Penile cancer always starts on the glans or the inner fold of the prepuce. It begins as a precursor (differentiated or undifferentiated PeIN) developing as a clinical tumor infiltrating through the basal membrane and into the lamina propria, corpus spongiosum and possibly corpus cavernosum. When both glans and prepuce are affected, it may be difficult to determine where the cancer originates from. Type of tumor and grade of malignancy decide the growth and risk of proliferation.
If left untreated, penile cancer destroys the glans and the prepuce, invades the corpus spongiosum and corpora cavernosa, and may destroy the entire penis. Buck's fascia serves as a barrier in the beginning, but eventually the tumor will invade the corpora cavernosa.
Penile cancer spreads lymphatically to lymph nodes in the groin in all stages (also cis), but most commonly, invading cancer exists before metastasizing. Penile cancer can also cause hematogenous metastasis, but this is atypical and occurs rarely.
Typically, spreading occurs to the lymph nodes in the groin, where the cancer can establish a large metastatic tumor before spreading further lymphatically to the intrapelvic lymph nodes. Dissemination can then stop before further spreading. This is therapeutically very important to be aware of.
Metastasis is observed in the lungs and liver, but also occurs in the bone, brain, and skin.
Primary tumors in the urethra, prostate, bladder, and rectum can metastasize to the penis.