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  • Each month the uterus goes through a cyclical change, first building up its endometrium or inner lining to receive a fertilized egg, then, if conception does not occur, shedding the unused tissue through the vagina in the monthly process called menstruation

    2. 2. Objectives Introduction of FGT Clinical manifestations of FGT pathology Pathology of Valva Pathology of Vagina Pathology of Cervix Pathology of Myometrium Pathology of Endometrium Pathology of Fallopian tube Pathology of Ovary Pathology Gestational and placental disorders
    3. 3. Female Reproductive System-The female reproductive system consists of-The ovaries-Secondary sex organs - which are involved in coitus,fertilization & development, birth & nursing of thebaby.-
    4. 4. Major Organs of FGT Vulva Vagina Cervix Uterus Uterine tubes [ fallopian tubes] Ovaries ( The gonads )
    5. 5. DISEASES OF F.G.T. INCLUDE:-Diseases of the vulva-Diseases of the vagina-Diseases of the cervix-Diseases of the Body of Uterus And Endometrium-Diseases of the Fallopian tubes-Diseases of the Ovaries-Gestational and Placental disorders
    6. 6. Pathological basis of signs & symptoms in the FGTSign or symptom Pathological basis-Vaginal discharge Inflammation-Vaginal bleeding In pregnancy Hemorrhage from placenta (placenta (praevia), placental bed (miscarriage) or decidua (ectopic pregnancy) Post-coital Hemorrhage from cervical lesion (carcinoma, erosion) Post-menopausal Hemorrhage from uterine
    7. 7. -Abnormal menstruation Psychological disturbance (timing or volume of loss) Hormonal dysfunction Defect in local haemostasis Uterine lesions (Fibroid,polyp, IUD)-Pain Pathologic distension/rupture (tubal ectopic pregnancy),Muscular spasm (uterine),Ischemia or infarction (ovarian torsion), menstrual pain due to adenomyosis, functional etc-Abdominal distension Ascites (Ovarian tumors involving peritoneum), uterine enlargement (pregnancy), ovarian cyst.
    8. 8. ABNORMAL UTERINE BLEEDING: The most common gynecologic problem in women during active reproductive life- Polymenorrhea: cycles shorter than 3 weeks- Oligomenorrhea: cycles longer than 6-7 weeks- Metrorrhagia: intermenstrual bleeding (MC organic )- Hypermenorrhea: excessive flow (MC organic )- Menorrhea: prolonged duration of flow- Menorrhagia: increase amount & duration of flow- Menometrorrhagia: prolonged flow with irregular intermittent spotting ( organic)
    9. 9. Causes of abnormal uterine bleeding according to age groupAge group CausesPre-puberty Precocious puberty ( hypothalamic, pituitary, or ovarian origin)Adolescence Anovulatory cycles , coagulation disordersReproductive age - Complications of pregnancy ( abortion, ectopic pregnancy, trophoblastic diseases) - Organic lesions ( leiomyomas, adenomyosis, polyps, endometrial hyperplasia , carcinomas) - Anovulatory cycles -Ovarian dysfunctional bleeding (i.e. inadequate luteal phase)Perimenopausal -Anovulatory cycles - Irregular sheddingPostmenopausal -Organiclesions ( carcinoma, hyperplasia, polyps) - Endometrial atrophy
    10. 10. DYSFUNCTIONAL UTERINE BLEEDING (FUNCTIONAL ENDOMETRIAL DISORDERS):Definition: It is abnormal bleeding in absence of organic uterine lesions. MCC is anovulatory cycles (hyperestrogenic states). It is due to:- Endocrine disorders - : pituitary, adrenal, and thyroid diseases.- Ovarian disorders - : polycystic ovaries, hormone secreting tumors.- Metabolic causes - : obesity, malnutrition,..- Unexplained causes - : (?? Cryptogenic).Morphology: - Premenstrual endometrial biopsy shows a persistent proliferation pattern with variable degree of hyperplasia, cystic glandular change -Sporadic endometrial breakdown & bleeding ( estrogen effect unopposedby progesterone).
    11. 11. Diseases of Vulva
    12. 12.  Inflammatory lesion of Valva Non neoplastic disorders Tumours of Valva
    13. 13.  Inflammatory lesions of the Vulva: All skin disorders can be seen Herpes virus infection: STD, HSV type 2, Painful ulceration in the skin. Intraepithelial blisters & viral inclusion & eosinophilic swelling of epithelial cells Syphilis: Primary syphilis - : Chancer - indurated lesion with central ulceration & LN – heals even without Tt. Secondary syphilis: Condyloma latum (inflammed hyperplasia of epithelium with underlying chronic inflammation rich in plasma cells & end arteritis obliterans), Silver stain demonstrates the spirochetes.
    14. 14. Genital Herpes
    15. 15. Primary syphilis: Chancer
    16. 16. Granuloma inguinale (Donovanosis):STD affecting the genitalia, inguinal & perianal region ,gram negative bacilli (Calymmatobacterium donovani) -Chronic valvular papule/nodule/ ulceration, tropical areas,can spread to other parts of FGT, ulcer margins showepithelial hyperplasia & Ulcer bed filled with neutrophilabscesses. Sliver stain demonstrates bacilli withinmacrophages (Donovan bodies)
    17. 17. Lymphgranuloma venereum:STD, Chlamydia trachomatis, tropical areas, vesicles thatrupture and form punched out painless ulcer, secondaryinfection, abundant granulation tissue, fibrosis, fistula,lymphatic obstruction (chronic form of the disease),necrotizing granuloma may occur
    18. 18. Candidiasis :Chronic irritation & inflammation, white thickdischarge, DM, may be associated with vaginitisDiagnosis: ME of skin scrapping or culture,nonspecific histological picture, fungi can bedemonstrated within the keratin layer orsuperficial epithelium by sliver stainBartholin’sAbscessCyst:inflammatory occlusion of the main duct of Bartholin’svulvo-vaginal gland, most common cause is gonorrheaVulvodynia (vestibular adenitis) : inflammation of theminor vestibular glands (unkown cause) causing verypainful ulceration. Treatment is often surgical.
    19. 19. Infection involving the lower and the upper genital tract (Pelvic inflammatory disease =PID)Definition: an ascending infection thatbegins in he vulva & spreads upward toinvolve the entire genital tract.
    20. 20. Causes:1- Sexually transmitted disease (STD):gonococcal (MC) or chlamydial infection:acute suppurative inflammation confinedto mucosa and submucosa (spread viamucosa).2- Postabortal or postpartal; caused bystaphylococci, streptococci, E. coli &clostridium perfringens. Spread is throughuterine wall leading to affection of serosaand peritoneum.
    21. 21.  Morphology: acute suppurative inflammation of the Bartholin’s glands, periuretheral glands, endocervical glands & fallopian tubes. Pathological lesions & complications: Acute salpingitis, salpingo-oophoritis, tubo-ovarian abscess, pyosalpinyx (distention of the fallopian tube with pus). It may cause peritonitis, septicemia, fibrous adhesion (intestinal obstruction), tubal occlusion & infertility or ectopic pregnancy.
    22. 22. *Non-neoplastic epithelial disorders(Vulvar Dystrophy- old name):Benign (non-dysplastic) mucosal alterations of the vulva; ofunknown etiology predominantly in peri & postmenopausalperiodsTypes: Two types that may coexist:G)Lichen Sclerosus et AtrophicusH)Lichen Simplex Chronicus
    23. 23. • Lichen Sclerosus et Atrophicus: gray, parchment-like areas, of thin atrophic epithelium + sube-pithelial fibrosis+ mononuclear peri-vascular reaction & occasionally marked hyperkeratosis.B) Lichen Simplex Chronicus (Squamous Hyperplasia = Hyperplastic Dystrophy):- It is the physiologic outcome to rubbing the vulva mucosa in response to pruritis .- PP causes: irritant exposure, dermatitis, pre-invasive or invasive neoplasm (biopsy is indicated)- Morphology: white plaques (leukoplakia) of thick hyperplastic & hyperkeratotic epithelium (without dysplasia) and leukocytic dermal inflammation..
    24. 24. N.B.: Neitherlichen sclerosusnor simplexchronicus isclassified aspremalignant perse, butcytogeneticabnormalities,including P53mutations, mayprecede the onsetof atypia in theselesions. Thus,they areconsidered “ RiskFactors” forvulvar neoplasia
    25. 25. TUMORS OF THE VULVA Benign tumors ♦ Condyloma Accuminatum: ♦ Papillary Hidradenoma ♦ Vulvar Intraepithelial Neoplasia (VIN= Vulvar Dysplasia) Malignant tumors ♦ Verrucous Carcinoma ♦ Invasive vulvar Squamous cell carcinoma ♦ Extramammary Paget’s Disease
    26. 26. Condyloma Accuminatum: multiple, benign, wart-like verrucousSTD, caused by HPV types 6&11. (vulva, perineum, vagina, rarelycervix). It is squamous cell papilloma with markedacanthosis,hyperkeratosis & parakeratosis, some showing cells withcytoplasmic clearing and nuclear atypia (i.e. koilocytic atypia =koilocytosis indicating viral infection).
    27. 27. Papillary Hidradenoma: benign, well circumscribed nodule of modified apocrine sweat gland. It is composed of tubular structures lined by both epithelial(columner) & myoepithelial cells.
    28. 28.  Vulvar Intraepithelial Neoplasia (VIN= Vulvar Dysplasia):- A premalignant intramucosal squamous neoplasm that frequently precedes invasive carcinoma occurs 4th – 5th decades.- Mucosal lesions with cellular anaplasia and marked nuclear atypia, caused by HPV type 16. Synonyms: VIN III= carcinoma in situ (CIS)= Bowen’s disease. Tends to progress to invasive carcinoma ( in old & immunosuppressed patients).-
    29. 29.  Differentiate (simplex) VINs are usually HPV-negative, associated with Lichen sclerosus or Lichen simplex chronicus. These precancers usually arise after menopause and leading to well differentiated keratinized squamous cell carcinoma in the 6th – 8th decade.
    30. 30. N.B. HPV - E6 protein of HPV type 16 & 18 can bind to P53 gene leading to P53 inactivation - E7 protein of HPV 16 & 18 binds to Rb gene products Leading to promotion of neoplastic growth through: 1- deregulation of cell cycle 2- Production of genomic instability 3- Increase telomerase expression -Types 6 & 11 of HPV with no or low risk of malignancy do not form a complex with P53 & typically give rise tobenign condylomas
    31. 31. Invasive vulvar Squamous cell carcinoma: mayarise de novo or on top of VIN. Spreads to inguinal LNs & isof poor prognosis. The prognosis depends on size, depth ofinvasion, and lymph nodes statusVerrucous Carcinoma: A rare locally aggressive neoplasm.Usually does not metastasize.,
    32. 32.  Extramammary Paget’s Disease: - An eczyma-like, red crusted sharply demarcated map-like areas ( on labia majora), characterized by large anaplastic tumor cells, lying singly or in small groups within the epidermis. The cytoplasm of the tumor cells is clear, and mucin positive.- Unlike Paget’s disease of the breast, the presence of underlying adenocarcinoma of the vulva is uncommon. Other rare tumors: Basal cell carcinoma, Malignant melanoma
    33. 33. DISEASES OF VAGINA1- Vginitis2- Tumors of vagina
    34. 34. 1-Vaginitis & vulvovaginitisSince both vulva and vagina are anatomically close to each other, often inflammation of one affects the other.Common infections – Bacterial - streptococci,staphalococci, E.coli, H. vaginalis Protozoal - Trichomonas vaginalis Viral - Herpes simplex Fungal – Candida albicans The most common causes of vaginitis are Candida albicans ( monaliasis) and Trichomonas ( Trichomonaliasis )
    35. 35. TUMORS OF THE VAGINA Benign tumors ♦ uncommon Malignant tumors ♦ squamous cell carcinoma ♦ Clear cell adenocarcinoma ♦ Embryonal rhabdomyosarcoma
    36. 36. Carcinoma: primary carcinoma of the vagina is rare, but 1-2%women with cervical squamous cell carcinoma develop aconcomitant squamous cell carcinoma in the vagina. Age: 60-70yrs. Morphology; plaque-like, fungating /ulcerative lesion thatinfiltrates cervix, urethera, bladder or rectum.Clear cell adenocarcinoma: is rare (MC in young women, whosemothers had received Diethylstilbestrol (DES) during pregnacy for treatment ofthreatened abortion). The tumor cells are vacuolated and contained glycogen.
    37. 37.  Embryonal rhabdomyosarcoma: uncommon, a highly malignant tumor of infants and children; polypoid bulky mass (Botryoid= grape-like) protruding from vagina. That is why also known as Sarcoma Botroides
    38. 38. Histopathology It is composed of rounded malignant (embryonal) rhabdomyoblasts, some tumor cells have a “tennis- racket” shape with striated cytoplastmic extension. Tumor cells are +ve for desmin & myosin immunostain. These cells are characterstically lying underneath the vaginal epithelium, called CAMBIUM LAYER The central core of polypoid masses composed of loose and myxoid stroma with many inflammatory cella
    39. 39. Embryonal Rhabdomyosarcoma- vagina
    40. 40. DISEASES OF THE CERVIX Inflammation of Cervix: Cervicitis Cervical Tumors
    41. 41.  Inflammation of Cervix: Cervicitis- May be acute or chronic; specific or non-specific- Non-specific: Strept., Staph., enterococci, E. coli- Specific (STD): gonococci, Chlamydia, Mycoplasma, Trichomonas, Candida….- Acute cervicitis: - rare (postpartal and nonspecific) - Neutrophilic infiltration beneath the lining mucosa
    42. 42. Chronic cervicitis: - More common Bacterial growth & alteration in pH - May be specific, non-specific or of unknown cause -- ----- - Common cause of leukorrhoea Predisposing factors – sexual intercourse, trauma of child birth, instrumentation and excess or deficiency of estrogen.
    43. 43. Morphology: Gross- eversion of ectocervix with hyperemea, edema and granular surface.Nabothian(retention cysts) may be grossly visible as pearly grey vesicles. Histopathology - squamous metaplasia, chronic inflammatory cells, columnar cell proliferation (micro- glandular change), reactive epithelial atypia (mistaken for CIN), and Nabothian cysts (due to occlusion of cervical gland ducts ) & squamous metaplasia
    44. 44. Normal epithelium of cervix & Chr. Cervicitis
    45. 45. Cervical Tumors Benign tumors ♦ Endocervical polyp ♦ Cervical intraepithelial neoplasia (CIN) Malignant tumors ♦ Invasive cervical carcinoma ♦ Adeno-squamous & Endocervical type Adenocarcinama
    46. 46. Cervical Tumors•Endocervical polyp: benign tumors composed of C.T. stromashowing dilated endocervical glands and lined by endocervicalepithelium•Squamous intraepithelial lesions (SIL)CERVICAL INTRAEPITHELIAL NEOPLASIA(CIN)-It is caused by a sexually transmitted disease; 2nd – 3rd decades ,caused by cancer-related (high risk) HPV type16,18,31,33,35,39,51,52,53,56,58,59.- It usually precedes invasive squamous cell carcinoma (4th – 5th decades)
    47. 47. - Risk factors: early age of first intercourse, multiple sex partners & high-risk male sex partners; that suggests a sexually transmitted oncogenic agent from male to female at an early age. HPV acts as a promotor, and herpes virus type II , tobacco, constitution , environment & others may be cofactors.
    48. 48.  Morpholgy: CIN I = dysplasia in the deeper 1/3rd of the epithelium & preserved maturation in the upper 2/3rd. CIN II = dysplasia in the deeper 2/3rd & less maturation. CIN III = dysplasia in all layers & no maturation i.e carcinoma in situ (CIS)
    49. 49. Normal Cervical lining & CIN I, II & III
    50. 50. Bethesda system : a new classification for CIN (National CancerInstitute) for reporting cervical & vaginal cytology.Besthesda HPV Morphology CIN Dysplasiasystem type-Low grade SIL 6,11 Koilocytic atypia, flat CIN I Mild(L-SIL) – condyloma-High grade SIL Progressive cellular 16,18 CIN II Moderate,(H-SIL) atypia , loss of & CIN severe, maturation III carcinoma in situ N.B.: The oncoproteins (E6 &E7) of high-risk HPVs deregulate the cell cycle, produce genomic instability, and increase telomerase expression. All these molecular events promote neoplastic cell growth. The low risk HPVs (HPV 6,11) do not possess these properties and typically give rise to benign condyloma. L-SIL –Low grade – Sq. Intraepithelial Lesion
    51. 51. INVASIVE CERVICAL CARCINOMA:-Up to 70% of CIN III (CIS) progress to invasive carcinoma.-Gross: fungating, ulcerative or infiltrative lesions-Histology: most cases are squamous cell carcinoma of varying degreeof differentiation (65% = large cell non-keratinizing, 25% large cellkeratinizing, 10% small cell poorly differentiated sq.c.c.)-Other non-squamous carcinomas (adenocarcinoma, adenosquamous,neuroendocrine=small cell undifferentiated) are less common andstrongly associated with HPV type 18.
    52. 52. Adeno-squamous & Endocervical type Adenocarcinama - Cervix
    53. 53.  Clinical staging:- Stage 0: CIS Stage I: confined to the cervix- Stage II: extending beyond the cervix but not into- the pelvic wall; into vagina but not to- lower 1/3 of vagina- Stage III: reaching the pelvic wall or lower 1/3 of- vagina- Stage IV: spreading out side the pelvis Prognosis: depends on stage ( 100% cure for stage 0 & 10% of stage IV).
    55. 55. ENDOMETRITIS: Acute endometritis: Histological : Neutrophilic infiltration of the endometrium, caused by Staph., Strept., …; following abortion, delivery or instrumentation. Chronic endometritis: Clinically : Abnormal endometrial bleeding Histological : Mononuclear (plasma cell & macrophages infiltration of the endometrium. Etiology : in chronic PID, tuberculous, in user of IUDs, actinomycosis and due to retained gestational tissue.
    56. 56. ADENOMYOSIS & ENDOMETRIOSIS:Adenomyosis : Defined as presence of nests of benignendometrial glands & stroma within the myometrium, deep in thewall of the uterus. It leads to uterine enlargement & irregularthickening of the uterine wall.-Possible cause – metaplasia or oestrogenic stimulation due toendocrine dysfunction of ovary-Clinically- menorrhagia, colicky dismenorrheoa and menstrualpain in the sacral or sacrococcycygeal regions.- Critaria for diagnosis – The minimum distance between theendometrial islands within the myometrium and the basalendometrium should be one low power microscopic field (2-3mm ).
    57. 57. Adenomyosis
    58. 58. Endometriosis:- Presence of nests of endometrial glands & or stroma outside the uterus in ovaries, fallopian tubes, pelvic peritoneum, uterine ligaments, and rarely in vulva, vagina, laparotomy scar, umbilicus, and appendix.- Ectopic endometrium may undergo cyclic menstrual changes and periodic bleeding. - Clinically: dysmenorrhea, dyspareunia , pelvic pain & infertility. - Diagnosis depends on the presence of 2 out of 3 following features : 1- Endometrial glands , 2-Stroma, and 3- RBCs or hemosiderin pigment.
    59. 59. Theories of endometriosis:- Tubal spread- Lymphatic spread- Hematogenous spread
    60. 60. ENDOMETRIAL INTRAEPITHELIAL NEOPLASIA = EIN( ENDOMETRIAL HYPERPLASIA )Definition: It is abnormal proliferation of endometrialglands.The most common cause of dysfunctional uterinebleeding (DUB) & is associated withhyperestrogenemia.
    61. 61. Types:1- Simple hyperplasia= cystic hyperplasia, mild hyperplasia: Cystic dilated glands, non-neoplastic, due to anovulatory cycles.2- Complex hyperplasia= adenomatous hyperplasia: Overcrowded, closely opposed glands. Some of these are neoplastic (contain PTEN (Phosphatase and tensin homolog ) mutations & considered as EIN). PTEN- tumor suppressor gene3-Atypical hyperplasia = complex / adenomatous hyperplasia with atypia: Overcrowded glands with cytological atypia. Most cases of this category are neoplastic (EIN) and many contain PTEN mutations
    62. 62. N.B.: Endometrial hyperplasia:- It is an important cause ofabnormal uterine bleeding.- A subset (EIN) is considered arisk factor for endometrialcarcinoma.-The risk of carcinoma increasesas function of the degree ofatypia.- Both endometrial hyperplasiaand adenocarcinoma areassociated withhyperestrogenism, microsatelliteinstability, and mutation of PTENgene.
    63. 63. Simple (cystic)glandular hyperplasiaComplex (adenomtous) hyperplasia without atypiaComplex (adenomatous) hyerplasia withatypia
    64. 64. TUMORS OF THE ENDOMETRIUM Benign tumors ♦ Endometrial polyp  Malignant tumors ♦ Endometrial carcinoma ♦ Papillary serous adenocarcinoma ♦ ENDOMETRIAL STROMAL SRCOMA (MALIGNANT MIXED MESODERMAL=MULLERIAN TUMOR)
    65. 65. TUMORS OF THE ENDOMETRIUMEndometrial polyp:- Sessile tumors composed of endometrial glands and stroma.- May be associated with hyperestrogenism or Tamoxifen therapy.- Usually benign, but may show foci of hyperplasia or cancer.
    66. 66. Endometrial carcinoma:- 7% of all invasive carcinomas in women- Most common invasive cancer of the female genital tract.Epidemiologic & pathophysiologic types:1- Endometrial adenocarcinoma: Common,55-65 yrs. Old.- Risk factors: Obesity, nulliparity, early menarche & late menopause, granulosa cell tumor of the ovary, breast cancer, diabetes, hypertension,infertility&unopposed estrogen..-
    67. 67.  Gross: Fungating polypoid or infiltrating mass (diffuse involving the entire endometrial surface).- Histopathology: Adenocarcinoma usually well differentiated with often associated with metaplastic changes ( squamous, secretory or mucinous differentiation). Other histological forms: adenosquamous or clear cell adenocarcinoma.- Containing mutations in PTEN gene, microsatellite instability, often pre-exciting EIN.
    68. 68. 2) Papillary serous adenocarcinoma: - Associated with older age , - Often arising in endometrial polyps or endometrial surface epithelium, and - Associated with multiple P53 mutations.-Spread: invades the myometrium, and spread by lymphatics & blood (MC to the lung). Serous tumors can spread quickly, even when non-invasive
    69. 69. - Prognosis: depends on extend of spread (stage).Excellent prognosis when the carcinoma is confinedto corpus uteri itself. However papillary serous tumorspreads quickly even when non-invasive.Biologically: more aggressive neoplasms are poorlydifferentiated carcinomas including clear cell &papillary serous carcinoma.Clinically Abnormal uterine bleeding
    70. 70. ENDOMETRIAL STROMAL SRCOMA ( MALIGNANT MIXEDMESODERMAL = MULLERIAN TUMOR ): TUMORS WITHSTROMAL DIFFERENTIATION-Rare tumors. Highly malignant. Derived from primitive stromal cells(mullerian mesoderm origin). Consists of glandular (carcinomatous) &stromal (sarcomatous) elements. The stromal elements may showmuscle, cartilage or osteoid differentiation.--Gross: bulky polypoid tumor protruding into endometrial cavity andvagina.
    71. 71. - Other variants of endometrial stromal tumors: 1)Benign stromal nodules: discrete nodules of stromal neoplasm within the myometrium. 2)Endometrial stromal sarcoma (Endolymphatic stromal myosis): well & poorly differentiated stromal neoplasm, may penetrate into lymphatic channels. 3)High-grade sarcoma not otherwise specified: high grade unclassified tumor capable of widespread metastases. Occurs in postmenopausal females; presents with uterine bleeding. Overall 5- years survival is 25%.
    72. 72. TUMORS OF THE MYOMETRIUM Benign tumors ♦ Leiomyoma Malignant tumors ♦ Leiomyosarcoma
    73. 73. Leiomyoma:-Benign smooth muscle tumor, MC overall tumor of females inthe active reproductive age, related to increased estrogenstimulation, and associated with a number of specific cytogeneticabnormalities.- Sharply circumscribed, round gray-white firm nodules, located - 1-within the myometrium (intramural), 2-beneath the serosa (subserous) 3-beneath the endometrium (submucous).
    74. 74.  It may undergo cystic degeneration and calcification.- May be asymptomatic or associated with abnormal uterine bleeding, pain, urinary disorders. - Malignant transformation is exceptionally rare (? almost none).
    75. 75. LEIOMYOSARCOMA -:- Uncommon, most arise de novo and not from leiomyomas. - Bulky, fleshy, infiltrative mass in the uterine wall-Disseminate in the peritoneal cavity & widely by blood stream.- Overall 5-years survival is 40%
    76. 76. Histologically distinguished from leiomyomas by: 1- More than 10 mitotic figures/ 10 H.P.F. ( with or without cellular atypia), or 2- Between 5-10 mitotic figures with cellular atypia.N.B.: Smooth muscle tumor of uncertain malignant potential: A subset of smooth muscle tumors displays some but not all of the features of malignancy
    78. 78. 1-INFLAMMATORY - SALPINGITIS:Suppurative salpingitis:-Infection by pyogenic organisms: streptococci, staphylococci,& gonococci (PID)-May cause tubo-ovarian abscesses, pyosalpinx, peritonitis &“violin string” adhesion that may cause intestinal obstruction.Tuberculous salpingitis:-Hematogenous dissimination from other foci . May beassociated with T.B. of endometrium & peritoneum.Histologically: caseating granulomas with giant cells.-May cause infertility, or ectopic pregnancy
    79. 79. TUMORS OF FALLOPIAN TUBE Benign tumors ♦ Uncommon Malignant tumors ♦ Adenocarcinoma
    80. 80. 2- TUMORS OF FALLOPIAN TUBE-- Rare. Most common is adenocarcinoma (like serous adenocarcinoma of the ovary).- Recently, adenocarcinoma of the fallopian tubes has been associated with BRCAI & BRCA 2 mutations?.- Many arise in the fimbriated portion of the tube.
    82. 82. OVARY Anatomy Manifestations of ovarian diseases Inflammatory - Oophritis Non-Neoplastic Ovarian Cysts Ovarian Tumors Classification of ovarian tumors Pathology of individual tumors
    83. 83. Normal Structure
    84. 84. Embryological developmentPrecursor Ovarian component Other female genital tract structures1.Coelomic epithelium Surface epithelium 1.Fallopian tubes( ciliated2. Ectopic endometrial columnar serous cells)epithelium—Mullerian 2.Endometrial lining(nonEpithelium ciliated columnar cells) 3. Endocervical glands (mucinous non ciliated)1.Yolk Sac Germ cells(toti potent)1. Sex cords Stroma of the ovary Endocrine apparatus of post natal ovary.
    85. 85. Importance of embryological development1.Primary Ovarian tumours are classified on thebasis of their site of origin.2.Still some tumours do not fall in any of thecategories and are put into Malignant (NotOtherwise Specified)3.A third category of neoplasms of the ovary areMetastatic tumours from non ovarian primaries.
    86. 86. OVARIAN DISEASESManifestations of ovarian diseases: - Pelvic pain - Menstrual irregularities ( abnormal pattern of ovarian hormone secretion). - Infertility; failure of ovulation (Stein-Leventhal). - Ovarian mass : either non-neoplastic (cysts) or neoplastic (cystic or solid).
    87. 87.  INFLAMMATORY - OOPHORITIS: - Inflammation of the ovaries is always secondary to salpingitis or peritonitis. - If chronic & bilateral leading to extensive fibrosis & infertility.
    88. 88.  NON-NEOPLASTIC OVARIAN CYSTS 1- Follicular and Luteal cysts: Common, 1-8 cm in diameter. They are lined by follicular (granulosa) cells or luteinized cells. Asymptomatic, but may rupture, causing peritoneal reaction & pain. 2 - Chocolate cysts: Blood-filled cysts, due to endometriosis of the ovaries.
    89. 89. 3 – Polycystic ovarian ( Stein - Leventhalsyndrome (PCOD) -: It is important cause of infertility. There is excessive productionof androgens, increase conversion of androgens to estrogen,insulin resistance, and inappropriate gonadotrophin production bythe pituitary.Morphology: Ovaries are large, white, many subcortical follicularcysts(0.5-1 cm.) in diameter, and covered by thickened fibrosedouter tunica. No corpora lutea (= no ovulation). Manifestations: Young females with Oligomenorrhea, infertility,obesity & hirsuitism.
    91. 91. OVARIAN TUMORS- Common forms of neoplasia in women.- 80-90% of ovarian tumors are benign.- Most ovarian tumors occur between 20-45 years.- Ovarian cancer is second MC malignancy of the female genital tract (after endometrial cancer).- Most ovarian tumors are derived from surface epithelium, and “CA-125” is the tumor marker for surface epithelial tumors of the ovary.- Malignant ovarian tumors present at a late stage, thus are associated with high mortality rate.- Known risk factors are nulliparity, family history, and specific inherited mutations (BRCAI & BRCAII) genes.
    92. 92. Tumour types-- a basic classificationSite of origin Types Frequency Age groupSurface epithelial 1.Serous 60%-70% 20 years and greatertumours 2.Mucinous 3.Endometroid 4.Clear cell 5.BrennerGerm cell 1.Teratoma 15%-20% 0 to 25 years and 2.Dysgerminoma greater 3.Endodermal Sinus(Yolk Sac Tumour) 4.ChoriocarcinomaSex cord stromal 1.Granulosa Theca cell tumours 5%-10% All agestumours 2.Sertoli-Leydig cell tumours 3.GynandroblastomaMiscellaneous 1.Lipid cell tumour Variable variable 2.GonadoblastomaMetastasis Krukenberg tumours 5% variable
    94. 94.  I. Surface mullerian epithelial tumors: (Benign, Borderline, and Malignant) 1-Serous tumors: composed of ciliated columnar (tubal type) epithelium 2- Mucinous tumors: composed of mucus-secreting (cervical canal type) epithelium 3- Endometrioid tumors: composed of glandular (endometrium-like) epithelium. 4- Brenner’s tumors: composed of transitional (urothelium-like) epithelium 5- Clear cell tumors.
    95. 95. II. GERM CELL TUMORS:1- Teratoma2- Dysgerminoma (seminoma ovarii)3- Yolk sac tumor= Endodermal sinus tumor4- Embryonal carcinoma (MC mixed with other types)5- Choriocarcinoma (MC mixed with other types)
    96. 96. III. SEX CORD-STROMAL TUMORS: 1- Granulosa-Theca cell tumor: secrete estrogen 2- Sertoli-Leydig cell tumor: secrete androgens 3- Fibroma: associated with Meig’s syndrome 4- Sex cord stromal tumor with annual tubules 5- Gynandroblastoma 6- Steroid (Lipid)cell tumors
    97. 97. SEROUS TUMORS-The MC cystic neoplasms of the ovary.- Cysts are lined by tall columnar, ciliated epithelial cells (fallopian tubetype) & filled with serous fluid. Types:1-Benign Serous Tumors (Cystadenomas): (60%), smooth lining & no papillary or solid areas. 20% are bilateral.2- Borderline Serous Tumors (low malignant potential): (15%), epithelial atypia, solid areas, but no stromal invasion. 30% arebilateral.3- Malignant Serous Tumors (Cystadenocarcinomas): (25%); multilayered epithelium, solid areas & papillary structuresinvasing the stroma. 65% are bilateral. The prognosis depends on stage, andthe presence of peritoneal implants means poor prognosis.
    98. 98. Diagrammatic representation of aggressiveness
    99. 99. Borderline serous cystadenoma- ovary
    100. 100. MUCINOUS TUMORSLarge cystic masses, huge size, and multiloculated. Cysts filled with stickygelatinous fluid. They either lined by tall columnar mucus-secreting epithelium(intestinal-type mucinous cystomas) or show papillary architectures and focalcilia (mullerian mucinous tumors), which may be associated with endometriosis.Types:1- Benign Mucinous Tumors (cystadenomas): 80%; large cysts with smooth lining & no atypia. 5% are bilateral.2- Borderline Mucinous Tumors (of low malignant potential): 10-15%; cellular atypia, but no stromal invasion.3- Malignant Mucinous Tumors (Cystadenocarcinomas): 5-10%; atypia, solid sheets & stromal invasion. 20% bilateral. Seeding in the peritoneum with malignant deposits causespseudomyxoma peritonei. Usually mucinous cystadenocarcinomas are of intestinal type.
    101. 101. Mucinous Cystadenocarcinoma
    102. 102. Borderline mucinous cystadenoma- ovary
    103. 103. SEROUS TUMOUR MUCINOUS TUMOUR Serous papillary cystic tumor  Mucinous cystic tumor of of borderline malignancy. borderline malignancy, There is extensive, orderly endocervical type. Many cells invagination of the neoplastic have abundant eosinophilic glands, most with intraluminal cytoplasm. papillae, into the stromal component of the neoplasm. The stroma is unaltered in appearance.
    104. 104. SEROUS MUCINOUS TUMOURS TUMOURS Cystadenocarcinomas–  Cystadenocarcinomas– more complex growth pattern, frank complex and solid growth effacement of stroma, usual pattern with atypia and features of malignancy and stratification, loss of glandular extremes of atypia. Concentric architecture and necrosis. calcifications (Psammoma Bodies) may be seen.
    105. 105. ENDOMETROID TUMOURS• 20% of all ovarian tumours.• Majority are carcinomas, if benign forms are present they are cyst adenofibromas.• Distinguished from serous and mucinous tumours by presence of tubular glands bearing close resemblance to benign or malignant endometrial glands.• 30% associated with carcinoma endometrium and 15% with endometriosis whereas 40% involve both ovaries.
    106. 106. ENDOMETRIOD CARCINOMA Gross: presence of both solid  Microscopic: Tubular and cystic areas glands resemble those of typical endometrial adenocarcinoma.
    107. 107. CLEAR CELL TUMOUR These are uncommon and aggressive tumours.Grossly can present in solid and or cystic pattern (figure solid tumour with cysts and necrosis)Microscopically: large epithelial cells with abundant clear cytoplasm.
    108. 108. BRENNER TUMOUR Uncommon adenofibromas Epithelial components– nests of transitional cells resembling urinary bladder. Most are benign,variable size(1cm to 30 cm). Gross—solid or cystic Microscopic – fibrous stroma resembling normal ovarian stroma seperated by sharply demarcated nests of urinary tract, with mucinous glands.
    109. 109. BRENNER TUMOUR Gross:A sharply Microscopically:Nests of demarcated, yellow-white transitional cells, some fibromatous tumor occupies containing cysts, lie in a a portion of the sectioned fibromatous stroma. surface of the ovary.
    110. 110. GERM CELL TUMORS - 15-20% of all ovarian tumors. It arises from totipotent germ cells capable of differentiation into the three germ layers. - Mostly benign cystic teratomas while Other tumours are found principally in children and young adults. - Homologous to germ cell tumours in male testis.
    111. 111. II. GERM CELL TUMORS:1- Teratoma2- Dysgerminoma (seminoma ovarii)3- Yolk sac tumor= Endodermal sinus tumor4- Embryonal carcinoma (MC mixed with other types)5- Choriocarcinoma (MC mixed with other types)
    112. 112. TERATOMAS Mature Monodermal Benign Immature or highlyteratomas Malignant specialized
    113. 113. 1-TERATOMAS1-Mature (Benign) Teratoma: MC germ cell tumors of the ovary, cystic(dermoid cysts), lined by skin & hairs, and filled with sebaceous secretion.There may be mature cartilage, bone (teeth) & other structures. 10-15% arebilateral. < 1% undergo malignant transformation (MC sq.c.c.).2-Immature (Malignant) Teratoma: Rare , solid, bulky, with areas of hemorrhageand necrosis. It contains embryonic elements of he three germ layers. Age:adolescent & young women. Grading is based on the amount of immatureneuroepithelium. It causes wide spread extraovarian metatases depending onthe degree of the immaturity of the including tissues.3- Monodermal (Specialized )Teratomas: differentiate along the line of singletissue. Examples:- Strauma ovarii is MC (mature thyroid tissue) – Carcinoidtumor.
    114. 114. MATURE CYSTIC TERATOMAGROSS: unilocular cysts with hair MICROSCOPIC: cyst wall stratifiedand cheesy material. Thin walled squamous epithelium and underlyinggray white wrinkled epidermis.hair, sebaceous,sweat glands and othertooth and calcification are found adnexa.other structures like thyroidwithin walls. tissue,cartilage bone may be seen.
    116. 116. 2- Dysgerminoma The ovarian counterpart of testicular seminoma. GROSS- Yellowish white to gray pink solid, fleshy tumors, of children & young adults -10% are bilateral. Microscopic picture: sheets of large cells separated by fibrous stroma infiltrated by small lymphocytes - Non-functional, but may be mixed with other germ cell elements that produce hCG- Malignant, but radiosensitive & chemosensitive, with relative good prognosis if treated early.
    117. 117. DYSGERMINOMA GROSS: Small nodules to  Microscopic:large vesicular very large size.Cut surface: cells, clear cytoplasm and well yellow white to gray pink defined boundaries and appearance and are soft centrally placed regular and fleshy. nuclei.cells in sheets or cords seperated by scant fibrous stroma, which has mature lymphocytes.
    118. 118. Dysgerminoma-ovary
    119. 119. 3- Endodermal Sinus Tumor ( Yolk Sac Tumor =Infantile embryonal carcinoma)-It arises from mutlipotent embryonal carcinoma cells differentiatingtowards yolk sac structures.- Affects children & adolescents; grows rapidly & spreads widely, butis radio- & chemosensitive.- Histologically: it shows cystic spaces into which papillary structureswith central blood vessels , the cyst spaces and papillarystructures are lined by immature epithelium giving glomeruloidor “Schiller-Duval” bodies; There are intracellular andextracellular hyaline droplet (characteristic feature). Tumorcells are positive for Alpha-fetoprotein (tumor marker).
    120. 120. Endodermal Sinus Tumour(Yolk Sac Tumour) Schiller Duval Bodies
    121. 121. 4- Choriocarcinoma - It is due to teratogenous development of germ cells. - Most cases exist in combination with other germ cell tumors. - Resembles gestational choriocarcinoma, highly malignant, spreads widely & elaborates hCG (tumor marker). - Microscopic picture: malignat syncitiotrophoblasts & cytotrophoblasts in a hemorrhagic stroma. N.B. Gonadal choriocarcinomas are more resistant to chemotherapy than Gestational choriocarcinomas.
    122. 122. III. SEX CORD-STROMAL TUMORS: 1- Granulosa-Theca cell tumor: secrete estrogen 2- Sertoli-Leydig cell tumor: secrete androgens 3- Fibroma: associated with Meig’s syndrome 4- Sex cord stromal tumor with annual tubules 5- Gynandroblastoma 6- Steroid (Lipid)cell tumors
    123. 123. 1- GRANULOSA - THECA CELL TUMOR- 5% of all ovarian tumors, of peri & post-menopausal women.- Usually unilateral, solid white yellow, consisting of theca cells & granulosa cells, arranged in “Call-Exner” rosettes.- Elaborated large amount of estrogen & may cause precocious sexual development in children, endometrial hyperplasia, cystic changes of the breast or endometrial carcinoma (estrogen effects).- Pure granulosa cell tumors are potentially malignant, clinical malignancy occurs in 5-25% of cases, but they are slowly growing & 10-years survival is above 85%.- Pure Theca cell Tumors - THECOMA
    124. 124. GRANULOSA CELL TUMOUR Gross: small partly solid, partly cystic and mostly unilateral.The neoplasm composed of yellow- white tissue with hemorrhage, some of which is intracystic
    125. 125.  Microscopically: granulosa cell arranged in various patterns like micro,macro follicular, trabecular,bands and sheets.CALL-EXNER BODIES characterstic rosette like structures having central rounded pink mass surrounded by granulosa
    126. 126. THECOMA Pure thecoma are almost always benign. Occur in post menopausal women. Oestrogen dominant tumours– endometrial disorders , carcinoma and cystic disease of breast. If androgen secreting – virilizing effects.
    127. 127. THECOMA Gross: a solid firm mass  Microscopically : spindle upto 10 cm in shaped theca cells along diameter.Section shows. with variable amount of solid, lobulated, yellow hyalinized collagen, tissue. cytoplasm of these cells is vacuolated and lipid laden.
    128. 128. 2- SERTLOI-LEYDIG CELL TUMORS ( Androblastoma=Arrhenoblastoma= Hilus Cell Tumors = Gonadoblastomas).Androgen producing neoplasm (rarely produce estrogen) -Recapitulate the testicular counterpart & produce masculinization or defemenization (Androgen) effeect. -Usually unilateral & benign. -Gross: cut surface is solid and colour gray to golden brown. -Microscopic picture: Tubules lined with Sertoli cells and Leydig cells interspersed in the stroma.3- GYNANDROBLASTOMA: Extremely rare - It consists of a mixture of granulosa/theca & sertoli/ leydig cells.
    129. 129. Sertoli Leydig Cell Tumor-Ovary
    130. 130. 4) FIBROMA Common ovarian tumours. Usually bilateral Harmonally inactive Meig’s syndrome: fibroma with pleural effusion and benign ascites. Gross large firm fibrous usually bi-lateral mass. Microscopic composed of spindle shaped well differentiated fibroblasts and collagen. Fibrothecoma: combination of fibroma and thecoma.
    131. 131. METASTATIC TUMOR - Very common, - The primary tumors is from abdominal and breast tumors. Krukenberg tumorA bilateral metastatic ovarian carcinoma, composed ofmucin-producing signet ring cells, metastasizing fromGIT, mostly from the stomach, it may producepseudomyxoma peritonei like well differentiatedappendicial tumors.
    133. 133. OVARIAN CYSTS Neoplastic cysts Non-neoplastic cysts-Cystadenoma - Follicular & Luteal cysts-- Benign cystic teratoma - Polycystic ovarian disease(Dermoid cyst). (PCOD).-Cystadenocarcinomas - Chocolate (Endometriotic) cyst.
    135. 135. ECTOPIC PREGNANCY : Disorders of earlypregnancyDefinition: implantation of the embryo in any siteother than uterus; Most common- the fallopiantube (> 90%), rarely in ovary or abdominalcavity. Associated with PID & endometriosis; but 50%occur with no known cause.
    136. 136.  May end in: 1- Spontaneous regression with resorption of the products of conception 2- Intratubal hemorhage (hematosalpinx) 3- Tubal abortion or rupture & extrusion into abdominal cavity → intraperitoneal hemorrhage and shock i.e. acute abdomen (medical emergency).- Diagnosis: High hCG, sonography & endometrial biopsy showing decidual reaction but no chorionic villi.
    137. 137. Disorders of late pregnancy1- Placental inflammation or infection: A) Disorder of ascending infection (Chorioamnionitis): - infection of the fetal membrane - Usually ascending from the vagina, in case of premature rupture of the membranes. - Most common cause is group B streptococci. - Acute suppurative inflammation of the chorion & amnion, and acute vasculitis of the umbilical cord (funisitis). B) Hematogenous (transplacental ) infection: - It is derived from maternal septicemia (Listeria, streptococcus & TORCH = Toxoplasma, Rubella, Syphilis, Cytomegalovirus, Herpes) → villous inflammation (villitis) and acute intervillositis.
    138. 138. 2- Toxemia of pregnancy:-Occurs in 6% of pregnancies, in the last trimester & most common inprimiparas.1- Pre-eclaspia = hypertension , proteinuria & edema, headache & visualdisturbances2- Eclampsia = severe pre-eclapsia + convulsions & coma. Associated with widespread endothelial injury & DIC (Desseminated Intravascular Coagulation) affecting kidneys, liver, brain & other organs.- Resembles GVH( Graft Versus Host Reaction , but etiopathogenesis is poorlyunderstood.- Delivery is the only definitive treatment for pre-eclampsia and eclampsia.Pathogenesis of Toxemia of pregnancy: Unclear; - The primary cause may be immune or genetic factors → mechanical or functionalobstruction of the uterine spiral arterioles → placental ischemia → endothelial injury &activation of disseminated intravascular coagulation, leading to decrease in glomerularfiltrate, CNS disturbances, abnormal liver functions, and fibrin thrombi and ischemiain most organs.
    139. 139. THEORIES OT TOXEMIA OF PREGNANCY:1- Inadequate placental implantation → decrease inuteroplacental perfusion and placental ischemia → increaseproduction of vasoconstrictors (e.g. thromboxane ,angiotensin) & decrease of vadodilators(e.g. prostaglandinI2, prostaglandin E2) → arteriolar vasocontriction & hypertension.2- Recently ; Factors imbalance → prematuretermination of placental vascular growth. There isabnormal increase in an anti-angiogenic factor (sflt-1)and reduction in pro-angiogenic factors (Vascularendothelial-derived growth factor= VEGF & placentalgrowth factor =PLGF ).
    140. 140. GESTATIONAL TROPHOBLASTIC DISEASES1- HYADATIDIFORM (VESICULAR) MOLE: defined by- 1- Enlarged edematous and hydropic change of chorionic villi which become vesicular(Cystic swelling). Gross -Grape like 2-Variable trophoblastic proliferation.Two types: - Complete (diploid) & - Partial/Incomplete (triploid). - 10% develop into invasive mole, and 2.5% develop intochoriocarcinoma.2- INVASIVE MOLE:- Penetrates the uterine wall, produce hemorrhage but does notmetastasize. - Responds well to chemotherapy.
    141. 141. Feature Complete mole Partial mole-Karyotype -Diploid (46 xxor 46xy), two sperms -Triploid(69 ). Two sperms fertilize an egg fertilize an empty egg. All genetic with normal chromosomes material is paternal -Rarely seen or absent- Fetal parts - Usually present with abnormalities - All villi - Some villi- Villous edema - Diffuse & circumferential - Focal and slight- Trophoblasticproliferation- Atypia -Often present -Abscent-Serum hCG - Elevated - less elevated-hCG in tissue - ++++ - +- Behavior - 2% choriocarcinoma - Rare choriocarcinoma
    142. 142. 3- Choriocarcinoma: - 50% follow hydatidiform mole & 25% follow normal pregnancy, 20% follow abortion & 5% follow ectopic pregnancy. - Highly malignant & metastasize widely.-Gross: Large, soft, yellowish white & fleshy with areas of hemorrhage and necrosis.-Histology: Abnormal proliferation of both cytotrophoblasts & cyncytiotrophoblasts invading the endometrium, bloodvessels, lymphatics, no chorionc villi are seen.- Spread: To lung, bone marrow, liver & other organs.
    143. 143. Clinical features: Vaginal bleeding & discharge in the course of apparently normal prgnancy, after miscarriage, or high hCG titers. N.B.: All gestational trophoblasticdisorders are associated with high level ofhCG (tumor marker).
    144. 144. 4- Placental site trophoblastic Tumor: - A rare tumor composed of proliferatingintermediate trophoblasts (larger than cytotrophoblastsbut mononuclear than cyncytial). - D.D. from choriocarcinoma by the absence ofcytotrophoblastic elements and low level of hCGproduction. - Mostly are locally invasive only, but malignant variants are distinguished by: - A high mitotic index, - Extensive necrosis, and - local spread. - About 10% result in metastases and death.
    145. 145. Thank You