Term
| where in the prostate does the majority of BPH arise? |
|
Definition
| the periurethral zone -> where it is more likely going to cause symptoms such as dysuria, bladder infections, frequency, urgency, and inability to empty the bladder |
|
|
Term
| where in the prostate does the majority of CA arise? |
|
Definition
| the posterior/peripheral zone -> less likely to give rise to urinary symptoms and more amenable to a DRE |
|
|
Term
| what characterizes benign gland tissue as seen in BPH histologically? |
|
Definition
| a benign gland as seen in BPH consists of stromal tissue and epithelial glandular tissue w/a basal and secretory layer. the *basal cell layer in BPH is important, b/c it is not seen in prostate CA* (can be stained for differentiation). |
|
|
Term
| what are the different kinds of prostatitis? |
|
Definition
| acute bacterial, chronic bacterial, chronic abacterial, and granulomatous prostatitis |
|
|
Term
| what are common causes of acute bacterial prostatitis? |
|
Definition
| e. coli, gram negative rods, enterococi, and staphylococci - bacteria similar to those seen in UTIs. |
|
|
Term
| what is the etiology of acute bacterial prostatitis? |
|
Definition
| intraprostatic *reflux of urine, *lymphohematogenous seeding of the prostate, and *sx manipulation/instrumentation |
|
|
Term
| how do pts w/acute bacterial prostatitis usually present? |
|
Definition
| fever, chills, marked dysuria, and increased prostate specific antigen (PSA) |
|
|
Term
| how is acute bacterial prostatitis diagnosed? |
|
Definition
| urine cx and clinical features |
|
|
Term
| why is chronic bacterial prostatitis more difficult to dx? |
|
Definition
| symptoms (if any) are more vague: lower back pain, some degree of dysuria/frequency/urgency (not as severe as acute type), perineal or suprapubic discomfort, pelvic pain |
|
|
Term
| how is chronic bacterial prostatitis diagnosed? |
|
Definition
| documentation of positive bacterial cx and WBCs in expressed prostatic secretions |
|
|
Term
| why is chronic bacterial prostatitis hard to tx? |
|
Definition
| antibx penetrate the prostate poorly (can have remitting or relapsing for months or years) |
|
|
Term
| what is the most common form of prostatitis? |
|
Definition
| chronic abacterial prostatitis |
|
|
Term
| what characterizes chronic abacterial prostatitis? |
|
Definition
| clinically, chronic abacterial prostatitis is indistinguishable from chronic bacterial prostatitis, but there is no hx of recurrent infections and bacterial cx's are negative. expressed prostatic secretions do however *contain more than 10 WBCs/HPF. |
|
|
Term
| what is granulomatous prostatitis? |
|
Definition
| granulomatous prostatitis obviously involves granulomas, not always with a clear etiology - though BCG (mycobacterial strain used for CA tx) in the bladder has been associated with granulomatous prostatitis (granuloma formation similar to TB). if BCG is determined to be the cause, no tx is necessary. other forms of fungal granulomatous prostatitis are seen mainly in immunocompromised pts. |
|
|
Term
| what is the hallmark of prostatitis? |
|
Definition
| high leukocyte level in prostatic secretions (obtained via prostatic massage) |
|
|
Term
| when are prostatic infarcts more likely to occur? |
|
Definition
| in large prostates w/nodular hyperplasia or due to infections, trauma, or indwelling catheters. prostatic infarcts are fairly rare. |
|
|
Term
| how does a prostate w/an infarct appear? |
|
Definition
| grossly: grayish yellow and streaked w/blood. peripheral margins will be infarcted and will be sharp/hemorrhagic. histologically: infarcts of the ischemic type will show coagulative necrosis involving glands and stroma. |
|
|
Term
| what is the clinical presentation of a pt with a prostatic infarct? do they cause an increase in PSA? |
|
Definition
| most are clinically silent, but may cause urinary retention due to edema. prostatic infarcts can cause an increase in PSA. |
|
|
Term
| is BPH more of an increase in cells or size? |
|
Definition
|
|
Term
| how do cells in BPH typically appear? |
|
Definition
| tall on one side, flattened on the other |
|
|
Term
| what are prostate calculi composed of? how are they visualized? are they palpable? |
|
Definition
| blood clots, epithelium, bacteria, phosphated salts, calcium carbonate, and calcium oxalate. prostate calculi are radiopaque (look like bird shot) and larger stones may mimic CA on palpation. |
|
|
Term
| what symptoms is BPH associated with? |
|
Definition
| urgency, frequency, nocturia (may present as insomnia), inability completely empty bladder, and difficulty starting/stopping the urinary stream. it can mimic prostate CA and may occur in conjunction w/CA (both are seen w/increased frequency as males age). |
|
|
Term
| how do BPH and prostate CA differ upon palpation? |
|
Definition
| prostate CA is more asymmetrical |
|
|
Term
| what characterizes BPH histologically? |
|
Definition
| there is an increased number of epithelial and stromal cells - esp in the periurethral zone (source of clinical symptoms), however there is *not always clear evidence of epithelial cell proliferation (sometimes more stromal proliferation). instead, the accumulation of epithelial cells is due to **impaired cell death w/an accumulation of senescent cells in the prostate. |
|
|
Term
| what is the role of androgens in BPH? are they required? |
|
Definition
| androgens *increase cellular proliferation and *inhibit cell death. androgens are *required for the development of BPH. |
|
|
Term
| what is the major androgen in the prostate? how/where is it formed? where does it bind? |
|
Definition
| DHT (dihydrotestosterone), which is formed from testosterone by the enzyme *2 5 alpha reductase. this enzyme is located mainly in the *stromal cells of the prostate, which are thus the main cells responsible for androgen dependent prostatic growth. DHT binds to the nuclear androgen receptor in stromal and epithelial cells, causing *stromal cells to proliferate and *senescent epithelial cells to pool in BPH. |
|
|
Term
| what characterizes the epithelial cells in BPH? |
|
Definition
| they are normal cells (not dysplastic - *glands have a normal basal cell layer), just not dying off, which over time will increase the size of the prostate. |
|
|
Term
| transcription of what genes are activated when DHT binds to the androgen receptor of stromal cells? what is the effect of this? |
|
Definition
| the androgen-dependent genes activated in stromal and epithelial cells in BPH are those for fibroblast growth factor (FGF), esp *FGF-7*, as well as FGF 1,2 and TGF beta. the effect of this is: increased proliferation of stromal cells and decreased death of epithelial cells. |
|
|
Term
| what characterizes the morphology of BPH? |
|
Definition
| BPH arises mostly in the inner aspect of the prostate (periurethral) and *early nodules are composed mostly of stromal cells, while *later nodules contain mostly epithelial cells. the nodule may encroach on the urethra, resulting in compression/urinary problems and *median lobe hypertrophy may occur (nodules project into the floor of the urethra). |
|
|
Term
| what characterizes the kinds of nodules seen in BPH grossly and histologically? |
|
Definition
| grossly: glandular nodules have a softer consistency w/white secretion while stromal nodules are firmer white-gray. there may be aggregations of small-large cystically dilated glands. histologically: an outer cuboidal and inner flattened epithelium (often 50-50 distribution on either side of the gland). the cells lining the glands are benign; normal nuclei and nucleoli; no increase in N:C ratio; glands are well-organized; architecture appears normal. |
|
|
Term
| what is the most common CA in men? |
|
Definition
| prostatic adenocarcinoma: 1 in 6 probability of dx for a male |
|
|
Term
| what demographic has the highest incidence of BPH? |
|
Definition
| african americans over the age of 40. asians have the lowest. |
|
|
Term
| what is the drop in prostate CA deaths likely due to? |
|
Definition
| early dx, better tx protocol |
|
|
Term
| what is the problem with PSAs as a screening protocol for prostate CA? |
|
Definition
| PSAs are relatively sensitive but not that specific - approx 15-20% of pts w/normal PSA levels actually have prostate CA |
|
|
Term
| what is the general screening recommendation for prostate CA? |
|
Definition
| every male regardless of history should get a baseline PSA+DRE at 50 yrs and if african american or if they have a first degree relative who had prostate cancer, subtract 5 years each. |
|
|
Term
| what dietary factors may help prevent prostate CA? |
|
Definition
| lycopene, vit D, selenium, and soy produces |
|
|
Term
| what is the role of androgens in prostate adenocarcinoma? |
|
Definition
| androgens (as in BPH) bind to androgen receptors (AR), inducing expression of pro-growth and pro-survival genes. the *X-linked AR gene contains a polymorphic sequence composed of CAG codon repeats (codes for glutamine), and the length of these CAG codon repeats affects AR function (leads to longer or shorter polyglutamine repeats). the shortest polyglutamine repeats are seen in african americans, and the longest are seen in asians, w/caucasians somewhere inbetween. (length of repeats inversely related to rate prostate ca in rat models) |
|
|
Term
| what characterizes anti-androgen therapy for prostate CA? |
|
Definition
| castration/chemical castration w/anti-androgens can induce disease regression, though most tumors ultimately become resistant to androgen blockade through *hypersensitivity to low levels of androgens or *activation by non-androgen ligands (ie increased activation of PI-3 kinase/AKT signaling pathway, which bypasses the need for androgen receptor ) |
|
|
Term
| what is the role of inherited polymorphisms in determining the risk for pts of prostate CA? |
|
Definition
| a pt w/1 first degree relative w/prostate CA has 2x the risk of developing it himself. a pt w/2 first degree relative w/prostate CA has 5x the risk of developing it himself. these pts tend to also develop prostate CA at a younger age. |
|
|
Term
| what is the rate of increased prostate CA risk for men w/a mutation of the tumor suppressor BRCA2? |
|
Definition
| 20x. BRCA2 mutations are also seen in ovarian and breast CA. |
|
|
Term
| what risk associated loci has been found to increase prostate CA risk in african americans? |
|
Definition
|
|
Term
| what is an example of an aquired somatic mutation which can lead to prostate CA? can this be tested for? |
|
Definition
| rearrangement of the ETS family transcription factor gene, putting it next to and under control of the androgen-regulated TMPRSS2 promoter. this leads to an androgen driven over-expression of the ETS transcription factors which causes epithelial cells to become more invasive. tumors with ETS genes may define a specific molecular sub-class of prostate ca and the ETS fusion genes may be detected in urine (implications for screening and early diagnosis) |
|
|
Term
| what is the most common epigenetic alteration related to prostate CA? |
|
Definition
| hypermethylation of gluathionine S-transferase (GSTP1) - which down regulates GSTP1. GTSP1 normally prevents a wide range of carcinogens. |
|
|
Term
| what are some possible biomarkers for prostate CA? |
|
Definition
| loss of E-cadherin (adhesion protein associated w/expression of high EZH-2 levels - a transcriptional repressor), **higher AMACR levels (alpha-methylacyl-CoA racemase - involved in beta-oxidation of branched chain AA**), and PCA3 (encodes a regulatory RNA) |
|
|
Term
| what characterizes prostate CA? |
|
Definition
| prostate CA is an adenocarcinoma which is firm, gritty, difficult to visualize and arises in the posterior peripheral zone 70% of the time (easy DRE access). |
|
|
Term
| what is more likely to be palpated, prostatic CA or early BPH? |
|
Definition
|
|
Term
| what characterizes the spread of prostatic CA? |
|
Definition
| locally, prostate CA can extend to the periprostatic tissue, seminal vesicles, and bladder. via lymphatics, prostate CA can spread to the obturator nodes and para-aortic nodes. hematogenously, prostate CA can met to bones - boney metastasis is typically *osteoblastic (most bone mets are osteoclastic) and usually involves the lumber vertebrae (*back pain*). |
|
|
Term
| what defines prostate CA histologically? |
|
Definition
| prostate CA has well defined gland patterns consisting of glands smaller than benign glands. there is more crowding (less stroma inbetween) and they lack branching and papillary infolding. **the outer basal cell layer seen in benign glands is absent in malignant glands (use markers to ID the basal cell layer)** AMACR (alpha-methylacyl-coenzymeA-racemase - upregulated in prostate CA) can also be screened for. |
|
|
Term
| how do the individual cells in prostate CA appear? |
|
Definition
| cytoplasm may be dark, nuclei are often large w/one or more large nucleoli, there is minimal pleomorphism (unique) and mitotic figures are uncommon (unique). |
|
|
Term
| why is it hard to dx prostate CA definitively? |
|
Definition
| there may be a focus of adenocarcinoma adjacent to many benign glands |
|
|
Term
| what is one thing prostate CA will show histologically that would not be seen in BPH? |
|
Definition
|
|
Term
| what is prostatic intraepithelial neoplasia? |
|
Definition
| architecturally benign glands lined by cytologically atypical cells w/**prominent nucleoi. PINs are then surrounded by a *patchy layer of basal cells and an *intact basement membrane. |
|
|
Term
| where is prostatic intraepithelial neoplasia found? |
|
Definition
| like CA in the peripheral zones of the prostate |
|
|
Term
| what is the link between prostate CA and PIN? |
|
Definition
| prostates containing CA have a higher incidence of PIN. PIN may be an intermediate lesion between normal glands and invasive CA. |
|
|
Term
| how does PIN low grade appear? |
|
Definition
| fairly benign, some prominent nucleoli |
|
|
Term
| how does PIN high grade appear? |
|
Definition
| nucleoli are more prominent |
|
|
Term
| what is the grading system for prostatic CA? |
|
Definition
| the gleason system, based on glandular patterns of differentiation: grade 1 is the most well differentiated (tumors w/round neoplastic glands forming well-circumscribed nodules) and grade 5 is poorly differntiated (tumor cells infiltrating the stroma, forming cords/nests/sheets). 2 grades are then taken and added up, so score goes from 2-10. 2-4 is well differentiated, 5-6 is intermediate, 7 is poorly differentiated, 8-10 is high grade tumor. |
|
|
Term
| what signs/symptoms may be associated with prostate CA bone mets? |
|
Definition
| pathologic compression fractures, which may give rise to some neuronal symptoms, parasthesias, sciatica, radiculopathy etc. |
|
|
Term
|
Definition
| prostate specific antigen, a product of prostatic epithelium normally secreted in semen which is a protease that cleaves and liquefies the seminal coagulum formed during ejaculation. it is important to screen for in the dx/tx of prostate CA. |
|
|
Term
| why is PSA controversial as a screening diagnostic for prostate CA? |
|
Definition
| PSA is organ specific, but not CA specific and may be elevated in other prostate problems such as BPH, prostatitis, prostate infarction, instrumentation, and ejacutation. 20-40% of organ confined CA also have low or normal PSA levels. |
|
|
Term
| what are normal serum PSA levels? |
|
Definition
| 0-4 ug/mL - only small amounts should be found in circulation, but these amounts are allowed to rise slightly in older pts. |
|
|
Term
|
Definition
| the ratio between serum PSA and prostate gland volume (calculated by dividing the PSA level by the estimated gland volume obtained from transrectal ultrasound) |
|
|
Term
|
Definition
| the rate of change of PSA over time - generally an increase of .75 ng/ml per year is suspicious and need to perform as series of tests to confirm this due to the variability between tests |
|
|
Term
| what are the age specific ranges for PSA? |
|
Definition
| upper levels of men age 40-49 is 2.5, upper levels of men age 50-59 is 3.5, upper levels of men age 60-69 is 4.5, upper levels of men age 70-79 is 6.5 |
|
|
Term
| what are the 2 forms PSA exists in? how does their serum level correlate w/prostate CA risk? |
|
Definition
| immunoreactive PSA exists in 2 forms: a major fraction bound to alpha 2 antichymotrypsin and a minor free fraction. a low % of free fraction indicates higher prostate CA risk (<10% = concern for cancer). |
|
|
Term
| what is one particularly useful application of PSA? |
|
Definition
| PSA levels can determine someone’s response to treatment - if PSA levels continue to rise while patient undergoing prostatectomy or radiation, may mean they are having recurrence of disease – so good in monitoring success of their treatment |
|
|
Term
| what are tx modalities for prostate CA? |
|
Definition
| watchful waiting, radical prostatectomy (impotence/incontinence), external beam radiation, brachytherapy (implanding radioactive seeds), and hormonal manipulation |
|
|
