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Pathology of Female Genital Tract

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1 Pathology of Female Genital Tract
Assoc. Professor Jan Laco, MD, PhD

2 Summary Vulva Vagina Cervix of uterus Body of uterus Fallopian tube
Ovary Diseases of pregnancy

3 1. Vulva Malformations and regressive changes Inflammations
Dystrophies Pseudotumors Tumors

4 Malformations and regressive changes
Hypertrophy of clitoris female pseudohermaphroditism enzymopathic adrenogenital syndrome Senile atrophy Edema generalized hydrops lymphedema – filariosis, lymphogranuloma venereum Varicosis vulvae pregnancy, delivery

5 Inflammations – vulvitis/vulvovaginitis
predisposing factors immunosupression (DM, uremia, malnutrition, ATB) bacterial gonorrhea (N. gonorrhoeae) syphilis (T. pallidum) – chancre (ulcus durum) + condylomata lata granuloma inguinale (Calymmatobacterium granulomatis) lymphogranuloma venereum (Chlamydia trachomatis L1-L3) viral HSV 2 HPV (condyloma acuminatum, VIN) mycotic Candida spp. (DM) parasitic Trichomonas vaginalis

6 Dystrophies = non-neoplastic epithelial disorders
clinically leukoplakia – flat whitish lesions histologically two forms: Lichen sclerosus (et atrophicus) postmenopause, autoimmunity ??? Mi: atrophy of squamous epithelium, loss of adnexa, hyalinosis of upper dermis, chronic inflammation sclerotic stenosis of vulva / introitus – clinically kraurosis vulvae 1-4% pts. – squamous cell carcinoma of vulva !!! Lichen simplex chronicus (hyperplastic dystrophy) hyperplastic epithelium with hyperkeratosis, NO atypia NO risk to carcinoma

7 Pseudotumors caruncula urethralis cysts
reddish painfull small nodul near external urethral oriffice recurrent infections Mi: inflammatory pseudotumor cysts skin adnexa (atheromas) Bartholin gland retention (up to 5 cm), may be infected (abscess), pain

8 Benign tumors condyloma acuminatum skin adnexal tumors
ethiology – HPV (low-risk types 6, 11), STD multiple flat / elevated red-brown lesions (mm-cm) vulva + perineum, perianal areas Mi: squamous cell papilloma – papillomatosis, acanthosis, parakeratosis, dyskeratosis - koilocytosis (koilos – empty) skin adnexal tumors papillary hidradenoma

9 Benign tumors Deep “aggressive“ angiomyxoma Angiomyofibroblastoma
young females – 2nd-3rd decades ~ Bartholin gland cyst Mi: hypocellular myxoid stroma + vessels local recurrence Angiomyofibroblastoma Cellular angiofibroma

10 Dysplasia vulvar intraepithelial neoplasia (VIN)
2 etiopathogenetic pathways differentiated VIN – mutation of TP53 usual VIN – HPV (high-risk types – 16, 18, 31) impaired structure / maturation of epithelium cellular atypia hyperchromazia, increased N/C ratio, mitoses grading: d-VIN x u-VIN I-III most severe form: CIS

11 Malignant tumors squamous cell carcinoma (SCCa)
most common vulvar malignancy cca 3% tumors of FGT after 60 Y, currently decrease of age ethiology + HR-HPV + young smokers + u-VIN … 30% SCCa - HR-HPV + old females + d-VIN/LSetA … 70% SCCa G: leukoplakia x exophytic x endophytic ulcerated Mi: variably differentiated SCCa local spread + LN 5-year survival: 75% (< 2 cm) x 10% (> 2 cm)

12 Malignant tumors Extramammary Paget disease
intraepithelially spreading carcinoma apocrinne anogenital glands primary intraepithelial from progenitor cell G: map-like lesions ~ dermatitis Mi: Paget cells in epidermis large cells with PAS+ pale cytoplasm NO invasion – persistance for several years, NO metastases invasion - metastases

13 Malignant tumors Malignant melanoma Adenocarcinoma
3-5% of vulvar malignancies Adenocarcinoma Basal cell carcinoma (skin)

14 Summary Vulva Vagina Cervix of uterus Body of uterus Fallopian tube
Ovary Diseases of pregnancy

15 Vagina Malformations / regressive changes Inflammations Adenosis
Pseudotumors Dysplasia Tumors

16 Malformations / regressive changes
Agenesis, atresia Vagina septa Vagina duplex Cysts of Gartner´s canal Senile atrophy Necrosis (radiation) + fistulas Injury – delivery, criminal abortus Hematokolpos

17 Inflammations – kolpitis (vaginitis)
+ vulvitis + cervicitis pruritus, discharge (fluor, leukorea) predisposing factors hypoestrogenism, DM, pregnancy, loss of normal flora (Lactobacillus Döderleini), alkalisation of vaginal milieu (cosmetics), ATB Candida, T. vaginalis non-specific atrophic kolpitis colpitis emphysematosa pregnancy, spontaneously dissappears

18 Adenosis presence of glandular instead of squamous epithelium in vagina endocervical x tubal / endometrial reddish spots squamous metaplasia + inflammation idiopathic x synthetic estrogen diethylstilbesterol risk: clear cell adenocarcinoma (1 in 1,000)

19 Pseudotumors endometriosis
implantant cysts from squamous epithelium in episiotomy scar dysontogenetic cysts granulation tissue (caro luxurians), e.g. after hysterectomy

20 Dysplasia - VaIN vaginal intraepithelial neoplasia
often associated with VIN and CIN the same ethiology and morphology VaIN more rare

21 Tumors benign malignant rare, mesenchymal (leiomyoma, fibroma)
carcinoma 1-2% of all tumors of FGT squamous cell carcinoma (90 %) 6th decade, + VaIN local spread, fistulas (urinary bladder, rectum) LN metastases, 5-year survival: 40-50% adenocarcinoma endometrioid clear cell (60% from pregnancies with DES, 17 years) embryonal rhabdomyosarcoma (sarcoma botryoides) malignant tumor of childhood (age 5 years)

22 Summary Vulva Vagina Cervix of uterus Body of uterus Fallopian tube
Ovary Diseases of pregnancy

23 Cervix of uterus ectocervix (squamous epithelium)
endocervix (columnar epithelium) between – transformation zone

24 Cervix of uterus Inflammations Pseudotumors Dysplasia Tumors

25 Inflammations - cervicitis
common, associated with vulvovaginitis STD Streptococci (S. agalactiae), staphylococci, enterococci, E. coli Ch. trachomatis, U. urealyticum HSV – indication for SC acute – may be erosions chronic – chronic inflammation (follicular cervicitis), mucosal hyperplasia (papillary cervicitis)

26 Pseudotumors cystosis (ovulosis, ovula Nabothi) endometriosis
ectropium overgrowth of metaplastic squamous epithelium blocks orifices of EC glands – retention cysts endometriosis endocervical polyp 5% of adult females, bleeding solitary / multiple, event. protrusion into vagina up to several cm hyperplastic and inflammatory changes of endocervical mucosa NOT precancerosis

27 Dysplasia – cervical intraepithelial neoplasia (CIN)
transformation zone ethiology – HR-HPV (16, 18, 31, 33), STD 30 Y, age decreasing !!! risk factors (+ SCCa) persistent HR-HPV infection (x immune system) early age at first intercourse multiple sexual partners, risk male partner Mi: cytologic atypia + impaired structure / maturation squamous - CIN I-III; endoC – LG-CGIN+HG-CGIN progression to SCCa: CIN I – 2%, CIN II – 5%, CIN III – 20% regression: CIN I – 50-60%, CIN III – 33%

28 Cervical intraepithelial neoplasia
prebioptic diagnostics – screening kolposcopy + Schiller´s test – application of Lugol´s solution normal epithelium (glycogen) brown dysplastic epithelium white cytology (smears) staining according Papanicolaou evaluation acc. Bethesda classification L-SIL (low-grade squamous intraepithelial lesion) = CIN I H-SIL (high-grade squamous intraepithelial lesion) = CIN II-III

29 Benign tumors condyloma acuminatum mesenchymal mostly on ectocervix
slightly elevated whitish lesions (flat condylomas) Mi: like vulvar mesenchymal mostly leiomyoma – problems during delivery

30 Malignant tumors squamous cell carcinoma – 75% of C tumors
on the basis of CIN in TZ 45 Y, age decreasing !!! G: exophytic x endophytic (ulceration, deformation) local spread to body of uterus, vagina, parametria, rectum, urinary bladder – fistulas, stenosis of ureters (hydronephrosis) metastases – LN, distant late 5-year survival: I – 90%, II – 82%, III – 35%, IV – 10% adenocarcinoma (adenosquamous) – 20% of C tumors mucinous, endometrioid, clear cell adenoma malignum, villoglandular adenoCa neuroendocrine carcinoma (small cell) – 5%

31 Summary Vulva Vagina Cervix of uterus Body of uterus Fallopian tube
Ovary Diseases of pregnancy

32 Body of uterus Inflammations Endometriosis Dysfunctional endometrium
Endometrial Hyperplasia Pseudotumors Tumors

33 Inflammations endometrial inflammation (endometritis) acute chronic
after delivery / abortus (placental residua, blood clots) pyogenic bacteria (streptococci) – ascendent spread purulent, discharge blockage – pyometra sepsis puerperalis chronic pathologic bleeding, pain, infertility ethiology – gonorrhea, after delivery /abortus, IUD – actinomycosis, Chlamydia spp., TBC lymphoplasmacellular inflammation in endometrium, granulomatous (TBC)

34 Inflammations myometrial inflammation – myometritis
+ endometritis – endomyometritis after delivery / abortus thrombophlebitis of uterine veins perimetrial inflammation - perimetritis from myometrium to peritoneum upon uterus part of pelveoperitonitis if the source is fallopian tube parametrial inflammation – parametritis (uterine ligg.) phlegmone cause – penetrating injury, gangrenous tumors

35 Endometriosis = endometrial mucosa (glands+stroma) in abnormal localization endometriosis interna, adenomyosis in myometrium of uterus from bazal zone menorrhagia, pelvialgia endometriosis externa peritoneum of pelvis, fall. tube, vagina, ovarium, vulva, GIT, urinary bladder, abdominal wall, LN, lungs, heart, skeleton from functional zone active during menstrual cycle – chocolate cysts infertility, dysmenorrhea, pelvialgia pathogenesis regurgitation – implantation of pieces of endometrium (in tube, scar) metaplastic – endometrial differentiation of coelomic epithelium (secondary Müllerian system) vascular / lymphatic dissemination

36 Dysfunctional endometrium
pathologic uterine bleeding quantitative (hyper- or hypo-menorrhea) time-inappropriate (poly- or oligo-menorrhea) menorrhagia + metrorrhagia premenarchal and postmenopausal bleeding causes – bleeding disorder, inflammations, endometriosis, polyps, benign and malignant tumors … + dysfunctional endometrium dysfunctional endometrium – impaired hormonal regulations, sometimes associated with uterine bleeding

37 Dysfunctional endometrium
dysfunctional non-secretory endometrium abnormal levels of estrogens decreased levels – hypoproliferative / atrophic endometrium increased levels – hyperproliferative / hyperplastic endometrium cause – anovulatory cycles dysfunctional secretory endometrium abnormal levels of gestagens decreased levels – hyposecretory endometrium cause – inadequate luteal phase increased levels - hypersecretory endometrium (like pregnancy) dysfunctional irregulatory endometrium imbalance between estrogens and gestagens e.g.: stromoglandular dissociation hormonal therapy, hormonal contraception

38 Endometrial hyperplasia
cause – hyperestrogenism exogennous administration anovulatory cycles estrogen-producing tumors (ovary), polycystic ovaries G: high endometrium (diffuse x focal) simplex x complex – no longer used simplex – hyperplasia of glands and stroma (glandular cystic h.) complex – reduction of stroma, structural abnormalities without atypia x atypical precancerosis – atypical complex hyperplasia 20-25% risk for endometrial adenocarcinoma

39 Pseudotumors polyps adenomyoma atypical polypous adenomyoma
placental polyp placental residua corporal polyp circumscribed hyperplasia of proliferative glands with fibrous stroma solitary / multiple (mm-cm), perimenopause adenomyoma smooth muscle tissue stroma atypical polypous adenomyoma benign x local recurrence

40 Malignant tumors of endometrium
endometrial adenocarcinoma (type I vs. type II) most frequent malignant tumor of FGT peak 55th-65th Y risk factors hypertension, diabetes mellitus, obesity early menarché, late menopause, infertility, anovulatory cycles hyperestrogenism (atypical complex hyperplasia) clinically – postmenopausal bleeding (dg. curettage) Grossly: polypous – late invasion diffuse – early invasion spread – myometrium, cervix, pelvis late metastases – regional LN, hematogennous rare 5-year survival: I – 90%, II – 30-50%, III a IV – 20%

41 Malignant tumors of endometrium
endometrial adenocarcinoma Mi: mostly endometrioid adenocarcinoma (K-ras mutation) resembles endometrium in cca 20 % benign squamous epithelium (adenoacanthoma) mucinous adenocarcinoma (like endocervical epithelium) serous adenocarcinoma (like ovarian) clear cell adenocarcinoma (like vagina) adenosquamous carcinoma (squamous areas malignant) squamous cell carcinoma (extremely rare) serous and clear cell carcinomas (early p53 mutation) histogenetically different, NO relationship to estrogens worse prognosis

42 Tumors of endometrial stroma
45 Y, bleeding Mi: uniform small cells encircling vessels Endometrial stromal nodul Grossly: well circumscribed yellowish nodule benign Endometrial stromal sarcoma infiltration in myometrium and into lymphatic vessels low-grade – local recurrence, late metastases high-grade – aggressive tumor

43 Myometrial tumors - leiomyoma
most common benign tumor in females, 30-50% fertile females 40-50 Y hormonal dependent progression during pregnancy, regression in postmenopause clinically – acc. position and size pain, bleeding, infertility, problems during delivery G: firm circumscribed whitish-pink nodule, fascicular mm-cm (up to 10 cm) solitary / multiple (uterus myomatosus) localization submucosal bleeding, polypoid on stalk – into cervical canal = myoma nascens, infarction intramural subserosal (sometimes polypoid)

44 Myometrial tumors - leiomyoma
Mi: elongated spindle-shaped cells with eosinophilic cytoplasm and cigarette-shaped nuclei regressive changes (edema, hemorrhage, hyalinization, calcification) rarer variants epithelioid (polygonal cells with pale cytoplasm) bizarre cellular mitotically active intravenous leiomyomatosis benign metastasizing leiomyoma

45 Myometrial tumors - leiomyosarcoma
rare de novo, NOT from leiomyoma peak – 60 Y Mi: malignant smooth muscle tumor mitoses, nuclear atypia, infiltrative growth, necroses variants epithelioid myxoid 5-year survival: 40%

46 Tumors from Müllerian mesoderm
postmenopause carcinosarcoma (MMMT) extremely aggressive, myometrial invasion, metastases epithelial c. – poorly diff. endometrioid Ca mesenchymal c. sarcomatous - homologous mixed tumor – carcinosarcoma rhabdomyo-, lipo-, chondro-, osteosarcomatous - heterologous mixed tumor - MMMT 5-year survival: 30% adenosarcoma

47 Other tumors Adenomatoid tumor from mesothelium
fallopian tube, ovary, epididymis small nodule in myo- / perimetrium benign

48 Summary Vulva Vagina Cervix of uterus Body of uterus Fallopian tube
Ovary Diseases of pregnancy

49 Fallopian tube Torsion infarction Inflammations Pseudotumors Tumors

50 Inflammations - salpingitis
most common disease ascendent infection, per continuitatem, hematogennously ethiology staphylococci, streptococci, E. coli, N. gonorrhoeae, actinomycosis acute catarrhal / purulent pus accumulation - pyosalpinx chronic thickening of tubal papillae with chronic inflammation fusion of papillae (sterility, tubal pregnancy) blockage of abdominal orifice – dilatation, serous content – sactosalpinx (hydro-) + ovary – salpingo-oophoritis (inflammatory adnexal pseudotumor) TBC 80-90 % of TBC of FGT hematogennous metastasis, young females

51 Pseudotumors endometriosis paratubal cysts
if large – torsion - infarction “salpingitis“ isthmica nodosa nodular thickening in isthmic part of tube, 1 cm compression of lumen Mi: proliferation of smooth muscle and glands lined by tubal epithelium complications - infertility, tubal pregnancy

52 Tumors adenocarcinoma adenomatoid tumor primary rare (???)
peripheral third of tube Mi: serous or endometrioid adenoCa 5-year survival: 20% adenomatoid tumor see uterus

53 Summary Vulva Vagina Cervix of uterus Body of uterus Fallopian tube
Ovary Diseases of pregnancy

54 Ovary Regressive changes Inflammations Pseudotumors Tumors

55 Regressive changes atrophy bleeding ovulation
hemorrhagic infarction by torsion endometriosis

56 Inflammations - oophoritis
primary extremely rare e.g. complication of parotitis epidemica mostly – salpingo-oophoritis chronic form – inflammatory adnexal pseudotumor ethiology – see tube

57 Pseudotumors - cysts follicular theka-luteinn luteal
solitary (cca 3 cm) x multiple (cystosis) wall – granulosa cells (failure of ovulation – cystic atresia) estrogens production – dysfunctional endometrium, rupture - bleeding theka-luteinn multiple and bilateral, mm follicular cyst with luteinized wall cause – gonadotrophic stimulation of ovaries (trophoblastic disease) luteal cystic corpus luteum gestagens production – dysfunctional endometrium

58 Pseudotumors - cysts inclusion (serous, Walthard´s)
invagination of surface ovarian „epithelium“ into stigmata, entrapped tubal epithelium solitary / multiple, serous content, variable size peri- / postmenopause flat or tubal epithelium precursor of serous carcinoma endometrioid (chocolate, Sampson´s) cyst filled by bloody content (tar-like), hemosiderin precursor of endometrioid carcinoma

59 Pseudotumors - cysts polycystic ovaries (Stein-Leventhal syndrome)
20-30 Y, 3-6% of females oligomenorrhea, infertility, hirsutism, obesity  ovarian androgens,  LH,  FSH G: enlarged ovaries with smooth surface Mi: thickened tunica albuginea multiple small follicular cysts (mm) absence of corpora lutea

60 Pseudotumors Stromal hyperplasia and hyperthekosis Massive edema
postmenopause hypersecretion of androgens Massive edema girls and young females unilateral extreme enlargement recurrent partial torsion ??? Luteoma of pregnancy 3rd trimestr, stimulation by increased level of hCG spontanneous regression after delivery virilization of mother and child

61 Tumors epithelial gonadostromal germinal
from surface coelomic „epithelium“ – mesothelium ectopic endometrial (endometriosis) gonadostromal from specialized gonadal stroma + sex cords germinal from germinal cells mixed germinal + gonadostromal gonadoblastoma (dysgenetic ovaries) other primary (mesenchymal) secondary

62 Epithelial tumors most common (70% of ovarian tumors)
90% of malignant ovarian tumors middle and older age from surface ovarian mesothelium ??? – secondary Müllerian system: serous mucinous endometrioid clear cell transicional (urothelium) mixed forms

63 Secondary Müllerian system – epithelia types
serous (tube) mucinous (endocervix) endometrioid (endometrim) clear cell

64 Epithelial tumors - morphology
cyst formation (unilocular, multilocular) cystadenoma x cystadenocarcinoma papillary protrusions papiloma x papillocarcinoma (on suface) cystadenopapilloma x cystadenopapillocarcinoma stromal component adenofibroma cystadenofibroma

65 Epithelial tumors - biologic behaviour
benign - adenoma borderline tumors (of low malignant potential) NO invasion recurrence and “implants“ formation on peritoneum / LN non-invasive x invasive (extra-ovarian LG serous carcinoma) endosalpingiosis epithelium – pseudostratification, nuclear atypia, mitoses malignant - carcinoma invasion metastases on peritoneum, omentum – ascites metastases in regional LN (retroperitoneum) distant metastases (liver, lungs)

66 Epithelial tumors histogenesis of carcinomas
non-serous from benign counterparts serous High grade serous carcinoma – de novo (tube, ovary, peritoneum) Low grade serous carcinoma – from benign counterparts hereditary ovarian syndromes malignant syndrome breast – ovary mutation BRCA1 and BRCA2 Lynch syndrome mutation of genes for DNA repair

67 Epithelial tumors risk factors late symptoms
family history, nulliparity late symptoms benign – compression of organs (GIT) malignant – malignant ascites (late stage) – bad prognosis onkomarker CA 125, HE4 bad prognosis – 5-year survival: 35% older age, positive family history grading staging

68 Serous tumors most common (cca 30% of ovarian tumors)
70% benign, 10% borderline, 20% malignant age rare before puberty benign 20th-50th Y malignant 40th-60th Y bilateral (66%) Mi: tubal epithelium, psammoma bodies

69 Mucinous tumors less common (25% of ovarian tumors)
85% benign, 5% borderline, 10% malignant bilateral (20%) Mi: intestinal x endocervical (seromucinous) pseudomyxoma peritonei rupture – mucin (event. tumor cells) into abdominal cavity multiple gelatinous nodules on peritoneum + mucinous content in abdominal cavity primary tumor frequently in GIT (appendix) !!!

70 Other epithelial tumors
endometrioid (5% of ovarian tumors) benign and borderline rare, carcinoma = 30% of ov. malignancies Mi similar with Ca of body of uterus association with endometriosis 20% bilateral, 20% synchronnous Ca of body of uterus clear cell benign and borderline rare, carcinoma = 5-10% of ov. malignancies transitional (urothelium), Brenner´s benign – Brenner tumor (2% of ov. tumors) fibrous stroma + islands of urothelium borderline and malignant – rare

71 Gonadostromal tumors 10% of ovarian tumors
1st-2nd decades 20-30%, adulthood % from specialized ovarian mezoderm – endocrine active estrogens, gestagens, androgens, silent female diff. – theca, granulosa cells male diff. – Leydig, Sertoli cells

72 Granulosa cell tumor – adult type
5% of ovarian tumors 40-60 Y estrogens – endometrial hyperplasia, event. carcinoma Mi: solid, trabecular, cystic, microcystic – Call-Exner bodies) small dark cells resembling granulosa cells coffee bean-like nuclei cca 1/3 behave malignant Granulosa cell tumor – juvenile type 1st-2nd decades pubertas praecox isosexualis malignant

73 Other gonadostromal tumors
thecoma / fibroma benign, estrogens-producing, postmenopause G: firm, yellowish, whitish Meigs syndrome - + ascites, hydrothorax Mi: spindle cells with pale cytoplasm (lipids) collagen fibres – fibrothecoma, fibroma rare Sertoli cell tumor - < 40th Y, estrogens, benign Leydig cell tumor – postmenopause, androgens, benign Sertoli-Leydig cell tumor (arrhenoblastoma) 2nd-4th decades, androgens, 20% malignant

74 Germinal tumors 15-20% of ovarian tumors mature teratoma
benign most frequent of germinal tumors, 15% bilateral young females dermoid cyst lined by epidermis + skin adnexa in wall small solid nodule (Rokitanski) – other mature tissues (cartilage, bones, teeth, fat, GIT and respiratory epithelia, thyroid gland, nervous tissue) monodermal teratoma – one component ovarian goiter carcinoid malignant transformation (1-2%) - SCCa immature teratoma rare, malignant grading acc. to amount of immature neuroepithelial tissue

75 Germinal tumors dysgerminoma embryonal carcinoma - rare yolk sac tumor
counterpart of testicular seminoma mostly 1st-3rd decades cca 2 % of ovarian tumors cca 50% of malignant germinal tumors good prognosis, 5-year survival: 80% embryonal carcinoma - rare yolk sac tumor childhood, adolescence, α-fetoprotein, bad prognosis choriocarcinoma worse prognosis than gestational choriocarcinoma, hCG

76 Secondary tumors ingrowth from other advanced primaries hematogennous
GIT, uterus hematogennous often bilateral (75%) Cas of stomach, large bowel, breast, lymphomas Krukenberg tumor bilateral enlarged firm “potato-like“ ovaries metastasis of poorly diff. mucin-producing adenocarcinoma with desmoplasia from GIT - stomach

77 Summary Vulva Vagina Cervix of uterus Body of uterus Fallopian tube
Ovary Diseases of pregnancy

78 Diseases of pregnancy Extra-uterine pregnancy Disorders of placenta
Toxemia of pregnancy Tumors of placenta

79 Extra-uterine (ectopic) pregnancy
cca 1 % of pregnancies tubal (90 %), ovarian, abdominal (peritoneal), tubal isthmus cause – abnormal implantation of fertilized ovum salpingitis, pelveoperitonitis - fusions leiomyoma of uterus normal development of embryo and placental tissues, decidual changes of mucosa x inadequate conditions for further growth abortus into abdominal cavity / uterus (resorption / calcification - lithopedion) tubal rupture – bleeding into abdominal cavity (haematocele rectouterina) acute abdominal emergency – between 3rd-8th week of pregnancy ortotopic endometrium - hypersecretory with decidual changes of stroma (Arias-Stella phenomenon) x NO chorionic villi

80 Disorders of placenta normally placenta in uterine fundus
umbilical cord insertio marginalis, amnialis nodules true x false placental size placenta biloba, triloba placenta succenturiata placenta praevia localization in lower segmentum, covers entry to cervical canal blockage of delivery severe bleeding + death of fetus – indication for SC premature separation of placenta retroplacental hematoma between placenta and uterine wall inadequate blood support of fetus - death embolism of amniotic fluid + blood loss – shock + DIC in mother

81 Disorders of placenta placenta accreta
NO decidua, adhesion to myometrium impaired spontanneous / instrumental detachment of placenta – bleeding pl. increta (deep into myometrium), pl. percreta (to serosa) frequently placenta praevia retention of placenta after delivery large pieces block uterine involution – bleeding small pieces – infection, placental polyp

82 Inflammations of placenta
chorioamniitis – inflammation of amnion / chorionn funisitis – inflammation of umbilical cord infection - ascendent x hematogennous muddy amniotic fluid Mi: neutrophils hematogennous infection TBC, listeriosis, toxoplasmosis, syphilis, viral infection only villi infected – villitis

83 Toxemia of pregnancy 6 % pregnancies, 3rd trimestr
EPH gestosis (preeclampsia) edema + proteinuria + hypertension eclampsia convulsive seizures (brain ischemia) - coma DIC - ischemic changes in liver, kidneys, heart, brain, placenta treatment – induction of delivery

84 Tumors of placenta – gestational trophoblastic disease
from trophoblast increased levels β-hCG (dg. + monitoring) hydatidiform mole invasive mole choriocarcinoma “placental site“ trophoblastic tumor intermediate trophoblast, 15% aggressive

85 Hydatidiform mole hydropic change of chorionic villi of all (complete mole) partial (partial mole) placental tissues complete mole (1-2 / 2,000 pregnancies, < 20 a > 40 Y) G: bunch-of-grapes from translucent cystic structures, fetus absence Mi: massive edema of avascular chorionic villi + diffuse hyperplasia of trophoblast without atypia cytogenetics: 46, XX (XY) of spermatozoan origin (empty egg) partial mole Mi: edema and proliferation of some of villi, fetus presence cytogenetics: triploid 69, XXY (fertilization by 2 sperms)

86 Hydatidiform mole clinically therapy – curettage + monitoring
abnormal uterine enlargement pathologic bleeding wiht mole pieces in 16th-17th week,  hCG therapy – curettage + monitoring 80-90% benign, 10% in invasive mole, 2-3% in choriocarcinoma (partial mole)

87 Invasive mole locally aggressive - trophoblast growth into myometrium, vessels, perforation of uterus x NO metastasis (spontanneous regression of emboli) Mi: edematous villi + atypically proliferating trophoblast in 10 % progression into choriocarcinoma

88 Choriocarcinoma highly malignant tumor from trophoblast
1 / 30,000 pregnancies (SE Asia – 1 / 2,000) 50% complete mole, 25% partial mole after delivery / abortus G: soft, hemorrhagic, necrotic mass Mi: highly atypical trophoblast (NO villi) early metastases (lungs, vagina, brain, liver) good prognosis – chemosensitive

89 WHO 2015 changes Precursor lesions LGT

90 Cervix precursor lesions
= LG squamous intraepithelial lesion (LSIL) = CIN I, flat condyloma, koilocytosis, atypical koilocytosis, condyloma acuminatum … def.: HPV-positive = HG squamous intraepithelial lesion (HSIL) = CIN II, CIN III, CIS … = adenocarcinoma in situ … HG-CGIN LG-CGIN no longer used

91 Vagina precursor lesions
= LG squamous intraepithelial lesion (LSIL) = VAIN I, flat condyloma, koilocytosis, atypical koilocytosis, condyloma acuminatum … def.: HPV-positive = HG squamous intraepithelial lesion (HSIL) = VAIN II, VAIN III, CIS …

92 Vulva precursor lesions
= LG squamous intraepithelial lesion (LSIL) = u-VIN I, flat condyloma, koilocytosis, atypical koilocytosis, condyloma acuminatum … def.: HPV-positive = HG squamous intraepithelial lesion (HSIL) = u-VIN II, u-VIN III, CIS … = differentiated VIN

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