A Case of Squamous Cell Carcinoma of the Anterior Urethra in a Man

Case Review A Case of Squamous Cell Carcinoma of the Anterior Urethra in a Man Navin Shah, MD,1 Thomas Huebner, MD,2 Shannon Cherone, MM, BM2,3 1Mid-Atlantic Urology Associates, Greenbelt, MD; 2Integrated Cellular and Molecular Diagnostics, Greenbelt, MD; 3University of Maryland, College Park, MD Squamous cell carcinoma (SCC) of the anterior urethra in men is rare, comprising less than 1% of all urologic cancers. The mean age at diagnosis is 60 years and it is nearly twice as common in black men compared with white men. We detail a case of SCC of the anterior urethra in a man presenting with an inguinal mass, meatal stenosis, and balanitis. [Rev Urol. 2019;21(2/3):133–135] ® © 2019 MedReviews , LLC KEY WORDS Urethra, anterior • Squamous cell carcinoma • HPV, p16 S quamous cell carcinoma (SCC) of the anterior urethra in men is rare, comprising less than 1% of all urologic cancers. The mean age at diagnosis is 60 years and it is nearly twice as common in black men compared with white men. We detail a case of SCC of the anterior urethra in a man presenting with an inguinal mass, meatal stenosis, and balanitis. Case Report A 78-year-old black man presented with a slow and interrupted urinary stream, hematuria, urge incontinence, nocturia, and urinary infection persisting for over a year. His medical history included chronic renal failure, cerebral vascular accident, and hypertension. On physical examination, the patient had meatal stenosis, balanitis, induration of the external meatus and anterior urethra, a 20-g prostate with right-sided hardness, and a left inguinal mass. A urinalysis demonstrated red and white blood cells. Urine culture and urine cytology were negative. Other laboratory study results included creatinine of 1.8 mg/dL and prostate-specific antigen (PSA) of 0.9 ng/mL. A CT scan of abdomen and pelvis without contrast showed a right renal cyst. He was given levofloxacin, 500 mg daily PO, for 8 days. A cystoscopy showed meatal stenosis and obstruction of the lateral lobes of the prostate gland. Excision of the inguinal mass demonstrated metastatic SCC to a lymph node (Figure 1). An in-situ hybridization study for human papillomavirus (HPV) subtype 16 was positive. Subsequent biopsy of the meatus and indurated anterior urethra demonstrated in-situ SCC with foci suspicious for invasion (Figure 2). Of Vol. 21 No. 2/3 • 2019 • Reviews in Urology • 133 SCC of the Anterior Urethra continued note, the tumor was diffusely and strongly immunoreactive for p16, a surrogate marker of HPV. A partial penectomy was performed and demonstrated invasive, moderately differentiated SCC with infiltration into the corpus spongiosum (pT2). HPV positivity was confirmed by immunohistochemistry. A positron emission tomography (PET) scan did not show any metastasis. The patient received platinum-based chemotherapy (cisplatinum and 5-fluorouracil) followed by radiation to the inguinal regions. Discussion Figure 1. Inguinal lymph node with metastatic squamous cell carcinoma (hematoxylin and eosin stain, 1003 original magnification). A B Figure 2. (A) Biopsy of the indurated meatus demonstrating in-situ squamous cell carcinoma (hematoxylin and eosin stain, 4003 original magnification). (B) Positive p16 immunohistochemical stain (4003 original magnification). 134 • Vol. 21 No. 2/3 • 2019 • Reviews in Urology Primary urethral carcinoma (PUC) is rare, accounting for less than 1% of genitourinary malignancies in both men and women. Ray and colleagues found only 23 cases of PUC over a span of 30 years.1 Analysis of the Surveillance, Epidemiology, and End-Results (SEER) database revealed that in men, the majority of PUC consists of urothelial carcinoma (54%), whereas SCC and adenocarcinoma are less common (35% and 12%, respectively).2 As the distal urethra is lined by both urothelial and squamous epithelium, a higher proportion of PUC encountered in the distal urethra are SCC compared with predominantly urothelial carcinoma in the proximal urethra. Younger patients typically experience more aggressive forms of PUC and have poorer outcomes. Partial penectomy with or without radiation and chemotherapy is considered in all cases depending on the cancer stage. In addition to its rarity, this case is also notable for expression of HPV subtype 16 in the nodal metastasis (demonstrated by an in-situ hybridization study) and strong, diffuse immunohistochemical expression of p16, a surrogate marker of HPV, in the tumor in the excisional biopsy and partial penectomy specimens. An SCC of the Anterior Urethra association with oncogenic HPV subtype 16 has been reported by several case series.1,3 Of note, 100% of SCC arising in the pendulous urethra (ie, distal to the peno-scrotal junction) in both studies were positive for HPV subtype 16, whereas the virus was rarely found in tumors arising in the non-pendulous urethra. The distal urethra has been regarded as a putative reservoir for HPV, both low-risk and high-risk/oncogenic subtypes, with some authors reporting detection rates from 8% to 20% in the general male population and 20% to 33% in high-risk male populations.6 Wiener and colleagues found metastatic disease in 75% of HPV subtype 16–positive cases and also demonstrated a trend toward prolonged survival in HPV-positive cases compared with HPV-negative cases.4 Patients with HPV-positive urethral SCC tend to have better survival outcomes than HPVnegative cases. Patient age greater than 75 years and advanced stage disease are predictors of poorer outcomes.4-6 This case involved inguinal lymph node metastasis, which is seen in 10% to 20% of cases of anterior and bulbar-membranous SCC.7 Regional lymphatic drainage patterns may contribute to better outcomes in distal urethral SCC compared with those more proximal as the distal tumors drain to the more accessible inguinal lymph node chain, whereas proximal tumor drain to deeper pelvic nodes. Some authors have suggested classifying distal urethral SCC much the same as penile and foreskin tumors due to the differences in prognosis of proximal and distal urethral tumors.3 Due to clinical rarity, a standard of care is difficult to establish.5 References 1. 2. 3. 4. 5. 6. 7. Ray B, Canto AR, Whitmore WF. Experience with primary carcinoma of the male urethra. J Urol. 1977;117:591-594. Aleksic I, Rais-Bahrami S, Daugherty M, et al. Primary urethral carcinoma: a Surveillance, Epidemiology, and End Results data analysis identifying predictors of cancer-specific survival. Urol Ann. 2018;10:170-174. Corbishley CM, Rajab RM, Watkin NA. Clinicopathological features of carcinoma of the distal penile urethra. Semin Diagn Pathol. 2015;32:238-244. Wiener JS, Effert PJ, Humphrey PA, et al. Prevalence of human papillomavirus types 16 and 18 in squamous-cell carcinoma of the penis: a retrospective analysis of primary and metastatic lesions by differential polymerase chain reaction. Int J Cancer. 1992;50:694-701. Antwerpen I, Gstrein L, Moskovszky L, et al. Primary urethral squamous cell carcinoma: a unique manifestation of a penile tumor. J Int Med Res. 2018;300060518813506. Cupp MR, Malek RS, Goellner JR, et al. Detection of human papillomavirus DNA in primary squamous cell carcinoma of the male urethra. Urology. 1996;48:551-555. Mohamed S, Fouad H, Balla B. Atypical evolution of squamous cell carcinoma of the male urethra: a rare case report. Saudi J Med Pharm Sci. 2017;3:1123-1127. The authors thank the following contributors to this project: James Elliott, MD (pathologist, Doctors Community Hospital, Lanham, MD) and Jonathan I. Epstein, MD (pathologist, The Johns Hopkins Hospital, Baltimore, MD) for diagnostic contributions. The authors have no conflict of interest to disclose. Vol. 21 No. 2/3 • 2019 • Reviews in Urology • 135