Prostate Pathology Flashcards
1
Q
Basic prostate anatomy
A
2
Q
What portion of the prostate does BPH typically occur?
A
- Periurethral zone
- Can compress the ureter causing problems w/ urination
3
Q
Where does prostate cancer typically start?
A
- In the posterior portion of the prostate near the rectum
*is noticeable during a DRE
- Typically wont give any noticeable signs
4
Q
Benign prostate gland with basal and secretory cell layer
A
5
Q
Prostatitis
A
- Acute bacterial prostatitis
- Chronic bacterial prostatitis
- Chronic abacterial prostatitis
- Granulomatous prostatitis
6
Q
Acute bacterial prostatitis bacteria
A
- Results from bacteria similar to those seen in urinary tract infections
- E. coli
- Gram (-) rods
- Enterococci
- Staphylococci
- May result form intraprostatic reflux of urine
- May seed the prostate via the lymphohematogenous route
- Surgical manipulation and instrumentation
- Fever, chills and dysuria
- Diagnosis made by urine cultures and clinical features
7
Q
Chronic bacterial prostatitis
A
- More difficult to diagnose
- May present w/ more vague symptoms, low back pain, dysuria, perineal and suprapubic discomfort
- May be asymptomatic
- Need to document pos. bacterial cultures and leukocytes in expressed prostatic secretions
- Difficult to treat b/c antibiotics penetrate the prostate poorly
8
Q
Chronic abacterial prostatitis
A
- Most common form of prostatitis
- It is indistinguishable from chronic bacterial prostatitis clinically
- No history of recurrent infections
- Expressed prostatic secretions contain more than 10 leukocytes pre high power field
- Bacterial cultures are neg.
9
Q
Granulomatous prostatitis
A
- An infectious agent may or may not be identified
- In US a common cause is the instillation of BCG in the bladder for treatment of bladder ca
- BCG is an attenuated mycobacterial strain that give rise to a histologic picture similar to systemic tuberculosis
- In granulomatous prostatitis in that case the presence of the granumomas are of no significance and need no treatment
- Fungal granulomatous prostatitis is seen mostly in immunocompromised pts
10
Q
Prostatic infarct
A
- Seen mostly in large prostates w/ nodular hyperplasia
- May be caused from infection or indwelling catheters or trauma
- Grayish yellow and streaked w/ blood
- Peripheral margins are sharp and hemorrhagic
- Infarcts are of ischemic type w/ coagulative necrosis involving glands and stroma
- Most are clinically silent but may cause urinary retention due to edema
- May cause increase in PSA (prostatic specific antigen)
11
Q
Prostatic calculi
A
- Calculi can form in glands
- Blood clots, epithelium and bacteria may be found in some stones
- Main inorganic components are phosphated salts, calcium carbonate and calcium oxalate
- Radiopaque and can be seen on x-rays
- Large stones may mimic carcinoma on palpation
12
Q
Benign prostatic hyperplasia presentation
A
- Common disorder in men >50
- Assoc. w/ many symptoms including freq., urgency, inability to empty the urinary bladder, difficulty starting and stopping the urinary stream
- Clinically can mimic prostate cancer and may be seen in conjunction w/ prostate ca
13
Q
BPH histology
A
- Have an increased number of epithelial and stromal cells especially in the periurethral zone which gives rise to the clinical symptoms
- However there is no clear evidence of epithelial cell proliferation; their just not dying off, resulting in accumulation
14
Q
BPH pathophysiology
A
- DHT formed in stromal cells binds to the nuclear androgen receptor (AR) in stromal and epithelial cells
- Binding of DHT to AR activates the transcription of androgen-dependent genes which result in the production of several growth factors and their receptors
*therefore stromal cells are responsible for androgen dependant prostatic growth
- Androgens increase cellular proliferation but also inhibit cell death
*androgens are required for the development of BPH
- Accumulation of epithelial cells due to impaired cell death w/ an accumulation of senescent cells in the prostate
15
Q
Major androgen in the prostate
A
- Dihydrotestosterone (DHT)
16
Q
DHT formation
A
- Major androgen in the prostate
- Formed by the conversion of testosterone by the enzyme type 2, 5 alpha reductase located mainly in the stromal cells of the prostate w/ little in the epithelial cells
17
Q
BPH growth factors
A
- Growth factors include fibroblast growth factor (FGF) especially FGF-7
- Other growth factors include FGFs 1 and 2, TGFbeta which promote fibroblast proliferation
- It is thought that DHT-induced growth factors increase the proliferation of stromal cells and increasing the death of epithelial cells
18
Q
BPH morphology
A
- Arises mostly in the inner aspect of the prostate
- Early nodules composed mostly of stromal cells while later nodules contain mostly epithelial cells
- Nodule may encroach on the urethra resulting in compression and urinary problems
- Median lobe hypertrophy: nodules project into the floor of the urethra
- Nodules vary in size and consistency
- Glandular nodules have a softe consistency w/ presence of a white secretion
- Stromal nodules are firmer white-gray
- Aggregation of small to large cysticlaly dilated glands and an outer cuboidal or flattened epithelium
19
Q
Nodules on both sides of the urethra histo slide
A
20
Q
BPH - inner columnar cells and outer flattened basal cells histo slide
A
21
Q
Prostatic adenocarcinoma
A
- Most common cancer in men
- 1 in 6 lifetime probability of being diagnosed w/ prostate cancer
- Significant drop in prostate cancer mortality in the last 20yrs
- Has a wide range of clinical types from very aggressive to clincally insignificant tumors
22
Q
Prostate cancer
A
- Increased incidence upon migration from a low-incidence region to one w/ a high incidence
- Fat intake may play a role
- Some dietary factors may delay cancer such as lycopene, vit. D, selenium, soy products
23
Q
Androgens in prostate cancer
A
- Androgens bind to androgen receptor inducing expression of pro-growth and pro-survial genes
- X linked AR gene contains a polymorphic sequence composed of repeats of the codon CAG which codes for glutamine
- Variation of length of CAG repeats can affect AR function
- Shortest polyglutamine repeats are seen in African Americans
- Intermediate polyglutamine repeats are seen in whites
- Longest are seen in asians
- Length of repeats is inversely related to the rate of prostate ca in rat models
24
Q
Anti-androgen therapy
A
- Castration or tx w/ anti-androgens usually induce disease regression
- Most tumor become resistant to androgen blockade
- Tumors may developa hypersensitivity to low lvls of androgens
- Tumors may be activated by non-androgen ligands
- Activation of alternating signaling pathways which bypass the need for androgen receptor such as in increased activation of P1-3 kinase/AKT signaling pathway
25
Inherited prostate ca polymorphisms
- Men w/ a 1st degree relative w/ prostate ca has 2x the risk
- Men w/ 2 first degree relatives have 5x risk
- These men also tend to develop ca at a younger age
- Men w/ mutations of the tumor suppressor BRCA2 have a 20-fold increased risk
- Most familial cases of ca are due to variations in other loci
- One risk assoc. loci is one 8q24 that appears to increase the risk among African American men
26
Acquired somatic mutations and epigenetic changes
- Rearrangement of an ETS family transcription factor gene next to the androgen-regulated TMPRSS2 promoter
- The rearrangement places the involved ETS gene under the control of the TMPRSS2 promoter and lead to their over-expression in an androgen-dependent fashion
- Over-expression of ETS transcripton factors makes prostate epithelial cells more invasive
- Tumors w/ ETS genes may define a specific molecular sub-class of prostate ca
- ETS fusion genes may be detected in the urine and may have implications for screening and early diagnosis
27
Prostate cancer epigenetic changes
- Most common epigenetic alteration in prostate cancer is hypermethylation of glutathionine S-transferase (GSTP1) which down regulates **GSTP1 expression**
**- GTSP1 prevents a wide range of carcinogens**
- Other genes silenced in prostate ca include a numberof tumor suppressor genes including PTEN, RB, p16/INK4a, MLH1, MSH2, and APC
28
Possible biomarkers of prostate cancer
- Often seen is loss of E-cadherin an adhesion protein which is assoc. w/ expression of high lvls of EZH-2 a transcriptional repressor that may contribute to prostate ca progression
- **AMACR** (alpha-methylacyl-CoA racemase) involved in the beta-oxidation of branched chain amino acids is **upregulated in prostate ca**
- PCA3 encodes a regulatory RNA
29
Prostate carcinoma
- It is an adenocarcinoma
- Smaller than benign glands
- In 70% of cases it arises in the peripheral zone classically in the posterior aspect allowing it to be palpated on DRE
- More likely to be palpated
- Firm and gritty feeling
- May be difficult to visualize
\*TRUS may help diagnose
30
Prostate carcinoma metastasis characteristics
- Local extension to periprostatic tissue, seminal vesicles and bladder
- Metastasis occurs via lymphatics to obturator nodes and para-aortic nodes
- Hematogenous spread leads to mets to bones
- Boney metastasis is typically **osteoblastic** and usually involves the lumbar vertebrae
31
Prostate carcinoma histology
- Produce well defined gland patterns
- More crowded and lack branching and papillary infolding
**- The outer basal cell layer seen in benign glands is absent in malignant glands use markers to identify the basal cell layer**
**- Alpha-methylacyl-coenzyme A- racemase (AMACR): is up regulated in prostate ca**
- **Nuclei are often large w/ one or more large nucleoli**
- Min. pleomorphism
- Mitotic figures are uncommon
32
Prostate carcinoma diagnosis
- Can be difficult to diagnose on needle biopsy
- May have a focus of adenocarcinoma adjacent to many benign glands
- Often underdiagnosed
- Perineural invasion
**- Diagnosis is made on a variety of findings include architecture, cytologic, and ancillary findings**
33
Prostatic intraepithelial neoplasia
- PIN, like cancer, is found in the peripheral zones of the prostate
- Prostates containing cancer have a higher incidence of PIN
- PIN may be an intermediate lesion b/w normal glands and invasive cancer
- Unknown how likely PIN will transform to invasive cancer
34
Prostatic intraepithelial neoplasia histology characteristics
- Architecturally benign glands lined by cytologically atypical cells w/ prominent nucleoli
- Divided into low grade and high grade based on **nuclear and nucleolar changes**
- PIN glands are surrounded by a patchy layer of basal cells and an intact basement membrane
35
PIN low grade histology slide
36
PIN high grade histology slide
37
Grading and staging prostate cancer
- Gleason systme is the grading system based on glandular patterns of differentiation
- Grade 1 - 5
- To calculate the grade of the tumor you must assign a number to the dominant pattern and anumber to the secondary pattern and add them
- The lowest Gleason score would be 2 while the highest is 10
- Scores 2-4 are well-differentiated
- Scores 5-6 are intermediated -grade
- Score of 7 is moderate to poorly differentiated
- Score 8-10 is a high grade tumor
38
Gleason grade 1 - 5
- Gleason sytem is the grading system for prostate cancer based on glandular patterns of differentiation
- Grade 1: most well differentiated tumors w/ uniform round neoplastic glands forming well-circumscribed nodules
- Grade 5: no glandular differentiation w/ tumor cells infiltrating the stroma forming cords, nests and sheets
39
Prostate carcinoma malignant vs benign gland histology slide
40
Prostatic carcinoma nuclei and cytoplasm histology slide
41
Perineural invasion histology slide
- Hallmark of a malignant prostatic growth is when the prostate starts growing around a nerve
42
Prostate specific antigen
- AKA PSA
- Product of prostatic epithelium and is normally secreted in the semen
- It is a serum protease that cleaves and liquefies the seminal coagulum formed during ejaculation
- Only small amounts should be found in circulation
43
Prostate specific antigen as a screening test
- Important test in the diagnosis and treatment of prostate cancer
- Use as a screening test is VERY CONTROVERSIAL
- PSA is organ specific, not cancer specific
- May be elevated in other prostate problems such as bpH, prostatitis, prostate infarction, instrumentation, ejaculation
- "Normal" PSA lvls are b/w 0-4 ng/ml
- Small lesions detected by elevated PSA may not progress to invasive ca
44
PSA density
- Ratio b/w the serum PSA value and volume of prostate gland calculated by dividing the PSA lvl by the estimated gland volume obtained from transrectal US
45
PSA velocity
- The rate of change in PSA value w/ time, increased rate of change of PSA is greater in cancer pts. compared to men w/o cancer, generally an increase of 0.75 ng/ml per year is suspicious, need to perform as series of tests to confirm this due to the variability b/w tests
46
Immunoreactive PSA
- PSA exists in 2 forms
- A minor free fraction
- A major fraction bound to alpha-1-antichymotrypsin
- The % of free fraction is lower in men w/ prostate cancer than in those w/ benign prostatic disease
\*free PSA \>25% = low risk ca
\*free PSA \<10% = high risk ca
