Chapter 21: Lower Urinary Tract - Ureters, Bladder, Urethra Flashcards
1
Q
Most common cause of hydronephrosis in children/infants?
A
Ureteropelvic junction (UPJ) obstruction
2
Q
If Ureteropelvic junction (UPJ) Obstruction occurs in children which sex is preferentially affected?
Bilateral or unilateral?
In adults?
A
- Children —> males; sometimes bilateral
- Adults —> woman; most often unilateral
3
Q
About 1/3 of children w/ recurrent UTI’s are found to have what?
A
Vesicoureteral reflux; most commonly dx in infancy/childhood
4
Q
Although rare, what is the most common primary malignant tumor of the Ureters?
Most often occurs when and causes what?
A
- Urothelial carcinomas
- 6th-7th decade of life causing obstruction
5
Q
What is the most common malignant mesenchymal tumor of the bladder seen in infants/children?
Often seen manifesting with what type of growth pattern?
A
- Embryonal rhabdomyosarcoma
- Manifest as a polypoid grapelike mass = Sarcoma botryoides
6
Q
What is the most common malignant mesenchymal tumor seen in the bladder of adults?
A
Leiomyosarcoma
7
Q
What are the 2 distinct precursor lesions of invasive urothelial carcinoma of the bladder and which is most common?
Type of grade for each?
A
- Papillary urothelial carcinoma (low- or high-grade) = most common
- Flat urothelial carcinoma in situ (uniformly high grade)
8
Q
Non-invasive high-grade urothelial carcinoma is associated with what genetic mutations allowing for progression to invasion?
A
Loss of TP53 or RB —> frequently progesses to muscle invasive dz
9
Q
Non-invasive low-grade papillary urothelial carcinoma is associated with what genetic mutations?
A
Gain of function FGFR3 and HRAS mutations
10
Q
What are 6 risk factors associated with urothelial carcinoma of the bladder?
A
- 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
11
Q
Loss of genetic material on which chromosome are particularly common in urothelial carcinoma?
A
- Chromosome 9
- Monosomy or deletions of 9p and 9q
12
Q
Which genetic mutation associated with urothelial carcinoma is a poor prognostic indicator?
A
p53
13
Q
What are 2 treatment options utilized in the majority of patients with non-invasive urothelial carcinoma of the bladder?
A
- Transurethral resection (TUR) and surveillance
- Intravesical therapy - chemotherapy or instillation of an attenuated strain of Mycobacterium bovis called bacillus Calmette-Guerin (BCG)
14
Q
What is the dominant and sometimes only clinical finding associated with urothelial carcinoma of the bladder?
A
Painless Hematuria
15
Q
What is the critical prognostic factor for bladder cancer?
A
- Extent of spread (STAGE) = critical prognostic factor
- Muscle invasion i.e., depth of muscle invasion is major prognostic issue to be established
16
Q
Major decrease in survival rates associated with bladder cancer is due to?
A
Invasion of the muscularis propria (detrusor m.)
17
Q
Unilateral ureteral obstruction typically results from _______ causes, whereas bilateral obstruction arises from ________ causes
A
Unilateral ureteral obstruction typically results from proximal causes, whereas bilateral obstruction arises from distal causes
18
Q
Sclerosing Retroperitoneal Fibrosis most often occurs in which age group and sex?
Characterized by and leads to what?
A
- M > F; occurs in middle to late age
- Fibrotic proliferative inflammatory process of retroperitoneal structures causing hydronephrosis –> urethral narrowing/obstruction
19
Q
A subset of Sclerosing Retroperitoneal Fibrosis is associated with what immunological related disease?
A
IgG4-related disease
20
Q
What are the 4 major extrinisic causes of Ureteral Obstruction?
A
- Pregnancy –> relaxation of smooth m. or pressure on ureters
- Periureteral inflammation –> salpingitis, diverticulitis, peritonitis
- Endometriosis
- Tumors
21
Q
Most cases of Sclerosing Retroperitoneal Fibrosis arise how and are known as?
A
- No obvious cause = considered primary or idiopathic
- Ormond disease
22
Q
What are some of the common secondary causes of retroperitoneal fibrosis, which may lead to ureteral obstruction?
A
- Drug exposures (ergot derivatives, β-blockers)
- Adjacent inflammatory conditions –> vasculitis, diverticulits, Chron’s
- Malignant disease –> lymphomas, urinary tract carcinomas
23
Q
Initial treatment and long term treatment of Sclerosing Retroperitoneal Fibrosis?
A
- Corticosteroids
- Eventually require ureteral stents or surgical extrication of ureters from surrounding fibrous tissue (ureterolysis)
24
Q
Acquired diverticulae of the bladder are most often seen in association with?
Clinical significance?
A
- Most often w/ prostatic enlargement (hyperplasia or neoplasia)
- Produce obstruction to urine outflow and marked bladder wall thickening
25
Bladder diverticulae are clinically significant because they may predispose to what?
- Sites of **u****rinary stasis**--\>**infection**and forming**bladder calculi**
- Predispose to **vesicoureteral reflux** if impinge on ureter
- Rarely, **carcinoma** may arise; tend to be in more advanced stage
26
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
27
Patients with exstrophy of the bladder have an increased risk of what malignancy?
Adenocarcinoma arising in bladder remnant
28
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
29
Which malignancy may potentially arise from a Urachal Cyst?
Bladder adenocarcinoma
30
Which gram negative, obligate intracellular parasite may cause cystitis?
*Chlamydia*
31
Which 2 organisms are a cause of cystitis in immunocompromised pts or those receiving long-term Abx?
1. *Candidia albicans = **more common***
2. *Cryptococcal agents*
32
Which virus may causes cystitis and hemorrhagic cystitis?
Adenovirus
33
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
34
What are 2 patterns of chronic cystitis that are **not** always related to infection?
1. **Follicular cystitis**
2. **Eosinophilic cystitis**
35
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**
36
How does chronic cystitis differ from acute in the nature of the inflammatory infiltrate?
**Chronic** associated with **mononuclear** inflammatory infiltrates
37
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**
38
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)
39
What will cystoscopy show in someome with Interstital Cystitis?
**Fissures/punctate hemorrhages** in bladder mucosa (glomerulations)
40
Chronic mucosal ulcers *(Hunner ulcers)* associated with Interstitial Cystitis is characterized by increased numbers of which immune cells?
Mucosal **mast cells**
41
What is Malakoplakia and what is it caused by?
Related to what infection?
- Chronic inflammatory reaction in the bladder
- **A****cquired****defects**in**phagocyte function**and related to chronic infection, mainly by***E. coli***and occasionally***Proteus***
42
Malakoplakia occurs with increased frequency in which patients?
**Immunosuppressed** transplant recipients
43
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**
44
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
45
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**
46
Polypoid Cystitis may be confused with what malignancy both clinically and histologically?
Papillary urothelial carcinoma
47
Cystitis glandularis and cystitis cystica are common lesions of the bladder characterized by what?
**Nests** of urothelium (**Brunn nests**) grow **downward** into **lamina propria**
48
Epithelial cells undergoing metaplasia in the **center** of Brunn nests taking on a **cuboidal** or **columnar** appearance is known as?
Cystitis **glandularis**
49
Which lesion is a result of implantation of shed renal tubular epithelial cells at sites of injured urothelium?
Nephrogenic adenoma
50
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**
51
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
52
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**
53
Papilloma urothelial tumors of the bladder are usually seen in which age group?
- Younger patients
54
Completely benign papillomas consisting of inter-anastomosing cords of cytologically bland urothelium that extends down into the lamina propria are called?
Inverted papillomas
55
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**
56
CIS or flat urothelial carcinoma may show scattered malignant cells in an otherwise normal urothelium, and this is known as?
Pagetoid spread
57
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**
58
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***
59
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**
60
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
61
What is the prognosis of SCC and adenocarcinoma of the bladder compared to urothelial carcinoma of the same stage?
**Worse** prognosis
62
For bladder tumors detected at early stages, what are the 2 mainstays of diagnosis?
1) Cytoscopy
2) Biopsy
63
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
64
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)
65
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**
66
What is the most common cause of bladder obstruction in a female?
**Cystocele** of the bladder
67
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**
68
Which organisms may be responsible for Non-Gonococcal Urethritis?
- ***Chlamydia** trachomatis (**D-K serotypes**)* = **gram negative, ovoid, non-motile**
- ***Mycoplasma*** = *Ureaplasma urealyticum*
69
Urethritis is most often accompanied by what in men and what in women?
- **Men** = prostatitis
- **Women** = cystitis
70
What is an example of inflammatory urethritis that is truly **noninfectious** in origin?
- **Reactive arthritis**
- **Triad** = arthritis, conjunctivitis, and urethritis
71
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
72
What is the most common cause of hypertrophy and trabeculation of the bladder wall in a male?
Secondary to **polpoid hyperplasia** of the **prostate**
73
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
74
How does a primary carcinoma of the urethra differ if it is proximally located vs. distally located?
- **Proximal** = urothelial differentiation
- **Distal** = SCC's
75
What cancer is associated w/ alpha-fetoprotein and alpha1 antitrypsina?
yolk sac tumor
| (in testes)
76
What cancer is characterized by KIT, OCT4, and PLAP staining?
seminoma
(embryonal carcinomas also have this, but seminoma is hallmark)
77
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
78
In what cancers can HCG levels be elevated?
choriocarcinomas
some syncytiotrophoblast-containing seminomas
79
What are schiller-duval bodies?
structures resembling endodermal sinuses
seen in yolk sac tumors
80
What characterizes choriocarcinoma?
* highly malignant testicular tumor
* often cause no test enlargement
* **cytotrophoblasts** (more regular cells)
* **syncytiotrophoblasts** (contain **HCG**)
81
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
82
How do testicular tumors spread?
seminomas: lymph first, then blood
Non seminomas: use blood more frequently, spread earlier
choriocarcinomas: hematogenous
83
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
84
What does the level of lactate dehydrogenase tell you about a testicular tumor?
correlates w/ mass of tumor cells
85
How are NSGCTs treated and what is their prognosis?
aggressive chemo
90% achieve complete remission
86
Which testicular tumor is radiosensitive?
seminoma
good prognosis
87
What are crystalloids or reinke?
rod-shaped crystals seen in leydig cell tumors in the cytoplasm
88
What is contained in the cytoplasm of leydig tumor cells?
lipid droplets
vacuoles
lipofuscin pigment
89
What type of testicular tumor produces androgens and sometimes estrogens?
leydig cell tumors
90
How do adults and children present w/ leydig cell tumors?
adults: testicular swelling or gynecomastia
children: precocious puberty
91
What characterize sertoli cell tumors?
hormonally silent
distinctive trabeculae that form cordlike structures and tubules
most are benign
92
What is the most common testicular neoplasm in men older than 60?
testicular lymphoma (non-hodgkin)
93
What are the most common testicular lymphomas?
diffuse large B-cell
Burkitt
EBV-positive extranodal NK/T cell
94
What is a chylocele?
lymph in tunica vaginalis
95
What are the 4 zones of the prostate?
peripheral
tranzitional (around urethra)
central
96
Where do most hyperplasias and carcinomas arise in the prostate?
hyperplasia: transitional zone
carcinoma: peripheral zone
97
What bacteria typically cause prostatitis?
e. coli
gram neg rods
enterococci
staphylococci
98
How do acute and chronic bacterial prostatitis differ in presentation?
acute: fever, chills, dysuria
chronic: low back pain, dysuria, suprapubic pain; may be asymptomatic
99
What is significant about treatment of bacterial prostatitis?
antibx poorly penetrate the prostate
100
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
101
What is the most common type of cancer in men?
adenocarcinoma of the prostate
102
What ethnic groups is prostate cancer common and uncommon in?
asians uncommon
most common in blacks
103
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
104
What is the significance of the BRCA2 gene in prostate cancer?
germline mutations --\> 20-fold risk in prostate cancer
105
What is the significance of HOXB13 in cancer?
germline mutation --\> incr risk in prostate cancer
106
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
107
What is the significance of basal cell layer in prostatic glands?
basal cells present in benign tumors
gone in malignancy
108
What is a reliable IHC marker used to diagnose prostate cancer?
AMACR
109
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
110
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
111
What are tumors in the ureters like?
primary tumors of ureter are rare
benign tumors sometimes happen and are usually of mesenchymal origin
112
What is a fibroepithelial polyp?
in ureters, bladder, ranal pelves and urethra
most commonly in the ureters
tumor-like lesion that presents as a small mass projecting into the lumen
113
What can radiation do to the bladder?
cause radiation cystitis
114
What 2 things can cause hemorrhagic cystitis?
cytotoxic antitumor drugs
adenovirus
115
What are the 2 types of chronic cystitis w/out infectious origin and what causes them?
follicular cystitis: lymphoid follicles w/in bladder mucosa and underlying wall
eosinophilic cystitis: infiltration w/ submucosal eosinophils
116
What is the main goal of biopsy in the treatment of interstitial cystitis?
to rule out carcinoma in situ, which can mimic interstitial cystitis
117
What types of bacteria are associated with malakoplakia?
E. coli and occasionally proteus
118
What are michaelis-gutmann bodies?
deposition of calcium in enlarged lysosomes of macrophages
seen in malakoplakia of the bladder
(look like dark circles in pink macrophages)
119
What is nephrogenic adenoma?
unusual lesion where shed renal tubular cells are implanted at sites of injured bladder urothelium --\> urothelium is replaced by cuboidal epithelium
120
What is phimosis?
orifice of the prepuce of the penis is too small to permit normal retraction
usually the result of repeated infection
121
What is balanoposthitis?
infection of the glans and prepuce of the penis
122
What is condyloma acuminatum?
benign wart caused by HPV
type 6 and 11 most common
branching, villous papillary CT stroma covered by hyperkeratosed epithelium
123
What are bowen dz and bowenoid papulosis both associated with?
infection w/ high risk HPV, most commonly typ 16
124
What is bowen dz?
solitary, gray-white lesion on the penis or shiny red, velvety plaques
hyperproliferative epidermis w/ dysplastic characteristics (pre-cancerous lesion)
intact basement membrane
125
What is bowenoid papulosis?
multiple reddish brown precancerous lesions on the penis
occurs in younger ppl than bowen dz, but histo is the same
virtually never develops into an invasive carcinoma and usually regresses spontaneously
126
what typically causes epididmytis and orchitis in children, the young, and old?
children: congenital abnormality and infection w/ gram neg rods
sexually active men under 35: chlamydia and gonorrhoeae
over 35: UTI stuff - e coli and pseudomonas
127
What are the most common genetic changes in prostate adenocarcenoma?
TPRSS2-ETS fusion genes
mutiations or deletions that activate the PI3K/AKT signalling pathway
128
What is the most common epigenetic alteration in prostate cancer?
hypermethylation of the GSTP1 gene
on chr 11q13
