Bladder Pathology Flashcards
1
Q
Mneumonic to help recall which abdominal viscera are retroperitoneal
A
“SAD PUCKER”
- S = suprarenal (adrenal) glands
- A = aorta/IVC
- D = duodenum (except the duodenal cap-first 2cm)
- P = pancreas (except tail)
- U = ureters
- C = colon
- K = kidneys
- E = (o)esophagus
- R = rectum
2
Q
Double and Bifed Ureters
A
- May be assoc. w/ distinct double renal pelves
- May be assoc. w/ anomalous development of a large kidney having a partially bifed pelvis terminating in separate ureters
- Double ureters may pursue separate courses in the bladder wall and drain thru a single ureteral orifice
- Most double ureters are U/L and are of no clinical significance
3
Q
Uretopelvic Junction Obstruction
A
- A congenital disorder that is the most common cause of hydronephrosis in infants and children which is more common in boys
- The condition has been ascribed to abnormal organization of smooth muscle bundles at the UPJ, to excess stromal deposition of collagen b/w smooth muscle bundles, or rarely to congenitally extrinsic compression of the UPJ by renal vessels
4
Q
Ureter Diverticula
A
- Saccular outpouchings of the ureteral wall
- Usually asymptomatic
- May cause stasis and secondary infections
- Dilation, elongation and tortuosity of the ureters may occur
5
Q
Disease states that result from obstruction of the ureter
A
- Hydroureter
- Hydronephrosis
- Pyelonephritis
6
Q
Causes of Intrinsic Obstructive Lesions of the Kidneys
A
- Calculi
- Strictures
- Tumors
- Blood clots
- Neurogenic
7
Q
Causes of Extrinsic Obstructive Lesions of the Kidneys
A
- Pregnancy
- Periureteral inflammation
- Endometriosis
- Tumors
8
Q
Most common primary malignant tumor of the ureter
A
- Urothelial carcinomas
- Resemble those arising in the renal pelvis
9
Q
Urothelial carcinomas
A
- Most common malignant tumor of the ureter
- Occur most frequently during the 6th and 7th decade of life and cause obstruction of the ureteral lumen
- Sometimes are multifocal and commonly occur concurrently w/ similar neoplasms in the bladder or renal pelvis
10
Q
Ureter Calculi
A
- Rarely >5mm in diameter
*larger renal stones typically cannot enter ureters
11
Q
3 points of ureter narrowing prone to calculi obstruction
A
- Ureteropelvic junction
*where the renal pelvis meets the ureter
- Ureterovesical junction
*where they enter the bladder
- Where the ureter crosses the iliac vessels
12
Q
Sclerosing retroperitoneal fibrosis
A
- Uncommon cause of ureteral narrowing or obstruction
- 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 than females
- Most have no obvious cause and are considered primary or idiopathic
*a subset of cases are related to IgG4-related disease (elevated lvls serum IgG4, fibroinflammatory lesions rich in IgG4–secreting plasma cells)
13
Q
Sclerosing retroperitoneal fibrosis causes
A
- Drugs
*ergot derivatives
*beta-adrenergic blockers
- Adjacent inflammatory conditions
*vasculitis
*diverticulitis
*crohn’s disease
- Malignant disease
*lymphoma
*urinary tract carcinoma
14
Q
Congenital anomalies of the bladder
A
- Diverticula
- Exstrophy
- Vesicoureteral reflux
- Urachal anomalies
15
Q
Vesicoureteral reflux
A
- 1-2% of otherwise normal kids
- May lead to renal infection and scarring
- Incompetence of vesicoureteral valves
- Bacteria may ascend ureter to renal pelvis
- Due to congenital absence or shortening of intravesical portion of ureter
- Ureter is not compressed during micturition
16
Q
Bladder Diverticula
A
- Pouch like defect of bladder wall that may be congenital or acquired
*congenital: failure of development of normal musculature
*acquired: obstruction to urinary outflow and thickening of bladder wall (increased pressure)
- Most asymptomatic but can predispose to calculi, infection and vesicoureteral reflux
- Often multiple
17
Q
Exstrophy of bladder
A
- Also called “Exstrophy-Epispadias Complex”
- Developmental failure during embryology of the anterior abdominal wall and bladder causing:
*open bladder
*exposure of bladder and urethral on surface of lower abdomen and dorsal penis
*low set umbilicus
*diastasis of symphysis pubis
*anteriorly displaced anus
*genital defects
18
Q
Exstrophy of bladder diagnosis
A
- US before birth
- At birth thru physical exam
- Treatment = surgery
19
Q
Urachal anomalies
A
- Urachus is a fibrous remnant of the allantois, a canal that drains the urinary bladder of the fetus that joins and runs within the umbilical cord, normally obliterated after birth
- May remain patent in part or in whole
*totally patent = fistulous urinary tract connecting bladder w/ umbilicus
20
Q
Urachal anomaly symptoms
A
- Infant has persistent wet belly button
21
Q
Bladder obstruction causes
A
- Neoplastic
*prostatic hyperplasia or carcinoma
*invasion by perivesicular lesions
*bladder tumors
- Inflammation
*cystitis
- Foreign body and calculi
- Injury to bladder innervation leading to a neurogenic bladder
22
Q
Cystitis
A
- Inflammation of bladder
- Pyruia (WBC’s in urine) is present in almost all pts w/ acute cystitis or pyelonephritis
- More likely to develop in women due to shorter urethras
- Frequently precedes pyelonephritis (infection of the kidneys) w/ retrograde spread of microorganisms into the kidneys and their collecting systems
23
Q
Cystitis causes
A
- Inflammation of the bladder
- Most commonly due to bacterial infection
*E. Coli
*S. Saprophyticus
*P. Mirabilis
*K. Pneumoniae
- Fungal infection
*candida
- Parasitic
*S. Haematobium
- Iatrogenic
*radiation
*hemorrhagic
*polypoid
- Idiopathic
*interstitial cystitis
- Sometimes a secondary complication of an underlying disorder assoc. w/ urinary stasis
*prostatic enlargement
*cystocele of the bladder
*calculi
*tumors
24
Q
Bacterial causes of cystitis
A
- E. Coli (most common cause)
- S. Saprophyticus
- P. mirabilis
- K. Pneumoniae
All gram (-) rods except staph saprophyticus (gram (+))
25
Fungal causes of cystitis
- Candida
26
Parasitic causes of cystitis
- S. Haematobium
27
Iatrogenic causes of cystitis
- Radiation
- Hemorrhagic
- Polypoid
28
Cystitis Symptoms
- Inflammation of the bladder is characterized by a triad of symptoms
1. Frequency- acute cases may necessitate urination every 15-20min.
2. Lower abdominal/suprapubic pain
3. Dysuria- pain or burning on urination
- Can be caused by a number of inflammatory lesions, many of which manifest w/ frequency and dysuria
- Acute or chronic bacterial cystitis is extremely common, particularly in women, and results from retrograde spread of colonic bacteria in most cases
29
Secondary complications that can causes cystitis
- Prostatic enlargement
- Cystocele of the bladder
- Calculi
- Tumors
30
Acute and chronic cystitis predisposing factors
- Bladder calculi
- Urinary obstruction
- Diabetes mellitus
- Instrumentation
- Immune deficiency
31
Acute and chronic cystitis diagnosis
- Tissue biopsy plays little role in diagnosis
- Diagnosis by urine culture, urinalysis and clinical symptoms
- Urinalysis for eval of pyuria is the most valuable lab diagnostic test for UTI
32
Most common cause of cystitis
- E. Coli
\*gram (-) rod (appear pink on histo slide w/ purple being gram (+))
\*facultatively anaerobic
33
E. Coli
- Gram (-) rod
- Facultatively anaerobic
- Most common cause of UTIs
34
Staphylococcus saprophyticus
- Gram (+) coccus
- Coagulase-neg.
- Commonly seen in sexually active females 17-27, it is the 2nd most common cause of community-acquired UTIs, after E.coli
35
Klebsiella pneumoniae
- Gram (-) rod
- Non-motile
- Facultatively anaerobic
- Encapsulated
- Appears as a mucoid lactose fermenter on MacConkey agar
36
Proteus mirabilis
- Gram (-) rod-shaped
- Facultatively anaerobic
- Urease activity
- Swarming motility (almost resembles tree rings on agar)
37
Malakoplakia
- Chronic cystitis assoc. w/ E. Coli and proteus
- Etiology is defects in phagocytic function
- Increased incidence in immunosuppressed and transplant pts
38
Malakoplakia appearance
- On cystocopy appear as soft yellow raised mucosal plaques which may resemble carcinoma on cystoscopy
- On microscopy appear with foamy macrophages, multinucleated giant cells and lymphocytes
- Michaelis-Gutmann bodies: laminated mineralized concretions of calcium deposition in lysosomes within macrophages
39
Michaelis-Gutmann bodies
- Present in malakoplakia
- Laminated mineralized concretions of calcium deposition in lysosomes within macrophages
40
Candiduria Risks
- Candida caused cystitis
- ICU pts
- Older age
- Diabetes mellitus
- Antimicrobial use
- Indwelling bladder catheters
41
Candiduria treatment
- Fluconazole
\*excreted into the urine in its active form (allowing for effects within the bladder)
42
Schistosoma
- Parasitic worm infection
- 3 major species causing human infections:
\*schistosoma mansoni (intestines and liver)
\*schistosoma haematobium (GU tract)
\*schistosoma japonicum (intestines and liver)
- Schistosoma eggs, which induce predominantly Th-2 immune responses
43
Schistosoma haematobium infection
- Early infection
\*inflammatory granulomatous reaction
\*eosinophilic infiltration
\*local tissue destruction and fibrosis
- Chronic infection
\*fibrosis and calcifications of bladder wall
\*bladder neck obstruction
\*hematuria
\*pyuria
- Assoc. w/ bacterial superinfection, acute renal failure, and development of bladder cancer (squamous cell carcinoma)
44
Schistosoma haematobium chronic infection major risk
- Squamous cell carcinoma
45
Schistosoma mansoni appearance on histology slide
46
Schistosoma japonicum appearance on histology slide
47
Schistosoma haematobium microscopic appearance
48
Schistosoma haematobium appearance on histology slide
49
Radiation cystitis
- Radiation cystitis may be acute or chronic and can occur any time the bladder is included in the treatment field
- Clinically, the acute symptoms of radiation cystitis may appear as early as 4-6wks after initiation of therapy
- Chronic symptoms appear as much as 10yrs later
- Can present w/ hematuria, suprapubic pain
50
Schistosoma mansoni microscopic appearance
- Elongated/oval egg w/ a lateral spine (protrusion of the lateral side)
51
Polypoid cystitis
- Inflammatory lesion resulting from irritation of the bladder mucosa
- Indwelling catheters are the most commonly cited culprits
- Urothelium shows broad bulbous polypoid projections as a result of marked submucosal edema
52
Hemorrhagic cystitis
- Surface urothelium is ulcerated or thinned
- Extensive hemorrhage in the bladder wall
- Can cause massive hematuria
- Caused by cyclophosphamide in 1950’s
\*unrelated to dose
\*metabolic byproducts get excreted thru kidney
\*pts given lots of fluid to counteract nowadays when on this drug
53
Interstitial cystitis
- "Chronic pelvic pain syndrome"
- Chronic form of cystitis that occurs most frequently in women
- Etiology of this troubling condition is unknown, its evaluation and diagnosis remain controversial, and its treatment is largely empiric
54
Interstitial cystitis clincal findings
- Suprapubic pain
\*intermittent
\*sever
- Urinary frequency
- Urgency
- Hematuria
- Dysuria
55
Interstitial cystitis cytoscopic findings
- Hunner ulcer
\*reddened lesions on the bladder mucosa
- Glomerulations
\*petechial red areas
- Fissures
- Later in the course, transmural fibrosis may appear, leading to a contracted bladder
56
Urothelial neoplasia epidemiology
- Carcinoma of the bladder affects men more than women at a ratio of 3 to 4:1
- ~80% of pts are b/w 50 and 80
- Cigarette smokers have an increased relative risk of developing bladder cancer up to 4x
- Developing cancer increases w/ cigarette smoking but not w/ cigar or pipe smoking; suggesting inhalation is an important factor
57
Human bladder carcinogens
- Aromatic amines
\*napthylamines
\*benzidine
\*biphenyls
- Phenacetin-containing analgesics
- Alkylating drug cyclophosphamide
58
Urothelial neoplasia (bladder cancer) presentation
- Painless hematuria; dominant and sometimes only clinical manifestation
- Frequency, urgency and dysuria occasionally accompany the hematuria
- When the ureteral orifice is involved, pyelonephritis or hydronephrosis may follow
59
Most common bladder cancer?
- Urothelial cell carcinoma
60
Urothelial cell carcinoma
- Approx. 90% of malignant bladder tumors are urothelial/transitional cell carcinomas
61
Grading of bladder cancer
- CIS = carcinoma in situ; cancer is not invading the basement membrane
- Ta = noninvasive papillary
- T1 = invasion past the basement membrane w/ projections into the lamina propria
- T2 = invasions of the detrussor muscles (muscularis propria); treated by cystectomy
- T3 = invasion of adipose tissue
- T4 = invasion into the organs (prostate, seminal vesicles,...)
62
Papilloma
- Individual finger-like papillae have a central core of loose fibrovascular tissue covered by epithelium that is histologically identical to normal urothelium
63
Low-grade non-invasive papillary UCC
- Mild degree of nuclear atypia consisting of scattered hyperchromatic nuclei, infrequent mitotic figures predominantly toward the base, and slight variation in nuclear size and shape
- These low-grade cancers may recur and, although infrequent, may also invade. Only rarely do these tumors pose a threat to the pts. life
- Particularly common (occurring in 30-60% of tumors) are losses of genetic material on **chromosome 9** (including monosomy or deletions of 9p and 9q). These abnormalities are often the only chromosomal changes present in superficial noninvasive papillary tumors
64
High-grade non-invasive papillary UCC
- Dyscohesive cells w/ large hyperchromatic nuclei
- Mitotic figures, including atypical ones, are frequent
- Compared to low-grade lesions, these tumors have a much higher incidence of invasion into the muscular layer, a higher risk of progression, and, when assoc. w/ invasion, a significant metastatic potential
65
Non-invasive papillary UCC treatment
- Transurethral resection of bladder tumor
\*TURBT
66
High-grade non-invasive papillary UCC
- Transurethral resection of bladder tumor
\*TURBT
- Intravesicular bacillus calmette-guerin (BCG)
- OR-
- Intravesicular chemotherapy
67
Carcinoma in situe of the bladder
- Defined by the presence of cytologically malignant cells within a flat urothelium
- Cystoscopy: usually appears as an area of mucosal reddening, granularity, or thickening w/o an evident intraluminal mass
- Is commonly multifocal and may involve most of the bladder surface and extend into the ureters and urethra
- If untreated, 50-75% of CIS cases progress to invasive cancer
68
Carcinoma in situ of the bladder treatment
- Intravesical therapy
\*BCG is standard treatment
- Cystecomy is common treatment for pts refractory to intravesical therapy
69
Invasive UCC
- Urothelial carcinoma that invades beyond basement membrane
- Loss-of-function mutatiosn in the **TP53 and RB** tumor suppressor genes are almost always seen in high-grade and, frequently, muscle invasive tumors
- May be papillary, polypoid, nodular, solid or ulcerate
- Background urothelium may be normal or erythematous
- Solitary or multifocal
70
Detrussor muslce histology
71
Invasive UCC treatment
- Invasion into lamina propria (T1) usually managed w/ intravesical therapy
- Invasion into muscularis propria (T2) usually managed by radical cystectomy; radiation therapy in some centers
\*neoadjuvant or adjuvant chemotherapy may be offered
72
Bladder squamous cell carcinoma etiology
- Developmental
\*bladder exstrophy
- Environmental exposure
\*tobacco smoking
\*bladder stones
\*chronic indwelling catheters
\*neurogenic bladder
- Infectious agents
\*s. haematobium
\*HPV assoc. is very rare
73
Bladder squamous cell carcinoma epidemiology
- Incidence varies by geographic region
\*5% of bladder tumors in USA
\*75% in Egypt/Sudan (endemic schistosomiasis)
74
Bladder squamous cell carcinoma prognosis
- Poor prognosis
\*high-stage disease at presentation is common
- Reported 5yr survival = 7-50%
\*in pT3 disease = 13%
75
Bladder squamous cell carcinoma treatment
- Surgical
\*radical cystecomy is standard therapy
- Adjuvant therapy
\*often have neoadjuvant or adjuvant radiation
\*adjuvant chemotherapy is less standardized
76
Bladder squamous cell carcinoma macroscopic appearanc
- Fungating, tan-white mass
- Typically large and deeply invasive, often ulcerated
77
Bladder squamous cell carcinoma microscopic appearance
- Diagnosis of squamous cell carcinoma should be reserved for those tumors that are purely or almost entirely keratin forming and exhibiting intercellualr bridges
- 2 major histologic features: **keratin pearls** and **intercellular bridges**
78
Metastatic tumors to the bladder
- Prostate
- Breast
- Melanoma
- Lung
- Kidney
- Stomach
- Pancreas
- Ovary
