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Urinary system outflow obstruction and urinary

system tumors

Doç. Dr. Işın Doğan Ekici

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URINARY OUTFLOW OBSTRUCTION

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Renal Stones

Urolithiasis is calculus formation at any level in the urinary collecting system, but most often the calculi arise in the kidney.

They occur frequently, as is evidenced by the finding of stones in about 1% of all autopsies.

Symptomatic urolithiasis is more common in men than in women.

A familial tendency toward stone formation has long been recognized.

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Pathogenesis

About 80% of renal stones are composed of either calcium oxalate or calcium oxalate mixed with calcium phosphate.

Another 10% are composed of magnesium ammonium phosphate, and 6% to 9% are either uric acid or cystine stones.

In all cases, there is an organic matrix of mucoprotein that makes up about 2.5% of the stone by weight

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The cause of stone formation is often obscure, particularly in the case of calcium-containing stones.

Probably involved is a confluence of predisposing conditions.

The most important cause is increased urine concentration of the stone's constituents, so that it exceeds their solubility in urine (supersaturation).

Pathogenesis

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50% of patients who develop calcium stones have hypercalciuria that is not associated with hypercalcemia.

Most in this group absorb calcium from the gut in excessive amounts (absorptive hypercalciuria) and promptly excrete it in the urine, and some have a primary renal defect of calcium reabsorption (renal hypercalciuria).

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In 5% to 10% of persons with this diagnosis there is hypercalcemia (due to hyperparathyroidism, vitamin D intoxication, or sarcoidosis) and consequent hypercalciuria.

In 20% of this subgroup, there is excessive excretion of uric acid in the urine, which favors calcium stone formation; presumably the urates provide a nidus for calcium deposition.

In 5% there is hyperoxaluria or hypercitraturia, and in the remainder there is no known metabolic abnormality. A high urine pH favors crystallization of calcium phosphate and stone formation.

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The causes of the other types of renal stones are better understood. Magnesium ammonium phosphate (struvite) stones almost always occur in persons with a persistently alkaline urine due to UTIs.

In particular, the urea-splitting bacteria, such as Proteus vulgaris and the staphylococci, predispose the person to urolithiasis.

Moreover, bacteria may serve as particulate nidi for the formation of any kind of stone. In avitaminosis A, desquamated cells from the metaplastic epithelium of the collecting system act as nidi.

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• Gout and diseases involving rapid cell turnover, such as the leukemias, lead to high uric acid levels in the urine and the possibility of uric acid stones.

• About half of the individuals with uric acid stones, however, have neither hyperuricemia nor increased urine urate but an unexplained tendency to excrete a persistently acid urine (under pH 5.5).

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• This low pH favors uric acid stone formation-in contrast to the high pH that favors formation of stones containing calcium phosphate.

• Cystine stones are almost invariably associated with a genetically determined defect in the renal transport of certain amino acids, including cystine.

• In contrast to magnesium ammonium phosphate stones, both uric acid and cystine stones are more likely to form when the urine is relatively acidic.

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Urolithiasis may also result from the lack of substances that normally inhibit mineral precipitation. Inhibitors of crystal formation in urine include Tamm-Horsfall protein, osteopontin, pyrophosphate, mucopolysaccharides, diphosphonates, and a glycoprotein called nephrocalcin, but no deficiency of any of these substances has been consistently demonstrated in individuals with urolithiasis.

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Morphology Stones are unilateral in about 80% of patients.

Common sites of formation are renal pelves and calyces and the bladder.

Often, many stones are found in one kidney. They tend to be small (average diameter 2-3 mm) and may be smooth or jagged.

Occasionally, progressive accretion of salts leads to the development of branching structures known as staghorn calculi, which create a cast of the renal pelvis and calyceal system. These massive stones are usually composed of magnesium ammonium phosphate.

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Stones may be present without producing either symptoms or significant renal damage.

This is particularly true with large stones lodged in the renal pelvis.

Smaller stones may pass into the ureter, producing a typical intense pain known as renal or ureteral colic, characterized by paroxysms of flank pain radiating toward the groin.

Often at this time there is gross hematuria. The clinical significance of stones lies in their capacity to obstruct

urine flow or to produce sufficient trauma to cause ulceration and bleeding. In either case, they predispose the sufferer to bacterial infection. Fortunately, in most cases the diagnosis is readily made radiologically.

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Hydronephrosis

Hydronephrosis refers to dilation of the renal pelvis and calyces, with accompanying atrophy of the parenchyma, caused by obstruction to the outflow of urine.

The obstruction may be sudden or insidious, and it may occur at any level of the urinary tract, from the urethra to the renal pelvis.

The most common causes are as follows

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Congenital: Atresia of the urethra, valve formations in either ureter or urethra, aberrant renal artery compressing the ureter, renal ptosis with torsion, or kinking of the ureter

Acquired: Foreign bodies: Calculi, necrotic papillae Tumors: Benign prostatic hyperplasia, carcinoma of the prostate,

bladder tumors (papilloma and carcinoma), contiguous malignant disease (retroperitoneal lymphoma, carcinoma of the cervix or uterus)

Inflammation: Prostatitis, ureteritis, urethritis, retroperitoneal fibrosis

Neurogenic: Spinal cord damage with paralysis of the bladder Normal pregnancy: Mild and reversible

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Bilateral hydronephrosis occurs only when the obstruction is below the level of the ureters.

If blockage is at the ureters or above, the lesion is unilateral.

Sometimes obstruction is complete, allowing no urine to pass; usually it is only partial.

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Pathogenesis Even with complete obstruction, glomerular filtration persists for

some time, and the filtrate subsequently diffuses back into the renal interstitium and perirenal spaces, whence it ultimately returns to the lymphatic and venous systems.

Because of the continued filtration, the affected calyces and pelvis become dilated, often markedly so.

The unusually high pressure thus generated in the renal pelvis, as well as that transmitted back through the collecting ducts, causes compression of the renal vasculature.

Both arterial insufficiency and venous stasis result, although the latter is probably more important.

The most severe effects are seen in the papillae, because they are subjected to the greatest increases in pressure.

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Accordingly, the initial functional disturbances are largely tubular, manifested primarily by impaired concentrating ability.

Only later does glomerular filtration begin to diminish. Experimental studies indicate that serious irreversible damage

occurs in about 3 weeks with complete obstruction, and in 3 months with incomplete obstruction.

However, functional impairment can be demonstrated only a few hours after ureteral ligation.

The obstruction also triggers an interstitial inflammatory reaction, leading eventually to interstitial fibrosis.

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Morphology Bilateral hydronephrosis (as well as unilateral hydronephrosis

when the other kidney is already damaged or absent) leads to renal failure, and the onset of uremia tends to abort the natural course of the lesion.

In contrast, unilateral involvements display the full range of morphologic changes, which vary with the degree and speed of obstruction.

With subtotal or intermittent obstruction, the kidney may be massively enlarged (lengths in the range of 20 cm), and the organ may consist almost entirely of the greatly distended pelvicalyceal system.

The renal parenchyma itself is compressed and atrophied, with obliteration of the papillae and flattening of the pyramids.

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On the other hand, when obstruction is sudden and complete, glomerular filtration is compromised relatively early, and as a consequence, renal function may cease while dilation is still comparatively slight.

Depending on the level of the obstruction, one or both ureters may also be dilated (hydroureter).

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Microscopically the early lesions show tubular dilation, followed by atrophy and fibrous replacement of the tubular epithelium with relative sparing of the glomeruli.

Eventually, in severe cases the glomeruli also become atrophic and disappear, converting the entire kidney into a thin shell of fibrous tissue.

With sudden and complete obstruction, there may be coagulative necrosis of the renal papillae, similar to the changes of papillary necrosis.

In uncomplicated cases the accompanying inflammatory reaction is minimal.

Complicating pyelonephritis, however, is common

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Bilateral complete obstruction produces anuria, which is soon brought to medical attention. When the obstruction is below the bladder, the dominant symptoms are those of bladder distention.

Paradoxically, incomplete bilateral obstruction causes polyuria rather than oliguria, as a result of defects in tubular concentrating mechanisms, and this may obscure the true nature of the disturbance.

Unfortunately, unilateral hydronephrosis may remain completely silent for long periods unless the other kidney is for some reason not functioning.

Often the enlarged kidney is discovered on routine physical examination. Sometimes the basic cause of the hydronephrosis, such as renal calculi or an obstructing tumor, produces symptoms that indirectly draw attention to the hydronephrosis. Removal of obstruction within a few weeks usually permits full return of function; however, with time the changes become irreversible.

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Hydroureter

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Bladder and urethra-non-neoplastic diseases

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CYSTITIS Infection with enteric bacteria Women > men (short urethra!) Predisposing factors

Pregnancy Calculi Medical procedures (catheter) Diabetes Chemotherapy Tumors

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Risk Factor of Cystitis

(FIVE Cs)

Coitus related (including pregnancy)

Calculi

Catheter

Cancer

Chemotherapy

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Forms of Cystitis

Acute – bacterial

Chronic – bacterial

Chronic interstital – unknown etiology (women)

Malakoplakia – E. coli + macrophages

Iatrogenic

-Cystitis is usually of bacterial origin, and has the same story as common pyelonephritis, which it precedes.

-Urosepsis still kills many adults of both sexes.

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Pathology of Cystitis

Neutrophils abound in the acute phase. In longstanding disease, there is a chronic inflammatory infiltrate and

there may be much fibrosis. Polypoid cystitis is not a tumor at all, but a reactive overgrowth

(collagen and/or extra ground substance) in response to ongoing inflammation.

S. hematobium : Squamous metaplasia in endemic areas usually results from infestation with S. hematobium. The bladder can be ruined by all the eggs in the muscularis

propria.

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Chemotherapy cystitis results from cyclophosphamide ("Cytoxan") or busulfan ("Myleran") administration, and radiation to the pelvic area can also produce a vicious cystitis. Giant cell cystitis" is a non-disease, merely describing the

presence of giant cells in patients who have had radiation or chemotherapy.

Hunner's interstitial / ulcerative cystitis is a poorly-understood process in which all three layers of the bladder become chronically inflamed.

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Acute cystitis

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Malakoplakia is a curious macrophage-rich response to E.coli/Proteus infections. The cells seem to have some problem

phagocytizing the bacteria. Grossly, soft ("malakos" in Greek) yellow

plaques. Microscopy: foamy, lipid-laden (von

Hensemann's) macrophages with calcified spherules (Michaelis-Gutmann bodies).

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Malakoplakia

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URETHRA

Posterior stricture: Males Often congenital

Urethral caruncle: Female Near the opening of the urethra Begins with plugging of the ducts of the glands Mixed inflammation of the lamina propria, and often with

pseudoepitheliomatous hyperplasia of the overlying squamous epithelium

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Urethral caruncule

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Urinary tract tumors

Renal Tumors

Urothelial Tumors

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Renal Tumors of Childhood Nephroblastic tumors:

● Nephroblastoma     ● Favorable histology     ● Unfavorable histology (diffuse / focal anaplasia)● Nephrogenic rests and nephroblastomatosis● Cystic nephroma and cystic partially differentiated nephroblastoma● Metanephric tumors     ● Metanephric adenoma     ● Metanephric adenofibroma     ● Metanephric stromal tumor

Mesoblastic nephroma:

● Clear cell carcinoma● Rhabdoid tumor of kidney

● Renal epithelial tumors of childhood:● Papillary renal cell carcinoma● Renal medullary carcinoma● Translocation associated RCC (Xp11.2 / t(6;11) translocations)

Rare tumors:● Ossifying renal tumor of infancy● Angiomyolipoma

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Renal tumors of Adult ● Renal cell carcinoma

● Renal cortical adenoma

Metanephric tumors:● Metanephric adenoma● Metanephric adenofibroma● Metanephric stromal tumor● Metanephric adenosarcoma

● Oncocytoma

Rare tumors with epithelial / parenchymal differentiation:● Carcinoid tumor● Small cell carcinoma● Primitive neuroectodermal tumor● Juxtaglomerular cell tumor● Teratoma● Nephroblastoma and other “pediatric” renal tumors● Multilocular cyst (cystic nephroma)● Mixed epithelial and stromal tumor● Spiradenocylindroma

Mesenchymal tumors:● Angiomyolipoma● Epithelioid angiomyolipoma● Medullary fibroma● Leiomyoma.......

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Many types of benign and malignant tumors occur in the urinary tract.

In general, benign tumors such as small (<0.5 cm) cortical papillary adenomas or medullary fibromas (interstitial cell tumors) have no clinical significance.

The most common malignant tumor of the kidney is renal cell carcinoma, followed in frequency by nephroblastoma (Wilms tumor) and by primary tumors of the calyces and pelvis.

Other types of renal cancer are rare and need not be discussed here.

Tumors of the lower urinary tract are about twice as common as renal cell carcinomas.

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Oncocytoma

● 4-7% of adult renal epithelial tumors● Adults age 50+; 2/3 men; usually incidental● May co-exist with renal cell carcinoma● Rarely associated with renal failure due to multiple

tumors or large bilateral tumor.Macroscopy: Well defined borders, mahogany brown

tumor with stellate central fibrous scarMicro: Benign tumor of uniform round / polygonal cells

with abundant, intensely eosinophilic and granular cytoplasm with uniform small, round and central nuclei with evenly dispersed chromatin.

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Renal Cell Carcinoma These tumors are derived from the renal tubular epithelium, and

hence they are located predominantly in the cortex. Renal carcinomas represent 80% to 85% of all primary malignant

tumors of the kidney, and 2% to 3% of all cancers in adults. This translates into about 30,000 cases per year; 40% of patients die

of the disease. Carcinomas of the kidney are most common from the sixth to seventh decades, and men are affected about twice as commonly as women.

The risk of developing these tumors is higher in smokers, hypertensive or obese patients, and those who have had occupational exposure to cadmium.

Smokers who are exposed to cadmium have a particularly high incidence of renal cell carcinomas.

The risk of developing renal cell cancer is increased 30-fold in individuals who develop acquired polycystic disease as a complication of chronic dialysis.

The role of genetic factors in the causation of these cancers is discussed below.

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Renal cell cancers were formerly classified on the basis of morphology and growth patterns.

However, recent advances in the understanding of the genetic basis of renal carcinomas have led to a new classification based on the molecular origins of these tumors.

The three most common forms are as follows:

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Clear cell carcinomas These are the most common type, accounting for 70% to 80% of

renal cell cancers. Histologically, they are made up of cells with clear or granular cytoplasm.

Whereas the majority of them are sporadic, they also occur in familial forms or in association with von Hippel-Lindau (VHL) disease.

It is the study of VHL disease that has provided molecular insights into the causation of clear cell carcinomas.

VHL disease is autosomal dominant and is characterized by predisposition to a variety of neoplasms, but particularly to hemangioblastomas of the cerebellum and retina.

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Hundreds of bilateral renal cysts and bilateral, often multiple, clear cell carcinomas develop in 40% to 60% of individuals.

Those with VHL syndrome inherit a germ-line mutation of the VHL gene on chromosome 3p25 and lose the second allele by somatic mutation.

Thus, the loss of both copies of this tumor suppressor gene gives rise to clear cell carcinoma.

The VHL gene is also involved in the majority of sporadic clear cell carcinomas.

Cytogenetic abnormalities giving rise to loss of chromosomal segment 3p14 to 3p26 are often seen in sporadic renal cell cancers.

This region harbors the VHL gene (3p25.3).

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The second, nondeleted allele is inactivated by a somatic mutation or hypermethylation in 60% of sporadic cases.

Thus, homozygous loss of the VHL gene seems to be the common underlying molecular abnormality in both sporadic and familial forms of clear cell carcinomas.

The VHL protein is involved in limiting the angiogenic response to hypoxia; thus, its absence may lead to increased angiogenesis and tumor growth.

An uncommon familial form of clear cell carcinoma unrelated to VHL disease also involves cytogenetic abnormalities involving chromosome 3p.

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Papillary Renal Cell Carcinomas These comprise 10% to 15% of all renal cancers. As the name

indicates, they show a papillary growth pattern. These tumors are frequently multifocal and bilateral and appear

as early-stage tumors. Like clear cell carcinomas they occur in familial and sporadic

forms, but unlike these tumors, papillary renal cancers have no abnormality of chromosome 3.

The culprit in the case of papillary renal cell cancers is the MET proto-oncogene, located on chromosome 7q31.

The MET gene is a tyrosine kinase receptor for the growth factor called hepatocyte growth factor.

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It is an increased gene dosage of the MET gene due to duplications of chromosome 7 that seems to spur abnormal growth in the proximal tubular epithelial cell precursors of papillary carcinomas.

In keeping with this, trisomy of chromosome 7 is seen commonly in the familial cases.

In these individuals, along with increased gene dosage there are activating mutations of the MET gene.

By contrast, in sporadic cases there is duplication or trisomy of chromosome 7 but there is no mutation of the MET gene.

Another chromosomal translocation, involving chromosome 8q24 close to the c-MYC gene, is also associated with some cases of papillary carcinoma.

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Chromophobe Renal Carcinomas

These are the least common, representing 5% of all renal cell carcinomas.

They arise from intercalated cells of collecting ducts. Their name denotes the observation that the tumor

cells stain more darkly (i.e., they are less clear) than cells in clear cell carcinomas.

These tumors are unique in having multiple losses of entire chromosomes, including chromosomes 1, 2, 6, 10, 13, 17, and 21.

In general, chromophobe renal cancers have a good prognosis.

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Morphology

Clear cell cancers (the most common form) are usually solitary and large when symptomatic (spherical masses 3-15 cm in diameter)

They may arise anywhere in the cortex. The cut surface of clear cell renal cell carcinomas

is yellow to orange to gray-white, with prominent areas of cystic softening or of hemorrhage, either fresh or old.

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The margins of the tumor are well defined. However, at times small processes project into the surrounding

parenchyma and small satellite nodules are found in the surrounding substance, providing clear evidence of the aggressiveness of these lesions.

As the tumor enlarges, it may fungate through the walls of the collecting system, extending through the calyces and pelvis as far as the ureter.

Even more frequently, the tumor invades the renal vein and grows as a solid column within this vessel, sometimes extending in serpentine fashion as far as the inferior vena cava and even into the right side of the heart.

Occasionally, there is direct invasion into the perinephric fat and adrenal gland.

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Depending on the amounts of lipid and glycogen present, the tumor cells of clear cell renal cell carcinoma may appear almost vacuolated or may be solid.

The classic vacuolated (lipid-laden), or clear cells are demarcated only by their cell membranes.

The nuclei are usually small and round. At the other extreme are granular cells, resembling the tubular epithelium, which have small, round, regular nuclei enclosed within granular pink cytoplasm.

Some tumors exhibit marked degrees of anaplasia, with numerous mitotic figures and markedly enlarged, hyperchromatic, pleomorphic nuclei. Between the extremes of clear cells and solid, granular cells, all intergradations may be found.

The cellular arrangement, too, varies widely. The cells may form abortive tubules or may cluster in cords or disorganized masses. The stroma is usually scant but highly vascularized.

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Papillary renal cell carcinomas exhibit varying degrees of papilla formation with fibrovascular cores.

They tend to be bilateral and multiple. They may also show gross evidence of necrosis, hemorrhage,

and cystic degeneration, but they are less vibrantly orange-yellow because of their lower lipid content.

The cells can have clear or, more commonly, pink cytoplasm. Chromophobe-type renal cell carcinoma tends to be grossly tan-brown.

The cells usually have clear, flocculent cytoplasm with very prominent, distinct cell membranes. The nuclei are surrounded by halos of cleared cytoplasm.

Ultrastructurally, large numbers of characteristic macrovesicles are seen.

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Renal cell carcinomas have several peculiar clinical characteristics that create especially difficult and challenging diagnostic problems.

The symptoms vary, but the most frequent presenting manifestation is hematuria, occurring in more than 50% of cases.

Macroscopic hematuria tends to be intermittent and fleeting, superimposed on a steady microscopic hematuria. Less commonly (because of wide use of imaging studies for unrelated conditions), the tumor may declare itself simply by virtue of its size, when it has grown large enough to produce flank pain and a palpable mass.

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Extra-renal effects are fever and polycythemia, both of which may be associated with a renal cell carcinoma but which, because they are nonspecific, may be misinterpreted for some time before their true significance is appreciated.

Polycythemia affects 5% to 10% of persons with this disease. It results from elaboration of erythropoietin by the renal tumor. Uncommonly, these tumors produce a variety of hormone-like substances, resulting in hypercalcemia, hypertension, Cushing syndrome, or feminization or masculinization. These, as will be recalled from, are paraneoplastic syndromes. In many individuals the primary tumor remains silent and is discovered only after its metastases have produced symptoms.

The prevalent locations for metastases are the lungs and the bones. It must be apparent that renal cell carcinoma presents in many fashions, some quite devious, but the triad of painless hematuria, a palpable abdominal mass, and dull flank pain is characteristic.

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Wilms Tumor (Nephroblastoma)

Although Wilms tumor occurs infrequently in adults, it is the third most common organ cancer in children younger than the age of 10 years.

It is therefore one of the major cancers of children. These tumors contain a variety of cell and tissue

components, all derived from the mesoderm. Wilms tumor, like retinoblastoma, may arise

sporadically or be familial, with the susceptibility to tumorigenesis inherited as an autosomal dominant trait.

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SUMMARY

Renal cell carcinomas account for 2-3% of all cancers in adults; classified into three types.

Clear cell carcinomas are the most common; associated with homozygous loss of the VHL tumor suppressor protein; tumors frequently invade the renal vein.

Papillary renal cell carcinomas are frequently associated with increased expression and activating mutations of the MET oncogene; tend to be bilateral and multiple, and show varying papilla formation.

Chromophobe renal cell carcinomas are less common; tumor cells are not as clear as in the other renal cell carcinomas.

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Tumors of the Urinary Bladder and Collecting

System

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The entire urinary collecting system from renal pelvis to urethra is lined with transitional epithelium, so its epithelial tumors assume similar morphologic patterns.

Tumors in the collecting system above the bladder are relatively uncommon; those in the bladder, however, are an even more frequent cause of death than are kidney tumors.

Nevertheless, in the individual case a small lesion in the ureter, for example, may cause urinary outflow obstruction and have greater clinical significance than a much larger mass in the capacious bladder.

Tumors of the Urinary Bladder and Collecting System (Renal Calyces, Renal Pelvis, Ureter, and Urethra)

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Morphology Tumors arising in the urinary bladder range from small benign

papillomas to large invasive cancers. These tumors are classified into a rare benign papilloma, a group

of papillary urothelial neoplasms of low malignant potential, and two grades of urothelial carcinoma (low and high grade).

The very rare benign papillomas are 0.2- to 1.0-cm frondlike structures having a delicate fibrovascular core covered by multilayered, well-differentiated transitional epithelium. In some of these lesions, the covering epithelium appears as normal as the mucosal surface from whence the tumors arose.

Such lesions are usually solitary. They almost invariably noninvasive and benign, and they rarely

recur once removed.

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Urothelial (transitional) cell carcinomas Range from papillary to flat, noninvasive to invasive, and low

grade to high grade. Low-grade carcinomas are always papillary and are rarely invasive, but they may recur after removal.

Whether the regrowth is a true recurrence or a second primary growth is uncertain. Increasing degrees of cellular atypia and anaplasia are encountered in papillary exophytic growths, accompanied by an increase in the size of the lesion and evidence of invasion of the submucosal or muscular layers.

High-grade cancers can be papillary or occasionally flat; they may cover larger areas of the mucosal surface, invade deeper, and have a shaggier necrotic surface than do low-grade tumors.

Occasionally, these cancers show foci of squamous cell differentiation, but only 5% of bladder cancers are true squamous cell carcinomas.

Carcinomas of grades II and III infiltrate surrounding structures, spread to regional nodes, and, on occasion, metastasize widely.

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In addition to overt carcinoma, an in situ stage of bladder carcinoma can be recognized, often in individuals with previous or simultaneous papillary or invasive tumors.

Indeed, wide areas of atypical hyperplasia and dysplasia may be present.

It is now thought that these epithelial changes and cancers in situ are caused by the generalized influence of a putative carcinogen on urothelium and that they may be the precursors of invasive carcinomas in some persons.

However, despite the presence of wide areas of epithelial lesions, the bladder tumors, even when multiple, are monoclonal in origin.

Apparently, clonal descendants of a single transformed cell can seed multiple areas of the mucosa.

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Clinical Course Painless hematuria is the dominant clinical presentation of all

these tumors. Because most arise in the bladder, we will consider these first. They affect men about three times as frequently as women and

usually develop between the ages of 50 and 70 years. Although most occur in persons with no known his-tory of

exposure to industrial solvents, bladder tumors are 50 times more common in those exposed to β-naphthylamine.

Cigarette smoking, chronic cystitis, schistosomiasis of the bladder, and certain drugs (cyclophosphamide) are also believed to induce higher rates of this cancer.

A wide variety of genetic abnormalities are seen in bladder cancers; of these, mutations involving several genes on chromosome 9 (including p16), p53, and FGFR3 are the most common

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The clinical significance of bladder tumors depends on their histologic grade and differentiation and, most importantly, on the depth of invasion of the lesion.

Except for the clearly benign papillomas, all tend stubbornly to recur after removal.

Lesions that invade the ureteral or urethral orifices cause urinary tract obstruction.

In general, with low-grade shallow lesions, the prognosis after removal is good, but when deep penetration of the bladder wall has occurred, the 5-year survival rate is less than 20%. Overall 5-year survival is 57%.

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Although papillary and cancerous neoplasms of the lining epithelium of the collecting system occur much less frequently in the renal pelvis than in the bladder, they nonetheless make up 5% to 10% of primary renal tumors.

Painless hematuria is the most characteristic feature of these lesions, but in their critical location they produce pain in the costovertebral angle as hydronephrosis develops. Infiltration of the walls of the pelvis, calyces, and renal vein worsens the prognosis.

Despite removal of the tumor by nephrectomy, fewer than 50% of patients survive for 5 years.

Cancer of the ureter is fortunately the rarest of the tumors of the collecting system.

The 5-year survival rate is less than 10%.

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Adenocarcinoma

Uncommon. Two types are distinguished by location: 1. arising from where the urachus used to

be, high on the front of the bladder, 2. arising around the trigone (usually) from

"cystitis glandularis" (maybe) or "colonic metaplasia".

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Squamous cell carcinoma

Usually arises in squamous metaplastic epithelium: the patient has

schistosomiasis, extremely aggressive and

lethal.

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Rhabdomyosarcoma

Children

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Thank you!