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 ®nancy% 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 ®nancy% 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 ®nant '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 ®nancy 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