Archivio Italiano di Urologia e Andrologia 2020; 92, 2114 CASE REPORT Penile verrucous squamous cell carcinoma: A rare case report Omer Yuksel, Emre Karabay, Osman Bilen, Çağatay Tosun, Levent Verim Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Department of Urology, Uskudar/Istanbul Turkey. Penile cancer is a rare type of urological cancer. Predisposing factors include phimo- sis, poor hygiene, and smoking. Circumcision in early child- hood has been shown to be protective against penile cancer. About 95% of penile cancers are squamous cell carcinomas, while verrucous type is a rare variant with frequent recur- rences, but with a favorable prognosis. The majority of patients are asymptomatic; however, patients may present with pain, discharge, and bad odor depending on the severity of the disease. Although hospital admission is often late due to psychosocial factors, cancer is often localized. Herein, we report a 61-year-old circumcised patient presenting with painful penile mass who was diagnosed with a penile verru- cous squamous cell carcinoma in the light of literature data. KEY WORDS: Penile cancer; Verrucous cancer; Penectomy. Submitted 17 November 2019; Accepted 12 December 2019 Summary No conflict of interest declared. DOI: 10.4081/aiua.2020.2.114 INTRODUCTION Penile cancer is the rarest of urological malignancies in male. Its annual incidence is 1/100,000 in the United States (US) and Europe. As it is more common in many countries worldwide, it is considered a global health problem (1). According to the American Cancer Society, 2,080 newly diagnosed penile cancer patients and 410 penile cancer-related death have been estimated in the US in 2019 (2). Its incidence is the highest in Brazil, Uganda, and India and the lowest in the Jewish and Muslim communities in which male infants and children are mostly circumcised. Male circumcision in early childhood has been shown to reduce the risk for penile cancer by three to five-fold, probably as it prevents chronic irritation (3). Predisposing factors being uncir- cumcised, balanoposthitis, balanitis xerotica obliterans (BXO), ultraviolet phototherapy, sexual promiscuity, sex- ual intercourse in early adolescence, history of condylo- ma, tobacco smoking, and sexual intercourse with a partner infected with Human Papillomavirus (HPV) (4). In addition, a high-risk HPV-DNA positivity has been associated with reduced survival (5). The most common type of penile cancer is squamous cell carcinoma (SCC). Penile SCC can be divided into several subtypes. The most common subtypes include usual SCC (48 to 65%), basaloid carcinoma (4 to 10%), warty carcinoma (7 to 10%), verrucous carcinoma (3 to 8%), papillary carcinoma (5 to 15%), and mixed carcinomas (9 to 10%). Verrucous carcinoma is a rare variant of well- differentiated SCC with low malignancy potential. Premalignant lesions include penile cutaneous horn, Bowenoid papulosis, and BXO, while potential risk fac- tors for the development of penile cancer are penile intraepithelial neoplasms, erythroplasia of Queyrat, and Bowen disease (3). Of these lesions, about 30% result in invasive cancer. Penile cancer, which is mostly seen in individuals aged 50 to 70 years, affects glans of penis (48%), prepuce (21%), both glans and prepuce (15%), coronal sulcus (6%), and penile shaft (< 2%). Initial physical examina- tion manifestations may widely vary from a small red- ness to a large ulcer or infiltrative lesion. Patients may present with itching, pain, bleeding, discharge, and bad odor depending on the severity of the disease. Hospital admission is often late due to psychosocial factors; 15 to 60% of patients seek a medical diagnosis and treatment at least one year after the symptom onset. Nonetheless, the disease is localized in 66% of patients. In the initial admission, inguinal lymph nodes must be evaluated. Penile cancer metastasizes in a predictable pattern with superficial and deep inguinal lymph nodes occurring first, followed by pelvic and periaortic lymph nodes. Distant metastasis is very rare (1 to 10%) and mostly occurs in the late stages of the disease (6). Disease stag- ing is based on the American Joint Committee on Cancer TNM Staging System depending on the depth of invasion, lymph node invasion, and distant metastases (6, 7). Herein, we report a 61-year-old circumcised patient pre- senting with painful penile mass who was diagnosed with a penile verrucous SCC in the light of literature data. CASE REPORT A 61-year-old male patient who was circumcised at the age of 13 years was admitted to our outpatient clinic with a painful penile mass. Although his complaints were present for two years, he did not seek a medical treatment due to psychosocial factors. Upon increased penile pain, he applied to our clinic. His medical histo- ry revealed no smoking history, except being a social smoker, dysuria, having multiple sexual partners or sex- ually transmitted disease, or previous surgery. He was on regular medical treatment for hypertension and diabetes mellitus. His familial medical history revealed rectal can- cer in his father. Physical examination revealed a 2-cm Karabay-Yuksel_Stesura Seveso 17/06/20 10:15 Pagina 114 115Archivio Italiano di Urologia e Andrologia 2020; 92, 2 Verrucous carcinoma of penis ulcerative mass with bleeding and itching advancing toward the coronal sulcus from the dorsal layer of the glans without urethral meatus involvement (Figure 1). Poor penile hygiene was observed. Inguinal region exam- ination showed no palpable lymphadenopathy. Skin biopsy of the penile ulcer was performed. Pathological examination result reported a well-differentiated penile verrucous SCC. Magnetic resonance imaging and positron emission tomography-computed tomography revealed TaNoMo clinical stage and partial penectomy was performed (Figure 2). Partial penectomy pathology was reported T3NxMx. No recurrence or metastasis was observed in the postoperative six months of follow-up. DISCUSSION Penile cancer is a rare type of cancer which accounts for less than 1% of cancers in men (8). Its prevalence is higher in developing countries. It more frequently affects uncircumcised, white men with low income (9). Squamous cell carcinoma is the most common type and 33% of SCCs originate from premalignant lesions. Possible mechanisms which stimulate malignant trans- formation include chronic irritation, tobacco smoking, and poor penile hygiene which induce chronic inflam- mation, metaplasia, and differentiation (10). Certain types of viral infections such as HPV may also lead to penile cancer through DNA damage. In addition, dam- ages in tumor suppressor genes such as p53 disrupt the cell cycle, resulting in DNA damage and malignant trans- formation (4, 5). Verrucous SCC of the oral cavity was first defined by Ackerman in 1948. It accounts for 3 to 8% of penile can- cers and 20% of verruciform lesions. It is a rare variant of exophytic, papillomatous, low-grade, and well-differ- entiated SCC. As verrucous SCCs mostly present with squamous epithelial hyperplasia and keratinization, mis- diagnosis is common, when diagnostic biopsy fails. Therefore, biopsy is strongly recommended for definitive diagnosis. Its etiology has not been fully understood, yet (11). Earlier studies have demonstrated that verrucous SCCs are associated with low-risk HPV infection (12). However, later studies using broad-spectrum HPV poly- merase chain reaction testing have revealed controversial results. In a study, Rubin et al. (12) reported that basaloid and warty SCCs were associated with HPV, while the HPV positivity rate was 33.3% and 34.9% for verrucous and usual SCCs, respectively. In another study, Stankiewicz et al. (13) reported an HPV-DNA positivity of 23% and 59% for verrucous and usual SCCs, respective- ly. These findings indicate a low-degree association between penile verrucous SCC and HPV. Although most of the current data regarding verrucous SCCs are based on case reports and case series, surgery is the mainstay of the treatment. The main strategy is wide excision of the mass or partial penectomy. Radical penec- tomy can be performed in rare cases. Recurrence of penile verrucous SCCs is high; one case with recurrence after 30 years has been reported in the literature (14). In early recurrence, additional resection and even radical penectomy can be performed. Distant metastasis is extremely rare and is not seen in almost none of patients with penile verrucous SCC. Therefore, inguinal lymphadenectomy is reserved for only very few patients. Hatzichristou et al. (15) performed inguinal lymphadenectomy in selected patients with penile verrucous SCC; however, no specific lesion could be detected. Thus, prophylactic inguinal lymphadenec- tomy is not recommended for this patient population. Early diagnosis and prevention are of utmost importance for the management of penile cancer. Neonatal circumci- sion, smoking cessation, and HPV vaccination have been suggested to decrease the incidence of penile cancer. REFERENCES 1. Parkin DM, Whelan SL, Ferlay J, et al. Cancer Incidence in Five Continents. Vol. VIII. http://www.iarc.fr/en/Publicaions/PDFs- online/Cancer-Epidemiology/IARC-Scientific Publication-No.- 155.Accessed March 12,2014. 2. American Cancer Society. Cancer Facts & Figures 2019. Atlanta: American Cancer Society; 2019. 3. Barnholtz-Sloan JS, Maldonado JL, Pow-Sang J, Guliano AR. Incidence trends in primary malignant penile cancer. Urol Oncol. 2007; 25:361-367. 4. Pizzocaro G, Algaba F, Horenblas S, et al. EAU penile cancer guidelines 2009. Eur Urol. 2010; 57:1002-1012. 5. Bezerra AL, Lopes A, Santiago GH, et al. Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer. 2001; 91:2315-2321. 6. Marchionne E, Perez C, Hui A, Khachemoune A. Penile squamous cell carcinoma: a review of the literature and case report treated with Mohs micrographic surgery. An Bras Dermatol. 2017; 92:95-99. 7. Edge SB, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manuel. (7th edn), New York, NY: Springer. 2010. 8. Wilson CN, Sathiyasusuman A. Associated risk factors of STIs Figure 1. Penile mass on physical examination. Figure 2. Partial penectomy material. Karabay-Yuksel_Stesura Seveso 17/06/20 10:15 Pagina 115 Archivio Italiano di Urologia e Andrologia 2020; 92, 2 O. Yuksel, E. Karabay, O. Bilen, Ç. Tosun, L. 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Penile verrucous carci- noma: a new case report in a circumcised man. Clin Oncol. 2019; 4:1594. 15. Hatzichristou DG, Apostolidis A, Tzortzis V, et al. Glansectomy: an alternative surgical treatment for Buschke-Löwenstein tumors of the penis. Urology 2001; 57:966-969. Correspondence Omer Yuksel, MD dr_omer_yuksel@hotmail.com Emre Karabay, MD (Corresponding Author) emrekarabay@gmail.com Osman Bilen, MD osmanbilen1212@gmail.com Çağatay Tosun, MD cagataytosun@hotmail.com Levent Verim, MD leventverim@hotmail.com Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Dept. Urology Tibbiye Street. No: 23 34668 Uskudar/Istanbul (Turkey) Karabay-Yuksel_Stesura Seveso 17/06/20 10:15 Pagina 116