AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

First described by Buschke and Löwenstein in 1925, the giant condyloma of Buschke and Löwenstein (GCBL) is a slow-growing, locally destructive verrucous plaque that typically appears on the penis but may occur elsewhere in the anogenital region. It most commonly is considered to be a regional variant of verrucous carcinoma, together with oral florid papillomatosis and epithelioma cuniculatum.

Related eMedicine articles of possible interest include the following:

• Squamous Cell Carcinoma
• Human Papillomavirus
• Warts, Genital

Medscape resource centers related to associated conditions include the following:

• HPV and Cervical Cancer Resource Center
• Biologic Therapies in Cancer Resource Center

Medscape CME courses on related topics are as follows:

• Human Papillomavirus in Cervical and Head-and-Neck Cancer
• Human Papillomavirus Infection and Oropharyngeal Cancer
• HPV-Related Disease in Men: Anal and Penile Cancer (Slides With Transcript)

Pathophysiology

GCBL is slow growing, highly destructive to contiguous tissue, and seldom metastasizes. Most commonly located on the glans penis, GCBL can be found on any anogenital mucosal surface, including the vulva, vagina, rectum, scrotum, and bladder.¹ Co-localization with human papillomavirus (HPV) types 6 and 11²; occasionally HPV types 16 and 18; and, on one occasion, HPV 54 has been shown. The E6 protein of HPV-6 and HPV-11 binds p53 tumor suppressor protein less efficiently than that of HPV-16 and HPV-18 but, theoretically, could lead to accelerated degradation of the p53 protein. The E6 protein also inhibits p53 transcription.

Alternatively, a mutation may occur in the p53 protein, leading to clonal proliferation. Several reports have shown some overexpression of p53 in genital warts and squamous cell carcinomas (SCCs), but one study concluded that despite the overexpression, p53 mutations were not present.³ Other implicated agents are chronic chemical exposure, chronic irritation, and poor hygiene.

Frequency

United States

GCBL is rare. Estimates of incidence show that GCBL accounts for 5-24% of penile cancers, which, in turn, are 0.3-0.5% of male malignancies. Another review assessed that verrucous carcinoma accounted for approximately 50% of all low-grade SCCs of the penis. GCBL located outside the penis is much more infrequent. Fewer than 50 cases of perianal tumors and only 20-30 cases of vulvar or bladder GCBL have been reported. The bladder lesions have been associated with schistosomiasis (ie, Schistosoma haematobium).

International

SCC of the penis is much more common elsewhere in the world compared with the United States. No specific data are available in the English literature regarding international incidence.

Mortality/Morbidity

If untreated, GCBL can be locally very destructive, extending into the pelvic organs and bony structures. Even with treatment, morbidity rates can be high because recurrences are very common with all treatment modalities. One case report noted recurrent lesions in the ischial tuberosities that required pelvic exenteration. Malignant transformation is reported in 30-56% of patients.

Race

No racial predilection is reported.

Sex

Most cases of GCBL occur in males on the glans penis. This condition is more common in males who are uncircumcised. The male-to-female ratio is 3.5:1.

Age

Two thirds of cases of GCBL occur in persons younger than 50 years. It is rarely reported in children. A recent trend toward a younger reported age at presentation is recognized.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

See Physical, below.

Physical

GCBL typically starts on the prepuce as a keratotic plaque and slowly expands into a cauliflowerlike mass, as large as 15 cm. The lesion may ulcerate or form a penile horn and typically is associated with a foul odor. Expansion to the corpus cavernosum and urethra may occur, with subsequent fistulation. Regional lymphadenopathy is common, primarily due to secondary infection, not metastases. Similar slow progression is noted on perianal lesions. Presenting symptoms of perirectal GCBL include perianal mass (47%), fistula or abscess (32%), and bleeding (18%).


GCBL of the perianal region, consisting of a slow-growing, ulcerated, cauliflowerlike mass.

Causes

Chronic phimosis and poor penile hygiene have been postulated as inciting or contributing events. This may account for the higher incidence in males who are uncircumcised. Populations with a higher incidence of circumcision have a lower rate of GCBL. In general, newborn circumcision has been estimated to be 99.9% effective in eliminating cancer of the penis. Chronic irritation, produced by a perianal fistula and ulcerative colitis, has been implicated as a causative factor. Immunosuppression secondary to HIV disease or due to immunosuppressive medication may be a predisposing factor. Other risk factors for GCBL are low socioeconomic status, drug abuse, use of oral contraceptives, presence of other sexually transmitted diseases, diabetes, smoking, and, possibly, pregnancy,⁴ which may be associated with an impaired immune response.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Human Papillomavirus

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Imaging Studies

GCBL has shown mild, heterogenous enhancement with gadolinium-diethylenetriamine pentaacetic acid (DTPA) contrast on MRI. This study may be useful in delineating the expansion of the lesion when planning for removal.⁵

Procedures

Biopsy is the diagnostic procedure necessary for evaluation. It must be sufficiently deep and generous to evaluate for possible foci of SCC because lesions with these changes have been shown to have a higher recurrence rate and to metastasize. Vacuolar change is not a reliable differentiator between GCBL and condyloma, and visualizing the base of the lesion and the characteristic broad, blunt, deeply penetrating rete pegs is necessary to make the diagnosis.

Although the rate of regional lymph node involvement is low, sentinel lymph node biopsy should be considered if clinical findings suggest the need for it.

Histologic Findings

GCBL characteristically has massive epidermal hyperplasia, hyperkeratosis, and parakeratosis and is markedly exophytic. Granular vacuolization may be present, and individual keratinocytes have large cytoplasm and a nucleus with prominent nucleoli.
 
Blunt-shaped masses of tumor project deeply into the dermis and contiguous structures. The tumor cells have little evidence of atypia and are not found inside blood vessels or lymphatics. Individual keratinocytes may show keratinization, but no horn pearls are seen. Lymphohistiocytic inflammation is usually present.
 
Giant condyloma acuminatum is differentiated histologically from ordinary condyloma acuminata by its thicker stratum corneum and the presence of an endophytic downgrowth, along with a tendency to invade deeper.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

The treatment of choice for GCBL is wide surgical excision. Surgery alone has resulted in a disease-free status in 45.5% of patients.⁶

In addition, oral and topical chemotherapeutic modalities have been used with mixed success as adjuvants to surgery or as treatment for recurrences. Topical therapy alone, such as with 5-fluorouracil,⁷ podophyllin, or interferon (IFN), are generally insufficient to control disease or prevent progression of the giant lesions. One case report noted that intralesional bleomycin in the wound bed of an incompletely resected tumor was effective, with no recurrence at 2 years. Topical cidofovir gel 1.5% used for several months produced clinical improvement, even in cases refractory to conventional treatment.^{8, 9}

The postulated viral origin of these tumors has led to the use of IFN with moderate success. One case of vaginal GCBL responded to 6 months of IFN 2-alfa, with apparent complete resolution. Although topical IFN lacked clinical efficacy, intralesional administration¹⁰ has produced complete responses in 47-62% of cases; however, the recurrence rate is 40%. Large lesions may be candidates for systemic IFN. A deeply infiltrating giant condyloma acuminatum experienced a major response after 9 months of continuous IFN administration at 10 MU thrice weekly, although no change in the tumor could be observed in the first several months.

Imiquimod was effective in combination with carbon dioxide laser ablation in a patient unable to tolerate surgery, whose tumor was positive for HPV-6.¹¹

Traditional systemic antitumor agents have also been used. One report described the use of bleomycin, cisplatin, methotrexate, and leucovorin in a patient with recurrence after multiple surgeries for GCBL.¹² An autopsy 1 year later showed no evidence of active disease. A separate report noted tumor shrinkage with mitomycin-C and 5-fluorouracil combined with fractionated radiotherapy; unfortunately, this patient manifested pulmonary metastases.¹³ Etretinate and photodynamic therapy with intravenous porphyrins have been used with some success in vaginal GCBL.

Radiation therapy remains controversial. Extensive evidence supports anaplastic transformation in oral/plantar verrucous carcinoma, but data in GCBL are mixed. While some studies show evidence of new aggressive behavior after radiation therapy, more than a few case reports document resolution of small tumors after radiation.¹⁴ One review recommended the avoidance of radiation if possible; but, if necessary, the use of a large dose of radiation to minimize chances of further mutation may be effective in a candidate who is a poor surgical risk.¹³ To support this view, one report describes successful treatment of a recurrent tumor with radiation at 4500 cGy in 25 fractions; the patient remained disease free when reevaluated at 20 months.

Bulky tumors have been shrunk with preoperative chemoradiation, followed by radical surgery, in some instances followed by reconstructive surgery. One regimen that lead to a complete response consists of mitomycin C and 5-fluorouracil administered concomitantly with radiation therapy 50.4 Gy to the tumor bed and prophylactic irradiation of the regional nodes.
 
Autologous vaccination with a preparation of condyloma cells was well tolerated clinically and produced good responses in an initial and recurrent giant condyloma acuminata. After more than 1 year of follow-up in this series, recurrence rates with various treatments were 50% for excision alone and bichloracetic acid, 85% for podophyllin and IFN alfa, and only 4.6% after excision and vaccination. Mean follow-up was 13 months (range, 6-23 mo).¹⁵

Surgical Care

Surgical excision is the treatment of choice. Its main advantage is the ability to histologically examine the entire specimen to ensure clear margins and to evaluate for foci of SCC. As a drawback, it typically requires at least a partial penectomy, but one series successfully used glansectomy only, with excellent functional and therapeutic results.¹⁶ Mohs surgery appears to be the most efficacious surgical treatment, allowing specimen examination and sparing most of the tissue.

Recurrences of giant condyloma acuminatum can be successfully addressed with radical surgery. The cure rate with radical surgery reportedly is 61%, versus only 25% with chemoradiotherapy with or without local excision. Some authors recommend radical electrocautery surgical resection whenever possible.¹⁷
 
Resection with the carbon dioxide laser has also been effective, with the advantage of permitting a bloodless field, and it has been used effectively in a pregnant patient. Carbon dioxide and argon lasers are used for relapsing cases or as an alternative first-line therapy.

Cryosurgery has been effective in several case reports, primarily on small lesions, with normal anatomy resulting after tumor resolution. Close monitoring is required because destruction of the entire tumor cannot be ensured.

FOLLOW-UP

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Deterrence/Prevention

Early circumcision has been found to be extremely effective in preventing penile carcinoma. Given the association with HPV, condom use would probably be effective in decreasing the incidence of GCBL.

Complications

Most complications of GCBL are the result of the growth of the tumor or of the treatment. As the lesion progresses, fistulization, foul odor, and secondary infections are common. Extensive lesions, particularly leading to complex fistulous tracts and discharge, may require a temporary colostomy. Less radical approaches may lead to local recurrence. Therefore, abdominoperineal resection has been recommended for patients with rectal sphincter involvement.

Prognosis

Inadequately treated GCBL has a relentless progression and is fatal by direct spread to pelvic organs. By definition, adequately treated GCBL has a low recurrence rate and, therefore, an excellent prognosis. However, one study of perianal/anogenital GCBL, with treatments ranging variously from podophyllin to pelvic exenteration, showed a 68% recurrence rate with a 21% mortality rate.

In another series of 42 patients, the median number of recurrences of giant condyloma acuminatum was 2 years (range, 1-7 y), and the median time to first recurrence was 10 months. A high rate of recurrence correlates with a long duration of disease.

Patient Education

For excellent patient education resources, visit eMedicine's Men’s Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education article Cancer: What You Need to Know.

MISCELLANEOUS

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

Any chronic anogenital lesion not responsive to simple therapies must have an adequate biopsy. If GCBL is in the differential diagnosis, the biopsy must extend deep enough to view the architecture and deep margin of the lesion.

ACKNOWLEDGMENTS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Christopher Norwood, MD, and Mary K. Mather, MD, to the development and writing of this article.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Figure 1: Giant condylomata acuminata of Buschke and Löwenstein of the perianal region, consisting of a slow-growing, ulcerated, cauliflowerlike mass.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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Article Last Updated: Mar 26, 2008