Pathoma: Female Gu And Repro

Front 1

Bartholin Cyst

Back 1

d/t inflammation and obstruction of gland

painful, unilateral, cystic lesion at lower vestibule adjacent to vaginal canal

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Condyloma

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*Large, warty neoplasm of vulvar skin
*Commonly d/t HPV types 6 and 11 or occasionally secondary syphilis
*HPV-associated condylomas characterized by KOILOCYTES, the hallmark of HPV-infected cells
*Rarely progress to carcinoma

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Lichen Sclerosis

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*Thinning of epidermis and fibrosis of dermis
*white patch (leukoplakia) with parchment-like vulvar skin
*Most commonly in postmenopausal women
*Benign but slightly increased risk of squamous cell carcinoma

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Lichen Simplex Chronicus

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*Hyperplasia of vulvar squamous epithelium
*White patch (leukoplakia) with thick, leathery vulvar skin
*Assoc with chronic irritation and scratching
*Benign, no increased risk of squamous cell carcinoma

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Vulvar Carcinoma

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*Carcinoma arising from squamous epithelium lining the vulva
*rare and presents as leukoplakia; need biopsy to distinguish from other leukoplakia
*Etiology can be HPV-related (in repro age women, d/t forms 16 or 18) OR NON-HPV related (in postmen women, most often arising from long-standing lichen sclerosis)
*Arises from VIN (Vulvar intraepithelial neoplasia), a dysplastic precursor lesion characterized by KOILOCYTIC change (disordered cellular maturation, nuclear atypia, increased mitotic activity)

Front 6

Extramammary Paget Disease

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*Characterized by Malignant epithelial cells in the epidermis of the vulva
*presents as erythematous, pruritic, ulcerated vulvar skin
*represents carcinoma in situ (usually no underlying carcinoma vs. paget disease of the nipple)
*Must be distinguished from MELANOMA of the vulve (Paget is PAS +, Keratin +, S100 - and Melanoma is PAS -, Keratin -, S100 +)

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Adenosis

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*focal persistence of columnar epithelium (Derived by Mullerian ducts) in upper vagina -- it is not replaced by squamous epithelium (derived from urogenital sinus) from the lower vagina as it should be
*Increased incidence with exposure to DES in utero

Front 8

Clear Cell Adenocarcinoma of Vagina

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-malignant proliferation of glands with clear cytoplasm
-rare, but feared, complication of DES-associated vaginal adenosis (from DES exposure in utero)

Front 9

Embryonal Rhabdomyosarcoma

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-Malignant mesenchymal proliferation of immature skeletal muscle
-presents as bleeding and GRAPE-LIKE mass protruding from the vagina or penis of a child (also known as sarcoma bactryoides)
-RHABDOMYOBLAST is characteristic cell, which exhibits cytoplasmic cross-striations and positive immunohistochemical staining for DESMIN (for muscle) and MYOGENIN (immature skeletal muscle)

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Vaginal Carcinoma

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--arising from squamous epithelium lining the vaginal mucosa
-- related to high-risk HPV (16, 18, 31, 33)
-- Precursor lesion is VAIN (vaginal intraepithelial neoplasia)
-- When spread to lymphatics, cancer from lower vagina (from UGS) goes to inguinal nodes and cancer from upper vagina (Mull ducts) goes to regional iliac nodes

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HPV

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--DNA virus, especially affecting the cervical transformation zone
-- usually eradicated by acute inflammation but persistent infection leads to increased risk of cervical dysplasia (CIN, cervical intraepithelial neoplasia)
-- High risk HPV produced E6 and E7 proteins --> increased destruction of tumor suppressor proteins p53 (E6) and Rb (E7)

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Cervical Intraepithelial Neoplasia (CIN)

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-- characterized by Koilocytic change, disordered cellular maturation, nuclear atypia, and increased mitotic activity
-- Grades based on extent of epithelial involvement (CIN I is < 1/3 of epith thickness, CIN II is < 2/3 thickness, CIN III is slightly less than full thickness, and CIS is entire epithelium)
-- Progress to CIS is not inevitable but the more dysplasia, the more likely to progress to carcinoma

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Cervical Carcinoma

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--invasive and arising from cervical epithelium
-- most common in middle aged women (40-50)
-- Presents as POSTCOITAL VAGINAL BLEEDING or discharge
-- HPV is key risk factor, but other risk factors include: smoking and immunodeficiency (AIDS defining illness)
-- most common subtypes are squamous cell carcinoma and adenocarcinoma
-- Advanced tumors INVADE BLADDER through uterine wall, blocking the ureters --> HYDRONEPHROSIS with post renal failture is common cause of death

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Pap Smear: Limitations and confirmatory test

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-- Confirm with colposcopy (visualization of cervix with magnifying glass) and biopsy
-- Limitations include inadequate sampling of transformation zone (leading to false negatives) and limited efficacy in screening for adenocarcinoma!!!

Front 15

Asherman Syndrome

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--secondary amenorrhea due to loss of the basalis (which usually generates endometrium) and scarring
--result of overaggressive dilation and curettage

Front 16

What does an anovulatory cycle result in?

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-- estrogen-driven proliferative phase without subsequent progesterone-driven secretory phase
--common cause of dysfunctional uterine bleeding, especially during menarche and menopause

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Acute Endometritis

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--chronic inflammation of the endometrium
--presents as abnormal uterine bleeding, pain and infertility
--characterized by lymphocytes and plasma cells (plasma cells necessary for diagnosis since lymphocytes can be normal)
--caused by retained products of conception, chronic pelvic inflamm disease (e.g. chlamydia), IUD, and TB

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Endometrial Polyp

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--Hyperplastic protrusion of endometrium
--presents as abnormal uterine bleeding
--Can be side effect of TAMOXIFEN use (d/t its anti-estrogen effects on breast but weak pro-estrogen effects on endometrium)

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Endometriosis

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--Endometrial glands and stroma outside of endometrial lining
--dysmenorrhea and pelvic pain (and infertility)
--Most commonly involved ovary (resulting in "Chocolate cyst"), but can also involve uterine ligaments, pouch of douglas, bladder wall, bowel serosa, fallopian tube mucosa (where scarring increases risk of ectopic pregnancy)
--implants appear as yellow-brown "gun powder" nodules
--increases risk of carcinoma (especially if in ovary)

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Adenomyosis

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Endometriosis involving the uterine myometrium

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Endometrial Hyperplasia

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--hypertrophy of endometrial glands relative to stroma
--consequence of unopposed estrogen (from obesity, estrogen replacement, polycystic ovarian syndrome)
--presents as post-menopausal uterine bleeding
--classified based on architectural growth pattern (simple or complex) and whether cellular atypia present
--MOST IMPORTANT predictor of progression to carcinoma is presence of cellular atypia (simple with atypia being the most likely to progress)

Front 22

Endometrial Carcinoma

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--malignant proliferation of endometrial glands
--postmenopausal bleeding
*Hyperplasia pathway: 75% of cases, related to hyperplasia from estrogen exposure (nulliparity, annovulatory cycles, obesity, early menarche/late menopause), histology is endometriod
*Sporadic pathway: 25% of cases, no evident precursor lesions, serous histology with papillary structures and psammoma body formation -- p52 mutation commo

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Leiomyoma (Fibroids)

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--benign, neoplastic proliferation of smooth muscle from myometrium (most common tumor in females)
--related to estrogen exposure
--multiple, well-defined, whorled masses
--usually asymptomatic (but can include uterine bleeding, infertility and pelvic mass)

Front 24

Leiomyosarcoma

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--MALIGNANT proliferation of smooth muscle from myometrium
--ARISES DE NOVO (not from leiomyomas)
--usually in postmenopausal women
--Gross exam shows single lesion with areas of NECROSIS and HEMORRHAGE

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Follicle

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Oocyte surrounded by granulosa and theca cells

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LH

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--estradiol surge induces LH surge --> ovulation (beginning of secretory phase of cycle)
-- LH acts on theca cells to induce androgen production

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FSH

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stimulates granulosa cells to convert androgen to estradiol (drives proliferative phase of endometrial cycle)

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PCOD (polycytic ovarian disease)

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*multiple ovarian follicular cysts due to hormone imbalance
*characterized by increased LH and decreased FSH
*increased LH --> excess androgen production (in theca cells) --> androgen converted to estrone in adipose tissue --> excess estrone causes less FSH (from negative feedback) --> cystic degeneration of follicles
*high levels of circulating estrone increase risk for endometrial carcinoma
*presents as obese young woman with infertility, hirsutism (from excess androgens), and oligomenorrhea (some pts have insulin resistance and DM type 2)

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Surface Epithelial Ovarian Tumors

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--most common type (70%)
--Derived from coelomic epithelium that lines ovary
-- Two subtypes: serous (full of watery fluid) and mutinous (full of mucus-like fluid)
-- both types are usually cystic and can be benign, borderline or malignant
--usually present late with vague abdominal pain or fullness and urinary frequency (sign of compression)

Front 30

Cystadenomas (serous or mucinous)

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--Benign surface epithelial ovarian tumors
--single cyst with flat, simple lining
--usually premenopausal

Front 31

Cystadenocarcinomas (serous or mucinous)

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--Malignant surface epithelial ovarian tumors
-- complex cysts with shaggy, thick lining
-- usually postmenopausal
**BRCA1 carriers have incr risk for serous carcinoma of ovary and fallopian tube
--spread locally, especially to peritoneum
--CA-125 is a useful marker to screen for recurrence and monitor treatment

Front 32

Endometrioid Tumor

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--less common subtype of surface epithelial ovarian tumor
--usually composed of endometrial-like glands
--usually malignant
--May arise from endometriosis

Front 33

Brenner Tumor

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--less common subtype of surface epithelial ovarian tumor
--composed of bladder-like epithelium
--usually benign

Front 34

Germ Cell Tumors (women)

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--second most common type of ovarian tumor
--women of reproductive age
--subtypes mimic tissue normally produced by germ cells:
*Fetal tissue -- cystic teratoma, embryonal carcinoma
*Oocytes -- dysgerminoma
*Yolk sac -- endodermal sinus tumor
*Placental tissue -- choriocarcinoma

Front 35

Cystic Teratoma

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--Composed of fetal tissue derived from two or three embryologic layers (e.g. hair, bones, skin, gut, catilage, thyroid)
--Most common germ cell tumor (overall) in women and sometimes bilateral
--Benign BUT presence of immature tissue (usually NEURAL) or somatic malignancy (usually SCC of skin) indicates malignant potential
--Struma ovarii is a teratoma composed primarily of thyroid tissue

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Dysgerminoma

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--composed of large cells with clear cytoplasm and central nuclei (resemble oocytes)
--most common MALIGNANT germ cell tumor
--testicular counterpart is called seminoma (relatively common in males)
--Good prognosis and response to radiotherapy
--Serum LDH may be elevated

Front 37

Edodermal Sinus Tumor

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-- mimic yolk sac
-- most common germ cell tumor in CHILDREN
-- Serum AFP often elevated
-- SCHILLER-DUVAL BODIES (glomerulus-like structures) classically seen on histology

Front 38

Choriocarcinoma

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-- composed of trophoblasts and syncytiotrophoblasts
-- mimics placental tissue but villi are absent
-- malignant, small, hemorrhagic with early hematogenous spread
-- HIGH B-hCG (prod. by synctiotrophoblasts) is characteristic!! --> may lead to thecal cysts in ovary
-- poor response to chemotherapy

Front 39

Embryonal Carcinoma

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-- Malignant and composed of large primitive cells
-- aggressive with early metastasis