Recurrence in patients with penile carcinoma occurs in about one third of cases, usually due to insufficient surgery or positive resection margins. An evaluation of surgical resection margins in penectomy specimens was performed to determine precise anatomic sites of tumor involvement, hoping to advance knowledge concerning the local routes of spread of penile carcinomas. A pathologic study of 80 partial penectomies revealed 14 positive margins. Margins were examined after their separation from the main specimen as follows: 1) proximal urethra and surrounding tissues consisting of urethral epithelium with Litree glands, lamina propria, corpus spongiosum, and penile fascia (periurethral cylinder); 2) proximal shaft with corresponding corpora cavernosa separated and surrounded by the tunica albuginea and penile fascia; and 3) skin of shaft with underlying corporal dartos. In 9 patients, only one site was involved by carcinoma, and in 5 there were multiple contiguous sites (for a total of 20 anatomic sites). The distribution of the various sites involved by carcinoma was as follows: urethral epithelium, 4 cases (2 in situ and 2 invasive carcinomas including intraluminal spread); lamina propria, 5 cases; corpus spongiosum, 3 cases; penile fascia, 6 cases; and corpora cavernosa and skin, 1 case each. One of the in situ lesions was discontinuous with the main glans tumor, and the other one was continuous with it. The penile fascia was the most commonly involved site followed by the urethral lamina propria and epithelium. Dissemination to outer skin, corpora cavernosa, and corpus spongiosum was less frequent. The highly vascularized and innervated loose connective tissue of the penile fascia appears to facilitate tumor spread. The urethra is either a pathway for in situ tumor progression from glans to urethra or part of a field prone to malignant transformation. The infrequent involvement of corpora cavernosa is probably due to the tunica albuginea acting as a barrier preventing tumor spread. Based on these observations and the examination of hundreds of penectomy specimens, we are proposing five probable routes of local spread for penile cancer: 1) horizontal and superficially spreading from one epithelial mucosal compartment (glans, coronal sulcus, and foreskin) to the other; 2) following the penile fascia; 3) through spaces created by feeding vessels in the tunica albuginea; 4) vertical spreading involving step-by-step different penile anatomic compartments; and 5) along the urethral epithelium.

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