Pathology of the Lower Urinary Tract and Male Genital System I Flashcards
Urothelium
- How many layers?
- What kind of cells are there?
- What layers are underneath it?
- 5-7 layers
- umbrella (superficial), intermediate, basal
- Lamina propria (loose connective tissue, delicate bundles of smooth muscle fibers-muscularis mucosae), and Muscularis propria (deep muscle, destrusor muscle, arranged in several layers)
Urothelium
- Function
- What ability does it have to carry out this functions?
- urine-blood barrier
2. tight junctions and desmosomes that allow it to dilate and contract while keeping the barrier intact
Ureter Congenital Abnormalities
- How common?
- What can an obstruction cause?
- What do pts with double ureters have?
- What is the most common cause of hydronephrosis in children?
- What can occur when there is a defect of ureteral muscle? (2)
- 2-3% of all autopsies
- reflux –> inflammation –> pyelonephritis
- double renal pelvis, bifid pelvis
- ureteropelvic junction obstruction (can also be acquired in young women)
- diverticula, megaureter
Ureteritis/Cystitis Cystica
- How do they occur?
- Gross look?
- Micro look?
- Malignant potential?
- urothelium invaginates into the lamina propria and forms von Brunn’s nests w/ degenerated central cells to form small cystic cavities
- translucent, submucosal, pearly-yellow cysts, usually up to 5 mm
- glandular metaplasia, cystic formation
- benign
Causes of UT Obstructions
- Intrinsic (5)
- Extrinsic (5)
- calculi, strictures, tumors, blood clots, neurogenic
2. pregnancy, periureteral inflammation, endometriosis, retroperitoneal fibrosis, tumors
Urinary Bladder- Congenital Abnormalities
- What is Exstrophy?
- What is Vesicoureteral reflux?
- developmental failure in the anterior wall of the abdomen and in the bladder- bladder sits exposed to outer elements; undergoes metaplasia which can –> adenocarcinoma
- Valve defect allows urine from the bladder to reflux back into the kidney and predisposes it to hydrnephrosis
Acute and Chronic Cystitis
- Define
- Who tends to get it? Why?
- What are some predisposing factors?
- What bacteria cause it?
- Symptoms
- Treatment
- bladder inflammation
- women, short urethra
- bladder calculia, urinary obstruction, diabetes mellitus, instrumentations, immune deficiency
- E coli, Proteus, Klebsiella, Enterobacter, Staph saprophyticus
- Frequency, pain (lower abdomen), dysuria (painful urination), fever
- Bactrim
Interstitial Cystitis
- AKA
- Define
- Who tends to get it? What age?
- Associated with what? (2)
- Chronic Pelvic Pain Syndrome
- Non-bacterial form of cystitis (negative cultures and cytology)
- 90% females, 30-50
- allergies, autoimmune diseases (SLE, RA, thyroiditis)
Interstitial Cystitis
- Symptoms
- Cytoscopic findings
- Histo findings
- Treatment
- What must be ruled out?
- intermittent, often severe, suprapubic pain, urinary frequency, urgency, hematuria, and dysuria
- fissures and punctate hemorrhages
- inflammation, neutrophils; some have chronic mucosal ulcers (Hunner’s ulcer), mast cells may be seen
- Empiric, treat symptoms
- carcinoma in situ
Malakoplakia
- Define
- Symptoms
- Cytoscopy
- Histology
- inflammatory condition that presents as a papule/nodule
- recurrent fever, bladder irritability, pain, hematuria, pyuria, weight loss
- multiple raised soft yellow to brown plaques and nodules
- dense infiltrate of large foamy macrophages with finely granular eosinophilic cytoplasm (von Hansemann histiocytes) and blue targetoid calcospherules (Michaelis-Gutmann bodies); Fe and Ca depositions
Malakoplakia
- Who tends to get it?
- Related to what?
- Where else can it present?
- females, fifth decade
- chronic bacterial infection (E. coli)
- colon, lung, kidney, other GU sites
Leukoplakia
- What is it?
- Etiology
- What can happen if it is extensive?
- Risk factor for what?
- Gross look
- Histo look
- squamous metaplasia
- long term irritation or chronic infection- stones, nonfunctioning bladders, schistosomiasis
- may interfere with contraction and dilatation
- development of carcinoma
- gray-white areas (due to keratin)
- keratinizing squamous epithelium
Bladder Cancer
- What is the good news/bad news?
- Which gender gets it more? Average age?
- Bladder is most common site for what?
- Presentation
- most are superficial- easy to treat; have a high recurrence rate, so must follow up
- male; 65
- urothelial carcinoma
- painless hematuria; irritative symptoms (dysuria, frequency, urgency)- in high grade carcinomas; flank pain, bone pain, pelvic mass
Etiology of Bladder Cancer
Cigarette Smoking (high risk) Arylamines (found in dye products) Chronic cystitis (schistosomiasis, UTI, indwelling catheter, urolithiasis) Cyclophosphamide- acrolein metabolite Long term analgesic usage (phenacetin) Pelvic Irradiation
Pathogenesis
- 90% are…
- 10% are…
- Mutations in the 90%
- Mutations in the 1%
- dysplasia (flat, noninvasive carcinoma)
- hyperplasia (papillary urothelial hyperplasia)
- RAS
- RB, p53
Bladder Cancer
- 2 Morphologic patterns
- What is staging based on?
- What does low grade urothelial Carcinoma in Situ look like?
- What does high grade urothelial Carcinoma in Situ look like?
- Papilloma or Flat (areas of red velvety patches)
- Depth of invasion
- oriented vertically, low nucleus/cytoplasm ratio
- large, oriented in every direction;
Papillary Urothelial Carcinoma, Low Grade
- Histo look
- How much nuclear atypia?
- Recurrence rate
- Progression rate
- How helpful is cytology?
- Treatment
- orderly appearance, both architecturally and cytologically
- minimal
- 50%
- 10%
- Not very, can’t be distinguished from other cells; stay diploid
- resect, follow up
Papillary Urothelial Carcinoma, high grade 1 Histo look (3 things) 4. invasion rate 5. How helpful is cytology? 6. Treatment
- discohesive, large hyperchromatic nuclei (higher cytoplasm/nucleus ratio)
- disarray with loss of polarity
- mitotic figures, including atypical ones
- 80%,
- helpful, can distinguish/ID cancer from other cells
- Chemo
Bacillus Calmette-Guerin
- What is it?
- What is it used for?
- Why?
- Designed to do what? (2)
- attenuated strain of Mycobacterium tb
- intravesical BCG immunotherapy is one of the most widely used approaches to manage superficial bladder cancer
- elicits a local cell-mediated immune reaction that destroys tumors
- treat established disease and prevent recurrence
Bladder Cancer Prognosis
- Low grade papillary lesions
- High grade papillary carcinoma
- Invasive carcinoma (in lamina propia)
- > 98% 10yr survival
- 75%
- 30%
Name other epithelial tumors of the bladder (3)
Squamous cell carcinoma
Adenocarcinoma
Small cell carcinoma
Mesenchymal Tumors of the Bladder
- How common?
- Which is most common in infancy?
- Which is most common in adults?
- exceedingly rare
- embryonal rhabdomyosarcoma
- Leiomyosarcoma
Urethra 1. 2 common causes of urethritis Tumor and Tumor-Like Lesions 2. What is a Caruncle? 3. What is Peyronie disease? 4. Common carcinomas?
- nongonococcal- E. coli; gonococcal: n. gonorrheae
- inflamed granulation tissue polyp
- fibrous bands involving corpus cavernosum of the penis
- proximal urothelial, distal squamous
Prostate
- 2 normal cells
- 2 main causes of inflammation
- How is this determined?
- Secretory cells and basal cells
- bacterial (acute and chronic) and abacterial
- bacterial cultures and microscopic examination of fractionated urine
Benign Prostatic Hyperplasia (BPH)
- Define
- How common?
- Symptoms
- Etiology
- hyperplasia of prostatic glands and stroma
- extremely common;
- compression of urethra (difficulties w/ urination), retention of urine in the bladder (–> distention and hypertrophy, cystitis, pyelonephritis) (only 30% have moderate to severe symptoms)
- DHT (converted from testosterone by 5 alpha reductase) can act in an autocrine loop on prostate secretory cells
BPH
- Gross look
- Histo look
- Prostatic enlargement due to presence of nodules in the preprostatic region (periurethral, transitional zone)
- nodularity due to proliferation or dilatation of glandular component and muscular proliferation of the stromal component
Prostate Cancer
- What kind?
- How common?
- Who tends to get it?
- adenocarcinoma
- most common cancer in men, second leading cause of cancer related death in men (ppl tend to die w/ PCA than of PCA)
- incidence increases w/ age, African ancestry>European ancestry>Asian ancestry; may be diet related
Prostate Cancer- Molecular bio
- Role of Androgen Receptor
- Role of BRCA2
- ETS gene
- What is the most common epigenetic alteration in PCA?
- Biomarkers of PCA (4; 2 impt ones)
- contains a polymorphic sequence composed of CAG repeats; pts w/ shortest CAG repeats have highest androgen sensitivity (often African Americans)
- germline mutation; 20 fold increase for PCA
- Somatic mutation resultis in chromosomal rearrangement placing ETS gene under control of TMPPRSS2 promoter
- hypermethylation of gluthation S-transferase which downregulates the gene chr 11q
- AMACR, PSA (prostate specific Ag), EZH-2, PCA3
Prostate Specific Antigen (PSA)
- What is it?
- What cells produce it?
- When is it elevated?
- What reduces it? (3)
- What is the upper limit of normal?
- serine protease composed of single-chain glycoprotein
- epithelial cells or normal, hyperplastic, and cancerous prostate tissue
- in pts w/ prostate cancer, BPH, prostatitis, trauma, infarct, DRE, ejaculation; increases with age
- 5 alpha reductase inhibitors, androgen deprivation, prostatectomy
- 4 ng/ml
- Define PSA density
- Define PSA velocity
- What else is measured?
- ratio between the serum PSA and volume of prostate gland
- rate of change in PSA value with time
- Ratio of free and bound PSA
Prostatic Intraepithelial Neoplasia (PIN)
- What is it?
- Is it invasive?
- What is it associated with?
- proliferation of neoplastic cells w/in large ducts
- does not progress to invasive carcinoma
- other carcinomas
Prostate Carcinoma (PCA)
- Gross Features (3)
- Histo Features (5)
- Gleason Grading System
- What is 3 good at?
- palpably hard, tan/white nodule; posterolateral portion of gland; most often tumor not grossly visible
- small glands w/ infiltrative pattern, nuclear enlargement, prominent nucleoli, single-cell layer, perineural invasion, intracytoplasmic mucins, crystals
- 1-10: primary (most common) grade + secondary (2nd most common) grade
- best marker to predict prognosis
PCA Staging
- What does T1 mean?
- T2?
- T3?
- T4?
- N1?
- M1?
- clinically inapparent lesion (dx on core biopsy)
- confined to prostate
- local extraprostatic extension
- surrounding organs
- presence in lymph nodes
- metastasis
PCA Treatment
- Confined to prostate
- Alternative?
- Advanced or metastatic disease?
- Radical prostatectomy
- Radiation
- Androgen deprivation