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Pathology of Female Genital Tract

Pathology of Female Genital Tract. Assoc. Professor Jan Laco, MD, PhD. Summary. Vulva Vagina Cervix of uterus Body of uterus Fallopian tube Ovary Diseases of pregnancy. 1. Vulva. Malformations and regressive changes Inflammations Dystrophies Pseudotumors Tumors.

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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 • congenital adrenogenital syndrome (21-hydroxlase) • Senile atrophy • Edema • generalized hydrops • lymphedema – filariosis, lymphogranuloma venereum • Varices • 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/SIL) • 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 of carcinoma development

  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. Dysplasiavulvar 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 (LSIL x HSIL)

  11. 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, M. Bowen = differentiated VIN

  12. 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)

  13. 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

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

  15. Summary • Vulva • Vagina • Cervix of uterus • Body of uterus • Fallopian tube • Ovary • Diseases of pregnancy

  16. Vagina • Malformations / regressive changes • Inflammations • Adenosis • Pseudotumors • Dysplasia • Tumors

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

  18. Inflammations – kolpitis (vaginitis) • + vulvitis + cervicitis • pruritus, discharge (fluor, leukorea) • predisposing factors • hypoestrogenism, DM, pregnancy, loss of normal flora (Lactobacillus Döderleini), alkalisation of vaginal milieu (normal pH  4.5), ATB • colpitis emphysematosa • pregnancy, spontaneously dissappears • dysmicrobia – NO inflammation, abnormal vaginal milieu • bacterial vaginosis – Gardnerella vaginalis

  19. 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)

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

  21. Dysplasia - VaIN • vaginal intraepithelial neoplasia • LSIL x HSIL • often associated with VIN and CIN • the same ethiology and morphology • VaIN more rare

  22. 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 …

  23. 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)

  24. Summary • Vulva • Vagina • Cervix of uterus • Body of uterus • Fallopian tube • Ovary • Diseases of pregnancy

  25. Cervix of uterus • ectocervix (squamous epithelium) • endocervix (columnar epithelium) • squamo-columnar junction • between – transformation zone

  26. Cervix of uterus • Inflammations • Pseudotumors • Dysplasia • Tumors

  27. 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)

  28. 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

  29. 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%

  30. 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

  31. 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

  32. Benign tumors • condyloma acuminatum • mostly on ectocervix • slightly elevated whitish lesions • Mi: see vulva • mesenchymal • mostly leiomyoma – problems during delivery

  33. 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 • usual, mucinous, endometrioid, clear cell • adenoma malignum, villoglandular adenoCa • neuroendocrine carcinoma (small cell) – 5%

  34. Summary • Vulva • Vagina • Cervix of uterus • Body of uterus • Fallopian tube • Ovary • Diseases of pregnancy

  35. Body of uterus • Inflammations • Endometriosis • Dysfunctional endometrium • Endometrial Hyperplasia • Pseudotumors • Tumors

  36. 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)

  37. 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

  38. 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

  39. Uterinebleeding • 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

  40. 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

  41. 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 … atypia = dysplasia • precancerosis – atypical complex hyperplasia 20-25% risk for endometrial adenocarcinoma

  42. 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

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

  44. Endometrial carcinoma • endometrioid • mucinous • serous • clear cell • undifferentiated

  45. Endometrial carcinoma

  46. 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

  47. 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)

  48. 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

  49. 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%

  50. Mixed tumors • carcinosarcoma (MMMT) • postmenopause • extremely aggressive, myometrial invasion, metastases • epithelial c. – poorly diff. endometrioid/serous Ca • mesenchymal c. • fibro-, leiomyo-sarcomatous - homologous mixed tumor – carcinosarcoma • rhabdomyo-, lipo-, chondro-, osteo-sarcomatous - heterologous mixed tumor - MMMT • 5-year survival: 30% • adenosarcoma

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