Pathophysiology
Summary
Bladder cancer primarily manifests as either urothelial carcinoma or squamous cell carcinoma. The urothelium, the epithelial lining that extends from the renal pelvis to the urethra, is often the site of origin for urothelial carcinoma. This type of cancer can be multifocal and tends to appear anywhere along the urothelial tract. Histologically, urothelial cancer features hypercellularity, hyperchromasia, and loss of cellular polarity. Exposure to aromatic amines & beta-naphthylamine, common in industries like rubber and paint, increases the risk of developing urothelial carcinoma. Smoking and treatment with the alkylating agent cyclophosphamide are also risk factors.
In cases where transitional epithelium undergoes chronic inflammation, metaplastic changes to tougher squamous epithelium occur. Infections such as Schistosoma haematobium can cause chronic inflammation and are linked to squamous metaplasia. Both urothelial and squamous cell carcinomas typically present with painless hematuria, either gross or microscopic. Congenital disorders affecting the genitalia begin early in development.
A patent urachus forms when the allantois, a fetal structure connecting the yolk sac to the urogenital sinus, fails to involute completely. This results in an open conduit between the bladder and the umbilicus, causing urinary leakage from the umbilical area. Other congenital malformations include hypospadias and epispadias, which involve aberrant locations for the urethral opening. Hypospadias, the most common congenital penile disorder, arises from incomplete fusion of the urogenital folds and is often associated with cryptorchidism. Epispadias occurs due to abnormal positioning of the genital tubercle and is frequently linked to bladder exstrophy.
In the realm of penile pathology, squamous cell carcinoma is the most prevalent type of penile cancer. This malignancy is particularly common in developing countries and is associated with several risk factors such as high-risk HPV strains, HIV infection, poor hygiene, and smoking. Clinically, it manifests as a painless lesion typically appearing on the glans or foreskin in men over 60.
Carcinoma in situ (CIS) involves full thickness epithelial expansion of malignant cells without invasion of the basement membrane. Bowen disease presents with a crusting, oozing erythematous plaque on the shaft of the penis, and has ~5% chance of progression to squamous carcinoma. Erythroplasia of Queyrat presents as a velvety red lesion on the glans penis, and has a 10-30% chance of progression.
To conclude, Peyronie disease is an acquired condition characterized by excessive fibrosis in the tunica albuginea, leading to penile curvature and contracture. This disease may result in penile pain and erectile dysfunction.
Lesson Outline
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FAQs
Several risk factors are associated with the development of urothelial carcinoma. Occupational exposure to aromatic amines or beta-naphthylamine, commonly found in the rubber, plastic, dye, paint, and leather industries, increases the risk of urothelial carcinoma. Smoking is another significant risk factor. Additionally, treatment with the antineoplastic and immunosuppressant drug cyclophosphamide can also increase the risk of developing this type of cancer
Both urothelial and squamous cell carcinoma can occur along the urothelial tract and frequently present with painless hematuria. Urothelial carcinoma is often multifocal and is thought to arise due to the diffusion of carcinogens or metastases in the urine. On the other hand, squamous cell carcinoma is commonly linked to chronic inflammation, which leads to a metaplastic change from transitional to squamous epithelium. Infections such as Schistosoma haematobium and chronic UTIs are notable contributors to the development of squamous cell carcinoma.
Several factors contribute to the risk of developing penile squamous cell carcinoma. Infection with high-risk strains of human papillomavirus (HPV), particularly strains 16 and 18. HIV infection, poor genital hygiene, and a history of phimosis in uncircumcised males also increase the risk. Smoking is another contributing factor. The condition typically manifests in men over the age of 60 as a painless lesion on the glans or foreskin.
There are three main forms of penile carcinoma in situ: Bowen disease, Erythroplasia of Queyrat, and Bowenoid papulosis. Bowen disease typically presents as a crusting, oozing erythematous plaque on the shaft of the penis, with about 5% of cases progressing to squamous cell carcinoma. Erythroplasia of Queyrat manifests as a velvety red lesion on the glans penis, with 10-30% of cases progressing to invasive squamous carcinoma. In contrast, Bowenoid papulosis presents with multiple red papules on the penis and rarely progresses to carcinoma.
Hypospadias and epispadias are the most prevalent congenital penile disorders. Hypospadias features a urethral opening on the ventral surface of the penis and can lead to urinary outlet obstruction. It is associated with an increased incidence of cryptorchidism. Epispadias, on the other hand, has the urethral opening on the dorsal surface and is often linked to bladder exstrophy, a condition where the interior bladder mucosa is exposed. Both disorders result from developmental anomalies: hypospadias from incomplete fusion of the urogenital folds, and epispadias from abnormal positioning of the genital tubercle.
