Microsoft PowerPoint - 女性生殖系統(藥學系2009.5)OCW

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1 Diseases of Female Genital Tract and Breast 女性生殖系統及乳房疾病朱娟秀醫學系病理學科分機 :

2 學習目標能說明女性生殖系統常見的疾病能說明乳房常見的疾病能說明子宮頸癌子宮內膜癌症卵巢癌及乳癌的危險因子組織分類及臨床表現參考資料 : Pathology for the Health-Related Professions, Ivan Damjanov, Saunders, Co. 3rd. ed. 2006, Chap 15, 16 2

3 Female Genital Tract Overview of Major Diseases Infections: Direct contact with the external world Many infections are venereal in nature Infections are an important cause of infertility Hormonal disorders: abnormal secretion of estrogen and progesterone Benign or malignant tumors Related to sexually transmitted diseases or hormonal influence Screening reduced the mortality of cervical ca. Disorders related to pregnancy 3

4 Inflammatory Diseases Anatomic classification Vulvitis, Vaginitis, Cervicitis, Endometritis, Salpingitis, Oophoritis Pelvic Inflammatory Disease (PID): inflammation of entire female genital tract Pathogenetic classification: ascending, hematogenous Chronologic classification: acute, chronic or recurrent Etiologic classification Bacteria: Neisseria gonorrhoeae (gonorrhea) Treponema pallidium (syphilis) Virus: HPV: Condyloma acuminatum HSV Chlamydia Fungus: Candida albicans (DM, pregnancy) Protozoal: Trichomonas vaginalis 4

5 Pelvic Inflammatory Disease Salpingo-oophoritis Tuboovarian abscess Pyosalpinx Hydrosalpinx Complications: peritonitis, bacteremia, infertility 5

6 Hormonally Induced Lesions Endometrial hyperplasia abnormal vaginal bleeding 長期 estrogen 刺激 : 無排卵週期, 停經, 肥胖, 長期服用分類 : Simple hyperplasia (cystic, mild hyperplasia) Complex hyperplasia (adenomatous hyperplasia) Atypical hyperplasia Simple hyperplasia with no atypia 6

7 Neoplasia and related disorders Carcinoma of the Cervix Carcinoma of the Vulva Carcinoma of the Vagina Tumors of the Uterus Endometrial Carcinoma Leiomyoma Endometriosis Tumors and tumorlike conditions of the ovary Ovary cysts Ovarian Neoplasms 7

8 Cervix 8

9 Risk Factors of Cervical Carcinoma Early age at first intercourse Multiple sexual partners Presence of cancer associated HPV Persistent detection of high risk HPV HPV low-risk: 6,11, 42, 44 high-risk: 16,18, 31,33 9

10 Intraepithelial Squamous Neoplasia of the Cervix Classification Dysplasia/CIS system: mild, moderate, severe dysplasia, carcinoma in situ CIN system: CIN I, CIN II, CIN III Bethesda system (NCI, 1988):)squamous intraepithelial lesion (SIL) low-grade SIL: condyloma, CIN I high-grade SIL: CIN II, CIN III 10

11 Squamous Cell Carcinoma of the Cervix 40~50 y/o Adenocarcinoma:10~15%; HPV-16,18; 可與 CIN 並存 11

12 Staging of Cervical Cancer Stage 0: CIS Stage I: Confined to uterus Stage II: Extend beyond the uterus but not onto pelvic wall. Carcinoma involves the vagina but not lower 1/3. Stage III: Extend onto pelvic wall or lower 1/3 of vagina Stage IV: Extend beyond true pelvis or involved mucosa of bladder or rectum 12

13 Carcinoma of the VulvaV Older women 85% squamous cell carcinoma 15% adenocarcinoma Preceded by carcinoma in situ and by preneoplastic lesion (vulvar intraepithelial neoplasia, VIN) 13

14 Carcinoma of the Vagina Older women Squamous Cell Carcinoma, preceded by vaginal intraepithelial neoplasia (VAIN) 14

15 Tumors of the Uterus Endometrial Carcinoma 55~65 y/o 危險因子 : 肥胖, 糖尿病, 不孕, 高血壓 Symptom: vaginal bleeding Diagnosis: Endometrial biopsy, diagnostic D & C 組織分類 : endometrioid carcinoma: > 75% serous, clear cell, squamous, mixed carcinoma 15

16 Staging of Endometrial Carcinoma I: confined to the corpus II: involved in the corpus & the cervix III: extend outside the uterus IV: extend outside true pelvis or involved mucosa of bladder or rectum 16

17 Tumors of the Myometrium Leiomyoma 25%, 生育期婦女最常見良性腫瘤成因未明分類 : Intramural Submucosal Subserosal Symptom: depend on size and location, mass effect, bleeding 17

18 Leiomyoma 18

19 Endometriosis Definition: presence of endometrial glands or stroma in locations outside the uterus Locations: ovary (chocolate cyst), uterine ligament, pelvic peritoneum, op scar, umbilicus, etc. S/S: dysmenorrhea, pelvic pain infertility(30~40%) 19

20 Potential Origins of Endometriosis Regurgitation Metaplastic Vascular or lymphatic dissemination Intraoperative implantation 20

21 Adenomyosis 肌層腺體症 Presence of endometrial glands or stroma in myometrium 21

22 Ovary 22

23 Ovary cysts Follicular cyst and luteal cyst Polycystic Ovarian Disease (Stein-Leventhal Syndrome) 年輕女性, 肥胖 (40%) 多毛症 (50%), 無排卵週期, 不孕 23

24 Tumors of Ovary Benign: 80%, 20~45 yrs Malignant: 20%, 40~65 yrs, high mortality S/S: abdominal pain, abdominal distension, ascites, GI and GU discomfort Peritoneal seeding (0.1~0.5 cm. nodules) CA-125: 80% serous & endometrioid ca. Risk factors: nulliparity, family history (BRCA1 gene) Cystadenoma; cystadenocarcinoma 24

25 Tumors of Surface Epithelium Incidence: 65 70% of ovarian tumors Micro: Benign, Borderline malignant, Malignant Classification: Serous tumors (53%) Mucinous tumors (31%) Endometrioid tumors (6%) Others 25

26 Tumors of Surface Epithelium Benign Outer surface Malignant Borderline 26

27 Teratoma Mature Teratoma 發生於生育年齡期含三胚層構造俱成熟性分化大部分是囊狀又稱 dermoid cyst Immature Teratoma 含 immature tissue < 20 y/o 生長快速, 會轉移 27

28 Dysgerminoma = seminoma of testis 75% 10~30 y/o most common in malignant germ cell tumor (1/2) Endodermal Sinus Tumor (Yolk Sac Tumor) 小孩及年輕婦女 α-fetoprotein (α- FP) 生長快速, 相當具侵襲性 28

29 Sex Cord-Stromal Tumors Granulosa Cell Tumor 2/3 postmenopause, estrogen effect Malignant potential (5~25%) Prognosis: good, 10 yrs survival rate: 85% 29

30 Metastatic Tumors Krukenberg s tumor: GI tract, bilateral, mucin-producing signet-ring cells 30

31 Gestational and Placental Disorders Pathology of fertilization Pathology of implantation Pathology of placentation Abortion Gestational trophoblastic disease Toxemia of pregnancy 31

32 Pathology of Fertilization Ovum-related factors: older women Sperm-related factors: azoospermia, oligospermia Genital organ factors: PID Systemic factors: immune mechanism, etc. 32

33 Pathology of Implantation Ectopic Pregnancy 1/150 fallopian tube (90%) ovary abdominal cavity Causes: PID, IUD.peritubal adhesion, normal (50%) S/S: severe abdominal pain Diagnosis: HCG, U/S, laparoscopy, endometrial Bx 33

34 Pathology of Placentation Placental anomalies size, shape Placental accreta: Absence of the decidua with adherence of the placenta directly to the myometrium Placenta previa: Implantation in the lower segment of the uterus 34

35 Abortion Interruption of pregnancy prior to the term of fetal viability (500gm or 20wks) Spontaneous or Induced 35

36 Gestational Trophoblastic Diseases Hydatidiform Mole 1/2000 pregnancy Complete mole: 46, XX, paternal origin Incomplete mole: oocytes fertilized with two spermatozoa, 69 陰道出血, HCG, 超音波 2.5% choriocarcinoma 36

37 Choriocarcinoma - Malignant tumor composed of cytotrophoblasts & syncytiotrophoblasts 50% hydatidiform mole 25% abortion 25% normal pregnancy HCG Bulky hemorrhagic nodules Invades the vein Metastasizes to lung, brain, liver Responds well to chemotherapy 37

38 Toxemia of Pregnancy Preeclampsia: hypertension, proteinuria, edema Eclampsia: more severe, convulsion, coma 初產婦較常見妊娠第三期, 但有高血壓, 腎臟病, hydatidiform mole 較早發生治療 : 輕度 : 臥床休息, 飲食, 抗高血壓藥嚴重 : 誘導分娩 38

39 Diseases of the Breast 乳房疾病 39

40 The Breast Overview of major disease Tumors: cancer is the most important disease affecting the breast Hormonally induced diseases Inflammatory diseases 40

41 Histology of the Breast 41

42 Inflammations Acute mastitis Lactating period, staphylococcus aureus, streptococcus Breast abscess Chronic inflammation 42

common change, hormone imbalance Three dominant

43 Hormonally induced changes Pubertal change: juvenile hyperplasia of the breast Fibrocystic changes Most common change, hormone imbalance Three dominant patterns of morphologic changes: Cyst, Fibrosis, Adenosis 43

5~2X Atypical hyperplasia: 5X Clinical significance

44 Epithelial Hyperplasia Mild hyperplasia: no increased risk Moderate and florid hyperplasia: 1.5~2X Atypical hyperplasia: 5X Clinical significance Elevate the risk of developing carcinoma Differentiation from carcinoma 44

45 Fibroadenoma Most common benign tumor Occurring at any age within the reproductive period, mainly in young women (<30 y/o) Well circumscribed Cut surface Outer surface 45

46 Risk Factors of Breast Cancer Age Age at Menarche Pregnancy: first fullterm pregnancy First degree relatives with breast cancer Proliferative breast disease Race Exogenous estrogens Radiation exposure Ca. of contralateral breast or endometrium Geographic factors Diet Obesity Cigarette smoking 46

47 Clinical Presentation of Breast Carcinoma Breast mass discovered by palpation Tumor discovered by mammography Pain (mastodynia) or painful breast mass Nipple retraction, eczematoid reaction, or discharge Distant metastases 47

48 Classification of Breast Carcinoma Carcinoma in situ Ductal Carcinoma In Situ (DCIS, Intraductal carcinoma) Lobular Carcinoma In Situ (LCIS) Invasive Invasive (infiltrating) ductal carcinoma: 80% Invasive lobular carcinoma Others 48

49 Paget's disease of the nipple Rare manifestation of breast cancer 49

50 Invasive ductal Carcinoma Usually firm to hard in consistency, irregular border 50

51 Prognostic and Predictive Factors 1. Invasive carcinoma or in situ disease 2. Distant metastases 3. Axillary LN status 4. Tumor size 5. ER & PR 6. Histologic type 51

52 Pathology of Male Breast Gynecomastia: Unilateral or bilateral Causes: indicator of hyperestrinism Liver cirrhosis Functioning testicular tumor Carcinoma 52

53 Summary (I) Cervical cancer is one of the common cancer in women. Nearly all cervical cancer is HPV-related. Endometriosis refers to location of endometrial glands and stroma outside the uterus. It occurs commonly in the ovary. Adenomyosis refers to growth of endometrium into the myometrium. Endometrial carcinoma is associated with estrogen excess and endometrial hyperplasia. 53

54 Summary (II) The most common benign tumor of female genital tract is leiomyoma. The neoplasms of ovary may be of epithelial, germ cell and sex-cord stromal origin. Fibroadenoma is the most common benign tumor of the breast. The prognosis of breast cancer is related to the stage, histological type, estrogen receptor status, etc. 54

子宫颈癌（Carcimoma of Cervix uteri）

子宫颈癌（Carcimoma of Cervix uteri） Carcimoma of Cervix uteri Carcimoma of Cervix uteri 13.15 13.15 1/3 40 Etiology Etiology 18 18 20 Centain infection with virus 1 transformation zone 2. Development of cervical carcer I mild (grade I) 1/3