Female Genital

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Molluscum contagiosum

- tan papules with umbilicated centers.

Molluscum contagiosum

Molluscum contagiosum

Herpesvirus

- highly transmissible DNA virus.
- hepatic ulcer phase is active.
- latent phase is inactive.
- painful, inflamed, shallow ulcers on the vulva, vagina, cervix, groin, buttocks, and thighs.
- pain, dysuria.
- diagnosed via Tzanck smear.
- sequelae are neonatal infections, spontaneous abortions.

Herpesvirus (showing herpetic vesicle)

Herpesvirus (showing ulcer base)

Herpesvirus (showing Tzanck smear)

Herpesvirus (showing multinucleated cells with intra-nuclear, "ground glass" viral inclusions)

Neonatal herpes infection

- 50% born to asymptomatic mothers.
- up to 80% mortality.
- causes conjunctivitis, keratitis, vesicular rashes, jaundice, seizures, and GI bleeds in newborn 2-12 days after delivery.
- treatment is C-section if an active maternal infection is present.

Candida albicans

- causes vaginitis.
- may be normal flora.
- diabetes, antibiotics, pregnancy, immunosuppression.
- leukorea (thick white vaginal discharge), pruritis.

Trichomonas vaginalis

- flagellated protozoan, sexually transmitted.
- yellow, frothy discharge, pruritis, dysuria, dyspareunia.
- "strawberry" cervix.

Gardnerella vaginalis

- gray-green malodorous (foul smelling) discharge.
- diagnosed by presence of "clue cells" on pap smear.

Pelvic inflammatory disease

- infection of pelvic organs by a variety of pathogens beyond the uterine corpus.
- usually caused by gonorrhea and chlamydia.
- symptoms include lower abdominal pain, cervical tenderness.
- complications include rupture of tuboovarian abscess, infertility from scarring of tubes, ectopic pregnancy, and intestinal obstruction from fibrous bands and adhesions.

Bartholin cyst

- cyst of the glands responsible for maintaining moisture of the vaginal mucosa's vestibular surface.
- may present as painless labial swelling.
- treatment is marsupialization which involves suturing the inner edge of the incision to external mucosa.

Lichen planus

- pruritic, papular, polygonal, and scaly eruption.
- caused by a cell-mediated immune response.

Lichen planus

Lichen sclerosus (LS&A)

- squamous atrophy.
- presents with white plaques showing epidermal atrophy.
- usually affects elderly and post-menopausal females.
- autoimmune.
- not considered precancerous, but is associated with increased risk of cancer development (1-4%).

Lichen sclerosus (LS&A)

Lichen sclerosus (LS&A)

Lichen sclerosus (LS&A) (showing squamous atrophy)

Lichen simplex chronicus (LSC)

- squamous hyperplasia.
- histology shows squamous hyperplasia, acanthosis, and hyperkeratosis.
- no cytologic atypia.

Condyloma acuminatum

- HPV 6 and 11.
- frequently multiple and papillary, but occasionally flat.
- histology shows koilocytes and mitosis.
- frequently regress.
- treatment is cryo, chemical, laser, or surgical excision.

Condyloma acuminatum (showing koilocytes)

Condyloma acuminatum (showing warty type)

Condyloma acuminatum (showing coalescing papules)

Condyloma acuminatum

Condyloma acuminatum (showing exophytic architecture)

Condyloma acuminatum (showing koilocytes)

Vulvar intraepithelial neoplasm (VIN)

- 30% will have dysplasia of vagina/cervix.
- multicentric on the vulva.
- high recurrence after surgery.
- risk of progression to invasive SCC depends on age, extent, and immune status.

Vulvar intraepithelial neoplasm (VIN)

Vulvar intraepithelial neoplasm (VIN)

Vulvar intraepithelial neoplasm (VIN)

Vulvar intraepithelial neoplasm (VIN)

Vulvar intraepithelial neoplasm (VIN)

Invasive SCC of vulva

- not very common (3% of genital cancers).
- presents as nodules or masses with a background of leukoplakia.
- usually solitary, but 10% multifocal when associated with condyloma.
- an ulcerated mass is malignant until proven otherwise.
- 2 types: warty/basaloid and keratinizing.
- impaired immune status is associated with more progressive disease.
- Lymph spread: inguinal-pelvic-iliac-paraaortic-lungs/liver.
- treatment is vulvectomy and lymphadenectomy.
- variant is verrucous carcinoma (fungating, non-metastasizing tumors that look like condyloma).

Invasive SCC of vulva

Invasive SCC of vulva

Invasive SCC of vulva

Verrucous carcinoma

Verrucous carcinoma

Verrucous carcinoma (showing no infiltration, unlike a typical SCC)

Accessory breast tissue

- "milk line" extends into vulva.
- breast tissue expands during pregnancy.

Papillary hidradenoma

- sharply circumscribed nodule in vulva with normal overlying skin.
- considered a benign tumor derived from apocrine glands.

Papillary hidradenoma

Papillary hidradenoma (showing a double layer of columnar cells)

Extramammary paget disease

- presents as a pruritic, red, crusted, sharply demarcated area on labia majora of elderly women.
- does not have underlying carcinoma.
- PAS +, mucin +, CEA +, EMA +.
- histology shows vacuolated cells, acanthosis, hyperkeratosis, and parakeratosis.
- treatment is wide local excison but may recur.

Extramammary paget disease

Extramammary paget disease (showing vacuolated cells and hyperkeratosis)

Extramammary paget disease (showing vacuolated cells)

Extramammary paget disease (PAS + cells)

Extramammary paget disease (CEA + cells)

Pigmented lesions of the vulva

- benign area can be indistinguishable from spreading melanoma.

Gartner duct cyst

- cyst of lateral vaginal wall.
- simple cyst with monolayer of benign cuboidal epithelium.
- treatment is excisional biopsy.

Vaginal adenosis

- abnormal development of glandular tissue in the vagina as a result of in utero exposure to diethylsilbestrol (DES) while the affected woman was a fetus.
- develops clear cell carcinoma of the vagina.
- is curable when small.

Clear cell carcinoma of the vagina

Embryonal rhabdomyosarcoma

- neoplasm of girls < 5 years of age.
- have a "grape like" appearance.
- presents as polypoid mass or vaginal bleeding.
- arises in lamina propria of vaginal wall.
- high rate of surgical cure if tumor < 3cm, which tends to be localized.
- grows by local invasion with spread to nodes and distant sites.

Clear cell carcinoma of the vagina (showing vacuolated tumor cells with gland formation)

Normal endocervical canal and lower uterine segment

Cervix (showing normal squamo-columnar junction)

Cervix (showing normal squamo-columnar junction)

Cervix (showing normal squamo-columnar junction)

Non-specific cervicitis

- loss of acidosis (bleeding, intercourse, douching, antibiotics) leads to loss of normal flora and overgrowth of other bacteria.

Specific causes of cervicitis

- gonococcus, chlamydia, mycoplasmas, herpes simplex virus.

Endocervical polyp

- common.
- may be as large as 5cm.
- benign.
- may cause "spotting of blood".
- treatment is polypectomy.

Endocervical polyp

Chronic cervicitis

Chronic cervicitis

Nabothian Cyst

- mucus-filled cyst on the surface of the cervix.
- keeps secreting until rupture.
- self limited.

Nabothian Cyst

Nabothian Cyst

HPV 16

Which HPV serotype is high risk?

E6

Which HPV protein inactivates p53?

E7

Which HPV protein binds to RB and upregulates cyclin E?

HPV (showing koilocytic atypia)

HPV (with HPV stained)

Ki-67 (marker of cell proliferation which should be confined to basal layer)

P16 (despite high levels, HPV infected cells proliferate because the target of the p16 (RB) is inactivated by E7)

Tranformation zone

Uterine cervix (showing vaginal cuff, cervical os, and exocervix)

Find:
- vaginal cuff.
- cervical os.
- ectocervix.

Normal cervix (black - squamo columnar junction, white - squamous metaplasia)

Find:
- squamo columnar junction.
- squamous metaplasia.

Condyloma acuminatum

Condyloma acuminatum

Condyloma acuminatum

Acetowhite

- white-appearing epithelium following the application of acetic acid.
- correlate with higher nuclear density.

Adenocarcinoma in situ (AIS)

- precursor lesion to invasive adenocarcinoma (15% of malignancies).
- very difficult to recognize.
- can be difficult to visualize as can extend up endocervical canal.

Cervical cancer

- 80% SCC, 15% adenocarcinoma.
- all associated with HPV.
- >50% present in women without pap smear screening.
- usually a small and shallow tumor.
- usually present with bleeding after coitus or advanced local invasion.
- 5 year survival.
- death is by invasion of local structures, especially obstruction of ureters (50% die in renal failure).
- treatment is radical hysterectomy.

SCC of the cervix

SCC of the cervix

SCC of the cervix

- pap smear.
- HPV DNA testing.

What should cervical cancer screening include?

HPV vaccine (gardasil)

- vaccine for HPV 6, 11, 16, 18.
- 100% immunity against HSIL at 5 years.
- males can be vaccinated (herd immunity).

Estrogen

What hormone predominates during the endometrial proliferative phase?

Progesterone

What hormone predominates during the endometrial secretory phase?

Menstrual cycle:
- top left - proliferative phase.
- top right - early secretory phase.
- bottom left - late secretory phase.
- bottom right - menstrual phase.

Find:
- proliferative phase.
- early secretory phase.
- late secretory phase.
- menstrual phase.

Abnormal uterine bleeding

- unscheduled or unexpected uterine bleeding.

Dysfunctional uterine bleeding

- unscheduled bleeding that is presumed to be a consequence of a hormonal/functional abnormality.

Oligomenorrhea

- intervals greater than 35 days. (infrequent)

Polymenorrhea

- intervals less than 24 days.

Menorrhagia

- excessive bleeding with normal intervals. (meno = prolonged)

Metrorrhagia

- excessive flow and duration at irregular intervals. (Metro = uterus or womb)

Menometrorrhagia

- irregular menses. = MMR

Withdrawal bleeding

- bleeding following the withdrawal of hormones.

Anovulatory cycles

- results in increased, prolonged, and unopposed estrogen stimulation.
- resulting endometrium is unstable and breaks down with bleeding.
- no known cause.
- biopsy shows irregular, dilated glands, no progesterone effect, and stromal breakdown.
- very common around menarche and in perimenopausal period.

Inadequate luteal phase

- abnormal corpus luteum function gives low progesterone in secretory phase.
- typically presents as infertility with menorrhagia or amenorrhea.
- biopsy shows histologic date is > 2 days behind the clinical date of menstrual cycle.

Oral contraceptives

- have marked effects on endometrium, depending on estrogen-progesterone ratio and sequence of ingestion (combined or sequential).

Acute endometritis

- limited to infections that arise after delivery or miscarriage, especially if there are retained products of conception, like placental fragments.
- infection is by vaginal bacteria like Strept Group A and Staph.
- treatment is by curetting the endometrial cavity to remove the fragments.

Chronic endometritis

- biopsy shows plasma cells which are not normal endometrial cells.
- typically associated with chronic PID, retained products of conception, IUD, tuberculosis).
- 15% are nonspecific (present with metromenorrhagia, dysmenorrhea, pain, infertility) and respond to antibiotics.

Endometriosis

- presence of endometrial tissue (glands and tissue) outside the uterus.
- presents with infertility, dysmenorrhea, pelvic pain, scarring of involved organs.

Chocolate cyst (endometrioma)

Endometriosis

Endometriosis

Endometriosis

Endometriosis

Adenomyosis

- presence of endometrial tissue in the myometrium.
- if forms a discrete mass, it is called an adenomyoma.
- presents with infertility, dysmenorrhea, pelvic pain, scarring of involved organs.

Adenomyosis

Adenomyosis

Endometrial polyps

- benign.
- may be pedunculated or sessile and up to centimeters in length.
- typically present with bleeding.
- treatment is surgical removal.

Endometrial polyp (note hemorrhagic tip of polyp)

Endometrial polyp

Endometroid adenocarcinoma (Type I)

- 80% of endometrial cancer.
- peak age 55-65 years.
- associated with conditions of unopposed estrogen.
- typically present with abnormal bleeding.
- involves PTEN mutations and microsatellite instability.

Endometroid adenocarcinoma (Type I)

Endometroid adenocarcinoma (Type I)

Endometrioid adenocarcinoma (Type I)

Invasion of myometrium by adenocarcinoma

Non-endometrioid adenocarcinoma (Type II) (p53 stain on top/bottom right)

- serous carcinoma.
- 15% of endometrial carcinomas.
- peak age 65-75 years, occurs 10 years later than endometrioid adenocarcinoma.
- p53 mutation.
- are all high grade lesions with aggressive course.
- early spread through lymphatics.

Stromal neoplasms

- adenosarcomas.
- endometrial stromal nodule.
- endometrial stromal sarcoma.

Endometrial stromal nodule

Endometrial stromal nodule

Endometrial stromal sarcoma

Endometrial stromal sarcoma

Leiomyomas (fibroids)

- benign smooth muscle neoplasm.
- symptoms depend on location.

Leiomyoma (showing low cellularity, bland nuclei, and no mitoses)

Leiomyosarcoma

- mass invading uterine wall or polypoid mass in lumen.
- diagnosed by high mitotic rate, cytologic atypia, and tumoral necrosis.
- peak incidence 40-60 years.
- metastasize by blood vessel invasion.
- 40% 5 year survival.

Leiomyosarcoma

Leiomyosarcoma (showing cytologic atypia and numerous mitoses)

Follicular cyst

- very common.
- may reach up to 5cm in size.
- forms when there is no LH surve and the cyst doesn't rupture to release its egg.
- usually harmless, often resorb after 2-3 menstrual cycles.
- smooth-walled unicameral (one chamber) simple cyst.

Corpus luteum cyst

- opening from released egg seals off the subsequent corpus luteum.
- may spontaneously resolve or grow to as large as 4cm.
- may hemorrhage or undergo torsion.

Torsion of ovary

- presents as sudden unilateral pain.
- often occurs in young women.
- mass >5cm.
- R/O ectopic pregnancy.
- diagnosed by ultrasound.

Polycystic ovary disease

- most common endocrine problem of reproductive age women.
- oligomenorrhea, hyperandrogenism, polycystic ovaries, obesity, acanthosis nigricans, diabetes.
- R/O other endocrine diseases (decreased T4, prolactinemia, cushing, acromegaly).
- diagnosed via ultrasound.

Polycystic ovary disease

Ovarian tumors

- asymptomatic until late presentation.
- disease of older women (60's).
- BRCA1/BRCA2 and MSH2 (lynch II syndrome) mutations.
- prognosis depends more on stage than on cell type.
- often bilateral.
- CA-125 and ultrasound screening.
- risk is decreased by tubal ligation and BCP.

Serous cystadenoma

- common.
- benign.
- lined by a single layer of epithelium.

Serous borderline carcinoma

- outgrowth on cyst wall.
- no invasion.
- often arise on and extend to peritoneum.
- 100% 5 year survival.

Serous borderline carcinoma

Serous borderline carcinoma

Serous borderline carcinoma

Serous borderline carcinoma (showing papillary architecture, clear line with stroma)

Serous borderline carcinoma (showing invasion and possible LVI)

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