BENIGN DISORDER OF THE REPRODUCTIVE ORGAN~dr. David Lotisna by: Dr.EzyanNon-neoplastic Disorders Iatrogenic endometrium- Exogenous hormones- Tamoxifen- IUD's Endometritis Metaplasias HyperplasiaMetaplasias Tubal metaplasia occurs in setting of estrogen excess or postmenopausal. Squamous metaplasia frequently occurs in hyperplasia, neoplasia, CEMI. Mucinous, papillary and eosinophic types are less common EndometritisAcute: Microabcesses - stroma / glands Classically postabortal Strep., Staphy., GCStroma: Stromal cells Stromal granulocytes

Endometrial Hyperplasia

Abnormal proliferation of endometrial glandular epithelium (and often stroma) that lacks stromal invasion. Wide spectrum of patients Associated with prolonged, unopposed exposure to estrogen Therapy depends on type / patient / setting Current Terminology: Simple hyperplasia Complex hyperplasia (adenomatous) Simple atypical hyperplasia Complex atypical hyperplasia

Early studies had lots of problems Endometrium is histologically complex Cytologic changes are difficult to judge Can't follow without biopsy

Sampling of the Endometrium Office biopsy procedures (Pipelle, Vabra aspirator, Karman cannula) will agree with a D&C performed in the OR ~95% of the time Office biopsy has a 16% false negative rate when the lesion is in a polyp or the cancer covers less than 50% of the endometrium Guido et al. J Reprod Med. 1995;40:553 Patients with persistent PMB after negative office biopsy should have D&C (+/- hysteroscopy) D&C is the gold standard sampling method preoperative D&C will agree with diagnosis at hysterectomy 94% of the time Proliferative phaseEarly secretory

Mid-secretory phasePost-menopousal atrophyEndometrial Simple Hyperlasia

Endometrial Hyperlasia - ComplexEndometrial Hyperplasia - Atypical

Endometrial Hyperplasia Classification and Risk of Progression to Cancer:

Kurman, et al. (Cancer. 1985 Jul 15;56(2):403-12.)

Type of HyperplasiaTotal Cases (n=170)Years of Follow up (mean=13.4)# Progressed to Cancer% Progressed to Cancer%Persistent Hyperplasia% Spont. Regression

Simple9315.211%19%80%

Complex2913.513%17%80%

Atypical,simple1311.418%23%69%

Atypical, complex3511.41029%14%57%

Combined No Atypia (n=122) 1.6%

Combined with Atypia (n=48) 23% (P=0.001)

Mean age at study entry= 40y/o Mean study F/U=13.4yrs

Treatment for Endometrial Hyperplasia without atypia: Progestin therapy continuous or cyclical Childbearing age: Progestin dominant OCPs or Depo-Provera 150mg IM q3 months or Provera 10mg po 10 days/month and May follow with ovulation induction after normal biopsy if pregnancy desired Peri or Postmenopausal: Provera 20mg po 10 days/month or Depo-Provera 200mg IM q2 months Repeat biopsy in 3-4 monthsTreatment for Atypical Endometrial Hyperplasia:

23% risk of progression to carcinoma (over 10 years) if untreated. Standard treatment when childbearing is complete is total hysterectomy (abdominal or vaginal) Frozen section to rule out carcinoma (up to 20% have coexisting endometrial cancer)

Conservative medical therapy can be attempted in younger patients who request preservation of fertility. D&C prior to initiation of medical therapy to rule out carcinoma Megace 40-80mg/day, Norethindrone acetate 5mg/day Conservative therapy may also be attempted in young patients with early, well differentiated endometrial carcinomas. Megace 120-200mg/day, Norethindrone acetate 5-10mg/day

Conservative/Medical Therapy:Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol. 1997 Sep;90(3):434-40.

Objective Determine efficacy of conservative treatment of AH/ECA in patients 50% solid tumor NUCLEAR GRADE Size, shape , staining and chromatin, variability, prominent nucleoli. High nuclear grade adds one point to FIGO gradeNeoplastic Disorders Endometrial polyps Endometrial stromal lesions Endometrial carcinomas Mesenchymal tumors Mixed tumors

BENIGN CONDITION OF CERVIX

Allergic Reaction Foreign Bodies Nabothian cysts Endometriomas Myomas Cervical Polyps Infection:- Trichomonas- Chlamydia- Gonorrhea- Herpes- Syphillis

Nabothian Cysts Cause: Obstructed endocervical gland Raised yellow or blue nodules 1-3 mm in diameter Require no treatmenr Endometriomas Endometriosis Cervical surgery? Red or blue 1-3 mm in diamters Contact bleeding Treatment in same as endometriosisMyomas (Fibroid) Cervix rare site If large may cause pressure symptoms Menorrhagia May obstruct vaginal delivery Diagnosis ultrasound Treatment same as other location

Uterine LeiomyomaCervical Polyps

Proliferation of smooth muscle cells Lesion of reproductive years 20 - 30% of women 30 years and older More common in blacks Present with bleeding, pain, pressure Pathogenesis: In reproductive yrs - rare after menopause Contain estrogen / progesterone receptors Hormones thought to play a role Gonadotropin releasing hormone agonists cause regression Lesions are monoclonal - G6PD or PCR Non-random chromosomal abnormalities quite common (40% of cases) 30% of abnormal karotypes involve region 12q14-15 (same area as involved in lipomas and rhabdosarcomas) Most common cervical tumor Consist of: - Ectocervical - Endocervical Friable, soft, red protrusions, Stalk ? Size few mm to several cm Sign and symptoms: Vaginal discharge Postcoital bleeding Generally do not become malignant May reoccur Cytology Inflammatory atypia

Diagnosis Biopsy Differential Diagnosis: Endometrial polyps May be precancerous lession Treatment: Remove by twisting on the stalk or excision Do not remove in pregnancy Sent to pathology

Endometrial polyps

Definition Are quite common, especially 40 - 50 yrs. Develop as focal hyperplasia of basalis. Benign localised overgrowth of endometrial glands and stroma, covered by epithelium, projecting above the adjacent epithelium Clonal lesions chromosome 6Clinical features Prevalence ~ 24% Classical feature: Fibrotic stroma, Prominent vascularity , Glands out of phase, Irregular gland architecture More common in women > 40 Present with intermenstrual or post-menopausal bleeding Infertility Persistent bleeding following curettage Common association with Tamoxifen usePathological findings Sessile or pedunculated Size: 1 mm and beyond may fill the endometrial cavity and project through the cervical os May be multiple May originate anywhere, but most commonly fundus

Histopathology Irregularly outlined glands that may be out of phase with endometrium Fibrovascular stalk or fibrous stroma with numerous thick walled vessels Metaplastic epithelium particularly squamous may be present Those in the lower uterine segment may contain endocervical glands Mesenchymal component contains endometrial stroma, fibrous tissue or smooth muscle. Absence of cytological atypia hyperplasia, carcinoma (any type) and carcinosarcoma may involve or be entirely confined to a polyp endometrial intraepithelial carcinoma may be identified in an atrophic polypBenign polyp in a hysterectomy specimen Note Endometrial epithelium on three surfaces Dilated glands Fibrotic stroma Scattered dilated thick walled blood vessels Note: Dilated thick-walled blood vessels Stromal fibrosis (less than previous image) Proliferative endometrial glands

Endometrial polyp (low power)features cystically dilated glands of various sizes and shapesEndometrial polyp (high power)characteristic features of thick walled blood vessels in a fibrous coreClassification Morphologically diverse lesions that are difficult to subclassify. Most are either hyperplastic, atrophic or functional. Hyperplastic resemble diffuse non polypoid endometrial hyperplasia no evidence that these have the same significance as diffuse hyperplasia, so best to avoid the term hyperplastic in the diagnosis Atrophic low columnar or cuboidal cells lining cystically dilated glands typically in post-menopausal patients Functional resemble normal cycling endometrium relatively uncommon

Tamoxifen related polyps Larger, sessile with a honeycomb appearance bizarre stellate shape of glands and frequent epithelial and stromal metaplasias often periglandular stromal condensation malignant transformation in up to 3% interestingly the cytogenetic profile is similar to non-iatrogenic lesionsDifferential Diagnosis Endometrial hyperplasia diffuse process, majority of fragments in curettage, absence of thick walled vessels polypoid endometrial carcinoma malignant epithelial cells adenofibroma adenosarcoma stromal cells cytologically atypical and mitotically active stromal cells packed tightly around non malignant glands leaf like patternClinical behavior and treatment At most 5% of polyps contain carcinoma polyps may represent a marker of increased cancer risk, but no evidence suggests they are more likely to become cancer than the adjacent endometium those containing atypical hyperplasia or carcinoma should be treated as per similar flat lesions

Hysteroscopy Not satisfactory for screening test Studies of the efficacy of hysteroscopy as a diagnostic tool vary widely Sensitivity reported ranging from 60-95% compared to D&C obtained at the same time Specificity 50-99%

DISEASES OF THE OVARY

Ovarian Cysts Follicular cysts Corpus Luteum DermoidBenign Ovarian CystsFollicular cysts Most common type of ovarian cyst Formed during first half of menstrual cycle dominant follicle fails to ovulate Can be up to 6 cm, most smaller can be very large with hyperstimulation from exogenous gonadotropins Follicular Cysts

Symptoms No specific symptoms May have effects on menses Cycts are estrogen rich and may produce irregular menses If large enough may produce feeling of heaviness, congestion and aching on affected side Torsion rare Occasionally may experience sharp abdominal pain and bleeding with rupture This set of symptoms may resemble ectopic pregnancyDiagnosis: Menopause and women on oral contraceptives should have NO cycts at any time of the menstrual cycle but new OCs such as triphasics and 20 mcg pills may allow ovulation Follicular cysts should be no larger than 6 cm, may be multiple, and often bilateral

Corpus Luteum Cysts

Formed by hematoma or excessive growth of corpus luteum Less common but more clinically significant than follicular cysts Formed in the latter half of menstrual cycle Normal corpus luteum of menstruation and pregnancy is no longer than 6 cm and non-cystic

Formed due to excess physiologic bleeding during the vascularization (second) stage of corpus luteum formation Rupture may occur from a normal size corpus luteum in the vascular stage as well as from a corpus luteum cyst Hyperstimulation from fertility drugs may cause multiple corpus luteum cysts Persistents corpus luteum cycts produces menstrual irregularities generally a delay in onset of menses, normally 3-4 weeks but can rarely be up 6 months Subsequent menses can be prolonged and heavy Crampy, dull, unilateral pain is common (ovarian distention from bleeding into the cavity)

Cysts can rupture anytime during luteal phase usually 1 week prior to menses causes generalized, severe abdominal pain may have pain radiating to back, shoulder, legs, rectal/bladder discomfort depending on amount of bleeding Actual rupture may be preceded by several days of slow bleeding into cysts capsule, resulting in adnexal discomfort Bleeding with corpus luteum cyst is often extensive Symptoms strongly resemble ruptured ectopic pregnancy or appendicitis Pregnancy test must be done to rule out ectopic pregnancy Menstrual and contraceptive history On physical exam most common finding is a small tender swelling on the side of adnexa that corresponds to the pain

Dermoid Cysts

Benign cystic teratoma Most common ovarian germ cell neoplasm 18-25% of all ovarian tumors Most frequently encountered ovarian tumor in women under age 20 Incidence peaks between age 20-40 Consists of tissue from all three embryonic germ cell layers: ectoderm, mesoderm, and endoderm Has thick, formed capsule lined with squamous epithelium beneath are sweat, apocrine, and sebaceous glands Cartilage, nervous tissue, and hair may be found Most notable component in component in 50% of dermoids is teeth Dermoid are founds on the long ovarian pedicle Torsion occurs in about 16% of cases No specific symptoms- May have feeling of heaviness or aching in pelvis - Pain may occur with torsion Management and diagnosis- often palpated in abdomen or anterior to uterus because of long pedicle

Dermoids fell light and floaty secondary to their sebaceous content May torse intermittently may twist and be painful during activity, but go back to normal during restDiagnosis: 12% of cases of dermoids are bilateral Most measure 5-10 cm in diameter Consistency on exam is tensely cystic Pregnancy test must be performed to rule out ectopic X-ray helpful because teeth will show up Ultrasound is now the most used method of diagnosis because certain tumor characteristics can now be seen on TVS