L11) Renal and urothelial neoplasms.PDF

Renal and urothelial neoplasms Prof. Dr. Dina Abdallah Professor of pathology Alexandria Faculty of medicine  Malignant Neoplasms The most common malignant neoplasm of the kidney is renal cell carcinoma ( 85% of renal cancers), followed in frequency by nephroblastoma (Wi...

Renal and urothelial neoplasms Prof. Dr. Dina Abdallah Professor of pathology Alexandria Faculty of medicine  Malignant Neoplasms The most common malignant neoplasm of the kidney is renal cell carcinoma ( 85% of renal cancers), followed in frequency by nephroblastoma (Wilms tumor) and by primary neoplasms of the calyces and pelvis. Renal Cell Carcinoma Origin; derived from the renal tubular epithelium, and hence they are located predominantly in the cortex. Incidence; These neoplasms represent 80% to 85% of all primary malignant neoplasms of the kidney and 2% to 3% of all cancers in adults.  Age and gender; fifth to seventh decades, men are affected about twice as women. Risk factors. - Environmental factors: smoking, hypertension, obesity, unopposed estrogen, and occupational exposure to petroleum, asbestos and cadmium. - Renal diseases: ESRD and CKD and acquired polycystic disease as a complication of chronic dialysis.  Clear Cell Carcinomas Clear cell carcinomas are the most common type of renal cell cancers (represent 65% of renal cell cancers) Although most are sporadic, they also occur in familial forms or in association with von Hippel-Lindau (VHL) disease; inherited as an autosomal dominant trait and is characterized by predisposition to a variety of neoplasms. The VHL gene also participates in the majority of sporadic clear cell carcinomas.  Gross, It arises anywhere in the cortex, as solitary large mass (spherical masses 3 to 15 cm) The cut surface is yellow to gray, white, with prominent areas of hemorrhage and necrosis. Tumor spread: Direct, to the calyces, pelvis, and ureter or to perinephric fat and adrenal gland. Hematogenous, it frequently invades the renal vein and grows as a solid column within this vessel, extending to the IVC and even into the right side of the heart. Microscopic features: Histologically, the tumor cells can be solid, trabecular, or tubular growths; individual cells are polygonal with abundant clear cytoplasm, and there is delicate vasculature.  Papillary Renal Cell Carcinomas Accounts for 10% to 15% of renal cell cancers and occurs in both familial and sporadic forms. The familial form is associated with mutations of the MET proto-oncogene. Gross, these neoplasms are frequently multifocal and bilateral and appear as early-stage tumors.  Microscopic, papillary growth pattern with fibrovascular cores.  Chromophobe Renal Carcinomas Constitutes 5% of renal cell cancers; they derive from CD intercalated cells. Although they exhibit multiple chromosome losses and extreme hypodiploidy, they have an excellent prognosis.  Clinical Features A triad of painless hematuria + a palpable abdominal mass + dull flank pain is characteristic. Macroscopic intermittent hematuria, superimposed on a steady microscopic hematuria, occurring in more than 50% of cases. Large tumors produce flank pain and a palpable mass. Extrarenal effects are fever and polycythemia, (5% to 10% of affected individuals) due to the production of erythropoietin by the cancer cells. Paraneoplastic syndrome: tumors produce other hormone-like substances, resulting in hypercalcemia (PTH) , hypertension (renin), Cushing syndrome (ACTH), or feminization or masculinization.  Wilms Tumor Wilms tumor, or nephroblastoma, is the most common primary tumor of the kidney in children. Age; most cases occurring in children between 2 and 5 years of age. Most (90%) of tumors are sporadic. Less than 10% of sporadic Wilms tumors are associated with WT1 mutations. WT1 gene is critical to normal renal and gonadal development; it is not surprising, therefore, that constitutional inactivation of one copy of this gene results in genitourinary abnormalities in humans.  Familial tumors related to germline mutations , occur in 5% to 10% of patients , the tumors in this group are associated with malformation syndromes, all involving chromosome 11p. Morphology: Wilms tumor typically is a large, solitary, well-circumscribed mass, although 10% are either bilateral or multicentric at the time of diagnosis. On cut section, the tumor is soft, homogeneous, and tan to gray, with occasional foci of hemorrhage, cystic degeneration, and necrosis.  Microscopic features, Wilms tumors are characterized by recognizable attempts to recapitulate stages of nephrogenesis. Triphasic histologic features: (1) Blastema → Sheets of small blue cells Note: blastema is primitive renal tissue (2) Immature stroma → fibrotic or myxoid and (3) Epithelial cell types in abortive tubules or glomeruli. Histologic anaplasia (approximately 5% of tumors are anaplastic Wilms tumor) is associated with a worse prognosis & very resistant to treatment. Clinical presentations: A palpable abdominal mass, across the midline and down into the pelvis. Fever, abdominal pain, hematuria, or intestinal obstruction by compression. Prognosis: Very good, and excellent results are obtained with a combination of nephrectomy and chemotherapy. Anaplasia is a harbinger of adverse prognosis, but only if it is diffuse.  Neoplasms of the urinary tract Bladder cancer accounts for approximately 5% of cancers and 3% of cancer deaths in the United States. Most bladder cancers are urothelial carcinomas followed by squamous cell carcinomas (which are much more common in countries such as Egypt, where urinary schistosomiasis is endemic). Adenocarcinomas of the bladder are rare. Age and gender; male to female ratio of 3:1, about 80% of patients are between 50 and 80 years of age.  Risk factors: - Cigarette smoking - Various occupational carcinogens. - Schistosoma haematobium infections (70% will be squamous cell carcinoma), causing chronic inflammatory response and metaplastic changes to ova within the bladder wall. - Chronic analgesic use. Changes include: a) Brunn nests; cell nest grow downward into the lamina propria, b) cystitis glandularis c) cystitis cystica cystic spaces filled with clear fluid lined by flattened urothelium d) intestinal metaplasia, glands with goblet cells. e) squamous metaplasia, as a response to injury, the urothelium.  Urothelial malignancy ranges from papillary (start low grade) to nodular or flat (start high grade). Most papillary lesions are low grade (