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Condyloma acuminatum generally has been considered a benign growth with no malignant potential. The present patient presented with condylomata acuminate of the penis and concomitant invasive squamous cell carcinoma. Partial amputation of the penis along with cauterization of the warts was successfully undertaken.
KEYWORDS: Condylomata acuminata; Concomitant; Squamous cell carcinoma; Penis.
CORRESPONDENCE: Dr. Sachit Sharma, MD, MCh. Department of Urology, PGIMS, Rohtak (Haryana), 124001 India ().
CITATION: UroToday Int J. 2010 Aug;3(4). doi:10.3834/uij.1944-5784.2010.08.02
ABBREVIATIONS AND ACRONYMS: HPV, human papilloma virus.
Genital wart infection is generally of transient nature with no sequelae . Rarely, it may progress to malignancy in the presence of cofactors like human papilloma virus (HPV) infection in the cervical or anal region, cigarette smoking, or concomitant immunosuppressed status . The present case of penile condylomata acuminata with concomitant squamous cell carcinoma is being reported because of the rarity of this clinical presentation.
A 50-year-old male patient presented with a fungating growth of the penis of 5 months duration (Figure 1). The growth was associated with a foul-smelling pus discharge. There was no history of bloody discharge, fever, or loss of weight. The patient was uncircumcised.
On examination, his pulse was 84 beats/minute and his blood pressure was 110/70 mmHg. He was afebrile with mild pallor. There was a growth measuring 5 cm x 6 cm x 6 cm over the glans. The undersurface of the growth was unhealthy with slough and pus discharge. There were multiple warts over the shaft of the penis (Figure 2). Bilateral inguinal lymph nodes were palpable, nontender, mobile, and ≤ 1 cm in size. The abdomen was soft and the per-rectal examination was normal. His chest was clear on auscultation.
Laboratory investigation revealed: hemoglobin level 11 mg%; blood sugar 84 mg/dL; blood urea 25 mg/dL; and serum creatinine 0.83 mg/dL. Venereal disease research laboratory (VDRL), human immunodeficiency virus (HIV), and hepatitis B surface antigen (HBsAg) tests were negative; serum calcium was 8.2 gm%. The electrocardiogram and skiagram of the chest were normal.
The patient was given spinal anesthesia. The surgeons partially amputated the penis with a margin of 2 cm. The lower penile skin flap was kept longer than the upper, and the urethra was taken out of the lower flap so that the skin suture line ran dorsally. The warts were cauterized.
Histopathological examination of the penile growth showed features of well-differentiated squamous cell carcinoma. Histopathology of the warty growths showed features of condylomata acuminata with koilocytosis. Lymph node biopsy showed only reactive hyperplasia and there was no lymphatic spread of carcinoma. The lesion had invaded the subepithelial connective tissue without lymphovascular invasion. According to the American Joint Committee on Cancer (AJCC) 2009 TNM classification, the lesion was T1a cN2 pN0 M0 or stage 1 (T1a N0). The lymphadenopathy subsided with antibiotics. The patient was healthy when evaluated 12 months after the operation. He had not developed any recurrence.
Genital warts include condylomata acuminata, bowenoid papulosis, and giant condylomata acuminata. Condylomata acuminata appear as lobulated papules that are typically 2-5 mm but may range from microscopic to several centimeters in size. Generally, they are believed to be caused by the benign HPV types 6 and 11, so biopsy is usually not done. Bowenoid papulosis is characterized by flat, hyperpigmented lesions. The disorder is caused by high-risk HPV (type 16), so biopsy is recommended. Giant condyloma acuminatum (Buschke-Lowenstein tumor) is a rare, aggressive, wart-like growth that is a verrucous carcinoma caused by HPV type 6 with no histologic malignant changes. Despite the histologically benign appearance, it behaves in a malignant fashion. It destroys adjacent tissues and has been regarded as an intermediate entity between an ordinary condyloma acuminatum and squamous cell carcinoma .
Condyloma acuminatum has been reported to be related to HPV infection, with some cases showing p53 protein low-grade overexpression . In contrast, p53 protein overexpression has been reported as common in penile squamous cell carcinoma, which is seldom related to HPV infection .
In the case reported, tests for HPV infection in the retrieved specimens were not conducted due to local unavailability. In 2001, a study by Bezerra et al  revealed no difference between patients with penile cancer who were HPV DNA-negative and DNA-positive for outcome measures of lymph node metastases and 10-year survival rate. However, a study published in 2006  showed that the disease-specific 5-year survival in the high-risk HPV-negative group was 78%, versus 93% in the high-risk HPV-positive group (log rank test P = .03). The latter finding suggests that the presence of high-risk HPV confers a survival advantage for patients with penile cancer. The virus plays an important role in oncogenesis through interaction with oncogenes and tumor-suppressor genes (P53 and Rb).
There are varied reports in the literature regarding the significance of the association between condylomata acuminate and squamous cell carcinoma. In 1977, Boxer et al  reviewed 65 cases of malignant degeneration of either condyloma acuminatum or Buschke-Lowenstein tumor. Light microscopic and ultrastructural evidence of malignant transformation of condyloma acuminatum was found by Kovi et al  in 1974. A more recent study found a nonsignificant positive association between condylomata acuminata and penile cancer , but this finding was contradicted by other recent data showing a greater than 20-fold risk of penile cancer in patients with condylomata acuminata . Squamous cell carcinoma arising in a giant condyloma acuminatum in the anorectal region and pelvis has been reported [3,11]. The hallmark of giant condyloma acuminatum has been described as a high rate of local recurrence and transformation into squamous cell carcinoma .
Diagnosis of genital warts can be done by inspection in virtually all cases. Auto-whitening of genital warts may distinguish them from genital papules. In cases requiring biopsy, histological evidence of HPV infection may be sought. Recurrence of genital warts is frequent because no effective virus-specific agent exists. Treatment options include observation, podophyllin, imiquimod (a local interferon inducer), bichloroacetic or trichloroacetic acid, cryotherapy, electrofulguration, CO2 laser, and 5-fluorouracil (5%) cream. Short-term intralesional interferon alpha-2b has also been shown to have activity against condylomata.
Penile squamous cell carcinoma is a common disease in India. However, the authors did not find a single case report of carcinoma of the penis with concomitant condylomata acuminata. The present case is being reported to exemplify the transitory character of condylomata acuminate and the rarity of the concomitant clinical presentation. This case also highlights the need to monitor patients with genital warts. Circumcision in cases of condylomata acuminata may help to decrease the incidence of carcinomatous change.
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