Understanding Urinary Tract Obstruction and Urolithiasis

Pathology of collective system of kidneys

Plan Urinary tract obstruction Tumors

Urinary Tract Obstruction Common cause of acute and chronic renal failure Terms: -obstructive uropathy -obstructive nephropathy -hydronephrosis

Urinary Tract Obstruction 20-35% prevalence among elderly men 3.8% (adults); 2.0% (children) postmortem examinations No gender difference until 20 years Women 20-60; Men > 60 Special considerations in pediatric patients

Etiology Types of obstruction: Mechanical blockage -intrinsic -extrinsic Function defects Congenital

Urolithiasis (Renal Calculi, Stones) Types of stones Calcium oxalate / phosphate (75%): due to hypercalciuria (idiopathic, 50%), hypercalcemia, hyperoxaluria (in vegetarians with oxalate rich diet), hyperuricosuria (hyperparathyroidism, bone disease, sarcoidosis) and rarely primary hyperoxaluria; are accompanied by foreign body giant cells and macrophages Struvite (triple stones, magnesium ammonium phosphate, 15%): due to urea splitting bacteria (Proteus, Staphylococcus); produce staghorn calculi Uric acid (6%): due to hyperuricemia, chemotherapy for leukemia, uricosuric drugs or excess dietary proteins; 50% lack elevated uric acid in blood / urine; may become staghorn calculi if in renal pelvis; elongated and rectangular crystals in collecting tubules or doubly refractile crystals in interstitium with giant cell reaction Cysteine (1%): due to genetic defects in cystine transport; autosomal recessive, affects 1 per 20,000; yellow-brown and radioopaque stones form at low urinary pH; crystals are flat hexagons in urine

Consequences of obstruction Reduced glomerular filtration rate Reduced renal blood flow (after initial rise) Impaired renal concentrating ability Impaired distal tubular function Renal salt wasting Renal tubular acidosis Impaired potassium concentration Postobstructive diuresis Progressive and permanent changes to the kidney occur Tubulointerstitial fibrosis Tubular atrophy and apoptosis Interstitial inflammation

Cystitis Cystitis A clinical diagnosis, usually with a triad of frequency, lower abdominal pain and dysuria (pain or burning during urination) There is usually no surgical specimen for acute cystitis, although it may be a finding in a specimen obtained for other purposes, or at autopsy Common in young women of reproductive age; also older men and women Most common bacterial agents are E. coli, Proteus, Klebsiella, Enterobacter The bladder may show no gross abnormalities Occasionally, the mucosa may be hyperemic with variable exudate

Squamous cell neoplasmsPure squamous cell carcinoma Verrucous carcinoma Squamous cell papilloma Urothelial tumors Glandular neoplasms Adenocarcinoma Enteric Mucinous Mixed Villous adenoma Urothelial carcinoma Infiltrating urothelial carcinoma Urothelial carcinoma with divergent differentiation With squamous differentiation With glandular differentiation With trophoblastic differentiation Urachal carcinoma Tumors of M llerian typeClear cell carcinoma Endometrioid carcinoma Nested urothelial carcinoma (including large nested variant) Microcystic urothelial carcinoma Neuroendocrine tumors Small cell neuroendocrine carcinoma Large cell neuroendocrine carcinoma Well differentiated neuroendocrine tumor Paraganglioma Micropapillary urothelial carcinoma Lymphoepithelioma-like urothelial carcinoma Plasmacytoid / signet ring / diffuse urothelial carcinoma Melanocytic tumors Malignant melanoma Nevus Melanosis Sarcomatoid urothelial carcinoma Giant cell urothelial carcinoma Poorly differentiated urothelial carcinoma Mesenchymal tumorsRhabdomyosarcoma Leiomyosarcoma Angiosarcoma Inflammatory myofibroblastic tumor Perivascular epithelioid cell tumor Benign Malignant Solitary fibrous tumor Leiomyoma Hemangioma Granular cell tumor Neurofibroma Lipid rich urothelial carcinoma Clear cell (glycogen rich) urothelial carcinoma Noninvasive urothelial lesions Urothelial carcinomain situ Noninvasive papillary urothelial carcinoma, low grade Noninvasive papillary urothelial carcinoma, high grade Papillary urothelial neoplasm of low malignant potential Urothelial papilloma Urothelial tract hematopoietic and lymphoid tumors Inverted urothelial papilloma Miscellaneous tumors Carcinoma of Skene, Cowper and Littre glands Metastatic tumors and tumors extending from other organs Epithelial tumors of the upper urinary tract Tumors arising in a bladder diverticulum Urothelial tumors of the urethra Urothelial proliferation of uncertain malignant potential Urothelial dysplasia

Benign tumors Urothelial papilloma Leiomyoma Hemangioma

Urothelial papilloma Papillary urothelial neoplasm characterized by delicate fibrovascular cores lined by urothelium of normal thickness and cytology Rare papillary urothelial neoplasm with a benign clinical course: rare recurrence if completely excised Exophytic tumor composed of thin papillary fronds lined by prominent umbrella cells

Leiomyoma Bladder leiomyomas are rare, accounting for 0.43% of all mesenchymal bladder tumor subtypes However, histopathologic analysis is required to confirm the diagnosis and exclude an underlying leiomyosarcoma. Excision is curative, with no risk of recurrence or spreading.

Hemangioma Vascular anomalies are common in children outside of the bladder but exceedingly rare within the bladder. Hemangiomas usually manifest as painless recurrent macroscopic hematuria. Histopathologically, the appearances of bladder hemangiomas are no different from those of hemangiomas identified elsewhere in the body. Usually solitary. Multiple bladder hemangiomas may be seen with Klippel-Trenaunay-Weber or Sturge-Weber syndrome. Even in the absence of a vascular malformation syndrome, cutaneous vascular malformations can be seen elsewhere in the body.

Borderline tumors Papillary Urothelial Neoplasm of Low Malignant Potential Epithelial lining of fibrovascular cores is thicker than normal urothelium No nuclear atypia or hyperchromatic nuclei in neoplastic urothelial cells Maybe exophytic papillary or endophytic papillary (inverted) Sympthom - Gross or microscopic hematuria

Malignant tumors Urothelial carcinoma in situ Infiltrating urothelial carcinoma Adenocarcinoma

Urothelial carcinoma in situ Flat lesion composed of cells in mid to upper epithelium with high cytologic grade By definition, no invasion into lamina propria Symptoms are similar to cystitis; hematuria is common 20 - 80% of CIS patients develop invasive disease if left untreated Often involves urothelium in other areas of GU tract Flat, grossly erythematous, granular or cobblestone mucosa No mass

Infiltrating urothelial carcinoma Urothelial carcinoma that has penetrated the basement membrane and invaded into the lamina propria or deeper Histologic characterization and depth of invasion are the most important factors for determining prognosis Urothelial carcinoma is morphologically heterogenous with many variants and subtypes Invasive urothelial carcinoma involving the lamina propria (T1) is often treated with conservative intravesical therapy and mucosal resection Invasive urothelial carcinoma involving the muscularis propria (T2) is often treated with radical cystectomy Fourth most common malignancy in men Eight most common malignancy associated with death in en Median age: 69 years in men and 71 years in women 4x higher in men than women Etiology: Tobacco smoking, Occupational exposures: aromatic amines, chlorinated hydrocarbons and polycyclic aromatic hydrocarbons including benzidine, Genetic predisposition

Urothelial Carcinomas of the Renal Pelvis

Adenocarcinoma Carcinoma derived from the urothelium and showing pure glandular differentiation Etiology: Chronic irritation of bladder - progression of extensive intestinal metaplasia (cystitis glandularis), exstrophy, diverticula, Schistosoma haematobium

Urachal Urachal adenocarcinoma adenocarcinoma Adenocarcinoma arising from the epithelium lined tubular structure known as urachus, an embryological derivative of the urogenital sinus and allantois that connects the bladder to the umbilicus The urachus lies in the space of Retzius, a space anterior to the peritoneum between the layers of umbilicovesical fascia (see Urachus) Involution usually happens before birth (by the fourth month of fetal life) and the urachus becomes a fibrous cord known as the median umbilical ligament In adults, it is usually 5 cm long and 6 mm broad Usually cystic lesion Treatment - Umbilectomy with partial cystectomy

BCG The Bacillus Calmette-Gu rin vaccine is used to protect against tuberculosis, but it can also be used as a therapy against bladder cancer BCG remains the most effective intravesical treatment for non-muscle-invasive bladder cancer Since the late 1970s, there has been evidence that instilling BCG into the bladder is an effective form of immunotherapy. While the mechanism is unclear, a local immune response appears to be triggered against the tumor. Immunotherapy with BCG prevents recurrences of superficial bladder cancer in up to 67% of cases. the vaccine is administered into the bladder itself through a catheter causes focal epithelial denudation with granulomatous inflammation of lamina propria