Pathology of Uterine Corpus.pdf

Pathology of Uterine Corpus Anatomy of Uterus 3 Layers: o Serosa § Outer layer § A thin connective tissue o Myometrium § Middle layer § Smooth muscle o Endometrium § Inner layer § Mucosal surface Endometrium 2 layers: o Functional Layer § Part that begins to grow at beginning of each menstrual cycle...

Pathology of Uterine Corpus Anatomy of Uterus 3 Layers: o Serosa § Outer layer § A thin connective tissue o Myometrium § Middle layer § Smooth muscle o Endometrium § Inner layer § Mucosal surface Endometrium 2 layers: o Functional Layer § Part that begins to grow at beginning of each menstrual cycle § Shed w menstruation o Basal Layer § Regenerates the functional layer each cycle Composed of Glands and Stroma o Glands secrete mucus o Stroma is the CT btwn the glands Growth and shedding during the menstrual cycle o Estrogen → Stimulates growth, increases size of glands, stroma o Progesterone → Stimulates secretory activity, decrease triggers menstruation Proliferative phase o Estrogen driven o ↑ Glands and stroma Secretory Phase o Progesterone driven o ↓ Proliferation o Secretory vacuoles appear o Prominent spiral arterioles Dysfunctional Uterine Bleeding Abnormal menstrual bleeding >5 days of unknown cause in childbearing age women Assoc w: o Abnormal hormone function o Abnormal endometrial growth (benign and malignant) Most common cause: anovulatory cycle Anovulatory Cycle Menstrual cycle w/o ovulation No ovulation → no corpus luteum formation o No luteal phase of ovary o No switch to progesterone secretion Excess endometrial growth from unbalanced estrogen “Unopposed growth” from lack of progesterone Irregular Bleeding Anovulatory is Common at two times: o Menarche § Underdeveloped hypothalamus-pituitary-ovary axis o Menopause § Loss of Ovulation § Continued Estrogen production Other disorders caused by Anovulatory cycle: o Endocrine disorders o Polycystic Ovary syndrome o Ovarian Failure o Metabolic Disorders (diabetes, psychological stress) ↑ Risk for endometrial hyperplasia and carcinoma due to unopposed estrogen effects EndometrITIS Inflammation of Endometrium Can be: o Acute (pregnancy-related) o Chronic (non-pregnancy related) Acute Endometritis (pregnancy related) Bacterial infection AFTER delivery or miscarriage Key risk factor: cesarean section delivery Prophylactic antibiotics used before C-section Often involves myometrium (“metritis”) Fever, abdominal pain, uterine tenderness Usually diagnosed clinically Polymicrobial infections o Gram positives, gram negatives, anaerobes o Staph, strep, E. coli, Bacteroides Broad-spectrum antibiotics used Classic regimen: clindamycin + gentamycin (Cure rate >90%) Alternative: ampicillin-sulbactam Retained Products of Conception (RPOC) Can lead to acute endometritis Placental/fetal tissue remaining in the uterus o May occur after delivery or miscarriage o Uterine bleeding and pelvic pain o Tissue becomes necrotic Prone to infection by flora from cervix/vagina o Diagnosis by history and imaging o Treatment: antibiotics +/- surgery Chronic Endometritis (Non-Pregnancy Related) Postpartum Intrauterine devices (IUDs) Pelvic Inflammatory Disease o Ascending infection o Chlamydia or gonorrhea o May involve uterus, fallopian tubes, ovaries o Treatment: antibiotics Causes Tuberculosis o Hematogenous spread from lungs o Biopsy: Acid- Fast Bacilli Associated with infertility Biopsy hallmark: plasma cells White blood cells normal in the endometrium Plasma cell indicates chronic inflammation Endometrial Polyps Hyperplastic growth of glands and stroma Most (95%) benign Project from the endometrium (exophytic mass) Often asymptomatic May cause painless uterine bleeding Treatment: removed surgically o Stop bleeding o Prevent infection o Small chance of malignancy Histology: o May see smooth muscle o Fibrous stroma o Polypoid growth on endometrium o Dilated glands o Thick-walled vessels Associated with unopposed estrogen Common near menopause o Ovarian estrogen production o Chronic anovulation → lack of progesterone Tamoxifen causes polyps Selective estrogen receptor modulator (SERM) Competitive antagonist of breast estrogen receptor (ER) o Used in ER-positive breast cancer Estrogen agonist in other tissues (bone/uterus) Partial agonist to endometrium Endometrial proliferation Hyperplasia Endometrial Polyp formation (up to 36% of women) May cause endometrial cancer Endometriosis Endometrial tissue (glands and stroma) outside of the uterus May occur anywhere Several common locations: o Ovary/Fallopian Tubes o Uterosacral ligaments o Rectovaginal septum o Pelvic peritoneum o Myometrium Symptoms: o Ectopic endometrial tissue hormone-sensitive § Growth from estrogen § Atrophy from progesterone withdrawal o Growth, bleeding, and inflammation in ectopic sites Classic Symptoms: o Cyclic pelvic pain o Dysmenorrhea, menorrhagia § Growth/bleeding of ectopic tissue § Dysmenorrhea: Painful periods § Menorrhagia: Heavy bleeding o Infertility § Many women are unaware of the disorder § Ovarian/fallopian lesions → infertility § ~40% of infertile women have endometriosis Other Symptoms: o Dyspareunia § Painful intercourse § Ectopic tissue near vagina o Dyschezia § Painful defecation § Ectopic tissue near rectum o Dysuria § Painful urination § Ectopic tissue near bladder Diagnosis: o Physical exam may be normal o Vaginal tenderness o Nodules in posterior fornix § Upper vagina behind cervix o Ovarian mass o Normal uterus size § Enlarged uterus is known as: adenomyosis o Retroverted uterus § Uterus tipped backward § Detected on physical exam § May be seen in normal women § More common in women with endometriosis o Definitive diagnosis: biopsy of lesion o Classic ovarian finding: chocolate cyst o Occurs in women of reproductive age o Improves at menopause and in pregnancy o Increased risk of ovarian epithelial cancer Adenomyosis Endometrial glands/stroma in myometrium Hyperplasia of basal endometrium into myometrium Diffusely enlarged uterus(globular) Two major symptoms: o Heavy menstrual bleeding o Painful menstruation Often co-exists with endometriosis Treatment: o Less responsive to medical therapy o Hysterectomy Treatment of Endometriosis Surgical removal Nonsteroidal anti-inflammatory drugs (NSAIDs): Reduce inflammation Oral contraceptive pills (OCPs) o First-line therapy o Suppress ovarian function o Key component: progestins o Suppress ovaries → cause anovulation o Anti-estrogen → limit endometrial growth Leuprolide o GnRH agonist (downregulates GnRH) o Binds to receptors in the pituitary o Pituitary desensitization leads to ↓ LH/FSH o ↓ estrogen production from ovaries Danazol o Steroid o Weak androgen and progesterone activity o Inhibits LH surge → anovulation o Suppresses ovarian function o Rarely used due to side effects o Adverse Effects: § Androgen effects — Weight gain — Edema — Decreased breast size — Acne and oily skin — Increased hair growth — Deepening of the voice § Low estrogen effects: hot flashes § Intracranial hypertension (pseudotumor cerebri) — Headache, papilledema Endometrial Cancer Leiomyoma Uterine Fibroid o Benign smooth muscle tumor of the uterus o Usually, multiple tumors o Occur in premenopausal women o Growth stimulated by estrogen o Usually resolves at menopause (↓ estrogen) Histology: o Smooth muscle cell proliferation w/o cytological atypia o Fibroids appear as discrete, yellow-gray tumors Fibroids: o Usually asymptomatic o Often detected as a pelvic mass on exam o Can be visualized with ultrasound o May cause: § Irregular bleeding (often heavier, longer menstrual flow) § Infertility § Pelvic pain Endometrial Hyperplasia Stimulation of endometrium by unopposed estrogen Absence of progesterone stimulation/withdrawal Usually occurs in peri/postmenopausal women Menstruation has slowed or stopped estrogen Anovulation → no progesterone from the ovary Any estrogen source → hyperplasia Sources of Estrogen o Obesity § Increased conversion androgens → estrogens (estrone) o Polycystic ovarian syndrome § Obesity/anovulation o Tamoxifen § Estrogen agonist o Hormone replacement therapy (estrogen only) o Ovarian granulosa cell tumor § Secrete estrogen § May present with uterine bleeding and adnexal mass Clinical Features o Presents as abnormal uterine bleeding o Same presentation as endometrial carcinoma o Same risk factors as endometrial carcinoma o Diagnosis: endometrial biopsy § Abundant, crowded glands Risk for endometrial carcinoma Graded based on histology o Architecture (simple, complex) o Cytological features (with or without atypical) Complex, atypical: high risk of cancer (endometrial carcinoma) Treatment: o Low-risk forms: Progestins § Oppose estrogen effects § Reverse hyperplasia § Improve bleeding o High-risk forms: Hysterectomy Leiomyosarcoma Malignant smooth muscle tumor of the uterus Arise de novo (not from fibroids) Occur in postmenopausal women Usually, a single large mass hemorrhagic or necrotic Aggressive Rapidly enlarging uterine masses Postmenopausal bleeding Unusual vaginal bleeding and pelvic pain p53 mutations and p16 overexpression Histology: o Appears as large necrotic tumor o Hypercellular tumor with marked cytological atypia, brisk mitosis and atypical mitosis Endometrial Carcinoma Most common gynecologic cancer Most common in postmenopausal women (80%) o Average age of diagnosis ~60 years old o Menopause: anovulation → with more estrogen exposure Classic presentation → Abnormal uterine bleeding o Commonly seen with uterine bleeding Associated with complex endometrial hyperplasia, diabetes, dysfunctional uterine bleeding, hypertension, infertility, obesity, prolonged estrogen use, tamoxifen use Endometrioid type is most common, followed by serous type. Clinical features: o Abnormal, dysfunctional, or postmenopausal uterine bleeding o Pelvic pain or mass/compression effect on adjacent structures o Abdominal bloating o Dyspareunia, dysuria (pain during intercourse, pain during urination) o General stigmata of malignancy, i.e., weight and appetite loss, malaise, fatigue o Rare cases asymptomatic Diagnosis → Endometrial biopsy o Often preceded by endometrial hyperplasia o Often driven by unopposed estrogen o Usually detected early o Often treated with total abdominal hysterectomy Pathophysiology: o Classified histologically o Major types: Endometriod and serous § Endometrioid subtype (Type I): Estrogen-dependent hyperplasia § Serous subtype (Type II): Estrogen independent Endometrioid Subtype Carcinoma: o Common o Due to estrogen-dependent hyperplasia o Risk factors: more estrogen = more risk o Resembles endometrium (endometrioid) Serous Subtype Carcinoma: o Estrogen-independent tumors o Pink, serous material on biopsy o Arise from atrophic endometrium post-menopause o 90% due to altered p53 tumor suppressor gene o Poor prognosis (aggressive) o Necrosis and Calcification commonly seen Stage IA IB II IIIA IIIB IIIC1 IIIC2 IVA IVB Endometrial Carcinoma FIGO Stage System Description Tumor is confined to the uterus with less than half myometrial invasion Tumor is confined to the uterus with more than half myometrial invasion Tumor involves the uterus and the cervical stroma Tumor invades serosa or adnexa Vaginal and/or parametrial involvement Pelvic lymph node involvement Para-aortic lymph node involvement, with or without pelvic node involvement Tumor invades bladder mucosa and/or bowel mucosa Distant metastases including abdominal metastases and/or inguinal lymph nodes Hereditary Non-Polyposis Colorectal Cancer/Lynch Syndrome (HNPCC) Germline mutation in DNA mismatch repair genes Leads to colon cancer Also increased risk of endometrial cancer o Most common non-colon malignancy o Lifetime risk up to 70% (3% in general population)