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Dermatologic Diseases of the Male Genitalia: Nonmalignant and malignant

Dermatologic Diseases of the Male Genitalia: Non malignant

Authored by Milton W Datta, MD, Assistant Professor, Department of Pathology, Medical College of Wisconsin

Coauthored by Hon Pak, MD, Chief of Dermatologic Surgery and Outpatient Clinic, Assistant Professor, Department of Dermatology, Wilford Hall Air Force Medical Center, Uniformed Services University; Scott M Acker, MD, Assistant Professor, Departments of Pathology and Dermatology, Medical College of Wisconsin; Peter Langenstroer, MD, Assistant Professor, Department of Surgery, Division of Urology, Medical College of Wisconsin

Milton W Datta, MD, is a member of the following medical societies: College of American Pathologists

Edited by Martha K Terris, MD, FACS, Chief, Section of Urology, Veterans Palo Alto Health Care System; Assistant Professor, Department of Urology, Stanford University Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Laurence Klotz, MD, Professor, Department of Surgery, University of Toronto School of Medicine, Canada; J Stuart Wolf, Jr, MD, Director of Michigan Center for Minimally Invasive Urology, Associate Professor, Department of Urology, University of Michigan Medical Center; and Stephen W Leslie, MD, FACS, Founder and Medical Director of the Lorain Kidney Stone Research Center, Assistant Clinical Professor, Department of Urology, Medical College of Ohio

Introduction, Definition of terms and anatomy
Nonmalignant lesions account for the majority of dermatologic disorders seen by urologists. They usually are not biopsied, but rather, they are treated empirically and are not commonly referred to dermatologists or pathologists. Throughout this article, the discussion focuses on diseases that are either specific to the male genitalia or make their initial appearance in this location. Disorders suggestive of systemic conditions or diseases are not discussed in this article. While rare in the United States and minimally emphasized in medical schools, a resurgence in some infectious diseases is occurring due to increased world emigration and the spread of resistant forms.
Topics in this article are divided into groups based on their initial clinical presentation and most common appearance. The underlying discussion focuses on diagnosis, treatment, and clinical outcome. Attempts are made to include the most recent and relevant treatment options, emphasizing the use of pharmaceuticals and their impact. US Centers for Disease Control and Prevention (CDC) recommendations are stressed, and promising experimental treatments are noted. While presenting a comprehensive review of each disorder is not the goal of this article, a thorough and understandable knowledge base for the treatment of patients is provided, along with references that lead to more detailed and comprehensive studies of the field.

Dermatology terms
In the field of dermatology, use of specific terms to describe clinical findings allows communication of essential information and may suggest a differential diagnosis. To the uninitiated, these terms can lead to confusion, frustration, and a review of other career options. Therefore, this article begins with definitions of terms used to describe the most common dermatologic appearances.
Macules: These are small defined areas of color change that are not palpable (ie, flat or sometimes collapsed, but not bumpy). Macules tend to be smaller than 1 cm.
Patch: This is a larger (>1 cm) area of color change that is nonpalpable (ie, level with the skin). In essence, a patch is a large macule.
Papules: These are small lesions that are palpable (ie, feels like a bump). They tend to be smaller than 1 cm and can be any color or texture.
Plaque: This is a large (>1 cm) raised area with palpable borders. Basically, it is a large papule with extensions along the edges. Note that the height is not increased. A plaque is large, raised, and flat. Edges can be palpated, and borders are well delineated. Like papules, they can be any color or texture. Often, this represents a confluence of papules.
Nodule: This is a large (>1.5 cm) papule. Unlike plaques, an increase in the lesion's height is noted.
Vesicles: These are fluid-filled bumps, usually smaller than 1 cm in diameter. The common term is blister. A distinct characteristic is that when it is incised and the fluid is removed, the vesicle collapses. It can be considered a fluid-filled papule.
Pustules: These are vesicles filled with neutrophils.

Dermatologic anatomy of the male genitalia

The male external genitalia are comprised of the penis and scrotum. The penis is divided into the more distal glans and the shaft or body, which is anchored by its root in the perineal pouch. The prepuce (foreskin) covers the glans. It is a thin loose covering of keratinizing skin with associated underlying eccrine (sweat) and sebaceous glands and a highly vascular stroma without underlying adipose tissue. The prepuce is composed of the following 5 layers: (1) external keratinizing epidermis, (2) underlying dermis with eccrine and sebaceous glands, (3) fine strands of dartos muscle, (4) lamina propria, and (5) internal squamous mucosa.
The glans is an extension of the highly vascular corpus spongiosum and is covered by squamous epithelium that is keratinized in the circumcised male. The scrotum extends the keratinized squamous epithelium with underlying dartos muscle and associated external spermatic fascia. Here the dermis contains hair follicles in association with eccrine, apocrine, and sebaceous glands. Scattered fat cells are present, although well-formed subcutaneous adipose tissue usually is not.
The majority of the dermatologic disorders are confined to the epidermis, underlying dermis, and associated adnexal structures. These areas include the keratinized epithelium, the underlying dermis with its rich vasculature, associated smooth muscle, and associated hair follicles and sweat and sebaceous glands.

TRICHOMYCOSIS AND FOLLICULITIS

Trichomycosis
Trichomycosis (see Trichomycosis Pubis) is an infection of the hair shaft that is found in areas bearing sweat glands, in particular the inguinal area. Treatment centers on the use of topical antibiotics and drying agents.

Pathophysiology
Corynebacterium tenuis, which prefers the moist microenvironment of the inguinal regions, is the causative organism associated with most cases. Although up to 33% of adults have colonization by this bacterium in the inguinal or axillary regions, factors such as hyperhidrosis initiate more extensive growth and clinical manifestations.

Clinical presentation/diagnosis
Patients typically present with yellow/black or red nodules on the hair shafts in the inguinal region. Nodules are often on the scrotum and occasionally on the base of the shaft of the penis. These lesions can be associated with erythema and itching. Superinfection with other dermatophytes has been noted.

Differential diagnosis
Clinical separation from other organisms often is not performed, and treatment focuses on empirical use of drying agents and topical antibiotics.

Treatment
Treatment involves alleviating the hyperhidrosis, focusing on the use of drying agents. Topical clindamycin is helpful in refractory or extensive cases.

Outcome
The main complication appears in immunocompromised hosts who can develop more extensive septicemia secondary to colonization of catheters and surgical sites. Treatment in the immune-competent host yields few long-term adverse effects.

Folliculitis
Folliculitis (see Folliculitis) is an infection of the hair shaft that occurs in the pubic area and clears with appropriate antibiotic treatment, as in other regions of the body.

Pathophysiology
This lesion often occurs from external trauma (shaving, rubbing), irritation from hyperhidrosis and moisture, or topical irritants. This environment leads to bacterial colonization and overgrowth, leading to subsequent clinical presentation. Organisms identified include Staphylococcus species but also can involve Pseudomonas and Candida species.

Clinical presentation/diagnosis
Patients often present with small red papules or pustules centered on hair follicles. These often are present at the base of the penile shaft or on the scrotum. Often, additional symptomatology is not present.

Differential diagnosis
The differential diagnosis is broad and includes infections with other organisms that could result in folliculitis under various circumstances. Because treatment often is empirical and cultures or biopsy are not performed routinely, clinical examination to exclude viral (Tzanck prep), fungal (potassium hydroxide [KOH] prep), or neoplastic (biopsy) causes are the most important. Folliculitis also can be part of the spectrum of disease presentation in Behçet disease (see Bechet Disease) and, thus, also should be considered in a patient with other systemic symptoms including oral and genital aphthae, uveitis, joint disease, and gastrointestinal disease.

Treatment
Treatment is directed at the offending organism. It includes improved hygiene, drying agents, and topical and oral antimicrobials or antivirals as necessary. Conservative therapy is reserved for sterile folliculitis.

Outcome
Outcome usually is satisfactory. Failures result from misclassification of the causative organism or the presence of a mixed culture of pathogenic organisms.

BALANOPOSTHITIS AND BALANITIS

Balanoposthitis
Defined as the inflammation of the foreskin and the glans in uncircumcised males, balanoposthitis (see Balanoposthitis) may have any of multiple bacterial and fungal origins. Complex infections also have been well documented. These often are due to a poorly retractile foreskin and poor hygiene that leads to colonization and overgrowth. Treatment centers on improved hygiene and circumcision, if needed.

Pathophysiology
Often identified in association with poorly retractile foreskins in young boys (<5 y), balanoposthitis is associated with bacterial infection secondary to poor hygiene. Anaerobic organisms have been associated with the diagnosis, although in most cases, the patient is treated empirically and a specific organismal etiology is not obtained. Candidal infection appears to be the most common cause of disease. The condition in older adult men often has other etiologies, including intertrigo; irritant dermatitides; and candidal, viral, or fungal infections.

Clinical presentation/diagnosis
In adults, a good clinical history focusing on topical irritants and home treatments, coupled with KOH and Tzanck preps, leads to the correct diagnosis. Biopsy seldom is needed, although a lack of response to treatment warrants a biopsy to rule out premalignant or malignant lesions.

Differential diagnosis
The differential diagnosis includes intertrigo (see Intertrigo); irritant dermatitides; and candidal (see Candidiasis, Cutaneous), viral, or fungal infections. As emphasized above, the use of clinical diagnosis and KOH and scrape preps often leads to the correct diagnosis. In addition, ulcerating lesions of the penis may result from bites with subsequent infection by oral flora. These lesions can be diagnosed based on clinical history and culture of the ulcer. Rare causes include amebiasis (see Amebiasis), usually in homosexual men, which should be suspected in patients with poor response to antibiotics. Examination for trophozoites is confirmatory.

Treatment
Topical antibiotics and antifungals or low-potency steroid creams often lead to clearing of the lesion. Treatment includes proper hygiene with washing and drying of the prepuce. Circumcision usually is effective if medical therapy fails.

Outcome

The outcome often is favorable. Treatment failures often lead to further clinical examination and further treatments tailored to the particular offending agent. Failure of response in the setting of appropriate treatment suggests malignancy. This necessitates a biopsy to rule out both primary and secondary malignancies involving the penis. One case report describes the presentation of acute promyelocytic leukemia as an ulcerating balanoposthitis.

Plasma cell balanitis
First described in 1952 by Zoon, plasma cell balanitis (Zoon balanitis, Balanitis Circumscripta Plasmacellularis) is characterized by the histologic appearance of an infiltrate rich in plasma cells. Although asymptomatic, these lesions may represent a variant of lichen planus. Histologically, these lesions do not share features with lichen planus. Treatment often involves circumcision, although topical steroids and retinoids have been used with some success, based on the possible origin in lichen planus.

Pathophysiology
Although the etiology is unclear, the possibility that this lesion is a plasma cell-rich variant of lichen planus has gained some attention, mainly due to the potential for response to anti-inflammatory treatments.
In one study, immunoglobulin E (IgE) and immunoglobulin G (IgG) were determined to be major immunoglobulin classes in plasma cellular infiltrate; thus, the disorder may have more in common with a hypersensitivity reaction than an infectious process. Other classes of immunoglobulins were produced in lesser quantities. Immunoperoxidase studies revealed low immunoglobulin M (IgM) levels and a mixed kappa-to-lambda ratio, which favored a polyclonal B-cell stimulation. Another premise explains the disorder as a disturbed preputial ecology that results in the nonspecific balanitis. Progression to a malignant B-cell proliferation has not been reported, although a report of carcinoma of the penis postdating Zoon balanitis has been published. No association with human papillomavirus (HPV) and Zoon balanitis has been identified.

Clinical presentation/diagnosis
Although the mean age at presentation is 53 years, patients aged 18-88 years are described in 2 series and presentation in children as young as 12 years has been described. Usually, plasma cell balanitis occurs in men, although a similar lesion has been described as plasma cell vulvitis in women. Typically, men are uncircumcised in most series. In one analysis of diseases in uncircumcised men, Zoon balanitis was present in uncircumcised males only.
Occasionally, discharge may be the presenting complaint. The clinical course typically is chronic, and delays in presentation average 12 months due to embarrassment or lack of access to health care. Delays in seeking treatment have been as long as 17 years. Usually, patients present with a single, large (>2 cm), bright red-to-brown, sharply circumscribed, moist patch on the glans or inner prepuce. Rarely, multiple patches occur that can erode and ulcerate. Clinical involvement typically (85%) is on both the glans and prepuce or prepuce only. Presentation on the glans alone is less common.
Histologic evaluation reveals a bandlike plasma cell infiltrate of the upper dermis, with dilated capillaries and associated extravasated red cells and hemosiderin deposition. The overlying epidermis is thin, with marked spongiosus and without cytological atypia. The spongiosus can be so marked that it accentuates the individual keratinocytes to give them a characteristic diamond-shaped appearance. The cellular population is composed of plasma cells, with associated macrophages, mast cells, and eosinophils. These findings are confirmed by electron microscopy.

Differential diagnosis
Often, the clinical resemblance to erythroplasia of Queyrat leads to biopsy of the lesions. See Erythroplasia of Queyrat (Bowen Disease of the Glans Penis). Subsequent histologic features allow separation from these entities. Occasionally, balanitis xerotica obliterans (see Lichen Sclerosus et Atrophicus) also may show dense plasmacytic infiltrates. Candidal balanitis also should be considered in the differential diagnosis. Although previously described as a separate entity, chronic pseudoerythroplastic balanitis now appears to be a different stage in the course of plasma cell balanitis.

Treatment
Previously, treatment focused on surgical excision or laser ablation, although the use of Retin-A has recently met with some success. The use of topical and intralesional corticosteroids has met with mixed results, with some groups advocating use and other groups finding them (particularly topical forms) ineffective. Experimental use of cyclosporin A has been attempted, with preliminary results that are hopeful.

Outcome
Although outcome with the use of newer treatments has yielded promising results, surgical removal of the foreskin has been advocated as standard case management. Circumcision was successful in 27 patients, with no recurrence after 3 years of follow-up. Most authors report a nearly 100% curative effect with adequate circumcision.

Candidiasis
Candidal balanitis (see Candidiasis, Cutaneous) is a relatively common disorder, most often present in uncircumcised men with poor hygiene. It has been associated with vulvovaginitis in the sexual partner, and treatment of both partners with antifungals usually yields an adequate result.

Pathophysiology
While common in uncircumcised men, the main association appears to be with poor hygiene and the entrapment of smegma under the prepuce. Additional factors that contribute to infection include surface maceration, diabetes mellitus, and immunosuppression. Candidal balanitis often is associated with vaginal infection in the sexual partner, thus leading to a co-infection. While many species have been isolated, Candida albicans is by far the most common.

Clinical presentation/diagnosis
Clinical presentation is bright red patches/papules with associated small pustules/erosions (satellite lesions) that most commonly involve the foreskin and glans. Patients also often describe itching and burning sensations after intercourse. Diagnosis using a KOH scrape reveals yeastlike fungus with budding and pseudohyphal forms. Biopsies often reveal a prominent neutrophilic infiltrate in the epidermis and associated chronic inflammation in the dermis. The diagnostic pseudohyphae usually are present colonizing the stratum corneum.

Differential diagnosis
The differential diagnosis includes dermatophytes and can be ruled out based on the clinical presentation of satellite lesions (uncommon in tinea) and the morphologic appearance on the KOH scrape.

Treatment
Treatment focuses on the cause of the papules and pustules, with antifungals used for presumed candidal infections. Topical azole creams or nystatin have been used successfully in the treatment of candidal balanitis. A positive culture alone is not sufficient for diagnosis, and other organisms also must be ruled out because Candida species may colonize other forms of balanitis.

Outcome
Treatment often is effective if the partner also is treated, removing possible reservoirs for future reinfection.

DERMATOPHYTES AND SCABIES

Dermatophytes
Dermatophyte infections include fungal organisms that colonize the keratinized epidermal layer and establish an associated inflammatory host reaction. When present in the groin/male genitalia, they are referred to as tinea cruris or "jock itch" (see Tinea Cruris). Clinical presentation is characterized by the annular scaly patch common to presentations in most other locations on the body. These lesions can be diagnosed by KOH scrape preps and treated with topical antifungals.

Pathophysiology
These infections often are present in communal showers at gym facilities and spread to the genital areas from the feet via towel drying. The fungi colonize the superficial layers of the epidermis and include the species Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

Clinical presentation/diagnosis

Patients usually present with red-brown circinate lesions with raised borders. These often involve the thighs, the groin, and, less commonly, the scrotum. Secondary excoriation and lichenification are common, and continued excoriation can lead to secondary bacterial infection.

Differential diagnosis
Involvement of the scrotum is associated more often with candidal infection (see Candidiasis, Cutaneous), and is suggested in this setting. The finding of satellite lesions is more in keeping with a candidal infection than dermatophyte.

Treatment
Topical antifungal creams are effective, along with drying agents. Also, towel drying should be performed from top to bottom, ending with the feet.

Outcome
Treatment with antifungals usually is sufficient, although recurrence is possible. Recurrent disease may cause postinflammatory hyperpigmentation.

Scabies
The first causative agent of a human disease was identified in 1687. It was scabies (see Scabies). The mite Sarcoptes scabiei causes these highly contagious pruritic lesions. While this contagion can be sexually transmitted, poor hygiene and living conditions also can lead to infection. Treatment is effective, but it must involve the entire living group and include removal of contaminated bedding and clothing.

Pathophysiology
While highly contagious, prolonged contact is necessary to cause transmission. This most often is achieved through contact with contaminated clothes or bedding. Scabies mites create burrows in the epidermis up to 1 cm in length and lay eggs within these nests. These eggs often elicit an IgE-mediated cellular immune response and the associated pruritus. In fact, patients often have elevated serum IgE levels. Larvae emerge from their burrows in 4 days and mature in 10-14 days.

Clinical presentation/diagnosis
Patients often present with severely pruritic scaly red patches that may be papular or nodular (more common on the male genitalia). Associated excoriation of the lesions is common due to severe itching that is worse at night or when the patient is warm. Diagnosis is made by teasing out samples of the mite with a needle or by scraping and identifying mite body parts or eggs from skin prep treated with KOH. While not often performed, biopsies reveal the female mite in the keratinizing horny layer, with eggs in the burrow staining positive with periodic acid-Schiff (PAS) stain. Epidermal spongiosus, associated dermal eosinophilia, and a prominent superficial and deep dermal inflammatory reaction also are present.

Differential diagnosis
Nodular and treated forms (scabies incognito) may make the diagnosis more difficult. The use of topical corticosteroids also may mask a more typical presentation. Secondary bacterial or viral herpes simplex virus (see Herpes Simplex) superinfection may result in presentation as vesicles and lead to misdiagnosis.

Treatment
Lindane 1% lotion or cream is recommended, with application and subsequent washing 8 hours later. This is not recommended for pregnant women or children younger than 2 years. In these patients, permethrin 5% cream is used. Antipruritic agents also are valuable to reduce the amount of excoriation and discomfort. Treatment also must cover additional family members and partners to remove the reservoir and eliminate reinfection. Often, itching continues for as long as a week after treatment, most likely due to the immune reaction to residual scabies material. If no response is observed, perform a second search for mites before a second round of treatment is given. Clothes and bedding should be washed in hot water and dried in a hot dryer before subsequent use.

Outcome
The first treatment usually is 90% effective. A particular crusted variant (hyperkeratotic or Norwegian scabies) exists, characterized by a more keratotic psoriasiform lesion that is seen in patients with HIV or other immunocompromised states. This lesion is highly contagious, even to individuals who are not immunocompromised, due to the high total mite burden and may lead to localized epidemic outbreaks. Bacterial superinfection, usually by staphylococcal or streptococcal species, may lead to localized and systemic findings and even acute glomerulonephritis.

INFECTIOUS AGENTS AFFECTING THE MALE GENITALIA

Lymphogranuloma venereum
While uncommon in the United States as a cause of genital ulcers, lymphogranuloma venereum (see Lymphogranuloma Venereum) accounts for up to 10% of genital ulcers in areas of India and Africa. Only 113 US cases were reported to the CDC in 1997. After a patient with an often-unidentified primary papule, inguinal lymphadenitis, and bubo formation presents for clinical care, treatment involves the use of antibiotics to clear the infection and prevent tertiary sequelae.

Pathophysiology
Chlamydia trachomatis, an obligate intracellular organism that infects macrophages, is the causative agent. Serotypes L1-3 have been associated with infection. Characterization of the rate of transmission or the reservoir of C trachomatis has not been defined clearly, although asymptomatic women are believed to be carriers of infection. Incubation periods of 3-30 days are reported. The patient often does not notice the initial presenting small papule or ulcer. The second stage has its onset 2-6 weeks later, with lymphadenitis of the inguinal nodes and associated lymphangitis.

Clinical presentation/diagnosis
The condition occurs in men aged 15-40 years, with presentation as an acute ulcerating disease more common in men than in women. The initial presentation (primary stage) occurs 1-4 weeks after exposure as a transient firm painless papule or ulcer that may not be noticed by either the patient or physician. Male patients tend to present during the second stage, with painful inguinal adenopathy that usually is unilateral. Subsequent rupture and bubo formation may be accompanied by fever, chills, headache, nausea, and arthralgias.
Diagnosis is hampered by the difficulty in culturing the organism. The best results are obtained using aspirates from an involved inguinal lymph node and cell-typing the culture after growth. Culture requires growth in cycloheximide treated McCoy or HeLa cells. Even under these conditions, yields of only 50% are reported. Serologic tests also are available and produce a strong reaction by compliment fixation tests in the second stage of disease. These tests have difficulty in separating the various serotypes for Chlamydia species, including those involved in conjunctivitis. In the appropriate clinical setting, an antibody titer of 1:64 or greater, or a 4-fold increase in titer, supports the diagnosis. Antibody titers do not correlate well with the clinical severity of the disease.

Differential diagnosis
The differential diagnosis includes granuloma inguinale and syphilis (see Granuloma Inguinale (Donovanosis) and Syphilis), both of which can be separated based on the clinical and smear findings.

Treatment
The recommended treatment is doxycycline at 100 mg PO bid or erythromycin at 500 mg qid. Treatments should be continued for 3 weeks and may need to be combined with aspiration of the lymph nodes. Incision and drainage may lead to nonhealing fistula formation.

Outcome
Untreated cases can lead to the formation of sinus tracts and third-stage disease, also referred to as genital anorectal syndrome. Rectal involvement is more prevalent in homosexual males and is associated with proctocolitis, perirectal abscesses, and lymphatic hyperplasia and lymphatic hemorrhoids. Scarring and local tissue destruction is the rule, with stricture, scarring, and lymphedema.

Ulcerating papules
Primary syphilis

Although recently decreasing in incidence, with 3.2 cases per 100,000 population in 1998, specific reservoirs of infection still are present, in particular in populations with HIV and in urban users of crack cocaine. Infection is initiated by sexual contact that transmits Treponema pallidum and establishes a primary infection (see Syphilis). Antibiotic treatment is effective, but if left untreated, secondary syphilis may result.

Pathophysiology
The causative organism is the spirochete T pallidum. Infection occurs mainly through contact with individuals in the primary and latent stages of the disease (within the first couple of years) and is acquired through direct sexual contact, with risk rates of 10-60%. Infection is through the skin and mucous membranes, and it leads to the chancre after a 2- to 4-week incubation period. Primary lesions last approximately 2 weeks, with healing occurring over 6 weeks.

Clinical presentation/diagnosis
Presentation usually is with a painless penile ulcerated lesion (chancre). A small red papule breaks down to form an indurated ulcer with a nonpurulent base. The lesions are located most commonly on the glans, foreskin, or scrotum, although up to 5% may present at extragenital locations. Anorectal lesions also are common in infected homosexual males and may present clinically as anal fissures. Nontender inguinal adenopathy also may be present.
Diagnosis is established with scrapings from the ulcer base examined by darkfield microscopy to detect the characteristic corkscrew motility of the organism or with fluorescence microscopy with antibodies to T pallidum. Serologic tests, including nontreponemal antibody titers via microhemagglutination assays (venereal disease research laboratory [VDRL], rapid plasma reagin [RPR]), can be used for screening and correlate with disease activity. Tests can decrease titers after 1 year. Increases by 4-fold indicate treatment failure or reinfection. A positive diagnosis can be obtained 7 days after chancre formation. False-positive results have been associated with collagen vascular disease, liver disease, HIV, and herpes infections. Thus, a positive test should be clarified using a second, more specific test such as the fluorescent treponemal antibody adsorption test (FTA-ABS).

Differential diagnosis
The differential diagnosis includes chancroid (see Chancroid) and lymphogranuloma venereum (see Lymphogranuloma Venereum), both of which are more confusing when presenting in atypical fashion or in individuals positive for HIV. Careful clinical examination and the preparation of smears for analysis lead to the correct diagnosis. The possibility of superimposed infections also should be considered when the presentation is atypical.

Treatment
Treatment with penicillin G (2.4 million U in single dose) still is the preferred and recommended treatment. Often, a second dose is administered a week later, a treatment that can yield a serologic cure. Doxycycline (100 mg bid for 2 wk) or tetracycline is an alternative in patients sensitive to penicillin. Patients should be aware that treatment might result in a transient acute febrile reaction with accompanying headache and myalgias (Jarisch-Herxheimer reaction) that usually occurs within 24 hours after initiation of treatment, especially in early cases. Treatment failures occur in all groups, thus serology must be checked at 3, 6, and possibly 12 months to ensure a decrease in antibody titers and a lack of reinfection.

Outcome
If left untreated, half the patients progress directly to secondary syphilis, with a variety of clinical signs and symptoms due to the hematogenous spread of the organism. Generalized constitutional symptoms, including headache, fever, and sore throat, are associated with mucocutaneous signs including a maculopapular rash that favors the extremities and mucous patches with central erosion. Eventually, the untreated course leads through a latent period (during which the patient continues to be infectious) to tertiary syphilis with multiorgan involvement. If the VDRL/RPR has not been reduced, a CNS fluid examination should be performed to rule out CNS involvement as a potential persistent reservoir. In addition, the CDC recommends that patients also be encouraged to check their HIV status. The clinical course of syphilis in patients infected with HIV often is atypical and can be accelerated.

Granuloma inguinale
Granuloma inguinale (donovanosis) is a sexually transmitted disease that is extremely rare in the United States, with only 8 cases reported to the CDC in 1997. See Granuloma Inguinale (Donovanosis). Occurring predominantly in tropical areas, including southeast Asia, India, the Caribbean, and aboriginal Australia, possible outbreaks may be related to travel from endemic regions. The papules are caused by Calymmatobacterium granulomatis and are readily treated with antibiotics when recognized. A prominent problem is the delay by patients in seeking treatment, leading to the need for aggressive treatment once they present with locally aggressive or systemic disease.

Pathophysiology
C granulomatis, a gram-negative pleomorphic obligate intracellular bacillus, is responsible for the disease and is present within histiocytes in the ulcerated lesions. The actual rate of infectivity is low, ranging from 0.4-0.5%, and extended incubation periods of 1-12 weeks are common. The disease is characterized by multiple subcutaneous papules that coalesce to form large ulcers where the infectious bacillus can be found within histiocytes. Autoinfection is common with the formation of so-called "kissing" lesions. While not as common as in chancroid, inguinal lymphadenitis can occur, with occasional erosion and bubo formation.

Clinical presentation/diagnosis
Typically occurring in patients aged 20-40 years, early presentation is characterized by single-to-multiple papules that form red nontender firm ulcers with bleeding granulation tissue bases. This ulcer is the clinical hallmark of the disease, and without treatment, progressive local tissue destruction occurs. Lymphadenopathy results more from bacterial superinfection than from actual donovanosis and, thus, is uncommon. While the classic presentation is recognizable to the vigilant, granuloma inguinale can take on a variety of phenotypes, with more severely ulcerative lesions, large dry vegetative masses, and painful foul-smelling necrotic variants. When an atypical presentation occurs, the presence of a superimposed infection also must be considered.
The histologic appearance of the prototypical ulcer reveals acantholytic epidermal borders with pseudoepitheliomatous hyperplasia. The ulcer bed contains prominent granulation tissue and vascular ectasia. Microabscess formation is present, and the abscesses contain large histiocytes with Donovan bodies (cytoplasmic vacuoles containing dark particulate material composed of bipolar staining bacilli). The identification of these Donovan bodies still is considered the simplest standard for diagnosis. Diagnosis can be made by taking tissue from the ulcer base and immediately crushing it between slides and staining with Giemsa or Wright stain. The bacilli, which appear as safety pin-shaped organisms, are readily identifiable within macrophages. Reliable culture is not available, with the last documented successful culture in 1962. Recent attempts at growth using coculture with monocytes have been reported. Work on an indirect immunofluorescence test also has been described.

Differential diagnosis
While the classical presentation is rather pathognomonic, variant presentations may confuse the diagnosis. The verrucous form may simulate condyloma (see Condyloma Acuminatum) or carcinoma, and the necrotic variant may lead to consideration of chancroid (see Chancroid). Smear cytology with stains should demonstrate the correct diagnosis.

Treatment
First-line treatment is with doxycycline (100 mg bid) or trimethoprim-sulfamethazine (TMP-SMZ) (double-strength bid) with treatment for at least 3 weeks or until all lesions have cleared. The CDC recommends ciprofloxacin (750 mg bid) or erythromycin (500 mg qid) as second-line treatments for refractory disease. Tetracycline resistance has led to this antibiotic no longer being recommended for treatment.

Outcome
Treatment usually is effective, but relapses do occur within 6-18 months. Monitoring of patients is recommended. Patients with granuloma inguinale are prominent reservoirs for HIV. While granuloma inguinale does not tend to produce generalized symptoms, systemic dissemination, if left untreated, can lead to death. Lymphatic obstruction can lead to lymphedema and scrotal elephantiasis. Scarring and fibrosis also are well-documented sequelae of untreated locally aggressive disease and may require surgical intervention for repair.

Chancroid
This sexually transmitted disease (see Chancroid) is found primarily in Africa, the Caribbean basin, and southwest Asia and is rare in the United States, where incidence is decreasing except among black and Hispanic heterosexual men. Of the outbreaks in the United States, 85% are in New York, California, Texas, and South Carolina and are associated with prostitution and crack cocaine use. It is the most common cause of genital ulcers in the developing world.

Pathophysiology
The causative organism is Haemophilus ducreyi, a gram-negative bacterium. It adheres to the surface of epithelial cells and produces cytotoxins that are associated with cellular damage and ulcer formation.

Clinical presentation/diagnosis
Presentation occurs 3 days to 2 weeks after exposure. Tender erythematous papules develop into painful acute ulcers 0.3-2 cm in size. They have a gray-yellow foul exudate; the base is friable, and it bleeds easily. In half the cases, chancroid is associated with painful lymphadenopathy. Approximately 25% of these patients experience progression of the lymphadenitis to a suppurative bubo that ulcerates.
Histologic features include the identification of 3 zones, a surface fibrinoid exudate with neutrophils and debris, an intermediate zone of vascular proliferation and thrombosis, and a deep zone of lymphoplasmacytic infiltrate.
Bacteria can be identified but often are easier to see in smears. Diagnosis by morphologic features alone is only 30-50% accurate. Gram stain of the ulcer base, revealing gram-negative coccobacilli in chains and clusters (described as the railroad-track/school-of-fish pattern) is helpful, although the polymicrobial flora of the ulcer bases makes diagnosis based on this difficult. Cultures are definitive, although the growth of the organism is problematic and must be performed using a mixed biplate culture method. Success in different laboratories varies from 0-80%.
Atypical presentations are common, often because patients have more than one disease. Because of the difficulty in diagnosis, the CDC recommends establishing a provisional diagnosis based on one or more painful genital ulcers, clinical presentation with lymphadenopathy suggestive of chancroid-negative T pallidum, and herpes simplex virus (HSV) laboratory results.

Differential diagnosis
Genital herpes and syphilis can mimic chancroid (see Syphilis). They often are found coincidentally due to the high rate of multiple infections in susceptible individuals. These diagnoses can be eliminated based on laboratory results and clinical impression. In particular, suppurative inguinal adenopathy is pathognomonic of chancroid.

Treatment
Treat with antibiotics. Differences in local sensitivity have been noted, and H ducreyi can acquire both gram-negative and gram-positive resistance factors. Current antibiotic treatments include a choice of the following: erythromycin base at 500 mg qid for 7 days, ceftriaxone at 250 mg IM single dose, or azithromycin at 1 g PO as a single dose. Ceftriaxone was effective in the United States but has been associated with treatment failures in Kenya. Fleroxacin has been effective in Kenya. TMP-SMZ has been ineffective. Due to the nature of the disease, sexual partners also should be treated. Vaccines for chancroid currently are in development.

Outcome
Antibiotic regimens should improve symptoms in 3 days; ulcers heal and adenopathy decreases in 7 days. The at-risk population also is at risk for HIV-1. Patients with HIV do not respond as well to the outlined antibiotic treatments.

INFLAMMATORY DISORDERS OF THE MALE GENITALIA

Balanitis xerotica obliterans
Often present in the genital and perianal skin, lichen sclerosus et atrophicus is referred to as balanitis xerotica obliterans when it involves the glans or prepuce, especially in the later stages of the disease (see Balanitis Xerotica Obliterans). This benign disorder of unknown, possibly autoimmune, etiology is observed in uncircumcised males and is an established cause of phimosis and meatal stenosis. Typically following an insidious course, it is associated with scarring and fissure formation. Treatment with corticosteroid immunosuppressive regimens improves the outcome dramatically.

Pathophysiology
Although it often develops in older men, one study reported the disorder in as many as 14% of prepubertal boys at circumcision. It is considered a form of inflammatory sclerosing dermatitis, with atrophy similar to lichen sclerosus of the vulva. Although balanitis xerotica obliterans has been associated with phimosis (14% of cases in one series) and observed with penile squamous cell carcinoma, most cases do not show such a relationship.
In preliminary descriptions, the cause was uncertain. However, recent evidence suggests an autoimmune origin. Autoimmune antibodies, including antismooth muscle or antiparietal cell antibodies, have been noted in these patients. Other associated autoimmune disorders include vitiligo, alopecia areata, hyperthyroid and hypothyroid disorders, pernicious anemia, and diabetes mellitus. The association with specific human leukocyte antigen (HLA) types, including HLA-A29, B44, B40, and Aw31, is significant. Researchers suggest dysregulated T-cell-mediated dermal immune response leads to destruction of the dermal collagen and basement membrane and exposure of keratinocytes to the dermis.

Clinical presentation/diagnosis
Balanitis xerotica obliterans occurs in young males (up to 14%) and older men (40%) who present with phimosis and undergo circumcision and usually involves the glans, prepuce, or urethral meatus, and, occasionally, the shaft. The clinical presentation is that of a well-defined, flattened, pale gray-to-white/ivory patch that looks like wrinkled cigarette paper or roughened lichenoid scale with prominent margins, usually involving the ureteral meatus. Often, the advanced lesion is firm due to the underlying dermal fibrosis. Unlike the pruritus associated with vulvar lesions, male lesions often are asymptomatic, although sometimes they itch or burn. While diagnosis often is based on clinical grounds, histology reveals characteristics of lichen sclerosus et atrophicus, including prominent orthokeratosis and hyperkeratosis in a setting of marked atrophy. Areas of hyperplasia and atrophy may alternate.
Cytologic atypia is not present within the epithelium. Basal cell vacuolization and clefting may occur, along with occasional bullae formation. Also, no associated orthokeratotic plugging of hair follicles exists because of a lack of follicles in commonly affected areas. Initially, the dermis is markedly edematous, with superficial homogeneous pale pink homogenization. It becomes progressively collagenous and hyalinized in advanced cases and may be associated with a mild lymphoplasmacytic infiltrate.

Differential Diagnosis
The differential diagnosis includes vitiligo (see Vitiligo), due to the presence of postinflammatory pigmentation changes and dermatophyte reactions with associated pruritus. Most of these can be eliminated based on clinical history, KOH scrape preparation, or biopsy if necessary.

Treatment
Often, circumcision is the treatment for foreskin lesions. Topical agents, such as hormonal testosterone creams, petrolatum, and antifungals, are largely ineffective. While high-dose topical steroids have been used with success in women (in some cases even reversing the course of disease), they have not been studied in detail in men. The promising results in women suggest the need to examine these treatments in men. Based on limited studies in men, clobetasol propionate 0.05% cream bid for 3-4 months may be a promising treatment option. However, long-term steroid treatment may cause local atrophy or lead to reactivation of latent infections such as HPV. Other treatment modalities involving surgery, laser therapy, and retinoids produce limited success.

Outcome
Association with squamous cell carcinoma has been reported, although a direct relationship of the 2 disorders is not well established.

Lichen planus
Overall a relatively uncommon skin disorder of unclear, possibly autoimmune, etiology, lichen planus involves the destruction of epithelial cells by the patient's T lymphocytes (see Lichen Planus). This slowly progressing lesion may respond to topical steroids and fade, leaving postinflammatory hyperpigmentation. While usually occurring in women, lichen planus may involve the male genitalia. The glans is a common site.

Pathophysiology
Usually, onset of genital lichen planus is in the fourth to sixth decades. Its course is slowly progressing and insidious. The exact etiology is unknown. However, a possible delayed hypersensitivity reaction to an unknown epidermal antigen is the current theory. The cellular immune response to basal epithelial cells causes initial destruction of the basal cell layer by T cells. Familial cases and cases associated with liver cell abnormalities, including chronic active hepatitis and primary biliary cirrhosis, have been reported. HLA-DR1 is associated with lichen planus. A more severe form associated with erosive gingivitis is argued to be similar to vulvovaginal syndrome in females.

Clinical presentation/diagnosis

The patient presents with several dome-shaped, markedly pruritic, pink-purple papules/plaques, which can have delicate white lines (Wickham striae), similar to those described in the oral cavity, crossing the surfaces. Often excoriated, these lesions commonly can present as multiple violaceous papules, except on the glans, where it can adopt an annular configuration. Lichen planus can ulcerate on surfaces subjected to trauma or on mucosal surfaces. The histologic appearance is that of acanthosis, hyperkeratosis, wedge-shaped hypergranulosis, and a dense bandlike inflammatory infiltrate that obliterates the dermal-epidermal junction, with basal cell vacuolization and Civatte/cytoid body formation. On mucosa, parakeratin with the characteristic inflammatory infiltrate may be present.

Differential diagnosis
The differential diagnosis includes psoriasis, which usually presents with less pruritus. Often, psoriasis involves other portions of the body, including the limbs, where it shows the more characteristic silver scale. The scaling of psoriasis usually is not present in genital lesions. Tinea cruris (see Tinea Cruris) tends to present with a raised border, a more cleared central area, and a peripheral scaling reaction. Candidiasis (see Candidiasis, Cutaneous) presents more acutely with erythema, edema, and satellite lesions. Balanitis xerotica obliterans (see Balanitis Xerotica Obliterans) shows atrophy and plugged hair follicles.

Treatment
Topical steroids have been used to treat of lichen planus. Courses of 4-6 weeks are necessary if postinflammatory hyperpigmentation is present for extended periods after treatment. Symptomatic relief with use of topical steroids (and even IV prednisone) has been reported. Whether they actually affect the clinical course is still in doubt. In some steroid-resistant cases without response to steroids (steroid resistance), treatment with cyclosporin A (3 mg/kg/d) is reported to lead to partial regression after 2 weeks, allowing for surgical intervention with circumcision.

Outcome
Characteristically, lichen planus resolves spontaneously and does not require treatment. Regardless of the method of treatment, most lesions heal in 6-18 months. These lesions can be associated with lichen planus at other sites, in particular, mucocutaneous involvement. Occasionally, lichen planus can result in phimosis, which necessitates subsequent circumcision. Squamous cell carcinoma has been reported to arise in lichen planus of the penis. In one case, the lesion was treated by Mohs surgery, and the patient was reported free of tumor 2 years postoperatively.

VIRAL LESIONS

Molluscum contagiosum
Named in 1817 by Bateman, molluscum contagiosum is a highly contagious viral infection that can present in the inguinal region (see Molluscum Contagiosum). It is characterized by umbilicated papules and has a distinct histologic appearance. Treatment usually involves curettage or topical remedies, and outcome is self-limited.

Pathophysiology
The causative agent is a DNA-containing poxvirus that infects the epithelium and leads to cellular proliferation and production of viral particles. These particles are then released by cellular rupture and lead to subsequent infection of neighboring cells. After an incubation period of 2-7 weeks, multiple papules surface and last for 2-6 months. Autoinfection is common, and treatment is focused on eradicating the virus and breaking the viral cycle.

Clinical presentation/diagnosis
In adults, molluscum contagiosum is transmitted sexually. It also can be acquired naively by children, usually presenting on the face, extremities, and upper trunk. Adult patients present with multiple, discrete, dome-shaped, 3- to 6-mm papules on the inner thigh, penis, and scrotum. The hallmark of central umbilication appears in only 25% of the lesions. These papules can have a pedunculated gross appearance, and milky-white material can be extruded from the central umbilication.
The characteristic histologic appearance of the lesions is a cup-shaped or cystlike invagination of epidermis with acanthosis. Epidermal cells from the stratum malpighii to the more superficial layers have characteristic viral cytoplasmic inclusions, (ie, molluscum bodies [Henderson-Patterson bodies]). These bodies initially are eosinophilic but become more basophilic as they progress to the surface of the epidermis and fill with poxvirus particles. The stratum corneum ruptures and releases the molluscum bodies at the surface, creating the characteristic milky-white material that can be extruded from the gross lesions.

Differential diagnosis
Clinical differentials include candidal infections when lesions are surrounded by an erythematous halo and folliculitis, which molluscum can mimic in atypical presentations (see Candidiasis, Cutaneous). Larger outbreaks with coalescent lesions, usually in patients who are immunosuppressed, may mimic furuncles or plaques. Disseminated histoplasmosis and cryptococcosis can mimic molluscum infections in individuals with HIV (see Histoplasmosis and Cryptococcosis). Molluscum can involve cysts and is included in the differential diagnosis of cystic sebaceous glands. Both can be diagnosed based on histologic examination.

Treatment
Treatment is curettage, cryotherapy, or laser vaporization. Application of podophyllin or silver nitrate to ablate the lesions has been used with mild success.

Outcome
While most lesions regress in 6-12 months, treatment prevents autoinfection and lowers the transmission risk. Involution occurs without scarring, and, on average, the full cycle, including reinoculation, runs a 2-year course. In patients who are immunosuppressed (including patients with HIV), multiple lesions can present as giant papular lesions that fail to regress, requiring more aggressive ablation. Treatment in these patients is centered on control of the spread rather than eradication of the virus.

Herpes simplex
This viral vesicular eruption, due to HSV, is the most common cause of genital ulcers in developed countries (see Herpes Simplex). Most cases are HSV-2 (US seroprevalence of 22%). Higher seroprevalence rates are reported in inner cities and developing countries. Also, HSV-1 is emerging as a significant cause of genital herpes. In 5-30% of initial cases, HSV-1 is involved. Because the virus can establish a latent infection, recurrent clinical manifestations are common, but their impact can be lessened with antiviral treatment.

Pathophysiology
HSV is caused by the sexual transmission of a double-stranded DNA herpesvirus that initiates a surface epithelial infection that subsequently involves the sensory nerve ganglia. The virus then establishes a latent state in these nerve cells that can be reactivated through multiple mechanisms including stress, sunlight, skin trauma, and cold or heat. They are mediated by prostaglandins, in particular prostaglandin E2 (PGE2) and prostaglandin F2 (PGF2). Recurrence is more common in men than in women and occurs more often in whites than in blacks.
Transmission occurs through viral shedding from active lesions and asymptomatic individuals; symptomatic lesions are more efficient in transmitting the virus. Most transmissions (up to 70%) occur during periods of asymptomatic shedding. While most cases are associated with HSV-2, HSV-1 is responsible for a larger share of sexually transmitted viral infections. Of note, transmission of HSV-1 is less effective than HSV-2 and is associated with lower rates of clinical recurrence and transmission.

Clinical presentation/diagnosis
Most patients are clinically asymptomatic; fewer than 10% report a history of infection. Initial symptoms may occur 2-4 weeks after infection, or they may delay for years after the initial exposure. Symptoms are systemic (fever, malaise, headache) and are more common in women than in men. Localized itching, pain, and dysuria can occur. Genital lesions include multiple vesicles with red bases that form pustules, rupture, and crust over.
A Tzanck smear can identify multinucleated epithelial cells with intranuclear inclusions and can establish a diagnosis in the right clinical setting; however, it is neither sensitive nor specific. Histologic appearance is of marked acantholysis with vesicles that contain proteinaceous fluid and degenerating cells, often with multinucleated forms. Characteristic intranuclear viral inclusions of HSV are noted. Culture of the virus can differentiate the 2 types, although sensitivity is only 50%, and the cultures must be established within the first 3 days of symptoms. Commercially available serologic tests using fluorescent antibodies cannot distinguish between HSV-1 and HSV-2.

Differential Diagnosis
The differential diagnosis is limited for herpes but includes chancroid and granuloma inguinale, both of which can be differentiated based on the different incubation periods, presence or absence of lymphadenopathy, and laboratory serologic tests. See Granuloma Inguinale (Donovanosis) and Chancroid.

Treatment
Elimination of the virus is not possible. Treatment centers on symptom control and infectivity. Initial clinical episodes should be treated with acyclovir (400 mg tid), famciclovir (250 mg tid), or valacyclovir (1 g bid) for 7-10 days or until ulcer healing is complete. These drugs shorten the duration of the lesions duration and reduce viral shedding but do not change the severity or frequency of recurrences. If antiviral treatment is initiated within 24 hours of recurrences, it can lessen the impact of the developing lesions in as many as 25% of patients.
Continuous treatment with acyclovir has been shown to reduce asymptomatic shedding and clinical outbreaks. As many as 80% of patients are symptom-free at 5 years. The decision to place a patient on continuous antiviral therapy is subjective and depends on the severity of recurrences and the psychosocial factors of the patient. CDC recommendations for continuous treatment are acyclovir at 400 g bid, famciclovir at 250 mg bid, or valacyclovir at 500-1000 mg qid, depending on the number of recurrences (> or <10 per y).

Outcome
Clinical manifestations are most severe in the first episode and can last up to 15 days. For 80-90% of patients who do not receive continuous antiviral treatment, recurrent episodes occur in the first year, with subsequent recurrences averaging 4 per year for HSV-2 and 1 per year for HSV-1. HSV is recurrent in 50-65% of patients, usually with gradually decreasing frequency. Disseminated herpes infections can occur in individuals who are immunosuppressed and those with complications associated with HSV with hepatitis and pneumonitis.

Warty papules
Condyloma acuminatum is the most common warty lesion of the penis, estimated to be present in as many as 5% of adults aged 20-40 years (see Condyloma Acuminatum). This sexually transmitted viral disease has a characteristic histology, extensive pathobiology, and established treatment options, but no known cure.

Pathophysiology
These epidermal lesions of disordered keratinocyte proliferation are caused by members of HPV, most commonly types 6 and 11 (90% of lesions), although in condyloma with evidence of epithelial dysplasia, types 16, 18, 31, 33, and 35 are noted. These DNA viruses spread through sexual intercourse and infect the keratinocytes, leading to the disordered proliferation of cells and subsequent formation of the condylomatous lesion. Basic biology has elucidated specific viral proteins involved in the disruption of the proliferative regulatory machinery of the keratinocyte, leading to cellular proliferation. In particular, viral proteins E6 and E7 lead to the sequestration, degradation, and disruption of 2 key cellular proteins, the retinoblastoma protein (RB) and p53, leading to a loss of cell-cycle control and the continued multiplication of cells.

Clinical presentation/diagnosis
Condylomata are associated with sexual transmission. In fact, the association between men with penile condylomata and sexual partners who have cervical lesions is high (50-85% of males whose sexual partners have HPV lesions have penile lesions).
Most often, condylomata are located at the corona of the glans or adjacent to the meatus, but they can occur on the scrotum and perineum. Frequently, they present as papillary cauliflowerlike lesions and can measure up to a few centimeters across. Also, flat lesions can occur. Detection using 5% acetic acid can reveal these and subclinical lesions as white areas (flat condylomata). Of note, the sensitivity and specificity of acetic acid detection of condylomata in males is not well established, and treatment based on the eradication of acetowhite areas is not a proven and recommended guideline.
Histology reveals proliferation of the squamous epithelium with acanthosis and papillomatosis. Orderly maturation, minimal cytologic atypia, and mitoses confined to the basal cell layer (key features lost in dysplasia and squamous cell carcinoma) are noted within the specimen. Hyperkeratosis, parakeratosis, and koilocytosis are common.

Differential diagnosis
Differential diagnoses (all that can be ruled out based on clinical history and histologic evaluation) include condyloma latum, seborrheic keratoses, nevi, and pearly penile papules. See Seborrheic Keratosis and Pearly Penile Papules.

Treatment
The goal of treatment is to remove warts and treat symptomatic problems. No treatment eradicates HPV infection. Treatments focus on the destruction or removal of the lesion and include cryotherapy, laser ablation, and surgical excision with histologic evaluation. Treatment with podophyllin has been successful, but it can cause cytologic atypia that may be misdiagnosed as carcinoma on subsequent biopsy. Also, podophyllin is not recommended for urethral lesions, where 5% 5-fluorouracil or thiotepa is preferred. Topical administration of imiquimod, an immune response modifier, has shown clinical utility.

Outcome
While condylomata may regress spontaneously, approximately half persist and thus necessitate treatment with podophyllin, cryotherapy, or laser ablation. Because it is sexually transmitted, sexual partners are at higher risk for cervical dysplasia and should be screened for HPV infection. Because it is sexually transmitted, sexual abuse must be suspected if children are diagnosed with condylomata.


MISCELLANEOUS BENIGN LESIONS OF THE MALE GENITAL TRACT

Pearly penile papules
Present in 8-20% of males, pearly penile papules (hirsutoid papillomas) are benign asymptomatic papules that may represent embryological remnants (see Pearly Penile Papules). Often, they are the cause of much consternation for the patient and are misdiagnosed by the unprepared physician.

Pathophysiology
Similar lesions have been noted in cats, dogs, and chimpanzees. These small papules are best described as embryological remnants. Pearly penile papules usually present in adolescence as multiple-grouped lesions along the corona and sulcus. Histologically, dilated ectatic vessels present in a fibrous stroma, and areas of epithelial thickening over this fibrovascular lesion have been described. Many authors believe these lesions are angiofibromas due to their histologic similarity. They tend to be fixed, do not regress, and can recur after incomplete excision.

Clinical presentation/diagnosis
These tend to present as 1- to 3-mm diameter, yellow-white, domelike papules arranged in a row on the corona of the glans in adolescent males. Presentation may occur in males in their second to fifth decades. Rare cases in children as young as 11 years have been reported. While asymptomatic, they are a source of great concern, and they often are presented as a sexually transmitted disease.

Differential diagnosis
The differential diagnosis includes molluscum contagiosum and condyloma acuminatum. These diagnoses can be ruled out based on clinical history and histologic findings (see Molluscum Contagiosum and Condyloma Acuminatum).

Treatment/outcome
These lesions require no treatment, although the patient may request excision for cosmetic reasons. They are of no clinical significance.

Penile cysts
In general, penile cysts are not common but have been well documented. The largest series presented (160 cases) was from Japan. Due to their asymptomatic nature, penile cysts may not come to clinical attention and may be more common.
These cysts often are divided into 2 main categories, median raphe cysts and epidermal inclusion cysts. Follicular cysts (epidermal inclusion cysts) are the most common cystic lesions of the penis and occur on the shaft. Median raphe cysts have various names, including mucoid cysts, urethral cysts, and apocrine cystadenomas. All are benign and can be treated with simple excision.

Pathophysiology
Follicular cysts (epidermal inclusion cysts) are believed to arise from hair follicles along the penile shaft due to blockage of the follicular infundibulum. Median raphe cysts arise from the urethral and paraurethral epithelium. Follicular cysts tend to be located at the base of the shaft in association with hair follicles and are not present at the urethral meatus. Median raphe cysts originate from the external paraurethral ducts (reflected by their site of origin) and present in association with the external meatus, urethra, or along the median raphe. Most median raphe cysts are lined by a stratified columnar epithelium and contain clear mucinous fluid. Electron microscopy reveals an intact underlying myoepithelium and secretory features, including microvilli and secretory granules characteristic of duct-lining epithelium as found in the paraurethral ducts.
Histologically, apocrine metaplasia is common. In some cases, squamous metaplastic epithelium leads to misdiagnosis of an epidermal inclusion cyst. These cysts are believed to arise from the paraurethral ducts that formed from the lacunae of Morgagni/branched paraurethral glands of Littré. Some have a direct connection to the urethra, and some lack communication. The cysts are present all along the median raphe, from the urethral meatus to the anus.

Clinical presentation/diagnosis
Most patients are asymptomatic and present with a painless mass. Often, patients have this lesion for quite some time. Forty patients in one study presented more than 20 years after onset, while in another set of 3 patients, the length of time to presentation was 3-26 years. Cysts range in size from 0.2-2 cm in diameter. Most present along the median raphe of the penis shaft.

Differential diagnosis
The differential diagnosis includes follicular cysts and median raphe cysts. These differ in clinical location (base of shaft vs along the median raphe) and histology (squamous infundibular epithelium vs urothelium).

Treatment
Usually, treatment involves complete excision, including communicating paraurethral ducts.

Outcome
Excision removes the cyst and subsequent risk of infection or rupture, usually from intercourse. Take care when excision involves cysts adjacent to the urethral meatus to prevent damage to the urethra. Documented recurrence in up to 2% of cases usually is due to incomplete excision of median raphe cysts that communicate with additional ducts.

Keloids
Hypertrophic keloidal scars, although rare, can occur on the penis, most commonly after surgery such as circumcision (see Keloid and Hypertrophic Scar). This exuberant response to injury can be controlled with steroid injections and surgical removal.

Pathophysiology
The postulated mechanism involves increased fibroblastic activity and collagen deposition that occludes local vessels and leads to ischemia, tissue damage, and additional fibroblastic repair reaction resulting in a positive feedback loop. A component of inflammatory response also may be crucial in the development of this disorder.

Clinical presentation/diagnosis
Keloids occur in patients aged 8-56 years and are associated with previous surgery for injury to the penis. While circumcision most often is the previous procedure, patients have been described with keloid formation secondary to hidradenitis suppurativa. Often, patients seek clinical care because of embarrassment and discomfort associated with sexual activity. Clinical examination reveals a large firm mass present at the site of tissue injury. Biopsy reveals abundant deposition of collagen in the dermis, with associated plump fibroblasts, thrombosed vessels, and inflammatory cells. Characteristic markedly thickened collagen bundles look like wax dripping.

Differential diagnosis
The differential diagnosis includes both benign and malignant tumors of the penis. Usually, these can be eliminated from the differential based on histologic analysis, rate of growth, and clinical presentation. In particular, penile neurofibromas have been described in association with neurofibromatosis, and reports of both benign and malignant schwannomas of the penis have been recorded.

Treatment
Treatment includes intralesional steroid injections (triamcinolone acetate once a mo for 7 mo) and surgical excision. Recurrence still is possible.

Outcome
While recurrence is possible, treatment often is satisfactory and allows return to sexual function.

Dermatologic Diseases of the Male Genitalia: Malignant

INTRODUCTION

Most malignant dermatologic lesions of the male genitalia are squamous in origin and associated with the human papillomaviruses (HPV). Rarely, tumors are derived from the cutaneous adnexa, melanocytes, or the urethral urothelium. Cutaneous metastases to the penis are strikingly uncommon and, when present, usually are in the setting of widely disseminated disease in an immediately antemortem patient.
An area of ongoing debate is the clinical definition of dysplasia or in situ carcinoma of the penis and scrotum. Initial descriptions were based on the variety of clinical presentations and associations with other tumors, which led to the description of 3 preneoplastic disorders: Bowen disease, erythroplasia of Queyrat, and bowenoid papulosis. The underlying pathologic similarity of these disease entities has been reinforced with the isolation of similar HPV subtypes in each disorder. As more cases are gathered, initial differences in the rate of progression to invasive carcinoma and the association with underlying internal malignancies are becoming less significant. In other words, what initially appeared to be 3 separate clinical entities may in fact be just the clinical spectrum of a single disease, all initiated by the same causative agent (HPV) and modified by associated immune and host defense mechanisms.
Variations in the clinical presentation of invasive carcinoma also lead to dissimilar predictions of outcome. Squamous cell carcinoma of the penis may present as specific associated variants (ie, exophytic/fungating type, verrucous type, invasive/ingrowing type). Similar differences are difficult to identify in melanoma or urothelial carcinomas of the male genitalia because of the limited number of cases to evaluate.

ERYTHROPLASIA OF QUEYRAT

Introduction
Initially described by Tarnowsky in 1891, erythroplasia of Queyrat (see Erythroplasia of Queyrat (Bowen Disease of the Glans Penis) was separated from Bowen disease based on clinical appearance and lack of association with internal malignancy. Today, the overlap between these 2 entities is more evident, and separation of the 2 remains controversial. Histologic appearance and rates of progression to squamous cell carcinoma are similar. The presence of an association with an internal malignancy may have more to do with the age of the patients and has been called into question for both diseases.

Pathophysiology
Usually, erythroplasia of Queyrat occurs in men aged 46-60 years, although it can occur at any age. The histologic features suggest a preinvasive squamous epithelial lesion that has demonstrated a definite risk (up to 10%) for progression to invasive malignancy. HPV has been isolated from this disease, including high-risk serotypes.

Clinical presentation/diagnosis

Patients present mainly with bright red, minimally elevated, glistening, velvety plaques. Often, erythroplasia of Queyrat involves the glans or prepuce. Occasionally, presentation can mimic a cutaneous horn. In half the patients, erythroplasia of Queyrat is a solitary lesion and often is present for months to years before clinical attention is sought. The histologic examination is similar to bowenoid papulosis and Bowen disease, with features of carcinoma in situ, including the following: full thickness alteration of the squamous epithelium, a loss of polarity, cytologic atypia, mitoses above the basal layer, dyskeratosis, and atypical mitoses. The underlying dermis has a marked chronic inflammatory infiltrate and vascular proliferation, but it does not show evidence of invasion of tumor into the underlying dermis.

Differential diagnosis
Differential diagnosis includes Zoon balanitis (see Balanitis Circumscripta Plasmacellularis) or any other nonhealing lesion that does not respond to medical treatment. Because of the risk of malignancy, these nonresponding lesions require biopsy to rule out this and other premalignant or malignant processes. Other lesions to be considered include drug eruption (see Drug Eruptions), psoriasis, or lichen planus (see Lichen Planus).

Treatment
Treatment of erythroplasia of Queyrat often involves removal or destruction of the lesion. Methods employed include cryotherapy, laser ablation, and surgical excision. Topical vesicants have been used for local control. Some authors recommend a surgical excision with a 0.5-cm margin around the lesion. This has the advantage of allowing pathologic examination of the specimen to rule out the presence of invasive tumor. Also, Mohs surgery has been used in the treatment of erythroplasia of Queyrat.

Outcome
The argument has been made that circumcision protects against this disease, possibly due to the decreased risk of poor hygiene associated with the deposition of high-risk detritus, including smegma, HPV, oils, and toxins. In a series of 100 cases, 22% of the patients developed recurrence, 8% developed invasive squamous cell carcinoma, and 2% developed squamous cell carcinoma with distant metastases. Other groups also have reported metastases.


BOWEN DISEASE

Introduction
Described by Bowen in 1912, this disease (see Bowen Disease) was considered unique due to its association with invasive squamous cell carcinoma and internal visceral malignancy. Subsequently, the rate of progression has been similar to that of erythroplasia of Queyrat. Association with invasive malignancy has thus been called into question.

Pathophysiology
Occurring in men aged 30-50 years, Bowen disease is an in situ histologic change involving the shaft of the penis. It may be associated with agents that damage skin, including ultraviolet light exposure and topical toxins such as arsenic. Recently reported isolation of HPV DNA places it in the category of virally induced squamous neoplasia.

Clinical presentation/diagnosis
Bowen disease usually presents on the shaft of the penis. It does not have the red color of erythroplasia of Queyrat but is a more crusted, sharply demarcated, scaly plaque. In rare examples, it can be more papillomatous. The plaque measures from millimeters to centimeters across. Often, it is silver-to-white in appearance and can resemble psoriasis or dermatitis. Lesions may be pigmented.

Differential diagnosis
Differential diagnosis includes Paget disease or squamous cell carcinoma (see Squamous Cell Carcinoma). The silver scaly appearance can resemble psoriasis or other dermatitis. Pigmented examples also can mimic melanoma or benign nevi. Pathologists can misdiagnose histologic atypia as condyloma with podophyllin treatment; thus, a clinical history of podophyllin should be noted.

Treatment
Often, treatment centers on excision and/or ablation. Surgical excision provides a histologic diagnosis. In severe cases, partial penectomy could be considered but only after more conservative measures have been exhausted. Yttrium-aluminum-garnet (YAG) laser ablation also has been reported as yielding satisfactory results.

Outcome
The rate of progression to squamous cell carcinoma is 5-10%, similar to that observed with erythroplasia of Queyrat. Of these cases, 30-50% are potentially metastatic. Initial reports suggested that as many as 33% of patients with Bowen disease develop visceral malignancies including respiratory, gastrointestinal, or urogenital cancers. More recent studies cast doubt on this association.

BOWENOID PAPULOSIS

Introduction
In 1978, Wade first described bowenoid papulosis (see Bowenoid Papulosis) as a specific disorder of young sexually active men. Patients presented with multiple small red papules on the genitalia that, while histologically concerning, tended to pursue an indolent clinical course.

Pathophysiology
Typically, bowenoid papulosis occurs in men aged 20-40 years. The mean age at presentation is 29.5 years. Association with HPV infection and isolation of high-risk HPV serotypes 16 and 18 from lesions of bowenoid papulosis have been documented, although other serotypes have been detected (31-32, 34, 39, 42, 49, 51-54). As with the histologically similar lesions of Bowen disease and erythroplasia of Queyrat, an association exists between bowenoid papulosis and progression to squamous cell carcinoma, although the rate (2.6%) is lower than that of erythroplasia of Queyrat or Bowen disease.
In addition, a link exists between bowenoid papulosis in males and cervical dysplasia in their female partners. Some studies seem to indicate that bowenoid papulosis is a clonal disorder. In some cases, development of bowenoid papulosis is associated with anergy and diminished helper T-cell response (not related to HIV), leading to the notion that decreased antiviral immunity may lead to the development of these premalignant lesions.

Clinical presentation/diagnosis
Patients typically present with multiple multicentric erythematous papules on the penile shaft or the perineum. The papules, which range from 2-10 mm, are not particularly itchy and do not tend to scale or ulcerate. Lesions tend to develop over a short time in young sexually active men who have multiple partners.

Differential diagnosis
Lesions may be clinically mistaken for condyloma (see Condyloma Acuminatum), seborrheic keratoses (see Seborrheic Keratoses), or nevi. Lesions that histologically tend to be verrucous could resemble condyloma but lack the microscopic full-thickness atypia. Usually, seborrheic keratoses have histologic evidence of a keratinizing granular layer, which is different from typical Bowen disease. Differential diagnosis also would include nonspecific balanitis, including Zoon balanitis (see Balanitis Circumscripta Plasmacellularis). The inability to identify a causative organism or a lack of response to a trial of antibiotics would warrant a biopsy to rule out bowenoid papulosis. Histologic features, in particular the lack of an extensive plasmacytic infiltrate, would differentiate from Zoon balanitis.

Treatment
Because progression to carcinoma is rare, these lesions usually are treated conservatively. Treatment centers on the ablation of the gross lesion, often with the use of local excision, topical vesicants, cryotherapy, or laser ablation.

Outcome
Progression from bowenoid papulosis to squamous cell carcinoma differs from Bowen disease and erythroplasia of Queyrat. While rare case reports exist and dermatologic specialists see some cases, incidence appears to be lower than other premalignant lesions. In some cases, bowenoid papulosis may regress spontaneously. Because of the association with HPV, this is considered a sexually transmitted disease. Studies of partners of patients with bowenoid papulosis found them to be at a higher risk for cervical dysplasia.

SQUAMOUS CELL CARCINOMA

Introduction
Squamous cell carcinoma (see Squamous Cell Carcinoma) is the most common tumor of the penis, accounting for more than 95% of all malignant penile tumors. Although rare in persons younger than 40 years, the actual age range is extensive, from 20-90 years. Most cases are present in uncircumcised men and are associated with poor hygiene. Areas of high rates of penile squamous cell carcinoma include Uganda, Brazil, Jamaica, Mexico, and Haiti.

Pathophysiology
Initial reports linked penile squamous cell carcinoma with the uncircumcised penis and documented high rates of tumors in uncircumcised Hindus and low rates among Jews who practice ritual circumcision. Later studies documented the low rate of penile tumors among Scandinavians who do not practice circumcision and indicated that the crucial factor was not the foreskin itself, but the link between the presence of the foreskin and hygiene. Squamous cell carcinoma of the penis has been associated with phimosis, or retention of the prepuce, although the presence of phimosis in itself indicates scarring from a previous possible infectious inflammatory reaction. Recent attention also has focused on smegma (oils, organisms, and debris that collect under the prepuce with lack of good hygiene), associated penile rashes, and infection by Mycobacterium smegmatis.
HPV infection is associated with 22-63% of these cases. Subtypes linked to penile squamous cell carcinoma include high-risk types 16 and 18, as well as 6, 11, and 30. An association also exists between penile cancer and spousal cervical cancer, although these statistics have been debated. The microscopic appearance is that of poorly differentiated cells, and these tumors are prone to high rates of local spread and metastasis. They demonstrate invasive/vertical growth patterns and often have associated necrosis and perineural and vascular invasion.

Clinical presentation/diagnosis
The clinical presentation is not of a subtle lesion. Often, patients delay seeking medical care for 6 months or longer because of embarrassment or shame. Frequently, bacterial superinfection or induration of the lesion results from attempts to self-treat with home remedies. The majority of lesions are present on the glans, on the prepuce, or at the coronal sulcus.
Presenting complaints often include penile pain, malignant priapism, discharge, and difficulty voiding. Lymphadenopathy is present in as many as 15% of presenting cases, particularly with the invasive/ingrowing subtype. At the time of presentation, palpation for involved lymph nodes is only 70% sensitive. Palpable nodes are present in 58% of patients at presentation, but less than half of these are subsequently found to have metastases. Often, the mass effect present at palpation is due to inflammation of the nodes from tumor superinfection.
Tumors are examined after penectomy. They usually are pathologically staged and are graded using the American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) staging and modified Broders systems, respectively. The TNM system classifies cases into stages I-IV based on the extension of the tumor. Most patients present as stage I (confined to the glans) or II (involving the glans and invading into the penile shaft). Histologic grading using the modified Broders classification divides tumors into 4 histologic grades ranging from well differentiated to poorly differentiated. Another grading system uses a 3-tier (well, moderate, poor) scale for differentiation, with 50% of cases being well differentiated. Of note, well-differentiated tumors metastasize to regional lymph nodes at a rate of 50%, while moderate or poorly differentiated tumors have an 80-100% nodal metastasis rate. Hematogenous metastasis is uncommon, accounting for fewer than 2% of cases at diagnosis.

Differential diagnosis
While clinical presentation is unlikely to cause diagnostic dilemma, the ability to recognize variants of squamous cell carcinoma is of some clinical benefit. Specific subtypes and variants include the verrucous exophytic-fungating/superficial spreading type and the invasive/vertical growth pattern type.
The warty or verrucous variants, called the giant condyloma of Buschke-Lowenstein (see Giant Condyloma Acuminata of Buschke and Lowenstein), are controversial because of their histologic overlap and the unclear biologic separation between these lesions. Often, these tumors have a prominent papillary configuration that also is observed upon histologic evaluation. Additional histologic features include a broad front of invasion and minimal cytologic atypia. Metastasis is rare and, when present, is associated with tumors of higher pleomorphism and microinvasion. Instead, these tumors are characterized by indolent growth and local recurrences at a rate of up to 80%. This rate can be reduced to 30% with partial penectomy. Aggressive treatment with radiation can be detrimental, with subsequent dedifferentiation. In rare cases, verruciform xanthoma mimics verrucous squamous cell carcinoma, which can be separated based on biopsy.
Usually, sarcomatoid or spindle cell variants of squamous cell carcinoma present as polypoid masses and appear to grow slowly. The actual prognosis for these variants is mixed, with some doing as poorly as typical squamous cell carcinomas. Cases with poor prognosis also often have a carcinomatous component (carcinosarcoma) that is readily identifiable. Differential diagnosis includes a synovial sarcoma of the penis, of which case reports exist.

Treatment
Treatment of choice is partial penectomy to control the spread of low-stage disease. Some groups have argued for local excision with conversion to partial penectomy upon recurrence, although this is not widely accepted. The effectiveness of prophylactic bilateral inguinal node dissection is controversial. Drainage from the penis is midline and can involve either side of the pelvic lymph node chain. In addition, high morbidity is associated with inguinal node surgery. On the other hand, lymphadenectomy can be curative of regional disease. The sensitivity for detecting involved lymph nodes drops from 70% to 15% after surgery due to postoperative inflammatory changes. Based on this, some advocate waiting for a few weeks until the inflammation subsides and operating on residual nodal masses. Groups also have applied lymph node mapping to penile cancers. Attempts at organ-sparing surgery have produced mixed results.
Some have attempted to control local disease with radiation therapy or have used radiation therapy for patients who are not candidates for penectomy. Brachytherapy has been used with success for local control of disease. The role of chemotherapy is unclear because of the difficulty in gathering a sizable number of patients. Commonly used agents include cisplatin and bleomycin and have yielded response rates of 15-23%. Combination chemotherapy and radiation using bleomycin-derived treatments have been successful in some cases, with response rates as high as 43%.

Outcome
Squamous cell carcinoma of the penis tends to be a locally advanced aggressive disease. Nodal metastases, usually to the inguinal and/or iliac nodes, are the most common route of dissemination. Of note, 5-15% develop second primary lesions, often located along the residua of the penis. Usually, complications are due to recurrence, which occurs in as many as 7% of patients.
Treatment usually focuses on local issues or the presence of bulky nodal disease. While hepatic, pulmonary, and osseous metastases have been documented, the development of hematogenous metastasis is rare and occurs in untreated cases. The 5-year survival rates for locally resected lesions range from 65-90%, but decrease to 20-50% if nodal metastasis initially were present. Usually, death occurs within 2 years if left untreated.

BASAL CELL CARCINOMA

Introduction
While basal cell carcinomas (see Basal Cell Carcinoma) are the most common human tumor, they are distinctly uncommon on the male genitalia. Most cases documented in medical literature have been case reports or letters. Treatment is related to local control. Metastases are uncommon. With complete removal, patient outcome is very good.

Pathophysiology
The propensity for development on sun-exposed skin explains the rarity of basal cell carcinoma on the male genitalia. Originating from the basal cells that generate the epidermis, these tumors tend to be locally destructive and do not readily metastasize. Besides sun exposure, risk factors include ionizing radiation, arsenic, and familial heritable forms including nevoid basal cell carcinoma syndrome and xeroderma pigmentosum.

Clinical presentation/diagnosis

Patients range in age at presentation from 22-81 years, with most cases in older men. The majority of patients have fair skin, although cases also have been reported in Japanese males and blacks. Most lesions have occurred on the shaft and scrotum and were present for years before patients sought treatment. The lesion is raised, with an area of central ulceration, pearly white borders, and telangiectatic edges. Histologic sections reveal nests of basaloid cells with peripheral palisading and a notable retraction artifact separating the nests from the dermis due to connective tissue mucin accumulating in the adjacent stroma.

Differential diagnosis
The most important differential diagnosis is primary adnexal carcinoma, such as eccrine porocarcinoma (see Eccrine Carcinoma). These tumors tend to have a more aggressive growth pattern and higher rate of metastasis and must be treated more aggressively. Differential diagnosis is based on histologic examination and the identification of syringotropism, lumen formation, and adnexal differentiation. Primary squamous cell carcinomas (see Squamous Cell Carcinoma) also must be separated because of their more aggressive course. Because of the nature of the differential diagnosis, histologic evaluation is required.

Treatment
Treatment for basal cell carcinoma focuses on local excision or ablation. This is in contrast to partial penectomy, which would be the choice of treatment for more aggressive tumors such as squamous cell carcinoma. Different treatment modalities stress the need for a definitive histologic diagnosis.

Outcome
Complete excision of the tumors can lead to uneventful follow-up. Incomplete treatment often results in local recurrence that can be treated by removal.

MELANOMA

Introduction
Melanoma (see Malignant Melanoma) is a relatively uncommon lesion of the male genitalia. Patients with melanoma have a poor prognosis due to presentation at an advanced stage because of embarrassment. While treatment still focuses on surgical intervention, long-term survival has not been reported. Recent rare cases of melanoma in situ with treatment by local excision may fair better.

Pathophysiology
Accounting for less than 2% of primary tumors of the penis, melanoma presents on the penis in less than 0.2% of cases. It may originate from the epidermal melanocytes or from the penile urethral urothelium. Most patients present with advanced disease. Inguinal nodal metastases are common (present in 43% of cases at presentation in one series).

Clinical presentation/diagnosis
Patients usually present when aged 50-70 years. One series documented an age range of 57-77 years. While the most common presentation is on the glans (55% in one series), melanoma has been described on both the prepuce (28%) and shaft (9%). The lesions often are macular with an irregular border and lack symmetry in their overall appearance. Often, areas of variegated pigmentation ranging from blue to black can be observed. When lesions have been present for some time, they may ulcerate or erode the underlying skin. Often, inguinal nodal enlargement can be palpated.

Differential diagnosis
Differential diagnosis centers around melanoma in situ and benign nevi or melanosis, both of which are rare on the penis. Postinflammatory hyperpigmentation also may confuse the clinical presentation but lacks the dark pigmentation observed in melanocytic neoplasia.

Treatment
Treatment usually is partial penectomy with possible inguinal lymph node dissection. Mapping is performed in some cases. Local treatment of melanoma in situ, with 0.5-cm borders, has been performed with some success.

Outcome
Because of the advanced stage at presentation, prognosis for most patients is poor, regardless of treatment. Survival for more than 2 years is extremely rare. In a series of 9 patients (2 with lymph node metastases), 7 died of disease, most within 2 years. However, 2 were alive 2 and 14 years after treatment.

KAPOSI SARCOMA

Introduction
Although it once was a rare neoplasm of the lower extremities in older Mediterranean men, Kaposi sarcoma (see Kaposi Sarcoma) has increased in incidence 7000-fold in the HIV/AIDS era. Now, Kaposi lesions often are a presenting symptom that heralds the onset of AIDS in individuals infected with HIV.

Pathophysiology
While the original form rarely was seen in the genital area, currently 20% of men with HIV and Kaposi sarcoma have genital involvement, and 3% of men positive for HIV present with Kaposi sarcoma of the genitalia. Association of this vascular tumor with herpesvirus infection has now been documented in HIV and non-HIV forms of disease.

Clinical presentation/diagnosis
Kaposi sarcoma tends to present on the genitalia as small violaceous-to-tan macules or papules but may eventually coalesce to form plaques. Occasionally, ulceration occurs, and complications can include lymphatic or urethral obstruction.

Differential diagnosis
In even more rare circumstances, other vascular tumors present on the penis and scrotum. Rare cases of angiosarcoma have been reported, but they are the exception when compared to Kaposi sarcoma of the same area. Benign hemangiomas can occur but usually are identified readily by the gross appearance of a smaller, unchanging macule or papule.

Treatment
While no cure has been identified, care is centered on limiting potential complications (obstruction) or cosmetic treatment. Intralesional chemotherapeutics, radiation therapy, and local tissue destruction by cryotherapy or laser therapy have been used with varying success.

Outcome
While no cure currently is known, the use of multidrug regimens to treat patients who are HIV-positive has led to increased patient survival and an increasing desire for local and cosmetic control of this tumor.