Chapter 21: Lower Urinary Tract - Ureters, Bladder, Urethra COPY Flashcards
Most common cause of hydronephrosis in children/infants?
Ureteropelvic junction (UPJ) obstruction
If Ureteropelvic junction (UPJ) Obstruction occurs in children which sex is preferentially affected?
Bilateral or unilateral?
In adults?
- Children —> males; sometimes bilateral
- Adults —> woman; most often unilateral
About 1/3 of children w/ recurrent UTI’s are found to have what?
Vesicoureteral reflux; most commonly dx in infancy/childhood
Although rare, what is the most common primary malignant tumor of the Ureters?
Most often occurs when and causes what?
- Urothelial carcinomas
- 6th-7th decade of life causing obstruction
What is the most common malignant mesenchymal tumor of the bladder seen in infants/children?
Often seen manifesting with what type of growth pattern?
- Embryonal rhabdomyosarcoma
- Manifest as a polypoid grapelike mass = Sarcoma botryoides
What is the most common malignant mesenchymal tumor seen in the bladder of adults?
Leiomyosarcoma
What are the 2 distinct precursor lesions of invasive urothelial carcinoma of the bladder and which is most common?
Type of grade for each?
- Papillary urothelial carcinoma (low- or high-grade) = most common
- Flat urothelial carcinoma in situ (uniformly high grade)
Non-invasive high-grade urothelial carcinoma is associated with what genetic mutations allowing for progression to invasion?
Loss of TP53 or RB —> frequently progesses to muscle invasive dz
Non-invasive low-grade papillary urothelial carcinoma is associated with what genetic mutations?
Gain of function FGFR3 and HRAS mutations
What are 6 risk factors associated with urothelial carcinoma of the bladder?
- Cigarette smoking –> 3-7x ↑ risk
- Industrial exposure to aryl amines
- Schistosoma hematobium (SCC-70%)
- Long-term use of analgesics
- Long-term exposure to cyclophosphamide
- Radiation
Loss of genetic material on which chromosome are particularly common in urothelial carcinoma?
- Chromosome 9
- Monosomy or deletions of 9p and 9q
Which genetic mutation associated with urothelial carcinoma is a poor prognostic indicator?
p53
What are 2 treatment options utilized in the majority of patients with non-invasive urothelial carcinoma of the bladder?
- Transurethral resection (TUR) and surveillance
- Intravesical therapy - chemotherapy or instillation of an attenuated strain of Mycobacterium bovis called bacillus Calmette-Guerin (BCG)
What is the dominant and sometimes only clinical finding associated with urothelial carcinoma of the bladder?
Painless Hematuria
What is the critical prognostic factor for bladder cancer?
- Extent of spread (STAGE) = critical prognostic factor
- Muscle invasion i.e., depth of muscle invasion is major prognostic issue to be established
Major decrease in survival rates associated with bladder cancer is due to?
Invasion of the muscularis propria (detrusor m.)
Unilateral ureteral obstruction typically results from _______ causes, whereas bilateral obstruction arises from ________ causes
Unilateral ureteral obstruction typically results from proximal causes, whereas bilateral obstruction arises from distal causes
Sclerosing Retroperitoneal Fibrosis most often occurs in which age group and sex?
Characterized by and leads to what?
- M > F; occurs in middle to late age
- Fibrotic proliferative inflammatory process of retroperitoneal structures causing hydronephrosis –> urethral narrowing/obstruction
A subset of Sclerosing Retroperitoneal Fibrosis is associated with what immunological related disease?
IgG4-related disease
What are the 4 major extrinisic causes of Ureteral Obstruction?
- Pregnancy –> relaxation of smooth m. or pressure on ureters
- Periureteral inflammation –> salpingitis, diverticulitis, peritonitis
- Endometriosis
- Tumors
Most cases of Sclerosing Retroperitoneal Fibrosis arise how and are known as?
- No obvious cause = considered primary or idiopathic
- Ormond disease
What are some of the common secondary causes of retroperitoneal fibrosis, which may lead to ureteral obstruction?
- Drug exposures (ergot derivatives, β-blockers)
- Adjacent inflammatory conditions –> vasculitis, diverticulits, Chron’s
- Malignant disease –> lymphomas, urinary tract carcinomas
Initial treatment and long term treatment of Sclerosing Retroperitoneal Fibrosis?
- Corticosteroids
- Eventually require ureteral stents or surgical extrication of ureters from surrounding fibrous tissue (ureterolysis)
Acquired diverticulae of the bladder are most often seen in association with?
Clinical significance?
- Most often w/ prostatic enlargement (hyperplasia or neoplasia)
- Produce obstruction to urine outflow and marked bladder wall thickening
Bladder diverticulae are clinically significant because they may predispose to what?
- Sites of urinary stasis–>infectionand formingbladder calculi
- Predispose to vesicoureteral reflux if impinge on ureter
- Rarely, carcinoma may arise; tend to be in more advanced stage
The exposed bladder mucosa in exstrophy of the bladder may undergo what transformation?
Is subject to what?
- Colonic glandular metaplasia
- Subject to infections which may spread to upper levels of urinary tract
Patients with exstrophy of the bladder have an increased risk of what malignancy?
Adenocarcinoma arising in bladder remnant
Abdominal pain and fever in a 4 yo w/ a CT showing a heterogenous mass in the midline anterior to the bladder is consistent with what?
Infected urachal remnant/cyst
Which malignancy may potentially arise from a Urachal Cyst?
Bladder adenocarcinoma
Which gram negative, obligate intracellular parasite may cause cystitis?
Chlamydia
Which 2 organisms are a cause of cystitis in immunocompromised pts or those receiving long-term Abx?
- Candidia albicans = more common
- Cryptococcal agents
Which virus may causes cystitis and hemorrhagic cystitis?
Adenovirus
Classic triad of cystitis sx’s?
1) Frequency –> every 15-20 mins in acute cases
2) Lower abdominal pain - suprapubic region
3) Dysuria - pain or burning on urination
What are 2 patterns of chronic cystitis that are not always related to infection?
- Follicular cystitis
- Eosinophilic cystitis
Patients receiving which drugs may develop hemorrhagic cystitis and are also at an increased risk for carcinoma of the bladder?
Cytotoxic antitumor drugs, such as cyclophosphamide
How does chronic cystitis differ from acute in the nature of the inflammatory infiltrate?
Chronic associated with mononuclear inflammatory infiltrates
In acute cystitis how does the mucosa appear and what type of inflammatory infiltrate is present?
- Hyperemia of the mucosa
- Neutrophilic infiltrate, sometimes associated w/ exudate
Chronic, persistent, painful form of cystitis characterized by intermittent, often severe suprapubic pain, urinary frequency, urgency, hematuria and dysuria without evidence of bacterial infection is known as?
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
What will cystoscopy show in someome with Interstital Cystitis?
Fissures/punctate hemorrhages in bladder mucosa (glomerulations)
Chronic mucosal ulcers (Hunner ulcers) associated with Interstitial Cystitis is characterized by increased numbers of which immune cells?
Mucosal mast cells
What is Malakoplakia and what is it caused by?
Related to what infection?
- Chronic inflammatory reaction in the bladder
- Acquireddefectsinphagocyte functionand related to chronic infection, mainly byE. coliand occasionallyProteus
Malakoplakia occurs with increased frequency in which patients?
Immunosuppressed transplant recipients
Major histomorphological characteristics of the mucosal plaques associated w/ Malakoplakia?
Soft, yellow, slightly raised and filled w/ large foamy macrophages w/ occasional multinucleate giant cells + lymphocytes
What are the characteristic morphological findings of the macrophages associated w/ Malakoplakia?
- Macrophages w/ adundant granular cytoplasm
- Laminated mineralized concretions due to deposition of calcium in enlarged lysosomes, known as Michaelis-Gutmann bodies, present in macrophages
Polypoid Cystitis is most commonly due to what?
What is the characteristic morphology of the urothelium?
- Indwelling catheters (most common), but any injurious agent may cause
- Urothelium thrown into broad bulbous polypoid projections as result of marked submucosal edema
Polypoid Cystitis may be confused with what malignancy both clinically and histologically?
Papillary urothelial carcinoma
Cystitis glandularis and cystitis cystica are common lesions of the bladder characterized by what?
Nests of urothelium (Brunn nests) grow downward into lamina propria
Epithelial cells undergoing metaplasia in the center of Brunn nests taking on a cuboidal or columnar appearance is known as?
Cystitis glandularis
Which lesion is a result of implantation of shed renal tubular epithelial cells at sites of injured urothelium?
Nephrogenic adenoma
Implantation of shed renal tubular cells at sites of injured urothelium (nephrogenic adenoma), the overlying urothelium may be focally replaced by what?
Assuming what type of growth pattern?
- Replaced by cuboidal epithelium
- Assume a papillary growth pattern
In two-pathway model, low-grade superficial papillary tumors are characterized by what genetic mutations first and then second?
1) FGFR3 and RAS mutations + chromosome 9 deletions
2) May then lose TP53 or RB —> invasion
What is the major pathologic finding of Papillary Urothelial Neoplasia of Low Malignant Potential (PUNLMP) that distinguishes it from papilloma?
- THICKENED urothelium covering papillary projections
- Also tend to be larger
Papilloma urothelial tumors of the bladder are usually seen in which age group?
- Younger patients
Completely benign papillomas consisting of inter-anastomosing cords of cytologically bland urothelium that extends down into the lamina propria are called?
Inverted papillomas
High-grade papillary urothelial cancers contain what morphologically distinct cells and other findings?
- Dyscohesive cells w/ large hyperchromatic nuclei
- Some cells are highly anaplastic
- Loss of polarity
CIS or flat urothelial carcinoma may show scattered malignant cells in an otherwise normal urothelium, and this is known as?
Pagetoid spread
The lack of cohesiveness in high-grade papillary urothelial carcinoma and flat urothelial CIS, results in what common finding?
Shedding of malignant cells into the urine
Where in the world is SCC of the bladder frequently seen and due to what?
- Middle East (i.e., Ehypt, Sudan)
- Due to endemic Schistosoma haematobium
SCC of the bladder is most commonly seen as what?
- Mixed urothelial carcinomas w/ areas of SCC
- Most are invasive, fungating tumors or are infiltrative and ulcerative
How likely is recurrence after resection of urothelial tumor?
If recurrence occurs, at which site does it happen?
- High likelihood of developing new tumors after excision
- Most of the subsequent tumors arise at different sites from the original lesion
What is the prognosis of SCC and adenocarcinoma of the bladder compared to urothelial carcinoma of the same stage?
Worse prognosis
For bladder tumors detected at early stages, what are the 2 mainstays of diagnosis?
1) Cytoscopy
2) Biopsy
How can the urine be used as a screening measure of bladder cancer?
Looking for what?
- Cytologic examination of cells in urine to detect chromosomal abnormalities (i.e., aneuploidy of Cr. 3, 7, and 17 and 9p deletions)
- Using FISH
Although rare, what type of lymphoma may involve the bladder as a either a primary lesion as well as component of systemic disease?
Non-Hodgkin lymphoma (diffuse large B-cell and MALT)
What are the features of sarcomas (mesenchymal tumors) which are distinct from other tumors of the bladder?
- Produce large masses
- Protrude into the vesicle lumen
What is the most common cause of bladder obstruction in a female?
Cystocele of the bladder
What is an early finding and late finding morphologically with obstruction of the bladder outlet?
- Early = thickening of bladder wall 2’ to muscle hypertrophy
- Late = muscle bundles enlarge and produce trabeculation of the bladder wall
- In course of time crypts form and may become diverticula
Which organisms may be responsible for Non-Gonococcal Urethritis?
- Chlamydia trachomatis (D-K serotypes) = gram negative, ovoid, non-motile
- Mycoplasma = Ureaplasma urealyticum
Urethritis is most often accompanied by what in men and what in women?
- Men = prostatitis
- Women = cystitis
What is an example of inflammatory urethritis that is truly noninfectious in origin?
- Reactive arthritis
- Triad = arthritis, conjunctivitis, and urethritis
A small, red, painless mass of the external urethral meatus, in an older female, consisting of inflammed granulation tissue covered by intact but extremely friable mucosa
Urethral caruncle
What is the most common cause of hypertrophy and trabeculation of the bladder wall in a male?
Secondary to polpoid hyperplasia of the prostate
Gonococcal urethritis is the earliest manifestation of infection by which organism?
What is the gram stain and morhphology of this organism?
- Neisseria gonorrhea
- Gram negative; diplococcus
How does a primary carcinoma of the urethra differ if it is proximally located vs. distally located?
- Proximal = urothelial differentiation
- Distal = SCC’s
What cancer is associated w/ alpha-fetoprotein and alpha1 antitrypsina?
yolk sac tumor
(in testes)
What cancer is characterized by KIT, OCT4, and PLAP staining?
seminoma
(embryonal carcinomas also have this, but seminoma is hallmark)
What is the difference in gene markers in seminomas and embryonal carcinomas?
both have OCT4 and PLAP
e carcinomas also have cytokeratin and CD30 and are neg for KIT
In what cancers can HCG levels be elevated?
choriocarcinomas
some syncytiotrophoblast-containing seminomas
What are schiller-duval bodies?
structures resembling endodermal sinuses
seen in yolk sac tumors
What characterizes choriocarcinoma?
- highly malignant testicular tumor
- often cause no test enlargement
- cytotrophoblasts (more regular cells)
- syncytiotrophoblasts (contain HCG)
What is distinct about non-germ cell malignancies that can arise within testicular teratomas?
chemoresistant - only hope for cure is in resection
retain isochromosome 12p
How do testicular tumors spread?
seminomas: lymph first, then blood
Non seminomas: use blood more frequently, spread earlier
choriocarcinomas: hematogenous
What are the 3 stages of testicular cancer?
1: confined to testis, epididymis, or spermatic cord
2. spread confined to retroperitoneal nodes below the diaphragm
3. metastases outside retro nodes or above diaphragm
What does the level of lactate dehydrogenase tell you about a testicular tumor?
correlates w/ mass of tumor cells
How are NSGCTs treated and what is their prognosis?
aggressive chemo
90% achieve complete remission
Which testicular tumor is radiosensitive?
seminoma
good prognosis
What are crystalloids or reinke?
rod-shaped crystals seen in leydig cell tumors in the cytoplasm
What is contained in the cytoplasm of leydig tumor cells?
lipid droplets
vacuoles
lipofuscin pigment
What type of testicular tumor produces androgens and sometimes estrogens?
leydig cell tumors
How do adults and children present w/ leydig cell tumors?
adults: testicular swelling or gynecomastia
children: precocious puberty
What characterize sertoli cell tumors?
hormonally silent
distinctive trabeculae that form cordlike structures and tubules
most are benign
What is the most common testicular neoplasm in men older than 60?
testicular lymphoma (non-hodgkin)
What are the most common testicular lymphomas?
diffuse large B-cell
Burkitt
EBV-positive extranodal NK/T cell
What is a chylocele?
lymph in tunica vaginalis
What are the 4 zones of the prostate?
peripheral
tranzitional (around urethra)
central
Where do most hyperplasias and carcinomas arise in the prostate?
hyperplasia: transitional zone
carcinoma: peripheral zone
What bacteria typically cause prostatitis?
e. coli
gram neg rods
enterococci
staphylococci
How do acute and chronic bacterial prostatitis differ in presentation?
acute: fever, chills, dysuria
chronic: low back pain, dysuria, suprapubic pain; may be asymptomatic
What is significant about treatment of bacterial prostatitis?
antibx poorly penetrate the prostate
How does granulomatous prostatitis most commonly happen?
instillation of BCG w/in bladder for tx of cancer –> granulomas form, but no clinical significance or tx
What is the most common type of cancer in men?
adenocarcinoma of the prostate
What ethnic groups is prostate cancer common and uncommon in?
asians uncommon
most common in blacks
What is the significance of the X-linked AR gene in prostate cancer?
short CAG repeats in gene = highest risk, in blacks
medium length in caucasians
asians have the longest = lowest risk
What is the significance of the BRCA2 gene in prostate cancer?
germline mutations –> 20-fold risk in prostate cancer
What is the significance of HOXB13 in cancer?
germline mutation –> incr risk in prostate cancer
What are the most common genetic changes in prostate cancer?
ETS-TMPRss2 chromosomal rearangement
deletions that activate P13K/AKT
hypermethylation in GSTP1 on chrom 11q13
What is the significance of basal cell layer in prostatic glands?
basal cells present in benign tumors
gone in malignancy
What is a reliable IHC marker used to diagnose prostate cancer?
AMACR
How does the Gleason system work?
rate 2 most common patterns 1 to 5 and add them together
2 = most differentiated, best prognosis
10 = worst
What are the stages of prostate cancer?
T1 = clinically inapparent lesion
T2 = cancer confined to prostate
T3 = local extraprostatic extension
T4 = invasion of contiguous organs/supporting structures
