Female GU Disorders Flashcards

Question

Microinvasive Squamous Cell Carcinoma

Answer 1

Only a **small area of invasive disease** is seen (\< 5x7 mm) Term ‘microinvasive’ is used

Answer 2

* Presents as **abnormal vaginal bleeding** _usually following intercourse or douching_ * 10-20% of pts report: * **Bloody malodorous discharge** * **Pain often radiating to the sacral region** * Sx of _locally advanced or metastatic disease:_ **weight loss, pallor, BLE edema, rectal pain, hematuria** * _Gross examination_: **Ulcerative, exophytic (fungating) or infiltrative** patterns of growth

Answer 3

* Spreads by **direct local invasion** to the _adjacent tissues_ * **Lateral spread** may reach **bony pelvis** * Can encompass and obstruct one or both ureters * Most common cause of death in these pts * **Lymphatic spread late** * **Hematogenous spread even later**

Answer 4

* **Variant of squamous cell carcinoma** * Well-differentiated * Can get **very large** * Does not invade ⇒ **won’t metastasize**

Answer 5

* **Atypical** * Glandular cells * Endocervical cells * Endometrial cells * **Endocervical adenocarcinoma in situ (AIS)** * **Adenocarcinoma** * Endocervical * Endometrial * Extrauterine * Not otherwise specified (NOS)

Answer 6

Originate from glandular columnar epithelium. * **In situ adenocarcinoma (AIS)** * **Only affects glands** * No stromal response to indicate invasion * **Invasive adenocarcinoma** * Incidence ↑ * May be up to 25% of cervical CA * Also associated w/ **HPV** * Some secrete **mucin** * Some are associated w/ **DES** (clear cell carcinoma)

Answer 7

* _Organism_: **C*alymmatobacterium granulomatis*** * _Clinical and histology_: * **Large ulcerated lesions** contain **inflamed granulation tissue** and **numerous** **MΦ** * Bacteria are found in the cytoplasm of neutrophils, histiocytes and plasma cells (**Donovan bodies**) * Assumes the shape of a safety pin * Infection is more common in the tropics

Answer 8

* Caused by ***Chlamydia trachomatis*** * Clinical:: * **Transient vesicles** on penis or vagina that are often unnoticed * Followed by **inguinal lymphadenopathy** w/ formation of "**bubos**" * Inflamed lymph nodes esp. in the groin area * Bubos contain infected, purulent material * Must be aspirated or they may rupture

Answer 9

* Many different types referred to by many different names * Lesions are usually **white, scaly and fissured** (**leukoplakia**) * _Two main types:_ * **Lichen sclerosis** (most common type) * **Squamous hyperplasia**

Answer 10

* **Spectrum of dysplastic changes ranging from mild to severe** * Characterized by **nuclear and epithelial atypia** * Similar to SIL of the cervix * _Clinical presentation:_ pts may be **asymptomatic** or have **pruritis** * _Gross appearance:_ * ⅓ of pts ⇒ lesions are **hyperpigmented** * Remainder are **pink, white, grey or red** * Can be **macular** or **papular**, **single** or **multiple** * _Microscopic appearance_: **dyskeratotic cells** scattered throughout lesion * **VIN I (mild dysplasia)**: changes confined to lower ⅓ * **VIN II (moderate dysplasia)**: changes in lower ⅔ * **VIN III (severe dysplasia and CIS)**: full thickness * **CIS**: also referred to as **Bowen's disease** * Caused by **HPV**, usually seen in young women **20-35 y/o** * **Progression to invasive carcinoma is rare (6%)** * If it occurs, usu. in **postmenopausal women or immunosuppressed pts**

Answer 11

* **Slowly growing intra-epithelial multi focal neoplasm** * Arises **de novo** in the **epidermis** from **totipotent intra-epithelial precursor cells** * Can involve the **dermis** * Occurs in **genital, perianal and axillary regions** * Lesion may be **pruritic** * Usu. seen in **post-menopausal Caucasian women** * **Rarely associated w/ underlying sweat gland adenocarcinoma** * Unlike Paget's disease of the nipple (100% of cases show underlying ductal breast carcinoma) * Treatment is **wide local excision** * **Recurrences are common** b/c Paget cells extend beyond confines of visible gross lesion

Answer 12

* _Gross:_ * Has a **red, eczematoid appearance** * Tends to occur on the **labia majora** * _Microscopic appearance:_ * **Paget's cells** often occur in **nests** surrounded by **small hyperchromatic basaloid cells** * Isolated Paget cells may **file upward in the epithelium** * Cytoplasm is **pale** and **occasionally vacuolated** * Nuclei are **vesicular** w/ **finely distributed chromatin** * Nucleoli are prominent * Mitotic figures are infrequent

Answer 13

* Incidence in U.S. is 1.5/100k, represents **3% of all genital carcinoma** * Seen in **older women**, **usually \> 60 y/o** * _Gross Appearance & Clinical Presentation_ * **Pain, discomfort, itching and exudation** * Tumor is usually an **exophytic or endophytic ulcer** located on _labia majora or labia minora_ * _Microscopic appearance_ * Usually **well-differentiated** * _Pattern of Spread_: * **Inguinal nodes** * LN w/in the **pelvis, rectum** * **Parailiac nodes**

Answer 14

* _Stage I:_ **Tumor confined to vulva**, **2 cm. or less in diameter**. No suspicious groin nodes. * _Stage II_: **Tumor confined to vulva \> 2 cm.** w/o suspicious groin nodes. * _Stage III:_ **Extension beyond vulva.** No suspicious groin nodes. * _Stage IV_: **Grossly positive groin nodes,** regardless of size of 1° tumor * Likelihood of regional node metastases most related to size of 1° tumor

Answer 15

* **Microinvasive Vulvar Squamous Carcinoma** * **Depth of invasion \< 1 mm.** and not associated w/ inguinal LN metastasis * Stage **IA** * Treatment is **local excision** * **Invasive carcinoma** * If lesion has a depth \> 1 mm. ⇒ **groin node dissection is done** * Other prognostic factors include _diameter of lesion, tumor ulceration, grade and confluent growth_

Answer 16

* **Distinct variant** of squamous carcinoma w/ a unique biologic course * Resembles a **large condyloma acuminatum** * Usually seen in **post-menopausal women** * Very well-differentiated squamous lesion * **Usually no nodal metastasis** * Tx w/ **wide local excision**

Answer 17

**Similar to adenocarcinoma seen in the cervix**

Answer 18

* _Bacteria_ * ***Garderella vaginalis*** **(*Hemophilus vaginalis*)** * Accounts for 90% of nonspecific infections * See clue cells on pap smear * _Fungal_ * ***Candida*** * _Parasite_ * ***Trichomonas vaginalis*** * _Virus_ * **HPV**

Answer 19

* Less common than VIN and CIN * Annual incidence is 3/100k * _Epidemiology is same as for cervical intra-epithelial neoplasia (CIN)_ i.e. **exposure to HPV** * VAIN most often affects the **upper vagina** * **Multi-focal** in \> 50% of pts * **Asymptomatic**, can be detected on **colposcopy** * **Microscopic changes are same as for CIN** * Many pts have other lower genital tract neoplasms (cervix, vulva)

Answer 20

* **Most common carcinoma of vagina** * Infrequent, accounts for 1% of all gynecologic malignancies * Seen mostly in **older women (60-70)** * Must be differentiated from _vaginal extension of cervical or vulvar cancer_ and from _metastatic tumors_ * Valid dx of 1° vaginal CA requires **no cervical or vulvar CA @ time of dx and for** **≥** **10 years before dx** * Commonly occurs in **upper portions of posterior wall** * Can _spread dorsally_ to the **parametrium, bladder and rectum** * Most often **metastasizes to pelvic lymph and inguinal nodes** * May be **silent lesions**, or present as **vaginal bleeding or discharge** (leukorrhea)

Answer 21

* **Most common neoplasm of lower genital tract in girls** * Seen in those **\< 5 y/o** * Originates from **undifferentiated mesenchyme** w/ _striated muscle differentiation_ (embryonal rhabdomyoblasts) * _Grossly distinctive_: **polypoid grape-like mass,** may be seen at **introitus** * Prognosis is poor

Answer 22

* **Synthetic, estrogen** administered to women w/ high-risk pregnancies in 1940's-1960's * _Prenatal Diethylstilbestrol (DES) exposure results in:_ * **Vaginal adenosis** * **Atypical adenosis** * **Dysplasia** * **Clear cell adenocarcinoma of vagina and cervix**

Answer 23

* Related to **prenatal Diethylstilbestrol (DES) exposure** * Involves **upper ⅓ of the vaginal anterior wall** * Mucosa is replaced by **glandular epithelium** * Can then undergo **squamous metaplasia** * Similar changes can occur in the **cervix** * _Pathogenesis:_ * Adenosis develops from **persistent residual embryonic glandular epithelium** * May be a **precursor lesion for clear cell adenocarcinoma** of the vagina * Adenosis → atypical adenosis → dysplasia → clear cell adenocarcinoma

Answer 24

* Related to **prenatal Diethylstilbestrol (DES) exposure** * \< 14% w/ DES exposer develop adenocarcinoma * Seen in **young women** (average age 19 years) * Tumor may be **large or small** * Usually **asymptomatic** * Located **in the upper ⅓** of **anterior vaginal wall** * Microscopically, **resembles clear cell carcinoma of uterus and ovary** * It spreads **locally** and later **metastasizes** to **pelvic LNs and blood stream**

Answer 25

* Continuously grows in size from birth → puberty * Signficant growth during pregnancy * Does not revert to nulliparous size until menopause

Answer 26

* _D__ay 1-14_ ⇒ **proliferative endometrium** * Preovulatory * Simple glands * Mitotic figures within endometrial glands * _Day 14_ ⇒ **ovulation** * Post-ovulatory * _Day 17_ ⇒ **subnuclear vacuoles** * Presence means that ovulation has occurred * _Day 21_ ⇒ **secretory endometrium** * Gland complexity * Stromal edema * Secretions in glands * _Day 23_ ⇒ **pre-decidua around vessels** * _Day 26_ ⇒ **entire stroma now decidualized** * _Day 28_ ⇒ **menstrual endometrium** * Structure breaks down * Endometrial balls * “Crumbling”

Answer 27

* **Abnormal bleeding** _w/o lesion of the endometrium_ * Very common * Seen most often around **menarche** and **menopause** * _Etiologies:_ * **Anovulatory Bleeding** * **Inadequate luteal phase** * **Irregular shedding**

Answer 28

* **Most common cause of DUB** * No corpus luteum ⇒ **excess** **estrogen, no progesterone** * Then estrogen declines and get bleeding * Bleeding variable in amount and erratic * Most are d/t **subtle hormonal imbalances** * Some cases 2/2 **obesity, malnutrition, chronic systemic disease, endocrine disorders, polycystic ovaries**, etc.

Answer 29

**Inadequate progesterone** secretion from corpus luteum ## Footnote **See menstruation 6-9 days after LH surge**

Answer 30

* Heavy bleeding d/t **extended secretion of progesterone** from corpus luteum * See **secretory and proliferative phases together** on biopsy * Proliferative endometrium with stromal breakdown

Answer 31

Fusion defects & Atresias

Answer 32

**Inflammation of the endometrium** * **Acute Endometritis** * Usually near time of **delivery or miscarriage** * Caused by **retained products of conception (POC)** * Infection by **Strep** or **Staph** * **Chronic Endometritis** * See **plasma cells** in endometrium * Risk factors include **IUD, PID, retained POC** * **Special forms of endometritis** * TB, Mycoplasma, Chlamydia, fungi, Herpes simples, CMV, Parasites, sarcoid

Answer 33

* _Estrogens_ * **Stimulates the endometrium** * **Duration of exposure** more important than dose * Can get **hyperplasia** or **carcinoma** from prolonged administration * _Oral Contraceptives_ * **Shortens proliferative phase**, **secretory changes develop slowly** * After a few cycles, **atrophied endometrium w/ decidualized stroma** * _Known adverse reactions d/t oral contraceptives:_ * **Thromboembolism** w/ sudden death * **Hepatic adenoma** that can present as sudden intraperitoneal bleeding, jaundice * **Intimal fibrosis** and luminal narrowing of small arteries

Answer 34

Induce **acute and chronic inflammation** and **decidual reaction** **↑ incidence of infections**, particularly **actinomycosis**

Answer 35

* **Endometrial glands and stroma outside the uterus** * ‘Ectopic endometrial tissue’ * _Most common sites of occurrence:_ 1. Ovary 2. Uterine ligaments 3. Rectovaginal septum 4. Cul de sac and pelvic peritoneum 5. Intestine and appendix 6. Mucosa of cervix, vagina, fallopian tubes 7. Laparotomy scars * Seen in women of **reproductive age** (6-10%) * _Clinical manifestations:_ * **Pelvic pain, dysmenorrhea, infertility, dysuria, rectal pain**

Answer 36

* **Regurgitation theory** * Retrograde flow of products of menstruation * 90% of women have this and most don’t have endometriosis * **Benign metastasis theory** * Spread by vessels or lymphatics * **Extrauterine stem/progenitor cell theory** * Cells @ ectopic locations that differentiate into endometrium

Answer 37

_Endometriotic implants show:_ * Release of **proinflammatory and other factors** * Endometriotic stromal cells contain **aromatase** ⇒ ↑ estrogen production * Not in normal endometrial stromal cells * Conveys a survival advantage * Ass. w/ **endometrioid and clear cell ovarian CA**

Answer 38

* _Gross:_ * **Dark, ‘powder burns’** on laparoscopy, _undergoes cyclic bleeding_ * Ovaries can have **large cysts** containing _degenerated bloody material_ (**chocolate cysts**) * **Uterus does not enlarge** (in contrast to adenomyosis) * _Microscopic:_ * **Endometrial glands and stroma** * May be difficult to identify d/t surrounding **hemorrhage** and **fibrosis** * Sometimes just see **hemosiderin-laden** **MΦ** * MΦ + correct clinical sx ⇒ dx of ‘_presumptive endometriosis_’ * **Atypical endometriosis** shows cytologic **atypia and/or glandular crowding** * Looks like atypical endometrial hyperplasia * May be precursor to endometriosis-related ovarian CA

Answer 39

* **Presence of endometrial glands and stroma within the myometrium** * Common, benign * Most often seen in **peri-menopausal women** * Present w/ **bleeding** and **dysmenorrhea** * Uterus can become **enlarged w/ thickened myometrium** * **Can respond to hormones and cycle** * Treatment: hysterectomy * **Does not have malignant potential**

Answer 40

* Common cause of **abnormal bleeding** * Seen in women in **40s and 50s** * Can be **sessile or pedunculated** * **Polypoid fragments** of tissue w/ _epithelium on three sides_ * **Stromal cells** contain **chromosomal rearrangements** similar to other _benign mesenchymal tumors_ * Glands are ‘along for the ride’ * Can become **hyperplastic** but **very rarely become malignant**

Answer 41

* Another cause of **abnormal bleeding** * **Precursor** to endometrial adenocarcinoma (most common type) * 1% becomes malignant * **Simple (non-atypical)** **→** **atypical** **(EIN) →** **carcinoma** * _Morphologically:_ * **↑ Gland to stroma ratio** * **Abnl epithelial growth** relative to normal endometrium * Vary in **size** and **shape**

Answer 42

* Linked to **prolonged estrogen stimulation** of the endometrium * Anovulation * ↑ Estrogen production * Exogenous estrogen * _Conditions promoting hyperplasia include:_ * **Obesity** * Peripheral conversion of androgen to estrogen * **Menopause** * **Polycystic ovarian disease** (including Stein-Leventhal syndrome) * **Functioning granulosa cell tumors** of the ovary * **Excessive cortical function** (cortical stroma hyperplasia) * **Prolonged admin of estrogenic substances** (estrogen replacement therapy) * Same influences pathogenetic in some **endometrial CA**

Answer 43

* **Inactivation of the PTEN** tumor suppressor gene * Via deletion and/or inactivation * Plays a role in development of **hyperplasia** and **endometrial carcinoma** * Seen in 20% of hyperplasia, 30-80% of endometrial carcinomas

Answer 44

* _Historically used 4 categories:_ * Based on **simple vs. complex** architecture & **no atypia vs. atypia** * **Low-grade hyperplasia** ⇒ no or minimal atypia * **High-grade hyperplasia** (aka atypical hyperplasia) ⇒ has characteristics of intraepithelial neoplasia * Morphologic features ⇒ gland crowding and cytologic atypia * Genetic characteristics ⇒ PTEN mutations * _Now WHO uses only two categories:_ * **Non-atypical hyperplasia** * **Atypical hyperplasia** aka “Endometrial Intraepithelial Neoplasia (EIN)”

Answer 45

* **↑ Gland-to-stroma ratio** but **retain** **intervening stroma** * **Rarely progress to adenocarcinoma** * May evolve into **cystic atrophy** when estrogen stimulation is withdrawn * _Management:_ * If no further fertility desired ⇒ **hysterectomy** * If fertility desired ⇒ **trial of progestin therapy** and follow up

Answer 46

* **Complex patterns of proliferating glands w/ nuclear atypia** * Glands are **complex** w/ **branching** and may be **‘back-to-back’** * Approaches appearance of adenocarcinoma * Cells are **rounded** instead of elongated and **poorly oriented to BM** * **Hysterectomy** in these pts shows **adenocarcinoma in 23-48%**

Answer 47

* Some endometrial hyperplasia can show altered cellular differentiation (**metaplasia**) * Including presence of **squamous, ciliated cell, and mucinous metaplasia** * May result from **∆** **in epithelial-stromal relationships** * Induces **basal endometrial cells** to follow different differentiation pathways * Less easily classified

Answer 48

* **Atypical hyperplasia** precursor lesion * Both show **PTEN mutations** * ↑ signaling via **PI3K/AKT** pathway * ∆ Expression of **estrogen receptor-dependent** target genes * Can see also _activating mutations_ in **KRAS** * **PIK3CA** mutations in CA, but not hyperplasia * May relate to ability to **invade** * _20% of sporadic tumors_ show **DNA mismatch repair gene defects** * Also seen in women from HNPCC families * _50% of poorly diff CA_ shows **TP53 mutations** * **Links demonstrating estrogen-dependence:** * Ovarian estrogen-secreting tumor & HRT ⇒ ↑ risk of endometrial CA * Extremely rare in women w/ ovarian agenesis and those castrated early in life

Answer 49

* **Obesity** * **DM** * Abnl glucose tolerance in \> 60% * **HTN** * **Infertility** * Pts are often nulliparous w/ hx of functional menstrual irregularities consistent w/ anovulatory cycles * **Unopposed estrogen stimulation**

Answer 50

* **Localized polypoid tumor** vs **diffuse tumor** involving _entire endometrial surface_ * Usu. spreads by **myometrial invasion** → periuterine structures * Can spread **into broad ligaments** ⇒ palpable mass on pelvic exam * Eventually, tumor disseminates to **regional LNs** * Later, may metastasize to **lungs, liver, bones, and other organs** * _Histology:_ * Tends to be **well-differentiated** and **mimic normal endometrial glands (85%)** * Called **endometrioid endometrial adenocarcinoma** * Others may show **mucinous, tubal, or squamous differentiation**

Answer 51

_3-step grading system for endometrioid tumors:_ * **Grade 1:** Well-differentiated, easily recognizable glandular patterns * **Grade 2:** Moderately-differentiated, well-formed glands mixed w/ solid sheets of malignant cells * **Grade 3:** Poorly-differentiated, solid sheets of cells w/ few glands, more nuclear atypia and mitotic activity

Answer 52

* Endometrial adenocarcinomas may show **mucinous, tubal, or squamous differentiation** * Up to 20% contain **foci of squamous differentiation** * Squamous elements may be **benign-appearing** * Some _moderately or poorly differentiated endometrioid CA_ contain **squamous elements that are malignant** * Previously called adenoacanthoma and adenosquamous carcinoma * Now just _grade carcinomas based on glandular differentiation alone_ and **use the term squamous differentiation**

Answer 53

* **Less estrogen-dependent** and **less often preceded by hyperplasia** than Type I * Often arise in setting of **endometrial atrophy** * Pts are usu. **older** @ time of dx * Accounts for **15% of endometrial carcinoma** * All non-endometrioid carcinomas classified as **grade 3 (poorly differentiated)** regardless of histologic pattern * _Subtypes:_ * **Serous adenocarcinomas** * Resemble subtypes of **ovarian** **CA** * **Clear cell carcinoma** * **Malignant Mixed Muellerian Tumor (MMMT)**

Answer 54

* 90% of Type II w/ mutations in tumor suppressor, **TP53** * 1° _missense mutations_ ⇒ **accumulation of altered protein** * Same mutation seen in **EIN** * Most common subtype is **serous carcinoma** * Suggests that serous CA starts as surface epithelial neoplasm → adjacent gland structures → endometrial stroma * **Poor prognosis** * Tends to **exfoliate** * Undergo **transtubal spread** * **Implant on peritoneal surfaces** like ovarian CA * Often beyond uterus at dx

Answer 55

* Arise in **small atrophic uteri** (post-menopausal women) * Tumors usu. **large bulky tumors** or **deeply invasive into myometrium** * Invasive lesions can show **papillary growth pattern** ⇒ **papillary serous carcinoma** * **Marked cytologic atypia** including _high N/C ratio, atypical mitotic figures, and prominent nucleoli_ * _Relatively superficial endometrial involvement_ may be ass. w/ **extensive peritoneal disease** * Suggests spread by routes other than direct invasion ⇒ **tubal or lymphatic transmission** * More common Type II * Can also have a **predominantly glandular growth pattern** w/ marked cytologic atypia * Poor prognosis

Answer 56

* Commonly Type II Endometrial CA * **Vacuolated spaces within cells** * Very poor prognosis

Answer 57

Applies to Type I and Type II * _Staging based on extension:_ * **Stage I:** confined to the corpus uteri itself * **Stage II:** involves corpus and cervix * **Stage III:** extended outside the uterus but not outside the true pelvis * **Stage IV:** extended outside the true pelvis or obviously involves mucosa of bladder or rectum * _Cases in various stages can also be sub-grouped into 3 grades:_ * **G1:** well-differentiated adenocarcinoma * **G2:** differentiated adenocarcinoma w/ partly solid (\< 50%) areas * **G3:** predominantly solid or entirely undifferentiated carcinoma or serous or clear cell carcinoma * Includes all Type II CA

Answer 58

* **Carcinosarcomas** ⇒ Malignant Mixed Mullerian Tumor (MMMT) * **Adenosarcomas** ⇒ composed of stromal neoplasias in association w/ benign glands * **Pure stromal (mesenchymal) neoplasms** ⇒ ranges from benign (stromal nodule) to malignant (stromal sarcoma) Together, these tumors comprise **\< 5% of endometrial malignancies**

Answer 59

* **Endometrial adenocarcinoma w/ stromal differentiation** * Consists of **adenocarcinoma** mixed w/ **stromal (sarcoma) elements** * Arising from the same cell type * _Sarcomatous components_ may include **striated muscle cells, cartilage, adipose tissue, and bone** * **Bulky, polypoid tumors**, can **protrude through cervical os** * _Outcome_ is determined by **depth of invasion and stage** * **Grade and type** of _adenocarcinoma_ matters too * _Poorest outcome_ w/ **serous differentiation** * Tumors are **highly malignant** * 5-yr-survival rate 25-30% * MMMTs occur in **postmenopausal women** and present w/ **postmenopausal bleeding** * Many have **hx of previous radiation therapy**

Answer 60

**Benign epithelial component w/ malignant mesenchyme** * **Large broad-based endometrial polypoid growths** * May **prolapse through cervical os** * Dx based on **malignant appearing stroma** + **benign but abnormally shaped endometrial glands** * Presents w/ **abnormal bleeding** * Women in **4^th to 5^th decade** * **Low grade malignancy** * 25% recur * Rarely spread beyond pelvis * **Estrogen-sensitive**

Answer 61

Neoplasms that _resemble normal stromal cells_: * **Stromal Nodule** (Benign Mesenchymal Endometrial Tumor) * _Well-circumscribed aggregates_ of **endometrial stromal cells** in the myometrium * Mean age **47 yrs** * Presents w/ **abnormal bleeding** * **Stromal Sarcoma** (Malignant Mesenchymal Endometrial Tumor) * **Neoplastic endometrial stroma** _lying between muscle bundles of the myometrium_ * Can _infiltrate myometrial tissue_ **OR** _penetrate lymphatic channels_ (old term: endolymphatic stromal myosis) * ~50% of these tumors recur * **Distant metastases** can occur _decades later_ * ~15% of pts die from metastatic tumors * 5-yr-survival rate 50% * Often ass. w/ **chromosomal translocations** that create **fusion genes** (like other sarcomas)

Answer 62

**Benign tumor of myometrium** * **Most common uterine neoplasm** * Maybe the most common tumor in women * Commonly known as ‘**fibroids’** * Present in **20-30% of women over age 30** * Usu. found in **middle aged women** * Most leiomyomas **regress after menopause** * Very common in **black women** * **Estrogen** can make leiomyomas larger * **Progesterone and pregnancy** ⇒ ± rapid ↑ in size and hemorrhagic degeneration

Answer 63

40% have **abnormal karyotype** **Simple chromosomal abnormality** * Rearrangement of chromosomes **12q14** and **6p** * Involves **HMGIC** and **HMGIY** **genes** * Encode _DNA-binding factors_ that _regulate chromatin structure_ * Up to 70% of leiomyomas have mutations in **MED12 gene** * Ultimately _stimulates gene expression_

Answer 64

* Many asymptomatic * Sx include: **pain, pressure sensation, bladder compression** **→** **urinary frequency, sudden pain if disruption of blood supply occurs** * _Submucosal leiomyomas_ are most responsible for **abnormal bleeding and infertility** * Cause **uterine enlargement** * Complications: **spontaneous abortion, DIC, dystocia, postpartum hemorrhage** * Malignant transformation (leiomyosarcoma) is _extremely rare_

Answer 65

* _Gross pathology:_ * **Sharply circumscribed**, discrete, round, firm, **gray-white** tumors w/ **‘whorled’** appearance * Usu. seen in **myometrium** of _uterine corpus_ * _Can occur within the:_ * Myometrium (**intramural**) * Just beneath the endometrium (**submucosal**) * Beneath the serosa (**subserosal**) * Rarely can involve _uterine ligaments, lower uterine segment, or cervix_ * _Large tumors_ may develop areas of yellow-brown to red softening (**red degeneration**) * _Histology:_ * **Whorled bundles of smooth muscle cells** that resemble uninvolved myometrium * Usu. individual muscle cells are **uniform in size and shape** and have characteristics of nl SM (oval nucleus and long, slender ‘cigar-shaped’ cytoplasm) * Should not see many mitotic figures

Answer 66

* _Common:_ * **Atypical or bizarre (symplastic) tumors** * See nuclear atypia and giant cells * **Cellular leiomyomas** * _Rare:_ * **Benign metastasizing leiomyoma** * Uterine tumor that extends into vessels and migrates to other sites, most commonly the lung * **Disseminated peritoneal leiomyomatosis** * Presents as multiple small nodules on the peritoneum

Answer 67

* Uterine leiomyomas, even when extensive, may be _asymptomatic_ * If asymptomatic, **don’t need to treat** * If _symptomatic_, treatment options include: * **Hysterectomy** * **Myomectomy** * **Embolization of vessels to the leiomyoma** * **Endometrial ablation** (if bleeding is the major sx)

Answer 68

* Rare * 1.3% of uterine malignancies, 25% of uterine sarcomas * 1/800 tumors of uterine smooth muscle * Peak incidence **40-60 y/o** * Pts usu. present w/ **vaginal bleeding, pelvic pain** * Leiomyosarcomas are **not thought to originate from an existing leiomyoma** * _Diagnosis:_ * Main criterion is **↑ mitotic figures** * Need _10 mitoses per 10 HPF_ * Moderate-marked nuclear or large (epithelioid) cells & 5 mitoses/10 HPF ⇒ ± **leiomyosarcomas dx** * Cellular tumors w/ 5-9 mitoses /10 HPF and minimal atypia ⇒ **‘tumors of uncertain malignant potential’** * Treat w/ **TAH-BSO** * May recur after surgery * **\> 50% metastasize** → _lungs, bone, brain_ * 5-yr-survival 40%

Answer 69

* _Gross:_ * Most leiomyosarcomas are **intramural** and **fairly large** (average size 9 cm) * **Soft, gray, fleshy** mass w/ **necrosis, hemorrhage** * _Microscopic:_ * Cells are **spindled**, can show **pleiomorphism/atypia** * ± Moderate-marked nuclear or large (epithelioid) cells * ± Hypercellularity

Answer 70

**Most common lesions of the ovary** * **Surface inclusion cysts** * Secondary to **invagination of surface epithelium** * **Follicle cysts** (aka Cystic follicles) * Arise from _unruptured follicles or follicles that rupture_ * **Seal and undergo atresia** * Lined by **surface epithelium** that may be **luteinized** * Often **multiple** * **±** **↑ estrogen** ⇒ endometrial hyperplasia * May **rupture** and cause abd pain * **Corpus luteum cysts** * Seen in **ovaries of repro age women** * May **rupture**

Answer 71

* Affects **6-10 % of reproductive age women** * _Clinical manifestations:_ * **Hyperandrogenism, menstrual abnl, polycystic ovaries, chronic anovulation, ↓ fertility** * **Insulin resistance and** **∆** **adipose tissue metabolism** * Ass. w/ **obesity and Type 2 DM** * Ass. w/ **premature atherosclerosis** * **↑ Risk for endometrial hyperplasia and carcinoma** * _Pathogenesis:_ * **Dysregulation of androgen biosynthesis** * **Insulin resistance** * Admin of insulin mediators ass. w/ resumption of ovulation * _Morphology of ovary:_ * **Numerous cystic follicles** or **follicle cysts that enlarge the ovaries** * Isolated cysts seen in 20-30% of all women

Answer 72

* Usually in **postmenopausal women** * Present w/ sx similar to PCOS * Gross: **uniform enlargement of both ovaries** w/ **white/tan** appearance on sectioning * Microscopic: **hypercellular stroma w/ luteinization of stromal cells**

Answer 73

* **80% of ovarian tumors are benign** * Benign tumors more common in **young women (20-45)** * Malignant tumors more common at **later age (45-65)** * Ovarian CA is **3%** of all cancer in females * 5^th most common cause of CA death in US women * **Higher mortality rate** than other genital CA * _Often dx after spread beyond the ovary_ * Most are **non-functional** * Some tend to be bilateral * Large tumors ⇒ **abd distension and discomfort, GI and urinary sx**

Answer 74

* _↑ Risk of ovarian CA:_ * **Nulliparous** or **low parity** * **BRCA1** or **BRCA2** **mutation** * 20-60% risk of ovarian CA by age 70 * Most are **serous cystadenocarcinomas** * _↓_ _Risk of ovarian CA:_ * **Oral contraceptive use**

Answer 75

WHO Classify according to _cell type of origin_: * **Surface/fallopian tube epithelium & endometriosis** (most common) * **Germ cells** * Pluripotent * Migrate to ovary from yolk sac * **Ovarian stroma** * Can also see **metastatic tumors** to the ovary

Answer 76

**Most common cell of origin for ovarian tumors** * _3 major histologic types of epithelium:_ * **Serous** * **Mucinous** * **Endometrioid** * Each can be **benign, borderline or malignant** * Depends on whether epithelial tumor cells invade ovarian stroma * _Next can subclassify by other components:_ * **Cystic areas** ⇒ cystadenomas * **Cystic and fibrous areas** ⇒ cystadenofibromas * **Mostly fibrous areas** ⇒ adenofibromas

Answer 77

* **Benign lesions** * Usually show **flat epithelium and cystic areas** * **Malignant lesions** * Usually show **papillary projections and solid areas** * Carcinomas can **extend through tumor capsule** & **seed peritoneal cavity** * Resulting in **ascites** * Tumors grow **slowly** * Tumors usu. large & has spread beyond the ovary @ dx * **CA-125** is a marker for some ovarian CA * **Borderline lesions** * Neither clearly malignant nor clearly benign * Are in a ‘borderline’ category

Answer 78

* **Serous tumors** (30% of all ovarian tumors) * Benign ⇒ **serous cystadenoma** * Borderline (low malignant potential) * _Malignant_ ⇒ **serous (+/- papillary) cystadenocarcinoma** * Most common ovarian CA (40%) * 65% are bilateral * **Mucinous tumors** * _Benign_ ⇒ **mucinous cystadenoma** * Borderline (low malignant potential) * _Malignant_ ⇒ **mucinous cystadenocarcinoma** * **Endometrioid tumors** * **Clear cell adenocarcinoma** * **Brenner Tumor**

Answer 79

* **_Type I_** * **Low grade** **tumors** * Often arise in ass. w/ **borderline tumors or endometriosis** * _Many histologic subtypes:_ * Low grade serous * Endometrioid * Mucinous * **_Type II_** * **High grade serous carcinoma** * Arises from **serous intraepithelial carcinoma**

Answer 80

Surface (Muellerian) Epithelium Tumors * **30% of all ovarian tumors** * 40% of all ovarian malignancies * #1 ovarian malignancy (50% if we count borderline) * **25% are malignant** * _Benign and borderline_ most common **ages 20-45** * _Malignant_ **later** (unless familial) * Often **large** * Many are **bilateral** * Especially if malignant * Lined by **serous (tubal-like) epithelium** *

Answer 81

* **Low grade serous ovarian CA** * Less nuclear atypia and better survival * May arise in ass. w/ serous borderline tumors * **High grade serous ovarian CA** * Arises from **in situ lesions** in _fallopian tube fimbriae_ or from **serous inclusion cysts** in _ovary_ * BRCA1/2 women s/p prophylactic BSO had _marked epithelial atypia_ in tubes * Named ‘**Serous Tubal Intraepithelial Carcinoma’ (STIC)** * Atypia also seen in _sporadic high grade serous ovarian tumors_ * Others arise from **cortical inclusion cysts** of _ovary_ or **implantation of detached fallopian tube epithelium** _where ovulation has disrupted ovarian surface_

Answer 82

* **Unsure of risk factors for benign and borderline** * _Risk factors for malignant serous tumors:_ * **Nulliparity** * **Family hx** * **Heritable mutations** * **BRCA1** (5% of ovarian CA pts under 70) * **BRCA2** * Women w/ either of these have 20-60% ovarian CA risk by age 70

Answer 83

* **Serous cystadenoma** * Composed of **one or several cysts** w/ _smooth inner & outer surfaces_ * Cysts are **lined by a layer of tall columnar**, **serous secreting**, **ciliated or non-ciliated cells w/ no atypia** * Occasional **short papillary projections**, lined by same kind of cells * _Outer surface_ of tumor is covered by **mesothelial cells** * When there is **abundant fibrous stroma**, benign serous tumor called a **cystadenofibroma**

Answer 84

* Not clearly malignant or benign * See **surface proliferation** * No definite invasion into stroma * Concerning for invasive disease ⇒ must watch after removal

Answer 85

_Depends of degree of differentiation_ * Composed of **numerous cysts** w/ **many papillary projections and solid areas** * Epithelium piles up ⇒ **\> 1** **layer over the surface of the cysts** * **Solid masses of epithelial cells** that _invade into wall of the cysts_ * Cells are **atypical** w/ features of malignancy * Can see **psammoma bodies** * Also seen in papillary thyroid CA and meningiomas

Answer 86

Depends on degree of differentiation: **low grade** vs **high grade** Even if it _has extended to the peritoneum_ * **Borderline serous tumors** * May _arise from or extend to peritoneal surfaces_ as **non-invasive implants** * Possible behaviors: * **Remain** **localized** ⇒ asymptomatic * **Slowly spread** ⇒ intestinal obstruction or other complications after many yrs * **Develop into low-grade carcinoma** * Even then will usu. progress slowly * **High-grade serous tumors** * **Often** **widely metastatic** throughout abd @ presentation * Pts can experience **rapid clinical deterioration**

Answer 87

5-yr survival rate from diagnosis of: * _Borderline serous tumor_ * Confined to ovary: 100% * Involving peritoneum: 90% * May have protracted course and recur so 5-yr survival ≠ cure * _Malignant serous tumor_ * Confined to ovary: 70% * Involving peritoneum: 25%

Answer 88

* **20-25% of all ovarian tumors** * **Mid adult life** * **Few are malignant** * 3% of all ovarian CA * **Only 5% are bilateral,** \< serous tumors * Rarely involve surface of ovary * Many show mutations of **KRAS proto-oncogene** * **Tall columnar, mucin-secreting cells** * Often **very large tumors** * Can be malignant, benign or borderline * **Pseudomyxoma peritoneii** is a complication in 2-5% of pts * Mucinous, jelly-like, material throughout abdomen * Tends to reaccumulate after removal * Also seen w/ mucinous tumors of appendix and colon

Answer 89

Benign 80% of ovarian mucinous tumors

Answer 90

* _Distinguished from cystadenomas by:_ * **Epithelial stratification, tufting, and/or papillary intraglandular growth** * May look similar to adenomas or villous adenomas of the intestine * Low malignant potential

Answer 91

* Malignant growth * **Confluent glandular growth** ⇒ “**expansile” invasion** * Tumors w/ marked epithelial atypia but no invasive features ⇒ **“****intraepithelial carcinomas”** * 95% 10-yr survival rate if Stage I * Stage I ⇒ 90% 10-yr survival rate * Even if invasive * Mucinous carcinomas that have _spread beyond the ovary_ ⇒ usually fatal, but rare

Answer 92

* **10-15% of all ovarian cancer** * Most are **malignant** * See **solid** and **cystic** growth * 40% are bilateral * **Histologically similar to endometrial carcinoma** * 5-yr survival for Stage I is 75% * ~15-20% of pts also have **endometriosis** * Present ~10 yrs earlier than w/o endometriosis * Up to **30% of pts** also have an **independent endometrial carcinoma** in the _uterus_ * Still a good prognosis, likely not a metastasis * _Subtypes_: **Clear cell adenocarcinoma, Brenner tumors**

Answer 93

See similar molecular similarities to _endometrial endometrioid carcinoma_ * Mutations in **PTEN, PIK3CA, ARIDIA and KRAS** ⇒ **↑ PIEK/AKT** pathway signaling * PTEN mutations also seen in atypical endometriosis * Mutations in **mismatch DNA repair genes** and **CTNNB1 (Beta-catenin)** * **TP53** mutations in _poorly differentiated tumors_ * Just like in endometrioid CA of endometrium

Answer 94

* **Uncommon variant of endometrioid carcinoma** * Can see similar neoplasm in _endometrium, cervix, uterus and vagina_ * May be **solid** or **cystic** * _Microscopic:_ * **Large cells** w/ **clear cytoplasm or hobnail type cells** * Arranged in **solid, tubular or papillary configuration** * **Aggressive tumor** * Poor prognosis if beyond ovary

Answer 95

* **Transitional cell tumors** * Subtype of endometroid tumors * **10%** of ovarian epithelial tumors * Most are **benign**; usually **unilateral** * Usually **solid** and **firm**, 1-20 cm in diameter * **Fibrous stroma** containing **scattered groups of transitional epithelial cells**

Answer 96

* Uncommon variant * **Pronounced proliferation of fibrous stroma** underlying columnar lining epithelium * **Benign** **tumor** * Usually **small** and **multilocular** * May have **mucinous, serous, endometrioid or transitional epithelial components**

Answer 97

* Often presents w/ _vague sx_: **GI complaints, urinary sx, pelvic pressure** * Often found when large * _Benign tumors_ are removed ⇒ pt recovers * _If malignant:_ * May see **ascites** ⇒ can contain malignant cell * Tumor can _spread throughout peritoneum_ ⇒ **tiny nodules seed the serosal surface** * May spread to _liver, lungs, GI tract, opposite ovary_ * **Serum CA-125** * Good marker for known disease to monitor recurrence/progression * Not for screening

Answer 98

* **15-20%** of ovarian tumors * Germ cells are **totipotent** ⇒ tumors can contain a variety of tissues * Most are **mature teratomas** (Dermoid Cysts) ⇒ benign * _Others include:_ * **Immature teratoma** * **Dysgerminoma** * **Endodermal sinus (yolk sac) tumor** * **Choriocarcinoma** * **Embryonal carcinoma** * **Mixed germ cell tumor**

Answer 99

* **Benign teratomas** * Most common type of ovarian germ cell tumor * Usually **cystic** ⇒ also called "**Dermoid cysts**" * 10-15% are bilateral * Filled w/ **sebaceous material, hair shafts, and other tissue types** * Malignant transformation is rare

Answer 100

* **Malignant teratomas** * Usually seen in **children and young adults** * Contain **immature embryonic tissues** * Mostly **solid** w/ focal **necrosis** and **hemorrhage**

Answer 101

Specialized type of **monodermal** ovarian teratoma Entirely composed of **mature thyroid tissue**

Answer 102

Ovarian counterpart of **seminoma** * **Always malignant**, usually **unilateral** * **50%** of _malignant ovarian germ cell tumors_ * 2% of ovarian tumors * 75% in **2^nd and 3^rd decades** * **Some produce gonadotropins** * _Microscopic:_ * Large cells w/ **clear cytoplasm** and **centrally located nuclei in cords or sheets** * Separated by **thin, fibrous septa** that contains **lymphocytes**

Answer 103

* **Malignant** and **very aggressive** * Seen in **children and young women** * See **yolk sac differentiation** w/ **Schiller-Duval** **bodies** * Looks like a glomerulus * Contain _intracytoplasmic_ **hyalin droplets** * Droplets contain **Alpha-fetoprotein (AFP)** and **alpha-1-antitrypsin (AAT)**

Answer 104

* Rare tumor * Histologically identical to _choriocarcinoma of placental origin_ * **Much more malignant** w/ **early widespread metastases** * Produce **chorionic gonadotropin (hCG)** * Often seen as a _component in combo w/ other germ cell tumor types_

Answer 105

* **Solid tumor** w/ **necrosis** and **hemorrhage** * Micro shows **solid sheets and nests** of **large, primitive cells** * Can see **syncytiotrophoblast-like cells** * Secrete **chorionic gonadotropin (hCG)** * Can also see **↑** **alpha-fetoprotein (AFP)** levels

Answer 106

* **5%** of all ovarian tumors * _Include:_ * **Granulosa cell tumor** * **Thecoma and Fibroma** * **Sertoli-Leydig cell tumor** (Arrhenoblastoma) * **Leydig cell tumor** (Hilus Cell Tumor) * **Lipid cell tumor**

Answer 107

* _Epidemiology:_ * **5% before puberty** * **40% after menopause** * 10% bilateral * _Gross_: **smooth surface, lobulated**, gray-yellow color * _Micro_: **microfollicular** w/ **Call-Exner bodies** * See **coffee-bean nuclei** * 75% associated w/ **↑ estrogen production** * Endometrial hyperplasia/carcinoma in adults * Precocious puberty in children * **↑** **tissue and serum inhibin** * Risk of recurrence or spread is 5-25%, usually indolent

Answer 108

* 65% in **post-menopausal women** * Nearly all are **benign** * _Gross:_ **round, firm, solid** * _Micro:_ **fascicles of spindle cells**, can sometimes see **fat** * May see **↑ estrogen production** in _thecomas_ * Can see **ascites** and **right sided hydrothorax** (**Meigs’ Syndrome**) w/ _fibroma_ * Can be associated w/ **Basal Cell Nevus syndrome**

Answer 109

* **Sertoli-Leydig cell tumor** * **Leydig cell tumor** (Hilus cell tumor) * **Lipid cell tumor** * Rare, yellow or brown * 25% malignant * **Ovarian gynandroblastoma** * **Sex-cord Tumor w/ Annular Tubules** * About 1/3 of cases are associated w/ **Peutz-Jegher**

Answer 110

* Ovarian **virilizing tumor** * Rare tumor * Average age is **25 y/o** * Resembles **immature testis** w/ _Sertoli and Leydig cells_ * **~15% are malignant**

Answer 111

* Ovarian **virilizing tumor** * Can see cells containing **Reinke crystals** * **Benign**

Answer 112

* Ovarian **virilizing tumor** * **Mix of Granulosa and Sertoli-Leydig cell tumor** * Pts have **abnl sexual development** and **gonads of indeterminant nature** * 50% have a **coexistent dysgerminoma**

Answer 113

* **7%** of ovarian tumors are _metastatic_ * **50%** of these are _bilateral_ * Most often originate from **stomach, large bowel, appendix, breast, uterus and lungs** * **Krukenberg tumors** * Usually bilateral and solid * Diffuse infiltration by signet ring cells * Most often from stomach

Answer 114

* Acute infection of the fallopian tube * Usu. caused by **bacteria from uterine cavity** * #1 organism is **Gonococcus** but can also involve ***E. coli*, bacteroides, strept, chlamydia** * Gonococci penetrate into _subepithelial connective tissue_ * Cause **acute inflammation** w/: * **Pus accumulation** in tube lumen w/ distension * Pus drains out of fimbriated end → pelvis * **Fibrinous exudate** on serosa * _Nongonococcal bacteria_ can get to tubes via **uterine lymphatics** * Complications: **PID, tubo-ovarian abscess (TOA)**

Answer 115

* **Residual inflammation and alteration in tubes** _after an acute episode or repeated episodes of acute inflammation_ * _Gross:_ * **Adherence of mucosal plicae** and/or **closure of fimbriated end** * **fibrous adhesions** between tubes, adjacent peritoneum and ovary * Can result in **pyosalpinx** and/or **hydrosalpinx** * _Micro_: **lymphocytic and plasmocytic infiltration**

Answer 116

* Subtype of chronic salpingitis * l% of pts w/ infertility problem have **tuberculosis of oviducts** * 10% of women pts _dying of tuberculosis_ have **tuberculous salpingitis** * Source is from 1° tuberculosis somewhere else in the body * Blood borne TB **preferentially involves fallopian tubes** vs other female genitalia * Lesion starts from the **mucosa** **→** **muscular layer**

Answer 117

Very common and benign

Answer 118

**Diverticular lesion** of tubal epithelium in _isthmus_

Answer 119

**Presence of tubal epithelium in sites other than fallopian tube.**

Answer 120

“**Mesothelioma**” * **Benign tumors** * Small nodule * Counterpart can be seen in testis or epididymis

Answer 121

* Very rare * Malignant tumors * 50% are stage I at dx * 40% of pts die w/in 5 years

Female GU Disorders Flashcards

(154 cards)