophysiology of angiokeratomas remains unknown, although 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).^[6] Other causative factors include acute or chronic trauma and nevoid or vascular malformations.^[12] One series reports that up to two thirds of patients have associated conditions.^[13] One report describes treatment of the varicocele followed by resolution of the angiokeratomas,^[6] and another report describes varicocele treatment followed by no improvement in the angiokeratomas.^[14]

Many cases have been described in which no cause for increased venous pressure was found. In a study of 435 military recruits aged 18-19 years, 10% (n = 46) were found to have varicoceles; none had angiokeratomas. They also surveyed 30 soldiers aged 45-55 years with varicoceles but found no angiokeratomas. They propose that the coexistence of varicocele and angiokeratomas is coincidental.^[14] Similarly, a study of 1552 Japanese males found no history of any venous obstructive disorders.^[15]

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.^[13]

Penile and vulvar angiokeratomas have also been noted status post radiation treatment of genitourinary malignancy.^[16] A 2006 report describes a man with a recurrent penile angiokeratoma after surgery.^[17] Another author describes angiokeratoma of Fordyce simulating penile cancer.^[18] Angiokeratomas have been described on the clitoris in a 14-year-old girl,^[19] as well as in conjunction with chronic infection with human papillomavirus in a 25-year-old woman.^[20]

Angiokeratomas of Fordyce have also been reported in association with nevus lipomatosus,^[21] oral mucosal angiokeratomas,^{[9, 22]} and papular xanthoma.^[23]

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.^[24]

Frequency

International

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

Mortality/Morbidity

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.^[25]

Race

Large series of angiokeratomas have been reported from America and Japan, which give a picture of disease predominantly in whites and in Japanese populations. Cases in blacks exist but are few in number.

Sex

Males have been reported far more often than females, although direct figures of comparison do not exist. Some suggest that female angiokeratoma cases are probably as common as male cases but are grossly underreported and underrepresented in the literature.^[26]

Age

Cases have been reported, ranging from children born with lesions to lesions developing in patients in their sixth decade.^[27] The only publication on vulval lesions, identified by pathology reports of removed lesions, 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 was as follows^[28] :

• 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%