Exam II Flashcards

1
Q

Histology: 1. The semniferous tubules, straight tubules and retes testis develop from _______.

  1. The prostate gland develops from multiple outgowoths that originate from the ________
A
  1. Indifferent gonads

2. Pelvic urethra

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2
Q

Histology: What is the significance of the stromal cells of the prostate in prostate cancer?

A

Stromal cells convert testosterone to DHT (via 5-a-reductase)

DHT = 30x more powerful than testosterone

DHT in adults = inc. stroma/epithelium (carcinoma)

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3
Q

Histology: What is the relationship between prostate carcinoma and bone?

A

–enlarged peripheral glands

Inc. PSA and PAP = inc. osteoblastic activity and differentiation

Inc. bone formation

NOTE: PSA (prostate specific antigen); PAP (prostatic acid phosphatase)

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4
Q

Histology: Leydig cells are large polygonal, acidophilic cells arranged in clusters. They are closely associated with blood vessels.

They contain prominent sER, lipid and mitochondria specifially for synthesis of what hormone?

A

Testosterone

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5
Q

Histology: Leydig cells are found in the interstitum of the testes. They appear around 7-8 weeks and remain until 5 mos (at which point they regress).

What do Leydig cells produce?

A
  1. Testosterone
  2. Insulin-like protein 3
    - -testes descent
  3. oxytocin (contract myoid cells)
  4. Crystals of Reinke
    - -inclusions (Leydig tumors)
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6
Q

UTI Pharm: E. coli is the most common cause of UTI’s (especially in females).

What are other common causes?

A
  1. Staphy. saprophyticus
  2. Klebsiella (hospital acquired)
  3. Proteus
  4. Candida (opportunistic)
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7
Q

UTI Pharm: Which of the following is a risk factor for developing a UTI?

a. sexual intercourse
b. delayed post-coital micturition
c. spermicides
d. structural abnormalities
e. catheterization

A

all of the above

Also:
-neurogenic bladder (SCI, stroke)

-immunosuppression (HIV, diabetes mellitus)

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8
Q

Pharm UTI: Cystitis is infection of the bladder. It is more common in women and typically presents with:

  • increased urinary frequency
  • urgency
  • dysuria (pain while urinating)
  • suprapubic pain (pain above pubic region)

What would most likely be seen on urinalysis?

A
  • hematuria
  • pyuria
  • nitrites
  • leukocyte esterase (WBC’s)
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9
Q

Pharm UTI: Treatment for cystitis often involves one of the following antibiotics:

  1. TMP-SMX
  2. Nitrofurantoin
  3. Fosfomycin
  4. Ciprofloxacin
  5. Phenazopyridine

This drug acts in the folic acid pathway. It binds bacterial folate reductase with 100,000 fold greater affinity than that of the mammalian enzyme. It also acts by inhibiting sequential steps in the pathway

A

TMP-SMX

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10
Q

UTI Pharm: What must you take into account before/when prescribing TNP-SMX?

A
  1. Hydrate
    - -drink fluids to flush bacteria and prevent crystaluria (SMX)
  2. AVOID in 3rd trimester
  3. AVOID if sulfa allergy
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11
Q

Pharm UTI: Treatment for cystitis often involves one of the following antibiotics:

  1. TMP-SMX
  2. Nitrofurantoin
  3. Fosfomycin
  4. Ciprofloxacin
  5. Phenazopyridine

This drug is chemically reduced to active metabolites by bacterial enzymes. These metabolites subsequently damage bacterial DNA and ribosomal proteins. It is rapidly excreted in the urine.

A

Nitrofurantoin

*brown urine

NOTE: mammalian enzymes generate metabolites much more slowly

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12
Q

Pharm UTI: Treatment for cystitis often involves one of the following antibiotics:

  1. TMP-SMX
  2. Nitrofurantoin
  3. Ciprofloxacin
  4. Fosfomycin
  5. Phenazopyridine

______ irreversibly inhibits enolpyruvyl transferase thereby blocking cell wall peptidoglycan synthesis

A

Fosfomycin

*excreted in urine and feces (no changes)

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13
Q

Pharm UTI: Treatment for cystitis often involves one of the following antibiotics:

  1. TMP-SMX
  2. Nitrofurantoin
  3. Fosfomycin
  4. Ciprofloxacin
  5. Phenazopyridine

This fluoroquionlone acts by inhibiting DNA gyrase and topo type IV.

A

Ciprofloxacin

*AVOID use in kids and pregnancy

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14
Q

Pharm UTI: Phenazopyridine is used as an analgesic to help reduce pain in the case of a UTI.

What effects will it have on urine?

A

Urine will be orange/red

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15
Q

Pharm UTI: What is the method for treating a recurrent UTI?

A
  1. low dose daily

OR

  1. single, post-coital dose
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16
Q

Pharm UTI: Pyelonephritis (kidney infections) typically present with flank pain and high fever. In addition, malaise and urinary symptoms similar to cystitis may be present.

What drug is used to treat pyelonephritis?

A

Ciprofloxacin

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17
Q

Pharm UTI: Prostatitis (uncomplicated w/ low risk of STD) is most likely due to E. coli infection. It may present with:

  • lower back pain
  • high fever
  • chills
  • symptoms similar to cystitis.

How is it treated?

A

Ciprofloxacin

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18
Q

Pharm UTI:

  1. A renal abscess that occurs in the setting of pyelonephritis, then you should suspect _____. You would treat with _______.
  2. An abscess associated with bacteriemia is most likely caused by ____. You would treat with _____.
A
  1. Suspect E. coli
    - -Piperacillin + Tazobactam
    (ext. spectrum inhibits cell wall synth + B-lac inhibitor)
  2. Suspect S. aureus
    - -Nafcillin (penicillinase-resistant penicillin)

NOTE: drain abscesses >5cm prior to administering antibiotics

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19
Q

Pharm UTI: If you suspect MRSA as the cause of a renal abscess, what would you use to treat it?

A

Vancomycin

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20
Q

Pharm UTI: Urethritis due to infection with Neisseria gonorrhea may be treated with Ceftriaxone + Azithromycin.

What are the functions of these drugs?

A
  1. Ceftriaxone
    - –3rd gen. cephalosporin
    - -inhibits cell wall synth
    * *injection
  2. Azithromycin
    - -macrolide
    - -inhibits 50s
    * *single, large dose
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21
Q

Pharm UTI: Urethritis due to infection with chlamydia trachomatis can be treated with what drug?

A

Azithromycin or Doxycylcine

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22
Q

Pharm UTI: Most of the drugs used to treat kidney disorders can lead to GI distress. List the other adverse effects of

  1. TMP-SMX
  2. Nitrofurantoin
  3. Fosfomycin
  4. Ciprofloxacin
  5. Piperacillin + Tazo
  6. Ceftriaxone
  7. Nafcillin
  8. Vancomycin
A
  1. TMP-SMX: Stevens-Johnson syndrome, megaloblastic anemia
  2. Nitrofurantoin: headache, change urine color
  3. Fosfomycin: headache
  4. Ciprofloxacin: tendonitis, phototoxicity, prolonged QT
  5. Piperacillin: yeast infection
  6. Ceftriaxone: HSR, yeast infection (cross w/ penicillin)
  7. Nafcillin: HSR
  8. Vancomycin: nephrotoxic, ototoxic, rash on face/upper torso
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23
Q

Pharm Micturition: Drugs for abnormal urinary retention include:

  1. Non-selective alpha 1 blockers
  2. Uro-selective alpha - 1 blockers

What are examples of non-selective alpha blockers? When are they clinically used?

A

-Doxazosin, Prazosin, Terasozin

–competitive a-1 blockers

Tx: BPH (urinary symptoms), HTN, PTSD (inc. sleep; dec. nightmares)

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24
Q

Pharm Micturition: Drugs for abnormal urinary retention include:

  1. Non-selective alpha 1 blockers
  2. Uro-selective alpha - 1 blockers

Alpha 1 blockers prevent constriction of the urinary sphincter thus preventing urinary retention. What are examples of uro-selective alpha blockers? When are they clinically used?

A

-Tamsulosin

  • -competitive uro-selective alpha-1 blockers
  • -DON’T reduce blood pressure

Tx: urinary symptoms (due to BPH)

NOTE: Alpha 1 receptors promote constriction of urinary sphincters (dec. urination)

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25
Pharm Micturition: What are the adverse effects of alpha-1 receptor antagonists?
1. Prazosin, doxazosin, terazosin - --1st dose syncope (MC) 2. DIzziness 3. Orthostatic hypotension
26
Pharm Micturition:___________ may be used to treat incontinence. Examples include: 1. Oxybutynin (oral, gel, transdermal patch) 2. Tolterodine (oral) These drugs are most commonly used to relieve bladder spasm, urinary and urgency incontinence, overactive bladder, leakage and lower urinary tract symptoms (men)
Muscarinic antagonists *block parasympathetic NOTE: Tx w/ behavioral approaches as well: weight loss, inc. urination and pelvic floor exercises
27
Pharm Micturition: _______ is a beta 3-agonist that aids in relaxing the detrusor muscle. It is most often used when muscarinic antagonists are not effective in regulating urination.
Mirabegron
28
Pharm Micturition: _______ occurs post-partum and has no real pharmacologic treatment. It may be improved by behavioral approaches including strengthening pelvic floor muscles or surgery.
Stress incontinence
29
Pharm Micturition: Adverse effects of these drugs include: -hot skin (hyperthermia) -blurred vision -dry mouth (xerostoma) -flushed skin -delirium -tachycardia -agitation -
Muscarinic antagonists *hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter NOTE: also contraindicated in glaucoma (closed angle) patients; prostatic hyperplasia and elderly patients (inc. dry mouth)
30
Pharm Micturition: Nocturnal enuresis (incontinence) in children is often treated by first trying to behavioral approaches including: 1. limiting night-time fluid intake 2. setting alarms 3. having child change wet sheets 4. NO punishments However, should these be ineffective, what pharmacological treatments may be used?
1. Desmopressin (synthetic vasopressin) - -can combine w/ behavioral (sleepover w/ friends) 2. Triciyclic anti-depressants (amitryptiline) - -3rd line only 3. Oxybutynyn (musc. antagonist) - -ONLY for daytime incontinence
31
Pharm Micturition: Muscarinic agonists such as Bethanecol may be used to treat urinary retention (non-obstructional). It is often used post-operatively, for post-partum or in the case of spinal cord injury. What is important to note about administering Bethanecol? What are contraindications?
-Must not be any mechanical obstruction of outflow (or drugs will exacerbate problem; perforation) Cx: - asthma - COPD - bradycardia
32
Pharm Micturition: Signs of muscarinic agonist toxicity includes: - salivation - lacrimation - urination - defecation - gastric upset - emesis (SLUDGE) What is another feature of toxicity?
Facial flushing | DUMBBELS diarrhea, urination, miosis, bradycardia, bronchospasm, emesis, lacrimation, salivation
33
Micturition: Micturition is the process of emptying the bladder (urination). The bladder progressively fills until the wall tension rises above threshold and activates the "micturition reflex". The lower urinary tract includes: 1. Ureters 2. Bladder 3. Detrusor Muscle 4. Trigone 5. Internal and External Sphincter The ureters are tubes that originate in the kidneys and pass into the trigone region of the bladder. They are composed of both longitudinal and circular SM, that function in syncytium (unitary). How do they propel urine to the bladder?
Peristaltic waves (from pelvis) *regulated by autonomic nervous system (Parasympathetic = inc. freq. of peristaltic waves; Sympathetic = dec. freq. of peristaltic waves) NOTE: Peristalsis can occur w/out autonomic innervation
34
Micturition: ________ pain fibers exist in the ureters and, when activated, can lead to severe pain.
Afferent pain fibers *ex: ureteral stone
35
Micturition: The urinary bladder is a SM chamber composed of two principal parts: the body and the bladder neck. The SM of the bladder is the _______ muscle, a 3 layered muscle that, upon contraction prevents urine reflux towards the kidneys.
detrusor muscle
36
Micturition: The internal sphincter is the SM in the distal portion of the bladder neck leading into the posterior urethra. True/False: The natural tone of the internal sphincter prevents emptying of the bladder until the pressure in the body of the bladder rises above critical threshold.
True
37
Micturition: This sphincter consists of voluntary striated skeletal muscle in the urogenital diaphragm. This sphincter can be contracted so as to prevent urination even in the presence of strong contractions from the detrusor muscle (forcing open the internal sphincter).
External sphincter * voluntary control via pudendal nerve * somatic innervation via motor neurons from sacral region)
38
Micturition: During the storage or filling phase, _________ dominates by relaxing the detrusor muscle (B-receptors) and contracting the internal sphincter (alpha receptors)
Sympathetic (Inferior hypogastric plexus) - post-ganglionic to bladder body and neck * afferent impulses from brain stretch receptors (Pontine Micturition Center) * efferent = inhibit pre-ganglionic parasymp. neurons
39
Micturition: During the voiding phase, ______ dominates via contraction of the detrusor muscle (Muscarinic receptors)
Parasympathetic - pre-ganglionic fibers to bladder - post-ganglionic to detrusor
40
During the voiding phase, the external sphincter voluntarily relaxes, and the internal sphincter is relaxed. 1. Urine enters the posterior urethra and ______ signal to the cortex that voiding is imminent. 2. _____ inhibition ceases and the detrusor muscle contracts. Micturition occurs (self-regenerating). 3. _____ contraction of the abdominal muscles
1. afferents 2. PMC (pre-ganglionic parasympathetic) inhibition ceases 3. voluntary contraction of the abdominal muscles
41
Micturition: As the bladder fills, the pressure within the bladder rises. The bladder tone is the relationship between the volume and the pressure. This relationship is measured by a cystometrogram. Describe what happens when there is an increase in pressure in the bladder
1. Inc. pressure; inc. stretch of detrusor 2. Stretch receptors send signal to sacral spinal cord (parasympathetic afferents) 3. Reflex (parasymp. efferent) 4. Constriction of detrusor 5. Urination NOTE: The bladder has a high compliance, and bladder tone is independent of extrinsic innervation.
42
Micturition: True/False: The purpose of the micturition reflex (autonomic function) is to enable near complete emptying of the bladder, thus providing a clean, sterile environment in the lower urinary tract
True
43
Anti-HTN: The short term goal of Anti-HTN treatment is to decrease elevated blood pressure to within the normal range. What is this range in the renal system?
130/80
44
Anti-HTN: There are 4 types of anti-HTN drugs: 1. ______: lower blood pressure by reducing blood volume (and also alter contractile tone of vascular SM). 2. _____: lower b.p. by reducing peripheral vascular resistance, inhibiting cardiac function, and increasing venous pooling. 3. ______: relax vascular SM 4. reduce peripheral vascular resistance and blunt the Na2+ handling effects of aldosterone
1. DIuretics 2. Sympatholytic drugs 3. DIrect vasodilators 4. Drugs that prevent production or action of Ang. II
45
Anti-HTN: Diuretics include 1. Thiazides (hydrochlorothiazide, Chlorthalidone) 2. Loops (Furosemide, Bumetanide) 3. K+ sparing diuretics (Spironolactone, Triamterene) Which of the above are the best monotherapy for treating mild/moderate HTN with normal heart function?
Thiazides * short term effects: dec. blood volume and cardiac output * long term effects: dec. sodium content of SM cells and dec. vascular resistance
46
Anti-HTN: Diuretics include 1. Thiazides (hydrochlorothiazide, Chlorthalidone) 2. Loops (Furosemide, Bumetanide) 3. K+ sparing diuretics (Spironolactone, Triamterene) Which of the previous are appropriate for patients with renal insufficiency, cardiac failure or cirrhosis where sodium retention is marked?
Loop diuretics *minimal chronic anti-HTN effects
47
Anti-HTN: Diuretics include 1. Thiazides (hydrochlorothiazide, Chlorthalidone) 2. Loops (Furosemide, Bumetanide) 3. K+ sparing diuretics (Spironolactone, Triamterene) Which of the above are mild diuretics that are useful for avoiding hypokalemia.
K+ sparing *often given with thiazide
48
Anti-HTN: What are common adverse effects of diuretics?
1. All - -gout attack 2. Thiazide and Loop - -hypokalemia 3. Potassium sparing - -Hyperkalemia
49
Anti-HTN: Sympatholytic drugs act to relax SM muscle. These include: 1. alpha-adrenoceptor antagonists (a-1) "sins" 2. B-receptor antagonists (propanolol, metoprolol) 3. a2 agonists (clonidine) What drugs SHOULD NOT be given to an asthmatic?
Propanolol (non-selective B-blocker) **B-blockers NOT monotherapy
50
Anti-HTN: Sympatholytic drugs act to relax SM muscle. These include: 1. alpha-adrenoceptor antagonists (a-1) "sins" 2. B-receptor antagonists (propanolol, metoprolol) 3. a2 agonists (clonidine) Which of the previous should only be used in the case of refractory hypertension?
clonidine (centrally acting)
51
Anti-HTN: WHat are the adverse effects of sympatholytics?
1. A-antagonists - -first dose syncope (especially w/ diuretic) 2. B-antagonists - -bradycardia, impaired glycogenolysis, bronchoconstriction * *bad for type 1 diabetes 3. Centrally acting (clonidine) - -dry mouth (cotton mouth) - -sedation
52
Anti-HTN: Phentolamine and Pheoxybenzamine are alpha antagonists that can be used for what conditions?
Pheochromocytoma and HTN emergencies
53
Anti-HTN: esmolol is a B-blocker that is given by I.V. When is it most often used? What must be taken into consideration when administering esmolol?
Use for HTN emergencies *do not want b.p. to drop >25-30% (compromises organ perfusion)
54
Anti-HTN: True/False - Aliskrein is a direct renin inhibitor. It is NOT meant to be used in combination with ACE or ARBs
True
55
Anti-HTN: What are the adverse effects and drug indications of 1. ACEs 2. ARBs 3. Aliskrein
1. ACE - -chronic cough - -hyperkalemia - -Cx: 2nd-3rd trimester pregnancy; renal artery stenosis 2. ARBs - -hyperkalemia - -Cx: pregnancy 3. Aliskrein - -Cx: pregnancy and renal impairement/diabetes
56
Anti-HTN: Calcium channel blockers act as direct vasodilators. They affect mostly the arteries. What are examples of calcium channel blockers and their actions?
1. Dihydropyridines (vascular effect) - -nifedipine, nicardipine, amlodipine 2. Non-dihydropyridines (vascular and heart) - -verapamil and diltiazem
57
Anti-HTN: These vasodilators are used in the case of severe HTN or HTN emergencies
- Minoxidil - Nitroprusside (IV) - Fenodopam (IV)
58
Anti-HTN: What are the adverse effects and contraindications of 1. Calcium channel blockers 2. Hydralazine 3. Minoxidil 4. Nitroprusside 5. Fenoldopam
1. Calcium blockers --reflex tachycardia (vascular only) --bradycardia (vascular/heart) Cx: any anti-HTN's 2. Minoxidil - -hypertrichosis 3. Nitroprusside - -thiocyanate/cyanide toxicity - -Cx: any hypo/hypertensive meds (esp. nitrates and erectile dysfunction)
59
Anti-HTN: Initial management of HTN may involve lifestyle changes including sodium restriction, reduction of body weight, or increased exercise. Pharmacological management may begin with monotherapy (if mild HTN -- thiazide). However, if a single drug does not adequately control blood pressure, drugs with ______ sites of action may be combined
Different sites of action ("stepped care") 1. diuretic (1st or 2nd) 2. If 3 drugs required: diuretic, sympatholytic or ACE inhibitor, and direct vasodilator. 3. a-2 agonists may be added at this point
60
Anti-HTN: True/False: ACE's and ARBs should NOT be given during pregnancy
True *no ACE, ARBs, aliskrein (or diuretics except in heart disease)
61
Anti-HTN: What type of diuretic is good for patients with osteoporosis?
Thiazide type
62
UTI: Acute cystitis (UTI) is one of the most common health care visits for adult females. It may be a cause of sepsis (urosepsis) in older patients, and it is less likely to occur in children unless there is an anatomic abnormality or unusual organism. What are clinical features of UTI's?
Symptoms: - urgency, frequency, dysuria - systemic symptoms: fever, malaise Gross: hyperemic mucosa (red, swollen mucosa) Cause: - Ascending infection (MC) (Gram negative: E. coli, Klebsiella, Enterobacter, Proteus)
63
UTI: Risk factors for urinary tract infections include: a. short urethra b. urinary stasis or incomplete emptying c. urinary obstruction d. sexual intercourse
All of the above * vesicoureteral reflux (pyelonephritis) * instrumentation (catheter) * pregnancy * sex and age differences * pre-existing renal lesions (diabetes, sickle cell, immunosuppression)
64
UTI: Urinalysis may be performed to diagnose: 1. Intrinsic functional renal disease (tubular/glomerular) 2. Infections (bladder) 3. Obstruction (urolithiasis/nephrolithiasis) What are they key components included in urinalysis?
1. pH 2. Specific gravity (ion conc.) 3. Bilirubin 4. Ketone bodies 5. Hemoglobin 6. Protein (proteinuria or albuminuria = renal disease) (<150 protein in urine daily) 7. RBCs and WBC;s 8. Crystals and casts (Tamm-Horsefall; uromodulin) in DCT and CD's
65
UTI: Presence of RBC's in urine is indicative of a ______ urinary tract infection. It is most commonly due to infection (cystitis/UTI)
Lower urinary tract (bladder, urethra, prostate) *may be due to infection or carcinoma of the bladder (older patient NOTE: RBC's look like refractile discs on urinalysis
66
UTI: 1. The presence of neutrophils on urinalysis is most often indicative of _______. 2. The presence of eosinophils on urinalysis most likely indicates _______.
1. Neutrophils --UTI (leukocyte esterase and nitrite) 2. Eosinophils - -drug induced nephritis (penicillin, cephalexin, NSAIDS) - -transplant rejection
67
UTI: Both nitrite and leukocyte esterase are useful in detecting the presence of UTI. Nitrite on urinalysis detects nitrate reducing bacteria (e.g. E. coli). It is positive if there is a significant number of nitrate-reducing bacteria present. Detection of leukocyte esterase on urinalysis is about 80% sensitive and specific. What does leukocyte esterase detect?
Esterase = present in lysosomes and neutrophils NOTE: Inc. frequency of void in UTI can diminish the sensitivity of nitrite strip
68
UTI: What are possible causes of the presence of Leukocyte esterase and Nitrites on urinalysis?
1. UTI - -female patient (dysuria, frequency, urgency, suprapubic pain) - -DD: pyelonephritis, urethritis * urine culture +positive 2. Sterile "pyuria" - -chlamydia urethritis - -bladder tumors or nephritis * urine culture negative
69
UTI: You receive urinalysis results that are positive for the presence of nitrites and esterase. What do you suspect?
Bacterial UTI
70
UTI: You receive the results from a patient's urinalysis. You see it is positive for esterase but NOT for nitrites. What do you suspect?
Sterile pyuria
71
UTI: Treatment for uncomplicated UTI's involve empiric therapy (TMP-SMX typically). Treatment is based upon clinical and urinalysis/dipstick findings. How are recurrent, severe cases in kids assessed?
Microbiologic culture *antibiotic sensitivity for optimum treatment selection
72
UTI: Collection of urine for culture by voiding is inherently non-sterile due to potential contamination by perineal, periurethral bacteria (skin bugs, stool elements). Because of this inherent limitation, one criterion for assessment of true infection is the "colony count" (quantitative) method. What is considered significant for true infection?
100,000 colonies/mL (or CFUs) of a single organism
73
UTI: Any UTI (of the bladder or urethritis) may potentially lead to kidney involvement/infection (pyelonephritis). Acute pyelonephritis is typically due to an ascending infection from the bladder that may involve hematogenous spread (though not common). What are the most common organisms involved in pyelonephritis?
E. coli (MC) Proteus Klebsiella Enterobacter
74
UTI: Urinary tract obstruction or stasis can lead to inc. risk of bacterial overgrowth or migration (reflux) up the ureter into the renal pelvis of the kidney. This is most commonly associated with what valve?
Incompetence of vesiculoureteral valve *evaluate w/ voiding cystourethrogram
75
UTI: True/False - In the absence of vesicoureteral reflux (or other congenital anomaly), most infections remain localized to the bladder (cystitis).
True
76
UTI: A patient presents with complaints of sudden pain at the costovertebral angle. She states she has been running a fever for the past two days. She also states that she has felt the need to urinate more frequently and urgently than normal. Upon palpation, you note tenderness at the costovertebral angle. Urinalysis reveals leukocyte casts. What do you suspect?
Acute pyelonephritis Clinical: - sudden pain at costovertebral angle - tenderness - fever - dysuria, frequency, urgency Mechanism: ascending infection (gram - enterics) Lab: Leukocyte casts
77
UTI: Acute pyelonephritis involves renal pelvis, tubules and interstitium. What are common causes for acute pyelonephritis? a. vesiculoureteral reflux b. instrumentation c. diabetes mellitus d. prostate hypertrophy
All of the above *MC in older females
78
UTI: What is a common histological feature of pyelonephritis?
Neutrophils within tubules
79
UTI: Pyelonephritis may also be caused by Polyoma virus (latent infection). When is polyomavirus most commonly seen? What are findings that can indicate polyoma virus infection?
Immunosuppression (allograft kidneys) Histology: - nuclear inclusion - interstitial inflammation (lymphocytes)
80
UTI: Complications of pyelonephritis include: 1. papillary necrosis 2. pyonephrosis 3. abscess 4. perinephric abscess 5. Septicemia 6. Chronic pyelonephritis Papillary necrosis most commonly occurs where? In what patients is it most likely to be seen?
--tips of pyramids (medulla more susceptible) --diabetes and sickle cell disease (not trait)
81
UTI: Complications of pyelonephritis include: 1. papillary necrosis 2. pyonephrosis (pus in collecting system) 3. abscess 4. perinephric abscess (cortical surface) 5. Septicemia 6. Chronic pyelonephritis True/False - Pyelonephritis is the nidus for seeding into the systemic circulation.
True
82
UTI: Complications of pyelonephritis include: 1. papillary necrosis 2. pyonephrosis 3. abscess 4. perinephric abscess 5. Septicemia 6. Chronic pyelonephritis Abscesses are more likely to form on the cortical surface. Multiple small abscesses are more likely to been seen in what condition?
hematogenous spread to the kidney
83
UTI: True/False - Candida pyelonephritis most likely starts in the bladder and is due to ascending infection. However, it is uncommon.
True *small numbers would be more suspicious of a skin/perineal contamination rather than a UTI
84
UTI: What labs would you most likely see in a patient with acute pyelonephritis?
1. Neutrophils 2. WBC casts 3. Viral changes in urothelial cells (on urine cytology; if polyoma virus)
85
UTI: Chronic pyelonephritis is caused by recurrent and persistent bacterial infection. It is most commonly due to 1. chronic urinary tract obstruction 2. urine reflux (vesiculoureteral) What are characteristics of chronic pyelonephritis?
1. Scarring and blunting (calyces and pelvis) 2. Gross deformities (irregular cortical scars) 3. Scars at upper and lower poles 4. Renal insufficiency (gradual) * important cause of end stage renal disease (dialysis)
86
UTI: dilation of calyces (caliectasis) may also be seen in chronic pyelonephritis. What leads to caliectasis?
inflammatory destruction of renal papillae -w/ atrophy and scarring of cortex
87
UTI: In chronic pyelonephritis, glomeruli are typically NOT involved. However, chronic interstitial inflammation, interstitial fibrosis and tubular atrophy may be seen. Which of the following is NOT a characteristic of tubular damage associated with chronic pyelonephritis? a. epithelial atrophy b. diffuse, eosinophilic hyaline casts c. "pinched off" spherical segments (resembling colloid; thyroidization) d. undifferentiated spindle cells
Answer: D NOT undifferentiated spindle cells (WIlm's)
88
UTI: True/False - chronic pyelonephritis is most commonly seen in patients with multiple recurrent UTI's. On histology you can see plasma cells
True
89
UTI: A type of chronic pyelonephritis associated with Proteus infection and obstruction. Histology includes: - foamy macrophages - lymphocytes, plasma cells and neutrophils Gross: large, yellow orange nodules
Xanthogranulomatous pyelonephritis **can grossly mimic renal cell carcinoma NOTE: foamy macros = breakdown of renal parenchyma
90
Renal tumors: Oncocytomas are benign neoplasms that are difficult to diagnose prior to surgery. These neoplastic cells derive from collecting duct intercalated cells. What are common presentations of oncocytomas?
- painless hematuria - flank pain - abdominal mass "dragging" sensation *similar to renal carcinoma
91
Renal tumors: A patient presents complaining of lower back pain. Histologic findings include: -plump cells with abundant, finely granular acidophilic (eosinophilic) cytoplasm and round nuclei that lack significant atypia. What do you suspect?
Oncocytoma --appearance due to abundant mitochondria Gross: - mahogany brown (mitochondrial lipochrome pigments) - central scar (not always)
92
Renal tumor: What can be seen on CT of a patient with oncocytoma?
-stellate central hypodensity (central scar)
93
Renal tumor: Small, papillary lesions on the kidney. Tumor size typically under 5mm. These tumors are most often associated with advanced age
Papillary renal adenoma NOTE: tumors that resemble clear cell, chromophobe or collecting duct renal carcinomas are NOT adenomas
94
Renal tumors: This benign tumor has a strong association with tuberous sclerosis. It is due to mutations in TSC2 or TSC1 resulting in loss of function (LOF). Features include: -mix of well differentiated adipose tissue, SM and thick walled vessels.
Angiomyolipoma * can resemble renal cell carcinoma (gross) * lacks necrosis
95
Renal tumors: True/False - Tuberous sclerosis is also associated with angiofibromas and astroglial hamartomas
True
96
Renal tumors: Malignant tumors include 1. Wilm's tumor (kids) 2. Renal cell carcinoma (clear cell MC) 3. Urothelial cell carcinoma (urine collecting system) ______ is a malignant tumor of embryonal renal elements. It is comprised of mixed components (blastemal, stromal and epithelial tissue). It also contains embryonic glomerular structures
Wilms tumor (Nephroblastoma) * most common abdominal solid tumor of children * ages 2-4
97
Renal tumors: Wilms tumors are most often sporadic and unilateral. However, 5% of cases arise from 3 different congenital syndromes that can pre-dispose to cancer (bilateral). These syndromes are: 1. WAGR 2. Denys-Drash 3. Beckwith-Wiedemann syndrome WAGR is associated with what clinical findings?
- Wilms tumor - Aniridia - Genitourinary anomalies - mental Retardation (intellectual disability)
98
Renal tumors: Wilms tumors are most often sporadic and unilateral. However, 5% of cases arise from 3 different congenital syndromes that can pre-dispose to cancer (bilateral). These syndromes are: 1. WAGR 2. Denys-Drash 3. Beckwith-Wiedemann syndrome Denys Drash syndrome is asociated with what clinical findings?
- Wilms tumor - intersexual disorders - glomerular mesangial sclerosis
99
Renal tumors: Wilms tumors are most often sporadic and unilateral. However, 5% of cases arise from 3 different congenital syndromes that can pre-dispose to cancer (bilateral). These syndromes are: 1. WAGR 2. Denys-Drash 3. Beckwith-Wiedemann syndrome Beckwith Widemann syndrome is associated with Wilms tumor along with what other clinical symptoms?
-overgrowth (gigantism, hemihypertrophy, visceromegaly, macroglossia)
100
Renal tumors: Wilm's tumor sporadic and syndrome lesions are associated with LOF mutations in what genes?
1. WT1 (tumor suppressor) 2. WT2 (near WT1) *chromosome 11
101
Renal tumors: Wilms tumor has a heterogenous histology, often containing varying proportions of the following elements: 1. blastema-like 2. epithelial 3. tumor stroma Describe the features
1. Blastema-like - -small ovoid cells w/ scanty cytoplasm - -nests and trabeculae 2. Epithelial --small, tubular structures (imature, glomeruli-like) 3. tumor stroma w/ undifferentiated spindle cells - -SM, SK muscle, fibroblasts, fat or neural differentiation
102
Renal tumors: Wilms tumor makes up 85% of pediatric renal neoplasms, with only 5% of cases being bilateral. How is it diagnosed?
- large, palpable abdominal mass w/ HTN and hematuria | - abdominal pain, intestinal obstruction, HTN, hematuria, symptoms of tumor rupture
103
Renal tumors: A malignant neoplasm of renal tubular (clear cells) or ductal epithelial cells. It makes up the majority of primary renal cancers, and is more common in men. It is often associated with smoking and obesity.
Renal cell carcinoma
104
Renal tumors: A patient presents with complaints of fever, flank pain and hematuria. He admits to a unintentional 10 lb weight loss. On PE you note a palpable mass. Labs reveal Polycythemia (Inc. EPO) and Hypercalcemia (PTHrP). You suspect
Renal cell carcinoma
105
Renal tumors: There are three main histologic types of renal cell carcinoma: 1. clear cell 2. chromophobe 3. papillary True/False - These tumors often involve renal vein and IVC invasion and are characterized by hematogenous spread (lungs and bone). Furthermore, these tumors are known for unusual metastatic sites.
True
106
Renal tumors: This type of renal cell carcinoma is associated with the VHL gene (chromosome 3). Loss of one VHL allele occurs in most sporadic clear cell cases, while mutations in the gene appear in more than half.
Clear cell renal cell carcinoma
107
Renal tumors: You receive the results from a biopsy of a patient with suspected renal tumor. Gross findings include a solid or focally cystic, yellow - orange mass with focal hemorrhage and necrosis. Histology reveals polygonal shaped clear cells w/ delicate vasculature (chicken wire). These clear cells are filled with lipids and carbs. The aforementioned features are gross and histologic findings for what renal tumor type?
Clear cell renal carcinoma
108
Renal tumors: Histology of a renal tumor biopsy (suspected renal cell carcinoma) reveals "finger like projections" w/ increased nuclear to cytoplasmic ratio. What type best fits this description?
papillary renal cell carcinoma
109
Renal tumors: Histology of a renal tumor biopsy (suspected renal cell carcinoma) reveals "plant cells" with prominent well defined cell walls. Staining is more eosinophilic This description best fits which type?
Chromophobe
110
Renal: Which of the following is the most important risk factor for renal cell carcinoma? a. obesity b. unopposed estrogen therapy c. HTN d. tobacco use
D: tobacco use NOTE: many cases occur sporadically w/out an identifiable risk factor; some are familial
111
Renal tumors: True/False - Almost ALL sporadic renal clear cell carcinomas have a deletion of the VHL tumor suppressor gene
True
112
Renal tumors: Renal cell carcinoma can present with flank pain, a palpable mass and hematuria. What are other possible symptoms of renal cell carcinoma?
- -inc. EPO and renin production - -fever - -weight loss, - -malaise, dragging - -renal vein thrombosis * can mimic other diseases * unusual metastatic sites
113
Renal tumors: True/False - Patients with renal cell carcinoma may be asymptomatic due to the large amount of growth space in the retroperitoneum
True
114
Renal tumors: What syndromes are commonly associated with renal cell carcinoma?
1. Cushing (inc. cortisol) | 2. Hypercalcemia (PTHrP)
115
Renal tumors: Metastasis is present at diagnosis in 25% of renal cell carcinoma patients. What are the most common sites of metastasis?
Lungs, Bones, also: regional lymph nodes, liver, adrenal, brain * unusual sites
116
Renal tumors: A cancer that involves the urothelial mucosal lining. It can involve the renal pelvis, renal calyces, ureters and bladder. It often shows a papillary configuration.
Urothelial cell carcinoma * MC in bladder * field effect (associated flat lesions)
117
Renal tumors: What are major risk factors for the development of urothelial cell carcinoma? a. smoking b. radiation c. aniline dyes d. schistosoma hematobium
All of the above * Smoking = primary * Schistosoma
118
Renal cell tumors: True/False: Because the bulky mass (urothelial cell carcinoma) can grow for some time in large, open spaces of the bladder, known exposure risk and hematuria will be the most useful diagnostic clues.
True
119
Renal tumors: Gross findings reveal large, bulky, papillary appearing mass with friable, yellow material and additional small lesions. This best describes what cancer?
urothelial cell carcinoma *friable yellow = ulcers, necrosis NOTE: Histology - papillary fronds or finger-like projections w/ fibrovascular cores
120
Renal tumors: With urothelial cell carcinoma, invasion into _______ layer indicates worse prognosis and higher stage. This may necessitate cystectomy.
invade musclaris propria NOTE: non-invasive treated locally (transurethral- resection)
121
Renal tumors: How should urothelial cell carcinoma be managed? a. local control (bleeding and growth) b. immediate surgery c. chemotherapy
Answer: A --local control of bleeding and growth * high recurrence * follow up: screen cytology w/ cystoscopy
122
Congenital/Cystic: This is the most common congenital kidney disorder. It is most often associated with Turner syndeom (45XO), or Trisomy 13, 18, 21. It is often an incidental finding and is seen with fusion at the lower pole.
Horseshoe kidney * inc. risk infection, calculi * abnormal course of ureter could lead to hydronephrosis
123
Congenital/Cystic: With a horseshoe kidney, the fused inferior pole gets hung up on the ________ artery.
Inferior mesenteric artery
124
Congenital/Cystic: Renal agenesis is the absence of kidney formation during embryogenesis. It is often associated with other abnormalities of the urinary tract or lower extremities. Bilateral renal agenesis often leads to
Stillbirth and Potter sequence
125
Congenital/Cystic: Unilateral renal agenesis is associated with ________ kidney hyperplasia. However, it is sufficient to maintain normal renal function.
Contralateral kidney hyperplasia *inc. risk of Progressive glomerular sclerosis (FSGS) due to overwork of nephron
126
Congenital/Cystic: In renal agenesis, the kidneys are absent from the retroperitoneum. True/False: A patient may present with oligohydramnios in utero (as amniotic fluid is derived from fetal urine) and may subsequently develop severe pulmonary hypoplasia at birth due to oligohydramnios.
True *severe pulmonary hypoplasia at birth due to oligohydramnios
127
Congenital/Cystic: Renal agenesis is associated with Potter sequence, Potter facies and Pulmonary hypoplasia. List the steps in Potter sequence
1. Renal agenesis 2. Oligohydramnios (little amniotic fluid) 3. Fetal compression 4. Flattened facies, hands and feet 5. positional abnormalities
128
Congenital/Cystic: Renal agenesis is associated with Potter sequence, Potter facies and Pulmonary hypoplasia. Pulmonary hypoplasia is defective development of both lungs (although one may be more affected than the other). What are other features seen in a patient with pulmonary hypoplasia (due to agenesis)?
-dec. weight, volume and acini (for body weight and gestational age) NOTE: MC due to lung compression (impedes growth in utero)
129
Congenital/Cystic: Renal agenesis is associated with Potter sequence, Potter facies and Pulmonary hypoplasia. What are features of Potter facies? a. flattened nose b. recessed chin c. post. rotated ears d. cleft lip
A-C * nose, chin, ears * can see talipes equinovarus (ankle, heel, foot turned upward; clubfoot)
130
Congenital/Cystic: Congenital hypoplasia is a rare congenital abnormality that results in histologically normal kidneys, but six or fewer renal _____ and _____.
renal lobes and calyces | medullary pyramids and cortex affected
131
Congenital/Cystic: ______ occurs with normal kidney development, but in an abnormal location. It most commonly occurs in the pelvis and fails to migrate up from the pelvis.
Ectopia *tortuosity of ureters = inc. pyelonephritis
132
Congenital/Cystic: Heritable renal tubular defects include: 1. Fanconi syndrome 2. Gitelman syndrome 3. Bartter syndrome 4. Liddle syndrome True/False: Each syndrome affects a different portion of the nephron.
True
133
Congenital/Cystic: A defect in reabsorption at the proximal tubule that leads to loss of - glucose and aa's - HCO3- - phosphate
Fanconi syndrome --loss of HCO3 = PT acidosis w/ normal anion gap --loss of phosphate = osteopenia
134
Congenital/Cystic: What are potential causes of Fanconi syndrome? a. Glycogen storage disease b. Drugs c. Lead d. Light chains (myeloma)
All of the above drugs, lead, light chains = acute tubular necrosis
135
Congenital/Cystic: ______ is an autosomal recessive disorder that involves the Thick ascending limb/loop NKCC co-transporter. It leads to metabolic alkalosis, hypOkalemia, and hypERcalciuria.
Bartter syndrome
136
Congenital/Cystic: An autosomal recessive disease that involves the DCT. It leads to metabolic AlKalosis, hypOkalemia, hypOcalciuria, and hypOmagnesemia.
Gitelman syndrome -similar to HCTZ effect (keeps Ca2+ out of urine)
137
Congenital/Cystic: An autosomal dominant disorder that occurs from a mutation that increases Na channel activity. This leads to inc. Na resorption in the collecting tubules leading to Na2+ retention and hypertension.
Liddle syndrome Clinical: - met. alkalosis - hypOkalemia - HTN - dec. aldosterone Tx: amiloride (K+ sparing)
138
Congenital/Cystic: This is an autosomal recessive disorder associated with 11-B-hydroxylase deficiency. It can be inherited or acquired (black licorice). Excessive cortisol proximal to the block activates mineralcorticoid receptors.
Syndrome of apparent mineralcorticoid excess - met. alkalosis - hypokalemia - HTN - dec. aldosterone
139
Congenital/Cystic: A cystic disease that results from abnormal metanephric differentiation. Cysts develop from the abnormal tubules. It occurs sporadically without defined inheritance.
Renal (multicystic) dysplasia *usually unilateral NOTE: DD from ARPKD
140
Congenital/Cystic: Renal dysplasia is commonly associated with which of the following disorders? a. ureteral agenesis b. glomerulonephritis c. ARPKD d. ureteropelvic junction obstruction
Answer: A, D -ureteral agenesis, ureterlopelvic jxn obstruction, ureteral atresia, ureterovesical stenosis (or post. urethral valves)
141
Congenital/Cystic: Renal dysplasia appears as undifferentiated tubular structures surrounded by primitive __1___ and possible __2___ tissue.
1. primitive mesenchyme 2. heterotropic tissue (cartilage) *immature glomeruli, tubules, cartilage surrounded by loos mesenchymal tissue ("spindled cells")
142
Congenital/Cystic: Renal dysplasia commonly presents as a palpable flank mass shortly after birth. Unilateral multicystic renal dysplasia is the MC cause of abdominal mass in ______. It is treated by removing the affected kidney.
newborns *can mimic neoplasm (Wilm's tumor)
143
Congenital/Cystic: Renal dysplasia commonly presents as a palpable flank mass shortly after birth. Bilateral dysplasia and diffuse cystic dysplasia can cause ______ and the resultant Potter sequence with life-threatening pulmonary hypoplasia
Oligohydramnios
144
Congenital/Cystic: An autosomal recessive disorder characterized by mutation in PKHD1 (fibrocystin), a gene that regulates cell diff., proliferation and adhesion. Cysts can be develop in the kidneys, liver and pancreas. Fibrocystin is found in primary cilia in these locations.
Juvenile polycystic kidney disease *pancreatic cysts, hepatic biliary dysgenesis and fibrosis NOTE: mutations that do not cause dysfunction = polymorphism
145
Congenital/Cystic: Juvenile polycystic kidney disease is an autosomal recessive disorder that typically leads to death in the neonatal period due to: 1. Pulmonary hypoplasia (from oligohydramnos; Potter) 2. Impaired lung development due to enlarged kidneys If a patient survives the neonatal period, what is expected?
- -varying time of onset/progression | - -congenital hepatic fibrosis
146
Congenital/Cystic: How can you differentiate between ARPKD and multi-cystic renal dysplasia?
1. ARPKD - -AR, PKHD1 mutation - -small, linear cysts of similar size - -smooth, external surface - -oligohydramnios, pulm. hypoplasia, congenital hepatic fibrosis 2. Multicystic renal dysplasia - -sporadic - -multiple cysts; vary size - -irregular external surface - -primitive mesenchyme (histo) - -unilateral (can remove) - -bilateral = oligohydromnios
147
Congenital/Cystic: Adult polycystic kidney disease (ADPKD) is due to mutations in _____ and _____. These cysts are NOT present at birth, and tend to progress to end stage renal failure. ADPKD accounts for 5% of dialysis or transplantation, and has high penetrance (nearly 100%).
- polycystin 1 (PKD1; chrom 16)) - polycystin 2 (PKD2; chrom 4) * primary cilia (tubular epithelial cells) * disrupted calcium signalling (normally inhibits renal tubule growth)
148
Congenital/Cystic: Which of the following is/are clinical/gross findings of ADPKD? a. numerous dilated cysts with clear fluid b. bilaterally enlarged kidneys (up to 4kg) c. colon diverticuli d. "washed" renal papillae
Answer: A-C *cysts can be present in liver, spleen, pancreas, lungs
149
Congenital/Cystic: ADPKD is usually asymptomatic until the onset of renal failure and progression to uremia. Onset is often insidious, with: - hematuria - proteinuria - polyuria - HTN (poorly controlled; inc. renin) What are other possible clinical symptoms?
1. "Dragging" sensation - -hemorrhage into cyst 2. Liver cysts - -asymptomatic 3. Berry aneurysms - -circle of willis - -rupture = death 4. Mitral valve prolapse 5. Coronary artery or HTN 6. Infection
150
Congenital/Cystic: A disorder characterized by multiple cystic dilations of the collecting ducts in the medulla. It is often innocuous, but may present with: - hematuria - infection - urinary calculi Renal function is usually normal.
Medullary sponge kidney *unknown pathogenesis
151
Congenital/Cystic: A patient presents with polyuria and enuresis (bed wetting). Labs reveal: 1. tubulointerstitial fibrosis 2. cysts at corticomedullary junction 3. polyuria due to impaired concentrating ability and sodium wasting What should you consider in your differential diagnosis?
Medullary cystic kidney disease and nephronopthisis Features: - small kidneys - cysts at corticomed. jxn - sodium wasting (deteriorating tubular fxn) - enuresis (bed wetting) - chronic renal failure - poor prognosis NOTE: 2 similar diseases w/ different genes involved
152
Congenital/Cystic: Polycystic kidney disease may be acquired. It is most often seen in dialysis patients. Features include: 1. normal sized kidneys w/ small cysts (<2cm) 2. ______ within cysts 3. risk for renal cell carcinoma
calcium oxalate within cysts
153
Congenital/Cystic: Thin-walled and fluid filled cysts (containing ultrafiltrate). They may become large and bleed or cause pain. Multiple of these cysts may be seen. However, they are typically asymptomatic and have no neoplastic risk or concern for renal failure.
Simple and complex cysts * common with age * bleed: microscopic hematuria * pain
154
Congenital/Cystic: ______ is usually an imaging designation. It conveys the presence of a solid component, septation and/or contrast enhancement. It may indicate neoplasm and requires follow up/removal.
Complexity (complex cyst) Simple cysts on CT: - thin walled - smooth contours - avascular - fluid signals (not solid)
155
Prostate: The prostate has 3 zones: 1. Peripheral 2. Transitional/Central 3. Periurethral Which site can be palpated on exam? Which site would we find BPH?
1. Peripheral - -palpated during digital rectal exam - -MC site for prostatic cancer 2. Transitional/Central - -site for glandular component 3. Periurethral - -site for fibromuscular (stromal) component * BPH
156
Prostate: A 26 year old male presents with complaints of feeling "ill." He states he has had a fever of 100.3, chills, and increased urgency to urinate. He also complains he has had lower back and perineal pain. Upon physical exam you note tenderness and bogginess in his prostate. Lab reveals gram negative rod, that is non-spore forming and facultative anaerobe (enterobacter). You suspect
Acute bacterial prostatitis * Clinical: - -high fever, mailaise, chills, dysuria, frequency, urgency, lower back, pelvic, perineal pain - -tender or boggy prostate Causes: - -gram negative enteric (enterobacter, E. coli, proteus) - -STD urethritis (gonorrhea, chlamydia)
157
Prostate: What is the pathogenesis of acute bacterial prostatitis?
1. Intra-prostatic reflux - -acute cystitis w/ reflux of infected urine into prostatic ducts) 2. Lymphovascular seeding/direct implantation - -surgery NOTE: biopsy not recommended (may lead to urosepsis)
158
Prostate: True/False - With regard to prostatitis, entry of microorganisms almost always occur via the urethra. In most cases, bacteria migrate from the urethra or bladder thorugh prostatic ducts with intra-prostatic reflux of urine
True
159
Prostate: Chronic bacterial prostatitis is often asympstomatic, but may present with lower back/perineal pain and dysuria. It may follow an episode of acute prostatitis or cystitis. Patients with chronic bacterial prostitis often have a history of recurrent _______
recurrent UTI's (w/ the SAME organism) *Antibiotics = poor penetration of prostate
160
Prostate: The most common form of prostatitis is Chronic non-bacterial prostatitis (i.e. chronic pelvic pain syndrome). It is characterized by pelvic pain in the absence of UTI and excludes presence of other conditions (e.g. urethritis, stricture, cancer). There are 2 types: Inflammatory and Non-inflammatory. Differentiate between the two.
1. Inflammatory - -WBC's in the EPS/voided bladder urine after prostatic massage 2. Non-inflammatory - -absence of WBC's *Unknown etiology (may be viral, trauma, chronic irritiation, nerve)
161
Prostate: The following histologic/lab features describe what disorder? 1. numerous, small, round dark blue lymphocytes (in stroma) 2. May have bacteria or no bacteria
Prostatitis * MC in males older than 50 * may follow UTI/cystitis
162
Prostate: Benign prostatic hyperplasia is common and is associated with increased age. What is the primary mediator of BPH?
DHT (potent androgen) 1. Stromal cells: convert testos. to DHT via 5-a-reductase 2. DHT binds local androgen receptors = inc. cell growth 3. Hyperplasia due to inc. sensitivity to DHT Tx: Finasteride blocks
163
Prostate: What can be seen on gross/microscopic of BPH? a. hyperplasia of glandular epithelail cells and stromal cells b. glands w/complex infoldings c. large hyperplastic nodules with numerous crowded glands d. arises in the peripheral zone
A-C only * arise in periurethral and central/transitional zone * compresses urethra as it passes through prostate
164
Prostate: WIth BPH, glands and stroma may be involved. On histology we would see large, hyperplastic nodules with numerous crowded glands. The glands are larger than normal, with infoldings, but surrounded by uniform, double layered cuboidal cells (no atypia). What is the role of the periurethral zone in the development of BPH?
--enables initial inc. in hyperplastic nodules NOTE: bulk of enlargement due to growth in peripheral zone
165
Prostate: On histology, what structures remain normal in BPH?
1. corpora amylacea - -rounded pink concretions 2. Columnar cells lining glands 3. Indistinct surrounding layer of basal cells
166
Prostate: True/False - Approximately 70% of men will have some microscopic hyperplasia by the age of 60, but only half of them will have prostatic enlargement. Only a subset of them will be symptomatic from urinary obstruction
True
167
Prostate: Because BPH causes narrowing of the prostatic urethra, it can lead to urinary obstruction. Thus, patients may present with - difficulty initiating or stopping urinary flow - nocturia - straining - incomplete emptying - dribbling/poor stream - inc. risk of cystitis What are methods for treatment?
1. Surgery - -transurethral resection 2. 5-alpha reductase inhibitors - -finesteride 3. alpha-1 receptor blockers - -"sins"
168
Prostate: What are complications of BPH? a. urinary obstruction b. post-renal azotemia c. bilateral hydronephrosis d. high post-residual volume (can't empty bladder)
All of the above * cystitis (stasis) * may progress to acute renal failure if not treated (renal azotemia)
169
Prostate: What is a marker of BPH?
Prostate specific antigen (PSA) -proteolytic enzyme (keeps seminal secretions liquid) Normal: 0-4ng/mL Elevated >4ng/mL in BPH
170
Prostate: True/False: Prostatic enlargement (obstructive lesion) can lead to urethral compression. This may be due to BPH, Carcinoma, or inflamation.
True
171
Prostate: Prostate cancer is the most common non-cutaneous malignancy in adult males, and is the 2nd leading cause of cancer death. It is more common in African Americans, and with advancing age. What are clinical features of prostate cancer?
1. Clinically "silent" - -MC diagnosed during screening of asymptomatic patients 2. Presents with back pain
172
Prostate: On histologic sample, Adenocarcinoma of the prostate appears with small, irregular, crowded glands with NO intervening stroma. What are other classic features?
1. Perineural invasion 2. Crystals 3. Prominent nucleoli ** Gross: MC in peripheral zone (palpable) --gritty, firm, pale yellow
173
Prostate: Prostate cancer (adenocarcinoma) is thought to derive from a precursor lesion "prostatic intra-epithelial neoplasia". What are risk factors for development of prostate cancer?
1. Advanced Age ** 2. Familial - -men w/ 1 first degree = 2x risk - -men w/ 2 first degree = 5x - -BRCA2 mutation 3. African American 4. Environmental 5. TMPRSS2-ETS fusion gene NOTE: early stage = androgen dependent (add'l mutations cause loss of dependence)
174
Prostate: The Gleason histologic grading system is an important prognostic factor. It gives a grade to both the predominant and secondary growth pattern. Add the two numbers together for total. It meausres the degree of _______ _______. Score is used to help determine treatment and prognosis.
tumor differentiation * well diff = low number * poorly diff = high number
175
Prostate: Prostate cancer is usually asymptomatic until late in the disease course. Due to high incidence and prevalence, screening is highly recommended. What are symptoms of symptomatic prostate cancer?
1. Urinary - -obstruction/UTI - -hematuria - dysuria 2. Low back/pelvic pain - -bone metastasis to vertebrae/pelvic bones - -Inc. alkaline phosphates (osteoblastic metastasis) 3. Extrinsic compression of spinal cord - -vertebral and sacral metastasis
176
Prostate: Screening for prostate cancer involves 1. Digital rectal exam 2. PSA The digital rectal exam is examiner dependent. Physician feels for _____, ______ and _____. It is often normal in cancer patients.
Nodules, asymmetry, induration
177
Prostate: Screening for prostate cancer involves 1. Digital rectal exam 2. PSA PSA is normal when <4ng/mL. Levels increase with age and rates of increase of often used in active surveillance (conservative management therapy). What are downsides to using PSA?
- -not sensitive or specific for cancer - -no PSA level guarantees absence of cancer - -can be normal in cancer - -higher levels = inc. sensitivity - -BPH, infarct and inflammation = inc. PSA
178
Prostate: Because PSA can be elevated in other conditions, other methods have been developed to determine which patients need further workup. These methods include: 1. PSA velocity 2. Free PSA 3. PSA density Explain each
1. PSA velocity - -rate of change > 0.75ng/mL/year - -PSA inc. more w/ prostate cancer than regular cells 2. Free PSA - -PSA can be free or protein bound - -ratio of free to total PSA is dec. in cancer (more bound) 3. PSA density - -adjusts for PSA prostate volume - -cancer = 10x more PSA than benign
179
Prostate: The following are different patterns of spread of prostate cancer: 1. direct spread 2. lymphatic spread 3. hematogenous Direct spread occurs often along the nerves (perineural invasion, while lymphatic involves the obturator, para-aortic, pelvic. What does hematogenous spread involve?
1. Bone - -MC extranodal site - -boney spread: lumbar spine, pelvis, proximal femur, ribs 2. Lung, liver
180
Prostate: Describe diagnosis of prostate cancer if: 1. PSA or DRE is abnormal 2. If cancer is present and staging should be done
1. Abnormal PSA or DRE - -Biopsy (via ultrasound; multiple) 2. If cancer is present a. Radionuclide bone scan (metastasis) b. MRI abdomen and pelvis (extent of disease) NOTE: level of PSA often (not always) correlates with volume and stage of disease. Serial PSA levels can help detect recurrence
181
Prostate: Prognosis of prostate cancer is dependent upon the histologic grade/margin status and the stage (most important; how far it has spread). Methods for treating prostate cancer include: 1. Radial prostatectomy 2. Radiation 3. Hormone therapy What are possible complications of each?
1. Radical prostatectomy (robot) - -erectile dysfunction, urinary incontinence 2. Radiation (external beam/radioactive implants) - -inc. risk 2o bladder/rectal cancer 3. Hormonal (androgen ablation therapy) - -tumors develop androgen independence - -Leuprolide (GnRH agonist)
182
Testes/Scrotum: During development, the testes are initially located within the abdomen (near kidneys). However, they slowly migrate through the inguinal canal into the scrotum during two major phases: 1. Transabdominal phase - testes migrate to lower abdomen or pelvic brim. 2. Inguinoscrotal phase - testes descent through inguinal canal into the scrotum. What hormones are released during these phases that influence testicular migration?
1. Transabdominal Phase - -MIF - -lower abdomen 2. Inguino-scrotal phase - -Androgens - -calcitonin gene-related peptide (genitofemoral nerve) - -inguinal canal to scrotume
183
Testes/Scrotum: ______ results from incomplete testicular descent. It is most common in the inguinal canal, but may remain intra-abdominal. It is most often unilateral, and patients tend to be asymptomatic.
Cryptochordism - -seen at birth (MC in pre-term infants) - -low birth weight: risk factor NOTE: many spontaneously descend by 1 year of age (uncommon after that)
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Testes/Scrotum: The following histologic abnormalities are noted: 1. Arrest in germ cell development 2. Thickening of tubular bm 3. Hyalinization of semniferous tubules 4. Absent spermatogenesis You suspect?
Cryptochordism - changes begin by age 2 (if uncorrected) - results in testicular atrophy (may be seen in contralateral descended testes too)
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Testes/Scrotum: True/False - Males born with cryptochordism are at increased risk of infertility due to arrested germ cell maturation and testicular atrophy. They are also at risk for germ cell tumors (seminoma) and/or torsion in undescended testes.
True tumors: intra-abdominal torsion: undescended testes ipsilateral inguinal hernia: some patients
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Testes/Scrotum: Treatment of cryptochordism involves orchiopexy (6-12 mos of age MC). The testicle is moved to its usual location within the scrotum. However, there is still an increased risk for the development of what?
--tumors *easier to ID in the scrotum
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Testes/Scrotum: Orchitis is inflammation of the testes that can lead to: 1. testicular pain/swelling 2. scrotal erythema 3. Fever What is the most common etiology for Orchitis?
Mumps *RNA paramyxovirus - usually few days after parotitis * testicular involvement: post-puberty * usually unilateral; infertility if bilateral
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Testes/Scrotum: Epididymitis is inflammation of the epididymis. 1. The most common causes in children and men > 35 are _______. 2. The most common causes in sexually active men < 35 are _______. It results in an epidiymal abscess and may extend into the testes.
1. E. coli, Pseudomonas | 2. Chlamydia (MC); N. gonorrhea
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Testes/Scrotum: Clinical symptoms of epididymitis include: 1. Scrotal pain, swelling 2. Urethritis/discharge (if STD) 3. Pain relief with elevation of affected hemiscrotum (also known as ______________). Epididymitis can spread to seminal vesicles, prostate and testes.
1. Positive Prehn's sign a. pain relief with elevation of affected hemiscrotum - -relieves weight of testis off epididymus - -acute epididymitis b. With torsion there is no pain relief NOTE: MC causes of acute scrotal pain in adults: torsion and epididymitis
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Testes/Scrotum: _________ describes abnormally dilated scrotal veins (pampiniform plexus and internal spermatic vein). It typically presents between ages 15 and 25 due to decreased venous drainage. It is often diagnosed by ultrasound and via its appearance as a "bag of worms"
Varicocele - -MC on left side (anatomic factors; 90 degree angle) - -Most decompress in supine position
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Testes/Scrotum: When should you consider another etiology other than anatomic in a patient with varicocele?
1. acute onset (either side) 2. right sided 3. do not decompress w/ horizontal recumbency
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Testes/Scrotum: Patients with varicocele may present with complaints of a dull ache or they may be asymptomatic. Often these patients present with fertility issues. Infertility results from poor venous drainage through the varicocele resulting in _____ scrotal temperature and thus decreased spermatogenesis and poor sperm production.
Increased scrotal temperature
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Testes/Scrotum: ______ refers to twisting of the spermatic cord which impairs venous drainage (and potentially arterial supply). Infarction can ultimately occur. It is most often due to a congenital lack of supporting attachment.
Testicular torsion "bell clapper deformity"
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Testes/Scrotum: A 13 year old male presents to the clinic with sudden onset of severe, unilateral testicular pain. His father, who accompanied him, states he has had nausea and vomiting for the past 24 hours. You note on PE elevated testicle (due to retraction upward) and negative cremasteric relfex. You suspect?
Testicular torsion - adolescent - absent cremasteric reflex (stroking skin in upper thigh -- retraction of testes on side of stimulus)
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Testes/Scrotum: Testicular torsion is a urological emergency. If History and Physical suggest torsion, the patient must have a urologic consultation. What is another diagnostic tool to help confirm torsion? How is it treated?
Diagnosis: - -Ultrasound - -if low index of suspension, evaluate blood flow/anatomy Treatment: --Surgery (asap) (testes anchored to scrotum)
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Testes/Scrotum: Hydrocele refers to fluid collection within the tunica vaginalis. There are two types of hydrocele: 1. Communicating 2. Non-communicating ______ is an imbalance of fluid production versus absorption
Non-communicating --filarial infestation (rare in U.S)
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Testes/Scrotum: Hydrocele refers to fluid collection within the tunica vaginalis. There are two types of hydrocele: 1. Communicating 2. Non-communicating In _____, the processus vaginalis remains patent and allows fluid to flow from the peritoneal cavity into the scrotum.
Communicating hydrocele
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Testes/Scrotum: Patients with hydrocele are most often children. It is the MC cause of scrotal enlargement in kids. How is it diagnosed?
Clinical: --soft, non-tender fullness of scrotum Diagnosis: --Transillumination (U/S = accurate)
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Testes/Scrotum: Presence of blood within the tunica vaginalis due to vascular damage . It usually arises secondary to trauma (ie-testicular fracture) or torsion
Hematocele
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Testes/Scrotum: Benign cystic accumulation of sperm. It often arises from the head of the epididymus. It causes a smooth, soft, well-circumscribed scrotal mass.
Spermatocele * usually asymptomatic * unknown etiology (maybe distal obstruction)
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Testicular tumors: Testicular tumors are relatively uncommon, but are more frequent in caucasians. Clinical presentation includes: 1. firm, painless mass 2. metastasis (if non-seminomatous; embryonal) What are risk factors for testicular tumor development?
1. Cryptochordism - -MC - -high risk if intra-abdominal 2. Testicular dysgenesis (testicular feminization, XXY) 3. Genetic pre-disposition - -1st degree relative w/ history
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Testicular tumors: Ultrasound is the best method for diagnosing testicular tumors. Tumors generally appear as hypo-echoic mass within the testes. Serum tumor markers may help confirm and suggest phenotype (e.g. AFP for yolk sac) and can be used for monitoring. What is the best determinant of prognosis?
Prognosis: --staging (imaging/surgery for nodal distant spread) Tumor burden: --LDH Treatment: Orchiectomy --w/ chemotherapy and radiotherapy
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Testicular tumors: Germ cell tumors are the most common type of test. tumor. Most have an extra copy of the short arm of chromosome 12 (isochromosome 12p). They can be classified based on: 1. Seminoma 2. Non-seminomatous (NSGST) What are examples of non-seminoma?
- Embryonal carcinoma - teratoma - yolk sac - choriocarcinoma
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Testicular tumors: Germ cell tumors are typically preceded by an ________ stage, known as intratubular germ cell neoplasia.
In situ
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Testicular tumors: Pre-treatment tumor marker levels are useful for 1. staging/prognosis 2. monitoring response to Tx 3. monitoring for recurrence (inc. levels) List the tumor markers assessed in testicular tumors
β-hCG, AFP, LDH NOTE: persistent elevation after orchiectomy indicates residual tumor
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Testicular tumors: The most common testicular tumor characterized grossly by: 1. yellow lobulations 2. usually NO hemorrhage or necrosis 3. Replaces the entire testes. It is may be associated with isochromosome 12p or may be hyperdiploid.
Seminoma *has to be "pure" otherwise classified as mixed germ cell
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Testicular tumors: Which is a histologic feature of seminoma tumors? a. T-cell lymphocytic infiltrate b. granulomas and giant cells c. syncitiotrophoblastic cells d. peripheral eosinophils
A-C - T-cell infiltrate ** - granulomas/giant - syncytiotrophoblastic (inc. B-hcg; no significance)
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Testicular tumors: You receive pathology report over a histologic specimen from a patient you suspect has testicular tumor. Report indicates: "Large monotonous cells w/ central nuclei, prominent nucleoli, and clear cytoplasm. Cells are separated by delicate fibrous septae, and have T-cell infiltrate" What do you suspect?
Seminoma
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Testicular tumors: Seminomas tend to display lymphatic spread more often than hematogenous. 1. The most common initial site of spread is ________. 2. The most common site of hematogenous metastasis is _____.
1. Retroperitoneal - -para-aortic LN's 2. Lungs
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Testicular tumors: Treatment of seminoma tumors involves radical orchiectomy and radiation w or w/out chemotherapy. What is the prognosis with these treatments?
Good - radiosensitive, chemosensitive - metastatic also curable
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Testicular tumors: A rare tumor seen in older patients (60s). It is slow growing with NO metastasis. Unlike seminomas, these tumors dont: 1. occur as part of mixed germ cell tumors 2. contain isochrom. 12p 3. arise from intratubular germ cell neoplasia
Spermatocytic seminoma *good prognosis NOTE: NO similarity with classic Seminoma
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Testicular tumors: Non-seminoma germ cell tumor that occurs at a younger age (20-40). These are often "mixed" type tumors that are hemorrhagic and necrotic. They are bulky, but don't replace the entire testes.
Embryonal carcinoma Histo: - pleomorphic anaplastic cells - primitive - mixed w/ other germ cell components
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Testicular tumors: Embryonal carcinoma most often has hematogenous before lymphatic spread. Metastasis occurs earlier than seen in seminomas and is not uncommon. How is it treated? prognosis?
Tx: --orchiectomy w/ or w/out chemo Prognosis: --not as good NOTE: metastatic sites: retroperitoneum, lung. liver
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Testicular tumors: _____ is the most common testicular tumor of children. It is seen in <3 years of age (better prognosis), but may be seen in older patients as a mixed germ cell tumor.
Yolk sac tumor Microscopic: - -various patterns - -Schiller-Duval bodies (primitive glomerulus) Marker: --AFP
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Testicular tumors: The most malignant of all germ cell tumors. Metastasis is often widespread prior to forming a local mass. It is characterized by 1. cytotrophoblastic tissue 2. syncitiotrophoblastic tissue
Choriocarcinoma Marker: --hcG 2nd-3rd decade of life
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Testicular tumors: Choriocarcinoma presents with 1. Gynecomastia 2. Symptoms of Metastatic disease Gynecomastia occurs due to _____, which shares a common a-subunit w/ LH. An increase can lead to inc. steroidogenesis.
hcG --inc. hcG = inc. testosterone and E2 --higher degree of E2 (and inc. ratio of E2 to testosterone)
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Testicular tumors: Choriocarcinoma presents with 1. Gynecomastia 2. Metastatic disease What are the MC sites of metastasis?
- hemoptysis (lung) - liver - neurologic (brain)
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Testicular tumors: ____ is a tumor derived from more than one germ cell layer. It may contain hair, skin, cartilage, teeth, neural tissue. It is the 2nd MC germ cell tumor in kids (~age 2). In adults, it is mixed.
Teratoma *ecto, endo, mesodermal tissue arranged haphazardly Two types: 1. Immature (embryonal; aggressive) 2. mature
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Testicular tumors: Leydig cells secrete primarily androgens and some estrogen. True/False: Leydig cell tumors can present at any age and can have various manifestations based on which hormone is being secreted.
True 1. Boys w/ androgen secreting tumors - -precocious puberty 2. Boys with E2 tumors: - -gynecomastia, feminized 3. Adults w/ androgen: - -asymptomatic 4. Adults w/ estrogen - -loss of libido, erectile dysf., infertility, gynecomastia
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Sex cord-stromal tumors: Leydig cell tumors often present with a non-tender, palpable testicular mass or nodule. It can present at any age. What are common histologic findings?
1. Crystals of Reinke - -characteristic, but not always present 2. Large, round polygonal cells w/ abundant pink cytoplasm 3. Intervening capillaries 3. Gross: golden brown
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Sex cord-stromal tumors: 1. Sertoli tumors are rare and often benign. Histology shows ______ formation. 2. Scrotal squamous cell carcinoma is due to ____ exposure.
1. Tubule formation 2. Soot exposure - -chimney sweep
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Tumors: _____ is the MC type of testicular cancer in older men. It is often bilateral. It may be primarily in the testes, but can have secondary seeding from other sites.
Lymphoma * diffuse B cell MC * no specific tumor markers
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Tumors: True/False: The testes is rarely involved with metastaic disease
True