Female genital tract V. Žampachová I. ÚP LF MU Inborn defects nComplicated embryogenesis, different original tissues (mesoderm → gonads; n paramesonephros → müllerian ducts → ovarian tubes, uterus, upper part of vagina n urogenital sinus → lover part of vagina, vestibulum n mesothelium → ovarian surface, tubal epithelium, endometrium FLORA of the REPRODUCTIVE SYSTEM nLactobacillus, Streptococcus, Corynebacterium, Mycobacterium. nCandida albicans nThe flora occupies the external genitalia. Internal reproductive structures normally remain sterile. n Genital tract infections nGenital tract – open to the outside, barriers necessary nBarrier function - vaginal flora, endocervical mucus nPredisposing factors – nonexistent barrier (age), barrier defect (loss of protective vaginal flora, menstruation, abortion, delivery + residua, instrumentation and other mucosal microtraumata, systemic diseases, drugs,…) n n Genital tract infections nAscending infection most usual (STD, G- fecal bacteria – E. coli, Proteus,…) nLower genital tract (STD – HSV, molluscum contagiosum, HPV, trichomonas, chancroid, granuloma inguinale; endogenous – candida) nEntire genital tract (STD – gonorrhea, chlamydia, mycoplasma, syphilis; endogenous – enteric bacteria), may end in PID n n gyn-inf-prehl01 gyn-PID-sch02 Robbin‘s Pathologic Basis of Diseaseobbin ind270 Acute endometritis and salpingoophoritis Sexually Transmitted Infections nSexually Transmitted Disease – STD/STI nInfection transmitted through vaginal, anal or oral sex nEvery sexually active individual is at risk nWomen acquire infections from men more than men from women n2/3 of STD occur in people under 25 yrs of age nInfection by multiple agents common (↑ risk) nFetus or infants – vertical transplacental or perinatal transmission of STD → abortus, inborn defects, neonatal infection. Diagnosis + treatment!! STI n ascending inf.: endometritis, salpingitis,PID n ↑ nsexual partner → horizontal transmission → STI n ↓ n vertical transmission: placenta (fetus, neonate) STD nViruses: HSV, HPV, HIV, hepatitis B, C nChlamydiae: Ch. trachomatis nMycoplasmas: M. urealyticum (urethritis) nBacteria: Neisseria gonorrhoeae, Treponema pallidum, Haemophilus ducreyi (chancroid), Klebsiella granulomatis (granuloma inguinale) nProtozoa: Trichomonas vaginalis (urethritis, balanitis, vaginitis) Genital herpes nAbout a week after exposure, painful red, fluid-filled blisters in the genital area (vagina, labia, cervix, penis, anus) nBlisters filled with clear fluid containing the virus, highly contagious nRupture → ulcers may last up to 6 weeks nThe first outbreak - the first episode infection nSubsequent episodes (recurrent infections) usually less severe Genital herpes nLatency period, no symptoms, the virus may be shed, patient infectious nThe virus dormant in nerve fibers in the spinal cord in between outbreaks nIn active stage, mostly in primoinfection → high risk of the newborn infection during delivery → haemorrhagic herpetic encephalitis Genital herpes nProdromal symptoms: burning, itching, tingling or throbbing nPain may radiate to the legs, thighs, groin or buttocks; patient may be more infectious during the prodromal period nRecurrent infections- herpetic lesions reappear, general malaise, headache, fever, dysuria, urinary retention, vaginal/urethral discharge may occur n ind260 HSV Genital warts nCondyloma accuminatum - HPV nMost HPV infections asymptomatic or unrecognized nMostly found in young, sexually active; associated with early onset of sexual activity, multiple sexual partners nTransmitted by all types of sexual contact nUsually cleared from host‘s organism nVaccination (already ↓ in low risk types manifestations – LSIL) Condyloma accuminatum Papilomatous architecture Genital warts nMay be asymptomatic; single or multiple painless cauliflower-like growths on the vulva, vagina, perineum, urethra, cervix, anus nProductive infection – low risk types (6, 11) nOther subtypes of HPV (i.e. 16, 18) strongly associated with cervical dysplasia and/or carcinoma nHPV - higher risk of vaginal, vulvar, penile, anal dysplasia/carcinoma nSome types in oral/laryngeal carcinoma Genital warts: complications nPossible urethral obstruction or destruction of normal tissue nCan be transferred to fetus during pregnancy or delivery nLarge warts may obstruct the birth canal; cesarean section may be necessary nInfants infected may develop a chronic respiratory condition – laryngeal papillomatosis Chlamydia: manifestations nIn females often asymptomatic until uterus and tubes infected; may present with dysuria, urinary frequency, vaginal discharge n(1/3 of males may be asymptomatic; dysuria, urethral discharge, testicular pain) nPatient infectious even if asymptomatic Chlamydia: complications nMay result in PID (pelvic inflammatory disease) nMajor cause of infertility, ectopic pregnancy in women; may cause stillbirth or spontaneous abortion (miscarriage) n(In males may result in epididymitis, prostatitis, sterility, Reiter’s syndrome) nIn neonates may cause blindness, pneumonia Gonorrhea n‘clap’; one of the most common STDs (second only to Chlamydia) nCaused by Neisseria gonorrhoeae; incubation period is 2-8 days nTransmitted by sexual contact, during passage through the birth canal nUsually targets the cervix, (male urethra) Gonorrhea nFemale: mostly asymptomatic until advanced disease; dysuria, urinary frequency or abnormal vaginal discharge n(Male: dysuria, serous, milky or purulent urethral discharge; regional lymphadenopathy) nComplications: (prostatitis, epididymitis, sterility); n PID, endometritis, salpingitis, peritonitis; n in neonates gonorrhea can infect the eyes, nose or anorectal region inf140 Purulent salpingitis - gonorrhea Syphilis nSpirochete Treponema pallidum nTransmitted from open lesions during sexual contact nOrganism can survive days in fluids nMay also be transmitted by infected blood, body fluids, including saliva nAverage incubation is 20-30 days nSpreads through blood, lymphatic system nCongenital syphilis - transplacental Syphilis: primary stage nChancre: painless ulcer in the site of innoculation; regional lymphadenopathy nchancre appears 3-4 weeks after infectious contact, disappears within 4-6 weeks nChancre may go unnoticed in women nHighly infectious during primary stage even if no symptoms are present nMicro: nonspecific, high amount of plasma cells in inflammatory infiltrate n n . Syphilis – primary 20-03 ind220 Syphilitic chancre – plasma cells in infiltrate Syphilis: secondary stage nSymptoms of secondary syphilis appear any time from 2 weeks to 6 months after initial chancre disappears, in 75% of untreated people nPrimary generalisation, flu-like symptoms, sore throat; generalized lymphadenopathy nSkin rash (especially on palms of hands and soles of feet) maculopapular, pustular; ncondylomata lata - mucus patches + erosions in oral cavity; flat, broad-based wart-like papules on labia, anus or corner of mouth, highly infectious; secondary alopecia nDisappears within 2-6 weeks Syphilis - secondary Condylomata lata SecSyphilisRash Syphilitic rash Syphilis nsecondary stage – early generalisation ind240 Syphilis: secondary stage in HIV+ n Chancroid (Soft chancre) n nHemophilus ducreyi nMostly tropical and subtropical areas nHIV co-transmission nFour to seven days after infection: tender, erythematous papule → irregular ulcer n More painful in males; not indurated; multiple; on external genitalia n Inguinal lymph nodes are enlarged and tender (buboes) nMicro: nonspecific ulcer, superficial zone of neutrophilic debris and fibrin, underlying zone of granulation tissue, lymphoplasmacytic infiltrate n n n n n n n n E. nGranuloma inguinale (Donovanosis) nKlebsiella granulomatis (Calymmatobacterium donovani) ntropical and subtropical areas nGross: papular lesion ( on genitalia) → ulcer nUlcer : protuberant, soft, painless mass; borders raised and indurated; abundant granulation tissue; mimicking carcinoma (pseudoepitheliomatous hyperplasia) nMicro: silver stains (e.g., the Warthin-Starry stain): encapsulated coccobacilli (Donovan bodies) in macrophages nlymph nodes typically spared (unlike chanchroid) nComplications: extensive scarring + lymphatic obstruction, possible lymphedema (elephantiasis) nScars in untreated cases → urethral, vulvar, or anal strictures n n n n n n n n n E. n Pathology of ovaries nPathological lesions: morphological, functional, commonly both nSigns: commonly late, nonspecific (menstruation cycle and/or fertility disturbances, pelvic pain, abdominal distention) → late diagnosis Pathology of ovaries nInborn defects: commonly a part of complex chromosomal disturbances (X0 Turner syndrome, gonadal dysgenesis), intrauterine infections, … nInflammation: usually chronic, part of nonspecific pelvic inflammatory disease nCysts: common, variable causes nTumors: variable origin, commonly cystic form Chronic inflammation n„tuboovarian abscess“ – mixture of chronic abscesses, proliferation of granulation and fibrotic tissue, multiple adhesions, stenoses nFecal bacteria, str., staph., actinomycetes nPelvic pain, fever in acute exacerbation, may → peritonitis, sepsis nRisk of infertility, GEU n n W7233-39-66 gbp360 PID - torsion Actinomycosis – sulphur granules Ovarian cysts nnon-neoplastic – inclusion c. (mesothelial, epithelial) n functional c. (follicular, luteal, polycystic ovary syndrome, ovarian hyperstimulation syndrome) n endometriosis nneoplastic (epithelial tumors, germ cell tu, sex-cord stromal tu, metastatic tu, etc.) Follicle cyst Thin walled, contains clear fluid, diameter ≥ 2 cm Micro: enlarged non-ruptured follicle, longer duration Hyperestrinism possible copy Image084 Ovarian follicle < 20 mm Polycystic ovarian disease Complex etiology, stopped normal follicular maturation, enlarged ovaries with smooth surface, multiple thin-walled cysts Profound hormonal + metabolic (insulin)disturbances Infertility (amenorrhea), obesity, hirsutism copy Corpus luteum cyst Yellow convoluted wall, smooth lining, may contain bloody fluid Not regressed corpus luteum, typical cells with foamy cytoplasm Corpus luteum cyst ov-corplut-mi03 Endometriosis nfoci of functional endometrium (glands + stroma) in an ectopic localisation novaria, cavum Douglasi, fallopian tubes, peritoneum, bladder, umbilical skin, … lung, bones …) ncyclical changes during MC nhaemorrhagic (chocolate) cysts, hemosiderin pigmentation npain, pelvic inflammatory disease + adhesions, infertility npossible source of endometrioid adenocarcinoma n10 % of women of reproductive age n n nadenomyosis: nendometrial diverticula (outpouching of basalis into myometrium, mostly no functional hormonal changes) gbp450 Endometriosis – „chocolate cyst“ ov-endometriosa-ma02 Endometriosis in appendix Endometriosis – decidual change Ovarian tumors ov-tu-sch01 Ovarian tumors nEpithelial tumors nmost common, 70 % nadults nGerm cell tumors n15-20 % nchildren, adults nSex cord-stromal tumors n5-10 %, any age nMetastasis n5 %, variable Classification/nomenclature 1.Epithelial tumors nEpithelial type nSerous nMucinous, endocervical-like and intestinal type nSeromucinous nEndometrioid nClear cell tumors nBrenner tumors nOthers Classification/nomenclature nEpithelial tumors nBiologic potential nBenign (commonly in form of cystadenoma) nBorderline (Low malignant potential) – moderate atypias, mitotic activity, architectonic changes (multilayering, irregular papillary budding), non-invasive peritoneal implants possible nMalignant n Epithelial tumors Form of growth nCystic nPapillary incl. inverted nSolid nIncreased amount of stroma, (adenofibroma) Classification/nomenclature nEpithelial tumors nNames: combination, i. e.: nMucinous cystadenoma nBorderline serous papillary tumor nClear cell carcinoma of ovary n n Classification n2. Sex cord-stromal tumors nPure stromal tumors n Tumors of the thecoma-fibroma group n Steroid (lipid) cell tumors nPure sex-cord tumors n Granulosa cell tumors nMixed sex cord-stromal tumors, n Classification n3. Germ cell tumors nTeratoma nImmature t. nMature (adult) t.: solid; cystic - dermoid cyst; monodermal - struma ovarii, carcinoid nDysgerminoma nYolk sac tumor nEmbryonal carcinoma nChoriocarcinoma (non-gestational) nMixed germ cell tumor n4. Other types (incl. mesenchymal, mesothelial, etc.) n5. Metastatic tumors n Serous cystadenoma nThin-walled multilocular cyst, variable size nClear fluid nLining smooth or papillary, micro ~ tubal epithelium, may be ciliated nPossible non-cystic superficial papillary form on ovary nBorderline tumor may be precursor of low-grade serous carcinoma gbp550 Serous cystadenoma gbp560 Serous cystadenoma Serous borderline tumor gbp580 Serous carcinoma nStromal invasion n2 different types – genetics, histology, prognosis nlow-grade serous carcinoma (ovarian origin) nhigh grade serous carcinoma (from serous tubal intraepithelial carcinoma) nConfluent wide papillae nPossible microcalcifications (psammomata) nCommonly partially solid in HG ca nGrowth into surrounding tissues nMetastatic spread in abdominal cavity nOral contraception has protective effect nRisk factors: smoking, obesity, genetics (BRCA) gbp530 serous carcinoma gbp540 Serous carcinoma – stromal invasion gbp510 Malignant cell clusters in ascites Mucinous cystadenoma nlarge cysts with a smooth outer surface nusually multilocular ncontain clear mucous material nMicro: tall mucin-secreting columnar cells, mostly endocervical type, may be intestinal type nComplications: huge size, abdominal distention, possible torsion, cyst rupture. gbp590 Mucinous cystadenoma Mucinous cystadenoma ov-mucin Mucinous borderline tumor ov-tu-max-ma01 Mucinous cystic borderline tumor Mucinous carcinoma nCommonly partially solid nMetastatic spread into abdominal cavity possible ndiff. dg. x „pseudomyxoma peritonei“, organisation of mucinous material → adhesions, fibrosis, stenosis, tumor origin usually in appendix nDiff. dg. x other mucinous carcinomas (GIT) Endometrioid tumors ncommonly malignant nhistologically mostly identical with endometrial adenocarcinomas (!diff. dg. primary x metastatic, in ¼ may be concurrent primary ca in endometrium and ovary) nmostly arises from foci of pre-existing ovarian endometriosis Endometrioid carcinoma Clear cell tumors nAlmost always malignant nComplex papillary and tubular pattern intermingled with sheets of highly atypical clear cells n diff. dg. x other clear cell tumors (renal, vaginal) n Clear cell crcinoma Brenner tumors nusually small, solid and benign nMicro: rounded islands of transitional-type epithelium embedded in a dense fibrous stroma. n Malignant forms rare. n Brenner tumor Germ cell tumors ndysgerminoma novarian counterpart of seminoma, rare, girls + young f. nembryonal carcinoma nsimilar to testis, rare, younger age nyolk sac tumor nsimilar to testis, younger age, 20 % of germ cell tu nchoriocarcinoma nsimilar to testis, nongestational, very uncommon nteratoma most common, nusually mature – benign: dermoid cyst, nimmature – malignant n malignisation in a mature teratoma n, ov-germtu-sch03 Dysgerminoma Embryonal carcinoma gbp5100 Dermoid cyst – mature cystic teratoma ov-dermcyst-mi01 Dermoid cyst – mature cystic teratoma Struma ovarii n Struma ovarii nIHC thyreoglobulin Sex cord-stromal tumors nGranulosa cell tumors nin adults potentially malignant, possible estrogen production – precocious puberty, risk of abnormal uterine bleeding, endometrial hyperplasia or ca nThecoma-fibroma nmost common, usually benign, possible association with ascites, rarely estrogen production nSertoli-Leydig cell tumors npossible masculinisation gbp5130 Granulosa cell tumor gbp5140 Granulosa cell tumor ov-fibrth-ma02 Ovarian fibroma – white-yellowish, solid, firm Ovarian fibroma Thecoma - solid, lobulated, yellow (lipid containing cells), estrogenic activity common; usually benign Metastatic tumors nGIT (stomach, colorectal, commonly mucinous adenocarcinoma) nbreast n! synchronnous primary endometrial ca + primary endometroid ovarian ca ov-kruk-celkma03 Krukenberg tumor, bilateral ovarian metastasis of GIT mucinous adenocarcinoma ov-kruk-ma01 Krukenberg tumor Fallopian tubes diseases nInflammation (risk of infertility or GEU) nCysts (paratubal) nTumors nserous adenofibroma, papilloma – benign nserous tubal intraepithelial carcinoma (STIC) n1 % of normal population n5-10 % in high risk (BRCA carriers), prophylactic surgery nsource of high grade serous ovarian ca nGEU (ectopic pregnancy) inf130 Acute salpingitis + tuboovarian abscess Acute salpingitis salpingitischr-ma03 Chronic salpingitis hydrosalp-ma01 Hydrosalpinx Tubal GEU – chorionic villi Pathology of uterine corpus ncongenital anomalies ninflammation nfunctional endometrial disorders npolyps (endometrial etc.) nadenomyosis nendometrial hyperplasia ntumors Clinical signs nDisordered puberty (praecox, tarda) nSterility, infertility (incl. repeated abortions) nClimacteric disorders n nAbnormal bleeding nPain (localization, type) nAbdominal distention nSystemic signs n Clinical signs nAbnormal bleeding: nAmenorrhea: no bleeding nOligomenorrhea: cycle > 35 d. nPolymenorrhea: cycle < 21 d. nHypomenorrhea: regular cycle , ↓ bleeding nMenorrhagia: regular cycle, ↑ bleeding nMetrorrhagia: irregular bleeding outside of the cycle, incl. prepuberty and postmenopause nMenometrorrhagia Abnormal bleeding nNewborn: maternal estrogen nChildhood: trauma!!, infection, tumor nAdolescence: hormonal imbalance, incl. anovulatory cycle, psychogenic/nutritional problems nFertile age: anovulatory cycle, pathologic pregnancy, hormonal imbalance/response, inflammation, polyp, neoplasia nPost/menopause: hyperplasia, polyp, neoplasia; atrophy n n n Inborn defects nTemporary uterine septum → if persistent, uterus didelphys, uterus bicornis. nMüllerian ducts atresia → complete aplasia of uterus etc. n W7233-37-01 Uterus bicornis – persistence of temporary embryonal septum W7233-37-03 Uterus didelphys ut-unicorn-ma02 Uterus unicornis with rudimentary horn Acute nonspecif. endometritis nmixed pyogenic flora (endogenous) Clostridium welchii; STD – Neisseria gonorrheae, Chlamydia trachomatis, mycoplasma – commonly into chronicity nsigns - fluor, metrorrhagia, local pain, systemic signs, sepsis possible (puerpueral) ngross – hyperemia, petechiae, endometrial ulcerations; gangrena nmicro – mixed inflammatory infiltrate in intersticium and glands, abscess, necrosis, thrombosis, haemorrhagia n n Acute nonspecif. endometritis nac. complications: ac. myometritis, parametritis (→ pelvic veins thrombosis), salpingitis (→ peritonitis), sepsis nchron. complications: chron. endometritis (→ irregular bleeding, infertility; plasma cells in infiltrate, stromal changes, irreg. glands) n tubal stenosis, adhesions (→ infertility, GEU); pelvic inflammatory disease (local + systemic symptoms) Acute endometritis, intraglandular neutrophils Disorders of menstruation cycle nPsychogenic – sec. amenorrhea, psychogenic sterility nHypothalamic nPituitary – idiopatic, sec. (infl., tumors,…) nGonadal nUterine nMetabolic – endocrine (thyr., adrenals), hepatic nNutritional ut-cyklus-sch03 Functional endometrial changes nDysfunctional bleeding – no organic lesions (inflammation, polyp, hyperplasia, tumor); no exogenous hormones nappearance of endometrium doesn‘t correspond to the cycle day (clinical data!) ncommonly focal stromal and glandular breakdown Estrogen-associated nirregular proliferation nanovulatory cycle – estrogenic stimulation (proliferation) without progestins, may progress to hyperplasia novulation bleeding – hormonal drop, edema, stromal breakdown n Irregular proliferation Ovulation endometrium subnuclear vacuoles, stromal edema + bleeding Progestin-associated nluteal insufficiency – insufficient secretory transformation nirregular shedding – irreg. response on hormone level drop nhypersecretion, Arias-Stella phenomenon – ↑ progestins + stimulation; clear cells, reactive atypias n Disordered early secretion - ovulation Irregular secretory endometrium Hypersecretion Iatrogenic endometrial changes nexogenous hormones – contraception: variable appearance, combination → inactive to atrophic endometrium, progestins → stromogland. dissociation etc. nhormonal substitution therapy: without HYE, combination prep. (risk of hyperplasia, ca) nIUD long-standing: inflammation(focal. ac., chron. – actinomycetes), ulceration, irreg. endometrium, metaplasia, thrombosis ntamoxifen: endom. polyps, hyperplasia, ca nsurgery, radiotherapy Stromoglandular dissociation stromogl-disoc-200 Epithelial changes - eosinophilic C:\Dokumentace\Dokumenty\Obrázky\edu-mikro\endom eos transf HE200.jpg Polyps nEndometrial polyp nPolypoid hyperplasia nHyperplasia and polyps in tamoxifenem ther. nPolypoid tumors – adenomyoma, carcinoma, submucosal leiomyoma, stromal tumors, etc. nPathological pregnancy (trofoblastic lesions, decidua etc.) nPseudotumors – pathol. material accumulation etc. Endometrial polyp nPossible iatrogenic origin (tamoxiphen) nup to ¼ women during fertile life ncommon in climacterium ndysfunctional bleeding npossible cause of infertility npossible start/localisation of endometrial ca n Endometrial polyp korp-polyp-hyperpl-40-k Endometrial polyp korp-polyp-cyst-40-k Endometrial ca in a polyp Adenomyosis nirregular bleeding, dysmenorrhea, pelvialgia nmore common in perimenopause after repeated births („diverticulosis“) nmay predispose to uterine prolaps into vagina nmyometrial reaction incl. hyperplasia npossible origo of endometrial tu in myometrium (! x ca invasion into myometrium) gbp490 Adenomyosis Adenomyosis Adenomyosis + leiomyoma adenomyosa-myom-40-k Adenomyosis adenomyosa-sekr-100-k Hyperplasia, intraepithelial neoplasia nNon-physiological non-invasive proliferation of endometrium, benign lesion (reactive) → premalignant condition (monoclonal) nHormone dysbalance - persistent estrog. stimulation without secretory transformation, incl. relative (progestin inssuf.). ~ endometr. ca type 1. nendogenous: path. ovarian regulation, polycystic ovaries, hormon. active processes (tu), obesity with hyperestrinism etc. n exogenous: hormon. therapy (pure estrogens) Hyperplasia, intraepithelial neoplasia nnon-atypical - reactive npresence of atypia - most important pathological sign – monoclonal – endometrioid intraepithelial neoplasia Non-atypical hyperplasia Image058 Endometrial intraepithelial neoplasia n(EIN) atypical hyperplasia > 1 mm, different from surrounding tissue n¼- one third with EIN in biopsy have cancer in hysterectomy (immediately – 1 year) nintraglandular or superficial n Atypical hyperplasia/EIN Atypical hyperplasia/EIN Uterine corpus tumors – WHO nEpithelial tu and related lesions: nEndometrial carcinoma nendometrioid incl. mucinous, nserous, nclear cell, nother endometrial carcinoma, incl. squamous cell, nmetaplastic (carcinosarcoma = malignant mixed müllerian tumor nothers n n n Endometrioid carcinoma nNew classification (WHO 2020) – different genetic characteristics n4 groups with different prognosis nproblematic implementation into do praxis nin ideal case integration of microscopic picture and mollecular characteristics (typical mutations, microsatellite instability, etc.) nPOLE-ultramutated endometroid ca, excellent prognosis nmismatch repair-deficient, intermediate risk np53 mutated, bad prognosis nno specific molecular profile, intermediate risk n n Precursor lesions, pseudotumors nEndometrial hyperplasia nwithout hyperplasia n Endometrial atypical hyperplasia / endometrial intraepithelial neoplasia nEndometrial polyps nTamoxifen related lesions n Uterine corpus tumors – WHO nMesenchymal tumors: nendometrial stromal lesions: n endom. stromal nodule (benign), low grade endom. stromal sarcoma, undifferentiated endom. stromal sarcoma nsmooth muscle tumors: leiomyoma (+ variants), tu of uncertain malignant potential, leiomyosarcoma (+ variants) ntumors from perivascular epitheloid cells (PECom) nother mesenchymal tumors Uterine corpus tumors – WHO nMixed epithelial and mesenchymal tumors: adenomyoma, adenosarcoma etc. nGestational trophoblastic disease nOther tumors: adenomatoid tumor (mesothelial), … nSecondary tumors Endometrial carcinoma nSigns: abnormal bleeding – menometroragia in pre- and perimenopause, metrorrhagia in postmenopause; n uncommonly accidental finding n rarely - generalisation nGross: exophytic, ulcerated, whitish n Endometrial carcinoma gbp420 Endometrial carcinoma n ntype 1 – cca 80%, estrogen-dependent, commonly in complex atyp. hyperplasia, endometroid type, low grade, 55-65 yrs, better prognosis n risk factors –↑ estrogenous stimulation (obesity, diabetes, hypertension, infertility incl. nulliparity, long fertile age, horm. active tu, horm. substitution) Endometrial endometrioid carcinoma endom-ca-400-k Endometrioid ca in adenomyosis Endometrioid ca + leiomyoma Endometrial carcinoma ntype 2 – cca 15-20%, not directly connected with permanent estrogenous stimulation, in later postmenopause, precursor: serous intraepithelial carcinoma, serous and clear-cell types, high grade, p53 mutation, aggressive, worse prognosis nStaging general – according invasion into the uterine wall, cervix, surrounding structures Serous adenocarcinoma Metaplastic carcinoma müll-carsar100-k Mesenchymal tumors nendometrial stromal lesions: cells similar to stroma in prolif. endometrium nendom. stromal nodulus: demarcated, benign nlow grade endom. stromal sarcoma (LG ESS): well differ., invasion into surrounding myometrium and vessels, slow growth, usually good prognosis nundifferentited endom. stromal sarcoma (HG ESS): aggressive with dissemination, highly atypical cells, high MI n copy Stromal nodule n LG ESS Leiomyoma nenlarging focus in pelvic region npain, irregular bleeding npossible infertility npressure on surrounding organs (ureters, bladder) nin pregnancy ↑ risk of abortion, possible barrier of normal delivery ut-myomy-sch02 Image074 Leiomyomas Leiomyoma myom-100-k Leiomyoma – regressive changes n Leiomyosarcoma nrare, de novo from myometrium nmostly in age of 40-60 nrecurrence common, haematogenous meta (lungs, bones, brain), abdominal dissemination nsolitary, rose-grey, soft, haemorrhagia, necrosis nmicro – variable differentiacion W7233-37-72 Leiomyosarcoma Leiomyosarcoma leiomyosa-400-k Breast ca metastasis camammy-meta-endom Pathology of the cervix ncervicitis npolyps nphysiological epithelial changes – metaplasia, nprecursor lesions: n squamous intraepithelial lesion (low grade, high grade – LSIL, HSIL = dysplasia /cervical intraepithelial neoplasia(CIN) nHPV-associated nHPV-independent nglandular: adenocarcinoma in situ ncarcinoma (invasive epithelial tumor) nother tumors Image060 Endocervical polyp cerv-polyp-metapl-mi01 Endocervical polyp with squamous metaplasia Cervical intraepithelial neoplasia nflat HPV condyloma (without dysplasia) nmild dysplasia (CIN I) nmoderate dysplasia (CIN II) nsevere dysplasia (CIN IIIa) ncarcinoma in situ (CIS, CIN IIIb) n nNew classification: nLow grade squamous intraepithelial lesion (LSIL): condyloma + CIN I nHigh grade SIL (HSIL): CIN II + CIN III n cerv-HPV-koilocyt-mi02 HPV – koilocytosis - LSIL cerv-HPV-imuno03 HPV – p16 immunohistochemistry Image068 HSIL gbp350 Invasive squamous cell carcinoma cerv-adenoskv-mi01 Adenosquamous carcinoma – alcian blue staining W7233-36-87 Cervical squamous cell carcinoma gbp340 cerv-ca-ma02 Image070 Cervical squamous cell carcinoma Vaginal pathology ninflammation npolyps, cysts nvaginal squamous intraepithelial neoplasia (VaIN) nvaginal adenosis (glands) ntumors n Vaginal tumors and pseudotumors nfibroepithelial polyps, glandular cysts nHPV lesions concurrent with cervical/vulvar ncondyloma accuminatum, vaginal intraepithelial neoplasia (VaIN I-III) → squamous carcinoma nHPV independent squamous cell carcinoma nglandular tumors n n nembryonal rhabdomyosarcoma (sarcoma botryoides) ngross – soft polypoid tumor protruding into vaginal lumen ngirls <5 years n n Embryonal rhabdomyosarcoma Rhabdomyoblasts (arrows) Vulvar pathology ninflammatory disorders (infectious, noninfectious) ncysts nvulvar intraepithelial neoplasia (VIN) nHPV-independent nsquamous intraepithelial lesion nHPV-associated nLSIL, HSIL ntumors Non-neoplastic epithelial disorders ngross appearance of leukoplakia – white plaque nmostly in peri-, postmenopausal women ninflammatory dermatoses (psoriasis, chronic dermatitis), pre- malignant lesions (VIN, ca), disorders of unknown etiology n nLichen sclerosus nepithelial atrophy + hyperkeratosis nsuperficial dermis – band of oedema + hyalinisation nperivascular mononuclear inflammatory cell infiltrate n → → stenosis of vaginal orifice (craurosis vulvae) n nLichen simplex chronicus – squamous cell hyperplasia nepithelial hyperplasia + marked hyperkeratosis nnot a precancerosis n Lichen sclerosus Vulvar neoplasia ncondyloma accuminatum nlow-risk HPV (6, 11) nsquamous cell papilloma with koilocytar epithelial transformation n nvulvar intraepithelial neoplasia – VIN; LSIL/HSIL n ncarcinoma nsquamous ca (90 %) HPV-associated, HPV-independent nadenocarcinoma, basal cell carcinoma n nmalignant melanoma W7233-35-53 Extensive HPV condylomatosis vulv-ca-ma02 Vulvar squamous carcinoma