Male Path 1 Flashcards
What are the three layers of the bladder?
- urothelium
- 5-7 layers
- umbrella (superficial), intermediate, and basal layer
- urine blood barrier
- ability to dilate and contract - lamina propria
- loose connective tissue, delicate bundles of smooth muscle fibers- muscularis mucosae - muscularis propria
- deep muscle, detrusor muscle; muscle wall arranged in several layers
What is the most common cause of hydronephrosis in children?
ureteropelvic junction obstruction
Ureteritis/ Cystitis cystica
up to 60% of bladder
- von Brunn’s nests with degenerated central cells to form small cystic cavities
- translucent submucosal pearly-yellow cysts, usually up to 5mm
NOT INFLAMMATION
What are intrinsic vs extrinsic obstructions of the urinary tract?
Intrinsic
- calculi
- strictures
- tumors
- blood clots
- neurogenic
Extrinsic
- pregnancy
- periureteral inflammation
- endometriosis
- retroperitoneal fibrosis
- tumors
What is exstrophy of the bladder?
developmental failure in the anterior wall of the abdomen and in the bladder
Acute and Chronic cystitis
women (short urethras)
- predisposing factor: bladder calculi, urinary obstruction, diabetes mellitus, instrumentation, immune deficiency
- Coli forms: e. coli, proteus klebsiella, enterobacter, staph saprophyticus
- frequence, pain, dysuria, fever
-peticheal hemorrhages and chronic inflammatory cells
Interstitial Cystitis-Chronic pelvic pain syndrome Epidemiology Patholgoy Symptoms Cystoscopic findings Histology Treatment
Non-bacterial form of cystitis (negative cultures and cytology)
90% female
30-50 years
- Associated with allergies and autoimmune
- intermittent, often severe, suprapubic pain, urinary frequency, urgency, hematuria, and dysuria
cystoscopic findings: fissures and punctate hemorrhages
Pathology:
- some patients have chronic mucosal ulcers (Hunner’s ulcer),
- MAST CELLS, could be seen-most important to distinguish from carcinoma in situ
Treatment: empiric. diminished bladder capacity
Malakoplakia Symptoms Cystoscopy Histology Epidemiology: Other sides:
Symptoms:
Recurrent fever, bladder irritability and pain, hematuria, pyuria, weight loss
Cystoscopy: multiple raided soft yellow to brown plaques and nodules
Histology:
-dense infiltrate of large foamy macrophages with finely granular eosinophilic cytopalsm (von Hansemann histiocytes)
-blue targetoid calcospherules (Michaelis-Gutmann bodies)
Epidemiology:
-more common in females, 5th decade
Related to chronic bacterial infection (e coli)
Other body sites: colon, lung, kidney, other GU side
Leukoplakia
Cause
Risk for
HIstology
long term irritation or chronic infection- stones, non functioning bladders, schistosomiasis
-if extensive may interfere with contraction and dilation
Risk factor for development of carcinoma *******
Histology-keratinizing squamous epithelium
Bladder Cancer
Epidemiology
Clinical Presentation
Etiology
Epidemiology
Male: Female 3:1
Age 50-80-average age diagnosis 65
Bladder is the most common site for urothelial carcinoma
Clinical Presentation
- Painless hematuria 80%
- irritative symptoms (dysuria, frequency urgency-mostly seen in high grade and invasive carcinomas)
- flank pain, bone pain, pelvic mass
Etiology
- Cigarette smoking**
- Arylamines
- Chronic cystitis
- Schistosomiasis—egypt
- UTI
- Indwelling catheters
- Urolithiasis - Cyclophosphamide-acrolein metabolite
- Long term analgesic usage (phenacetin)
- pelvic irradiation
What are the steps of the papillary pathway of bladder cancer, which is 80% of bladder cancer?
- Hyperplasia (papillary urothelial hyperplasia)
- Genetically instable?!? FGFR3
- Low grade carcinoma
- RAS?
- High grade carcinoma
- Invasive Carcinoma
What are the steps of the non papillary pathway of bladder cancer, which is 20% of bladder cancer?
- 9p-, 9q-, p16
- Dysplasia (flat noninvasive carcinoma)
3a. Genetically instable p53 (~60%)–High grade carcinoma—Invasive Carcinoma
3b. (
If untreated 50%-70% of carcinoma in situ progress to what?
muscle invasive cancer
Urothelial papilloma
1% of papillary urothelial tumors
Papillary urothelial neoplasm of low malignant potential (PUNLMP)
papillary urothelial lesion with orderly arranged cells within papillae with minimal architectural abnormalities and minimal nuclear atypia
M> F (3-5:1)
MALE
- cytology negative
- increased urothelial thickness, preserved polarity
- mitoses-very rare, basal
local recurrence 30%, progression 5%
Molecular findings
- diploid with low proliferative rate
- FGFR3 mutation-85%
Low grade urothelial carcinoma
- slender papillary branching fronds with minimal fusion
- easily recognized variation in architectural and cytological features-nuclear enlargement
- mytosis may be present at any level
- cytology-mostly negative
local recurrence 50-70%
progression 10%
Molecular findings
- diploid with low proliferative rate
- FGFR3 mutation-88%
- altered expression of CK20, CD44, p53 and p63 may be seen
High grade urothelial carcinoma
Papillary fronds with obvious disordered arrangement (fusion) and cytologic atypia
- pleomorphism, altered polarity, mitosis
- low power diagnosis
- cytology positive
- local recurrence 36-60%
- progression 40-60%
- disease specific mortality 15%
Molecular findings:
- aneuploid with high proliferative rate
- altered expression of CK 20, CD44, p53 and p63
As tumor grade and pathology stage progress, what occurs with FGFR3 and P53?
P53 increases
FGFR3 decreases
Can you detect low grade by flushing out bladder cells?
no only high grade, low grade look normal
What is the treatment of small, papillary, low grade tumors?
resection and follow up (cystoscopies +cytology) for the rest of life
What is the treatment of multiple tumors?
intravesical chemotherapy
What is the treatment of CIS, papillary high grade, T1?
intravesical immunotherapy (BCG)
What is the treatment for T2-4, tumors refractory to BCG, CIS in prostatic urethra?
cystectomy
What is the treatment for metastases ?
chemo
How does BCG-bacillus calmette guerin- work ?
- Attenuated strain of mycobacterium tuberculosis
- Intravesical BCG immunotherapy is one of the most widely used approach to manage superficial bladder cancer
- Elicits a local cell-mediated immune reaction that destroys tumor cells
- designed to treat established disease
- designed to prevent recurrence
What is the prognosis for low grade papillary lesions?
98% 10 year survival
What is the prognosis for high grade papillary carcinoma?
75% 10 year survival
What is the prognosis for invasive carcinoma?
30% 10 year survival (once tumor is in lamina propria)
What are other epithelial tumors of the bladder?
- squamous cell carcinoma-schistosomaias, indwelling catheters
- adenocarcinoma-can’t take out
- small cell carcinoma
What are the most common mesenchymal tumors of the bladder in infancy?
embryonal rhabdomyosarcoma
What are the most common mesenchymal tumors of the bladder in adults?
leiomyosarcoma
What is the cause of nongonococcal urethritis? gonococcal urethritis?
nongonococcal urethritis- E coli
gonococcal urethritis- Neisseria gonorrhea
Caruncle
inflamed granulation tissue polyp
peyronie disease
fibrous bands involving corpus cavernosum of the penis-penis erections
carcinoma of the urethra are what in the proximal and distal?
proximal urothelial, distal squamous
What are the two cells that make up the normal prostate?
- secretory cells
2. basal cells
Nodular Hyperplasia-Benign prostatic hyperplasia?
Hyperplasia of prostatic glands and stroma
- Extremely common
- 40y-20%
- 60y-70%
- 80y-90%
- 30% moderate to severe symptoms (mostly due to secondary effects)
- compression of urethra-difficulties urination (frequency, nocturia, difficulties with starting and stopping, overflow dribbling, dysuria)
- retention of urine in the bladder-distension and hypertrophy, cystitis, pyelonephritis
What is the etiology of BPH?
Androgens, specifically DHT
autocrine fashion on gland
-drugs that inhibit 5a reductase are used in treating BPH
What does BPH look like grossly? Histologically? Secondary changes?
Gross: Prostatic enlargement due to presence of nodules in the preprostatic region (periurethral, transitional zone)
Micro: Nodularity due to proliferation or dilation of glandular components and muscular proliferation of stromal component
Secondary changes: hypertrophic bladder
Prostate cancer
Epidemiology
Gross Features
Microscopic Features
Adenocarcinoma-the most common cancer in men, second cause of cancer death in men (although only European>Asian
Gross:
palpably hard, tan/white nodule
posterolateral portion of gland
MOST OFTEN tumor is not grossly visible
Histologically:
- small glands with an infiltrative pattern
- nuclear enlargment
- PROMINANT NUCLEIOLI
- SINGLE CELL LAYER-without basal layer
- perineural invasion
Prostate cancer
Molecular
MOST COMMON:
Hypermethylation of glutathione S-transferase which downregulated the gene (chr 11q). Other epigenetically silenced genes are PTEN, RB, p16, INK4a, MLH1, MLH2, and APC
Androgen Receptor: X linked AR gene contains a polymorphic sequence composed of CAG repeats
(patients with shortest CAG repeats have the highest androgen sensitivity)
BRCA2 germline mutation (13q): 20 fold increased risk for PCA
Somatic mutation resulting in chromosomal rearrangement placing ETS gene under the control of the TMPPRSS2 promoter. ETS fusion genes could be detected in urine (DONT need to know this one)
What are biomarkers of PCA?
PSA
AMACR
EZH-2
PCA3
What is PSA?
serine protease composed of a single-chain glycoprotein
- produced by epithelial cells of normal hyperplastic and cancerous prostatic tissue
- secreted into seminal fluid where it dissolves seminal coagulum
Elevated:
pastatic ca, BPH, prostatitis, trauma, infarct, DRE, ejaculation
Reduced by: 5 a reductase inhibitors, androgen deprivation, prostatectomy
PSA levels increase with age
PSA> 4ng/ml is abnormal (n=0-4)
PSA density-ratio between the serum PSA value and volume of prostate gland
PSA velocity-rate of change in PSA value with time
-decreased fraction of free PSA in cancer
Prostatic Intraepithelial neoplasia
proliferation neoplastic cells within large ducs
-natural history unknown
Incidence
Benign prostate-4-18% (high grade PIN)
Prostate with cancer-33-100% (high grade PIN)
-doesnt mean you are going to have invasive carcinoma
What is the grading scale of prostate cancer?
Based on architectural pattern
Five grades-1-5
Gleason score-primary dominant grade + secondary subdominant grade (2-10)
BEST Marker to predict Prognosis
Where does prostate cancer metastasize to?
osteoblastic metastases
What is the treatment of prostate cancer?
Organ confined: radical prostatectomy
Alternative treatment of localized disease: radiation
Advanced/metastatic disease: androgen deprivation
