Systems Pathology 2: Unit 2

What is the outer part of the female genitals?

Vulva

What is the most common condition of the vulva?

Inflammation = vulvitis

Causes of Vulvitis

(1) Allergic Contact Dermatitis (eczema)

(2) Infection

(3) Injury/Trauma

Allergic Contact Dermatitis (Eczema of the vulva)

Erythema, oozing/crusting, and itching

Caused by soaps, lotions, detergents, deodorants, or urine

What are some common infections of the vulva?

— HPV

— HSV-2

— N. gonorrhoeae

— C. albicans

— Treponema pallidum (syphilis)

— Trichomonas vaginalis

Condyloma Acuminatum

Aka veneral/genital warts (she will use this on exam)

HPV-6 & HPV-11

Flesh/skin-toned warts

Common location = vagina, vulva, cervix, and around the anus

What is Condylomata Lata?

Genital warts associated with secondary syphilis, NOT HPV

Bartholin Cyst

Inflammation of the Bartholin's glands (aka great vestibular glands)

Obstruction/dilation

— trauma, infection, etc. of the vulva can obstruct the ducts, causing this swelling

Develops quickly and could be painless or painful (dyspareunia = pain with sex)

What does the Bartholin Gland do? Where is it located?

Located to the Right and Left of the vaginal opening

Secretes mucus to lubricate the vagina

What is a Bartholin abscess?

Infection of the Bartholin Cyst

Now no longer a cyst —> infection (will be painful)

Bartholin Cyst: Dx and Tx

Dx: history, pelvic exam, sample of secretions from vagina/cervix to test for STI, biopsy if postmenopausal or over 40

Tx: depends on the size of cyst, how painful, and if infected or not

— home treatment or surgical drainage in worse cases

— antibiotics if infected (infections are rarely STIs and often involve multiple infective infective microbes that are native to the vaginal flora)

Recurrence = marsupialization or gland removal

DDx: Vulvar Lipoma

Could appear like a Bartholin Cyst

Lichen Simplex Chronicus (Neurodermatitis)

Hyperplasia & Hyperkeratosis (thick and leathery)

— chronic irritation (scratching makes it itchier)

— not contagious, but interferes with sleep, sexual function, and quality of life

— no cellular atypia (no caner risk)

May develop outside the vulvar area —> often associated with irritating occupational exposures or habitual rubbing behaviors (OCD)

Lichen Simplex Chronicus: Tx

Remove irritant

Anti-itch medicated creams (calcineurin inhibitor ointment may help)

Lichen Sclerosus

Atrophy of the skin

— suspected to be autoimmune

— patchy, smooth, white skin that appears thinner than normal

— near minora

— dermal fibrosis and vaginal constriction

Lichen Sclerosus: who?

Ages 8 & 60 (bimodal)

Lichen Sclerosus: Tx

Creams/ointments (corticosteroids) to return skin to normal appearance and reduce scarring

What is potential risk with Lichen Sclerosus?

Squamous Cell Carcinoma develops in about 5%

Vulvar Carcinoma (Neoplasia)

Rare

Exophytic (grows out — early) or ulcerative (grows in — more advanced stages)

MC = squamous cell carcinoma (90%)

— lymphatic metastasis (30% 5-year survivability if mets)

Vulvar Carcinoma: Who?

Older women (>60 years)

HPV-Related Squamous Cell Carcinoma

HPV-16 & 18**

— "high risk" strains

Vulvar intraepithelial neoplasia (VIN) —> not cancer yet, but have the risk because HPV has infected the cells (precancerous lesion)

HPV-Related SCC: Who?

— middle-aged

— smokers

— immunodeficiency

Non-HPV-Related Squamous Cell Carcinoma*

MC SCC

— older women

— Lichen Sclerosus (no VIN)*

What is used to check a female's internal pelvic organs?

Bimanual Pelvic Exam

— exam the vagina, cervix, uterus, ovaries, and rectum

— checking for pain, enlargement, size/shape/nature of uterus, presence of masses, palpates ovaries, and rectum check

What is a growth that occurs in or near the uterus, ovaries, fallopian tubes, and the connecting tissues?

Adnexal mass

Is the vagina a common site for primary pathology?

No —> rare for primary pathology

BUT a site for infection or cancer metastasis

Agenesis of the vagina

Rare congenital condition = absence of vaginal development

Tx = surgery

Vaginal Atresia

Congenital, abnormal narrowing or closure of the vaginal canal

Tx: self dilation (stretch the canal) or surgery

Septate Vagina/Vaginal Septum/Duplicate Vagina/Double-Barreled Vagina

Congenital anomaly that inappropriately divides the vagina

2 types:

(1) transverse (tissue runs horizontally and closes/blocks the vagina)

(2) vertical/complete (often associated with cervical and uterine septum)

Transverse Vaginal Septum: how?

Congenital (causes not really known)

Transverse Vaginal Septum: symptoms

— no monthly periods (amenorrhea)

— periods that last beyond normal 4-7 day cycle

— abdominal pain caused by blood collecting in the upper vagina

Transverse Vaginal Septum: Dx and Tx

Most cases isn't diagnosed until a girl reaches puberty and experiences problems with her period

— Dx starts with medical history and physical exam

— additional imaging such as ultrasound or MTI

Tx: surgery to remove the wall of tissue

Longitudinal/Vertical Vaginal Septum: Symptoms

Many may not have symptoms or even be aware until puberty and have difficulty using tampons

— or when become sexually active and have difficulties or discomfort during intercourse

Other symptoms:

— pain when inserting or removing a tampon

— menstrual blood that leaks even when using a tampon

— pain during intercourse

Longitudinal/Vertical Vaginal Symptom: Dx and Tx

Dx: Medical history and physical exam

— also imaging

Tx:

— observation only (if no pain or complications)

— surgery to remove tissue

What is the most common gynecological condition?

Vaginitis (vaginal inflammation)

MC types of vaginitis

(1) Bacterial infection (45%) — bacterial vaginosis (gray discharge)

(2) Yeast infection (Candida albicans; white discharge)

(3) Trichomoniasis (sexually transmitted parasite; yellow/green discharge)

Symptoms of Vaginitis

— leukorrhea (excessive malodorous discharge)

— pain during sex or urination

— itching

Vaginitis: Risks

— diabetes

— recent antibiotic use

— immunodeficiency

— pregnancy

— recent abortion/miscarriage

— STI

Vaginal Cancer: Symptoms

— unusual vaginal bleeding (Ex: after intercourse or after menopause)

— watery vaginal discharge

— lump or mass in vagina

— painful urination

— frequent urination

— constipation

— pelvic pain

Vaginal Intraepithelial Neoplasia (VaIN)

Cells infected by HPV

Cells in the vagina appear different from normal cells, but not different enough to be considered cancer

Vaginal Cancer: Risk Factors

— age

— vaginal intraepithelial neoplasia (VaIN)

— multiple sex partners*

— early age at first intercourse*

— smoking

— HIV infection

How common are primary vaginal cancers?

Primary vaginal cancers are rare

80% of cancer discovered in the vagina are metastatic tumors from other locations (such as cervical, colorectal, endometrial, bladder, and even some breast, melanoma, or kidney)W

What are the primary types of vaginal cancer?

(1) Vaginal Squamous Cell Carcinoma (85%)

(2) Vaginal Clear Cell Adenocarcinoma

(3) Vaginal Melanoma

(4) Vaginal Sarcoma Botryoides

Vaginal Squamous Cell Carcinoma

85% of primary vaginal cancers

benign in the thin, flat (squamous) cells that line the surface of the vagina

— rare and MC in elderly

HPV-16 & HPV-18 —> Vaginal intraepithelial neoplasia (VaIN)

Vaginal Clear Cell Adenocarcinoma

Begins in the glandular cells of the surface of the vagina

— red/glandular foci (foci = cells that look notably different than surrounding cells)

Very rare —> people who's mothers took Diethylstillbestrol (DES) = 40x risk

Vaginal Melanoma

Develops in the melanocytes

Vaginal Sarcoma Botryoides

Rare —> young girls

Soft/polypoid mass

— develops in the connective tissue or muscle cells in the vaginal walls

Embryonal/pediatric rhabdomyosarcoma = rare type of cancer that forms in soft tissue, most often affects children

Complications of vaginal cancer

May also metastasize to distant areas, such as the lungs, liver, and bones

What is the lower, narrow end of the uterus that forms a canal between the uterus and vagina?

Cervix

Roles:

— menstruation

— pregnancy

— fertility

— vaginal delivery

— protects the uterus

Cervicitis

Inflammation of the cervix

— MC "benign"

Often asymptomatic

— leukorrhea

— bleeding

— fever

— pain/discomfort during sex

***Prompt pelvic exam

Infectious causes of cervicitis

— chlamydia (MC — 40% of cases)

— trichomoniasis

— candidiasis

— gonorrhea

— genital herpes

— HPV

Bacterial overgrowth (bacteria normally present in the vagina)

Non-infectious causes of cervicitis

— Allergic reactions (spermicides, latex, douches, feminine deodorants)

— acute = postpartum

— chronic = reproductive age women (fluctuating estrogen levels)

Cancer of the cervix is strongly associated with exposure to what?

HPV Exposure

— early intercourse (prior to age 17 — HPV tends to infect the immature squamous cells in the transformation zone of cervix = super susceptible to infection)

— multiple sex partners

— male partners with several past partners

High-risk HPVs (70% = 16 & 18**; 20% = 31, 33, 34, 45, 52, 58)

Most HPV is transient (months of normal immune system)

Why are HPV-16 and 18 high risk?

Contain growth promoting genes E6 and E7, which suppress p53 and pRB genes

Cervical Intraepithelial Neoplasia (CIN) — again, does not mean cancer, but HPV has infected the cells (infected a while ago)

What is a sign of Cervical Intraepithelial Neoplasia (CIN)?

Koilocytosis = "halo cells"

— at the transformation zone (area of cervix where internal columnar cells transition into squamous cells — rapid during puberty)

— often asymptomatic and diagnosed often via a PAP smear

HPV-induced changes to squamous cells:

— anaplasia/dysplasia cellular changes

— enlarged nuclei

— irregular/wrinkled borders

— darker (hyperchromasia)

When is CIN most likely to appear?

MC at about age 30

Cervical cancer occurs about 15 years later (age 45)

Low-Grade CIN

CIN I = observation

— 60% regress

— 30% persists

— 10% progress to high-grade (monitored with more regular PAP)

High-Grade CIN

CIN II & III = excision

— 30% regress

— 60% persists

— 10% —> cancer

Managed with colposcopy

Colposcopy

Use a colposcope to look for any problems on the cervix or in the vagina (use sepculum to spread the walls of the vagina for the microscope to view)

— use acetic acid solution to make abnormal tissues appear white

— Schiller test (use an iodine solution)

May also take a small tissue sample

Tx for HPV in the cervix

Options:

— freezing (cryosurgery)

— laser

— surgical removal (loop electrosurgical excision procedure = LEEP or cold knife conization)

Invasive Carcinoma of the Cervix

ALL cases are from previous HPV infection

— Squamous cell carcinoma = 75%

— Adenocarcinomas = 20%

— Carcinoids = 5%

Diagnosed at around age 45

What 3 main vaccinations can help prevent against HPV in the U.S.?

(1) Gardasil

(2) Gardasil 9

(3) Cervarix

Since 2016, only use Gardasil 9 (protects against types 6, 11, 16, and 18)

Cervical Cancer mainly happens where?

Transformation zone

Cervical Cancer Symptoms

Asymptomatic in early stages

Later stages:

— leukorrhea

— bleeding

— dysuria

— painful sex (dyspareunia)

Prognosis depends on staging (spread)

Invasion —> renal failure = MC cause of death

Cervical Cancer Metastasis related to size

1% Mets if < 3mm

10% if > 3mm

Cervical Cancer: Who?

MC in women who lack screening

Cervical Cancer: Tx

Hysterectomy and lymph node excision

Smaller = cone biopsy or LEEP

Invasive cervical cancer causes what physical appearance?

"Barrel Cervical"

Endometritis

Inflammation of the endometrium (uterus)

(1) Infectious

(2) Non-infectious

Infectious Endometritis

Causes: gonorrhea, chlamydia, TB

Pelvic Inflammatory Disease (PID)

Noninfectious Endometritis

Retained products — Ex: conception, abortion, intrauterine device (IUD)

Symptoms:

— fever, abdominal pain

— menstrual abnormalities

— infertility or ectopic pregnancy

Endometriosis

Functional endometrial tissue located outside the uterus

— multiple masses (about 1-2 cm)

— grows and bleeds, but does not heal like normal uterus tissue —> heals via fibrosis

Locations: ovaries peritoneum, pouch of Douglas, uterine ligaments, fallopian tubes

— nodes, heart, lungs, bone, etc.

Endometriosis Symptoms

— dysmenorrhea

— dysuria

— pelvic pain

— sterility

— painful BMs and intercourse

Endometriosis: Who?

10% of reproductive-age women

Causes half of female infertility

Endometriosis: Dx

Pelvic exam, ultrasound, MRI, laproscopy

3 Theories behind Endometriosis (why it happens)

(1) Regurgitation (endometrial lining moves up the tubes and "regurgitates" out the fallopian tubes)

(2) Metaplasia

(3) Benign "metastasis" (vascular or lymphatic spread)

Endometriosis: physical appearance

"Chocolate cyst" seen on laparoscopic examination

Endometriosis: Tx

Mild cases — monitor and watch

Severe — pain medications (during menstruation); hormonal therapy (aromatase inhibitors — less estrogen production); surgery (remove it)

What is profuse/prolonged menstruation?*

Menorrhagia (more than 3-5 days)

What is irregular bleeding between periods (spotting)?*

Metrorrhagia

What is the resumption of uterine bleeding at least 6 months after a woman experiences menopause?*

Postmenopausal bleeding

What is the infrequent/irregular/inconsistent menses or an interval between menstrual cycles that extends beyond 35 days?*

Oligomenorrhea

What is the abnormal uterine bleeding in the absence of an organic lesion/pathology?*

Dysfunctional uterine bleeding (idiopathic uterine bleeding)

What are some potential causes of abnormal uterine bleeding?*

— leiomyomas (smooth muscle tumor), leiomyosarcomas, endometritis, endometrial hyperplasia, endometrial carcinoma, etc.

— anovulatory cycle (no ovulation) = inadequate luteal phase

— retained endometrium = prone to breakdown/bleeding

— idiopathic

Endometrial Hyperplasia

Overgrowth of endometrial cells

Causes of endometrial hyperplasia

Increased estrogen (obesity, PCOS, HRT)

— estrogen producing tumor or failed ovulation

Endometrial cancer

Serial biopsies —> "atypia"

— without cellular atypia = low risk (1-3%)

— with cellular atypia = high risk (20-30%)

3-50% transform into carcinoma

Tx = hysterectomy

What is the MC female genital tract cancer?

Endometrial Carcinoma

Endometrial Carcinoma symptoms

Enlarged uterus, leukorrhea, metorrhagia

Endometrial Carcinoma: Who?

Age 55-65

Endometrial carcinoma metastasis

Lymphatic mets = late stage

Types of Endometrial Carcinoma

(1) Endometrial Adenocarcinoma (80%)

— endometrial hyperplasia

— perimenopausal

— Risks = high estrogen**, obesity, diabetes, Lynch Syndrome, infertility, HTN

(2) Serous Adenocarcinoma (15%)

— endometrial atrophy

— TP53 mutations**

— aggressive

— NOT associated with endometrial hyperplasia or elevated estrogen

— 70-90 years old

Endometrial Polyps/Uterine Polyps

MC perimenopausal (but any age can occur)

Abnormal uterine bleeding and cancer risk

Smooth Muscle Tumors of the Uterus

(1) Uterine Leiomyoma

(2) Uterine Leiomyosarcoma

Uterine Leiomyoma

Uterine fibroids

— Benign and often multiple

— reproductive-age women; African Americans

— increased estrogens (oral contraception, obesity)

— shrink with menopause

Uterine Leiomyosarcoma

Malignant and solitary

— post-menopausal

— metastasis to lungs (MC) — 5 year survival = 40%

— Tx = excision, commonly recur

Early may be asymptomatic; Later = abnormal bleeding, high amounts of cellular atypia, and tissue necrosis

Histology = cigar shaped nuclei

What are the other terms for a Fallopian Tube?

Salpinx (plural = salpinges or salpinxes)

Means a trumpet-shaped tube

Also called Oviducts/Uterine tubes

What is inflammation of the fallopian tubes?

Salpingitis

What are the two main causes of Salpingitis?

(1) Microbial = chlamydia, gonorrhea, Strep., Staph.

— can cause PID or sepsis

(2) Other: ectopic pregnancy, endometriosis, tumor, etc.

— fever, abdominal pain, pelvic mass

— risk for ectopic pregnancy/sterility

Fallopian tube carcinoma

Adenocarcinoma; rare

Dx: late, invades peritoneal cavity

Genetics: TP53, BRCA1, BRCA2 increases the risk