Squamous cell carcinoma (SCC) of the renal pelvis is an uncommon histologic subtype of upper urinary tract cancer, accounting for approximately 0.5%–8% of renal pelvic malignancies, with reported incidence varying widely among studies and populations (1, 2). It typically arises in association with chronic irritation due to renal calculi, infection, or hydronephrosis, leading to squamous metaplasia and subsequent malignant transformation (1). Owing to its indolent onset and nonspecific symptoms, the disease is often diagnosed at an advanced stage and carries a poor prognosis. Penile metastasis is an exceptionally rare manifestation of disseminated malignancy and most frequently originates from genitourinary primaries such as prostate and bladder carcinoma (3). Penile involvement associated with renal pelvic SCC has not been previously described. Here, we report the first documented case of penile involvement most consistent with metastatic renal pelvic SCC and explore potential metastatic routes and pathological implications.

A 74-year-old man presented with a rapidly enlarging nodule on the right side of the glans penis that had developed over 4 months. He was referred to our institution with a presumptive diagnosis of primary penile carcinoma. Past medical history included hypothyroidism and appendectomy. Family history and psychosocial history were unremarkable or unavailable. On physical examination, a firm nodule was palpated in the right glans; no ulceration was evident, and no palpable inguinal lymphadenopathy was identified. Laboratory evaluation revealed an elevated SCC antigen (37.3 ng/mL). Magnetic resonance imaging (MRI) of the penis demonstrated a well-enhancing mass within the glans (Figures 1A, B). Contrast-enhanced computed tomography (CT) of the abdomen revealed a large left renal pelvic mass measuring 89 mm, with a renal stone, hepatic metastases, and hilar lymphadenopathy, without pelvic or inguinal lymphadenopathy (Figures 1C, D). Ureteroscopy confirmed a solid tumor occupying the left renal pelvis. A biopsy specimen was obtained from the renal pelvic lesion for histopathologic evaluation. A biopsy of the penile lesion was performed. Histopathological examination of both renal pelvic and penile lesions demonstrated keratinizing SCC (Figures 2A, B). Immunohistochemistry revealed p40 and p63 positivity, with PAX8 and p16 negativity (Figures 2C–G). Given the synchronous advanced renal pelvic SCC, concordant histology between both sites, and the absence of regional lymphadenopathy, the penile lesion was considered most consistent with metastatic involvement; however, a synchronous primary penile SCC cannot be completely excluded. A key diagnostic challenge was distinguishing metastatic involvement from a synchronous primary penile SCC. Because of the disseminated disease burden and rapid clinical decline, no surgical or systemic anticancer therapy was initiated, and best supportive care was provided. The patient’s condition rapidly declined, and he died 1 month after diagnosis. The overall clinical course is summarized in Figure 3.

Microscopic examination of both lesions revealed keratinizing SCC with intercellular bridges. Immunohistochemically, tumor cells expressed p40 and p63, confirming squamous differentiation (4), while PAX8 negativity excluded renal cell carcinoma (5). The lack of p16 expression indicated an HPV-independent pathogenesis (6); however, p16 is an imperfect surrogate marker, and HPV-independent primary penile SCC remains possible. Assessment of ureteral involvement was not feasible because histopathological evaluation was limited to biopsy specimens from the renal pelvic lesion.

Penile metastasis is a rare manifestation of disseminated malignancy (7–11). Reviews indicate that approximately 69% of penile metastases arise from genitourinary primaries, predominantly prostate (31%) and bladder (25%) cancers, followed by colorectal (13%) and renal (7%) origins (9–11). Renal pelvic SCC as a primary source of penile metastasis has not been previously documented. The main mechanism is retrograde venous dissemination through the pelvic venous plexus linking the dorsal penile vein to the prostatic and vesical venous systems (10, 12). Other possible routes include retrograde lymphatic spread, arterial dissemination, direct extension, and iatrogenic seeding (10, 13). In this case, the absence of pelvic or inguinal lymphadenopathy and the presence of hilar lymph node involvement suggest venous reflux as a plausible mechanism. Accordingly, we present a hypothetical venous route whereby tumor emboli travel from the renal vein → inferior vena cava → internal iliac → prostatic → dorsal penile venous plexus (Figure 4).

The strength of this report lies in the detailed pathological concordance between the renal pelvic and penile lesions and the imaging-based inference of a plausible metastatic route. However, this case has limitations, including the inability to completely exclude a synchronous primary penile carcinoma.

While p40/p63 expression reflects basal-type squamous differentiation, these markers are not site-specific and do not independently indicate metastatic potential. Therefore, their expression should be interpreted in conjunction with clinicopathological findings (4, 14). Loss of p16 expression distinguishes HPV-independent SCCs and supports chronic inflammation as the oncogenic driver (15). These molecular traits may explain the tumor’s unusual capacity for hematogenous spread to the penis.

We describe, to our knowledge, the first documented case of penile involvement most consistent with metastatic renal pelvic SCC. The case highlights a rare but plausible route of dissemination via retrograde venous spread. Understanding these mechanisms is essential for appropriate diagnostic consideration and palliative management of penile lesions in patients with advanced upper urinary tract SCC.