伴隨雙側鼠蹊淋巴結轉移之高風險 HPV 相關陰莖鱗狀細胞癌經部分陰莖切除合併輔助放射治療：病例報告

蘇一廷、陳建志

台灣基督長老教會馬偕醫療財團法人馬偕紀念醫院 泌尿科

High-Risk HPV-Related Penile Squamous Cell Carcinoma With Bilateral Inguinal Nodal Metastases Treated With Partial Penectomy and Adjuvant IMRT: A Case Report

Yi-Ting Su, Marcelo Chen

 Department of Urology, MacKay Memorial Hospital, Taipei, Taiwan

Case presentation:

A 53-year-old man with a history of end-stage renal disease (ESRD) on hemodialysis, hypertension, sicca syndrome, NK/T-cell lymphoma status post concurrent chemoradiotherapy, and colon adenocarcinoma in situ status post laparoscopic right hemicolectomy, presented with a 1-month history of bleeding from the preputial orifice. He also reported inability to retract the prepuce for 2 months. Physical examination revealed complete phimosis, bleeding from the preputial opening, and a firm, indurated glans. Bilateral, non-mobile inguinal lymph nodes measuring approximately 2 cm were palpable. Non-contrast MRI of the whole abdomen demonstrated a 1.8cm nodule in penile gland. Chest CT revealed no definite pulmonary metastasis.

On June 10, 2025, dorsal slit of the prepuce and biopsy of the glans lesion were performed. Intraoperatively, complete phimosis, a rough, irregular, reddened glans surface with oozing, and hard nodules at the left corpus cavernosum were noted. Histopathology of the glans biopsy showed carcinoma. Immunohistochemistry was positive for p40, GATA3, and diffusely and strongly positive for p16, supporting the diagnosis of HPV-related squamous cell carcinoma of the penis. On August 1, he underwent surgery with partial penectomy and bilateral inguinal lymph node excision. Intraoperatively, a penile mass involving the corpus cavernosum was palpated, and one immobile enlarged node measuring about 2 cm was excised from each inguinal region. Frozen-section examination of the penile margin showed no tumor involvement.

Final pathology of the partial penectomy specimen revealed a unifocal, moderately differentiated, HPV-related squamous cell carcinoma measuring 6.1×3.5×3.2cm. The tumor exhibited infiltrative deep borders and invaded the corpus cavernosum. Lymphovascular invasion and perineural invasion were present. All margins were free of tumor. Both the right and left inguinal lymph nodes were positive for metastatic carcinoma with extranodal extension.

Postoperatively, the patient was referred to radiation oncology, and adjuvant radiotherapy was recommended. An intensity-modulated radiotherapy (IMRT) plan was arranged to treat the bilateral inguinal regions, delivering 45 Gy in 25 fractions with a 0.5cm bolus, followed by a conedown boost of 14.4 Gy in 8 fractions to the high-risk inguinal nodal areas, for a total dose of 59.4 Gy.

Discussion:

Penile squamous cell carcinoma (SCC) is a rare malignancy, and human papillomavirus (HPV)-related tumors represent a distinct etiological and molecular subset. Recent European and international guidelines emphasize the central role of accurate staging—particularly of the regional lymph nodes—as lymph node status remains the most important prognostic factor for survival in penile cancer. [1] In the present case, the patient had a large HPV-related SCC of the penis with corpus cavernosum invasion (pT3) and bilateral inguinal nodal metastases with extranodal extension (pN3), placing him in a high-risk category with poor prognosis.

HPV–associated penile SCC represents a distinct molecular subset characterized by basaloid or warty histology and diffuse p16 overexpression [2], while HPV-independent tumors are usually of the keratinizing usual type and frequently show TP53 alterations and chronic inflammatory changes. [3]

Several recent systematic reviews and meta-analyses have shown that HPV- or p16-positive tumors are generally associated with improved disease-specific and disease-free survival, although the impact on overall survival is modest and heterogeneous across studies. In a meta-analysis including nearly 4000 patients, p16 positivity was associated with significantly better OS, DFS and DSS, whereas HPV DNA positivity mainly correlated with improved DSS and DFS but not OS, suggesting that HPV-negative penile cancers tend to behave more aggressively. [4] Nevertheless, current international guidelines still consider nodal stage and traditional histopathological risk factors as the key prognostic determinants, and HPV status alone is not yet used to guide treatment intensity. [2]

In summary, this case illustrates the current management of high-risk, HPV-related penile SCC with corpus cavernosum invasion and bilateral inguinal nodal metastases with extranodal extension in a medically complex patient on hemodialysis. Radical surgery with partial penectomy and bilateral inguinal lymphadenectomy followed by adjuvant IMRT to the inguinal nodal basins aligns with current international guideline recommendations for pN3 disease. Decisions regarding the addition of systemic therapy should be individualized in a multidisciplinary setting, taking into account comorbidities, renal function, and post-radiotherapy disease status on functional imaging.