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

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Presentation on theme: "Pathology of Female Genital Tract Assoc. Professor Jan Laco, MD, PhD."— Presentation transcript:

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

2 Summary 1. Vulva 2. Vagina 3. Cervix of uterus 4. Body of uterus 5. Fallopian tube 6. Ovary 7. 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 – 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 – 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 – 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)

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 – 3-5% of vulvar malignancies Adenocarcinoma Basal cell carcinoma (skin)

14 Summary 1. Vulva 2. Vagina 3. Cervix of uterus 4. Body of uterus 5. Fallopian tube 6. Ovary 7. 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 – rare, mesenchymal (leiomyoma, fibroma) malignant – 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 1. Vulva 2. Vagina 3. Cervix of uterus 4. Body of uterus 5. Fallopian tube 6. Ovary 7. 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) – 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 – 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 1. Vulva 2. Vagina 3. Cervix of uterus 4. Body of uterus 5. Fallopian tube 6. Ovary 7. Diseases of pregnancy

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

33 Inflammations endometrial inflammation (endometritis) – acute 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 – 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 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 1. Vulva 2. Vagina 3. Cervix of uterus 4. Body of uterus 5. Fallopian tube 6. Ovary 7. 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 – % 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 – primary rare (???) – peripheral third of tube – Mi: serous or endometrioid adenoCa – 5-year survival: 20% adenomatoid tumor – see uterus

53 Summary 1. Vulva 2. Vagina 3. Cervix of uterus 4. Body of uterus 5. Fallopian tube 6. Ovary 7. 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 – 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) – 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 – 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 – 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 1. serous (tube) 2. mucinous (endocervix) 3. endometrioid (endometrim) 4. 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 – 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 – association with endometriosis 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 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 – 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 – 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 1. Vulva 2. Vagina 3. Cervix of uterus 4. Body of uterus 5. Fallopian tube 6. Ovary 7. 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, 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 – 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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