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Flashcards in Kidney tumors & LUT path Deck (54):
1

Renal cell carcinoma

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

2

RCC risk

cigarette smokers
occupational exposure to cadmium
dialysis-associated acquired cysts

3

RCC, VHL

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

4

RCC appearance

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

5

RCC how invasive

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

6

RCC clinical features

"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

7

Papillary renal cell carcinoma

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)

8

Chromophobe Renal Carcinomas

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

9

Wilms Tumor (Nephroblastoma)

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

10

Wilms Tumor (Nephroblastoma)
malformations

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)

11

WAGR syndrome

Wilms tumor (33%)
Aniridia
Genital abnormalities
mental retardation

12

Denys-Drash syndrome

gonadal dysgenesis
renal abnormalities

13

Beckwith-Wiedemann Syndrome (BWS)

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.

14

Wilms Tumor (Nephroblastoma) clinical course

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

15

Horseshoe kidney

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.

16

Congenital anomalies

double ureters
Ureteropelvic junction obstruction
Sclerosing retroperitoneal fibrosis

17

double ureters

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).

18

Ureteropelvic junction obstruction

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%)

19

Sclerosing retroperitoneal fibrosis

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

20

Ureter benign neoplasms

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

21

Ureters malignant neoplasms

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

22

Bladder congenital anomalies

diverticula
Exstrophy
Obstructive Lesions

23

diverticula

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)

24

Exstrophy

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)

25

Obstructive Lesions

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).

26

Acute and chronic cystitis

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

27

Acute and chronic cystitis

Hemorrhagic cystitis
Suppurative cystitis
Chronic cystitis
Interstitial cystitis
Polypoid cystitis
Malacoplakia

28

Hemorrhagic cystitis

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

29

Suppurative cystitis

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

30

Chronic cystitis

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

31

Acute and chronic cystitis triad

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)

32

Interstitial cystitis

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

33

Polypoid cystitis

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

34

Malacoplakia

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

35

Malacoplakia info

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)

36

Bladder neoplasms

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)

37

two distinct precursor lesions to invasive carcinoma

noninvasive papillary tumors
carcinoma in situ (CIS)

38

noninvasive papillary tumors

arise from papillary urothelial hyperplasia and exhibit a range of atypia

39

carcinoma in situ (CIS)

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

40

Urothelial neoplasms

Papillomas
Superficial urothelial carcinomas
Squamous cell carcinomas

41

Papillomas

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

42

Superficial urothelial carcinomas Grade I

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

43

Superficial urothelial carcinomas Grade II

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

44

Superficial urothelial carcinomas Grade III

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

45

SCC

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

46

Urothelial carcinomas demo

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

47

Urothelial carcinomas risk factors

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

48

Urothelial carcinomas clinical & prognosis

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

49

Muscle-invasive urothelial cancer

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

50

Urothelial carcinomas diagnosis

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

51

Urethritis

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

52

Nongonococcal urethritis

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

53

Urethral caruncle

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

54

Urethra neoplasm

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