Pathoma-Lecture-Notes

Fig - tram track appearance of membranoproliferative glomerulonephritis
7.5.What are two types of membranoproliferative glomerulonephritis and what are they associated
with?

• Divided to two types based on immune deposit type-
○ Subendothelial (type 1) - associated with hepatitis B, hepatitis C. Type 1 has more tram
tracks association.
○ Within basement membrane (type 2) - pt have C3 nephritic factor (autoantibody) (HY). This
antibody binds and stabilizes c3 convertase.

• Compliment system is hyperactive which causes the disease.
• Membranoproliferative disease can cause nephritic, nephrotic or both
8. Describe how diabetes leads to nephrotic disease.
• High blood glucose leads to non-enzymatic glycosilation of vascular baement membrane which

makes it more leaky leading to nephrotic syndrome
• Protein also leaks to vessel wall and leads to hyaline arteriolosclerosis).
• Non enzymatic glycosilation means that blood sugar is so high that they stick to basement

membrane without use of enzyme.
9. What's histology finding of diabetic nephrotic syndrome. What's its treatment
• Characterized by sclerosis of mesangium aka Kimmelstein-Wilson nodules - pathogmnenomic.
• Efferent arteriole is affected more than afferent. This causes high filtration pressure.
• Treat by ACE-i because it relieves pressure in efferent arteriole.

Renal Page 3.4

Fig - Kimmelstein-Wilson nodule
10. Describe how amyloidosis leads to nephrotic disease (most common organ affected in systemic

amyloidosis is kidney).
• amyloid deposits in mesangium leading to nephrotic syndrome
• characterized by apple-green birefringence in polarized light
• mesangial nodules in diabetes and amyloidosis are immunofuorescence negative. Diabetic

nodules are PAS positive, but amyloid nodules are PAS negative, why?

Renal Page 3.5

12.4 Nephritic Syndrome

1. What are features of nephritic syndrome?
• Hallmark is glomerular inflammation and bleeding
• RBC casts and dysmorphic RBC in urine hallmark of glomerular bleeding

○ Tram hosefall proteins and RBC make RBC cast

○ Dysmorphic RBC is caused by
• Can present with some proteinurea (<3.5g/day)
• Oligurea and azotemia
• Salt retention with periorbital edema

2. What are biopsy findings of nephritic syndrome?
• Hypercellular and inflamed glomeruli
• Immune deposits activate complement. C5a attracts neutrophil which cause damage

2.5. What are some causes of nephritic syndrome?

S.N. Pathology Description

1 Post Strep GN Occur in kids after group A B-hemolytic strep infection (if the
pathogen has M protein virulence factor)

2 IgA Seen in kids after mucosal infection
Most common nephropathy worldwide

3 Alport syndrome Inherited mutation in type IV collagen

4 Goodpasture Can lead to RPGN

5 Diffuse proliferative GN, Can lead to RPGN
Post strep in adults

6 Wegner Granulomatosis Can lead to RPGN

7 Microscopic polyangitis Can lead to RPGN

8 Chug Strauss syndrome Can lead to RPGN

3. Describe etiology of post- streptococcus glomerulonephrits (PSGN).
• Occurs after group A B-hemolytic strep (specially nephritogenic strains) infection of skin (impetigo)
or pharynx.
• The nephritogenic strain carries M protein virulence factor that increases chance of nephrotic
syndrome
• Impetigo - highly contagious skin infection of kids

4. What is presentation of PSGN.
• Hematuria (cola colored urine
• Oligurea
• Hypertension
• Periorbital edema
• Usually seen in kids but may occur in adult

5. What are biopsy findings of PSGN.
• Hallmark - subepithelial humps on EM
• Granular immunofluorescence- humps are made from immune deposition
• Hypercellular inflamed glomeruli

Renal Page 4.1

Fig - subepithelial hump seen in PSGN

6. What is prognosis of PSGN.
• Supportive. The reason is because the immune deposits start subendothelially and move to
epithelial site where they make a hump. Eventually, they just fall off. So disease heals by itself.
• Some adults develop RPGN

Rapidly progressive glomerulonephritis (RPGN)
7. What is RPGN?

• Rapidly progressive glomerulonephritis is a nephritic syndrome that progress to renal failure in
weeks to months.

• Hallmark - biopsy shows cresents in bowman space. Crescent made up of fibrin and macrophage
(HY)

Fig - cellular crescent seen in RPGN. Note crescent made of fibrin and macrophage (inflammatory
stuff - not collagen)

8. What are etiologies of RPGN?
• Etiologies can be distinguished based on immunofluorescence pattern

IF Pattern Disease Comment
s

Linear (anti-basement Goodpasture syndrome
membrane Ab)
PSGN (most common)
Granular (immune complex Diffuse proliferative GN
deposition) Wegner Granulomatosis (C-ANCA positive)
Microscopic Polyangitis (P-ANCA)
Negative IF (pauci-immune) Chrug-Strauss Syndrome (P-ANCA, granuloma,
eosinophila, asthma)

Renal Page 4.2

eosinophila, asthma)
9. Describe Goodpasture syndrome

• Antibodies are made against collagen in glomerulur and alveolar basement membrane
• Pt presents with hematuria and hemoptysis
• Classically seen in young adult males
10. Describe diffuse proliferative glomerulonephritis (nephritic syndrome).
• Diffuse Ag-Ab deposition in sub-endothelial location
• Most common type of renal disease in SLE (lupus) (VHY) - most common cause of death in lupus

patients is renal failure
11. How do you distinguish Wegner granulomatosis vs Goodpasture syndrome?

• Both of them may have hemoptysis and hematuria with RPGN. However, if you see sinus
problems, then suspect Wegner. Because in Wegner's, nasopharynx is affected.

• Distinguish by IF as well
13. Describe IgA nephropathy (nephritic)

• Most common nephropathy worldwide
• IgA deposition seen in mesangium - gives granular IF

Fig - mesangial immune deposition seen in IgA nephropathy
14. What is presentatin of IgA nephropathy

• Most commonly seen in kids after mucosal infection (recall that IgA is dumped in mucosal layer)
• When infection goes away, hematuria decreases as well. New infection leads to new episode of

hematuria. This can slowly lead to renal failure
15. Describe Alport's syndrome

• Inherited defect of type IV collagen (recall type IV collagen is found in basement membrane)
• GBM becomes thin and splits
• Presents with isolated hematuria, sensory hearing loss and ocular disturbances

Renal Page 4.3

12.5 Urinary Tract Infection (UTI)

1. What are common features of UTI?
• UTI are infection of urethra (urethritis), bladder (cystisis) or kidney (pyelonephritis). Higher up the
infection, more likely it is systemic
• Most UTI are ascending infections
• Risk factors are - being female, urinary stasis, sexual intercourse, catheders

2. What is cystisis?
• Inflammation of bladder
• Presentation-
○ Dysuria (pain with urination)
○ Urinary frequency and urgency
○ Suprapubic pain
○ Lack of systemic signs

3. What are lab findings in cystisis?
• Urinalysis : cloudy urine with >10 WBCs/hpf (high power field)
• Dipstick: positive leukocyte esterase (due to pyuria - pus in urine; wbc make this)
• positive nitrites (bacterias convert nitrates to nitrites
• Gold standard is culture. It yields >100,000 colony forming unites

4. What are etiology of cystisis?
• E. Coli - 80% of cases
• Staphylococcus saprophyticus - increased incidence in young, sexually active women
• Klebsilla pneumoniae
• Proteus mirabilis - gives alkaline urine with ammonia scent
• Enterococcus faecalis

5. What does sterile pyuria suggest?
• Sterile pyuria is pus in urine (>10 WBC/hpf and positive leukocyte esterase) but negative bacteria
culture of urine
• It suggests urethritis with due to Chlamydia trachomatis or Neisseria gonorrhoeae

6. Describe presentation of pyelonephritis.
• Mostly caused due to vesicoureteral reflux (reflux of urine)
• Presentation-
○ Fever, flank pain (you won't see fever in cystisis because there's no systemic signs there) -
flank pain is due to sensitization of nerves of renal capsule
○ WBC casts, leukocytosis - WBC coming up through tubules creates a cast
○ Symptoms of cystisis - dysuria, urinary frequency, urgency, suprapubic pain

7. What are common pathogens for pyelonephritis?
• E coli (90% of times)
• Klebsiella species
• Enterococcus faecalis

8. Describe chronic pyelonephritis.
• It is interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis
• Seen due to vesiculoureteral reflux (in chidren) or obstruction - malformation of ureter entering

Renal Page 5.1

• Seen due to vesiculoureteral reflux (in chidren) or obstruction - malformation of ureter entering
bladder increases can increase chances of vesiculouretal refux

9. What are clinical features of chronic pyelonephritis?
• See cortical scarring with blunted calyces
• Scarring of upper and lower pole is characterstic of vesiculoureteral reflux
• Histology
○ See "thyoidization of kidney" - atrophic tubules have proteinaceous mateiral resembling
thyroid follicles.
○ Waxy casts may be present in urine

Fig - thyroidization of kidney seen in chronic pyelonephritis
10. pelvic inflammatory disease (PID) - infection of the upper part of the female reproductive system

namely the uterus, fallopian tubes, or the ovaries.(pyelonephritis version of cystitis)
□ Untreated PID can lead to fibrosis that can lead to infertility and ectopic pregnancy

Renal Page 5.2

12.6 Nephrolithiasis

1. What are risk factors for kidney lithiasis?
• High concentration of solute in urine/ low urine volume

2. What is presentation of lithiasis?
• Colicky pain(pain that starts and stops suddenly; occurs due to muscular contraction of hollow
tube)
• Hematuria and unilateral flank tenderness
• Stone usually passed in hours; if not, may need surgery

3. Explain different type of kidney stones.

Compositio Frequency Causes Treatment Comments
n
Staghorn
Calcium Most common Most common- idiopathic HCTZ (calcium sparring stone - nidus
oxalate for infection
and/ type hypercalcuria (exclude diuretic)
Calcium
Phosphate (usually see in hypercalcemia as a cause for

adults) hypercalcuria)

Also seen in Chron's

Can be seen in ethylene glycol

ingestion

Ammonium Second most Most common - alkalization of Surgically remove stone
Magnesium common urine by urease positive
Phosphate type pathogen (ex- proteus
(AMP) vulgaris, klebsiella);

Aka struvite
stone

Uric acid Third most Most common in pt with Hydration and alkalization
common (5%) gout, hyperuricemia (lukemia of urine (KHCO3);
Radiolucent or myeloproliferative allopurinol for gout-
(others are disorders) decreases uric acid
radiopaque) Risk factors - acidic PH, hot,
arid climite, low urine volume

Cysteine Rare; most Associated with cystinuria Hydration and May form
commonly (genetic disorder where alkalinization of urine staghorn
seen in there's low reabsorption of stone
children cysteine from tubules)

Notes:
• In Chron's, damage to small intestine causes increased absorption of oxalate. This results in high
chance of forming calcium oxalate in urine
•

Renal Page 6.1

Fig - staghorn AMP stone. If you see staghorn stone in adult, think uric acid stone; if you see
in kid, think cysteine stone.

Renal Page 6.2

12.7 Chronic Renal Failure

1. What are causes of ESRD?
• Glomerular, tubular, inflammatory or vascular insults (anything can lead to it)
• Most common causes are diabetes, HTN, and glomerular disease

2. What are some presentations of ESRD?
• Uremia (symptom of azotemia)
• HTN - due to salt and water retention
• Hyperkalemia (kidney can't exchange sodium with potassium) leading to anion gap metabolic
acidosis
• Hypocalcemia -
○ Vit D is activated by 1 alpha hydroxylase in kidney in PCT
○ Kidney can't excrete phosphate and hyperphosphatemia leads to decrease in free calcium in
blood
• Anemia (renal peritubular interstitial cells makes erythropoietin) (HY).
• Renal osteodystrophy - damage to bone due to kidney problem
○ Osteitis fibrosa cystica - hypocalcemia leads to high PTH which decalcifies the bones;
eventually leads to fibrosis and cyst formation
○ Osteomalacia - when osteoid isn't mineralized (due to low calcium in blood)
○ Osteoporosis

2.5. What is presentation of uremia?
- Mental status change, seizure, encephalopathy
- Pericarditis
- Metallic taste and breath (due to urea), uremic frost on skin (skin deposition of urea) - pt have
nausea and don't eat much and causes anorexia
- Classic signs - pericarditis, uremic fretor, uremic frost

2.75. What are classic indication of dialysis?
- A - acidosis (anion gap acidosis due to hyperkalemia)
- E - electrolyte imbalance (hyperkalemia)
- I - ingestion
- O - overload (volume) - due to salt and water retention
- U - uremia

3. What is prognosis of ESRD?
- Patients need to put on dialysis or transplant

4. What are some changes that happen when patients are put on dialysis?
- ESRD kidneys are small and shrunken (small kidney = chronic kidney disease); putting on dialysis
leads to cyst formation
- Big and cystic kidney = polycystic kidney disease. Small and cystic kidney = ESRD kidney on dialysis
- Pt have high risk for renal cell carcinoma in the shrunken kidney(HY)
- Patient get local amyloidosis in the joints.

Renal Page 7.1

Questions

Is acute kidney injury, acute renal failure and uremia the same thing?

Renal Page 8.1

12.8 Renal Neoplasia

Angiomyolipoma
1. What's angiomyolipoma? What's its associated with?
- Hamartoma made up of blood vessels, smooth muscle and adipose tissue (clear from name)
- It's associated with tuberous sclerosis (HY) (syndrome with benign tumor primarily in brain, eyes,
heart, kidney, skin and lungs. Common presentation: seizures, developmental delay, intellectual
disability and autism)

Wilm's tumor (nephroblastoma) (most common malignant renal tumor in children; average age 3
years)

1. What's histologic hallmark of Wilm's tumor?
- Blastema (primitive kidney mesenchyme cells that make glomerulus, tubules and stromal cells)

2. What's presentation of Wilm's tumor?
- Average age of presentation - 3 years

Renal Page 9.1

- Average age of presentation - 3 years
- Unilateral flank pain, humaturia and HTN (due to renin production)

3. What are etiologies of Wilm's tumor?
- 90% of cases are sporadic. Syndromic tumor are associated with 3 following syndromes:

WAGR syndrome (HY) Denys-Drash Beckwith-Wiedemann syndrome
syndrome

W = Wilm's tumor - Wilm's tumor - Wilm's tumor
A = Aniridia (lack of iris)
G = genital abnormalities - Progressive - Neonatal hypoglycemia
R = Retardation (developmental
and motor) glomerular disase - Muscular hemihypertrophy (big muscles

- Male on one side of body)

pseudohermaphro - Organomegaly (specially tongue)

ditism

- Deletion of WT1 tumor - Mutation of WT1 - Mutation of WT2 gene cluster
suppressor gene (located in
11p13) gene (imprinted genes at 11p15.5),

particularly IGF-2

Renal cell carcinoma
1. What are presentations of renal cell carcinoma? What are some paraneoplastic syndromes?
- Classic triad is hematuria, palpable mass and flank pain (see hematuria most often)
- Paraneoplastic syndromes (HY):
○ Erythropoietin production (reactive polycythemia vera)
○ Renin production (HTN)
○ PTHrP (hypercalcemia)
○ ACTH (cushings)

- Left sided varicocele (HY) - left spermatic vein drains to left renal vein; right spermatic vein drains
directly to IVC (sometimes the tumor can block renal veins)

2. What is pathogenesis of renal cell carcinoma (HY)?
- Mutation of VHL (3p) tumor suppressor gene
- It leads to increased IGF-1 (insulin like growth factor)(it promotes growth) and increased HIF

transcription factor (increases VEGF and PDGF)

3. What is staging of renal cell carcinoma?
- T - based on size and involvement of renal vein (occurs commonly and increases risk of

hematogenous spread to lung and bone)
- N - spread to retroperitoneal lymph nodes)

4. Differentiate sporadic and hereditary versions of renal cell carcinoma.

Sporadic tumor Heriditary tumor

- Classically seen in males (avg age 60) as - Classically seen in young adults and are often
single tumor in upper pole of kidney bilateral

- Major risk factor is smoking - Ex- Von Hippel-Lindau disease
• Autosomal dominant disorder

Renal Page 9.2

• Autosomal dominant disorder
• Associated with inactivation of VHL gene

(increased risk of hemangioblastoma of
cerebellum, pheo, and renal cell carcinoma)
-

5. What are gross and histologic features of renal cell carcinoma?
- Clear cell type is most common type of renal cell carcinoma (have clear cells)
- Gross exam reveals yellow mass)

Fig: gross feature (left) and microscopic feature (right) of renal cell carcinoma

Renal Page 9.3

12.9 Lower Urinary Tract Carcinoma

1. What constitutes the lower urinary tract?
- Renal pelvis, Ureter, Bladder, Urethra

2. What are 3 common malignant tumor of lower urinary tract and what are their risk factors?

Cancer Risk factor Common
location

Urothelial (transitional cell) carcinoma - Cigarette smoking (major) - polycyclic Bladder.
(MOST COMMON CANCER OF LOWER URINARY aromatic hydrocarbon (major),
TRACT- urothelium lines entire lower urinary tract) napthylamine
- Azo dyes (cancer seen in hair dressers)
- Long term cyclophosphamide or
phenacetin use

Squamous cell carcinoma - Arises after squamous metaplasia (urinary Bladder
tract doesn't have squamous cells)

• Chronic cystitis (older woman)
• Schistosoma hematobium (HY)

infection (middle eastern male)
• Long standing nephrolithiasis

Adenocarcinoma - No glandular cells in bladder: Bladder
• Arises from urachal remnant (HY)
(tumor at dome of bladder - HY)
• Cystitis glandularis - columnar
metaplasia due to chronic bladder
inflammation
• Exstrophy (failure to form caudal
portion of anterior abdominal and
bladder wall) - bladder exposed to
outside world which increases risk
in future to have cancer

Fig: extrophy

- Urachal remnant - urachus is remnant of channel between bladder and umbilicus (urine drains this way in
fetus during 1st trimester of pregnancy). It's lined by glandular cells. From 12th week of gestation, it's called
median umbilical ligament.

2. What are clinical characters of urothelial carcinoma?
- Generally seen in older adults as painless hematuria
- Tumor are multifocal and recur (entire urothelium is mutated via mechanism called field defect - ex- cigarette

smoking hits entire urothelial lining)

3. What are two pathways of urothelial carcinoma (HY)?

Flat Papillary

- Develops as high grade flat tumor and - Develops as low grade papillary tumor.
invades - Eventually becomes high grade papillary tumor and invades

- Associated with early p53 mutation (HY) - Not associated with early p53 mutation

Renal Page 10.1

LP is lamina propria

Renal Page 10.2

Chapter 13: Female Genital System
and Gestational Pathology

13.1 Vulva

1. Describe the following conditions about vulva.

Anatomy Skin and mucosa outside hymen (labias, mons pubis and vestibules)

Histology Lined by keratinized squamous epithelium

Bartholyn cyst - Unilateral, painful, cystic dilation of Bartholin gland (drains to inferior
vestibule)

Condyloma - Painless genital warts
- Cause:
Lichen sclerosis vs
lichen simplex • HPV 6, 11 more common STD (condyloma acuminatum - has
chronicus koliocytes - hallmark of HPV infected cells)

• Syphillis less common (condyloma latum)
- RARELY PROGRESS TO CANCER

Lichen sclerosis Lichen simplex chronicus
- Hyperplasia of vulvar squamous
- Vulva epidermis thins and fibrosis epithelium due to chronic
(sclerosis) happens in dermis - irritation and scratching
autoimmune etiology - Presents as leukoplakia with thick
leathery vulvar skin hyperplasia
- Presents as leukoplakia with - Any age; usually young
parchment like vulvar skin
- Benign - no increased risk of SCC
- Most common in postmenopausal
women

- Benign - increased risk of SCC

Vulvar carcinoma
Epidemiology - Relatively rare (small portion of female genital cancer)

Female GU Page 3.1

Epidemiology - Relatively rare (small portion of female genital cancer)
- Generally seen in women of reproductive age (HPV cases) or >70 age (lichen
Cause sclerosis cases)

Presentation - HPV 16, 18 (most common)
Pathophys of - Non-HPV cases arise most often from long standing lichen sclerosis (generally
HPV cases seen in >70 age)

- Presents as leukoplakia; need biopsy to distinguish from other causes of
leukoplakia

- Arises from vulvar intraepithelial neoplasia (VIN) - neoplasia limited to
epithelium - dysplasia characterized by koliocytic change, disordered cellular
maturation, nuclear atypia

Extramammary paget disease

Definition - Presence of malignant epithelial cells in epidermis of vulva (carcinoma in situ) -
usually no underlying malignancy (contrast to Paget disease of nipple where
there's underlying carcinoma)

Presentation - Erythematous, pruritic, ulcerated vulvar skin

Fig: paget disease of nipple vs vulva (can occur in scrotum and other places
too)

Distinguish Paget cells - PAS+ve, keratin +ve and S100 -ve

from melanoma Melanoma - PAS-ve, keratin -ve and S100 -ve (PAS - shows mucus)

Female GU Page 3.2

13.2 Vagina

1. What type of cell lines the vagina?
- Non-keratinizng squamous epithelial cell

2. Describe vaginal adenosis.

Definition - Persistence of columnar epithelial cells in upper vagina

Cause - Use of diethylstilbestrol (DES) in utero - given to reduce pregnancy complication
(crosses placenta)

Pathophys - During development, squamous epithelium from lower 1/3rd of vagina (derived
from urogenital sinus) grows up to replace columnar cells (derived from
Mullerian ducts)

Complication - Progression to clear cell adenocarcinoma of vagina

Clear cells adenocarcinoma
Histology - Malignant proliferation of glands with clear cytoplasm
Cause - One is vaginal adenosis caused by diethylstilbestrol (DES)

Embryonal rhabdomyosarcoma (rhabdo = skeletal; myo = muscle)

Histology - Malignant proliferation of immature skeletal muscle
- +ve immunohistochemistry for desmin and myogenin
- May see cross striation of skeletal muscle

Presentatio - Rare cancer
n - Bleeding and grape like mass protruding from vagina or penis (seen <5 years) -

mass called SARCOMA BOTRYOIDES

Fig: biopsy and sarcoma botryoides of embryonal rhabdomyosarcoma

Vaginal carcinoma - Malignant proliferation of squamous epithelium lining vaginal canal
Histology

Female GU Page 4.1

Cause - Mostly HPV 16, 18, 31, 33

Precursor lesion - Vaginal intraepithelial neoplasia (VAIN) - neoplasm in epithelum

Lymph spread - Cancer from upper 1/3rd of vagina - inguinal lymph nodes
- Cancer from lower 2/3rd of vagina - iliac nodes

Female GU Page 4.2

13.3 Cervix

1. What are differences between exocervix and endocervix?

Exocervix Endocervix

Cervix that’s visible on vaginal exam Cervix that’s not visible on vaginal exam

Lined by nonkeratinizing squamous epithelium Lined by single layer of columnar cells

- Transformation zone - juction between exocervix and endocervix.

Cervical intraepithelial neoplasia (CIN)

Definition - Characterized by koliocytic change

Progression - Can progress to carcinoma in situ and invasive squamous cell carcinoma of cervix
- Progression not inevitable

Grades of - CIN I - involves <1/3rd of thickness of epithelium
dysplasia - CIN II - involves <2/3rd of thickness of epithelium
- CIN III - involves almost complete thickness of epithelium
- Carcinoma in situ (CIS) - involves entire thickness of epithelium but hasn’t invaded
basement membrane
- CIN I, II and III are reversible (reversibility of I>II>III); CIS irreversible

HPV

Prognosis - Mostly affects lower genital tract, especially cervix in transformation zone
- Infection usually eradicated by acute inflammation; persistent infection can lead to cervical
dysplasia and cervical intraepithelial neoplasia (CIN)
- Most common cause of SCC of genitourinal tract

Pathophys - Produces proteins:
• E6 - inactivates p53
• E7 - inactivates Rb

Vaccinatio - HPV 6, 11
n • Prevent against condolymata acuminata

- HPV 16, 18
• Prevent against CIN and cervical cancer

Cervical carcinoma

Types - Squamous cell carcinoma (80% of cases)
- Adenocarcinoma (15% of cases)
- Other - clear cell carcinoma, transitional cell carcinoma

Presentation - Mostly seen in middle aged woman (40-50 years)
- Presents as postcoital bleeding

Risk factor - HPV infection (main) - can cause both SCC and adenocarcinoma
- Immunosuppression (cervical carcinoma AIDS defining illness)
- Smoking

Complication - Hydronephrosis and post renal failure common cause of death
• Tumor invades through anterior uterine wall to bladder and blocks the ureters

Screening of cervical carcinoma - pap smear (THE MOST SUCCESSFUL SCREENING TEST DEVELOPED TO DATE)
- Cervical cancer went from being the most common to one of least common gynecologic cancers in US

Female GU Page 5.1

- Cervical cancer went from being the most common to one of least common gynecologic cancers in US

Goal - Catch dysplasia (CIN) before it develops to carcinoma
- Usually, it takes 10-20 years for CIN to develop to carcinoma

Frequency - Do pap smear every 3 years from >21 years

Process - Using a brush, scrape cells from transformation zone
- Dysplastic cells can be low grade (CIN I) or high grade (CIN II, III)

Confirmatory - Colposcopy - take chunks of tissue for biopsy
test

Limitations - Pap smear great for squamous cell carcinoma but not for adenocarcinoma of cervix
- If transformation zone not sampled, then false negative results may be seen

Normal
histology and
pap smear

Fig: right - normal squamous epithelial cells (small nuclei with abundant cytoplasm) present
in exocervix; left – normal squamous epithelial cells (red arrows), normal columnar
epithelial cells from endocervix – blue cytoplasm and cilia sometimes seen

Abnormal pap

Female GU Page 5.2

Abnormal pap
smear

Fig: black arrows indicate normal squamous epithelial cells with small round nuclei. Red
arrow - koliocytes - abnormally large and pleomorphic nuclei

Female GU Page 5.3

13.4 Endometrium and Myometrium

Basics - Mucosal lining of uterus
Endometrium - Smooth muscle underlying the endometrium

Myometrium Proliferative Estrogen driven Endometrium grows
phase
Hormone cycle of Endometrium prepares for
endometrium implantation
Endometrium falls
Secretory phase Progesterone driven

Menstrual Due to loss of
phase progesterone

1. Describe the following pathologies.

Ascherman - Secondary amenorrhea due to loss of basalis (stem cell) and scarring
syndrome - Result of overagessive dialation and curettage (D&C)

Anovulatory - Lack of ovulation
cycle - Due to lack of ovulation, corpus luteum doesn't develop and progesterone isn't
made. Endometrium develops by estrogen but fails to be maintained; so it falls
off
- Common cause of dysfunctional uterine bleeding during menarche and
menopause

2. Differentiate acute and chronic endometritits.

Acute endmetritis Chronic endometritis

Bacterial infection of endometrium Chronic inflammation of endometrium characterized
by presence of plasma cells and lymphocytes in
biopsy (Plasma cell necessary to made diagnosis)

Cause: Causes:
- Usually due to retained product of - retained products of conception,
conception (after delivery or - IUD,
miscarriage) - serves as nidus of - TB, or
infection - pelvic inflammatory disease (gonorrhea,
chlamydia)

Presents as fever, abnormal uterine Presents as abnormal uterine bleeding, pain, and
bleeding and pelvic pain infertility

Endometrial polyp
Definition - Polyps formed due to hyperplastic protrusion of endometrium

Female GU Page 6.1

Presentatio - Abnormal uterine bleeding
n

Cause - Classic cause is tamoxifen (has anti-estrogenic effect on breast but pro-estrogenic
effect on endometrium)

Endometriosis - Endometrial glands and stroma outside uterine endometrial lining (the glands
Definition follow normal menstruation cycle)

Cause - Most likely due to retrograde menstruation with implantation at an ectopic site
Common
sites - Ovary (most common) - makes hemorrhagic (aka chocolate) cyst
- Uterine ligament - cause pelvic pain
- Pouch of douglas - pain with defecation
- Bladder wall - pain with urination
- Bowel serosa - abdominal pain and adhesions
- Fallopian tube mucosa - scarring increases risk for ectopic tubal pregnancy
- Adenomyosis - if endometriosis occurs in myometrium of uterus
- Sites classically appear as yellow-brown 'gun powder' nodules

Fig: common sites of endometriosis (left); chocolate cyst (right)

Presentatio - Pain that occurs prior to, during or after menstruation
n - Pain can occur during sexual intercourse, urination or bowel movement

- Some women have severe disabling pain and some have chronic pain in low back or
pelvis

Complicati - Increased risk of carcinoma at site of endometriosis (especially in ovary - aka
on endometoid tumor which is a malignant tumor of surface epithelium)

Endometrial hyperplasia

Definition - Hyperplasia of endometrial gland relative to stroma

Cause - Unopposed estrogen
• Obesity
• Polycystic ovary syndrome
• Estrogen replacement

Presentation - Classic is postmenopausal uterine bleeding

Classification - Based on architectural growth pattern (simple or complex)
- Or based on presence or absence or cellular atypia

Prognosis - If cellular atypia present, may progress to carcinoma (major complication

Female GU Page 6.2

Endometrial carcinoma (most common invasive carcinoma of female genital tract)

Definition - Malignant proliferation of endometrial glands

Epidemiology - Most common invasive carcinoma of female genital tract

Presentation - Classic is postmenopausal uterine bleeding

Causes - Via hyperplasia pathway (75% of cases) or sporadic pathway (25% of cases)

1. Differentiate endometrial carcinoma that arises by hyperplasia pathway or sporadic pathway.

Hyperplasia pathway Sporadic pathway

- Risk factors are increased estrogen - Carcinoma arises sporadically in atrophic endometrium

exposure: without any evident precursor lesion

• Early menarche/late - P53 mutation common; tumor is agressive

menopause

• Nulliparity (no babies)

• Infertility with anovulatory

cycle

• Obesity

- Average age of presentation 60 - Average age of presentation is 70 years
years

- Histology is endometroid (normal - Histology is serous and characterized by papillary

endometrium) structures with psammoma bodies

Leiomyoma (fibroma) - most common tumor in females

Definition - Benign neoplastic proliferation of muscle in myometrium

Epidemiolo - Most common tumor in females
gy - Common in premenopausal women; often multiple

Cause - Related to estrogen exposure

Presentatio - Usually asymptomatic; if symptomatic, may see abnormal uterine bleeding,
n infertility and pelvic mass

- Enlarges during pregnancy; shrink after menopause
- DO NOT PROGRESS TO LEIOMYOSARCOMA

Leiomyosarcoma

Definition - Malignant neoplastic proliferation of muscle in myometrium

Epidemiology - Often seen in postmenopausal women

Cause - Arise de novo; do not arise from leiomyoma

Female GU Page 6.3

Presentation - Single lesion with area of necrosis and hemorrhage
- Histology shows cellular atypia, mitotic activity and necrosis

Female GU Page 6.4

13.5 Ovary

1. Describe functional anatomy of ovary.
- Functional unit of ovary is follicle. Follicle has an oocyte surrounded by Granulosa and theca cells.

Cell type Location +ve Response
stimulus

Granulosa Located right around FSH Convert androgen from theca cells to
cells follicle estrogen (estradiol)

Theca cells Surround Granulosa LH Produce androgens
cells

- Estradiol surge causes LH surge which leads to ovulation (beginning of secretory phase of
endometrial cycle)

- After ovulation, follicle becomes corpus luteum which primarily secretes progesterone (drives
the secretory phase and prepared endometrium for possible conception)

2. Define hemorrhagic corpus luteal cyst and follicular cysts.

Cyst type Presentation/cause

Hemorrhagic corpus - Caused by hemorrhage into corpus luteal cyst. (Corpus luteal cysts are

luteal cyst formed if corpus leutem fails to disintegrate and instead persists)

- Normal; commonly found during early phase of pregnancy

Follicular cyst - Caused due to degeneration of follicles
- Normal in women (if present in small number) and have no clinical
significance

Polycystic ovarian disease (PCOD) : LH:FSH >2

Definition - Presence of multiple ovarian follicular cysts

Epidemiology - Affects 5% of women of reproductive age

Pathophysiol - Main finding is LH:FSH>2
ogy • High LH stimulates theca cells to produce lots of androgen (gives
hirsuitism)
• Androgen converted to estrone in adipose tissue. It gives -ve feedback to
FSH secretion; Granulosa cells and eventually the follicle degenerates
making cyst

Presentation - Presentation based on LH:FSH>2
• Hirsuitism (Due to excess androgens)
• Infertility (due to degenerated follicles)
• HIGH RISK OF ENDOMETRIAL CARCINOMA (due to high estrone)
• Insulin resistance and type 2 diabetes (10-15 years later)

- Classic pt is obese young woman wih infertility, oligomenorrhea, and hirsutism.

Female GU Page 1.1

13.6 Ovarian Tumors

1. What are the types of ovarian tumors?
- Ovary has 3 cell types: surface epithelium, germ cells and sex cord-stroma. Each cell type can give tumor

Tumor type Tumor subtype Epidemiology/remarks

Surface - Common (have cyst): - Most common ovarian tumor (70% of cases)
epithelium • Serous tumor (filled with water) - BRCA1 - Worst prognosis of all female genital tract cancer (often detected
mutation associated with serous late) - presents as vague abdominal discomfort or sign of bladder
carcinoma compression (urinary frequency)
• Mucinous tumor (filled with mucin)

- Less common (occur from metaplasia):
• Endrometriod tumor
• Brenner tumor

Germ cells - Tumor subtype based on tissue made by germ - Second most common ovarian tumor (15% of cases)
cells - All are malignant except cystic teratoma

Oocytes - Dysgerminoma (most common
malignant germ cell tumor)

Placental - Choriocarcinoma
tissue

Fetal - Embryonal carcinoma
tissue - Cystic teratoma (most common
germ cell tumor)

Yolk sac - Endodermal sinus (yolk sac)
tumor (most common germ cell
tumor in kids) - Schiller-Duval
bodies

Sex cord - Granulosa-theca Granulosa and theca
stroma tumor cells
Sertoli and leydig cells
- Sertoli-Leydig cell
tumor Fibroblasts

- Fibroma

-
Surface epithelial tumors

1. How are serous and mucinous tumor classified into benign, borderline, and malignant?

Benign (aka cystadenoma) Borderline Malignant (aka cystadenoCARCINOMA)

- Has single cyst with simple, flat lining - In between feature between benign - Has complex cyst with thick, shaggy lining
ad malignant
- Better prognosis than malignant but
has malignant potential

- Mostly seen in premenopausal women - Mostly seen in postmenopausal women
(30-40 years) (60-70 yrs)

Female GU Page 2.1

(30-40 years) (60-70 yrs)

2. What ovarian cancer is BRCA1 mutation associated with?
- Serous carcinoma (serous cystadenocarcinoma)
- Pt can get prophylactic salpingo-oophrorectomy along with bilateral mastectomy as prophylasxix.

3. Differentiate between endometroid tumor and brenner tumor. Brennor tumor
Endometroid tumor Tumor made up of bladder like
Tumor made of endometrial like gland (may arise from endometriosis) epithelium

Mostly malignant Mostly benign
15% endometroid carcinoma associated with independent endometrial carcinoma
(endometriod type) Benign; bladder epithelium; brennor

4. Describe the following features of surface epithelial tumors of female reproductive tract.
Distant metastasis Peritoneum (via direct contact) - see omental caking
Serum marker CA-125 - monitor treatment response and screening for recurrence

Germ cell tumors
1. Describe the following germ cell tumors

Dysgerminoma Choriocarcinoma Embryonal Cystic teratoma Endodermal sinus (yolk
carcinoma sac) tumor

- Malignant tumor with cells Malignant tumor - Malignant tumor - Tumor made up of fetal Malignant tumor that
mimics yolk sac
that resemble oocytes (large composed of composed of tissue derived from >2

cells, clear cytoplasm, cytotrophoblasts and large primitive embronic layers (ex-skin,

central nuclei) - fried egg syncytiotrophoblasts cells hair, cartilage, thyroid etc)

apperance

Malignant Malignant (trophoblasts Malignant - Mostly benign but if Malignant
are very invasive (aggressive) immature tissue (neural or
somatic malignancy)
present, indicates
malignant potential

- Most common malignant - Most common germ cell - Most common germ
germ cell tumor
- Seminoma is male tumor cell tumor in kids
counterpart (histologically
indistinguishable)

Fig: fried egg appearance on Fig: Tumor is small, Fig: hair and teeth seen in Fig: Schiller-Duval
biopsy hemorrhagic and spreads cystic teratoma bodies (glomerulus like
hemotageneously early structure) classically
seen on biopsy.

- Good prognosis; responds to - Poor response to

radiotherapy chemotherapy

- Serum LDL maybe elevated - High Beta-HCG - Hyperthyroidism in case of
characterstic (made by Struma ovarii (teratoma
syncytiotrophoblasts) - mainly composed of
may lead to thecal cysts thyroid tissue)
in ovary

Female GU Page 2.2

Sex cord-stromal tumors
1. What are sex cord stromal tumors?
- Tumors resemble sex cord stromal tissue of ovary

2. Differentiate between three types of sex cord stromal tumors.

Granulosa-theca cell tumor Sertoli-Leydig cell tumor Fibroma

Tumor of granulosa and theca cells Composed of Sertoli cells that make Tumor of fibroblast

tubules and Leydig cells between tubules

Malignant, but minimum risk of metastasis Benign tumor

Presentation based on excess estrogen Cells may produce androgens: - Associated with pleural effusions and
production
- See hirsuitism and virilization (more ascites (meigs syndrome) - syndrome
- Prior to puberty - precocious puberty
- Reproductive age - menorrhagia and masculine) resovles with removal of tumor
metrorrhagia
- Postmenopause - endometrial
hyperplasia with postmenopausal
uterine bleeding

Fig: characterstic intracytoplasmic Reinke
crystals of Sertoli-Leydig cell tumor

Metastasis
1. Describe the two common tumor metastasis to ovary.

Source Presentation

Krukenberg tumor Gastric carcinoma (diffuse - Mucinous tumor

type) - Mostly bilateral (if unilateral, think primary mucinous

carcinoma of ovary)

Pseudomyxoma peritonei (myxoma = Mucinous tumor of - Huge amount of mucus in peritoneum "jelly belly"
tumor of connective tissue with mucus appendix
and gelatinous material)

Female GU Page 2.3

Pseudomyxoma peritonei (myxoma = Mucinous tumor of
tumor of connective tissue with mucus appendix
and gelatinous material)

Female GU Page 2.4

13.7 Gestational Pathology

Ectopic pregnancy
Definition - Implantation of fertilized ovum at site other than uterine wall
- Most common site is fallopian tube
Risk - Key risk is scarring (secondary to pelvic inflammatory disease or endometriosis)
Presentation - Lower quadrant abdominal pain a few weeks after a missed period
Prognosis - Surgical emergency; bleeding and fallopian tube rupture can occur

Spontaneous abortion

Definition - Abortion <20 weeks of gestation (usually during first trimester)

Epidemiology - Common; occurs in up to 1/4th of pregnancies

Presentation - Vaginal bleeding with passage of fetal tissue
- Cramp like pain

Cause - Most often due to chromosomal abnormalities (especially trisomy 16)
- Hypercoagulable states (ex - antiphospholipid syndrome)
- Congenital infection
- Exposure to teratogens (especially during first 2 weeks of pregnancy)

Teratogens
1. What is common timewise effect of teratogen exposure?

0-2 weeks of gestation Spontaneous abortion

3-8 weeks Risk of organ malformation

3-9 months Risk of organ hypoplasia

2. What are the effects of following teratogens?

Teratogen Effects

Alcohol - Most common cause of mental retardation
- Facial abnormalities and microcephaly

Cocaine - Intrauterine growth retardation and placental abruption

Thalidomide - Limb defects

Cigarette smoke - Intrauterine growth retardation

Isotretinoin - Spontaneous abortion
- Hearing and visual impairment

Tetracycline - Discolored teeth

Warfarin - Fetal bleeding

Phenytoin Digit hypoplasia and cleft lip/palate

Placenta previa, placenal abruption and placenta accreta Placenta accreta
1. Differentiate the above three.
Placenta implants to myometrium
Placenta previa Placental abruption with little or no intervening decidua

Placenta implants Separation of placenta from
and closes cervical decidua (modified mucous

Female GU Page 7.1

and closes cervical decidua (modified mucous with little or no intervening decidua
os (opening) membrane that lines the uterus - Accreta - placenta grows
during pregnancy) superficially on myometrium
prior to delivery of fetus - Increta - placenta grows into
myometrium
- Percreta - placenta grows
completely through
myometrium and may invade
bladder or bowel

- Presents as - Presents as painful 3rd trimester - Presents with difficult delivery of
the placenta and postpartum
painless 3rd bleeding and fetal insufficiency bleeding
- Often requires hysterectomy
trimester bleeding

- Often requires C-

section delivery

- COMMON CAUSE OF STILLBIRTH

Preeclampsia, eclampsia and HEELP

Preecclampsia Eclampsia HELLP

- Pregnancy induced hypertension, - Preeclampsia + - Preeclampsia + thrombotic
proteinuria, and edema, usually arise
in 3rd trimester seizures microangiopathy involving liver
- HTN may be severe leading headache
and visual abnormality (see hemolysis, Elevated Liver
- Caused due to abnormality In
maternal-fetal vasculr interface in enzymes and Low Platelets) - think
placenta
as HUS of liver

- Resolves with delivery - Warrant - Warrant immediate delivery
immediate
delivery

Sudden infant death syndrome

Definition - Death of infant (1 month - 1 year old) without obvious cause

Presentation - Infants often expire during sleep

Risk factors - Sleeping on stomach
- Exposure to cigarette smoke
- Prematurity

Female GU Page 7.2

Hydatidiform mole (molar pregnancy)

Hydatidiform mole Benign tumor that develops in uterus, caused by genetic error caused
due to abnormally fertilized egg.

Presentation - Uterus expands as if a normal pregnancy is present
- Uterus is much larger and B-HCG is much higher than expected for
Classification date of gestation
Treatment - Grape like large villi pass through vagina in 2nd trimester of pregnancy
Complication
- Suction curettage
- Monitor B-HCG subsequently to ensure entire mole is removed
completely

- Choriocarcinoma may arise after spontaneous abortion, normal
pregnancy or hydatidiform mole or as a spontaneous germ cell tumor
- Choriocarcinoma that arise from gestational pathway respond well to
chemotherapy; those from germ cell pathway don't.

1. Differentiate partial and complete hydatidiform mole.

Partial mole Complete mole

Genetics Normal ovum fertilized by two sperm Empty ovum fertilized by two sperm

(or 1 sperm with double (or 1 sperm with double

chromosome); 69 chromosome chromosome); 46 chromosome

Fetal tissue Present Absent

Villous edema Some villi are hydropic (edematous); Most villi are hydropic
some are normal

Trophoblastic - Focal proliferation present around - Diffuse proliferation around hydropic
proliferation hydropic villi villi

Risk for Minimal 2-3%

choriocarcino

ma

Female GU Page 7.3

Chapter 14: Male Genital System
Pathology

14.1 Penis

1. Describe the following penis conditions.

Pathologies Presentation Cause

Priaprism - Continuous penile erection, unrelated to sexual
arousal (medical emergency as ischemia and
thrombosis can lead to gangrene

Hypospadis - Opening of urethra on inferior surface of penis - Due to failure of
urethral folds to close

Epispadias - Opening of urethra on superio surface of penis - Due to abnormal
Phimosis - Very tight foreskin on glans penis positioning of genital
tubercle
- Associated with bladder
exstrophy (bladder
located outside body
cavity)

Paraphimosis - Foreskin trapped behind glans penis

Condyloma - Warty growth on genital skin - HPV 6, 11
acuminatum Characterized by

Male GU Page 1.1

Condyloma - Characterized by
acuminatum koliocytic changes

Lymphogran - Necrotizing granulomatous inflammation of inguinal - Chlamydia trachomatis
uloma lymphatics and lymph nodes (serotype L1-L3)
venereum - Perianal involvement may result in rectal stricture
(heals by fibrosis)

Squamous cell carcinoma of penis

Risk factors - HPV 16, 18, 31, 33 (2/3rd of cases)
- Lack of circumcision (foreskin as nidus of irritation and inflammation if not
maintained well)

Precursor Bowen disease (carcinoma in situ of penile shaft or scrotum)
lesions: - Presents as leukoplakia
- Presents in 5th decade of life

Erythroplasia of Queyrat (carcinoma in situ on glans) - Bowen's disease of glans)
- Presentas as erythroplakia

-

Male GU Page 1.2

-
Bowenoid papulosis (insitu carcinoma)

- Presents as multiple reddish papules
- Seen in younger pt (40's) compared to Bowen disease and erythroplasia of
Queyrat

Male GU Page 1.3

14.2 Testicle

Cryptorchidism (crypt = underground vault; orchid = penis)

Definition - Failure of testicle to descend to scrotal sac (testis develop in abdomen)
- Mostly unilateral

Epidemiolog - MOST COMMON CONGENITAL MALE REPORDUCTIVE SYSTEM
y ABNORMALITY

- Affects 1% of male births

Presentation Very prominent lydig cells on histo

Treatment - Most cases resolve spontaneously
- Orchiopexy <2 years if doesn't resolve (surgery to bring testis to right
position)

Complication - Testicular atrophy with infertility
- Increased risk for seminoma

Orchitis (inflammation of testis) Notes Increased risk for
1. What are causes of orchitis? sterility?
Cause
- Seen in sexually active young adults Yes
Chlamydia trachomatis and/or - Libido not affected because Leydig
Neisseria gonorrhoeae cells are spared

E Coli and Pseudomonas - Seen in older adults
- Caused by spread of UTI pathogen to
Mumps reproductive tract

Autoimmune orchitis - Seen in teenagers (if <10 years, Yes
orchitis not seen)

- Characterized by granulomas
involving seminiferous tubules

Testicular torsion

Definition Twisting of spermatic cord which obstructs spermatic vein leading to
hemorrhagic testicular infraction in ~6 hrs

Cause Congenital failure of testes to attach to inner lining of scrotum (via processus
vaginalis)

Presentatio Sudden testicular pain and absent cremasteric reflex (nerves present in cord)

Male GU Page 2.1

Presentatio Sudden testicular pain and absent cremasteric reflex (nerves present in cord)
n

Varicocele, hydrocele and spermocele

1. Differentiate varicocele, hydrocele and spermocele.

Varicocele Hydrocele Spermatoce
le

Definiti - Dilation of spermatic vein - Fluid collection in tunica Cystic
on
vaginalis dialation of

epididymis

Cause - Mostly left sided as left testicular vein - Incomplete closure of
drains to left renal vein; right testicular processus vaginalis and
vein goes straight to IVC. (seen in renal its communication with
cell carcinoma because carcinoma peritoneal cavity - in kids
frequently involves renal vein) - Blockage of lymphatic
- Seen in large percent of infertile males drainage - adults

- Presents as 'bag of worms' with scroal
swelling

Male GU Page 2.2

14.3 Testicular Tumors

1. Describe following features of testicular tumors.

Presentation - Firm, painless testicular mass that can't be transilluminated

Biopsy - Do radical orchiectomy (mass not biopsied due to risk of seeding the scrotum)

Epidemiology - Most tumors are malignant germ cell tumors

2. What are the types of testicular tumors?
- Classification is based on whether they arise from germ cells or sex cord-stroma; lymphoma also a cause.

Germ - Tumor subtype based on tissue made by germ cells (can use seminoma vs non seminoma for clinical

cells purposes)

( mostly Seminoma - Seminoma (most common testicular tumor)
maligna
nt) Mixed germ cell tumor - Mixed germ cell tumor
(>95% - Prognosis based on worst component

of Placental tissue - Choriocarcinoma

testicul Fetal tissue - Teratoma
ar Yolk sac - Embryonal carcinoma
tumors)
- Endodermal sinus tumor (most common germ cell tumor in kids)

Sex cord - Leydig cell tumor - Produce androgens
stroma - Precocious puberty in children or gynecomastia in adults
(mostly - May see Reinke crystals on biopsy
benign)

Fig: characteristic intracytoplasmic Reinke crystals of Leydig cell tumor

- Sertoli cell tumor - Usually clinically silent

Lymphoma - Most common cause of testicular mass in males >60 years
- Mass often bilateral
- Most common type is diffuse large B cell lymphoma

- Don't see epithelial carcinoma in testes because they aren't surrounded by epithelium They're surrounded by
tunica vaginalis (mesenchyme)

Germ cell tumors
1. Describe the following features of germ cell tumors.

Male GU Page 3.1

1. Describe the following features of germ cell tumors.

Epidemiolo - Most common testicular tumor (>95% of cases)
gy - Mostly seen in 15-40 year olds

Risk factor - Cryporchidism
- Klienfelter syndrome

Division Seminoma Non-seminoma

Most common
testicular tumor

55% of germ cell 45% of germ cell tumors
tumors

Highly responsive to Variable response to treatment
radiotherapy

Metastasize late Metastasize early

Excellent prognosis Poor prognosis

Include teratoma, embryonal carcinoma, endodermal sinus tumor,
choriocarcinoma and mixed germ cell tumor

2. Differentiate the following testicular tumors.

Seminoma Teratoma Embryonal Endodermal sinus Choriocarcinoma
carcinoma (yolk sac)
Malignant; spreads
Most common Most common early
testicular tumor testicular tumor in
children
Malignant Malignant (in Malignant
Malignant

females, it's mostly

benign)

- Large cells with clear - Mature fetal - Immature cells - Schiller-Duval - Tumor of
that may
cytoplasm and tissue from >2 produce glands bodies on histology cyncytiotrophoblasts
- Forms
central nuclei embryonic layers hemorrhagic (glomerulus like) and cytotrophoblasts
mass with
- Forms homogenous necrosis (placenta like tissue

mass with no but absent vilil)

hemorrhage or

necrois

- B-HCG rarely - AFP or B-HCG - AFP or B-HCG - AFP increased - B-HCG increased
increased increased incresed (syncytiotrophoblasts
produce it)

- Alpha subunit of HCG
similar to FSH, LH and
TSH; may see
hyperthyroidism and
gynecomastia

Male GU Page 3.2

14.4 Prostate

1. Describe histology of prostate gland.
- Consists of gland and stroma (connective tissue) which is maintained by androgens (stromal cells

make DHT by 5 alpha reductase from testosterone)
- Glands are 2 cell layer thick

○ Inner luminal cells
○ Outer basal cells

Fig: G is for glands; S for stroma Chronic prostatitis
- Chronic inflammation of prostate
2. Describe acute vs chronic prostatitis.
- Presentation:
Acute prostatitis • Dysuria with pelvic or lower back
pain
- Acute inflammation of prostate (mostly due to
bacteria) - Prostatic secretion:
• WBC high
- Causes: • -ve bacterial culture
• Chlamydia and gonorrhoeae in young adult
• E coli and pseudomonas in old adults

- Presentation:
• Dysuria with fever and chills
• On DRE, prostate is tender and boggy

- Prostatic secretion:
• WBC high
• +ve bacterial culture

Benign prostate hyperplasia

Cause - Age related change (present in most men >60 years)
- No increased risk of cancer

Male GU Page 4.1

Pathophys - No increased risk of cancer

Clinical - Related to increased dihydrotestosterone (DHT)
features • DHT made from testosterone by 5alpha-reductase in stromal cells
• DHT acts on androgen receptors on stromal and epithelial cells resulting in
hyperplastic nodules

- Presentation based on pinching of urethra
• Problems starting and stopping urine stream; dribbling
• Impaired bladder emptying - high risk of infection and hydronephrosis
• Nocturia; polyuria
• Hypertrophy of bladder wall muscle - increased risk for bladder diverticula
• Microscopic hematuria maybe present

Labs - Slightly increased prostate specific antigen (PSA) - made by prostatic glands and it
Treatment liquefies semen (still <10 ng/ml)

- Alpha1 antagonist (terazosin) to relax smooth muscle - also lowers BP
- Alpha1a antagonist (tamsulosin) - don't act on vascular smooth muscle; use for
normotensive pt
- 5alpha reductase inhibitor (reduce androgenerigc stimulation of prostate and
reduce its size)

• decrease conversion of testosterone to DHT
• Takes months to produce affect
• Helps with baldness
• Side effect - gynecomastia and sexual dysfunction

Prostate adenocarcinoma

Epidemiolog - Most common cancer in men
y - 2nd most common cause of cancer-related death in men

Risk factors - Age
- Race (AA>Caucasians>Asians)
- Diet high in saturated fats

Presentatio - Mostly clinically silent (tumor arises on posterior peripheral region of prostate;
n don't see urinary symptoms)

Screening - PSA and DRE from 50 years age
- PSA:

• Normal serum PSA increases with age due to BPH (~2.5 for 40-49; ~7.5 for
70-79)

• PSA > 10 ng/ml highly worrisome for any age
• Also see decreased free PSA as cancer makes PSA that’s bound.

Diagnosis Biopsy:
• See small invasive glands with prominent nucleoli
• Ducts maybe only one layer thick instead of having basal and laminal layer

Male GU Page 4.2

Grading Fig: notice nucleus with prominent nucleoli
Metastasis
Treatment - Based on tumor architecture alone (not on nuclear atypia)
- Multiple region of tumor have different architecture
- Gleason scoring:

• Take two distinct areas and grade each (1-5). Total score = 10
• High grade = worse prognosis

- Lumbar spine or pelvis common site
- See osteoblastic metastasis

• Presents as lower back pain
• Increased serum alk phosphatase, PSA and prostatic acid phosphatase (PAP)

- Prostatectomy for localized
- Hormone suppression for advanced disease (goal to reduce testosterone and DHT)

• GnRH analog (ex - leuprolide) - reduces LH and FSH production
• Flutamide - competitive inhibitor of androgen receptor

Male GU Page 4.3

Chapter 15: Endocrine Pathology

15.1-15.2 Anterior and Posterior Pituitary Gland

Hormones by hypothalamus Hormones made by ant. pituitary

1. Thyrotropin releasing hormone (TRH) 1. Thyrotropin (aka thyroid stimulating hormone)

2. Gonadotropin releasing hormone (GNRH) 2. Gonadotropin (FSH and LH)

3. Corticotropin releasing hormone (ACRH) 3. Adrenocorticotropin (ACTH)

4. Growth hormone releasing hormone 4. Growth hormone

5. Somatostatin 5. Prolactin (lactotropin) - most common pituitary adenoma

6. Prolactin inhibiting hormone (dopamine)

Hormones in post. Pituitary (made in hypothalamus)

1. ADH (aka vasopressin)

2. Oxytocin - uterine contraction during pregnancy

Anterior pituitary
1. What type of tumor is pituitary adenoma?
- Benign tumor of anterior pituitary cells.
- Can be functional (hormone producing) or non-functional (silent)

2. What are clinical presentation of non-functional tumor of pituitary?
- Bitemporal heminopsia (due to mass effect)
- Hypopituitarism (due to mass effect)
- Headache

3. What are most common functional tumor of ant. Pituitary?
- Prolactionma (most common pituitary adenoma) - 50% of adenomas
- Growth hormone (somatostatin) cell adenoma - 10-15% of adenomas
- ACTH cell adenoma - 10% of adenoma
- TSH cell, LH producing, and FSH producing adenomas are rare

4. What are clinical presentation of prolactinoma? How do you treat?
- In females - galactorrhea and amenorrhea (prolactin inhibits GNRH synthesis and release)
- In males - decreased libido and headache. Males don't get galactorrhea because they don't have

sufficient breast tissue.
- Treat - give prolactin inhibiting hormone (aka dopamine), dopamine agonists (bromocriptine or

cabergoline) or surgery

5. What is functional unit of breast?
- Terminal duct-lobular unit. Lobular unit has glands that make milk. Males only have terminal duct but

not lobular unit so can't make milk. Females develop lobular unit after puberty.

Endocrine Page 1.1

Fig - rough sketch of terminal duct (TD) and lobular unit (LU)

6. What is clinical presentation of Growth hormone adenoma?
- In kids - gigantism
- In adults - acromegaly

○ Enlarged bones of hand, feet, jaws, large tongue.
○ Growth of visceral organs (cardiac failure is most common cause of death in these patients)
- Secondary diabetes mellitus present (because GH inhibits glucose intake by cells; GH induces
gluconeogenesis by liver)

7. How do you diagnose growth hormone adenoma? How do you treat?
- Elevated GH and IGF-1 (insulin like growth factor) - IGF is made by liver in response to GH
- Lack of GH suppression in response to oral glucose (why)
- Treatment-

○ Octreotide (somatostatin analog)
○ GH receptor antagonist
○ Surgery

Hypopituitary
8. When do we see hypopituitarism?
- When >75% of pituitary parenchyma is lost

9. What are some causes of hypopituitarism?
- Pituitary adenoma (common cause in adults ) - mass effect or apoplexy (bleeding in adenoma)

reduces hormone production
- Carniopharyngioma (common cause in kids) - same reason as above
- Sheehan syndrome (HY) - during pregnancy, there's high need of hormones so pituitary doubles in

size but its blood supply doesn't. Blood loss during parturition can trigger pituitary infraction.
○ Presents as poor lactation, loss of pubic hair (HY) and fatigue.

- Empty sella syndrome - herniation of arachnoid or pia into pituitary can damage pituitary.
○ Can occur congenitally too

Posterior pituitary
10. What are clinical presentation and causes of central diabetic insipidus? What is diagnosis and

treatment?
- Presentation (based on loss of free water)

○ Polyuria and polydipsia
○ Hypernatremia and high serum osmolality
○ Low urine osmolality and specific gravity
- Causes - damage (tumor, trauma, infection or inflammation) to hypothalamus or pituitary

Endocrine Page 1.2