The penis consists of three separate cylindrical structures and originates from the genital tubercle at the cranial end of the cloacal membrane in utero. Normal development is under the direct control of androgenic hormonal stimulation. The penis is composed of three parts: the shaft/body, anterior (glans, corona, foreskin) and posterior (perineal attachments). The corpora cavernosa join beneath the pubis to form the major portion of the body of the penis. These two cylinders of the penis are separated by a septum which allows the vascular spaces to freely communicate. They are enclosed by the tough tunica albuginea, which is predominantly collagenous and meets distally to separate the heads of the copora cavernosa from the corpus spongiosum of the glans. It completely encases the copora cavernosa and appears to constitute an important biological barrier to the dissemination of PeScc (Velazquez et al. 2004; Leijte et al. 2008; Heyns, Mendoza-Valdes, and Pompeo 2010).
The corpus spongiosum tapers and runs on the underside of the corpora cavernosa and then expands to cap them as the glans penis. The corona separates the base of the glans from the shaft of the penis. The spongiosum is traversed throughout its length by the anterior urethra, which begins at the perineal membrane. Proximally, it is lined by stratified and pseudostratified columnar epithelium, distally by stratified squamous epithelium. The mucus-secreting glands may be seen as small outpouchings of the mucosa.
Buck's fascia surrounds both cavernosal bodies dorsally and splits to surround the spongiosum ventrally. This important layer can clearly be defined on MRI and provides crucial information for surgeons pre-operatively, when planning
University College London 67 conservative surgical techniques (Kayes et al. 2007). In the perineum, Buck's fascia
fuses with the tunica albuginea deep to the muscles of the erectile bodies. Distally, it fuses with the base of the glans at the corona.
The skin of the penile shaft is highly elastic and without appendages (hair or glandular elements), except for the smegma-producing glands at the base of the corona. Distally, it folds over the glans as the foreskin (double-membrane) and attaches firmly below the corona. Its blood supply is independent of the erectile bodies and is derived from the external pudendal branches of the femoral vessels. These vessels enter the base of the penis to run longitudinally in the dartos fascia as a richly anastomotic network. The skin of the glans is immobile as a result of its direct attachment to the underlying, thin tunica albuginea (Heitz, Pottek, and Schreiter 1998; Velazquez et al. 2003).
A rich network of lymphatics of the glans and the copora cavernosa courses along the dorsal vein to the symphysis pubis and drains into superficial and deep inguinal lymph nodes which are anatomically separated by the deep fascia of the thigh (fascia lata). The superficial group of nodes (12 to 15 nodes) are situated in the deep membranous layer of the superficial fascia of the thigh (Camper's fascia). The sentinel lymph node group (1 to 3 nodes) can be identified by their anatomical location at the anterior or medial aspect of the superficial epigastric vein (Cabanas 1977; Cabanas 2000). The node of Cloquet is the most cephalad of the deep group and is situated within the femoral canal (Shen et al. 2000). The external iliac lymph nodes receive drainage from the deep inguinal, obturator, and hypogastric groups. In turn, drainage progresses to the common iliac and para-aortic nodes. The earliest route of dissemination in penile carcinoma is to loco-regional lymphatics. Penile carcinomas
University College London 68 have a predictable pattern of local, regional and systemic spread (Cabanas 1992;
Horenblas et al. 1993). Locally invasive tumours initially penetrate the lamina propria, supeficial dartos or superficial corpus spongiosum layers (Figure 1.8). Later invasion involves deep corpus spongiosum, tunica albuginea, corpora cavernosa and preputial skin (Figure 1.9). Urethral invasion is not unusual in early or late stages depending on the site of origin of the initial tumour. Advanced tumour with local tissue destruction often represent higher staged and aggressive disease states (Figure 1.10), Intrapenile satellitosis (nodules of carcinoma separated from the main tumour mass) is a late phenomenon related to aggressive tumour behaviour (Velazquez et al. 2005).
University College London 69 Figure 1.7
University College London 70 Figure 1.8
University College London 71 Figure 1.9
University College London 72 Subsequently, loco-regional involvement occurs in a step-wise fashion, involving
initially the superficial inguinal nodes before spread occurs to the deeper inguinal layer and finally onto pelvic and distant sites. It is extremely rare to observe disease ‘skipping’ nodal stations. The presence of lymphatic metastases strongly impacts on prognosis.
Patients with locally controlled disease have five year overall survival rates of greater than 90%; decreasing dramatically to approximately 30-50% if lymph node positive. There is a striking deterioration in survival outcomes with the increasing number of nodes involved and also the level of nodal involvement. Currently, 5 year survival is 0-38% from pelvic metastases in published series (Ravi 1993; Ornellas et al. 2008).
It has been shown that early lymph node clearance compared to delayed/therapeutic dissection, conveys a clear survival advantage (Kroon et al. 2005a; McDougal 2005). However, patient selection is notoriously difficult, as current staging techniques lack the required accuracy (section 1.5.3). Additionally, radical regional lymph node dissection carries high rates of mortality (3%) and morbidity (50-90%) (Horenblas et al. 1993; Pizzocaro, Piva, and Nicolai 1996; Sanchez-Ortiz and Pettaway 2004). Complications encountered may include: wound infections, wound dehiscence, flap necrosis, disabling lymphoedema and seroma formation.
This clinical paradigm highlights the current limitations that clinicians and scientists face when treating men with PeScc. Novel management algorithms should aim to stratify patients appropriately to: (i) surveillance programmes, (ii) aggressive surgical protocols and (iii) adjuvant chemotherapeutic treatments. It is important that novel biomarkers accurately reflect the biological status of the disease and predict disease
University College London 73 progression for high risk patients. Overall, future discoveries should ultimately
minimise unnecessary co-morbidity and impairment to the patient’s quality of life whilst improving overall survival.