PATHOLOGY 375 Lecture 11 Female Reproductive System, Breast, and Skin Pathology PDF

PATHOLOGY 375 LECTURE 11:FEMALE REPRODUCTIVE SYSTEM, BREAST AND SKIN PATHOLOGY. Dr. Farhia Kabeer, MD, PhD Post doctoral research Fellow Dept. of Pathology and laboratory medicine Faculty of Medicine, University of British Columbia OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function...

PATHOLOGY 375 LECTURE 11:FEMALE REPRODUCTIVE SYSTEM, BREAST AND SKIN PATHOLOGY. Dr. Farhia Kabeer, MD, PhD Post doctoral research Fellow Dept. of Pathology and laboratory medicine Faculty of Medicine, University of British Columbia OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 2 FEMALE REPRODUCTIVE SYSTEM STRUCTURE AND FUNCTION • Structure: – Vulva (labia majora, labia minora, clitoris, urethral orifice) – Vagina. – Cervix. – Uterus. – Fallopian tubes. – Ovaries. • Function: – Reproduction. – Regulated by hypothalamic-pituitaryovarian axis. https://www.ncbi.nlm.nih.gov/books/NBK66055.2/figure/CDR0000258027__79/?report=objectonly https://connect.springerpub.com/binary/sgrworks/e777798523876718/0bc08ed4e02c8c9a705b12d45e99c90bf63cd8b53168d33eb1ca58d23c4b0ee5/9780826162557_fig10_3.png 3 4 Fig 15-2. Hypothalamus pituitary ovarian axis . Pathology for the Health Professions, 2012 https://viosfertility.com/blog/the-menstrual-cycle/ FEMALE REPRODUCTIVE SYSTEM STRUCTURE AND FUNCTION • Histology: – Stratified squamous mucosa (vulva, vagina, ectocervix). – Glandular epithelium (endocervix, endometrium, fallopian tube). – Germ cells (ovary). 5 DEVELOPMENTAL ABNORMALITIES • • Rare. Examples: – – – Agenesis (failure of all or part of an organ to develop during embryonic growth) of vagina. Agenesis of uterus. Anomalies of uterus. 6 https://www.amboss.com/us/knowledge/Anomalies_of_the_female_genital_tract https://mrkh.com/mrkh-information DEVELOPMENTAL ABNORMALITIES • • Disorder of sexual development (DSD). – Infants born with genitals that do not appear typically male or female or have an appearance discordant with chromosomal sex. – Includes karyotypes that do not result in atypical genital development, such as 45X (Turner) and 47XXY (Klinefelter). Hermaphroditism: – Discordance between genotypic and phenotypic sex. – Historic term, replaced by 3 more specific terms. – True hermaphroditism: • Have both male and female gonads. • One ovary + one testis, or fused ovotestis. – Male pseudohermaphroditism: • Genotypically male, phenotypically female. – Female pseudohermaphroditism: • Genotypically female, phenotypically male. https://commons.wikimedia.org/wiki/File:IAM_363T_-_Hermaphroditus_statue.jpg 7 OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 8 INFECTIOUS DISEASES • • • Pathogenetic classification: • Descending infection (e.g. TB: hematogenous). • Ascending infection: • More common. • Acquired through sexual contact (STD). Anatomic classification: Inflammation of…. Salpingitis Fallopian tubes Endometritis Endometrium Cervicitis Cervix Vaginitis Vagina Vulvitis Vulva Pelvic inflammatory disease (PID)àinfection of upper genital tract structures (uterus, fallopian 9 tubes, ovaries, neighboring pelvic organs). INFECTIOUS DISEASES • Sexually transmitted diseases: – Common (HSV, Chlamydia, HPV). – May present with vaginal discharge, lesions, pelvic pain, dyspareunia (painful intercourse). • Genital herpes (Herpes Simplex Virus 2): – Majority asymptomatic (subclinical). – Vesicles (coalesce and ulcerate) may appear 37 days after exposure. – No cure, virus remains dormant in neural ganglion cells, may recur. – Important to be aware because don’t want vaginal delivery if active lesions or prodromal symptoms (vulvar pain, burning). https://www.webmd.com/genital-herpes/ss/slideshow-genital-herpes 10 Slide from neoplasia lecture INFECTIOUS DISEASES • Human papilloma virus (HPV): – Labial, vaginal and cervical warts (condyloma). – Certain types associated with carcinoma (see previous lecture and section on cervical carcinoma later). – Condyloma acuminatum: • Anogenital wart. • Usually caused by HPV 6,11 transmitted through contact with infected skin or mucosa. 11 https://commons.wikimedia.org/wiki/File:SOA-Condylomata-acuminata-female.jpg INFECTIOUS DISEASES • Chlamydia (bacteria Chlamydia trachomatis): – Most common bacterial STD (in both men and women). – Presents with urethritis or cervicitis with discharge, pelvic inflammatory disease (PID). • Gonorrhea (bacteria Neisseria gonorrheae): – Urethritis or cervicitis with discharge, PID. • Syphilis (spirochete bacteria Treponema pallidum). – Usually presents as vulvar ulcers. – Three stages of disease (primary, secondary, tertiary). https://www.rchsd.org/health-articles/pelvic-inflammatory-disease-pid/ 12 PELVIC INFLAMMATORY DISEASE • • • • Infection of upper reproductive tract. Usually secondary to ascending infection of STD (Neisseria, Chlamydia). May cause: – Salpingitis. – Tubo-ovarian abscess (abscess involving fallopian tube and ovary). – Peritonitis. Complications: – Infertility secondary to scarring of fallopian tubes. – Ectopic pregnancy. – Spread of infection. https://commons.wikimedia.org/wiki/File:Ectopic_pregnancy_on_laparoscopy.png 13 VAGINITIS • • • Inflammation of vagina. Three main causes (all infectious). – Bacterial vaginosis (most common cause): • Most often caused by bacteria Gardnerella vaginalis. • Not classified as STD. • Result of a disruption in the normal vaginal microflora. – Candidiasis (second most common). • Caused by fungus. Not STD. – Trichomonas: • Trichomonas vaginalis. STD. Less common non-infectious causes: atrophic vaginitis, foreign body (retained tampon, condom), irritant and allergens. 14 Fig 8-10.Netter's Illustrated Human Pathology 2014. OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 15 ENDOMETRIOSIS • • • • Term for the presence of endometrial tissue (uterine glands + stroma) located outside the uterus. Various locations, typically ovary, peritoneum. Cycle in response to hormonal influences. Pathogenesis: – Retrograde menstrual flow theory. – Traumatic implantation. – Embryonic rests (ectopic endometrial tissue). • • Benign condition, very common (15-20% of reproductive age women), may cause pain, infertility Ovarian endometriosis à chocolate cyst of ovary (aka. endometriotic cyst, endometrioma) https://commons.wikimedia.org/wiki/File:Blausen_0349_Endometriosis.png 16 https://commons.wikimedia.org/wiki/File:Blausen_0349_Endometriosis.png https://www.webpathology.com/image.asp?case=524&n=1 ENDOMETRIAL HYPERPLASIA • • • Normal menstrual cycle requires normal functioning of the hypothalamic-pituitaryovarian axis. Endometrial hyperplasia is thickening of the endometrial mucosa due to hormonal imbalance, ie. continued estrogen stimulation with inadequate progesterone. Anovulatory cycles: – No ovulation à no progesterone secretion à unopposed estrogenic stimulation à proliferation à endometrial hyperplasia. – Functional causes vs organic causes. 17 ENDOMETRIAL HYPERPLASIA • • Anovulatory cycles: – Functional causes: • More common. • Pubertal girls (normal cycles not yet established), anxiety, athletes, anorexia nervosa, bulimia. – Organic: • Excess estrogen (OCP, tumors). Hyperplasia: – Increased gland to stroma ratio. – Increases risk of endometrial adenocarcinoma. – Without atypia à 2-3% develop cancer. – With atypia à 25-30% develop cancer. 18 OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 19 NEOPLASMS OF LOWER REPRODUCTIVE TRACT • • • Most common lower reproductive tract cancer = cervical carcinoma. Vulva and vaginal carcinoma are rare. Carcinoma of vulva: – Squamous cell carcinoma. – Raised wart-like or ulcerated lesion. – Pre-neoplastic change may present as white or red patch (Leukoplakia and Erythroplakia, respectively). – Biopsy to assess. – Surgical excision +/- adjuvant therapy. Carcinoma of vagina: – Squamous cell carcinoma. – Clear cell carcinoma. • Women born to mothers on DES (Diethylstilbestrol – synthetic estrogen) during pregnancy. • Rare, no longer given to pregnant mothers. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171828/ 20 NEOPLASMS OF LOWER REPRODUCTIVE TRACT Carcinoma of cervix: • Was previously most common form of gynecologic carcinoma (most common = endometrial carcinoma, most common cause of death = ovarian carcinoma). • Reduced mortality due to Pap test (early diagnosis). • Cause unknown. • Risk factors: – Sexual intercourse at early age, multiple partners, HPV infection (certain types), other STDs. – Environmental component (tobacco). New Cancer Cases Cancer Deaths 21 CARCINOMA OF CERVIX • Figures from neoplasia lecture (“pre-malignant”). Squamous cell carcinoma most common. – Precursor lesion = dysplasia aka Cervical Intra-epithelial Neoplasia (CIN), graded mild, moderate, severe (CIN I, II, III), – Lack of normal maturation of squamous epithelium. – Occurs at transition (transformation) zone of exocervix and endocervix. – Cells may shed into vagina (Pap smear). – HPV types 16 and 18 most commonly associated with carcinoma. 22 https://commons.wikimedia.org/wiki/File:HpvInfectedSquamousEpithelialCell.png https://upload.wikimedia.org/wikipedia/commons/f/ff/Blausen_0221_CervicalDysplasia.png Virology . 2013 Oct;445(1-2):21-34. http://www.bccancer.bc.ca/screening/cervix/results/your-next-pap-test https://www.mayoclinic.org/tests-procedures/pap-smear/about/pac-20394841 23 Abnormal PAP smear results à colposcopy, biopsy. If moderate to severe dysplasia à Loop electrosurgical excision procedure (LEEP) 24 https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/womens-health/gynecologic-malignancies/ OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 25 NEOPLASIA OF THE UTERUS • Body of uterus consists of two tissue types: endometrium (glandular) and myometrium (smooth muscle). • Leiomyoma (fibroid): – Benign neoplasm derived from smooth muscle in wall of uterus. – Most common uterine neoplasm. – Responsive to estrogen, arise during reproductive age. – Usually asymptomatic. – May produce symptoms due to mass effects, bleeding. • Leiomyosarcoma: – Malignant neoplasm derived from smooth muscle in wall of uterus. – Very rare. 26 27 https://www.mayoclinic.org/diseases-conditions/uterine-fibroids/symptoms-causes/syc-20354288 https://commons.wikimedia.org/wiki/File:Myom.jpg https://webpath.med.utah.edu/FEMHTML/FEM028.html NEOPLASIA OF THE UTERUS Endometrial adenocarcinoma: • Malignant neoplasm derived from epithelial cells in endometrium. • Most common malignant tumor of female reproductive tract. • Elderly females, vaginal bleed. • Risk factors à related to increased estrogen: – Exogenous estrogen (hormone replacement therapy). – Obesity (fat tissue converts androgens to estrogen). – Longer lifetime exposure to estrogen (nulliparous or early menarche, late menopause). – Estrogen secreting tumors. • • • • Stage most important prognostic feature. Grade is also important (low, intermediate, high). Diagnosis: endometrial biopsy, dilation and curettage. Therapy: hysterectomy +/- adjuvant therapy. 28 OVARIAN CYSTS • • • • • Fluid filled cavities lined by epithelium. Usually arise from unruptured follicles (follicular cysts). – May also represent cystic corpus luteum or inclusions of surface cells (epithelial inclusion cyst). Usually small, solitary, asymptomatic. If large, then further investigation to rule out neoplasm. Polycystic ovary syndrome: – Multiple cysts in both ovaries due to complex hormonal disturbances. – Presents with menstrual irregularities. – Patients do not ovulate. – Cause of infertility. https://ndnr.com/wp-content/uploads/2015/10/43905013_ml.jpg 29 OVARIAN NEOPLASMS • • • Second most common group of tumors of female reproductive tract. Highest mortality of female reproductive tract tumors. Three major groups of neoplasms based on histogenesis: – Surface epithelial tumors (most common). – Germ cell tumors. – Sex cord stromal tumors. – Metastases (endometrial, breast and stomach carcinoma most common). • Malignant ovarian tumors are uncommon in young females. Fig 15-14. Histogenesis of ovarian tumors. Pathology for the Health Professions, 2012 30 OVARIAN NEOPLASMS • • • • • Risk factors not well defined. After each ovulationà ovarian surface epithelium ruptures àheals by proliferation à proliferating surface epithelial cells have increased risk of transformation. Turner’s syndrome (ovarian dysgenesis) à do not develop ovarian cancer. Oral contraceptives not linked to ovarian neoplasms (suppress ovulation, thus, reduces risk of ovarian carcinoma). Increased risk with BRCA1 and BRCA2 gene mutations. – Tumor suppressor genes, responsible for repairing damaged DNA). – Also increased risk of breast carcinoma. 31 OVARIAN NEOPLASMS • • Surface epithelial tumors: – 70% of ovarian neoplasms. – Spectrum of histologic types. • Serous, mucinous, endometrioid, clear cell and transitional cell types. Serous epithelial tumors: – Most common. – Typically cystic, filled with clear fluid. – Classification: benign, borderline malignant, and malignant tumors. – 30% of benign tumors and 60% of malignant tumors are bilateral. – Distinction of benign versus malignant requires histologic examination. J Oncol . 2010;2010:932371. 32 OVARIAN NEOPLASMS • Mucinous epithelial tumors: – Also typically cystic, filled with viscus fluid. – Benign, borderline malignant, and malignant tumors. – Compared to serous, more likely to be benign and less commonly bilateral. • Endometrioid epithelial tumors: – Typically solid. – Usually Malignant. • Highest mortality of female reproductive tract tumors.... – Early-stage ovarian cancer rarely causes any symptoms. – Advanced-stage ovarian cancer has non-specific symptoms. 33 OVARIAN NEOPLASMS – GERM CELL TUMORS • • • • Germ cell tumors (20% of ovarian tumors): – Typically occur in young women. Teratoma: – Most common ovarian neoplasm in young women. – Aka. ‘dermoid cyst’ à often cystic, contain hair, sebaceous material. – May contain teeth, bone cartilage. – Benign, but need to be resected as malignant transformation (malignant teratoma) possible. Immature teratoma: – Teratoma that contains immature neural tissue. – May behave malignantly. Other germ cell tumors: dysgerminoma (equivalent to seminoma in men), yolk sac, choriocarcinoma, embyronal carcinoma. https://radiopaedia.org/articles/mature-cystic-ovarian-teratoma-1 34 OVARIAN NEOPLASMS – SEX CORD STROMAL • • • • • Sex-cord stromal tumors: – 10% of ovarian tumors. – Originate from ovarian stromal cells. – Tumor types: fibroma, thecoma, granulosa cell tumor, Sertoli-Leydig cell tumor Fibroma: benign neoplasm of fibroblasts. Thecoma: – Benign neoplasm composed of theca cells (surround follicle produces hormones). – May produce estrogens à risk of endometrial carcinoma. Granulosa cell tumor: – Neoplasm of granulosa cells. – Benign or malignant and may produce estrogen. Sertoli-Leydig cell tumor: – Secrete androgens à virilization. http://medcell.med.yale.edu/histology/ovary_follicle.php 35 OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 36 PATHOLOGY OF PREGNANCY - INFERTILITY • • • • Ovum related: – Immature ovum (incomplete meiotic division). Sperm related: – Azospermia (no sperm). – Oligospermia (low sperm count). – Immotile sperm. Genital organ factors: – PID. – Asherman’s syndrome: scar tissue in uterus or cervix typically from dilation and curettage (D&C) procedure. Systemic factors: – Poorly understood. – Eg. Immune mechanism (antibodies to spermatozoa or ova). https://www.britannica.com/science/fertilization-reproduction 37 PATHOLOGY OF PREGNANCY - INFERTILITY Ectopic pregnancy: • Implantation of fertilized ovum outside the uterine cavity • Usually fallopian tube. – Abnormal fallopian tube from PID, surgery, endometriosis. • Adhesions prevent normal passage of zygote à implants and penetrates wall of fallopian tube. • May erode through wall and rupture. • Rupture à massive blood loss. – Surgical emergency. https://www.emra.org/emresident/article/defusing-ectopic-pregnancy/ 38 Placenta: • Arises from trophoblast cells of morula. • Disc implants onto endometrium. • Umbilical cord vessels provides nutrients and removes waste from fetus. Slide from genetics and development lecture à 39 https://www.mountsinai.org/health-library/diseases-conditions/placental-insufficiency DISEASES OF PREGNANCY - PLACENTAL ANOMALIES • Placenta accreta: – Abnormally deep penetration of placental villi into wall of uterus. – Risk of retaining placenta after delivery and post partum hemorrhage. • Placenta previa: – Abnormal placental implantation site in lower uterine segment. – Prone to bleeding and risk of premature delivery. 40 https://www.babycenter.com/ims/2020/05/PLACENTAL-ACCRETA-with-text-FINAL_wide.jpg.pagespeed.ce.uLrwOae6Eq.jpg https://www.babycenter.com/pregnancy/health-and-safety/placenta-previa_830 DISEASES OF PREGNANCY - ABORTION • • Abortion: interruption of pregnancy prior to fetal viability (<500 g, 20 weeks). Spontaneous abortions (ie. not induced): – No identifiable cause (1/3 of all pregnancies). – Further classified …... • Complete abortion. • Incomplete abortion. • Missed abortion. • Threatened abortion. • Inevitable abortion. 41 DISEASES OF PREGNANCY - ABORTION • • • • • Complete abortion: – Fetus and placenta expelled, normal function returns. Incomplete abortion: – Retention of some fetal or placental material. Missed abortion: – Death of fetus in utero, passed several weeks later. Threatened abortion: – Cervical os closed, spotting of blood. Inevitable abortion: – the cervix has dilated, but the products of conception have not been expelled. 42 DISEASES OF PREGNANCY – GESTATIONAL TROPHOBLASTIC DISEASE • • • • • • GTD = group of abnormalities of placentation resulting in tumor-like changes or malignant transformation. Placental villi consists of two cell types: cytotrophoblasts and syncytiotrophoblasts. Gestational trophoblast have to ‘invade’ the tissue (similar to malignant/invasive cancers). GTD are diseases that involves proliferation of these cells types. Benign: Hydatidiform mole. – Complete and incomplete types. Malignant: Choriocarcinoma. 43 https://en.wikipedia.org/wiki/File:ChorionicVillus.png https://www.sciencedirect.com/topics/medicine-and-dentistry/syncytiotrophoblast-cell GESTATIONAL TROPHOBLASTIC DISEASE • • Hydatidiform mole: – Trophoblastic proliferation, hydropic degeneration of chorionic villi. – Features: enlarged uterus with no fetal movement, high HCG (produced by trophoblasts), cluster of grapes on ultrasound. – Complete mole: • More common, no identifiable fetus, abnormal fertilization (46 chromosomes, all paternal). – Incomplete mole: • Usually some fetal parts, abnormal fertilization (oocyte fertilized by two spermatozoa à 69 chromosomes). Choriocarcinoma: – Rare highly malignant tumor of gestational trophoblasts. – Most often arises from pre-existing complete mole. https://medium.com/@gravid.net/what-is-molar-pregnancy-ae432ca4ad79 https://commons.wikimedia.org/wiki/File:Partial_Hydatidiform_Mole_(3460188720).jpg 44 DISEASES OF PREGNANCY - TOXEMIA OF PREGNANCY • • • • Disease of pregnancy of unknown pathogenesis (possibly endothelial cell dysfuntion) resulting in characteristic symptom complex in the mother. Includes preeclampsia and eclampsia. Preeclampsia: – Presents with triad of hypertension, edema, and proteinuria. – Typically occurs in third trimester. – May progress to eclampsia. Eclampsia. – Hypertension, edema, proteinuria and seizures. – Life threatening (for both mother and baby). – Must treat seizures and deliver baby. 45 OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 46 BREAST STRUCTURE AND FUNCTION Function – Function is to produce milk (nourish newborn). Structure – Modified apocrine sweat gland. – Lobules (ducts + terminal buds) drain into larger duct system. – Hormonally influenced changes. – Males, pre-pubertal females have nipple + ducts. – Post-pubertal female: • Proliferation of ducts and early acini. – Pregnant female: • Terminal buds develop into acini. • Prolactin released in response to infant’s suck. • Milk produced. 47 https://www.mskcc.org/cancer-care/types/breast/anatomy-breast https://commons.wikimedia.org/wiki/File:Lactational_change_-_high_mag.jpg BREAST PATHOLOGY - INFLAMMATION • Acute mastitis: – Acute inflammation of the breast. – Warm, red, edema, painful. – Most common inflammatory disorder of breast. – Affects ~10% of lactating women. – Bacterial infection: bacteria invade through milk ducts or from skin/nipple lacerations or injures secondary to breastfeeding. – Abscess may develop. https://en.wikipedia.org/wiki/File:Mastitis_in_breast.jpg\ • Chronic mastitis: – Rare disease of unknown etiology. – May mimic breast cancer, requires biopsy. 48 BREAST PATHOLOGY - FIBROCYSTIC CHANGE • • • • Benign changes (fibrosis and cyst formation) in breast tissue due to various factors including hormonal influences and age. Females of reproductive age. Clinical features: – Pain, nodularity, sensitivity on palpation. Pathological findings: – Fibrosis of intralobular stroma. – Cystic dilation of epithelial ducts. – Epithelial hyperplasia. 49 https://commons.wikimedia.org/wiki/File:Fibrocystic_change_-_intermed_mag.jpg BREAST PATHOLOGY - GYNECOMASTIA • • • • • Increased proliferation of male breast. Usually due to hormonal changes (increase in estrogen to androgen ratio). Cause depends on age group: – Newborn: high estrogen milieu of pregnancy. – Adolescents: during puberty. – Older men (or any age): • Cirrhosis. • Estrogen secreting tumour. • Medications. Commonly seen during puberty. Proliferation of excretory ducts and stroma (no lobules). 50 https://commons.wikimedia.org/wiki/File:Adolescent_with_Gynecomastia.jpg https://commons.wikimedia.org/wiki/File:Gynecomastoid_hyperplasia_-2-_intermed_mag.jpg OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 51 BREAST PATHOLOGY - NEOPLASMS Fibroadenoma • Most common benign neoplasm of breast. • Proliferation of stromal elements (fibro) and epithelial elements (adenoma). • Well circumscribed, firm, mobile mass. • Believed to be abnormal exaggerated response of breast to hormones. – Typically affect young females. – Enlarged during pregnancy. – May regress after menopause. 52 https://commons.wikimedia.org/wiki/File:Breast_fibradenoma_(1).jpg https://en.wikipedia.org/wiki/File:Fibroadenom.jpg BREAST PATHOLOGY - NEOPLASMS Breast cancer (carcinoma): • Most common cancer in females and second most common cause of cancer related deaths in women. • Incidence increasing, ~1 in 9 women will develop cancer in her lifetime. • Hormonal, environmental and genetic influences. – Familial breast cancers: • BRCA-1, BRCA-2 tumor suppressor genes. • Increased incidence of other cancers. • Majority of breast cancers are not hereditary. • Risk factors: modifiable and non-modifiable. 53 https://www.cancer.gov/news-events/cancer-currents-blog/2016/brca-testing-breast-cancer BREAST CANCER • Non-modifiable risk factors: – Age, race, female sex (100x males). – Genetic predisposition. – Hormonal factors: • Prolonged estrogen exposure: – Early menarche (<11yo), late menopause (>50 yo). – Nulliparous (women that have not had any offspring). – Personal history of contralateral breast carcinoma or other malignancy (eg. endometrial carcinoma). – Dense breasts. 54 https://www.wikihow.com/Decrease-Your-Breast-Cancer-Risk http://www.bccancer.bc.ca/screening/breast/breast-health/breast-density BREAST CANCER • Modifiable risk factors: – Limit alcohol intake. – Stop smoking. – Maintain healthy body weight. – Breastfeed. – Weigh risk and benefits of hormone replacement therapy for menopausal symptoms. – Avoid unnecessary radiation exposure. 57 https://www.wikihow.com/Prevent-Breast-Cancer BREAST CANCER • • There are different forms of breast cancer. Most common breast cancer is infiltrating ductal carcinoma. – Adenocarcinoma that arises from the ductal epithelial cells. – Pre-invasive stage à ductal carcinoma in situ (DCIS). – Tumor is firm and presents with palpable mass because of desmoplastic response of stroma (stromal reaction to tumor). – Most arise in upper outer quadrant. – Lymphatic spread (axillary nodes drain most of the breast). 58 BREAST CANCER • • Early detection: – Mammography. – Breast self-examination – not recommended anymore. If abnormality found, needs to be biopsied à fine needle aspiration, core biopsy or incisional biopsy. 59 Screenshot from JAMA animated video Breast Cancer Screening Recommendations for Women at Average Risk. www.youtube.com/watch?v=TDeGl4hJqYQ https://www.ncbi.nlm.nih.gov/books/NBK65715.2/figure/CDR0000257995__145/?report=objectonly https://commons.wikimedia.org/wiki/File:Blausen_0144_BreastSelfExam_3Methods.png 60 https://www.mayoclinic.org/tests-procedures/breast-biopsy/about/pac-20384812 61 BREAST CANCER • • Therapy: – Surgical resection. • Lumpectomy. • Mastectomy. • Axillary dissection. – Radiation. – Chemotherapy. • Tamoxifen. • Herceptin. Prognosis: – Staging most important. – Histologic subtypes, histologic grade. – Estrogen receptor and HER2 receptor status. 62 https://www.bcm.edu/healthcare/specialties/oncology/cancer-types/breast-cancer/breast-cancer-surgery/lumpectomy https://www.mayoclinic.org/tests-procedures/mastectomy/about/pac-20394670 OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 63 SKIN STRUCTURE AND FUNCTION • Structure • 3 layers: • Epidermis (keratinocytes, melanocytes). • Dermis (connective tissue, adnexal structures). • Subcutis (adipose tissue). • Functions • Protection. • Regulation of body temperature. http://www.brainkart.com/article/Skin---Anatomy-and-Physiology_18672/ 64 SKIN PATHOLOGY – EXTERNAL INJURY • Skin can be injured by variety of external means. • Classified as mechanical trauma, thermal, electrical and radiation injury. • Mechanical trauma: • Blunt force trauma may cause contusion (bruise), abrasion, laceration. • Sharp force trauma can be classified as incision or stab wound. • Electrical injury. • Inadequately isolated electrical wires or lightening. • Passage of electricity through skin generates heat which burns tissue. • Can also interfere with conduction system of heart. • Radiation injury. • Two most important forms of radiation injury: • UV light (non-ionizing) from sun: sunburn, promote carcinogenesis. • Ionizing radiation (e.g. atomic bombs, medical use) also promotes carcinogenesis. 65 SKIN PATHOLOGY – THERMAL INJURY • Classified as either burns from heat or cold injuries (frostbite). • Extent of injury depends on temperate, duration and mode of exposure (solid, liquid, gas), anatomic site of injury. • Burns traditionally classified and graded as: • First degree (involves epidermis only): • Erythema, swelling, pain. • Second degree: (involves dermis). • Superficial or deep partial thickness. • Blisters, pain. • Third degree (full thickness of dermis involved, often injure subcutaneous tissue). • Leathery gray to charred and black, no pain. • Fourth degree: underlying soft tissue, muscle, bone. https://www.cancercarewny.com/content.aspx?chunkiid=22574 • Total surface area of burn is important (“rule of nines”). 66 Depth Superficial (epidermal) Appearance Dry, red Blanches with pressure Superficial partialthickness (dermis) Sensation Healing time Painful 3 to 6 days Blisters Moist, red, weeping Blanches with pressure Painful to temperature and air and touch 7 to 21 days Deep partialthickness (dermis) Blisters Wet or waxy dry Variable color Blanching with pressure may be sluggish Painful to pressure only >21 days, usually requires surgical treatment Full-thickness (dermis) Waxy white to leathery gray to charred and black No blanching with pressure Deep pressure only Rare, unless surgically treated Deeper injury (ie, fourth degree) Extends into fascia and/or muscle Deep pressure Never, unless surgically treated 67 https://en.wikipedia.org/wiki/Wallace_rule_of_nines Assessment and classification of burn injury, UpToDate Accessed 12/1/2020: https://www.uptodate.com/contents/assessment-and-classification-of-burn-injury OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 68 IDIOPATHIC AND IMMUNE DISORDERS • Many skin diseases have no identifiable causes. • Presumed to be mediated by immune mechanisms. • Eczema (atopic dermatitis): • Chronic inflammatory disorder (children > adults) characterized by red, dry, scaly, itchy skin. • Type I hypersensitivity reaction (allergen exposure: direct skin contact, inhaled or ingested). • • Often associated with asthma and allergic rhinitis. Urticaria (hives, welts, wheals): • Acute, transient, intensely itchy, red raised plaques. • Mast cell degranulation (via IgE or direct activation). • Triggers: allergic (medication, food, insect bite) vs nonallergic (infections, cold temperature). 69 https://www.webmd.com/skin-problems-and-treatments/eczema/ss/slideshow-eczema-overview https://commons.wikimedia.org/wiki/File:EMminor2010.JPG IDIOPATHIC AND IMMUNE DISORDERS • Seborrheic dermatitis: • Chronic, relapsing mild dermatitis. • Infants à ‘cradle cap’. • Severity varies from minimal scaliness of scalp (dandruff) to widespread involvement (face, trunk). • Psoriasis: • Relatively common (1-2% of population). • Papules and patches covered by scale on extensor surfaces (elbows, knees). 70 https://en.wikipedia.org/wiki/Cradle_cap https://www.webmd.com/skin-problems-and-treatments/psoriasis/ss/slideshow-psor-overview OBJECTIVES 1. 2. 3. 4. 5. 6. Describe the structure and function of the female reproductive system. Describe developmental and infectious diseases of the female reproductive system. Describe endometriosis and endometrial hyperplasia. Describe neoplasms of the lower female reproductive tract. Describe neoplasms of the uterus and ovary. Describe diseases associated with pregnancy (infertility, implantation, placental anomalies, abortion, gestational trophoblastic disease, toxemia of pregnancy). 7. Describe the structure and function of normal breast. 8. Describe mastitis, fibrocystic change and gynecomastia. 9. Describe benign and malignant breast neoplasms. 10. Describe the structure and function of the skin. 11. Describe different types of external injury to skin and grading of burns. 12. Describe idiopathic and immune skin disorders. 13. Describe features of common skin neoplasms. 71 SKIN NEOPLASMS • Neoplasms classified based on cell type: • • • https://commons.wikimedia.org/wiki/File:Basal_cell_carcinoma.jpg https://skincancer909.com/home/squamous-cell-carcinoma/ Epithelial: basal cell carcinoma, squamous cell carcinoma. • Both very common malignant epithelial neoplasms • Both occur usually on sun exposed surfaces. • Melanocytic – nevus (mole), melanoma. • Dermal connective tissue. • Metastasis. Basal cell carcinoma • Does not metastasize, excellent prognosis. • Nodule with telangiectatic vessels (thread-like red lines). Squamous cell carcinoma • <2% metastasize, good prognosis. • Firm, scaly nodule. 72 MELANOCYTIC NEOPLASMS • Nevus (mole) – benign neoplasm of melanocytes. • Melanoma – malignant neoplasm of melanocytes. • Related to sun exposure. • Different histological types (superficial spreading most common). • Clinical features worrisome for melanoma. • A – Asymmetry. • B - Border irregularity. • C - Color irregularity. • D - Diameter > 6 mm. • E – Evolution (changing in size, shape or color or new). • Depth of invasion important prognostic factor. https://share.baptisthealth.com/mole-or-melanoma-5-signs-of-skin-cancer/ 73