Urinary Tract Tumors

Here we'll learn about urinary tract tumors. Accounts for approximately 90% of all primary renal neoplasms. Tumors arise from tubule epithelial cells in the renal cortex; they tend to occur at the renal poles, and can range from 1 cm to several times the size of the kidney. Renal cell carcinoma is often asymptomatic until it reaches an advanced stage, at which point patients may present with hematuria, abdominal masses and pain, weight loss, and anemia. Another sign to look for is a non-reducing right-sided varicocele, which is an enlargement of the veins that drain the testis. Varicoceles are caused by right renal vein occlusion, which drains the right testicular venous system. Paraneoplastic disease, including hypertension, hypercalcemia, and polycythemia, develops in a minority of patients. We need to look for metastases, particularly in the lung, liver, brain, and bone. Be aware that renal cell carcinoma can trigger thrombus formation in the renal vein or inferior vena cava and disseminate hematogenously.

• Acquired polycystic kidneys (i.e., in dialysis patients), cigarette smoking, hypertension, diabetes, chronic analgesic use, and exposure to various chemicals, particularly trichloroethylene.
• Genes associated with renal cell carcinoma include VHL and PBRM-1; both are tumor suppressor genes located on chromosome 3.
• Black men in their 60's and 70's are at higher risk of renal cell carcinoma.

Patients with the familial syndrome Von Hippel Lindau have an increased risk of renal cell carcinoma

• Von Hippel Lindau is an autosomal dominant disorder characterized by the growth of cysts and tumors in the kidneys, CNS, retina, reproductive organs, pancreas, and adrenal glands.

The most common subtype of renal cell carcinoma is clear-cell renal cell carcinoma, followed by the papillary and chromophobe subtypes. Clear-cell renal cell carcinoma is characterized by strands of fibrosis weaving among collections of polygonal clear cells filled with lipids and carbohydrates, which give the tumor a yellowish color. Diagnosis: We can diagnose renal cell carcinoma with contrast CT or MIR; Treatments: include partial or radical nephrectomy with possible chemotherapy. Research currently focuses on immune-checkpoint therapies, because renal cell cancer cells induce apoptosis of cytotoxic lymphocytes. Bladder cancer is the most common neoplasm of the upper urinary tract and the 7th most common cancer worldwide. It is most often diagnosed in males over 60 years old. Hematuria, dysuria, and burning while urinating. We also need to watch for urinary tract obstructions that can lead to hydronephrosis and infection. Unfortunately, bladder cancer commonly reoccurs. We need to watch for metastasis, particularly to the lymph nodes, lungs, liver, and bone. Diagnosis: We can use cystoscopy, imaging, and biopsy to diagnose bladder cancer. Treatments Depend on how invasive the cancer is: If there is no muscularis invasion, we can use endoscopic resection intravesical therapy. If the muscularis has been invaded, we need to perform cystectomy, possibly with chemotherapy. Urothelial cell carcinoma is the most common form of bladder cancer (formerly called transitional cell carcinoma), which accounts for approximately 90% of all bladder cancers. This form of cancer can affect any of the structures lined by urothelial cells: the urethra, bladder, ureters, and renal pelvis. The mucosal layer lines these structures and comprises transitional cells and lamina propria; carcinoma originates in the transitional cells. Lesions can be papillary or flat, and start out in the mucosa, but can invade deeper tissues. Key risk factors include smoking, exposure to paint, petroleum, and certain dyes; urothelial cell carcinoma is also associated with Lynch syndrome (aka hereditary nonpolyposis colorectal cancer). Squamous cell bladder carcinoma is less common than urothelial cell cancer; in these patients, chronic bladder irritation or infection triggers transitional cell transformation to squamous cells. A key risk factor is infection with schistosomiasis. Common, benign neoplasms that are most often found in patients over 50 years old. We often see these tumors in Birt-Hogg-Dubé syndrome (BHD is a genetic condition that primarily effects the skin, but also predisposes to benign tumors in the lungs and kidneys). On gross inspection, we'll see a mahogany-brown mass with a central stellate star; Histologically, these tumors are characterized by nests of cells with prominent nucleoli and eosinophilic cytoplasm. Patients have excellent prognosis, but we can remove the tumors to prevent metastasis to the liver and bone. Papillary adenomas are another common benign neoplasm; they are often seen in older patients with end-stage renal disease. The most common renal cancer in children ages 2-4; they are the most common pediatric cancer overall. A large, palpable flank mass, hematuria, and hypertension. Prognosis depends in part on the histopathology:

• "Favorable" histology is characterized by embryonic glomerular structures with blastema, epithelial tubules, and mesenchyme (stroma).
• "Unfavorable" histology is characterized by more anaplasia; we'll see hyperchromatic, enlarged pleomorphic nuclei with abnormal mitotic figures.

Nephroblastomas are associated with several childhood syndromes caused by mutations on chromosome 11, including:

• WAGR complex (Wilms tumor, Aniridia, Genitourinary malformation, Range of developmental delays; WT1 deletion)

• Denys-Drash syndrome (Wilms tumor, diffuse mesangial sclerosis, male pseudohermaphroditism.; WTI mutation)

• Beckwith-Wiedemann syndrome (Wilms tumor, macroglossia, organomegaly, hemihyperplasia, omphalocele; alterations in genes that control body growth on chromosome 11).

With favorable histology, prognosis is good; treatment includes surgery and radiation therapy.