Kidney tumors & LUT path

Question 1

Renal cell carcinoma

Answer 1

derived from the renal tubular epithelium, located primarily in cortex
renal adenocarcinoma
represent 80-85% of all primary malignant tumors of the kidney
men > women; peak age: 50s-60s

Question 2

RCC risk

Answer 2

cigarette smokers
occupational exposure to cadmium
dialysis-associated acquired cysts

Question 3

RCC, VHL

Answer 3

most common (70-80%)
most sporadic, but some familial forms
associated with von Hippel-Lindau (VHL) disease
-predisposition to many neoplasms, but particularly to hemangioblastomas of the cerebellum and retina
-in 40-60% of cases, hundreds of bilateral cysts and multiple clear cell carcinomas develop
-due to homozygous loss of VHL gene on 3p25; mutation of this gene is also involved in sporadic clear cell carcinoma

Question 4

RCC appearance

Answer 4

typically a yellow to orange mass in the upper pole of the kidney

Question 5

RCC how invasive

Answer 5

very invasive!
often extends through calyces, pelvis, even ureters
may enter renal vein and extend as far as right atrium

Question 6

RCC clinical features

Answer 6

“Classic” triad (10%): hematuria, palpable mass, and flank pain
polycythemia, hypertension
paraneoplastic syndromes: Cushing syndrome, hypercalcemia
high incidence of metastasis on initial presentation
-lungs, bones, regional lymph nodes

Question 7

Papillary renal cell carcinoma

Answer 7

papillary growth pattern
frequently multifocal and bilateral
also occur in familial and sporadic forms, but different gene from VHL
-overdose of MET (encodes a tyrosine kinase) caused by amplification of the gene
*MET signals growth of proximal tubule epithelial cells
*amplification is due to trisomy of chromosome 7 (sporadic or familial)

Question 8

Chromophobe Renal Carcinomas

Answer 8

least common
tumor cells stain more darkly than cells in clear cell carcinomas
cancer cells show multiple losses of entire chromosomes (hypodiploidy)

Question 9

Wilms Tumor (Nephroblastoma)

Answer 9

well-circumscribed mass
soft
very large
tan to gray
occasional foci of hemorrhage and necrosis

Question 10

Wilms Tumor (Nephroblastoma) 
malformations

Answer 10

3rd most common cancer in children <10 yoa (most occur between 2-5 yoa)
Three groups of congenital malformations are associated with Wilms tumor,
-all due to mutations in genes (WT1and WT2) on chromosome 11:
WAGR syndrome
Denys-Drash syndrome
Beckwith-Wiedemann Syndrome (BWS)

Question 11

WAGR syndrome

Answer 11

Wilms tumor (33%)
Aniridia
Genital abnormalities
mental retardation

Question 12

Denys-Drash syndrome

Answer 12

gonadal dysgenesis

renal abnormalities

Question 13

Beckwith-Wiedemann Syndrome (BWS)

Answer 13

enlargement of individual body organs (e.g., tongue, kidneys), or entire body segments (hemihypertrophy)

• disorder of genomic imprinting
• region on ch 11 normally only expressed from paternal chromosome, while other is silenced. In BWS, the maternal copy is no longer imprinted.

Question 14

Wilms Tumor (Nephroblastoma) clinical course

Answer 14

readily palpable abdominal mass
may present with fever and abdominal pain, hematuria, or intestinal obstruction
good prognosis: survival for 2 years implies cure

Question 15

Horseshoe kidney

Answer 15

This is a congenital anomaly that most often occurs in association with other anomalies or syndromes with specific genetic defects such as trisomy 18. However, it can also occur as an isolated anomaly. The possible problem here is that the ureters take an abnormal course across the “bridge” of renal tissue and this can lead to partial obstruction with hydronephrosis.

Question 16

Congenital anomalies

Answer 16

double ureters
Ureteropelvic junction obstruction
Sclerosing retroperitoneal fibrosis

Question 17

double ureters

Answer 17

Derived from a double or split ureteral bud
Double ureters are seen exiting from each kidney and extending to the bladder that has been opened. A small segment of aorta is seen between the normal, smooth-surfaced kidneys. A partial or complete duplication of one or both ureters occurs in about 1 in 150 persons. There is a potential for obstructive problems due to the abnormal flow of urine and the entrance of two ureters into the bladder in close proximity, but most of the time this is an incidental finding (except to a urologist).

Question 18

Ureteropelvic junction obstruction

Answer 18

most common cause of hydronephrosis in adults and children
usually presents in infants and children
-more commonly in boys and in the left ureter
In adults, more common in women and usually unilateral (80%)

Question 19

Sclerosing retroperitoneal fibrosis

Answer 19

An uncommon cause of ureteral narrowing or obstruction
Characterized by a fibrous proliferative inflammatory process encasing the retroperitoneal structures and causing hydronephrosis
Occurs in middle to late age
70% of cases are idiopathic (Ormond disease)
-An autoimmune reaction, sometimes triggered by drugs, has been proposed

Question 20

Ureter benign neoplasms

Answer 20

Primary neoplasia of the ureters is rare
The two most common benign tumors are:
Fibroepithelial polyps
-A tumor-like lesion presenting as a small mass projecting into the lumen
-Occurs more commonly in the ureters (L>R), but may occur in the bladder, renal pelves and urethra
Leiomyomas

Question 21

Ureters malignant neoplasms

Answer 21

Similar to those found in the renal pelvis, calyces, and bladder
Majority are transitional cell carcinomas
Most frequent: 50-60 yoa
Occasionally found concurrent with neoplasms in kidney and bladder

Question 22

Bladder congenital anomalies

Answer 22

diverticula
Exstrophy
Obstructive Lesions

Question 23

diverticula

Answer 23

A pouchlike eversion or evagination of the bladder wall
May arise as congenital defects, but more often are acquired from persistent urethral obstruction (e.g., prostatic hyperplasia)

Question 24

Exstrophy

Answer 24

A developmental failure that causes the bladder to flatten and protrude, inside out, through the abdominal wall
subject to chronic infection and inflammation → increased tendency to develop carcinoma later in life (esp. adenocarcinoma)

Question 25

Obstructive Lesions

Answer 25

Obstruction from nodular prostatic hyperplasia has led to prominent trabeculation seen on the mucosal surface of this bladder with hypertrophy. The stasis from obstruction predisposes to infection. The obstruction can also lead to bilateral hydroureter and hydronephrosis. The enlarged prostate gland seen here not only has enlarged lateral lobes, but also a greatly enlarged median lobe that obstructs the prostatic urethra. This led to obstruction with bladder hypertrophy, as evidenced by the prominent trabeculation of the bladder wall seen here from the mucosal surface. Obstruction with stasis also led to the formation of the yellow-brown calculus (stone).

Question 26

Acute and chronic cystitis

Answer 26

``` infection of the urinary bladder Common organisms: E. coli Proteus Klebsiella Enterobacter ```

Question 27

Acute and chronic cystitis

Answer 27

``` Hemorrhagic cystitis Suppurative cystitis Chronic cystitis Interstitial cystitis Polypoid cystitis Malacoplakia ```

Question 28

Hemorrhagic cystitis

Answer 28

Associated with a hemorrhagic component May follow cytotoxic antitumor drugs (e.g., cyclophosphamide) and bladder radiation Adenovirus infection is also a cause

Question 29

Suppurative cystitis

Answer 29

accompanied by a large suppurative exudate | ulceration of large areas of mucosa = ulcerative cystitis

Question 30

Chronic cystitis

Answer 30

results from persistence of infection | gives rise to fibrous thickening in the muscularis propria → thickening and inelasticity of the bladder wall

Question 31

Acute and chronic cystitis triad

Answer 31

Frequency of urination every 15-20 minutes in some acute cases Lower abdominal pain localized over the bladder or suprapubic region Dysuria In some cases, systemic signs of inflammation may be present (fever, chills, and general malaise)

Question 32

Interstitial cystitis

Answer 32

A persistent, painful form of chronic cystitis -occurs most frequently in women -associated with inflammation and fibrosis of all layers of the bladder wall Characterized by intermittent (often severe) suprapubic pain, urinary urgency and frequency, hematuria, and dysuria without evidence of bacterial infection, and cystoscopic findings of fissures and punctate hemorrhages Some patients exhibit features of chronic mucosal ulcers (Hunner ulcers) unknown etiology, but may be autoimmune

Question 33

Polypoid cystitis

Answer 33

An inflammatory condition resulting from irritation of the bladder mucosa Caused by anything injuring the bladder mucosa (most commonly, indwelling catheters)

Question 34

Malacoplakia

Answer 34

an inflammatory reaction characterized macroscopically by soft, yellow, slightly raised mucosal plaques 3-4 cm in diameter contain large, foamy macrophages with occasional multinucleate giant cells and interspersed lymphocytes -macrophages "stuffed" with bacterial remnants

Question 35

Malacoplakia info

Answer 35

lysosomal calcium deposits Clearly related to chronic bacterial infection (mainly E. coli and occasionally Proteus sp.) -Occurs with increased frequency in immunosuppressed transplant recipients -likely a defect in phagocytic or degradative function of macrophages (they become overloaded with undigested bacterial products)

Question 36

Bladder neoplasms

Answer 36

The incidence of bladder epithelial tumors in the U.S. has been steadily increasing and is now >57,000 new cases annually include cancers of epithelial (95%) and mesenchymal origin Range from small benign lesions to aggressive cancers associated with a high risk of death Many are multifocal at presentation May be seen in any site that is lined by urothelium (distal renal pelvis to the urethra)

Question 37

two distinct precursor lesions to invasive carcinoma

Answer 37

noninvasive papillary tumors | carcinoma in situ (CIS)

Question 38

noninvasive papillary tumors

Answer 38

arise from papillary urothelial hyperplasia and exhibit a range of atypia

Question 39

carcinoma in situ (CIS)

Answer 39

defined by the presence of any cytologically malignant cells within a flat urothelium may range from full-thickness cytologic atypia to scattered malignant cells in an otherwise normal urothelium (pagetoid spread) cells typically lose cohesiveness and are shed in the urine untreated, 50-75% progress to invasive cancer

Question 40

Urothelial neoplasms

Answer 40

Papillomas Superficial urothelial carcinomas Squamous cell carcinomas

Question 41

Papillomas

Answer 41

represent ~1% of bladder tumors most frequent in young patients small finger-like papillae that are histologically identical to normal urothelium does not progress to cancer and rarely recur

Question 42

Superficial urothelial carcinomas Grade I

Answer 42

low malignant potential aka, papillary urothelial neoplasms of low malignant potential (PUNLMP) always papillary and rarely invasive may recur after removal

Question 43

Superficial urothelial carcinomas Grade II

Answer 43

aka, low-grade papillary urothelial carcinomas increasing degrees of cellular atypia and pleomorphism in papillary exophytic growths infrequently invade surrounding structures; rarely life-threatening

Question 44

Superficial urothelial carcinomas Grade III

Answer 44

aka, high-grade urothelial carcinoma may be papillary or flat flat urothelial CIS are highly aggressive lesions that progress more rapidly than the papillary tumors

Question 45

SCC

Answer 45

Represent ~3-7% of bladder cancers in U.S. Often cover large areas of the bladder and are deeply invasive at time of diagnosis In countries where schistosomiasis is endemic, they occur with much greater frequency

Question 46

Urothelial carcinomas demo

Answer 46

More common in men, industrialized nations, and in urban dwellers men: women ratio is ~3:1 80% of patients are 50-70 yoa With rare exception, is not familial

Question 47

Urothelial carcinomas risk factors

Answer 47

Cigarette smoking! -most important influence -50-80% of all bladder cancers in ♂s associated with use of cigarettes (cigars, pipes, and smokeless tobacco confer a much smaller risk) Industrial exposure to arylamines (particularly β-naphthylamine) -Cancers appear 15-40 years after exposure Schistosoma haematobium in endemic areas (Egypt, Sudan) -Most are SCCs (70%), rest are TCCs Long-term use of analgesics Heavy long-term exposure to cyclophosphamide Prior exposure of bladder to radiation -Received in conjunction for other pelvic malignancies -Occurs many years post-radiation

Question 48

Urothelial carcinomas clinical & prognosis

Answer 48

Classically produce painless hematuria (dominant and sometimes only manifestation) Frequency, urgency, and dysuria sometimes also present When ureteral orifice affected, hydronephrosis or pyelonephritis may occur After excision, new tumors (and of higher grade) may develop Most important factors for progression-free survival are: grade, presence of lamina propria invasion, and associated CIS low grade = 98% 10-year survival high-grade = 40% 10-year survival 70% of patients with SCC die within a year

Question 49

Muscle-invasive urothelial cancer

Answer 49

Detected early, may be superficial in the lamina propria, but may progress to advanced local invasion and metastases -invade prostate, seminal vesicles, ureters, retroperitoneum *some produce fistulas to vagina or rectum -hematogenous dissemination is rare, but can involve liver, lungs, and bone marrow The extent of spread at time of initial diagnosis is the most crucial factor in determining the prognosis

Question 50

Urothelial carcinomas diagnosis

Answer 50

The clinical challenge is early detection and followup Cystoscopy and biopsy are mainstays of diagnosis urine markers?: telomerase, CEA, etc.

Question 51

Urethritis

Answer 51

Gonococcal urethritis Nongonococcal urethritis not a serious clinical problem itself, but may cause considerable local pain, itching, and frequency

Question 52

Nongonococcal urethritis

Answer 52

most frequently caused by Escherichia coli and other GNBs (coliforms) Is accompanied by cystitis in ♀s and prostatitis in ♂s Chlamydia is cause in 25-60% of ♂s and 20% in ♀s Also a component of Reiter syndrome -classic triad = arthritis, conjunctivitis, and urethritis

Question 53

Urethral caruncle

Answer 53

Presents as a small painful red mass about the external urethral meatus in ♀s Found at any age, but more common in postmenopausal extremely friable; slight trauma causes ulceration and bleeding due to chronic irritation of a prolapsed urethra may mimic carcinoma

Question 54

Urethra neoplasm

Answer 54

Primary carcinoma is uncommon Tends to occur in advanced age in ♀s Cancers also occur within the prostatic urethra (see later)