Exam 2

Question 1

The urinary and genital systems are developed from what layer embryologically?

Answer 1

Intermediate mesoderm

Question 2

What are the three nephric structures?

Answer 2

1. Pronephros: never functionally excretory, degenerates
2. Mesonephros: functional for 4 to 6 weeks, degenerates
3. Metanephros: definitive kidney

Question 3

Intermediate mesoderm in cervical region gives rise to what in the fourth week of embryogenesis?

Answer 3

The mesonephric duct (Wolffian Duct)—> pronephros —> mesonephros —> metanephros

Question 4

What does the mesonephric duct in males give rise to?

Answer 4

Ductus deferens and the ureteric bud (only ureteric bud in females)

Question 5

Ureteric buds penetrate a portion of the sacral intermediate mesoderm to form what?

Answer 5

Metanephric blastema (which will eventually become the nephron/glomeruli

Question 6

What makes up a uriniferous tubule?

Answer 6

1. A nephron, derived from the metanephric blastema
2. Collecting tubule, derived from the ureteric bud

Question 7

Kidneys initially developed in the pelvic region, and ascend in what weeks?

Answer 7

Between the sixth and ninth week

Question 8

Ascending kidneys are progressively revascularized by a series of arterial sprouts from the dorsal aorta. If one or more of these transient renal arteries fails to regress, what results?

Answer 8

Accessory renal arteries

Question 9

What is an ectopic ureter?

Answer 9

Failure of ureter to open into the inferior lateral wall of the bladder, and instead opens to the neck of the bladder causing incontinence. Can also attach to uterus/vaginal wall

Question 10

Why do supernumerary kidneys occur?

Answer 10

Duplication of ureteric bud before connecting with the metanephric blastema

Question 11

What is crossed renal ectopia?

Answer 11

The left/right kidney crosses to the opposite side and fuses with that kidney (typically left)

Question 12

What’s the difference between autosomal dominant and autosomal recessive polycystic kidney disease?

Answer 12

Autosomal recessive is diagnosed at birth (many perpendicular long cysts) and may cause renal insufficiency, pulmonary hypoplasia, and death

Question 13

Bilateral renal agenesis from oligohydramnios can cause what?

Answer 13

Potter sequence: fatal

Question 14

What is the cloaca?

Answer 14

A region that is partitioned by the urorectal septum into a ventral urogenital sinus (becomes splatter, pelvic urethra, genital tubercle) and dorsal anorectal canal

Question 15

What are the different urachal malformations?

Answer 15

1. Urachal fistula (urine dribbling from abdomen)
2. Urachal sinus (discharge from sinus, no direct connection to the bladder)
3. Urachal cyst (small or large, no opening to the outside or to bladder)

Question 16

What is megacystis?

Answer 16

Pathologically large urinary bladder. Caused by congenital disorder that blocks outflow of urine from the bladder (typically seen in males), may lead to megacystitis and renal failure in early childhood

Question 17

What is exstrophy of the bladder?

Answer 17

• typically seen in males
• exposure and protrusion of the mucosal surface of the posterior wall of the bladder to the outside world
• caused by incomplete median closure of the inferior part of the anterior abdominal wall and the anterior wall of the bladder

Question 18

The primitive gonad first appears as what?

Answer 18

A genital ridge of the proliferating intermediate mesoderm on the medial surface of the mesonephros

Question 19

What are the origins of the suprarenal (adrenal) glands?

Answer 19

• cortex: mesenchyme of the urogenital ridge
• medulla: neural crest cells from adjacent sympathetic ganglia

Question 20

What is perimenopause?

Answer 20

• time before, during, and after menopause
• irregular menses for four years pre-menopause
• starts around 37-38 years old, when pool of oocytes starts depleting

Question 21

What is menopause?

Answer 21

• permanent cessation of menses
• amenorrhea, hypoestrogenenemia
• median age of 51
• premature in smokers, ovarian insufficiency, PCOS, endometriosis

Question 22

What are the concerns of a patient going through menopause?

Answer 22

HHAVOCS:

• hot flashes
• heat intolerance
• atrophy of vagina
• osteoporosis
• coronary artery disease
• sleep impairment, sexual dysfunction

Question 23

Explain early perimenopause:

Answer 23

• estrogen levels relatively unchanged
• increased FSH level
• CBD risk factors: increased C-IMT and vascular remodeling, decreased endothelial function

Question 24

Explain late perimenopause:

Answer 24

• decreased estrogen levels and decreased AMH
• very increased FSH
• increased fat mass (abdomen) and decreased lean muscle mass
• Decrease energy expenditure, increased energy intake
• CVD risk: dyslipidemia, increased C-IMT and vascular remodeling, decreased endothelial function, increased insulin resistance, increased sleep disturbance

Question 25

Explain postmenopause:

Answer 25

* decreased estrogen for two years after, then stabilizes * significantly increased FSH for two years, then stabilizes * increased abdominal fat, decreased lean mass for two years then stabilizes * decreased Sleep and physical activity expenditure, decreased fat oxidation * CVD: lipidemia, insulin resistance, glucose intolerance, sleep disturbance

Question 26

What are the hormonal changes of menopause?

Answer 26

• follicles decrease • estrogen decreases • inhibin decreases • FSH increases (increases LH and GnRH due to lack of negative feedback from estrogen

Question 27

Postmenopausal estrogen comes from where?

Answer 27

Aromatization of adrenal androgens in the muscle and adipose tissue

Question 28

What happens when progesterone production stops?

Answer 28

• unopposed estrogen (leads to high levels) • increased endometrial cancer in early menopause • increased abnormal bleeding • decreased androgen production from ovaries and adrenals

Question 29

What are the indications for hormone replacement therapy in menopause?

Answer 29

• hot flashes, vaginal atrophy, osteoporosis high risk

Question 30

What are the contraindications of hormone replacement therapy?

Answer 30

• pregnancy, undiagnosed vaginal bleeding, active VT, current gallbladder disease, liver disease, unopposed estrogen with uterus, cardiovascular disease

Question 31

What are the side effects of hormone replacement therapy?

Answer 31

Vaginal bleeding, breast tenderness, mood changes

Question 32

What is an FDA approved medication for hot flashes?

Answer 32

• Paxil (paroxetine), an SSRI • Venlafaxine may also work (SNRI)

Question 33

What are the screening recommendations for cervical cancer?

Answer 33

• begin screening at 21 • start HPV screen at 25 • <25 normal screening every three years • >25 normal and negative HPV screen get every five years, if HPV every three years years • discontinue at age 65 if adequate screening throughout the lifetime

Question 34

What are some risk factors for cervical cancer?

Answer 34

• HPV, smoking, early coitarche, DES exposure, immunocompromised, multiple sexual partners

Question 35

Both squamous cell and adenocarcinoma of the cervix come from what problem?

Answer 35

Disordered epithelial gross at the basal layer of the transformation zone (squamoepithelial junction)

Question 36

Why are HPV 16, 18 the highest risk for cervical cancer?

Answer 36

They produce the E6 gene that inhibits P53, and E7 that inhibits pRb ~ can cause cervical, anal, penile, oral, tongue, throat, vulvar cancer

Question 37

What are the levels of cervical cancer results?

Answer 37

1. Negative intraepithelial lesion or malignancy 2. ASCUS (atypical squamous cells of unknown significance) 3. LSIL (low-grade squamous intraepithelial lesion) 4. HGSIL (high-grade squamous intraepithelial lesion)

Question 38

What is a colposcopy?

Answer 38

• putting vinegar (acetic acid) on the transformation zone of the cervix—> if cells change to white, this is indicative of disease • biopsy required for white changes • Endocervical curettage (ECC) • endometrial biopsy if a typical glandular cells present

Question 39

What is kisspeptin?

Answer 39

* a neuropeptide that controls the activation of gonadotrophin releasing hormone **(GnRH)** neurons, and contains **estrogen receptors for feedback** * located in the anteroventral periventricular nucleus and the arcuate nucleus of the hypothalamus

Question 40

Kiss-1 of the AVPV is responsible for what?

Answer 40

**surge** • activates GnRH neuron by projection onto and direct stimulation of the preoptic area

Question 41

Kiss-1 of the ARC (arcuate nucleus) is responsible for what?

Answer 41

**pulse** * inhibits GnRH * co-expresses neurokinin B (opioid dynorphin B, NKB and Dyn) * oscillations of NKB and Dyn drive the pulse release of kisspepin, which intern drives the pulse of GnRH

Question 42

What does FSH from the anterior pituitary stimulate?

Answer 42

Granulosa cells in the ovarian follicles to synthesize aromatase (which converts androgens from the theca interna cells into estradiol) ~ increasing estrogen levels feedback to inhibit FSH release

Question 43

During the follicular phase of the menstrual cycle, FSH stimulates what?

Answer 43

The maturation of ovarian follicles

Question 44

What is luteinizing hormone?

Answer 44

• LH stimulates steroid release from the ovaries, ovulation, and the release of progesterone after ovulation by the corpus luteum • causes theca interna cells to produce androstenedione (androgen) • **at critical concentration of estradiol, negative feedback on LH is shut off and positive feedback of LH creates the LH SURGE, which initiates ovulation**

Question 45

What drugs promote folliculogenesis/cause hyperstimulation of follicles?

Answer 45

• FSH, LH, aromatase inhibitors, estrogen antagonists • examples: clomiphene (E2 antagonist), and letrozole (aromatase inhibitor)

Question 46

What drug induces ovulation?

Answer 46

• hCH (analog of LH that binds to the LH/hCG receptor of the granulosa and theca cells of the ovary to cause LH surge) • examples: ovidrel, pregnyl, novarel, chorex, profasi

Question 47

What drugs can control the timing of of ovulation OR can be used as uterine fibroid treatment?

Answer 47

• GnRH agonist/antagonists • examples: leuprolide (GnRH agonist), ganirelix/cetrorelix (GnRH antagonist)

Question 48

What drugs maintain pregnancy?

Answer 48

• progestins • example: levonorgestrel

Question 49

What drugs are used as contraception OR post menopausal symptom relief?

Answer 49

• estrogen/progestins • examples: ethinyl estradiol + norethindrone or medroxyprogesterone acetate

Question 50

What drugs are used for endometriosis and PCOS treatment?

Answer 50

• estrogen/progestins, aromatase inhibitors, GnRH agonist/antagonists • examples: E2/PR (estrogen/progesterone), letrozole/anastraxole/exemestane (aromatase inhibitors), goserelin/leuprolide (GnRH agonists), degarelix (GnRH antagonist)

Question 51

What are uterine stimulants?

Answer 51

• oxytonics or uterotonics • mech: increased tone of muscles and induce uterine contractions • used for: induce/facilitate labor, decrease postpartum hemorrhage, induce abortion

Question 52

What are uterine relaxants?

Answer 52

• tocolytics • mech: inhibit uterine contractions • used to: stop premature labor, by time for fetal lungs to develop (not used long-term)

Question 53

What is oxytocin (Pitocin)?

Answer 53

• **uterotonic that activates Gq protein coupled receptors and initiates contraction** • used for: labor induction, facilitation of labor, postpartum hemorrhage, milk letdown postpartum • SE: vasodilation (hypotension, reflex tachycardia), water retention (ADH activation), uterine uterine hyperstimulation (rupture, impaired O2 delivery to baby)

Question 54

What is ergonivine?

Answer 54

• **uterotonic that is an alkaloid from a fungus that grows on cereal grasses such as wheat/rye that prolongs tetany** • used for: postpartum hemorrhage • SE: vasoconstriction (HTN), vasospasm of arteries (angina), nausea/vomiting, blurred vision, headache

Question 55

What are prostaglandin drugs used in pregnancy?

Answer 55

• **Dinoprostone (PGE2), misoprostol (PGE1) • activates Gq protein coupled receptors** • used for: facilitation of labor, postpartum hemorrhage, induction of abortion • SE: N/V/D, uterine pain, uterine hyperstimulation, Dinoprostone can lead to bronco construction **~ fetal SE= PDA cannot close**

Question 56

What are the tocolytics used for uterine relaxation?

Answer 56

• terbutaline (beta2 agonist) • nephedipine (Ca2+ channel blocker) • indomethacin (Cox inhibitor) • atosiban (oxytocin receptor antagonist) ~ all used for the prevention or arrest of preterm labor

Question 57

Explain Terbutaline as a tocolytic

Answer 57

* selective **beta-2 adrenergic receptor agonist** that stimulates Gs protein coupled receptor, raising cAMP and interfering with myosin light chain kinase (MLCK) * SE: stimulates sympathetic system (tachycardia, palpitations, tremor, nervousness)

Question 58

Explain nephedipine as a tocolytic

Answer 58

* Ca2+ channel blocker (preferentially binds vascular smooth muscle)—> no effective contractions * SE: vasodilation, flushing, dizziness

Question 59

Explain indomethacin as a tocolytic

Answer 59

* cyclooxygenase (COX) inhibitor (nonselective COX 1/2)—> **inhibits the formation of prostaglandins** * SE: premature closure of ductus arteriosus in fetus, hemorrhages (decreases platelet aggregation)

Question 60

Explain atosiban as a tocolytic

Answer 60

• oxytocin receptor antagonist with a rapid onset • not approved in the USA, only in Europe

Question 61

Explain magnesium sulfate as a pregnancy drug

Answer 61

• historical tocolytic due to decrease of calcium • used as a neuroprotective for fetus (given to women at risk of preterm birth) • used to prevent seizures associated with eclampsia

Question 62

Chromosomal sex

Answer 62

• determined at fertilization (46XX, 46XY)

Question 63

Gonadal sex

Answer 63

* differentiation based on gene expression cascade kicked off by transcription factor **SrY** on the Y chromosome (otherwise leads to **beta catenin Wnt4** female pathway)

Question 64

Genital sex is determined by what?

Answer 64

Differentiation due to steroid hormones and other factors produced by differentiated gonads (both internal and external)

Question 65

What is the pathway of development into a female?

Answer 65

Genital ridge —> bipotential gonad —> XX —> **beta-catenin, Wnt4, Rspo1** —> ovary with granulosa/thecal cells—> follicles creating estrogen —> **Mullerian duct forming female internal genitalia + female external genitalia**

Question 66

What is the pathway of development into a male?

Answer 66

Genital Ridge —> bipotential gonad —> **SrY, Sox9** —> testes with Sertoli and leydig cells —> Sf1 via sertoli and leydig —> AMH, testosterone —> regression of Mullerian duct, DHT + wolffian duct —> Wolffian leads to internal male genitalia, DHT leads to penis, prostate, scrotum

Question 67

What happens embryogenically at five weeks?

Answer 67

Proliferation of epithelium and underlying mesenchyme medial to the primitive kidney results in a **gonadal Ridge and formation of the gonadal cords**

Question 68

What happens embryogenically at week six?

Answer 68

Primordial germ cells have migrated from yolk sack into the genital ridge to become gametes

Question 69

What does the Wolffian duct become?

Answer 69

Vas deferens, epididymis, seminal vesicle

Question 70

What does the Mullerian duct become?

Answer 70

Oviduct, uterus, cervix, upper portion of vagina

Question 71

What is required for testosterone from leydig cells to become dihydrotestosterone required for descent of testes and development of male genitalia?

Answer 71

5-alpha reductase

Question 72

What is Turner syndrome?

Answer 72

• 45, X genotype (paternal sex chromosome is missing) • female phenotype but dysfunctional ovaries—> secondary sex characteristics do not develop • other characteristics: **short stature, high arched palate, webbed neck, shield-like chest, inverted nipples, bicuspid aortic valve, renal anomalies**

Question 73

What is Klinefelter syndrome?

Answer 73

* 47, XXY genotype * male sex and phenotype * characterized by: **infertility, gynecomastia, impaired sexual maturation, atrophic testes, small penis, reduced/lack of secondary male characteristics**

Question 74

What are the three main categories of differences of sex development (DSD)?

Answer 74

1. Gonadal dysgenesis 2. Undervirilization of 46, XY males 3. Overvirilization of 46, XX females

Question 75

What is ovotesticular DSD (true gonadal intersex, 46,XX)?

Answer 75

• both testicular and ovarian tissue is present • occurs when both medulla and cortex of gonads develop • phenotype can be either male or female female but external genitalia is ambiguous

Question 76

What is overvirilization (46, XX) DSD?

Answer 76

• clitoral enlargement and labial fusion, persistent urogenital sinus • can be caused by **congenital adrenal hyperplasia or exposure to exogenous androgenic agents during pregnancy**

Question 77

What is undervirilization (46, XY) DSD?

Answer 77

• external and internal genitalia variable depending on degree of development • can be caused from a 5-alpha reductase deficiency (cannot convert testosterone to DHT)

Question 78

What is androgen insensitivity syndrome (46, XY)?

Answer 78

• genetic basis: loss of function mutation of the X linked androgen receptor gene • may lead to complete loss of function: female secondary sexual characteristics and external genitalia, vagina ends in blind pouch and uterine structures are rudimentary or absent. **testes present** • partial: some masculinization of external genitalia, enlarged clitoris. **Testes present** ~ testes maybe removed due to high risk of tumor development

Question 79

Why do anomalies of the female reproductive tract occur?

Answer 79

* arrested development of the uterovaginal primordium during the eighth week of embryogenesis (incomplete/failure of paramesonephric duct or incomplete canalization of the vaginal plate)

Question 80

What is diethylstilbestrol (DES) known for?

Answer 80

• used as a miscarriage preventative in the 1950s-1970s • **DES alters differentiation of the Mullerian-derived structures and changes the expression patterns of HOX genes** • daughters exposed in utero developed: 1. Vaginal clear cell carcinoma 2. Vaginal adenosis 3. T-shaped uterus (infertile)

Question 81

What is cryptorchidism?

Answer 81

• undescended testes due to disrupted androgen signaling • typically resolves within the first year, if not it can **result in sterility or germ cell tumors**

Question 82

What is hypospadias?

Answer 82

• external urethral orifice is on the ventral surface of the penis • caused by inadequate production of androgens or inadequate receptor sites

Question 83

What can testicular dysgenesis syndrome lead to?

Answer 83

• increase in testicular cancer • hypospadias • cryptorchidism • decrease in sperm count

Question 84

What can phthalate syndrome lead to in males?

Answer 84

• smaller/malformed penis • undescended testicles • shortened anogenital distance

Question 85

What is endometriosis?

Answer 85

• ectopic endometrial tissue at a site outside of the uterus leading to intrapelvic bleeding and adhesions (most commonly the ovary) • may cause: infertility, pelvic pain, dysmenorrhea dysuria, pain on defecation/rectal wall involvement

Question 86

What are some unique histology findings of endometriosis?

Answer 86

• endometrioma: chocolate cyst • adenomyosis: growth of endometrium into the myometrium

Question 87

What is the regurgitation theory of endometriosis?

Answer 87

Retrograde flow of endometrial tissue from the fallopian tube with origin from the uterine endometrium

Question 88

What is the benign metastasis theory of endometriosis?

Answer 88

Vascular/lymphatic spread with origin from the uterine endometrium

Question 89

What is the metaplastic theory of endometriosis?

Answer 89

Arises directly from coelomic epithelium (pelvic/abdominal peritoneum) or metaplasia of mesonephric rests, with origin from cells outside of the uterus giving rise to endometrial tissue

Question 90

What is the extrauterine stem/progenitor cell theory of endometriosis?

Answer 90

Stem cells from bone marrow can give rise and differentiate into endometrial tissue, the origin is from cells outside of the uterus

Question 91

What is a beneficial treatment for endometriosis?

Answer 91

**Aromatase inhibitors:** estrogen increases survival and persistence of endometriotic tissue

Question 92

What are common mutations in endometriosis?

Answer 92

**PTEN, ARID1A** (Seen in endometriosis cysts, atypical endometriosis, and associated cancers)

Question 93

What does disordered proliferative/non-menstrual shedding look look like on histology?

Answer 93

Question 94

What is the most common cause of dysfunctional uterine bleeding?

Answer 94

**Anovulatory cycle:** failed ovulation results in prolonged to unopposed estrogen driven proliferation phase causing dilated glands and stromal condensation

Question 95

What is acute endometritis?

Answer 95

• an ascending infection from the lower genital tract (commonly group A hemolytic streptococci, staphylococci) • symptoms: fever, elevated WBC count, pelvic pain • PMN rich stromal infiltrate • curettage and antibiotics are curative

Question 96

What is chronic endometritis?

Answer 96

• abnormal bleeding, pain, discharge, infertility • may be due to chlamydia, many with no identifiable cause

Question 97

What is the histology of chronic endometritis?

Answer 97

* **presence of plasma cells** * sarcoidosis or TB may show granulomas

Question 98

What are endometrial polyps?

Answer 98

* exophytic benign masses of varying size projecting into the endometrial cavity * may be asymptomatic or cause abnormal bleeding * association with tamoxifen (breast cancer drug that causes weak proestrogenic affect in the endometrium)

Question 99

Why is endometrial hyperplasia important?

Answer 99

* it is a cause of abnormal uterine bleeding and a precursor to the most common type of endometrial cancer (hypertrophic, endometrioid) * defined as: increase in gland compared to stroma and **increased gland to stroma ratio > 1:1**

Question 100

What are the causes of endometrial hyperplasia?

Answer 100

**prolonged estrogen stimulation** * anovulation * obesity * estrogen replacement therapy/tamoxifen for breast cancer * ovarian stromal hyperplasia * ovarian granulosis cell tumor * PCOS

Question 101

What are the common gene mutations of endometrial hyperplasia?

Answer 101

• **inactivation of PTEN—> overactive PI3K/AKT growth pathway** • Cowden syndrome may develop endometrial carcinoma (germline PTEN mutation)

Question 102

Type 1 endometrial carcinoma (endometrioid)

Answer 102

• age of onset: 55-65 • **clinical: unopposed estrogen, obesity, hypertension, diabetes** • morphology: **endometrioid** • **precursor: hyperplasia** • gene mutation: PTEN, ARID1A, PIK3CA, KRAS, FGF2, MSI, WNT signaling, TP53 • spread: lymphatics, indolent

Question 103

Type 2 endometrial carcinoma (atrophic, serous)

Answer 103

* age of onset: 65-75 * clinical: **atrophy, thin physique** * morphology: **serous, clear cell, mixed Mullerian tumor**, with psammoma body formation and papillary formation * precursor: **serous endometrial intraepithelial carcinoma** * genetic mutations: **TP 53**, aneuploidy, PIK3CA, FBXW7, CHD4, PPP2R1A * spread: aggressive intraperitoneal and lymphatic spread

Question 104

Endometrial carcinoma pathways

Answer 104

• type 1: hyperplasia (unopposed estrogen) endometrioid, non-atypical hyperplasia via PTEN, MLH1, KRAS, etc. • type 2: sporadic atrophic endometrium via TP53/aneuploidy, etc.

Question 105

Endometrial carcinoma staging

Answer 105

• stage 1: confined to corpus uteri • stage 2: involves corpus and cervix • stage 3: extends outside the uterus, but not outside the true pelvis • stage 4: extends outside true pelvis and involves mucosa of the bladder or rectum

Question 106

What is a malignant mixed Mullerian tumor?

Answer 106

* endometrial adenocarcinoma with component of malignant mesenchymal tissue * **homologous stroma:** resembles normal uterine stroma (leiomyosarcoma, endometrial stromal sarcoma) * **heterologous stroma:** resembles stroma not present in the uterus (skeletal= rhabdomyosarcoma, cartilage= Chondrosarcoma, bone= osteosarcoma)

Question 107

What is a uterine leiomyoma (also known as fibroids)?

Answer 107

* benign smooth muscle neoplasm occurring singly or with multiple nodules * sharply circumscribed, round nodules with myometrial location * micro: uniform spindle cells, rare mitotic figures,**White, tan and whorled**

Question 108

What is uterine leiomyosarcoma?

Answer 108

• malignant mesenchymal neoplasm with different differentiation towards smooth muscle • arises from myometrial or endometrial stromal precursor cells • genetic mutation: **MED12**

Question 109

Fungal/yeast infection of the vagina/cervix

Answer 109

* **Candida:** normal vaginal flora, symptomatic overgrowth due to disturbance in microenvironment * diabetes, antibiotics, pregnancy, altered immunity may cause infection * pseudohyphae/yeast on KOH prep or Pap smear

Question 110

Herpes simplex two

Answer 110

* genital mucosa and skin infection leading to red papules/vesicles/painful ulcers on the vulvar surface and cervix/vagina * systemic symptoms include fever, malaise, tender inguinal nodes * **latent in the lumbosacral nerve ganglia**

Question 111

What are the three M’s of herpes simplex 2 virus infection?

Answer 111

1. Multinucleation 2. Margination 3. Molding

Question 112

Molluscum contagiosum: pox virus

Answer 112

• typically an STI in adults: genitals, inner thigh, lower abdomen, buttocks • pearly dome shaped papules with center depression/dimple • six week incubation period, can last month to a year

Question 113

What does molluscum contagiosum look like on histology?

Answer 113

• distinctive cup shaped lesion composed of molluscum bodies in the epidermis above the stratum basale

Question 114

What is trichomonas vaginalis?

Answer 114

* flagellated protozoan transmitted sexually * 4 days-4 weeks: develops **yellow frothy discharge,** discomfort, dysuria, painful intercourse * red vagina and cervical mucus with dilated vessel **(strawberry cervix)**

Question 115

What is bacterial vaginosis?

Answer 115

• infection with gardnerella vaginalis (coccibaccilli covered squamous cells on Pap smear) • thin gray/green odorous discharge

Question 116

What is primary syphilis (Treponema pallidum)?

Answer 116

• chancre: perineal or vulvar shallow ulcer 3 to 4 weeks post infection • lymphocytic and plasma cell rich infiltrate, perivascular epithelial hyperplasia

Question 117

What is secondary syphilis?

Answer 117

* 4-8 weeks post chancre constitutional symptoms * mucocutaneous lesions, moist papules **(condyloma lata)**, and a scaly rash of the palms and soles * latency can last many years

Question 118

What is tertiary syphilis?

Answer 118

• characterized by **gumma (granulomatous lesions)** • multiple disseminated lesions that show granulomas, lymphocytes, histocytosis cells microscopically

Question 119

What are the most common causes of pelvic inflammatory disease?

Answer 119

1. Neisseria gonorrhea: a sense along mucosal surfaces beginning in the endocervix 2. Chlamydia: ascends through lymphatics, deeper infection

Question 120

What are the acute complications of pelvic inflammatory disease?

Answer 120

• peritonitis • bacteremia leading to endocarditis, meningitis, suppurative arthritis

Question 121

What are the chronic complications of pelvic inflammatory disease?

Answer 121

• infertility • tubal obstruction • ectopic pregnancy • pelvic pain • adhesions and intestinal obstruction

Question 122

What is a Bartholin cyst?

Answer 122

• inflammation of the Bartholin gland duct leading to obstruction and cyst formation (transitional or squamous lining)

Question 123

What is lichen sclerosus of the vulva?

Answer 123

• smooth white plaques or macules which may coalesce • thinning of the epithelium, labia becomes **atrophic**, and the vaginal orifice constricts • due to activated T cells in the subepithelial infiltrate, an autoimmune disorder

Question 124

What is lichen simplex chronicus (squamous cell hyperplasia) of the vulva?

Answer 124

* non-specific condition from rubbing or scratching to relieve pruritus * **thickened epidermis and hyperkeratosis** with variable dermal lymphocytes, no cytologic atypia

Question 125

What is condyloma acuminatum?

Answer 125

* **genital wart: exophytic and verrucoid** * can be vulvar, perineal, perianal, vaginal, or cervical * typically caused by **HPV 6 or 11** * micro: papillary tree-like branching stromal cores, koilocytosis with perinuclear halo, wrinkled nuclear membrane, binucleation

Question 126

Squamous cell carcinoma: Basaloid and warty

Answer 126

• related to HPV 16 • younger age, peaks at 50 • arises from VIN, multicentric

Question 127

Squamous cell carcinoma of the vulva: keratinizing

Answer 127

* related to **long-standing lichen sclerosis or squamous hyperplasia** * more common, peaks in 70+ * high frequency of **TP53** mutations

Question 128

Vulvar carcinoma staging

Answer 128

Question 129

What is extramammary paget disease (vulva glandular neoplasia)?

Answer 129

• pruritic, red crusted map-like area on labia minora • IHC: cytokeratin 7+, CEA and mucicarmine +

Question 130

What is vaginal adenosis?

Answer 130

• vagina initially covered by endocervical type glandular epithelium and a small patches remain following normal squamous replacement during development • seen more commonly in women exposed in utero to DES

Question 131

Vaginal intraepithelial neoplasia (VaIN)

Answer 131

* almost all associated with HPV 16, 18 * greatest risk factor is prior cervical or vulvar carcinoma * **upper vagina more commonly involved** (spreads to iliac nodes) * lower 2/3 of vagina less commonly involved (spread to inguinal nodes)

Question 132

What is sarcoma bottyoides (embryo rhabdomyosarcoma)?

Answer 132

• vaginal neoplasia seen in infants and children under five • polypoid grape-like masses protruding from the vagina • mesenchymal tumor with different differentiation towards skeletal muscle • can mimic and inflammatory polyp • local invasion of peritoneal cavity and urinary tract

Question 133

What is polycystic ovarian syndrome?

Answer 133

• a complex endocrine disorder characterized by hyperandrogenism, menstrual abnormalities, polycystic ovaries, chronic anovulation, and decreased fertility • presents with obesity, hirsutism, type two diabetes, premature atherosclerosis • multiple cystic follicles with luteinizing theca layer hyperplasia

Question 134

What is ovarian carcinoma?

Answer 134

• a malignant lesion with bilateral spread and nodal metastasis (and liver/lung) • cytologically positive ascites fluid with orangeophilic psammoma bodies

Question 135

What seromarker can be used to monitor disease progression and recurrence for **ovarian carcinoma?**

Answer 135

CA-125

Question 136

What are the three classifications of ovarian neoplasia?

Answer 136

1. Surface epithelial: fallopian tube epithelium and endometriosis (older ages) 2. Germ cell: Pluripotent cells from the yolk sack (younger ages) 3. Sex cord/Stromal

Question 137

What are the types of surface epithelial ovarian neoplasia?

Answer 137

1. Serous 2. Mucus 3. Endometrioid ~ all can have benign, borderline, or malignant forms

Question 138

What gene mutations increase the risk for surface epithelial/stromal ovarian neoplasia?

Answer 138

Type 1: low-grade, arise in borderline tumors, **KRAS, BRAF, ERB2, wild type TP53** Type 2: high-grade, arise from serous intra-epithelial carcinoma, **BRCA1, BRCA2, TP53, wild type KRAS and BRAF**

Question 139

What is a malignant serous tumor type 1?

Answer 139

• low-grade micropapillary serous carcinoma • micro: more complex testing, micropapillary pattern, moderate cytologic atypia

Question 140

What is an ovarian benign serous cystadenoma?

Answer 140

• thin-walled cyst with variable solid tissue and smooth inner lining • micro: simple layer of psychologically bland serous epithelium

Question 141

What is an ovarian malignant serous tumor type 2?

Answer 141

• either cystadenocarcinoma or adenocarcinoma, with increased solid tissue and complex papillations, necrosis commonly present • Increased cytologic atypia, destructive stromal invasion with desmoplastic reaction

Question 142

What is a unique feature of borderline ovarian tumors?

Answer 142

They can spread to peritoneal services with **non-invasive implants and slow progression**

Question 143

What genetic mutation is consistently present in ovarian mucinous neoplasia?

Answer 143

KRAS

Question 144

Ovarian benign mucinous tumors:

Answer 144

• cystadenoma, cystadenofibroma • intact, surface rarely involved • can be large (25kg) • often multiloculated cystic filled with thick mucin

Question 145

What are the cell types of an ovarian benign mucinous tumor?

Answer 145

• tall columnar epithelium with basal nuclei and apical mucin vacuole vs goblet cell • minimal nuclear stratification

Question 146

What changes as an ovarian mucinous tumor becomes borderline from benign?

Answer 146

• increased complexity of gland contours and pilling/tufting of epithelium

Question 147

What are the unique features of ovarian mucinous carcinoma?

Answer 147

* more solid, less cystic. Necrosis common * metastasis from G.I. tract is common (**appendix**) * if bilateral, typically metastatic * confluent glandular growth, destructive stromal invasion and desmoplasia (marked cytologic atypia)

Question 148

What is pseudomyxoma peritonei?

Answer 148

* **mucinous ascites** and cystic epithelial implants on peritoneal surfaces * commonly from the **appendix** or G.I. origin, may be ovarian/ovarian involvement

Question 149

Ovarian tumors typically metastasize to where?

Answer 149

• uterus, fallopian tube, contralateral ovary, pelvic peritoneum (Mullerian origin) • breast and G.I. tract

Question 150

What is a Kruckenberg tumor?

Answer 150

Bilateral metastatic mucinous signet ring carcinoma of the ovaries, often gastric origin (diffuse carcinoma)

Question 151

What are the mutations seen in ovarian endometrioid neoplasia (and ovarian clear cell carcinoma)?

Answer 151

• increased PI3K/AKT pathway • PTEN, PIK3CA, ARD1A, KRAS • mismatch DNA repair genes (HPCC) • TP53 mutations

Question 152

What does ovarian endometrioid carcinoma look like microscopically?

Answer 152

• low-grade • well formed endometrial type glands with confluent growth

Question 153

What does ovarian clear cell carcinoma look like?

Answer 153

Question 154

What is a Brenner tumor?

Answer 154

* benign surface epithelial tumor composed of bladder-like epithelium * ovarian transitional cell neoplasia * sharply demarcated nests of transitional cells in ovary stroma * Usually solid, can have cystic transitional component

Question 155

What is the most common ovarian germ cell neoplasia?

Answer 155

**Benign cystic teratoma (dermoid cyst)** • young women in active reproductive years • lined with squamous, skin, hair, sebaceous glands, teeth (calcification)

Question 156

What are the monodermal variants of an ovarian mature cystic teratoma?

Answer 156

1. Stroma ovarii: all thyroid 2. Carcinoid: all neuroendocrine 3. Stromal carcinoid: thyroid and neuroendocrine

Question 157

What is an ovarian dysgerminoma?

Answer 157

* ovarian counterpart of testicular seminoma, malignant ovarian germ cell tumor * elevated hCG, **KIT mutations** * large vascular cells with clear cytoplasm **(fried egg)** and lymphoid infiltrates * very chemo responsive

Question 158

What is an ovarian yolk sac tumor?

Answer 158

* extraembryonic differentiation of malignant germ cells seen in children/young women * **elevated AFP, alpha-fetoprotein** * rapid growing pelvic mass, unilateral * **schiller duval bodies:** central vessel surrounded by epithelium in a space led by epithelium

Question 159

What is an ovarian choriocarcinoma?

Answer 159

• malignant mixed germ cell tumor that secretes high levels of hCG • chemo resistant, fatal

Question 160

What are unique features of ovarian granulosa cell tumors (seen in older women)?

Answer 160

1. Call-exner bodies (gland like structures with central acidophilic material) 2. Coffee bean nuclei (longitudinal groove in the nuclei)

Question 161

What is the most common genetic mutation for an adult granulosis cell tumor?

Answer 161

FOXL2 ~ serum inhibin stain can be a biomarker for identification/monitoring

Question 162

What are the tumors arising in ovarian stroma that are composed of fibroblasts, plump spindle cells with a lipid droplets or a mixture of the two?

Answer 162

Fibroma, thecoma, fibrothecoma * present with ascites, Meig’s syndrome * association with basal cell Nevus syndrome * presents at younger age

Question 163

What is Meig’s syndrome?

Answer 163

ovarian fibroma + ascites + hydrothorax on the right side

Question 164

What do ovarian fibroma/thecoma/fibrothecomas look like microscopically?

Answer 164

• spindle cells with scant cytoplasm • variable lipid vacuoles and luteinization • varying collagen bands

Question 165

Over 50% of Sertoli/Leydig tumors have mutations of what?

Answer 165

DICER1: encoding an endonuclease involved in proper processing of micro-RNAs • these tumors are typically benign, hormonally active, and produce masculinization or defeminization

Question 166

What is seen microscopically in sertoli leydig tumor?

Answer 166

Sertoli: • tubules of well differentiated columnar cells • basal nuclei, uniform Leydig: • plump polygonal cells • pink cytoplasm/round nucleus • **crystalloid of Reinke**

Question 167

Ovarian pure Leydig cell tumors

Answer 167

Question 168

Natural birth control methods require what?

Answer 168

• female with regular, predictable cycles • both partners dedicated

Question 169

What are the best birth control methods for STI protection?

Answer 169

Male/external and female/internal condoms

Question 170

What is unique about the diaphragm as a form of birth control?

Answer 170

It must be left in for at least six hours (max 48) post intercourse in order to not disturb the barrier and allow sperm through

Question 171

The sponge birth control method has what side effects?

Answer 171

Increased rate of yeast infections, UTIs, and toxic shock syndrome if left in place for extended period

Question 172

What are the absolute contraindications for an estrogen/progesterone birth control?

Answer 172

• previous thromboembolic event/stroke • hx of CAD or 2+ risk factors for ASCVD • hx of estrogen dependent tumor • liver disease • pregnancy • undiagnosed abnormal uterine bleeding • smoker over age 35 and >15cigs/day • migraine headaches with neurological symptoms • uncontrolled hypertension • diabetes > 20 years with nephropathy, retinopathy or neuropathy

Question 173

What are the non-contraceptive benefits of combined estrogen/progesterone birth control?

Answer 173

• reduction in dysmenorrhea, heavy menstrual bleeding, and ovarian/endometrial cancers • improves acne, hirsutism, benign breast disease, osteopenia, and osteoporosis • decreases functional ovarian cysts

Question 174

What are the formulation options for the combined estrogen/progesterone birth control?

Answer 174

• oral • vaginal ring • transdermal patch

Question 175

What is drospirenone?

Answer 175

• a spironolactone analog with anti-mineralocorticoid and lower endogenic effects • improves weight stability and water retention in individuals taking contraceptives • SE: may increase serum potassium, increase in VTE risk

Question 176

What is a monophasic estrogen/progesterone pill?

Answer 176

Same fixed dose for 21/7-24/4 days

Question 177

What is a biphasic, triphasic estrogen/progesterone pill?

Answer 177

• varying doses through the first three weeks + a placebo week

Question 178

What are extended cycle estrogen/progesterone pills?

Answer 178

84 or 365 days of fixed dose hormones (breakthrough bleeds more common initially)

Question 179

When using the vaginal ring, when do you need a back up contraception?

Answer 179

If it has been outside of the vagina for longer than three hours

Question 180

Transdermal estrogen/progesterone patches are contraindicated in what patients?

Answer 180

BMI > 30

Question 181

What are the formulations for progesterone only birth control?

Answer 181

• oral (minipill) • injectable • implant • IUD

Question 182

What are the issues to consider when talking about progesterone only birth control?

Answer 182

* irregular bleeding * potential androgenicity side effects * Slow return to fertility * breakthrough ovulation if pills are missed * effects on bone health

Question 183

Timing is the most critical with what birth-control formulation?

Answer 183

Progesterone only mini pill (must be within three hours otherwise backup contraception is needed)

Question 184

What is levonorgestrel?

Answer 184

• plan B • one step, take within **72 hours** of unproductive intercourse

Question 185

What is ulipristal acetate?

Answer 185

• Ella, morning after pill • can use up to **120 hours, five days** post unprotected intercourse • progesterone agonist/antagonist • side effects of headache, nausea/dizziness more common than Plan B

Question 186

IUD comparison graph:

Answer 186

Question 187

What are the major contraindications of IUDs?

Answer 187

• pregnancy • congenital or acquired uterine cavity malformation • acute pelvic infection • uterine bleeding of unknown cause • breast cancer (for hormone based) • Wilson’s disease/copper allergy (for copper IUD)

Question 188

What post procedure follow-up must be done following vasectomy?

Answer 188

Semen analysis to assure no motile sperm (three months following vasectomy, approximately 20 ejaculations) ~ other form of contraception is needed until this follow up

Question 189

What is the primary cause of cervicitis or vaginitis?

Answer 189

Anything that causes the pH to rise and disrupts the balance of lactobacilli which can lead to overgrowth of organisms

Question 190

What is the difference between chronic cervicitis and acute?

Answer 190

Chronic: lymphocyte rich, germinal centers form (follicular cervicitis) Acute: neutrophilic infiltrate, sometimes purulent

Question 191

What are cervical polyps?

Answer 191

• benign lesions (small bumps to large masses protruding through the cervical os) that may cause bleeding • micro: loose fibrovascular stroma covered by benign endocervical epithelium • removal is curative

Question 192

What is a cervix Nabothian cyst?

Answer 192

* most common cervical cyst, forms when squamous metaplasia obstructs gland outlets leading to dilation with mucus * patients typically have multiple, they are typically superficial but can extend through the cervix wall

Question 193

What is cervical microglandular hyperplasia?

Answer 193

* benign proliferation of endocervical glands with polypoids * micro: tightly packed glandular units, small lumens, flattened epithelium, squamous metaplasia common

Question 194

What’s the difference between low risk and high risk HPV causing cervical malignant/pre-malignant disease?

Answer 194

Low risk: condylomata (6 and 11) High risk: dysplasia, progression to cervical cancer (16, 18, 31, 33)

Question 195

Where does HPV typically infect in the cervix?

Answer 195

Basal squamous cells where exposure occurred, **immature squamous metaplasia at the transformation zone (squamocolumnar junction)**

Question 196

What is the pathogenesis of high-risk HPV causing cervical cancer?

Answer 196

**HPV viral proteins E6 and E7** • **E7 binds RB** and promotes its degradation, inhibits p21 and p27, cyclin dependent kindness inhibitors • **E6 binds p53** promoting its degradation, up regulating telomerase

Question 197

Where is the viral DNA when considering low risk condyloma versus high-risk cancer?

Answer 197

Low risk: viral DNA is extrachromosomal High risk: viral DNA is integrated into the host genome, increasing E6 and E7 expression and dysregulating oncogenes

Question 198

What is the progression of cervical pre-malignant disease?

Answer 198

CIN1 (LSIL) —> CIN2-3b (HSIL)

Question 199

What is the most common cervical carcinoma?

Answer 199

Squamous cell carcinoma (80%), adenocarcinoma (15%), adenosquamous or neuroendocrine (5%)

Question 200

How is early micro-invasive cervical carcinoma treated?

Answer 200

**Cone biopsy** (invasive disease treated with hysterectomy and regional node dissection/radiation and chemotherapy)

Question 201

How does microinvasive versus invasive squamous cell carcinoma of the cervix look microscopically?

Answer 201

Question 202

How does adenocarcinoma in situ versus invasive adenocarcinoma of the cervix look microscopically?

Answer 202

Question 203

What do the Pap smear cells look like for an LSIL-CIN1?

Answer 203

Question 204

What do the Pap smear cells look like for an HSIL-CIN2-3?

Answer 204

Question 205

How is HPV testing compared to Pap smear for cervical carcinoma screening and prevention?

Answer 205

HPV test is more sensitive but less specific than the Pap smear.

Question 206

What are the order of actions for cervical carcinoma screening?

Answer 206

1. Pap smear. If atypical squamous cells: 2. HPV screening. If 16 or 18: 3. Reflex testing (colposcopy with acetic acid). If positive: 4. Biopsy (cone if malignant)

Question 207

What are the two layers of the embryonic disc?

Answer 207

1.**Epiblast:** the thicker layer, consisting of high columnar cells that forms the floor of the amniotic cavity and is continuous with the amnion 2. **Hypoblast:** consisting of small cuboid cells forming the roof of the exocoelomic cavity

Question 208

What is an important characteristic of the second week of embryo development?

Answer 208

The appearance of the primary chorionic villi

Question 209

What is an extrauterine implantation?

Answer 209

• ectopic pregnancy • blastocyst implants outside of the uterus and may cause rupture of the uterine tube and hemorrhage into the peritoneal cavity in the first eight weeks • may be confused with appendicitis due to similar pain symptoms

Question 210

What is placenta previa?

Answer 210

• Implantation of the blastocyst in the inferior segment of the uterus near the internal os of the cervix • may cause bleeding, and C-section requirement

Question 211

Relatively large doses of progestin/estrogen prevent what?

Answer 211

Implantation of the blastocyst

Question 212

What is gastrulation?

Answer 212

Occurs in the third week of development, giving rise to the three germ layers (ectoderm, mesoderm, endoderm)

Question 213

The ectoderm gives rise to what?

Answer 213

Epidermis, CNS, PNS, eyes, internal ears, neural crest cells, connective tissues of the head

Question 214

The mesoderm gives rise to what?

Answer 214

Skeletal muscles, blood cells, lining of blood vessels, visceral smooth muscular coats, serosal lining of body cavities, ducts and organs of the reproductive and excretory systems, majority of the cardiovascular system

Question 215

The endoderm gives rise to what?

Answer 215

Epithelial linings of the respiratory and digestive tracts, glandular cells of organs such as liver and pancreas

Question 216

What is the primitive streak?

Answer 216

• appears on the surface of the epiblast of the bilaminar embryonic disc • marks the beginning of an embryo patterning of craniocaudal axis

Question 217

What functions as the primary inductor (signaling center) in the early embryo?

Answer 217

The notochord

Question 218

What is neurulation?

Answer 218

• neural plate invagination forming neural grooves which can then become neural tubes

Question 219

What do the neural crest cells give rise to?

Answer 219

The sensory ganglia of the spinal and cranial nerves

Question 220

What are somites?

Answer 220

•Cells derived from the primitive node forming the Paraxial mesoderm. • Responsible for the craniocaudal patterning of the body • found on either side of the neural tube

Question 221

What are the two major folds in embryological development?

Answer 221

**1. Craniocaudal fold:** creates cylindric embryo, cranial and caudal regions ventrally as the embryo elongates **2. Lateral towards the medial:** folding of the sides of the developing embryo produces right and left lateral faults resulting in an Omphaloenteric duct

Question 222

What forms in week five of embryogenesis?

Answer 222

• enlargement of head: growth of brain/face • cervical sinus forms • kidneys

Question 223

What happens in week six of embryogenesis?

Answer 223

• movement of trunk and limbs • external ear development • intestinal growth (herniation allowing for proliferation)

Question 224

What happens in week seven of embryogenesis?

Answer 224

• differentiation of digits • upper limb ossification

Question 225

When does substantial weight gain occur in embryogenesis?

Answer 225

Weeks 21 to 25

Question 226

When do slow and fast eye movements occur in embryogenesis?

Answer 226

Slow: weeks 13 to 16 Fast: weeks 21 to 25

Question 227

When do the lungs and pulmonary vasculature develops efficiently enough to provide adequate gas exchange?

Answer 227

Weeks 26 to 29

Question 228

When can the CNS direct rhythmic breathing movements and control body temperature?

Answer 228

Weeks 26 to 29

Question 229

What contributes to the differentiation of outer cells to trophoblast and inner cells to the pluripotent inner cell mass in the pre-implantation embryo?

Answer 229

* asymmetric daughter cell inheritance of **transcriptional regulators** among outer and inner cells during cleavage * environmental signals/cell polarization suppressing **hippo** signaling in the outer cells * a double negative feedback loop of transcription regulator expression between inner and outer cells

Question 230

The left-right asymmetry of the human body is a result of what event during embryonic development?

Answer 230

Directional pattern of ciliary beating at the primitive note

Question 231

When do the two major global demethylation events that occur in the human life cycle take place?

Answer 231

1. In blastomeres during cleavage 2. In primary germ cells at the time of embryonic gonad formation

Question 232

In which cells are chromosome parent of origins specific imprints erased during a global DNA methylation event?

Answer 232

Primordial germ cells

Question 233

What mechanism best explains cell fate decisions occurring in the germ layers (ectoderm, mesoderm, endoderm)?

Answer 233

Combinatorial patterns of transcription factor and signaling molecule activity

Question 234

During the process of fertilization, what causes critically important events (exocytosis of cortical granules, resumption and completion of meiosis 2, activation of the first cell cycle and development program of the zygote)?

Answer 234

A rise cytoplasmic calcium in the oocyte

Question 235

What is the difference between oogonia and spermatogonia entering meiosis?

Answer 235

Oogonia: enter meiosis before birth, arrest at prophase 1 Spermatogonia: enter meiosis beginning at puberty

Question 236

What persists in adult men but is absent in adult women, leading to adult men producing sperm throughout their life but the amount of eggs a woman has is finite?

Answer 236

1. Spermatogonia persist in adult men (men can make more sperm cells) 2. Oogonia are absent in adult women (women cannot make any more eggs)

Question 237

Left to right assymmetry in embryogenesis arises from what?

Answer 237

The ability of primitive node cilia to concentrate **Nodal on the left side** of the embryo, resulting in regional activation of **Ptx2**

Question 238

Dorsal-ventral neural cell identities in the neural tube are instructed by what?

Answer 238

Opposing gradient of **BMP and SHH** ~ also opposing gradients of transcription factors such as **Pax6, Pax7, and NKx6.1**

Question 239

What transcription factors are involved in the cranial-caudal axis determination?

Answer 239

**FGF, Wnt3, retinoic acid (RA), clusters of HOX genes**

Question 240

Different gradients of what transcription factors lead to gastrulation decisions (endoderm, endoderm, or mesoderm)?

Answer 240

BMP4 and Oct4

Question 241

Gata6 promotes what type of differentiation: epiblast or hypoblast?

Answer 241

Hypoblast

Question 242

NANOG promotes what type of differentiation: epiblast or hypoblast?

Answer 242

NANOG helps maintain pluripotency and an inner cell mass/embryoblast **(future epiblast fate)**

Question 243

CDX2 promotes what type of differentiation: inner cell mass or trophoblast?

Answer 243

Trophoblast

Question 244

Oct4/Nanog/Sox2 promotes what type of differentiation: inner cell mass or trophoblast?

Answer 244

Intercell mass and the maintenance of pluripotency

Question 245

Cranial-caudal axis patterning in the **LIMB** is dependent on what?

Answer 245

SHH expressed in the ZPA (zone of polarizing activity)

Question 246

Deletion of 15q13-q15 in the male homolog leads to what?

Answer 246

**Prader-Willi syndrome:** characterized by hypotonia, hypogonadism, short stature, hyperphagia, cognitive impairment

Question 247

Deletion of 15q13-q15 in the female homolog leads to what?

Answer 247

**Angleman syndrome:** characterized by developmental delay, stiff/a toxic movements, hyperactivity, severe cognitive impairment, a happy disposition

Question 248

What is secreted by the embryo shortly after fertilization to allow for implantation preparation?

Answer 248

Pre-implantation factor (PIF)

Question 249

What is a morula?

Answer 249

Cell mass > 4 cells (blastomeres)

Question 250

What happens to the cells of a blastocyst?

Answer 250

* **inner cell mass:** becomes **embryoblast** which forms the tissues of the embryo proper * **outer cell mass:** becomes **trophoblast** which forms the placenta

Question 251

The trophoblast differentiates into what two layers?

Answer 251

1. **Cytotrophoblast:** mitotically active and proliferative 2. **Syncytiotrophoblast:** multinucleated cell mass that is invasive and erode into the epithelium/stroma. Secrete progesterone, estrogen, hCG, lactogens

Question 252

What is the decidua?

Answer 252

• all but the deepest portion of the endometrium becomes transformed into the decidua graviditatis which is shed with the placenta at parturition (birth) • decidualization is stimulated by progesterone

Question 253

What makes up the Chorion?

Answer 253

• syncytiotrophoblast, cytotrophoblast, extraembryonic somatic mesoderm

Question 254

What is the difference between the primary/secondary/tertiary chorionic villi?

Answer 254

• Their components: 1. Primary is only Syncytiotrophoblast and Cytotrophoblast 2. Secondary contains connective tissue (mesenchyme) 3. Tertiary contains blood vessels

Question 255

What are the three components of the placenta?

Answer 255

1. Decidua basalis 2. Decidua capsularis 3. Decidua parietalis

Question 256

What is the decidua basalis?

Answer 256

• Placental area that underlies the implantation site between the conceptus and myometrium. • Constitutes maternal portion of the placenta • sight of decidual reaction: most extensive villar invasion

Question 257

What is the decidual capsularis?

Answer 257

• area of the placenta between the conceptus and the uterine lumen • becomes attenuated as the embryo grows, eventually fusing with the decidua parietalis and eliminating the uterine cavity

Question 258

What is the decidua parietalis?

Answer 258

Remainder of the endometrium where there is no implantation or connection to the fetus

Question 259

What are the TORCH pathogens that can cross the placenta barrier?

Answer 259

T: toxoplasmosis/toxoplasma gondii O: other R: rubella C: CMV H: herpes simplex ~ other: hip B, Coxsackie virus, syphilis, varicella zoster, HIV, Parvo B19

Question 260

What is hCG?

Answer 260

* human chorionic gonadotropin, a peptide produced by syncytiotrophoblasts * helps maintain corpus luteum and its production of progesterone/estrogen during the first trimester

Question 261

What takes over the secretion of progesterone from the corpus luteum in pregnancy?

Answer 261

Syncytiotrophoblasts

Question 262

What is human placental lactogen (hPL)?

Answer 262

* peptide produced by syncytiotrophoblasts that affect growth, lactation, lipid and carbohydrate metabolism * **mimics prolactin and growth hormone** to provide glucose and ketones for fetal nutrition

Question 263

Why and how is prolactin, prostaglandins, and relaxin produced in pregnancy?

Answer 263

Produced by the decidual cells derived from the stromal connective tissue of the mother— softens pubic symphysis prior to parturition

Question 264

What is spontaneous abortion?

Answer 264

• loss of pregnancy before 20 weeks gestation (most occur before 12 weeks) • **fetal causes:** chromosomal abnormalities such as aneuploidy, polyploidy, translations, mutations • **maternal causes:** endocrine factors, uterine defects, systemic vascular disorders, infections

Question 265

What is an early medicinal treatment for ectopic pregnancy?

Answer 265

Methotrexate

Question 266

What are the types of twins?

Answer 266

• mono or dizygotic • mono or dichorionic • mono or diamniotic

Question 267

What is twin-twin transfusion syndrome (monochorionic complication)?

Answer 267

• vascular anastomosis from one side to the other, sometimes an AV shunt occurs leading to preferential blood flow to one twin at the expense of the other (one under perfused, one fluid overloaded)

Question 268

What is placenta accreta?

Answer 268

Absent decidua, abnormal adherence of villous tissue to myometrium

Question 269

What is placenta increta?

Answer 269

Absent decidua, placental villa invade into the myometrium

Question 270

What is placenta percreta?

Answer 270

Absent decidua, placental villa invade through the myometrium

Question 271

What is placenta abruption?

Answer 271

* acute clinical syndrome characterized by pain, uterine tetany, fetal distress, and sometimes DIC * acute abruption has no morphological placental abnormality, chronic has some organization of indents in the placenta or adherens

Question 272

What correlates with increased morbidity and mortality in acute chorioamnionitis?

Answer 272

Villous edema due to decreased blood flow

Question 273

What is wrong with this placenta?

Answer 273

• acute chorioamnionitis • featuring green discoloration of surface membranes, opaque membranes, cloudy amniotic fluid due to neutrophils and bacteria

Question 274

Neutrophilic acute inflammation of basalis, chorion, and amnion along with funisitis of the cord indicates what?

Answer 274

Acute chorioamnionitis

Question 275

What will histology show of a placenta infection due to hematogenous bacterial spread (such as listeria)?

Answer 275

• acute necrotizing villitis/intervillositis • subtrophoblastic acute inflammation and necrosis of villi • may cause fetal demise

Question 276

What is preeclampsia?

Answer 276

• a systemic syndrome characterized by widespread maternal endothelial dysfunction that present during pregnancy with **hypertension, edema, and proteinuria**

Question 277

What is eclampsia?

Answer 277

A severe form of preeclampsia including CNS involvement leading to seizures, coma, death

Question 278

Severe preeclampsia can develop what syndrome?

Answer 278

HELLP syndrome (hemolytic anemia, elevated liver enzymes, and low platelets)

Question 279

What is the pathogenesis of preeclampsia and eclampsia?

Answer 279

• trophoblasts failed to remove the smooth muscle of the spiral artery leading to abnormal placenta vascular and malignant hypertension

Question 280

What uterine vessel pathology is seen in preeclampsia and eclampsia?

Answer 280

1. Fibroid necrosis of vessel walls 2. Subendothelial lipid/macrophages 3. Luminal thrombi

Question 281

Poorly controlled gestational diabetes can lead to what?

Answer 281

A baby with increased birthweight (macrosomia), and long-term complications including obesity and diabetes later later in life. Mother can also develop over diabetes 10-20 years post-delivery

Question 282

What is a hydatidiform mole?

Answer 282

* cystic swelling of the chorionic villi and variable trophoblastic proliferation resulting from the fertilization of an empty egg (complete, commonly 46XX) or fertilization of an egg with two sperm (incomplete)

Question 283

What is a common ultrasound pattern seen with hydatidiform moles?

Answer 283

“Snowstorm pattern”

Question 284

How does a hydatidiform mole present clinically?

Answer 284

• with spontaneous miscarriage or curettage due to abnormal ultrasound showing villous enlargement • complete moles have extraordinarily high hCG levels

Question 285

What is an invasive hydatidiform mole?

Answer 285

* molar pregnancy that invades into or even perforates the uterine wall * villi may embolize to lung or brain (but do not grow at those sites) * presents with vaginal bleeding, uterine enlargement, persistently elevated hCG * Tx: responds to chemotherapy, hysterectomy may be required with rupture

Question 286

What is choriocarcinoma?

Answer 286

• malignant neoplasm of the trophoblastic cells derived from a previously normal or abnormal pregnancy (predominantly cytotrophoblasts and syncytiotrophoblasts) • pts with hx of complete moles have a strong risk of choriocarcinoma

Question 287

What does choriocarcinoma look like grossly/microscopically?

Answer 287

• fleshy tan tumors with extensive red hemorrhagic look, deep invasion of myometrium is typical • proliferating cytotropho/syncytiotrophoblasts with abnormal forms • abundant blood and necrosis

Question 288

What is more chemo responsive: gestational or non-gestational choriocarcinoma?

Answer 288

Gestational (100% chemo response rate). Non-gestational is much more resistant to chemotherapy

Question 289

What are some COVID-19 related fetal demise placental findings?

Answer 289

• necrotizing vasculitis/endothelialitis • acute necrotizing villitis • villous infarction • intervillous fibrin deposition • intervillous histiocytic/neutrophilic inflammation

Question 290

What type of gland is a mammary gland?

Answer 290

Exocrine: - merocrine (eccrine) release of protein - apocrine release of lipids

Question 291

What hormones are required for the development of the mammary gland?

Answer 291

• estrogen • growth hormone/IGF-1

Question 292

What is witch’s milk?

Answer 292

The production of milk from a newborn of either sex due to the passing of maternal hormones before birth and during breast-feeding

Question 293

Postnatal mammary gland development: picture/image

Answer 293

Question 294

How do the development of mammary glands/breast change during pregnancy?

Answer 294

• rapid epithelial growth increasing fat and blood flow • alveoli form • continuous high levels of prolactin • colostrum and milk secreted by luminal epithelial cells • suckling releases oxytocin to cause contraction of epithelial cells to eject milk • weaning: luminal epithelial cells complete a ptosis and evolution occurs (returning to inactive/puberty state)

Question 295

Mammary gland: inactive, pregnant, lactating picture/graph

Answer 295

Question 296

What is the milk flow secretion (apocrine secretion of fats)?

Answer 296

Intralobular duct —> interlobular duct —> lactiferous duct —> lactiferous sinus —> lactiferous duct —> nipple

Question 297

What is the TDLU?

Answer 297

• terminal duct lobular unit consisting of the terminal ductules/acini, intralobular collecting duct, and intralobular stroma (loose CT)

Question 298

What is the skin make up of the nipple?

Answer 298

• stratified squamous keratinized epithelial— no sweat glands/hair follicles • melanin increases during pregnancy • sensory: tall connective tissue papillae with Meissner’s corpuscles • smooth muscle arrangements: circumferential and longitudinal

Question 299

Describe the Areola

Answer 299

• gland of Montgomery (tubercles) on surface • sweat and sebaceous glands present, produces oily secretions that keep the areola and nibble lubricated and protected • produces all factory substance that encourages babies to latch on and breast-feed

Question 300

What are the alveoli of the mammary gland?

Answer 300

• secretory units formed during pregnancy at the distal ends of the intralobular ducts • cuboidal and squamous epithelium • secrete lipids (apocrine) and protein (merocrine/eccrine)

Question 301

What are the cells of the mammary alveoli?

Answer 301

1. Epithelium: • luminal epithelial cells (cuboidal, milk secretion) • myoepithelial cells (contraction for oxytocin letdown reflex) 2. Connective tissue: • adipose, fibroblasts, immune cells

Question 302

What does an inactive mammary gland look like?

Answer 302

* higher visualization of loose connective tissue, small compressed ducts

Question 303

What does an active/late pregnancy mammary gland look like?

Answer 303

• MANY alveoli, filling with milk • less visualization of loose connective tissue (compressed) • plasma cell infiltrates

Question 304

What does a lactating mammary gland look like?

Answer 304

* active and resting alveoli depending on milk holding/milk release

Question 305

What are the postmenopausal changes of mammary glands?

Answer 305

• atrophy of gland and stroma • cyst formation is common • connective tissue has fewer fiber blasts, fewer collagen fibers, fewer elastic fibers (droopy appearance)

Question 306

What does estrogen do to mammary glands?

Answer 306

Stimulates the ductal cell proliferation

Question 307

What does progesterone do to mammary glands?

Answer 307

• stimulates alveolar growth • high levels inhibit milk production • causes breast tenderness and increased size during luteal phase of menstrual cycle

Question 308

What does prolactin do to mammary glands?

Answer 308

* **pre-parturition:** promotes maturation of ducts and alveoli * **post-parturition:** promotes milk production, modifies lipid metabolism, stimulates casein and lactose production

Question 309

Milk ejection, letdown reflex

Answer 309

Suckling stimulates hypothalamus—> oxytocin release + increased prolactin and production of milk at the alveolus —> myoepithelial contraction to eject milk from filled alveoli

Question 310

When is a clinical breast exam performed?

Answer 310

When signs and symptoms are actively present

Question 311

How is a clinical breast exam performed?

Answer 311

**1. Visualize:** arms down, arms up, hands on hips, leaning forward **2. Palpate:** using finger pads, move in a vertical strip palpating in small concentric circles. Apply light, medium, and deep pressure at each examining point

Question 312

What are concerning clinical findings of the breast?

Answer 312

• lump/contour change • skin tethering • new/changing nipple inversion • surface ulceration or nipple scaling • edema or peau d’orange (skin of an orange) • erythema, warmth

Question 313

What is a dominant mass in breast tissue?

Answer 313

A palpable breast mass that is three-dimensional, distinct from surrounding tissues, and a symmetrical relative to the other breast. It **persists throughout the menstrual cycle**

Question 314

What is an indeterminate mass of the breast?

Answer 314

An area of vague or indiscrete nodularity or thickening that differs from the surrounding tissue. The finding is not matched in a mirror image location in the opposite breast

Question 315

What’s in an important history finding for breast masses?

Answer 315

The relationship to menses

Question 316

What are the best evaluations of a dominant breast mass in someone older than 40 years old?

Answer 316

**1. Mammography** 2. Ultrasound 3. MRI

Question 317

What are the best evaluations of a dominant breast mass in someone older than 40 years old with a suspicious mammogram?

Answer 317

1. Ultrasound 2. MRI breast 3. Image guided core biopsy 4. Mammography short interval follow up

Question 318

What are the best evaluations of a dominant breast mass in someone older than 40 years old and a non-suspicious mammogram?

Answer 318

1. Mammography short interval follow up 2. Ultrasound of the breast

Question 319

What is the best evaluation of a dominant breast mass in someone younger than 30 years old?

Answer 319

**1. Ultrasound** (due to the young, highly fibrotic breast tissue making mammography indeterminant) 2. Mammography 3. MRI

Question 320

What is a method used to further identify lesions on mammography?

Answer 320

Spot compression of the mass mammography

Question 321

When is fine needle aspiration of a breast mass indicated?

Answer 321

• palpable lesion • cystic structures ~ cannot use with implants, or lesions near the chest wall

Question 322

If a patient comes in for unknown nipple discharge, what is the work up?

Answer 322

• urine pregnancy test • thyroid testing • serum prolactin level • check medication list (OCPs, anti-hypertensive/ACEis, and medication can cause discharge) • if >30, imaging with mammogram/ultrasound

Question 323

Flowchart for nipple discharge with no mass:

Answer 323

Question 324

What is acyclic breast tenderness?

Answer 324

* diffuse, typically bilateral tenderness often occurring in the luteal phase of the menstrual cycle * predominantly women during their 30s/40s (uncommon in postmenopausal) * pain is described as heaviness/soreness

Question 325

What is non-cyclic breast tenderness?

Answer 325

• sharp, burning, unilateral pain • tends to affect older populations of women 40+ in postmenopausal state • cause is unknown, work is recommended

Question 326

What is polythelia and why does it occur?

Answer 326

Additional supernumerary nipple anywhere on the milk lines

Question 327

What is polymastia?

Answer 327

More than two breasts

Question 328

What is athelia?

Answer 328

Absence of one/both nipples

Question 329

What is amastia?

Answer 329

The absence of breast and nipple (and potentially the pectoralis muscle-Poland syndrome)

Question 330

What are the most common UTIs seen in pregnancy?

Answer 330

E. coli, staph aureus, kpebsiella, proteus ~ can progress to pylonephritis, screen with UA, UC, leukocyte esterase and nitrate positive in G- specimen

Question 331

What are the most common UTIs seen in pregnancy?

Answer 331

E. coli, staph aureus, klebsiella, proteus ~ can progress to pylonephritis, screen with UA, UC, leukocyte esterase and nitrate positive in G- specimen

Question 332

Is there complication to pregnancy with vaginal candidiasis?

Answer 332

No— but treat with **climatrozole or miconazole**

Question 333

Bacterial vaginosis in pregnancy

Answer 333

• increases risk for preterm premature rupture of membranes (PPROM), preterm delivery, and puerperal infections • Tx: oral or vaginal metronidazole, vaginal clindamycin • diagnosis: wet prep, clue cells, fishy odor (whiff test with KOH), and a gray vaginal discharge

Question 334

Group B streptococcus infection during pregnancy

Answer 334

• can lead to UTI, choriamnionitis, endometriosis, neonatal sepsis • treat with IV penicillin G when in labor or if prolonged rupture of membranes

Question 335

Chorioamnionitis in pregnancy

Answer 335

• infection of the membranes leading to maternal fever, elevated maternal white blood count, uterine tenderness and fetal tachycardia (> 160 BPM) • can cause PPROM, indication for delivery • Tx: ampicillin and gentamycin

Question 336

What infections affect fetuses in pregnancy?

Answer 336

• herpes Symplex virus • varicella zoster • parvo B19 • CMV • rubella • HIV • Neisseria gonorrhea • chlamydia trachomatis • hepatitis B • syphilis • toxoplasmosis

Question 337

What is done for pregnant patients with herpes simplex virus?

Answer 337

• suppressive antiviral therapy starting at 36 weeks (valtrex, acyclovir) • c-section if active lesions in order to avoid vertical transmission to the baby • no routine screen recommended

Question 338

What are the complications of varicella zoster pregnancy?

Answer 338

* teratogen: congenital varicella syndrome * live virus vaccine: cannot give pregnancy

Question 339

What is congenital varicella syndrome?

Answer 339

Cutaneous scars, CNS abnormalities, ocular abnormalities, limb abnormalities

Question 340

What is a major complication of parvovirus B19 (fifth disease) and pregnant patients?

Answer 340

Fetal hydrops: fetal hemolytic anemia

Question 341

How does HIV in infection impact delivery in pregnant patients?

Answer 341

• c-section has shown to lower transmission rates if viral load >1000 • HRT treatment in labor, full anti-retrovirals • treat neonate post delivery

Question 342

What are the risks of Neisseria gonorrhea in childbirth and what are the treatments?

Answer 342

* transmission during delivery, newborn conjunctivitis= most common cause of **blindness** * tx: erythromycin ointment at birth, treatment with ceftriaxone

Question 343

Can a hepatitis B vaccination be given during pregnancy?

Answer 343

Yes

Question 344

Complications of syphilis and pregnancy

Answer 344

• routine screening at first visit and 28 weeks, re-screen at delivery in high-risk populations • risk of congenital syphilis • Tx: maternal penicillin treatment

Question 345

Explain congenital syphilis newborn appearance

Answer 345

• saber shins • saddle nose • deafness • Hutchinson teeth

Question 346

How can toxoplasmosis be avoided in pregnant patients?

Answer 346

• avoidance of gardening, soil, unfiltered drinking water, raw/undercooked or cured meats/meat products • infected, Tx: sulfadiazine-pyrimethamine, **<18wks Tx with spiramycin**

Question 347

What complications does listeria cause in pregnant patients?

Answer 347

• listeria can lead to fetal death, premature birth, or infected newborn • avoid unpasteurized products and soft cheeses, avoid hotdog/deli meat unless he did to 165°

Question 348

How does fetal surveillance change for gestational diabetes patients?

Answer 348

• diet controlled: normal routine OB care • medication: NST or BPP weekly after 32 weeks, twice weekly if uncontrolled • all: growth ultrasound at 36-37 weeks delivery recommended induction at 39 weeks, discuss C-section if baby >4500g for concern of dystocia

Question 349

What is preterm labor?

Answer 349

• cervical change associated with uterine contractions prior to 37 weeks • in nulliparous women, uterine contractions with at **least 2 cm dilation and 80% or greater effacement** (multiparous women may have 2-4 centimeter dilations without preterm labor)

Question 350

What are the treatments for preterm labor (typically due to irritable uterus)?

Answer 350

• cortical steroids to improve fetal outcomes • antibiotics for prophylaxis of GBS infection/unknown • limited tocolysis: nifedipine or indomethacin • magnesium for mild tocolytic and neuroprotective

Question 351

What are the common antenatal cortical steroids for lung maturation of a fetus?

Answer 351

1. Betamethasone (two 12 mg intramuscular doses 24 hours apart) 2. Dexamethasone (6 mg intramuscular doses every 12 hours for four doses)

Question 352

What evaluation should be done first with an antepartum bleeding pt?

Answer 352

ULTRASOUND

Question 353

What is vasa previa?

Answer 353

• umbilical cord vessels that insert in the membranes with the vessels overloading the internal cervical os, vulnerable to fetal exanguination upon rupture of the membranes

Question 354

Placenta 1. Accreta, 2. Increta, 3. Percreta

Answer 354

1. Placenta accreta: invasion of the placenta attaching to the myometrium of the uterus 2. Placenta increta: penetrates into the myometrium 3. Placenta percreta: penetrates through the myometrium, potentially invading other organs (bladder, bowel)

Question 355

What is a placenta abruption and what is the treatment?

Answer 355

* vaginal bleeding and abdominal pain due to **detachment of the placenta from the endometrial lining.** Typically accompanied by hypertonic uterine contractions, uterine tenderness, and non-reassuring fetal heart rate pattern * TX: stabilize, prepare for preterm delivery, prepare for hemorrhage, determine RH status

Question 356

What are the fetal risks of hypertension in pregnancy?

Answer 356

• intrauterine growth restriction • pre-term delivery • placenta insufficiency

Question 357

What are the potential treatments of chronic hypertension and pregnant patients?

Answer 357

• BP > 140/90 • beta blocker, calcium channel blocker, methyldopa, diuretic

Question 358

What drug is contraindicated in chronic hypertension of pregnant patients?

Answer 358

**Ace inhibitors:** associated with hydramnios and neonatal renal failure

Question 359

What is the definition of gestational hypertension?

Answer 359

Hypertension without proteinuria at > 20 weeks gestation (BP> 140/90). No hx of hypertension

Question 360

What medications can reduce risk for preeclampsia?

Answer 360

* **calcium supplementation** if low dietary Calcium (uncommon in the USA) * **Low dose aspirin** from 12-36 weeks

Question 361

What are the severe features of preeclampsia?

Answer 361

• blood pressure > 160/110 • pulmonary edema/cyanosis • impairment of liver function • visual or cerebral disturbances • pain in the epigastric area or RUQ not responsive to treatment • decreased platelet count < 100,000 • renal insufficiency, creatinine doubled or >1.1

Question 362

What is eclampsia?

Answer 362

• pre-eclampsia with new onset grand mal seizures (death due to stroke, intracranial hemorrhage, ARDS) • tx: magnesium sulfate (anticonvulsant), and hypertensive, immediate delivery removal of placenta

Question 363

What are the blood pressure treatments used in patients with eclampsia?

Answer 363

• hydralazine • labetalol • nifedipine • alpha-methyldopa • additional: magnesium sulfate to prevent seizures

Question 364

What is a reactive result of a non-stress test of a fetus?

Answer 364

2 accelerations in 20 minutes (this is good). If non-reactive, considered juice/stimulation/BPP

Question 365

What is oxytocin stress testing?

Answer 365

* completed when a non-stress test is non-reassuring, IV oxytocin to induce contractions and assess FHT with the contractions * desired result: FHT variability without decelerations during contractions

Question 366

What are the five categories on a biophysical profile (BPP)?

Answer 366

1. Amniotic fluid volume 2. Fetal tone 3. Fetal activity 4. Fetal breathing movements 5. Fetal heart rate reactivity (nonstress test) ~ score of 0 (bad) or 2 if normal, desired score: 8 to 10

Question 367

What are the complications of multifetal gestation?

Answer 367

• **ALL:** growth restriction, PDT, chromosomal anomalies • **Mono/Di:** twin to Twin transfusion syndrome, single fetal growth restriction, increased chromosomal anomalies, single fetal demise • **mono/mono:** cord entanglement

Question 368

What are the maternal complications of multifetal gestation?

Answer 368

• hypertension, preeclampsia • anemia • hyperemesis, increased N/V • gestational diabetes • cholestasis of pregnancy (itchy palms/soles) • dematoses of pregnancy • need c-section

Question 369

What is the first line antidepressant drug used during pregnancy?

Answer 369

SSRIs: most commonly sertraline (but also citalopram, fluoxetine) Others: SNRIs (venlafaxine, duloxetine) bupropion

Question 370

What does the bishop’s score for induction measure?

Answer 370

• position • consistency • effacement • dilation • fetal station

Question 371

What are the ways to cause cervical ripening?

Answer 371

• membrane stripping/ mechanical ripening with balloon catheter • prostaglandins (Dinoprostone, misoprostol) • amniotomy (manual water break) • oxytocin/pitocin

Question 372

When are serum hCG level detected?

Answer 372

8-11 days post-conception

Question 373

What functions to support the pregnancy with progesterone production during the first 6 to 7 weeks gestation?

Answer 373

A single corpus luteum

Question 374

What are some MSK findings of pregnant woman?

Answer 374

* **striae gravidarum** (stretch marks) * **diastasis recti** (abdominal wall midline separation) * **linea nigra** (midline of the abdominal skin becomes darker) * **melasma gravidarum** (mask of pregnancy, brownish patches on the skin of the face/neck)

Question 375

Why does physiological anemia of pregnancy occur?

Answer 375

The plasma volume increases by 40 to 50% and the red cell mass increases only by 25%, causing a decrease in the hemoglobin concentration

Question 376

What are the three main factors that contribute to respiratory changes in pregnancy?

Answer 376

1. The mechanical effects of the enlarging uterus on other body structures 2. The increased total body oxygen consumption 3. The stimulant effects of progesterone long-term

Question 377

How does renal/endocrine physiology change during pregnancy?

Answer 377

* **Renal plasma flow and the GFR increase by 40%** leading to lower levels of creatinine and urea in the serum * **insulin response is increased** early and pregnancy, potentially leading to insulin resistance and just additional diabetes

Question 378

How much weight should a woman with a normal BMI gain during pregnancy?

Answer 378

25 to 35 pounds

Question 379

What is the equation to determine due date of pregnancy?

Answer 379

LMP -3 months +7 days

Question 380

How early must a physical exam be performed in pregnancy in order to get an accurate assessment of uterine size and dating of pregnancy?

Answer 380

Before 12 weeks gestation

Question 381

What are the screening tests, and what are the diagnostic tests for genetics in the prenatal period?

Answer 381

**screening:** cfDNA, first trimester screening, quad screening, SMA, cystic fibrosis testing **diagnostic:** chorionic villi sampling and a genetic amniocentesis

Question 382

What is cfDNA (NIPT) testing?

Answer 382

Non-invasive prenatal testing: genetic test using fetal cells in maternal circulation. Can be done as early as 10 weeks.

Question 383

What is done during first trimester screening (between 11 and 14 weeks)?

Answer 383

• blood to measure PAPP-A and hCG • ultrasound to measure the nuchal translucency • trisomy 13, 18, 21

Question 384

What are common second trimester screenings?

Answer 384

• quad screening: AFP, estriol, hCG, inhibin-A • Trisomy 18, 21, and neural tube defects

Question 385

When is the anatomy screen ultrasound done in during prenatal care?

Answer 385

20 weeks

Question 386

When do glucose screenings and syphilis testing occur during the prenatal period?

Answer 386

Around 28 weeks

Question 387

When is Group B strep testing done in a pregnant person?

Answer 387

36 weeks

Question 388

What are the three stages of labor?

Answer 388

1.) begins with the onset of regular contractions and lasts until the cervix is completely dilated 2.) begins with complete dilation and ends with the delivery of the baby 3.) delivery of placenta and inspection/repair of the vagina, cervix, and perineum

Question 389

Cervical examination: what is dilation?

Answer 389

The degree of potency, expressed in centimeters, of the internal os of the cervix

Question 390

Cervical examination: what is effacement?

Answer 390

A process by which the cervix is drawn intra-abdominally by the uterine corpus, resulting in **shortening and thinning of the intravaginal portion of the cervix.** It is expressed in percentages or centimeters of cervical length

Question 391

What are the cardinal movements of labor?

Answer 391

The mechanisms of labor that allow the baby to adapt to the pelvis during the second stage of labor: **descent, flexion, internal rotation, extension, external rotation, expulsion**

Question 392

What are some common fetal presentations?

Answer 392

• Vertex presentation is normal • face, brow, breach, shoulder are not normal

Question 393

How are the 4 degrees of perineal lacerations classified?

Answer 393

**First-degree:** involving the mucosa/skin **Second-degree:** extending into the submucosal tissues (most common) **Third-degree:** involving the anal sphincter **Fourth- degree:** involving the rectal mucosa

Question 394

What is the most common indication for a C-section?

Answer 394

Dystocia: wrong presentation or the baby doesn’t fit

Question 395

What is epigenetics?

Answer 395

The study of heritable changes in gene expression

Question 396

Excess weight during pregnancy is associated with what pregnancy/childbirth complications?

Answer 396

• high blood pressure • Preeclampsia • preterm birth • gestational diabetes • macrosomia • Birth injury/C-section required • neural tube defects or other birth defects

Question 397

Maternal deficiency of folate could result in what?

Answer 397

**Neural tube defects of the fetus**. Mother should start folate supplementation one month before conception and at least during the first 12 weeks of pregnancy (the neural tube closes by 28 days post conception)

Question 398

Maternal deficiency of iron could lead to what?

Answer 398

• poor physical growth (low birthweight/premature) neurological development (impaired cognitive/behavioral development), cellular functioning, and synthesis of hormones in the fetus • anemia in the mother

Question 399

Maternal deficiency of iodine could result in what?

Answer 399

* adverse effects of the **infant brain:** spectrum of low IQ to severe mental delay (cretinism) * hypothyroidism

Question 400

Maternal deficiency of calcium/vitamin D could result in what?

Answer 400

* poor development of **fetal bones and teeth (rickets)** * vitamin D is also important for reduction of inflammation, modulation of cell growth, neuromuscular/immune function, and glucose metabolism of the infant

Question 401

Maternal deficiency of omega-3 fatty acids result in what?

Answer 401

• poor fetal brain and retina development • neurodevelopmental delay

Question 402

What are some man-made toxins to avoid during pregnancy?

Answer 402

• PFAS • DES • pthalates • EDCs including plastics

Question 403

Infants who are breast-fed have a reduced risk of what?

Answer 403

• asthma/severe lower respiratory disease • obesity/type one diabetes • acute otitis media • SIDS • gastrointestinal infections • (preterm) necrotizing enterocolitis

Question 404

Mothers who breast-feed have a lower risk of what?

Answer 404

• high blood pressure • type two diabetes • ovarian cancer • breast cancer

Question 405

What is infertility?

Answer 405

The inability to get saved after 12 months of regular intercourse without using contraception in women less than 35, or after six months and a woman older than 35

Question 406

What tests are used as an assessment of ovarian reserve?

Answer 406

Day three FSH, estradiol, AMH

Question 407

What are the indications for an operative vaginal delivery?

Answer 407

Maternal exhaustion, inability to push effectively, maternal cardiac disease, non-reassuring fetal heart tracing

Question 408

Why is cephalohematoma of the newborn a complication of operative delivery?

Answer 408

Prolonged application of the vacuum

Question 409

What are the most common indications for a C-section in the United States?

Answer 409

• failure to progress • non-reassuring FHTs • malpresentation • **cord prolapse**

Question 410

What pregnancies must be assumed to be ectopic until proven otherwise?

Answer 410

Post sterilization (salpingectomy)

Question 411

What are the three approaches to treatment of ectopic pregnancy?

Answer 411

1. Hemodynamically stable patient: methotrexate 2. Surgery (salpingectomy, or salpingostomy) 3. Expectant Management (absorbed miscarriage)

Question 412

What is considered a threatened abortion?

Answer 412

First trimester bleeding

Question 413

When is RhoGAM (anti-D immunoglobulin) given in pregnancy?

Answer 413

• in the third trimester to prevent the formation of antibodies • given after the baby is born if the baby is Rh positive, and mom is Rh negative

Question 414

What is the definition of primary amenorrhea?

Answer 414

No spontaneous uterine bleeding by age 15 in the presence of normal sex characteristics, or by the age of 13 in the absence of any secondary sexual characteristics

Question 415

What is the definition of secondary amenorrhea?

Answer 415

The absence of menstrual bleeding for >3 months in women with previously normal menses, or >6 months in women with irregular menses

Question 416

What are the causes of amenorrhea due to disorders of outflow tract?

Answer 416

1. Imperforate hymen 2. Transverse vaginal septum 3. Mullerian agenesis 4. Androgen insensitivity syndrome 5. Asherman’s syndrome (intrauterine scars/tissue adhesions due to trauma/surgery)

Question 417

What are the causes of amenorrhea due to disorders of the ovary?

Answer 417

1. Turner syndrome (45, XO) 2. 46XX gonadal dysgenesis 3. 46XY gonadal dysgenesis 4. PCOS 5. 17 Alpha hydroxylase deficiency

Question 418

What are the causes of amenorrhea due to disorders of the anterior pituitary?

Answer 418

1. Hyperprolactinemia (prolactinoma) 2. Sellar masses: cyst, meningioma 3. Sheehan syndrome: necrosis of pituitary postpartum 4. Damage to pituitary: radiation, hemochromatosis, sarcoidosis 5. Thyroid disease

Question 419

What is functional hypothalamic amenorrhea?

Answer 419

Abnormal GnRH secretion causing a decrease in LH surges, no follicular development, and low estradiol. Typically seen from eating disorders, exercise, and stressO

Question 420

What is an isolated GnRH deficiency, also known as idiopathic hypogonadotropic hypogonadism?

Answer 420

Kallman Syndrome: genetic

Question 421

What are common systemic illnesses resulting in amenorrhea due to decreased GnRH secretion?

Answer 421

Celiac, type one diabetes, IBS, juvenile rheumatoid arthritis, syphilis, tuberculosis

Question 422

Evaluation of primary amenorrhea flow chart

Answer 422

Question 423

What is oligomenorrhea?

Answer 423

Menses at intervals greater than 35 days

Question 424

What’s the difference between intermenstrual and midcycle spotting bleeding?

Answer 424

Intermenstrual: bleeding between regular periods Midcycle spotting: just prior to ovulation, from declining estrogen

Question 425

PALM-COEIN system of abnormal uterine bleeding:

Answer 425

**PALM indicates structural causes, COEIN indicates non-structural causes** P-polyp A- adenomyosis L- leiomyoma/fibroid M- malignancy and hyperplasia C- coagulopathy O- ovulatory dysfunction E- endometrial (hyperplasia/carcinoma/sarcoma/infection/inflammatory/PID) I- iatrogenic (meds) N- not yet classified

Question 426

What medications can lead to ovulatory dysfunction unintentionally?

Answer 426

Steroids, thyroid hormones, hormones, anticoagulants, SSRI, herbs such as ginkgo, ginseng, soy, IUDs

Question 427

What is the Rotterdam criteria for diagnosis of PCOS?

Answer 427

Need two of three: 1. Oligo-ovulation or anovulation 2. Clinical or lab evidence of hyperandrogenism 3. Positive ultrasound for polycystic ovaries

Question 428

What is the American embryological society (AES) criteria for the diagnosis of PCOS?

Answer 428

Need all three: 1. Clinical or lab evidence of hyperandrogenism 2. Oligo-ovulation or anovulation and/or ultrasound changes 3. Exclusion of other androgen excess of ovulatory disorders

Question 429

What is the treatment of acute, heavy bleeding from the vagina leading to a hemodynamically unstable patient?

Answer 429

• high dose IV estrogen to help regrow the endometrium • IV fluids • blood products • consider D&C • follow with progesterone withdrawal bleed

Question 430

What is the medical management of a patient who is hemodynamically stable, but has acute heavy bleeding from the vagina?

Answer 430

• oral contraceptives • NSAIDs • anti-fibrinolytics • GnRH agonist

Question 431

What are common treatments for long-term, prolonged, heavy menstrual bleeding?

Answer 431

1. Mirena IUD (progesterone only) 2. Endometrial ablation 3. Hysterectomy

Question 432

If you have a woman patient with right or left lower quadrant abdominal pain, what is the first evaluation that should be done?

Answer 432

• Beta hCG and a transvaginal ultrasound to evaluate pregnancy, complications of pregnancy, and/or reproductive tract pathology

Question 433

Explain the serum hCG levels of a pregnant patient:

Answer 433

The hCG doubles every 29 to 53 hours during the first 30 days after implantation of a viable IUP. Slower rise indicates abnormal pregnancy

Question 434

What are the most prevalent and penetrant breast cancer genetic mutations?

Answer 434

**BRCA1, BRCA2**

Question 435

What is the three step process of BRCA mutation leading to cancer?

Answer 435

1. Inheritance of genetuc mutation in BRCA1 or BRCA2 in one allele 2. Increased somatic mutations because BRCA1 and BRCA2 are DNA repair proteins 3. By random chance this process often causes somatic genetic alteration in the second allele of the BRCA gene, extreme genetic alterations can lead to cancer

Question 436

BRCA1 is often inactivated how?

Answer 436

sporadic tumors by epigenetic mechanism: promoter methylation

Question 437

What do BRCA1 and BRCA2 do in the body?

Answer 437

They are essential components of homologous recombination arm of DNA repair machinery ~ BRCA1 is required for differentiation, at the luminal progenitor site

Question 438

What kind of tumors are created by BRCA1 mutations?

Answer 438

• progenitor luminal cells accumulate • basal-like sporadic tumors • often **triple negative**

Question 439

BRCA mutations leading to inactivation of DNA repair creates what new drug targets for breast cancers?

Answer 439

**1. PARP inhibitors** (olaparib) **2. Immune checkpoint blockade therapy** (PD 1/PD 1L inhibition- Pembrolizumab)

Question 440

What is PARP?

Answer 440

**Poly (ADP-ribose) polymerase:** recognizes DNA breaks, adds an ADP ribose unit to the site of breaks allowing for recruitment of repair factors

Question 441

What are the two most prevalent types of sporadic breast cancer, and what are their signaling pathways?

Answer 441

1. Estrogen receptor alpha positive (estrogen/ER alpha) 2. HER2 overexpression (EGF/EGFR family)

Question 442

What controls proliferation of normal luminal cells of the breast tissue indirectly?

Answer 442

Extracellular estrogen via: • estrogen binding ER alpha receptor • ER alpha promotes transcription of secreted growth factors **(amphiregulin)** • growth factors act on nearby cells **(paracrine)** to promote proliferation

Question 443

How do tumor cells regulate growth?

Answer 443

Directly via estrogen promoting transcription of cell cell cycle regulators such as **cyclin D1**, and cells expressing ER undergo proliferation

Question 444

How does ER promote transcription of a different set of genes in patients with breast cancer?

Answer 444

Overexpression of **FOXA1**, where chromatin becomes tonically open, allowing for ER to bind and promote **cyclin D1** (a key regulator of the G1/S transition in the cell cycle)

Question 445

What is tamoxifen?

Answer 445

• an ER antagonist cancer therapy used in breast cancer • synthetic estrogen molecule, binds ER receptor and inhibits it/encourages interaction with co-prepressors and not coactivators

Question 446

What are aromatase inhibitors and why are they used in breast cancer?

Answer 446

• block synthesis of estrogen in non-ovarian tissues (adipose, adrenal) in order to remove estrogen from the equation • in pre-menopausal women, GnRH depression (leuprolide) is required to inhibit estrogen from the ovaries

Question 447

What is the HER2/ERBB2/Neu overexpression breast cancer?

Answer 447

• HER2 is a member of the EGFR family (receptor tyrosine kinase) —> when activated, they initiate signaling pathways that promote proliferation and survival

Question 448

Why is overexpression of ERBB2/HER2 oncogenic?

Answer 448

* **the ERBB2/HER2 dimerization domain is constitutively open** * it does not require ligand binding for activation and dimerization and therefore the cell cycle can proceed independently of external growth factors

Question 449

What are the drugs at target ERBB2/HER2?

Answer 449

**1. Trastuzumab** monoclonal antibody: binds at extracellular domain of ERBB2 **2. Lapatinib:** small molecule inhibitor binds and blocks kindness active site (therefore EGFR/ERBB2 heterodimer activity)

Question 450

When is chemotherapy used in breast cancer?

Answer 450

• ER positive, estrogen dependent only • premenopausal: SERMs- tamoxifen • postmenopausal: SERMs + aromatase inhibitors

Question 451

When is an aromatase inhibitor used in breast cancer (letrozole/anastraxole/exemestane)?

Answer 451

Post menopausal women. You cannot use in pre-menopausal women unless combined with ovarian suppression such as GnRH agonist (continuous)

Question 452

What is a PI3K inhibitor drug used in breast cancer?

Answer 452

Alpelisib

Question 453

How is male breast cancer treated?

Answer 453

• identical to female breast cancer: - Tamoxifen - Chemotherapy if needed (doxirubicin, cyclophosphamide, paclitaxel) - aromatase inhibitor, + GnRH agonist

Question 454

If a patient possesses a deleterious BRCA mutation, what drug is available for the treatment of breast cancer?

Answer 454

PARP inhibitor (olaparib)

Question 455

The GAIL model of risk measurement and breast cancer can **NOT** be used in what patients?

Answer 455

• women with prior breast cancer • women age < 35 • women with history of chest irradiation • women possessing BRCA gene mutations • men

Question 456

What are the absolute contract indications to breast-feeding?

Answer 456

• maternal HIV or human T cell lymphotrophic virus • infant with galactosemia • mother using street drugs such as meth, cocaine, or PCP (not including MAT/MOUD pts) • mother with confirmed/suspected Ebola virus

Question 457

What are the contraindications to breast-feeding calling for a temporary cessation?

Answer 457

• untreated brucellosis • mother is taking certain medication/DI with radiopharmaceuticals • mother has active Herpes simplex virus infection with lesions on breast • active tuberculosis or varicella at delivery (expressed milk is OK)

Question 458

What is lactogenesis 1?

Answer 458

• **Secretory differentiation occurring during pregnancy** • **first trimester:** estrogen and progesterone cause lobular proliferation and ductal growth • **second trimester:** alveoli multiply and nipple/areolar changes due to human placenta lactogen (HPL) and prolactin • **third trimester:** final stage of mammary growth and development due to progesterone

Question 459

What is lactogenesis 2?

Answer 459

• **Secretory activation in days 3-8 postpartum find as the onset of copious milk production/milk coming in** • under neuroendocrine control • progesterone levels drop after delivery • prolactin increases due to nipple stimulation • oxytocin is released by infant cues/stimulation • cortisol decreases (can be inhibitory of milk production if High)

Question 460

What is lactogenesis 3?

Answer 460

* **galactopoesis: day 9 and onward, maintenance of established milk supply** * supplied by control and demand: feedback inhibitor of lactation, increase release with prolactin

Question 461

What are the common bacterial causes of mastitis, and what is the treatment?

Answer 461

Causes: staph aureus, strep group A or B, e. Coli, coag negative negative staph Tx: dicloxacillin, cephalosporin (cephalexin, first gen), or clindamycin for allergic reactions to penicillin

Question 462

What are the treatment options for MRSA mastitis?

Answer 462

• Trimethoprim Sulfamethoxazole (TMP-SMX) • vancomycin

Question 463

Explain causes, diagnosis, and treatment of breast abscesses

Answer 463

• **risk factor:** delayed or in adequate treatment of mastitis, commonly MRSA • **diagnosis:** ultrasound, microbio • **Tx:** drainage and antibiotics (serial breast aspirations)

Question 464

What drug gets into breastmilk 100%?

Answer 464

Alcohol: milk alcohol levels are equal to blood alcohol levels. ~ advisory: waiting two hours for every 8 ounces of wine/2 beers to resume breast-feeding

Question 465

What are the differences in appearance of acute mastitis with staph vs strep?

Answer 465

Staph: may form abscesses Strep: more diffuse cellulitis spread Both: neutrophilic inflammation in the breast duct, usually in the first month of breast-feeding. Treated antibiotic, surgical draining occasionally needed

Question 466

What is duct ectasia?

Answer 466

• palpable periaerolar mass often associated with thick whitish secretions and skin retraction • presents in the 5th to 6th decade in multiparous women • rupture results in chronic inflammation **(lymphocytes, macrophages, plasma cells)** and granulomatous reaction

Question 467

What is lymphocytic mastopathy (sclerosing lymphocytic lobulitis)?

Answer 467

• single or multiple hard palpable masses or mammographic densities due to fibrosis (keloid like) • atrophic ducts and lobules with thick basement membranes and prominent lymphocytic infiltrate • **most common with type one diabetes or autoimmune thyroid disease**

Question 468

What characteristics make breast fat necrosis mimic cancer?

Answer 468

* painless palpable mass * skin thickening or retraction * mammographic density * calcifications

Question 469

What is the morphology of breast fat necrosis?

Answer 469

* acute hemorrhage and liquefactive necrosis with PMN (neutrophil) and macrophages * fibroblasts and chronic inflammatory cells * giant cells, calcifications, hemosiderin

Question 470

What are the complications of silicone implants in the breast?

Answer 470

• capsular contraction producing distortion • leakage causing foreign body reaction, infection, hematoma • breast implant associated anaplastic large cell lymphoma (rare)

Question 471

Breast benign epithelial lesions that are fibrocystic and nonproliferative commonly have what type of metaplasia?

Answer 471

Apocrine

Question 472

What is ductal hyperplasia without atypia of the breast?

Answer 472

* increase number of luminal and myoepithelial cells fill and distend the lumen of a duct or lobule

Question 473

What is sclerosing adenosis of the breast?

Answer 473

• increase number of acini in the lobule causing compression and distortion • fibrosis creating infiltrative appearing nests and cords of cells mimicking carcinoma • **IHC reveals presence of myoepithelium**

Question 474

What is a papilloma of the breast?

Answer 474

• proliferative, without atypic hyperplasia and **multiple branching fibrovascular cores covered by benign epithelium with a dilated duct** • 80% have nipple discharge • may have atypical papilloma or DCS association

Question 475

What is a complex sclerosing lesion of the breast?

Answer 475

* sclerosing adenosis, papillomas, and epithelial hyperplasia with a **radial scar** * **myoepithelial layer present on immunoperoxidase**

Question 476

What is atypical ductal hyperplasia of the breast?

Answer 476

• monomorphic cell population expanding in the duct resembling DCIS • cribiform-like spaces, partial filling of involved duct

Question 477

What is atypical lobular hyperplasia of the breast?

Answer 477

* lesion with cells identical to LCIS (lobular carcinoma in situ) * Fill and distends less than 50% of the acini within a lobule * **loss of E-cadherin**

Question 478

What are the **intralobular** stroma tumors?

Answer 478

• fibroadenoma: benign • Phyllodes tumor: malignant

Question 479

What are the interlobar stromal tumors?

Answer 479

• lipoma • myofibroblastoma • fibromatosis • hemangioma • angiosarcoma • rhabdomyosarcoma • liposarcoma

Question 480

What is a fibroadenoma?

Answer 480

• most common benign tumor of the breast peeking between ages 20-30 • palpable mass or mammographic nodule that is well circumscribed and rubbery • estrogen responsive: changes size with pregnancy and age

Question 481

What is a phyllodes tumor?

Answer 481

• malignant tumor of the sixth decade consisting of **stromal** overgrowth and **leaf-like features** • high cellularity, mitotic rate, and pleomorphism • hematogenous spread in 1/3 of high-grade cases

Question 482

What does a phyllodes breast tumor look like under the microscope?

Answer 482

Low grade: left High grade: right

Question 483

What benign lesions contain calcifications that can be seen on mammography?

Answer 483

1. Apocrine cysts 2. Hyalinized fibroadenomas 3. Sclerosing adenosis

Question 484

How do malignancy associated calcifications look on mammogram?

Answer 484

1. Small, irregular, numerous, clustered, pleomorphic 2. Associated stellate density 3. Ductal pattern (DCIS): linear calcifications

Question 485

95% of breast malignancy is what type of tumor?

Answer 485

Adenocarcinoma arising from the terminal duct lobular unit (TDLU): either ductal or lobular

Question 486

What is ductal carcinoma in situ?

Answer 486

* malignant clonal proliferation of epithelial cells limited to ducts by the basement membrane * **myoepithelial cells are present in ducts and lobules as well as intact basement membrane** * two subtypes: comedo with necrosis and non-comedo without

Question 487

What are the subtypes of DCIS?

Answer 487

• Comedo • cribiform • micropapillary

Question 488

What is breast DCIS Paget disease of the nipple?

Answer 488

• rare manifestation of breast cancer leading to unilateral erythematous eruption involving the nipple with a scaly crust. Pruritus is common • Typically poorly differentiated, ER- , HER2+ • mucicarmine stain and CEA/CK7 highlight the Paget cells

Question 489

What is lobular carcinoma in situ of the breast?

Answer 489

LCIS is a clonal proliferation of cells within ducts and lobules that grow in a dyscohesive fashion, usually due to an acquired loss of the tumor suppressive adhesion protein: **E-cadherin**

Question 490

What do the cells of breast LCIS look like?

Answer 490

• rounded discohesive shape due to lack of e-cadherin, CDH1 • mucin positive signet ring cells are common • typically ER+, PR+, HER2-

Question 491

What is invasive mucinous (colloid) carcinoma?

Answer 491

• soft, gelatinous mass that is often well circumscribed • island of tumor cells in **pools of mucin** • usually ER+, HER2-

Question 492

What does invasive tubular carcinoma look like?

Answer 492

• well formed tubules around a central scar and characteristic teardrop or tadpole shapes • apocrine snouts on the luminal side • low-grade DCIS often present • **No myoepithelial present— differentiates from noninvasive radial scar)** • always Nottingham grade 1

Question 493

What is papillary carcinoma of the breast?

Answer 493

• true papillae with fibrovascular cores • columnar cells= low-grade • intracystic and non-invasive or invasive

Question 494

What is invasive apocrine carcinoma?

Answer 494

• abundant pink granular cytoplasm, vesicular chromatin with prominent nucleolus cells that resemble those lining cutaneous apocrine glands/apocrine metaplasia seen in FCC • often HER2+

Question 495

What are the features of invasive micropapillary carcinoma of the breast?

Answer 495

• no fibrovascular core • hollow balls of cells with peripheral space • mimic papillae • common lymphatic invasion • often HER2+

Question 496

What are the features of invasive medullary carcinoma of the breast?

Answer 496

• pushing border, no desmoplasia • syncytial cell growth with lymphoid infiltrates • pleomorphic/prominent nuclei • minimal or absent DCIS • common pattern in BRCA tumors • often ER- and HER2- • medullary carcinoma features

Question 497

Breast cancer and men is typically associated with what?

Answer 497

• Klinefelter’s syndrome (XXY) • BRCA2 mutations • ER+ • ductal (NST)

Question 498

How does rubella virus impact pregnancy?

Answer 498

• **congenital rubella syndrome:** deafness, cardiac anomalies, cataracts, mental retardation • vaccination cannot be given in pregnancy due to live attenuation

Question 499

How does cytomegalovirus or CMV impact pregnancy?

Answer 499

• congenital CMV: hearing loss is common, potential growth restriction

Question 500

What is the discriminatory zone of hCG levels?

Answer 500

> 2000, or >3500 at some clinics. This indicates at approximately what hCG level a gestational sac should be able to be seen on imaging