Renal Pathology Chapter 21 Part 1 Flashcards
Renal pelves, ureters, bladder, and urethra (except terminal portion) lined by
-special form of transitional epithelium called urothelium
Urothelium is composed of
- 5-6 layers of cells with oval nuclei, often with linear nuclear grooves, and a surface layer consisting of large, flattened “umbrella cells” with abundant cytoplasm
- epithelium rests on a well-developed basement membrane, beneath which is a lamina propria
Lamina propria in the urinary bladder contains
-wisps of smooth muscle that form discontinuous muscularis mucosae
If urine flow is obstructed and intravesical pressures rise,
-the bladder musculature undergoes hypertrophy
Retroperitoneal tumors or fibrosis may
may entrap the ureters, sometimes obstruct them
As ureters enter the pelvis,
they pass anterior to either the common iliac or the external iliac artery
In the female pelvis, the ureters
lie close to the uterine arteries and are therefore vulnerable to injury in operations on the female genital tract
3 points of slight narrowing of ureters
- at the ureteropelvic junction, where they enter the bladder, and where they cross the iliac vessels
- renal calculi may become impacted in these spots when they pass form the kidney to the bladder
As the ureters enter the bladder,
they pursue an oblique course, terminating in a slit-like orifice
-obliquity of this intramural segment of the ureteral orifice permits the enclosing bladder musculature to act like a sphincteric valve, blocking the upward reflux of urine even in the presence of marked distention of the urinary bladder
A defect in the intravesical portion of the ureter leads to
vesicoureteral reflux
In middle-aged and older women, relaxation of pelvic support leads to
prolapse (descent) of the uterus, pulling with it the floor of the bladder
-in this fashion, the bladder is protruded into the vagina, creating a pouch (cystocele) that fails to empty readily with micturition
Double ureters
- almost invariably associated with totally distinct double renal pelves or with the anomalous development of a large kidney having a partially bifid pelvis terminating in separate ureters
- may pursue separate course to the bladder, but commonly are joined within the bladder wall and drain through a single ureteral orifice
- most are unilateral and of no clinical significance
Ureteropelvic junction (UPJ) obstruction
- congenital disorder that is the most common cause of hydronephrosis in infants and children
- cases that present early in life are bilateral in 20% of cases, are often associated with other congenital anomalies, and preferentially occur in males
- agenesis of the contralateral kidney in a minority of cases
- in adults, more common in women and often unilateral
UPJ obstruction has been ascribed to
abnormal organization of smooth muscle bundles at the UPJ, to excess stromal deposition of collagen between smooth muscle bundles, or rarely to congenitally extrinsic compression of the UPJ by the renal vessels.
Diverticula
- saccular outpouchings of the ureteral wall
- may be congenital or acquired
- most are asymptomatic, but urinary stasis within diverticula sometimes leads to recurrent infection
Ureteritis
- associated with inflammation
- typically not associated with infection and is of little clinical consequence
Ureteritis Follicularis
-accumulation or aggregation of lymphocytes forming germinal centers in the sub epithelial region may cause slight elevations of the mucosa and produce a fine granular mucosal surface
Ureteritis cystica
-at other times the mucosa may become sprinkled with fine cysts varying in a diameter from 1-5 mm lined by flattened urothelium
Small benign tumors of the ureter are generally of
mesenchymal origin
Fibroepithelial polyp
- tumor-like lesion that presents as a small mass projecting into the lumen, often in children
- occurs more commonly in the ureters but may also involve the bladder, renal pelves, and urethra
- polyp is composed of loose, vascularized connective tissue overlaid by urothelium
Primary malignant tumors of the ureters resemble
those arising in the renal pelvis, calyces, and bladder
- majority are urothelial carcinomas.
- occur most frequently during the 6th or 7th decades of life and cause obstruction of the ureteral lumen
- sometimes multifocal and commonly occur concurrently with similar neoplasms in the bladder or renal pelvis
Unilateral obstruction of the ureter
-typically results from proximal causes
Bilateral Obstruction of the ureter
arises from distal cause, such as nodular hyperplasia of the prostate
Sclerosing Retroperitoneal Fibrosis
- uncommon cause of ureteral narrowing or obstruction and is characterized by a fibrotic proliferative inflammatory process encasing the retroperitoneal structures and causing hydronephrosis
- occurs in middle to late age and is more common in males
- at least a subset related to IgG4-related disease
- Often involves other tissues, particularly exocrine organs such as the pancreas and salivary glands
- can also be associated with drug exposures, adjacent inflammatory conditions, or malignant disease
Vesicoureteral reflux
most common and serious urinary bladder congenital anomaly
-major contributor to renal infection and scarring and in consideration of pyelonephritis
Congenital diverticula of the bladder
-may be due to a focal failure of development of the normal musculature or to some urinary tract obstruction during fetal development
Acquired diverticula
- most often seen with prostatic enlargement producing obstruction to urine outflow and marked muscle thickening of the bladder wall
- increased intravesical pressure causes outputting of bladder wall
Exstrophy of the bladder
- developmental failure in the anterior wall of the abdomen and the bladder, so that the bladder either communicates directly through a large defect with the surface of the body or lies as an opened sac
- exposed bladder mucosa may undergo colonic glandular metaplasia and is subject to infections that often spread to upper levels of the urinary system
- patients have an increased risk of adenocarcinoma arising in the bladder remnant
Urachal anomalies
- urachus remains patent
- when totally patent, a fistulous urinary tract connects the bladder with the umbilicus
- in other instances, only the central region of the arches persist, giving rise to urachal cysts, lined by either urothelium or metaplastic glandular epithelium
Bacterial pyelonephritis is frequently preceded by
- infection of the urinary bladder, with retrograde spread of microorganisms into the kidneys and their collecting systems
- common agents are E. coli, Proteus, Klebsiella, and Enterobacter
- Women more likely to develop cystitis as a result of shorter urethras
Predisposing factors to cystitis
-bladder colliculi, urinary obstruction, diabetes mellitus, instrumentation, and immune deficiency
All forms of cystitis are characterized by a triad of symptoms:
- frequency, which in acute cases may necessitate urination every 15-20 minutes
- lower abdominal pain localized over the bladder region or in the suprapubic region
- dysuria–pain or burning on urination
Most cases of cystitis produce
nonspecific acute or chronic inflammation of the bladder
In acute cystitis, there is
there is hyperemia of the mucosa and neutrophilic infiltrate, sometimes associated with exudate
Hemorrhagic cystitis
- patients receiving cytotoxic anti tumor drugs
- adenovirus infection
Chronic cystitis associated with
-mononuclear inflammatory infiltrates
Follicular cystitis
-presence of lymphoid follicles within the bladder mucosa and underlying wall
Eosinophilic cystitis
-infiltration with submucosal eosinophils, typically non-specific subacute inflammation but may also be a manifestation of a systemic allergic disorder
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
- occurs most frequently in women
- characterized by intermittent often severe, suprapubic pain, urinary frequency, urgency, hematuria and dysuria, and cystoscopic findings of issues and punctate hemorrhages (glomerulations) in the bladder mucosa after luminal distention
- unknown etiology
- some cases associated with chronic mucosal ulcers
- increased numbers of mucosal mast cells
- transmural fibrosis may appear late in the course
Malakoplakia
- chronic inflammatory reaction that appears to stem from acquired defects in phagocyte function
- arises in setting of chronic bacterial infection, mostly by E. coli or Proteus
- occurs more often in immunosuppressed patients
- soft, yellow, slightly raised mucosal plaques filled with large, foamy macrophages mixed with occasional multinucleate giant cells and lymphocytes
- macrophages have abundant granular cytoplasm due to phagosomes stuffed with particulate and membranous debris of bacterial origin
- Michaelis-Gutmann bodies in macrophages
Polypoid Cystitis
inflammatory lesion resulting from irritation of the bladder mucosa
- indwelling catheters or any injurious agent may give rise to lesion
- urothelium is thrown into broad bulbous polypoid projections
Cystitis glandularis and cystica
- common lesions of the urinary bladder in which nests of urothelium (Brunn nests) grow downward into the lamina propria
- epithelial cells in center of nest undergo metaplasia and take on a cuboidal or columnar appearance (glandularis), or retract to produce cystic spaces lined by flattened urothelium (cystica)
Squamous metaplasia
-as a response to injury,t he urothelium is often replaced by nonkeratinizing squamous epithelium, which is more durable lining
Nephrogenic adenoma
- results from implantation of shed renal tubular cells at sites of injured urothelium
- overlying urothelium may be focally replaced by cuboidal epithelium, which can assume a papillary growth pattern
Bladder cancer accounts for
-about 7% of cancers and 3% of cancer mortality in the U.S.
About 95% of bladder tumors are
of epithelial origin, the remainder are mesenchymal tumors
-most epithelial tumors are urothelial type
Urothelial tumors represent
- about 90% of all bladder tumors and can be small benign lesions that do not recur to aggressive dancers that are often fatal
- many are multifocal
- can be seen at any site where there is urothelium
2 distinct precursor lesions to invasive urothelial carcinoma
- noninvasive papillary tumors (most common)
- flat noninvasive urothelial carcinoma (carcinoma in situ)
Major decrease in survival in urothelial carcinoma is associated with
invasion of the muscularis propria (detrusor muscle)
Contributors to urothelial carcinoma
- cigarette smoking
- industrial exposure to aryl amines (cancers appear 15-40 years after initial exposure)
- schistosoma haematobium infections in endemic areas (Egypt, Sudan)
- Long-term use of analgesics
- Heavy long-term exposure to cyclophosphamide
- Irradiation
Low-grade superficial papillary tumors are characterized by
- FGFR3 and RAS mutations and chromosome 9 deletions
- of these, a minority may then lose TP53 and/or RB function and progress to invasion
Noninvasive high-grade flat or papillary lesions are initiated by
TP53 mutations and, with loss of chromosome 9 and acquisition of other, still to be characterized mutations, progression to invasion ensues
Most urothelial tumors arise from
lateral or posterior walls at the bladder base
Papillary urothelial lesions are
- red, elevated excrescences ranging in size from less than 1 cm in diameter to large masses up to 5 cm in diameter
- multiple discrete tumors are often present
Majority of papillary tumors are
low grade
Papillomas represent
1% or less of bladder tumors, and are usually seen in younger patients
Papillomas typically arise
- singly as small, delicate, structures, superficially attached to the mucosa by a stalk and are referred to as exophytic papillomas
- individual finger-like papillae have a central core of loose fibrovascular tissue covered by epithelium that is histologically identical to normal urothelium
- recurrences and progression are are but may occur
Inverted papillomas
-completely benign lesions consisting of inter-anastomosing cords of cytologically bland urothelium that extend down into the lamina propria
Papillary urothelial neoplasms of low malignant potential
- share many histologic features with papilloma, differing only in having thicker uorthelium
- these tumors tend to be larger than papillomas and may be indistinguishable form low- and high-grade papillary cancers
Low-grade papillary urothelial carcinomas
- have an orderly architectural and cytologic appearance
- cells are evenly spaced and cohesive
- mild degree of nuclear atypia consisting of scattered hyper chromatic uncle, infrequent mitotic figures predominantly toward the base and slight variation in nuclear size and shape
- may recur, and infrequently may invade
High-grade papillary urothelial cancers
- contain dyscohesive cells with large hyperchormatic nuclei.
- some are highly anapestic
- mitotic figures frequent
- disarray and loss of polarity
- much higher incidence of invasion into the muscular layer, higher risk of progression, metastatic potential
- aggressive tumors may extend into the bladder wall, and, in more advanced stages, invade the adjacent prostate, seminal vesicles, ureters, and retroperitoneum
- some tumors produce fistulous communications to the vagina or rectum
Carcinoma in situ
- presence of cytologically malignant cells within a flat urothelium
- may range from full-thickness cytologic atypia to scattered malignant cells in an otherwise normal urothelium, the latter termed pagetoid spread
- usually appears as an area of mucosal reddening, granularity, or thickening without an evident intraluminal mass
Invasive urothelial cancer may be associated with
papillary urothelial cancer, usually high grade, or adjacent CIS
Almost all infiltrating urothelial carcinomas are
-high grade, and as a result grading of the infiltrating component is not critical, as opposed to the importance of grading noninvasive papillary urothelial carcinoma
Ta bladder carcinoma
-noninvasive, papillary
Tis bladder carcinoma
carcinoma in situ (noninvasive, flat)
T1
lamina propria invasion
T2
muscularis propria invasion
T3a
microscopic extravesicle invasion
T3b
grossly apparent extravesicle invasion
T4
invades adjacent structures
Squamous cell carcinomas
- pure ones nearly always associated with chronic bladder irritation and infection
- mixed urothelial carcinomas with areas of squamous carcinoma are more frequent than pure ones
- most are invasive, fun gating tumors or are infiltrative and ulcerative
Bladder tumor clinical features
- painless hematuria
- frequency, urgency, and dysuria occasionally
- when the ureteral orifice is involved, pyelonephritis or hydronephrosis may follow
Sarcomas
- uncommon
- inflammatory myofibroblastic tumors and various carcinomas may assume sarcomatoid growth patterns and be mistaken histologically for sarcomas
- tend to produce large masses that protrude into the vesicle lumen
- soft, fleshy, gray-white gross appearance suggest sarcomatous nature
Most common sarcoma in infancy or childhood is
embryonal rhabdomyosarcoma
Most common sarcoma in the bladder in adults is
leiomyosarcoma
