Case of the Month

March 2011

Frans Radebe
National Institute for Communicable Diseases

A 28 years old HIV-infected man presented at a Sexually Transmitted Infections (STIs) clinic with a giant wart of 4 years duration. Genital examination revealed the giant wart (figure 1) on the shaft of his penis.

Figure 1: Giant genital wart of the shaft penis

RPR for syphilis was negative, as was urine PCR for other STIs except Trichomonas vaginalis, which was positive. His CD4 count was 74 cells/mm3. A biopsy sample taken from the giant wart was PCR positive for HPV-6, 11, 55, 58, 59, 68, 73, 83 and cp6108.

The patient was referred for the commencement of antiretroviral.

Question 1: What is the likely diagnosis and what are the clinical features of this lesion?

Answer to Q1

First described by Buschke and Lowenstein in 1925, the Giant Condyloma of Buschke and Lowenstein (GCBL) is a slow-growing locally destructive plaque that typically appears on the penis but may occur elsewhere in the anogenital region3 . It is commonly considered to be a variant of verrucous carcinoma due to their aggressive local evolution together with oral florid papillomatosis and epithelioma cuniculatum. There has been considerable debate regarding the exact nature and aetiology of these lesions.

GCBL is slow growing, highly destructive 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. It co-localizes with human papillomavirus (HPV) types 6 and 11 and occasionally HPV types 16, 18 and 545. Other implicated agents apart from p53 protein mutation found in genital warts and squamous cell carcinomas are chronic exposure to chemicals, chronic irritation and poor hygiene.

GCBL is rare and accounts for 5-24% of penile cancers and 50% of all low-grade squamous cell carcinomas of the penis3. The bladder lesions have been associated with schistosomiasis. The condition is common to males who are uncircumcised and occur in persons younger than 50 years.

If untreated, GCBL can cause destruction of tissues extending into the pelvic organs. In 20-30% of cases malignant transformation may occur1 . Recurrence is common, even with treatment.

GCBL starts on the prepuce as a plaque and slowly expands into a cauliflower-like mass, as large as 15cm. The lesion may ulcerate or form a penile horn and typically is associated with a foul odor. Presenting symptoms of peri-rectal GCBL include peri-anal mass, fistula or abscess and bleeding.

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.

Question 2: What are the risk factors for development of this lesion?

Answer to Q2

Chronic phimosis and poor penile hygiene contribute to the development of GCBL. This may account for the higher incidence in males who are uncircumcised. In general, newborn circumcision has been estimated to be 99.9% effective in eliminating cancer of the penis 9,10 . Immunosuppression secondary to HIV infection or immunosuppressants may be a predisposing factor. Other risk factors include:

  • low socioeconomic status
  • drug abuse
  • use of oral contraceptives
  • presence of other sexually transmitted diseases
  • diabetes
  • smoking
  • pregnancy which may be associated with an impaired immune response.

Question 3: How would you treat the case and how may this lesion have been prevented?

Answer to Q3

GCBL tumor is technically benign, although it displays aggressive local invasive behavior that makes it difficult to manage. Delays in consultation which can be several years after the onset of the first symptoms, can be the consequence of a slowly developing lesion and to psycho-social factors such as the fear of the possibility of a cancer diagnosis and its implications8.

The recommended treatments for GCBL include

  • topical applications4
    • podophyllin
    • radiation therapy
    • electrotherapy
  • systemic immunotherapy
  • systemic chemotherapy
  • surgery

Adjunct therapies in more advanced or recurrent lesions include7.

  • radiotherapy
  • photodynamic therapy
  • imiquimod

The most important consideration in developing a treatment strategy is which strategy would achieve the best clinical result with the least morbidity to the patient.

Preventative measures:

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. The HPV vaccine (Gardasil) is indicated for the prevention of condyloma acuminata due to HPV types 6 and 11 in boys, men, girls, and women aged 9-26 years. The vaccine is administered as 3 separate doses adminstered at 0, 2, and 6 months.

References & Further reading:

  1. Bjorck M, Athlin L, Lundskog BA. Giant condylomata acuminatum (Buschke-Lowenstein tumor of the anorectum with malignant transformation). Eur J Surg 1995; 161: 691-694.
  2. Chao MW, Gibbs P. Squamous cell carcinomas arising in a giant condyloma acuminatum (Buschke-Lowenstein tumor) Asian J Surg. Jul 2005; 29 (3): 238-40.
  3. Mical A, Innocenzi D, Nasca M, Musumeci ML, Ferrau F, Greco M. Squamous cell carcinoma of the penis. J AM Acad Dermatol Sep 1996; 38: 432-51.
  4. Ilkay AK, Chodak GW, Vogelzang NJ, Gerber GS. Buschke-Lowenstein tumor: therapeutic options including systemic chemotherapy. Urology 1993; 42: 599-602.
  5. Boshart M, zur hausen H. Human papillomaviruses in Buschke-Lowenstein tumor: J Virol 1986; 58: 963-966.
  6. Arany I, Tyring SK. Systemic immunosuppression by HIV infection influences HPV transcription and thus local immune responses in condyloma acuminatum. Int J STD & AIDS 1998; 9: 268-271.
  7. Klutke JJ, Bergman A. Interferon as an adyuvant for genital condyloma acuminatum . Int J Gynecol Obstet 1995; 49: 171-174.
  8. Ristvedt SL, Trinkaus KM. Psychological factors related to delay in consultation for cancer symptoms. Psychooncology 2005; 14: 339-350.
  9. Kauffmann CL. Giant condylomata acuminate of Buschke-Lowenstein tumor: Differential Diagnosis. http//emedicine.medsacpe.com/article/1132178-diagnosis
  10. Ambriz-Gonzalez G, Escobedo-Zavala L.et.al Buschke-Lowenstein tumor in childhood. J Pediatr Surg. Sep 2005; 40 (9) 25-7
Outcome of the Case

The patient responded well to cryotherapy and 20% Podophyllin and was referred for commencement of ART. Subsequently the patient was lost to follow-up due to his incarceration where the prison doctor recommended surgery. No further follow-up of the patient was possible. Treatment with chemo-radiotherapy in this case would have resulted in complete resolution of the disease without the need for further surgical intervention.

Lessons learnt

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.

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