Kidney tumors & LUT path Flashcards
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
RCC risk
cigarette smokers
occupational exposure to cadmium
dialysis-associated acquired cysts
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
RCC appearance
typically a yellow to orange mass in the upper pole of the kidney
RCC how invasive
very invasive!
often extends through calyces, pelvis, even ureters
may enter renal vein and extend as far as right atrium
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
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)
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)
Wilms Tumor (Nephroblastoma)
well-circumscribed mass soft very large tan to gray occasional foci of hemorrhage and necrosis
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)
WAGR syndrome
Wilms tumor (33%)
Aniridia
Genital abnormalities
mental retardation
Denys-Drash syndrome
gonadal dysgenesis
renal abnormalities
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.
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
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.
Congenital anomalies
double ureters
Ureteropelvic junction obstruction
Sclerosing retroperitoneal fibrosis
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).
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%)
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
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
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
Bladder congenital anomalies
diverticula
Exstrophy
Obstructive Lesions
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)
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)
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).
Acute and chronic cystitis
infection of the urinary bladder Common organisms: E. coli Proteus Klebsiella Enterobacter
Acute and chronic cystitis
Hemorrhagic cystitis Suppurative cystitis Chronic cystitis Interstitial cystitis Polypoid cystitis Malacoplakia
Hemorrhagic cystitis
Associated with a hemorrhagic component
May follow cytotoxic antitumor drugs (e.g., cyclophosphamide) and bladder radiation
Adenovirus infection is also a cause
Suppurative cystitis
accompanied by a large suppurative exudate
ulceration of large areas of mucosa = ulcerative cystitis
Chronic cystitis
results from persistence of infection
gives rise to fibrous thickening in the muscularis propria → thickening and inelasticity of the bladder wall
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)
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
Polypoid cystitis
An inflammatory condition resulting from irritation of the bladder mucosa
Caused by anything injuring the bladder mucosa (most commonly, indwelling catheters)
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
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)
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)
two distinct precursor lesions to invasive carcinoma
noninvasive papillary tumors
carcinoma in situ (CIS)
noninvasive papillary tumors
arise from papillary urothelial hyperplasia and exhibit a range of atypia
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
Urothelial neoplasms
Papillomas
Superficial urothelial carcinomas
Squamous cell carcinomas
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
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
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
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
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
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
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
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
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
Urothelial carcinomas diagnosis
The clinical challenge is early detection and followup
Cystoscopy and biopsy are mainstays of diagnosis
urine markers?: telomerase, CEA, etc.
Urethritis
Gonococcal urethritis
Nongonococcal urethritis
not a serious clinical problem itself, but may cause considerable local pain, itching, and frequency
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
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
Urethra neoplasm
Primary carcinoma is uncommon
Tends to occur in advanced age in ♀s
Cancers also occur within the prostatic urethra (see later)
