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What Caused This Growth on the Penis?

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Author: 
Jason William Suszko, MSIV, and Amor Khachemoune, MD, CWS

PATIENT PRESENTATION

A 64-year-old African-American male was referred to the dermatology consult service for evaluation of a large genital lesion. The patient stated that the lesion started as a small, painless wart-like growth on the glans penis. Over several years, it had progressively enlarged to become painful, pruritic and malodorous. With time, the patient complained of pain including when ambulating and urinating. The patient denied any known history of immunodeficiency, infection with HIV or human papillomavirus (HPV). The patient did not report a history of homosexual activity. The patient’s past personal and family medical histories were unremarkable. On physical examination, there was a cauliflower-like pink exophytic mass involving the glans penis measuring approximately 3 cm x 3 cm. The mass was ulcerated with a bloody, purulent discharge. A fetid odor permeating from the lesion was also noted. Regional lymph nodes were not enlarged. The remainder of the examination was normal.

What is Your Diagnosis?

PATIENT PRESENTATION


A 64-year-old African-American male was referred to the dermatology consult service for evaluation of a large genital lesion. The patient stated that the lesion started as a small, painless wart-like growth on the glans penis. Over several years, it had progressively enlarged to become painful, pruritic and malodorous. With time, the patient complained of pain including when ambulating and urinating. The patient denied any known history of immunodeficiency, infection with HIV or human papillomavirus (HPV). The patient did not report a history of homosexual activity. The patient’s past personal and family medical histories were unremarkable. On physical examination, there was a cauliflower-like pink exophytic mass involving the glans penis measuring approximately 3 cm x 3 cm. The mass was ulcerated with a bloody, purulent discharge. A fetid odor permeating from the lesion was also noted. Regional lymph nodes were not enlarged. The remainder of the examination was normal.

What is Your Diagnosis?

Diagnosis: Buschke-Lowenstein Tumor

Buschke-Lowenstein tumor (BLT) also known as giant condyloma acuminatum of Buschke-Lowenstein is a rare genital lesion affecting the penis most commonly, but also anogenital regions. Dr. Abraham Buschke and Dr. Ludwig Lowenstein first described BLT in 1925 as a fast-growing, cauliflower-resembling lesion of the glans penis.1-5 In spite of its benign histological features, it is a rapid-growing, locally invasive and destructive tumor.6 It also has a high propensity for local recurrence and neoplastic transformation into squamous cell carcinoma (SCC). Currently, BLT is regarded as a regional variant of verrucous carcinoma induced by HPV.5,7

Historical Note


Condyloma acuminata, or genital warts, are described as soft, papillomatous growths on the penis or anogenital regions caused by HPV subtypes 6 and 11.8 In 1925, Drs. Buschke and Lowenstein described condyloma acuminata as papillary fibroepitheliomas localized to the coronal sulcus. They also reported on the giant condyloma acuminatum of Buschke-Lowenstein, and described it as a neoplasm of the glans penis that bore resemblance to common condyloma acuminatum and squamous cell carcinoma, but differed clinically and histopathologically. “We have, however, seen cases that presented a clinical picture of papillary carcinoma and differed histologically from other uncomplicated condyloma acuminata in that the affected areas, glans, foreskin and shaft of the penis had become largely part of the tumor mass.”2 Believing BLT was restricted to uncircumcised men, Buschke and Lowenstein hypothesized that the irritation induced by phimosis and smegma resulted in proliferation and coalescence of previously existing condyloma acuminata into giant condyloma acuminata. Treatment in their era consisted of amputation and radiation trials, which apparently led to favorable outcomes and limited recurrence.

Buschke and Lowenstein referred to the atypical condyloma acuminata referenced above as a carcinoma-like condyloma, due to its giant proliferation and locally invasive yet non-metastasizing nature. During their era, it had not yet been accepted that a non-metastasizing neoplasm could be classified as a carcinoma. BLT is currently referred to as verrucous carcinoma of the penis or low-grade, non-metastasizing squamous cell carcinoma.7

Clinical Presentation


BLT commonly starts as a keratotic lesion or typical condyloma acuminata that progressively expands into a large cauliflower-like tumor mass attached through a broad base to the glans, sulcus or shaft of the penis.4,7,9 The surface can alternatively be described as a cobblestone or pebbly pattern, and can become ulcerated and associated with a pus or bloody discharge.9 The tumor is locally invasive, and it is not uncommon for it to expand into the corpus cavernosum and the urethra, forming fistulas. Patients have commonly reported pain and pruritus secondary to the lesion.9 Inguinal lymph nodes may be enlarged due to inflammation or secondary infection, but not metastases.7 Unsurprisingly, this condition presents most commonly in men, with a male-to-female ratio of 2.7 to 1.10 Males affected are usually less than 50 years of age, uncircumcised, and commonly immunosuppressed.10 There are two reports of BLT in children, and one in an infant.11,12,13 Circumcised men can also be affected, albeit much less commonly.14 BLTs localized to other anogenital surfaces, such as the anus, vulva, vagina, urethra and bladder, are extremely rare, including a few cases in pregnant women.4 BLT in the perianal region appears similar to BLT on the penis. Fistulas, abscesses and rectal bleeding are also common in perianal BLT.15

Pathology


BLT is a poorly circumscribed neoplasm that is exoendophytic with notable squamous epidermal hyperplasia, hyperkeratosis and parakeratosis. Rete ridges are expansively elongated and terminate deeply, often into the corpus cavernosum, as club-shaped bases. The rete ridges consist of keratinocytes with large amounts of cytoplasm but showing otherwise no atypia, abnormal mitotic figures or bizarre growth patterns. A dense, lymphohistiocytic cell infiltrate is present in the upper dermis. Koilocytes indicative of HPV infection may be present in the granular layer. Despite BLT’s propensity to invade the dermis and deeper structures, tumor cells are notably absent from blood vessels and lymphatics. BLT is differentiated from typical condyloma acuminata by its thicker stratum corneum and endophytic nature.2,7,16

Differential Diagnosis


The differential diagnosis of BLT may include any tumorous growths in the genital area, caused by infectious (eg, condyloma lata), neoplastic (eg, Paget’s disease, Kaposi’s sarcoma), granulomatous (eg, Schistosomiasis), or inflammatory (eg, extracutaneous Crohn’s) diseases, most notably, those listed in Table 1.

Pathogenesis


HPV is the most common viral sexually transmitted pathogen and is the causative agent for condyloma acuminata. The oncogenic potential of HPV results from two virally encoded genes, E6 and E7.8 Almost all cases of BLT are associated with low-risk HPV types, including 6 and 11; however, it is unclear why some condyloma acuminata progress to form giant condyloma acuminata or BLTs. Some risk factors identified include immunosuppression, chronic irritation associated with phimosis and smegma, and poor personal hygiene.15

Prognosis

BLT is locally invasive as well as destructive; most complications extend from the growth of the tumor. Without treatment, the tumor can extend into pelvic organs and bone, thereby increasing the risk of fistula formation, secondary infections, the need for radical surgeries — such as penectomy and colostomy — and mortality. A surgical or combined chemotherapeutic and surgical approach offers the best prognosis; however, recurrence rates as high as 67% and mortality rates of 20% to 30% have been reported.15,17 Early and aggressive surgical intervention provides the best overall outcome.

Management and Prevention

Treatment Options

Treatment can be divided into medical and surgical management. Wide surgical excision is often the treatment of choice for BLT as it best prevents recurrence. Depending on the extent of the tumor, extensive removal of penile tissue and even penectomy may be required. Recently glansectomy, excision of only the glans penis, has been used on BLT confined only to the glans as a tissue-sparing alternative to more radical procedures, such as penectomy.9

Medical management has included oral and topical use of chemotherapeutic drugs, such as podophyllin, 5-fluorouracil, interferon-alpha methotrexate, bleomycin, mitomycin C, cisplatin, retinoids and imiquimod. However, they have met varied success in destroying tumor cells and preventing recurrence.6,9,15,18-21 Other alternative methods used include radiotherapy, cryotherapy, laser and electrocauterization, and autologous vaccinations with preparations of condyloma cells.15,22,23 While chemotherapy options are generally not as effective as surgery, pharmaceutical treatment is initially recommended to shrink the tumor mass, and thereby maximizing tissue preservation before extensive or radical surgery.

Prevention

Due to the increased risk of uncircumcised men to BLT and other penile carcinomas, early circumcision may be an effective means to reduce BLT. In addition, regular use of barrier devices during sexual activity, and HPV vaccination such as with Gardisil may reduce BLT by reducing transmission of HPV.

Our Patient

The patient in the case presentation was followed by the surgical urologic service. There was no follow up by dermatology.

Jason William Suszko, is a fourth year medical student at the University of Nevada School of Medicine and is applying to dermatology residency programs.

Dr. Khachemoune, the Section Editor of Derm Dx, is with the Department of Dermatology, State University of New York, Brooklyn, NY

Disclosure: The authors have no conflict of
interest with any material presented in this month’s column.