Female Repro183 cards

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1

Causes of vulvitis

1. contact irritant dermatitis 2. contact allergic dermatitis 3. infection

2

Vulvitis caused by contact irritant dermatitis

- Rxn to irritants in urine (incontinence), soaps, detergents, deoderants - Erythematous (red) weeping/crusting papules and plaques (looks same as allergic dermatitis)

3

Vulvitis caused by contact allergic dermatitis

- Rxn to antigens in perfumes, creams, lotions - Erythematous (red) weeping/crusting papules and plaques (looks same as irritant dermatitis)

4

Vulvitis due to infection

- STDs - HPV, HSV, gonorrhea, etc.

5

Bartholin cyst

- Complication of vulvitis - Inflammation causes obstruction of excretory ducts in the Bartholins glands - Painful, large cyst requiring marsupialization (drainage surgery) - Usually unilateral; located laterally and below vagina

6

Behcet's disease

- Rare, immune-mediated systemic vasculitis - Triad: 1. Oral apthous ulcers (canker sores) 2. Genital ulcers 3. Ophthalmic inflammation (uveitis)

7

Lichen sclerosis - definition - clinical

- Disease with possible autoimmune etiology causing thin, FIBROTIC area of vulva - MC in postmenopausal females - Smooth white plaques (leukoplakia) on skin - **May progress to SCC in 1-5%**

8

Lichen sclerosis - micro

- THIN epidermis - Loss of rete pegs - Hydropic degeneration - Dermal fibrosis - Scant perivascular inflammation

9

Lichen simplex chronicus - definition/cause - clinical

- Skin disorder caused by chronic irritation from scratching - Smooth white plaques (leukoplakia) on skin - **No increased risk of cancer (unlike lichen sclerosis), but often found next to SCC**

10

Lichen simplex chronicus - micro

- THICK epidermis (especially stratum granulosum) - Hyperkeratosis (alot of keratin) - No atypia (atypical cells) - Dermal inflammation

11

Condylomata acuminata - Definition/cause - Prognosis

- Warty lesion occurring in the anogenital region - Caused by HPV types 6 & 11 - Low risk of malignant transformation

12

Condylomata acuminata - micro

- KOILOCYTOSIS = HPV viral effect (seen with any HPV infection): perinuclear cytoplasmic vacuolization and wrinkled nuclei

13

Condylomata acuminata - Treatment

- Podophyllin, trichloroacetic acid (TCA) - Imiquimod (Aldara): activates immune system - CO2 laser/cryotherapy - Prevention: guardasil vaccine (types 6, 11, 16, 18)

14

Condylomata lata

- Secondary syphilis - Flat, moist, minimally elevated lesions (not warty like acuminata)

15

Syphilis - tests

- Screen: VDRL, RPR - Confirm: FTA

16

Low risk strains of HPV

6, 11-->condylomata

17

High risk strains of HPV

16, 18, 31, 33, 51, 55 --> dysplasia (VIN, VAIN, CIN) --> SCC

18

Carcinoma of the vulva

1. Squamous cell carcinoma (SCC) - Woman > 60 yo - Preceded by lichen sclerosis (big risk factor) - Well differentiated, alot of keratin (pink pearls) 2. HPV-related SCC

19

HPV-related SCC of vulva - cause - commonly seen in... - precursor

- Less common than vulva SCC preceded by lichen sclerosis - HPV 16, 18 - Middle aged, smokers, immunodeficiency - Precursor: vulvar intraepithelial neoplasia (CIN)

20

Carcinoma of vulva - Clinical

- VIN/carcinoma may present as leukoplakia, exophytic tumors, or ulcerative endophytic tumors - MC site: labia majora (but also minora and clitoris) - Localized for long period before spreading - Risk of metastasis correlates with size and depth of invasion

21

Vulvar tumor metastasis - Labia--> - Clitoris-->

Labia--> superficial inguinal nodes Clitoris--> deep inguinal nodes

22

Extramammary Paget disease - key features

- Intraepidermal spread of malignant epithelial cells in the skin of the vulva - Majority of cases have no underlying tumor (unlike pagets of the breast, which almost always has underlying tumor) - Thought to be an adenocarcinoma

23

Extramammary paget disease - origin

- Majority of cases are thought to arise from epidermal progenitor cells - Small # of cases arise from sweat glands

24

Extramammary Paget Disease - micro

- EPIDERMIS infiltrated by large epithelioid cells with abundant cytoplasm (occur as single cells and clusters) - Cells contain MUCIN (PAS+)! (adenocarcinoma) - May resemble melanoma (also in epidermis)

25

Melanoma vs. extramammary paget disease

Melanoma: PAS-, mucin-, keratin-, S100+ EMPD: PAS+, mucin+, keratin+, S100-

26

Extramammary paget disease - clinical

- Red, scaly, crusted or oozing plaque that may resemble inflammatory dermatitis - If confined to epidermis, good prognosis, but may recur - Invasion of dermis may lead to metastasis

27

Gartner's duct cyst

- Benign vaginal cystic lesion that occurs in lateral vaginal walls - Remnant of wolfian duct (mesonephric duct) - Non-mucous secretions

28

Vaginitis - general

- White vaginal discharge (leukorrhea) - Normal commensal organisms may become pathogenic with: 1. diabetes 2. systemic antibiotic therapy 3. immunodeficiency 4. pregnancy/recent abortion

29

Vaginitis - types

1. trichomonas vaginitis 2. candidal (monilial) vaginitis

30

Trichomonas vaginalis

- Found in 10% of asymptomatic women - Symptomatic infection (vaginitis) occurs due to predisposing risk factors, or superinfection with a more aggressive strain - Watery, copius gray-green discharge - "Strawberry cervix:" red, inflamed

31

Candidal (monilial) vaginitis

- Part of normal flora in 5% of females - Symptomatic infection occurs due to predisposing risk factors or superinfection with more aggressive strain - Curdy white discharge

32

Tumors of vagina

1. Squamous cell carcinoma (SCC)- MC 2. Clear cell adenocarcinoma 3. Embryonal rhabdomyosarcoma (sarcoma botryoides)

33

SCC of vagina

- MC tumor of vagina (but vagina tumors are uncommon) - Women > 60 yo - Same risk factors as cervical cancer (HPV, immunosuppression, smoking, etc.) - Precursor lesion: Vaginal intraepithelial neoplasia (VAIN) - May represent cervical SCC that has spread to vagina

34

Clear cell adenocarcinoma of vagina - Associations - Age - Location

- Associated with mothers who took Diethylstilbestrol (DES) during pregnancy - Mean age: 17 yo (daughters of women who took DES) - Location: upper vagina and cervix

35

Clear cell adenocarcinoma of vagina - percursor

VAGINAL ADENOSIS: - Mullerian-type glandular epithelium in vaginal mucosa - Red, granular foci that don't stain with Lugol's iodine solution

36

Clear cell adenocarcinoma of vagina - effects of DES (in child)

- Stenosis of fallopian tubes (-->infertility) - Stenosis of endometrial cavity--> "T-shaped endometrial cavity" - Stenosis of cervix (-->infertility)

37

Embryological derivation of vagina

- Lower 2/3 of vagina comes from urogenital sinus - Upper 1/3 vagina comes from Mullerian duct (also cervix, uterus, and fallopian tubes)

38

Embryonal rhabdomyosarcoma - general - age - gross

= sarcoma botryoides - Malignant striated muscle tumor -**Infants and children <5 yo** - Gross: soft, gelatinous, grape-like masses that fill and protrude from the vagina - Typically arises in anterior wall of vagina

39

Embryonal rhabdomyosarcoma - micro

- *Rhabdomyoblast (diagnostic): round or elongated (tadpole or strap) cells with granular eosinophilic cytoplasm and evidence of cross-striations - Cells grow crowded together below the surface epithelium in a cambium layer

40

Embryonal rhabdomyosarcoma - immunostain - treatment

- Immunostain: 1. Desmin + 2. Actin + 3. MYOD-1 + (most specific) 4. Myogenin + - Tx: combination surgery, chemotherapy, radiation. Curable in 66% of cases.

41

Complications of pelvic inflammatory disease

- Inflammation-->scarring-->infertility - Ectopic tubal pregnancies (due to scarred fallopian tubes)

42

HPV - tropism

- HPV has tropism for immature squamous metaplasia of the transformation zone of the cervix

43

Cervical cancer - general - age

- #8 cause of cancer death in women (was #1 in 1940's) - MC in women 45-55 y.o. (~ 10-15 years after HPV infection)

44

Cervical cancer - risk factors

- Early age of 1st intercourse - Multiple sexual partners - Male partner with multiple previous partners - Smoking - Immunosuppression - Persistent infection with high-risk HPV

45

Cervical cancer - genetics

- HPV types 16 &18: integrates in host genome, contain viral oncogenes E6, E7 which inactivate tumor suppressor genes p53 and RB - Acquired somatic mutations of LKB1 found in 20%

46

LKB1 gene

- Acquired somatic mutation of LKB1 found in 20% of cervical cancers - LKB1 is a serine-threonine kinase that phosphorylates and activates AMPK (metabolic sensor that regulates growth through the mTOR complex) - Also mutated in Peutz-Jeghers syndrome and lung cancer

47

Cervical intraepithelial neoplasia (CIN)

- Precursor lesion of cervical cancer - Not actually neoplasia, but dysplasia! - Peak incidence: ~30 y.o. - Peak incidence of invasive SCC: ~45 y.o.

48

Categories of CIN

(cervical intraepithelial neoplasia- precursor lesions) - CIN I = LSIL (low grade squamous intraepithelial lesion) - CIN II/III = HSIL (high grade squamous intraepithelial lesion) - CIN III also called carcinoma in situ

49

Cervical cancer - colposcopy

- Acetic acid highlights areas to be biopsied. - May be microscopic areas or large, exophytic tumors.

50

Cervical cancer - micro

- MC type: squamous cell carcinoma - Others: adenocarcinoma (HPV) and neuroendocrine carcinoma (aggressive)

51

Cervical cancer - treatment

- HSIL and small microinvasive SCC (<3 mm): cone biopsy - Invasive tumors (>3-4 mm): hysterectomy and LN dissection

52

Cervical cancer - advanced disease

- Local invasion of the bladder and ureters (tumor invades anteriorly into posterior wall/trigone of bladder, where ureters enter)--> block ureters--> hydronephrosis--> RENAL FAILURE/death

53

Endocervical polyps - general - gross

- BENIGN polypoid mass arising from endocervical mucosa - Gross: soft, smooth, glistening surface with underlying cystic spaces containing mucous

54

Endocervical polyps - micro

- Mucin-secreting lining with edematous stroma - Chronic inflammation and squamous metaplasia may be present

55

Endocervical polyps - Clinical - Prognosis

- May bleed - NO MALIGNANT POTENTIAL

56

Endometrial polyps - General - Prognosis

- Polyp arising from the endometrium - Usually benign; rare risk of malignant transformation

57

Endometrial polyps - micro

- Composed of endometrium resembling the basalis layer - Small muscular arteries - Cystically dilated glands - Stromal cells (between glands) are monoclonal and neoplastic

58

Endometrial polyps - clinical

- MC around menopause - Abnormal uterine bleeding

59

Menorrhagia

Profuse or prolong bleeding at regular intervals

60

Metorrhagia

Irregular bleeding at regular intervals

61

Oligomenorrhea

Bleeding at intervals greater than every 35 days

62

Amenorrhea

No uterine bleeding for at least 6 months

63

Common pathologic causes of abnormal uterine bleeding

- Endometrial polyps - Endometritis - Leiomyomas (fibroids) - Endometrial hyperplasia (old ppl) - Endometrial carcinoma (old ppl) *AGE is important

64

Dysfunctional uterine bleeding

- Abnormal uterine bleeding without structural or organic uterine pathology (no lesion!) - Diagnosis of exclusion (rule out polyps, leiomyomas, etc.) - 90% cases due to anovulatory cycle (failure of ovulation; missed cycle) - Inadequate luteal phase

65

Endometritis - Clinical

- Fever - Abdominal pain - Menstrual irregularities (can be acute or chronic)

66

Acute endometritis

- Neutrophilic infiltrate and microabscesses - Post-delivery or miscarriage

67

Chronic endometritis

- Presence of PLASMA CELLS in endometrium - Causes: pelvic inflammatory disease e.g. via intrauterine device/IUD (ACTINOMYCES)

68

Actinomyces

- Often infects IUDs-->chronic endometritis - Gram positive filamentous bacteria with sulfa granules

69

Adenomyosis - general - clinical

- Growth of the basal layer of endometrium downward into the myometrium - Clinical: menorrhagia, dysmenorrhea (menstrual pain), pelvic pain prior to onset of menses

70

Adenomyosis - micro

- Benign-appearing endometrial glands/stroma within the myometrium - Composed of stratum basalis (not functionalis), thus do not undergo cyclic bleeding - Reactive hypertrophy of muscle--> enlarged, globular uterus with thickened, trabeculated wall

71

Endometriosis - general - hypotheses

- Presence of endometrial glands/stroma OUTSIDE OF UTERUS - Theories: 1. Regurgitation theory 2. Metaplastic theory 3. Vascular/lymphatic disseminated theory

72

Endometriosis - mechanism

- Ability of endometrial tissues to survive depends on: 1. increased levels of PGE2 2. increased levels of aromatase-->estrogen production

73

Endometriosis - micro

- Endometrial glands/stroma - Hemosiderin pigment (iron); + prussian blue stain

74

Endometriosis - locations

(multifocal) - *Ovary (MC site): chocolate cyst (endometrioma) - Uterine ligaments/fallopian tubes - Pouch of douglas - Peritoneal cavity: red-brown areas = "powder burns" - Rectovaginal septum

75

dyspareunia

Pain during intercourse

76

Leiomyoma - general - age/race - cause

= "FIBROIDS" - Benign tumor of myometrial smooth muscle - Very common in reproductive aged females - Blacks >> whites - Monoclonal - Stimulated by estrogen (pregnancy, OC); regress at menopause

77

Leiomyoma - gross - locations

- Often multiple - Firm ("fibroid"), well-circumscribed, grey/white mass - Whirled cut surface - Locations: intramural (in wall), subserosal (outside of uterus; polypoid mass; palpable), submucosal (inside uterus; pushes on endometrium-->bleeding, abortion)

78

Leiomyoma - micro

- Bundles of smooth muscle - Foci of fibrosis, calcification, and degeneration

79

Leiomyoma - clinical - prognosis

- MC presenting sign: menorrhagia (if submucosal) - Palpable mass/dragging sensation (if subserosal) - Malignant transformation to sarcoma is VERY RARE

80

Leiomyosarcoma - general - age

- Malignant tumor of myometrial smooth muscle - MC in postmenopausal women - Arise DE NOVO, rather than from pre-existing meiomyomas

81

Leiomyosarcoma - gross

- Usually solitary (leiomyomas multiple) - Soft, hemorrhagic, necrotic mass

82

Leiomyosarcoma - micro

- Tumor necrosis - Cytologic atypia - *Increased mitotic activity - Well-differentiated tumors do better than anaplastic tumors

83

Leiomyosarcoma - clinical - prognosis/spread

- MC in postmenopausal women - Recurrence is common after resection - Metastasis to LUNGS