21 Female Reproductive Disorders and Breast Disorders

Sexually Transmitted Diseases (STDs) and Other Genital n!ections

Summary of infections
Ta"le 21#1$ Sexually Transmitted Diseases and Other Genital n!ections
%atho&en Description and Treatment
Calymmatobacterium
granulomatis
STD; gram-negative coccobacillus that causes granuloma inguinale
Organism phagocytized by macrophages (Donovan bodies)
Creeping raised sore that heals by scarring; no lymphadenopathy
!" do"ycycline or trimethoprim-sulfametho"azole
Candida albicans #easts and pseudohyphae (elongated yeasts)
!is$ factors% diabetes antibiotics pregnancy OC&
&ruritic vaginitis 'ith a 'hite discharge and fiery red mucosa
!"% fluconazole (single dose)
Chlamydia trachomatis (ost common STD; often coe"ists 'ith Neisseria gonorrhoeae
)ncubation period *-+ 'ee$s after e"posure; red inclusions (reticulate bodies) in
infected metaplastic s,uamous cells
)nfections in males% -S. epididymitis proctitis
)nfections in females% urethritis cervicitis &)D perihepatitis (/0C syndrome-scar
tissue bet'een peritoneum and surface of liver from pus from &)D) proctitis
)nfections in ne'borns% con1unctivitis (ophthalmia neonatorum) pneumonia
&C! test for ,uic$ diagnosis
!"% azythromycin 2g (single dose) do"ycycline
C. trachomatis
subspecies
3ymphogranuloma venereum
&apules 'ith no ulceration; inguinal lymphadenitis 'ith granulomatous
microabscesses and draining sinuses
3ymphedema of scrotum or vulva; 'omen may also develop rectal strictures
!"% du"ycycline
Gardnerella vaginalis 4ram-negative rod that causes bacterial vaginosis
(alodorous vaginal discharge; vaginal p0 5676
Organisms adhere to s,uamous cells producing 8clue cells8
!"% metronidazole
Hemophilus ducreyi STD; gram-negative rod that causes chancroid
&ainful genital and perianal ulcers 'ith suppurative inguinal nodes
!"% ceftria"one or azythromycin 2g (single dose)
0S9-* STD; virus remains latent in sensory ganglia
!ecurrent vesicles that ulcerate; locations-penis vulva cervi" perianal area
Tzanc$ preparation% scrapings removed from the base of an ulcer; see
multinucleated cells 'ith eosinophilic intranuclear inclusions
&regnancy% if virus is shedding baby is delivered by cesarean section
!"% acyclovir (decreases recurrences)
0&9 STD; types : and 22 associated 'ith condylomata acuminata (venereal 'arts);
fernli$e or flat lesions in genital area (e7g7 penis vulva cervi" perianal)
Types 2: and 2; associated 'ith dysplasia and s,uamous cancer
9irus produces $oilocytic change in s,uamous epithelium; cells have 'rin$led
py$notic nuclei surrounded by a clear halo
!"% topical podophyllin
Neisseria gonorrhoeae ( STD; gram-negative diplococcus that infects glandular or transitional epithelium;
symptoms appear *-6 days after se"ual e"posure
)nfection sites similar to C. trachomatis
Complications% ectopic pregnancy male sterility disseminated gonococcemia (C6-
C< deficiency) septic arthritis /0C syndrome
&C! test for ,uic$ diagnosis
!"% ceftria"one
Treponema pallidum (/i STD; spirochete that causes syphilis
&rimary syphilis% solitary painless indurated chancre; locations-penis labia mouth
Secondary syphilis% maculopapular rash on trun$ palms soles; generalized
lymphadenopathy; condylomata lata 'hich are flat lesions in same area as
condylomata acuminata
Tertiary syphilis% neurosyphilis aortitis gummas
Congenital syphilis
-onspecific screening tests% !&! or 9D!3; titers decrease after !"
Confirmatory treponemal test% /T=-=>S; positive 'ith or 'ithout !"
?arisch-0er"heimer reaction% intensification of rash in primary or secondary syphilis
may occur due to proteins released from dead organisms after !" 'ith penicillin
!"% penicillin
Trichomonas vaginalis ( STD; flagellated protozoan 'ith tumbling motility
&roduces vaginitis cervicitis and urethritis; stra'berry-colored cervi" and fiery red
vaginal mucosa; greenish frothy discharge
!"% metronidazole (both partners)
Sexually Transmitted Diseases (STDs) and Other Genital n!ections
Summary of infections
Ta"le 21#1$ Sexually Transmitted Diseases and Other Genital n!ections
%atho&en Description and Treatment
Calymmatobacterium
granulomatis
STD; gram-negative coccobacillus that causes granuloma inguinale
Organism phagocytized by macrophages (Donovan bodies)
Creeping raised sore that heals by scarring; no lymphadenopathy
!"% do"ycycline or trimethoprim-sulfametho"azole
Candida albicans #easts and pseudohyphae (elongated yeasts)
!is$ factors% diabetes antibiotics pregnancy OC&
&ruritic vaginitis 'ith a 'hite discharge and fiery red mucosa
!"% fluconazole (single dose)
Chlamydia trachomatis (ost common STD; often coe"ists 'ith Neisseria gonorrhoeae
)ncubation period *-+ 'ee$s after e"posure; red inclusions (reticulate bodies) in
infected metaplastic s,uamous cells
)nfections in males% -S. epididymitis proctitis
)nfections in females% urethritis cervicitis &)D perihepatitis (/0C syndrome-scar
tissue bet'een peritoneum and surface of liver from pus from &)D) proctitis
)nfections in ne'borns% con1unctivitis (ophthalmia neonatorum) pneumonia
&C! test for ,uic$ diagnosis
!"% azythromycine 2g (single dose) do"ycycline
C. trachomatis subspecies 3ymphogranuloma venereum
&apules 'ith no ulceration; inguinal lymphadenitis 'ith granulomatous
microabscesses and draining sinuses
3ymphedema of scrotum or vulva; 'omen may also develop rectal strictures
!"% do"ycycline
Gardnerella vaginalis 4ram-negative rod that causes bacterial vaginosis
(alodorous vaginal discharge; vaginal p0 5676
Organisms adhere to s,uamous cells producing 8clue cells8
!"% metronidazole
Hemophilus ducreyi STD; gram-negative rod that causes chancroid
&ainful genital and perianal ulcers 'ith suppurative inguinal nodes
!"% ceftria"one or azythromycin 2g (single dose)
0S9-* STD; virus remains latent in sensory ganglia
!ecurrent vesicles that ulcerate; locations-penis vulva cervi" perianal area
Tzanc$ preparation% scrapings removed from the base of an ulcer; see
multinucleated cells 'ith eosinophilic intranuclear inclusions
&regnancy% if virus is shedding baby is delivered by cesarean section
!"% acyclovir (decreases recurrences)
0&9 STD; types : and 22 associated 'ith condylomata acuminata (venereal 'arts);
fernli$e or flat lesions in genital area (e7g7 penis vulva cervi" perianal)
Types 2: and 2; associated 'ith dysplasia and s,uamous cancer
9irus produces $oilocytic change in s,uamous epithelium; cells have 'rin$led
py$notic nuclei surrounded by a clear halo
!"% topical podophyllin
Neisseria gonorrhoeae STD; gram-negative diplococcus that infects glandular or transitional epithelium;
symptoms appear *-6 days after se"ual e"posure
)nfection sites similar to C. trachomatis
Complications% ectopic pregnancy male sterility disseminated gonococcemia (C6-
C< deficiency) septic arthritis /0C syndrome
&C! test for ,uic$ diagnosis
!"% ceftria"one
Treponema pallidum STD; spirochete that causes syphilis
&rimary syphilis% solitary painless indurated chancre; locations-penis labia mouth
Secondary syphilis% maculopapular rash on trun$ palms soles; generalized
lymphadenopathy; condylomata lata 'hich are flat lesions in same area as
condylomata acuminata
Tertiary syphilis% neurosyphilis aortitis gummas
Congenital syphilis
-onspecific screening tests% !&! or 9D!3; titers decrease after !"
Confirmatory treponemal test% /T=-=>S; positive 'ith or 'ithout !"
?arisch-0er"heimer reaction% intensification of rash in primary or secondary
syphilis may occur due to proteins released from dead organisms after !" 'ith
penicillin
!"% penicillin
Trichomonas vaginalis STD; flagellated protozoan 'ith tumbling motility
&roduces vaginitis cervicitis and urethritis; stra'berry-colored cervi" and fiery red
vaginal mucosa; greenish frothy discharge
!"% metronidazole (both partners)
'ulva Disorders
>artholin gland abscess
(ost often caused by Neisseria gonorrhoeae
-on-neoplastic dermatoses
27 3ichen sclerosis
a7 .sually occurs in postmenopausal 'omen
b7 Thinning of the epidermis
&archment-li$e appearance of s$in
c7 Small ris$ for developing s,uamous cell carcinoma
*7 3ichen simple" chronicus
a7 @hite pla,ue-li$e lesion (leu$opla$ia)
Due to s,uamous cell hyperplasia
b7 Small ris$ for developing s,uamous cell carcinoma
>enign and malignant tumors
27 &apillary hidradenoma
a7 >enign tumor of the apocrine s'eat gland
b7 &ainful nodule on the labia ma1ora
*7 9ulvar intraepithelial neoplasia (9)-)
a7 Dysplasia ranges from mild to carcinoma in situ
b7 Strong human papillomavirus (0&9) type 2: association
c7 &recursor for developing s,uamous cell carcinoma
+7 S,uamous cell carcinoma
a7 (ost common cancer
b7 !is$ factors
i7 0&9 type 2:
ii7 Smo$ing cigarettes
iii7 )mmunodeficiency (e7g7 =)DS)
c7 (etastasize first to the inguinal nodes
A7 B"tramammary &agetCs disease
a7 !ed crusted vulvar lesion
b7 )ntraepithelial adenocarcinoma
i7 Tumor derives from primitive epithelial progenitor cells
ii7 (alignant &agetCs cells contain mucin
(ucin is &=S (periodic acid-Schiff) positive7
iii7 Spreads along the epithelium
!arely invades the dermis
67 (alignant melanoma
a7 (elanoma cells are histologically similar to &agetCs cells
b7 .nli$e &agetCs cells melanoma cells are &=S negative7
'a&ina Disorders
!o$itans$y-Duster-0auser syndrome
27 =bsence of the upper vagina and uterus
*7 =natomic cause of primary amenorrhea
4artnerCs duct cyst
27 !emnant of the 'olffian (mesonephric) duct
*7 &resents as a cyst on the lateral 'all of the vagina
>enign and malignant tumors
page A6+
page A6A
27 !habdomyoma
a7 >enign tumor of s$eletal muscle
b7 Other locations are the tongue and heart7
*7 Bmbryonal rhabdomyosarcoma
a7 Occurs in girls younger than 6 years old
b7 -ecrotic grape-li$e mass protrudes from the vagina
+7 Clear cell adenocarcinoma of the vagina
a7 Bpidemiology
i7 Occurs in 'omen 'ith intrauterine e"posure to diethylstilbestrol (DBS)
DBS 'as used to prevent a threatened abortion7
ii7 DBS inhibits mEllerian differentiation7
(ullerian structures% tubes uterus cervi" upper one third of
vagina
iii7 9aginal adenosis
!emnants of mEllerian glands
&roduces a ridge in the upper portion of the vagina
&recursor lesion for clear cell adenocarcinoma
iv7 Small ris$ for developing the cancer (2%2FFF)
v7 Cancer may involve upper vagina or cervi"7
b7 Other DBS abnormalities
i7 =bnormally shaped uterus that th'arts implantation
ii7 Cervical incompetence
Common cause of recurrent abortions
A7 9aginal s,uamous cell carcinoma
a7 &rimary s,uamous cell carcinoma has an 0&9 type 2: association7
b7 (ost cancers are an e"tension of a cervical s,uamous cancer into the vagina7
(ervix Disorders
Clinical anatomy and histology
27 Cervi" includes the endocervi" G e"ocervi"
o The e"ocervi" begins at the cervical os7
*7 B"ocervi" is normally lined by s,uamous epithelium7
+7 Bndocervical glands are normally lined by mucus-secreting columnar cells7
A7 Bndocervical epithelium normally migrates do'n to the e"ocervi"7
a. B"posure to the acid p0 of the vagina produces s,uamous metaplasia7
b. The area undergoing metaplasia is called the transformation zone7
i7 This zone is 'here s,uamous dysplasia and cancer develop7
ii7 )t must be sampled 'hen performing a cervical &apanicolaou (&ap)
smear7
c. (etaplastic s,uamous cells bloc$ endocervical gland orifices7
i7 Obstruction of outflo' of mucus produces nabothian cysts7
ii7 -abothian cysts are a normal finding in adult 'omen
=cute and chronic cervicitis
27 =cute cervicitis
a7 =cute inflammation is normally present in the transformation zone7
b7 &athologic acute cervicitis
Causative agents% Chlamydia trachomatis, N. gonorrhoeae, Trichomonas
vaginalis, Candida, and herpes simple" virus (0S9-*)
c7 /ollicular cervicitis
ii Caused by C. trachomatis
iii &ronounced lymphoid infiltrate 'ith germinal centers
iiii Chlamydia infects metaplastic s,uamous cells7
Cells contain vacuoles 'ith red inclusions (reticulate bodies)7
Blementary bodies are infective particles7
ivi Cervicitis is the primary source for con1unctivitis and pneumonia in
ne'borns7
*7 Chronic cervicitis occurs 'hen acute cervicitis persists7
Cervical &ap smear
page A6A
page A66
>ecause the transformation zone is the site for s,uamous dysplasia and
s,uamous cancer it must be ade,uately sampled7 The presence of
metaplastic s,uamous cells or mucus-secreting columnar cells indicates
proper sampling7 =bsence of these cells means that the &ap smear must be
repeated7
27 &urpose
a7 Screening test to rule out s,uamous dysplasia and cancer
b7 To evaluate the hormone status of the patient
*7 Sample sites
o 9agina e"ocervi" transformation zone
2. )nterpretation of the &ap smear
a7 Superficial s,uamous cells indicate ade,uate estrogen7
b7 )ntermediate s,uamous cells indicate ade,uate progesterone
c7 &arabasal cells indicate a lac$ of estrogen and progesterone
d7 -ormal nonpregnant adult 'oman
HFI superficial s,uamous cells +FI intermediate s,uamous cells
e7 &regnant 'oman
2FFI intermediate s,uamous cells from progesterone effect
f7 Blderly 'oman 'ith lac$ of estrogen and progesterone
=trophic smear 'ith parabasal cells and inflammation
g7 @oman 'ith continuous e"posure to estrogen 'ithout progesterone
2FFI superficial s,uamous cells
Cervical polyp
27 -on-neoplastic polyp
*7 &rotrudes from the cervical os
o &roduces postcoital bleeding
3. Not precancerous
Cervical intraepithelial neoplasia (C)-)
page A6:
27 Bpidemiology
a7 (a1ority of cases are associated 'ith 0&97
i7 3o' ris$-types : 22
ii7 0igh ris$-types 2: 2;
iii7 0&9 produces $oilocytosis in s,uamous cells
Clear halo containing a 'rin$led py$notic nucleus
b7 !is$ factors
i7 Barly age of onset of se"ual intercourse
ii7 (ultiple high-ris$ partners
iii7 0igh-ris$ types of 0&9 in the biopsy
iv7 Smo$ing oral contraceptive pills (OC&s) immunodeficiency
*7 Classification of C)-
a7 C)- )
(ild dysplasia involving the lo'er third of the epithelium
b7 C)- ))
(oderate dysplasia involving the lo'er t'o thirds of the epithelium
c7 C)- )))
Severe dysplasia to C)S involving the full thic$ness of the epithelium
ii &rogression from C)- ) to C)- ))) is not inevitable7
a7 !eversal to normal is more li$ely in C)- )7
b7 !e,uires 2F years to progress from C)- ) to C)- )))
c7 !e,uires 2F years to progress from C)- ))) to invasive cancer
=verage age for cervical cancer is A6 years old7
Cervical cancer
27 Bpidemiology
a7 3east common gynecologic cancer
Due to early detection of C)- 'ith &ap smears
b7 (a1ority are s,uamous cell carcinoma (H6-;FI of cases)
Small cell cancer and adenocarcinoma are less common types7
c7 Cause and ris$ factors
Same as those listed for C)-
*7 Clinical findings
a7 (alodorous discharge
b7 &ostcoital bleeding
+7 Cancer characteristics
a7 B"tends do'n into the vagina
b7 B"tends out into the lateral 'all of the cervi" and vagina
c7 )nfiltrates the bladder 'all and obstructs the ureters
&ostrenal azotemia leading to renal failure is the most common cause of
death7
d7 Distant metastases (e7g7 lungs)
Reproductive %hysiolo&y and Selected )ormone Disorders
Se,uence to menarche
27 >reast budding (thelarche)
*7 4ro'th spurt
+7 &ubic hair
A7 ="illary hair
67 (enarche
a7 (ean age of 2*7; years
b7 =novulatory cycles for 2 to 276 years
Summary of the normal menstrual cycle
page A6<
)n fertility 'or$ups endometrial biopsies are commonly performed on day *2
to see if ovulation has occurred7 &resence of secretory endometrium on day
*2 confirms that ovulation has occurred7
page A6<
page A:F
Synthesis of se" hormones in the ovary
27 &roliferative phase
a7 Bstrogen-mediated proliferation of glands
Most variable phase of the cycle
b7 Bstrogen surge occurs *A to +: hours prior to ovulation7
ii Stimulates luteinizing hormone (30)
&ositive feedbac$
iii )nhibits follicle-stimulating hormone (/S0)
-egative feedbac$
Serum 30 greater than /S0
iiii 30 surge initiates ovulation7
*7 Ovulation
a7 Occurs bet'een days 2A and 2:
b7 Ovulation indicators
ii )ncrease in body temperature
Bffect of progesterone
iii Subnuclear vacuoles in endometrial cells
iiii (ittelschmerz
&eritoneal irritation from blood from the ruptured follicle
+7 Secretory phase
a7 &rogesterone-mediated
Least variable phase of the cycle
b7 )ncreased gland tortuosity and secretion
c7 Bdema of stromal cells
d7 Changes occurring after fertilization
ii /ertilization usually occurs in the ampullary portion of the fallopian tube7
iii /ertilized egg spends + days in the fallopian tube7
iiii /ertilized egg spends * days in the uterine cavity7
)mplants in the endometrial mucosa on day *2
ivi =n e"aggerated secretory phase occurs in pregnancy7
Called the =rias-Stella phenomenon
*7 (enses
a7 )nitiated by dropoff in serum levels of estrogen and progesterone
Cells undergo apoptosis7
b7 &lasmin prevents menstrual blood from clotting7
B"cess clotting is a sign of menorrhagia7
ii /unctions of /S0
a7 &repares the follicle of the month
b7 )ncreases aromatase synthesis in the granulosa cells
c7 )ncreases the synthesis of 30 receptors
ii /unctions of 30
a7 30 in the proliferative phase
ii )ncreases the synthesis of 2H-$etosteroids (DS) in the theca interna (see
2H-DS are dehydroepiandrosterone (D0B=) and
androstenedione7
iii D0B= is converted to androstenedione7
iiii =n o"idoreductase converts androstenedione to testosterone
ivi Testostorone enters granulosa cells and is aromatized to estradiol
b7 30 surge is induced by a sudden increase in estrogen7
Ovulation occurs 'hen 30 is higher than /S07
b7 30 in the secretory phase
Theca interna primarily synthesizes 2H-hydro"yprogesterone7
ii 0ormone changes in pregnancy
a7 0uman chorionic gonadotropin (hC4)
ii Synthesized in the syncytiotrophoblast lining the chorionic villus
iii =cts as an 30 analogue by maintaining the corpus luteum of pregnancy7
iiii Corpus luteum synthesizes progesterone for ; to 2F 'ee$s7
b7 Corpus luteum involutes after ; to 2F 'ee$s7
ii &lacenta synthesizes progesterone for the remainder of the pregnancy7
iii Spontaneous abortion may occur if placental production of progesterone
is inade,uate7
Oral contraceptive pills (OC&s)
27 (i"ture of estrogen G progestins (progesterone)
a7 >aseline levels of estrogen prevent the midcycle estrogen surge7
&revents the 30 surge and ovulation
b7 &rogestins arrest the proliferative phase and cause gland atrophy7
c7 &rogestins inhibit 30 'hich also prevents the 30 surge7
*7 OC&s render the cervical mucus hostile to sperm7
+7 OC&s alter fallopian tube motility7
Sources and types of estrogen
27 Bstradiol
a7 &rimary estrogen in nonpregnant 'omen
b7 Derived from aromatization of testosterone in granulosa cells
*7 Bsterone%
a7 @ea$ estrogen produced during menopause
b7 Derived from adipose cell aromatization of androstenedione
=ndrostenedione is synthesized in the adrenal corte"7
+7 Bstriol
a7 Bnd product of estradiol metabolism
b7 &rimary estrogen of pregnancy
Derives from fetal adrenal placenta and maternal liver
Sources and types of androgens
27 =ndrostenedione
o B,ual derivation from ovaries and adrenal corte"
*7 D0B=
a. (ainly synthesized in the adrenal corte" (;FI)
b. !emainder is synthesized in the ovaries7
*7 D0B=-sulfate
o =lmost e"clusively synthesized in the adrenal corte"
+7 Testosterone
a. Derived from conversion of androstenedione to testosterone
b. (a1ority of testosterone is synthesized in the ovaries7
Smaller amount is synthesized in the adrenal corte"
Se" hormone-binding globulin (S0>4)
27 >inding protein for testosterone and estrogen
a7 )n both men and 'omen S0>4 is primarily synthesized in the liver7
b7 Bstrogen increases synthesis of S0>4 in the liver7
c7 =ndrogens obesity hypothyroidism all decrease the synthesis of S0>47
*7 S0>4 has a greater binding affinity for testosterone than estrogen7
a7 )ncreased S0>4 decreases free testosterone levels7
b7 Decreased S0>4 increases free testosterone levels7
Common cause of hirsutism in 'omen (see belo')
-ormal changes in pregnancy
27 &lasma volume and red blood cell (!>C) mass
a7 >oth are increased
)ncrease in plasma volume is greater than the increase in !>C mass7
b7 Causes a 2gJd3 drop in hemoglobin (0b) (dilutional effect)
c7 )ncreases glomerular filtration rate
ii Creatinine clearance is increased7
iii )ncreased clearance of urea and creatinine7
Serum levels are at the lo'er limit of normal7
*7 !espiratory al$alosis
a7 Bffect of estrogen and progesterone stimulating respiratory center
b7 Decrease in &aCO* causes a corresponding increase in &aO*7
+7 )ncreased serum thyro"ine and cortisol
a7 Bstrogen stimulates synthesis of thyroid-binding globulin and transcortin7
b7 )ncreased binding proteins increases total thyro"ine and cortisol7
c7 (etabolically active free hormone levels are normal
No clinical signs of overactivity
(enopause
27 (ean age 6* years old
*7 )ncrease in /S0 and 30
a7 Due to drop in estrogen and progesterone respectively
b7 Serum /S0 is the best screen7
+7 Clinical findings
a7 Secondary amenorrhea
b7 0ot flushes night s'eats
0irsutism and virilization
27 Bpidemiology and pathogenesis
a7 0irsutism is e"cess hair in normal hair-bearing areas7
9irilization is hirsutism G male secondary se" characteristics7
b7 (ale secondary se" characteristics
ii )ncreased muscle mass
iii =cne
iiii Bnlarged clitoris (clitoromegaly)
(ost important finding
b7 >oth conditions are due to increased androgens of ovarian or adrenal origin
ii Ovarian origin-testosterone is primarily increased
iii =drenal origin-D0B=-sulfate is primarily increased
*7 Selected ovarian disorders
a7 &olycystic ovarian syndrome (&OS)
ii )ncreased pituitary synthesis of 30 and decreased synthesis of /S0
iii )ncreased 30 increases androgen synthesis7
0irsutism occurs more often than virilization7
iiii =ndrogens are aromatized to estrogen in the adipose cells7
Causes an increase in estrogen
)ncreases the ris$ for developing endometrial hyperplasia and
cancer
ivi )ncreased estrogen has a positive feedbac$ on 30 and negative
feedbac$ on /S07
Suppression of /S0 causes follicle degeneration7
/luid accumulation produces subcortical cysts that enlarge the
ovaries
vi Clinical findings
(enstrual irregularities
Oligomenorrhea is the most common complaint7
0irsutism infertility obesity (6FI of cases)
vii 3aboratory findings
30%/S0 ratio above *
)ncreased testosterone and androstenedione
)ncreased estrogen
b7 Obesity hypothyroidism
Decreased S0>4 causes an increase in free testosterone
b7 Ovarian tumors 'ith increased androgen production
ii =drenal disorders
o =drenogenital syndrome and Cushing syndrome
(enstrual dysfunction
page A:*
page A:+
27 (enorrhagia
o 3oss of blood greater than ;F m3 per period
*7 Dysmenorrhea
a. &ainful menses
b. &rimary type
i7 Due to increased prostaglandin /*K (&4/*K)
ii7 )ncreases uterine contractions
c. Secondary type
(ost often due to endometriosis
*7 Dysfunctional uterine bleeding (D.>)
ii Definition
i7 >leeding unrelated to an anatomic cause
ii7 Caused by a hormonal imbalance
b. =novulatory D.>
i7 Occurs at the e"tremes of reproductive life
(enarche to age *F years
&erimenopausal period
ii7 B"cessive estrogen stimulation relative to progesterone
=bsent secretory phase of the cycle
&roduces endometrial hyperplasia and bleeding
c. )nade,uate luteal phase
i7 Ovulatory type of D.>
ii7 )nade,uate maturation of the corpus luteum
)nade,uate synthesis of progesterone
Delay in development of the secretory phase
Decreased serum 2H-hydro"yprogesterone on day *2
d. )rregular shedding of the endometrium
i7 Ovulatory type of D.>
ii7 &ersistent luteal phase 'ith continued secretion of progesterone
iii7 (i"ture of proliferative and secretory glands in the menstrual effluent
*7 Causes of abnormal bleeding by age
Ta"le 21#2$ (auses o! *"normal Bleedin& "y *&e
*&e Brac+et (auses o! Bleedin&
&repubertal 9ulvovaginitis% poor hygiene infection (e7g7 gonorrhea) se"ual abuse foreign bodies
Bmbryonal rhabdomyosarcoma
(enarche to *F years
old
=novulatory D.> (most common cause)
9on @illebrandCs disease
*F to AF years old &regnancy and its complications (most common cause)
Ovulatory types of D.>
&)D hypothyroidism submucosal leiomyomas adenomyosis endometrial polyp
endometriosis
AF years or older =novulatory D.> (most common cause in perimenopausal period)
Bndometrial hyperplasiaJcancer (most common cause in menopause)
D.> dysfunctional uterine bleeding; &)D pelvic inflammatory disease7
=menorrhea
page A:+
page A:A
27 Bpidemiology
a7 &rimary amenorrhea
i7 =bsence of menses by 2: years of age
ii7 (ost cases are due to constitutional delay7
/amily history of delayed onset of menses
b7 Secondary amenorrhea
i7 =bsence of menses for + months
ii7 (ost cases are due to pregnancy7
*7 &athogenesis
a7 0ypothalamic or pituitary disorder
i7 Decreased synthesis of /S0 and 30
Decreased synthesis of estrogen and progesterone
0ypogonadotropic (L /S0 and 30) hypogonadism
ii7 No 'ithdra'al bleeding after receiving progesterone
Bndometrial mucosa is not estrogen-stimulated7
iii7 B"amples
0ypopituitarism prolactinoma
=nore"ia nervosa
b7 Ovarian disorder
i7 Decreased synthesis of estrogen and progesterone
)ncrease in serum /S0 and 30 respectively
0ypergonadotropic (M /S0 and 30) hypogonadism
ii7 No 'ithdra'al bleeding after receiving progesterone
Bndometrial mucosa is not estrogen-stimulated7
iii7 B"amples
TurnerCs syndrome
Surgical removal of ovaries
c7 Bnd-organ defect
i7 &revents the normal egress of blood
(ore li$ely cause of primary amenorrhea
ii7 -ormal levels of /S0 30 estrogen and progesterone
iii7 No 'ithdra'al bleeding after receiving progesterone
iv7 B"amples
)mperforate hymen !o$itans$y-Duster-0auser syndrome
=sherman syndrome
!emoval of stratum basalis o'ing to repeated curettage
d7 Summary of amenorrhea
Ta"le 21#,$ Di!!erential Dia&nosis o! *menorrhea
Disorder FS)-.) /stro&en /xamples
0ypothalamicJpituitary disorder L L 0ypopituitarism
=nore"ia nervosa prolactinoma
Ovarian disorder M L TurnerCs syndrome
Bnd-organ defect - - )mperforate hymen =sherman syndrome
Constitutional delay - - /amily history of delayed onset of menses
0terine Disorders
Bndometritis
27 =cute endometritis
a7 (ost often due to bacterial infection follo'ing delivery or miscarriage
b7 4roup > streptococcus (Streptococcus agalactiae is a common pathogen7
*7 Chronic endometritis
a7 Causes
i7 !etained placenta
ii7 4onorrhea intrauterine device (!ctinomyces israeli
b7 Dey histologic finding is the presence of plasma cells
=denomyosis
27 )nvagination of the stratum basalis into the myometrium
a7 4lands and stroma thic$en myometrial tissue
b7 &roduces uterine enlargement
*7 Clinical findings
o (enorrhagia dysmenorrhea pelvic pain
Bndometriosis
The rectal pouch of Douglas is anterior to the rectum and posterior to the
uterus7 )t is the most dependent portion of the female pelvis7 )t can be
palpated by digital rectal e"amination7 )t is a common site to collect blood
(e7g7 ruptured tubal pregnancy) malignant cells (e7g7 seeding by ovarian
cancer) endometrial implants and pus (e7g7 pelvic inflammatory disease)7
27 /unctioning glands and stroma are located outside the uterus7
*7 &athogenesis
a7 !everse menses through fallopian tubes (most common)
b7 Coelomic metaplasia vascular or lymphatic spread
+7 Cyclic bleeding of gland and stromal implants
A7 Common sites
o Ovaries (most common) rectal pouch fallopian tubes intestine
2. Clinical findings
a7 Dysmenorrhea
b7 &ainful stooling during menses
)mplants located in rectal pouch
c7 )ntestinal obstruction and bleeding during menses
d7 )ncreased ris$ for ectopic pregnancy
e7 Bnlargement of ovaries
>lood-filled cysts
67 3aparoscopy useful for diagnosis and treatment
o )mplants have a 8po'der burn8 appearance
Bndometrial hyperplasia
27 Bpidemiology and pathogenesis
a7 &rolonged estrogen stimulation
b7 !is$ factors
i7 Barly menarche or late menopause
ii7 -ulliparity
iii7 Obesity
)ncreased aromatization of androgens to estrogen
iv7 &OS ta$ing estrogen 'ithout progesterone
c7 Classification
i7 Simple hyperplasia
)ncreased number of cystically dilated glands
No glandular cro'ding
ii7 Comple" hyperplasia
)ncreased number of dilated glands 'ith branching
4landular cro'ding
iii7 =typical hyperplasia
4landular cro'ding and dysplastic epithelium
)ncreased ris$ for endometrial cancer
*7 Clinical findings
a7 (enorrhagia or irregular uterine bleeding
b7 )ncreased ris$ for progression to endometrial carcinoma
Bndometrial polyp
27 >enign polyp that enlarges 'ith estrogen stimulation
*7 Does not progress to endometrial carcinoma
+7 Common cause of menorrhagia in *F- to AF-year-old age brac$et
Bndometrial carcinoma
27 Bpidemiology and pathogenesis
a7 (ost common gynecologic tumor
b7 &rolonged estrogen stimulation
Same ris$ factors as endometrial hyperplasia
c7 OC&s decrease ris$
d7 )ncreased ris$ for breast cancer
e7 Types of endometrial cancer
ii @ell-differentiated adenocarcinoma
(ost common type
=denoacanthoma
Contains foci of benign s,uamous tissue (no prognostic
significance)
=denos,uamous carcinoma
Contain foci of malignant s,uamous cancer ('orse
prognosis)
iii &apillary adenocarcinoma
0ighly aggressive cancer
*7 Cancer characteristics
a7 Spreads do'n into the endocervi"
b7 Spreads out into the uterine 'all
c7 3ungs are the most common site of metastasis
+7 Clinical findings
o &ostmenopausal bleeding
3eiomyoma (8fibroids8)
27 Bpidemiology
a7 >enign smooth muscle tumor
b7 (ore common in blac$ =mericans than 'hites
c7 Bstrogen sensitive tumors
(ay become larger during pregnancy
*7 Tumor characteristics
a7 Commonly undergo
ii Degeneration
iii Dystrophic calcification
iiii 0yalinization
!eason for the term 8fibroids8
b7 They do not transform into leiomyosarcomas7
*7 Clinical findings
a7 (enorrhagia ('hen located in submucosa)
b7 Obstructive delivery
3eiomyosarcoma
27 (ost common sarcoma of the uterus
*7 Tumor characteristics
o -umerous atypical mitoses and foci of necrosis
(alignant mi"ed mEllerian tumors (carcinosarcomas)
27 Bndometrial adenocarcinoma G malignant mesenchymal (stromal) tumor
a7 &rimarily occur in postmenopausal 'omen
b7 >ul$y necrotic tumors that often protrude through the cervical os
*7 (esenchymal component may include muscle cartilage and bone
+7 Strong association 'ith previous irradiation
A7 &oor prognosis
Fallopian Tu"e Disorders
0ydatids of (orgagni
27 Cystic mEllerian remnants
*7 (ost often located around the fimbriated end of the tube
&elvic inflammatory disease (&)D)
27 Causes of &)D
a7 (ost often due to N. gonorrhoeae or C. trachomatis
b7 Other pathogens
"acteroides #ragilis, streptococci Clostridium per#ringens
*7 (ost common cause of hydrosalpin"
o &us resorbs leaving a clear fluid distending the tube
Salpingitis isthmica nodosa (S)-)
page A:;
page A:<
27 )nvagination of the mucosa into the muscle
a7 &roduces nodules
b7 =nalogous to adenomyosis
*7 Complications
o )nfertility ectopic pregnancy
Bctopic pregnancy
27 Bpidemiology and pathogenesis
a7 )mplantation of a fetus outside the normal uterine location
b7 Sites of implantation
i7 (a1ority occur 'ithin the tubes
(ost are in the broad ampullary portion belo' the fimbriae7
ii7 Ovaries abdominal cavity
c7 Causes
i7 (ost common cause is scarring from previous &)D7
ii7 Bndometriosis altered tubal motility S)-
*7 Clinical findings
a7 Sudden onset of lo'er abdominal pain
.sually : 'ee$s after a previous normal menstrual period
b7 =bnormal uterine bleeding adne"al mass hypovolemic shoc$
ii Complications
a7 !upture 'ith intra-abdominal bleed
(ost common cause of death in early pregnancy
b7 (ost common cause of hematosalpin"
>lood in the tube
ii Diagnosis
a7 N-hC4 is the best screening test7
i7 .rine screen is usually sensitive enough7
ii7 Serum test is used if the urine screen is negative7
iii7 &ositive test does not prove that an ectopic pregnancy is present7
b7 9aginal ultrasound is the confirmatory test7
Chec$ for an amniotic sac
b7 3aparoscopy is used in e,uivocal cases7
Ovarian Disorders
/ollicular cyst
27 (ost common ovarian mass
*7 -on-neoplastic cyst
o =ccumulation of fluid in a follicle or previously ruptured follicle
+7 !upture produces sterile peritonitis 'ith pain7
A7 .ltrasound is the best screening test7
Corpus luteum cyst
27 (ost common ovarian mass in pregnancy
*7 -on-neoplastic cyst
a7 =ccumulation of fluid in the corpus luteum during pregnancy
b7 (ay be confused 'ith an amniotic sac
Oophoritis
(ay be a complication of mumps or pelvic inflammatory disease
Stromal hyperthecosis
27 Occurs primarily in postmenopausal 'omen
o Causes ovarian enlargement
*7 0ypercellular ovarian stroma
a. 9acuolated stromal hilar cells are present that synthesize androgens
b. (ay cause hirsutism or virilization
*7 =ssociation 'ith acanthosis nigricans and insulin resistance
Ovarian tumors
Ta"le 21#1$ (lassi!ication o! Ovarian Tumors
Tumor (haracteristics
Sur!ace#Derived
Tumors

Serous tumors (ost common group of primary benign and malignant tumors
(ost common group of tumors that can be bilateral
Cysts are lined by ciliated cells (similar to fallopian tube)
Serous cystadenoma (benign); serous cystadenocarcinoma has psammoma bodies
(dystrophically calcified tumor cells); most common tumor that is bilateral
(ucinous tumors Cysts lined by mucus-secreting cells (similar to endocervi")
3arge multiloculated tumors
Seeding produces pseudomy"oma peritonei
(ucinous cystadenoma (benign); may be associated 'ith >rennerCs tumors; mucinous
cystadenocarcinoma
Bndometrioid (alignant tumors associated 'ith endometrial carcinoma (26-+FI of cases); tumor
resembles endometrial carcinoma
Commonly bilateral
>renner tumor .sually benign
Contain @althardCs rests (transitional-li$e epithelium)
Germ (ell Tumors
Cystic teratoma .sually benign; less then 2I become malignant (usually s,uamous cancer)
Bctodermal differentiation (hair sebaceous glands teeth) most prominent
(ost of these derivatives are found in a nipple-li$e structure in the cyst 'all called
!o$itans$y tubercle
)mmature malignant types contain mature and immature components (e7g7 muscle
neuroepithelium)
Struma ovarii type has functioning thyroid tissue
Dysgerminoma (ost common malignant germ cell tumor; characteristic increase in serum 3D0; same
histologic picture as seminoma of testis
=ssociated 'ith strea$ gonads of TurnerCs syndrome
#ol$ sac tumor (alignant tumor; most common ovarian cancer in girls OA years old
Contain Schiller-Duval bodies (resemble yol$ sac)
)ncreased K-fetoprotein
Sex#(ord Stromal
Tumors

Thecoma-fibroma >enign tumor associated 'ith (eigsC syndrome (ascites right-sided pleural effusion);
regression of effusions follo's removal of tumor
Commonly calcify
4ranulosa-thecal cell
tumor
3o'-grade malignant tumor
/eminizing tumor (produces estrogen) that contains Call-B"ner bodies
Sertoli-3eydig cell >enign masculinizing tumor (produces androgens)
&ure 3eydig cell tumors contain cells 'ith crystals of !ein$e
4onadoblastoma (alignant tumor 'ith mi"ture of germ cell tumor (dysgerminoma) and se"-cord stromal
tumor; associated 'ith abnormal se"ual development in ;FI of cases
Commonly calcify
Tumors 2etastatic to
Ovary

Dru$enberg tumor (ay affect both ovaries; contains signet-ring cells from hematogenous spread of a
gastric cancer
3D0 lactate dehydrogenase7
page AHF
page AH2
page AH2
page AH*
27 Bpidemiology and pathogenesis
a7 Tumors are more li$ely benign in 'omen younger than A6 years of age7
b7 !is$ factors
i7 -ulliparity
)ncreased number of ovulatory cycles increases ris$7
)ncreased ris$ for surface-derived ovarian tumors
ii7 4enetic factors
(utations of "$C!% and "$C!& suppressor genes
3ynch syndrome
TurnerCs syndrome
)ncreased ris$ for dysgerminoma
&eutz-?eghers syndrome
)ncreased incidence of se" cord tumors 'ith annular
tubules
iii7 Smo$ing cigarettes
iv7 OC&s decrease ris$
Decreased number of ovulatory cycles
*7 Classification of ovarian tumors
a7 Surface-derived tumors
i7 =ccount for :6I to HFI of ovarian tumors
ii7 Derive from coelomic epithelium
iii7 =ccount for the greatest number of malignant ovarian tumors
iv7 (alignant tumors commonly seed the omentum
b7 4erm cell tumors
i7 =ccount for 26I to *FI of ovarian tumors
ii7 Cancers are similar to those seen in the testicle
iii7 = relatively small number of tumors are malignant7
c7 Se" cord-stromal tumors
i7 =ccount for +I to 6I of ovarian tumors
ii7 Derive from stromal cells
iii7 (ay be hormone-producing
iv7 (a1ority of tumors are benign
d7 (etastasis
i7 =ccounts for 6I of ovarian tumors
ii7 Common primary cancers metastasizing to ovaries
>reast stomach (e7g7 Dru$enberg tumors)
+7 Clinical findings
a7 Signs of seeding from malignant surface-derived cancers
i7 (alignant ascites and increased abdominal girth
ii7 )nduration in the rectal pouch on digital rectal e"amination
iii7 )ntestinal obstruction 'ith colic$y pain
b7 &alpable ovarian mass in a postmenopausal 'oman
Ovaries should not be palpable in menopausal 'omen7
b7 (alignant pleural effusion
Common site for ovarian cancer metastasis
c7 Cystic teratomas undergo torsion leading to infarction7
!adiographs sho' calcification from bone or teeth
d7 Signs of hyperestrinism from estrogen-secreting tumors7
i7 >leeding from endometrial hyperplasiaJcancer
ii7 2FFI superficial s,uamous cells in a cervical &ap smear
b7 0irsutism or virilization from androgen-secreting tumors
A7 Tumor mar$ers
c7 )ncreased serum cancer antigen 2*6 (C= 2*6)
d7 Only increased in surface-derived malignant tumors
Gestational Disorders
&lacental anatomy
page AH*
page AH+
27 (aternal surface
o Contains cotyledons covered by a layer of decidua basalis
*7 /etal surface
a. Bntirely covered by the chorionic plate
b. Chorionic villi vessels converge 'ith the umbilical cord7
c. Chorion is covered by the amnion7
*7 Chorionic villusJumbilical cord
a. Chorionic villi pro1ect in the intervillous space7
i7 Space contains maternal blood from 'hich o"ygen is e"tracted7
ii7 Spiral arteries from the uterus empty into the space7
b. Chorionic villi are lined by trophoblastic tissue7
i7 Outside layer is composed of syncytiotrophoblast7
Synthesizes hC4 (see above)
Synthesizes human placental lactogen (0&3)
Directly correlates 'ith placental mass and has anti-
insulin activity
ii7 )nside layer is composed of cytotrophoblast7
c. Chorionic villus vessels coalesce to form the umbilical vein7
d. .mbilical cord
i7 Contains one umbilical vein and t'o umbilical arteries
.mbilical vein contains o"ygenated blood7
ii7 Single umbilical artery
)ncreased incidence of congenital anomalies
)nfections
27 Bpidemiology
a7 (ost are due to ascending bacterial infections
i7 Complication of premature rupture of membranes
ii7 4roup > streptococcus is the most common pathogen7
b7 Congenital infections (e7g7 cytomegalovirus syphilis)
*7 /unisitis and placentitis
o )nfection of the umbilical cord and placenta respectively
2. Chorioamnionitis
a7 )nfection of the fetal membranes
b7 Danger of neonatal sepsis and meningitis
Selected placental abnormalities
27 &lacenta previa
a7 )mplantation over cervical os
b7 &ainless vaginal bleeding
*7 =bruptio placentae
a7 &remature separation of placenta due to formation of a retroplacental clot
Separates the placenta from the implantation site
b7 !is$ factors
ii 0ypertension
iii Smo$ing cigarettes
iiii Cocaine addiction advanced maternal age
b7 &ainful vaginal bleeding
*7 &lacenta accreta
a7 Direct implantation into muscle 'ithout intervening decidua
b7 !e,uires a hysterectomy after delivery of the baby
+7 Succenturiate lobes
a7 =ccessory lobes of the placenta located along the margin
b7 !is$ for hemorrhage if the accessory lobes are detached
A7 Bnlarged placenta
a7 Diabetes mellitus
b7 !h hemolytic disease of ne'born
c7 Congenital syphilis
67 T'in placentas
a7 (onochorionic types are associated 'ith identical t'ins7
ii )dentical t'ins derive from a single fertilized egg7
iii (onoamniotic 'ith a single amniotic sac
Type for Siamese t'ins or tangling of umbilical cords
iiii Diamniotic 'ith separate amniotic sacs
ivi /etal-to-fetal transfusion can occur in either type7
b7 Dichorionic placentas
ii Can be identical or fraternal t'ins
/raternal t'ins occur 'hen separate eggs are fertilized7
iii &lacentas can be diamniotic or separated
&reeclampsiaJeclampsia
page AHA
page AH6
To"emia of pregnancy
27 Bpidemiology
a7 .sually occurs in the third trimester (*Ath to *6th 'ee$)
b7 &reeclampsia in the first trimester
=ssociated 'ith a molar pregnancy (see belo')
c7 (ore common in 'omen older than +6 years of age
*7 &athogenesis
a7 =bnormal placentation
Causes mechanical or functional obstruction of the spiral arteries
b7 -ormal vasodilators are decreased7
B"amples-&4B* nitric o"ide
c7 9asoconstrictors are increased7
B"amples-thrombo"ane =* angiotensin ))
d7 -et effect is placental hypoperfusion7
+7 &athologic findings
a7 &remature aging of the placenta
b7 (ultiple placental infarctions
c7 Spiral arteries sho' intimal atherosclerosis
A7 Clinical findings
a7 Diastolic hypertension (increased vasoconstrictors)
b7 &roteinuria often in nephrotic range
c7 Dependent pitting edema
Due to loss of albumin in the urine
d7 4eneralized seizures
ii &reeclampsia G seizures is called eclampsia7
iii (gSOA is used for treatment7
b7 !enal disease
S'ollen endothelial cells in the glomerular capillaries
b7 3iver disease
&eriportal necrosis 'ith increased transaminases
c7 0B33& syndrome
0emolytic anemia and disseminated intravascular coagulation
4estational trophoblastic neoplasms
page AH:
27 0ydatidiform moles
a7 >enign tumors of the chorionic villus
Complete and partial moles
b7 Complete mole is the most common type7
ii The entire placenta is neoplastic7
iii Dilated s'ollen villi 'ithout fetal blood vessels
iiii No embryo is present7
ivi A:PP (<FI of cases)
>oth chromosomes are of male origin7
Bgg is fertilized by t'o haploid spermatozoa 'ith P
chromosomes7
vi )ncreased ris$ for developing choriocarcinoma
vii Clinical findings
&reeclampsia develops in the first trimester
.terus is too large for gestational age
)ncreased hC4 for the gestational age
8Sno'storm appearance8 'ith ultrasound
b7 &artial mole
ii -ot all villi are neoplastic or dilated7
iii Bmbryo is present7
Triploid (:<PP#)
Bgg 'ith *+P is fertilized by a *+P and a *+# sperm7
iiii No increased ris$ for developing a choriocarcinoma
*7 Choriocarcinoma
a7 (alignant tumor composed of syncytiotrophoblast and cytotrophoblast
Chorionic villi are not present7
b7 !is$ factors
ii Complete mole (6FI of cases)
iii Spontaneous abortion (*6I of cases)
iiii -ormal pregnancy (*6I of cases)
b7 Common sites of metastasis
ii 3ungs and vagina
iii 3esions are hemorrhagic
c7 B"cellent response to chemotherapy
4ood response does not apply to non-gestationally derived cancer7
=mniotic fluid
page AH:
page AHH
27 Composition
a7 /etal urine
b7 0igh salt content causes ferning 'hen dried on a slide
B"cellent sign of premature rupture of the amniotic sac
c7 S'allo'ed and recycled by the fetus
d7 &olyhydramnios
ii B"cessive amniotic fluid
iii Causes
Tracheoesophageal fistula duodenal atresia
b7 Oligohydramnios
ii Decreased amount of amniotic fluid
iii ?uvenile polycystic $idney disease
*7 K-/etoprotein (=/&) in pregnancy
a7 )ncreased maternal =/&
ii Open neural tube defect
iii !elated to folate deficiency
iiii /olate stores should be ade,uate be#ore pregnancy7
-eural tube is already developed by the end of the first month of
gestation7
b7 Decreased maternal =/&
Do'n syndrome
ii 3ecithinJsphingomyelin (3%S) ratio
a7 3ecithin
ii Synthesized by type )) pneumocytes
iii Decreases alveolar surface tension to prevent atelectasis
b7 3%S ratio greater than * in amniotic fluid indicates ade,uate surfactant7
c7 Cortisol and thyro"ine increase surfactant synthesis7
(aternal administration of glucocorticoids increases surfactant synthesis
if babies must be delivered before term7
b7 )nsulin inhibits surfactant synthesis7
.rine estriol in pregnancy
27 Derived from the fetal adrenal gland placenta and maternal liver
a7 /etal zone of the adrenal corte"
i7 Converts pregnenolone synthesized in the placenta to D0B=-sulfate
ii7 /etal zone is absent in anencephaly (absent brain)7
b7 /etal liver
D0B=-sulfate is 2:-hydro"ylated to 2:-O0-D0B=-sulfate7
b7 (aternal placenta
i7 &lacental sulfatase cleaves off the sulfate from 2:-O0-D0B=-sulfate7
ii7 2:-O0-D0B= is converted by aromatase to free unbound estriol7
b7 (aternal liver
i7 /ree estriol is con1ugated to estriol sulfate and estriol glucosiduronate7
ii7 >oth compounds are e"creted in maternal urine and bile7
*7 Decreased levels of estriol
o Sign of fetal-maternal-placental dysfunction
2. Do'n syndrome triad
a7 Decreased urine estriol
b7 Decreased =/&
c7 )ncreased N-hC4
Breast Disorders
Clinical anatomy
page AHH
page AH;
27 0igh-density locations of breast tissue
a7 .pper outer ,uadrant
.nderscores 'hy cancer is most commonly located in this ,uadrant
b7 >eneath the nipple
*7 0ormone effects during menstrual cycle
a7 Bstrogen
Stimulates ductal and alveolar gro'th
b7 &rogesterone
Stimulates alveolar differentiation
+7 0ormone effects in lactation
a7 &rolactin
Stimulates and maintains lactogenesis
b7 O"ytocine
ii !eleased by suc$ling refle"
iii B"pulsion of mil$ into ducts
*7 3ymph nodes
a7 Outer ,uadrant cancers
Drain to the a"illary lymph nodes
b7 )nner ,uadrant cancers
Drain to the internal mammary nodes
3ocations for breast lesions
-ipple discharges
27 4alactorrhea; causes other than lactation%
a7 (echanical stimulation of the nipple
(ost common physiologic cause of galactorrhea
b7 &rolactinoma
(ost common pathologic cause of galactorrhea
c7 &rimary hypothyroidism
ii (ost common nonpituitary endocrine disease causing galactorrhea
iii Decreased serum thyro"ine increases thyrotropin-releasing factor (T!/)7
T!/ stimulates prolactin7
b7 Drugs (e7g7 OC&s)
*7 >loody nipple discharge
o )ntraductal papilloma ductal cancer
2. &urulent nipple discharge
a7 =cute mastitis due to Staphylococcus aureus
b7 .sually occurs during lactation or breast-feeding
*7 4reenish bro'n nipple discharge
o (ammary duct ectasia (plasma cell mastitis)
>reast pain
27 (ost common cause is fibrocystic change
*7 (ondorCs disease
a7 Superficial thrombophlebitis of veins overlying the breast
b7 &resents as a palpable painful cord
/ibrocystic change
27 Bpidemiology and pathogenesis
a7 (ost common breast mass in 'omen younger than 6F years old
b7 3imited to the reproductive period of life
c7 Distortion of normal cyclic breast changes
*7 Small and large cysts
a7 Some cysts have hemorrhage into the cyst fluid7
Called 8blue domed8 cysts
b7 9ary in size 'ith the menstrual cycle
c7 No malignant potential
+7 /ibrosis
o No malignant potential
2. Sclerosing adenosis
a7 &roliferation of small ductulesJacini in the lobule
&attern is often confused 'ith infiltrating ductal cancer7
b7 Often contain microcalcifications
A7 Ductal hyperplasia
c7 Ducts are estrogen-sensitive7
d7 &athologic findings
ii &apillary proliferation is called papillomatosis7
iii =pocrine metaplasia refers to the presence of large pin$-staining cells7
iiii =typical ductal hyperplasia
)ncreased ris$ for developing cancer
)nflammation
27 =cute mastitis (see above)
*7 (ammary duct ectasia (plasma cell mastitis)
a7 -onbacterial infection
b7 (ain ducts fill up 'ith debris7
Causes dilation rupture and inflammation
c7 (ay produce s$in and nipple retraction simulating cancer
+7 Traumatic fat necrosis
a7 Trauma to breast tissue
b7 (icroscopic findings
ii 3ipid-laden macrophages 'ith foreign body giant cells
iii /ibrosis dystrophic calcification
b7 &ainful indurated mass
c7 (ay produce s$in retraction simulating cancer
*7 Silicone breast implant
a7 &olymer of silica o"ygen and hydrogen
b7 Silicone gel can lea$ or the implant can rupture
ii &roduces foreign body giant cells and chronic inflammation
iii =ssociation 'ith autoimmune disease is not proved7
>enign breast tumors
27 /ibroadenoma
a7 (ost common breast mass in 'omen younger than +6 years old
b7 >enign tumor derived from the stroma
Stroma proliferates and compresses the ducts
c7 Discrete movable painless or painful mass
(ultiple lesions may be present7
d7 )ncreases in size during pregnancy
Bstrogen-sensitive
e7 !arely becomes malignant
*7 &hyllodes tumor
a7 >ul$y tumor derived from stromal cells
b7 (ost often benign but can be malignant in some cases
0ypercellular stroma 'ith mitoses are signs of malignancy7
c7 3obulated tumor 'ith cystic spaces containing leaf-li$e e"tensions
Often reach massive size
+7 )ntraductal papilloma
a7 (ost common cause of bloody nipple discharge in 'omen younger than 6F years
old
b7 Develop in the lactiferous ducts or sinuses
c7 -o increased ris$ for cancer
>reast cancer
page A;F
page A;2
Ta"le 21#3$ Types o! Breast (ancer
Type (omments
4oninvasive
Ductal carcinoma in situ -onpalpable
&atterns% cribriform
(sieve-li$e)
comedo (necrotic
center)
Commonly contain
microcalcifications
One third
eventually invade
3obular carcinoma in-situ -onpalpable;
virtually al'ays an
incidental finding in
a breast biopsy for
other reasons
3obules distended
'ith bland
neoplastic cells;
one third
eventually invade
)ncreased
incidence of
cancer in the
opposite breast
nvasive
)nfiltrating ductal carcinom One third
overe"press
($""& oncogene
Stellate-shaped
indurated gray-
'hite tumor
4ritty on cut
section
)nduration caused
by reactive
fibroplasia
(desmoplasia)
&agetCs disease of nipple B"tension of DC)S
into lactiferous
ducts and s$in of
nipple producing a
rash 'ith or
'ithout nipple
retraction
&agetCs cells
(edullary carcinoma =ssociated 'ith
"$C!% mutations
>ul$y soft tumor
'ith large cells and
lymphoid infiltrate
)nflammatory carcinoma Brythematous
breast 'ith
dimpling li$e an
orange (peau
dCorange)
&lugs of tumor
bloc$ing lumen of
dermal lymphatics
cause localized
lymphedema
9ery poor
prognosis
)nvasive lobular carcinoma -eoplastic cells
arranged in linear
fashion or form
concentric circles
(bullCs-eye
appearance)
Tubular carcinoma Develops in
terminal ductules
)ncreased
incidence of
cancer in opposite
breast
Colloid (mucinous) carcinoma .sually occurs in
elderly 'omen
-eoplastic cells
are surrounded by
e"tracellular mucin
page A;+
= 'inged scapula may occur due to damage of the long thoracic nerve7 There
is also a danger for developing lymphedema7
page A;+
page A;A
27 Bpidemiology
a7 (ost common cancer in adult 'omen (2%; lifetime ris$)
(ean age is :A years old7
b7 Second most common cancer producing death in 'omen
c7 (ost common breast mass in 'omen over 6F years old
*7 !is$ factors
a7 /amily history and genetics
ii )ncreased ris$ if breast cancer involves first-generation relatives
(other sister
iii 4enetic basis is involved in fe'er than 2FI of cases
=utosomal dominant "$C!% and "$C!& association
3i-/raumeni multicancer syndrome
)nactivation of T)*+ suppressor gene
iiii Other gene relationships
$!S oncogene ($""&, $" suppressor gene
b7 &rolonged estrogen stimulation
ii Barly menarcheJlate menopause
iii -ulliparity
iiii &ostmenopausal obesity
=romatization of androstenedione to estoron
ivi 0ormone replacement therapy
c7 =typical ductal hyperplasia
d7 Bndometrial cancer ionizing radiation smo$ing cigarettes
e7 Common denominators for increased ris$ of cancer
ii &rolonged estrogen stimulation
iii 4enetically susceptible bac$ground
*7 Clinical findings
a7 &ainless mass in the breast
.sually in the upper outer ,uadrant
b7 S$in or nipple retraction
c7 &ainless a"illary lymphadenopathy
ii (ammography
a7 &rimarily a screening test
Detects nonpalpable breast masses
b7 Does not distinguish benign from malignant lesions
c7 Screening usually starts annually at age AF7
d7 )dentifies microcalcifications
(ost often occur in ductal carcinoma in situ and sclerosing adenosis
ii Types of breast cancer
ii -atural history treatment and prognosis
a7 Spread first by lymphatics and then hematogenously
ii Outer ,uadrant cancer spreads to a"illary nodes7
iii )nner ,uadrant cancers spread to internal mammary nodes7
b7 B"tranodal metastasis
ii Common sites of metastasis
3ungs bone liver brain ovaries
iii (ay metastasize 2F to 26 years after treatment
iiii &ain in bone metastasis is relieved 'ith radiation7
c7 Staging
ii B"tranodal metastasis has greater significance than nodal metastasis
iii Sentinel node biopsy
Sampling of the initial node that drains the tumor
)f negative for metastasis the other nodes in that group are
usually negative7
)f positive for metastasis there is a one-third chance that other
nodes in that group have metastases7
d7 Bstrogen and progesterone receptor assays
ii (ost often positive in postmenopausal 'omen
iii Clinical significance
Confers an overall better prognosis
Candidate for antiestrogen therapy 'ith tamo"ifen
e7 Other tests performed on tissue
ii S phase fraction
=bove 6I is poor prognosis7
iii D-= ploidy
Diploid tumor is better than an aneuploid tumor7
iiii ($""& oncogene status
&oor prognosis if amplification is present7
f7 Surgical procedures
ii (odified radical mastectomy
!emoval of nipple-areolar comple" breast tissue pectoralis
minor a"illary nodes
iii >reast conservation therapy
3umpectomy 'ith microscopically free margins
!emoval of level ) and )) a"illary nodes
>reast radiation
g7 Overall *6I of 'omen 'ith breast cancer die from their disease7
4ynecomastia
page A;A
page A;6
27 >enign glandular proliferation in the male breast due to estrogen
a7 Subareolar mass
b7 (ore often unilateral than bilateral
c7 Due to estrogen stimulation
*7 &hysiologic gynecomastia
a7 -ormal in ne'born puberty elderly
b7 )n general surgery is not indicated7
+7 &athologic gynecomastia
a7 Cirrhosis
)nability to metabolize estrogen
b7 DlinefelterCs syndrome
c7 Drugs
B"ample-spironolactone 'hich bloc$s androgen receptors
>reast cancer in men
27 !is$ factors
a7 "$C!& suppressor gene
b7 DlinefelterCs syndrome
*7 .sually have a poor prognosis