Pathoma - Chapter 13 - FemaleGenitalSys

The vulva represents what? Skin and mucosa of the female genitalia that is external to the hymen

The vulva is lined by what cells? Squamous epithelium

What is a Bartholin cyst?Cystic dilation of Bartholin gland. Arises due to inammation and obstruction of the gland; usually occurs in women of reproductive age

.

"Unilateral lesion in the lower vestibule adjacent to the vaginal canal" sounds like? Bartholin cyst

Presentation of Bartholin cyst? Unilateral, painful cystic lesion.

What is a condyloma? What is it due to? Warty neoplasm of vulvar skin, often large. MC due to HPV 6 or 11.

HPV can infect ___________. the lower genital tract (vulva, vagina, cervix)

What key changes can you see in cells that are infected with HPV? Koilocytic change (raisin-looking nucleus with halo)

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How can HPV be divided? Low risk type and high risk type.

How do we know whether an HPV strain is high or low risk? DNA-sequencing allows us to determine or subclassify HPV as high or low risk.

HPV is a _________ (DNA/RNA) virus. DNA (remember we use DNA-sequencing to classify it)

High risk HPV? 16, 18, 31, 33

What classic lesion is a low risk HPV gonna produce? Condyloma. Can occur anywhere along lower genital tract.

What do we call the lesions that develop in the lower genital tract after infection with high risk HPV? (1) Cervix: CIN (2) Vagina: VAIN (3) Vulva: VIN

Condyloma ___________ (often/rarely) progresses to carcinoma. rarely

What is this? Condyloma


What is this? Higher power micrograph of previous picture of a condyloma. Note the raisinoid appearance of nucleus.

What is Lichen sclerosis? How does it present?Thinning of the epidermis with brosis of the dermis. Classically presents with leukoplakia with a parchment (pergament)-like. It feels su

per thin.

Lichen sclerosis is usually seen in ___________. postmenopausal women

Lichen sclerosis is __________ (benign/malignant). Benign, but is associated with a slightly increased risk for squamous cell carcinoma.

What is Lichen simplex chronicus?Sort of the opposite of Lichen sclerosis with thickening of the skin.

We see leukoplakia with thick leather like skin due to hyperplasia of vulvar squamous epithelium.

What is Lichen simplex chronicus associated with? Chronic irritation ("chronicus") and scratching.

Lichen simplex chronicus is __________ (benign/malignant). Benign, no increased risk for squamous cell carcinoma. ("Simplex; it's a simple entity that doesn't want to do any harm")

Vulvar carcinoma arises from? Squamous epithelium lining the vulva.


Vulvar carcinoma is ____________ (moderately frequent/relatively rare). relatively rare

Vulvar carcinoma accounts for a _________ (signicant/small) percentage of female genital cancers. small

How does vulvar carcinoma present? With leukoplakia. You need biopsy to distinguish it.

What vulvar pathologies present with leukoplakia? (1) Lichen sclerosis (2) Lichen simplex chronicus (3) Vulvar carcinoma

What pathways can lead to vulvar carcinoma? (1) HPV-related - High risk HPV (2) Non-HPV related - Long-standing lichen sclerosis

At what age would you expect to see vulvar intraepithelial neoplasia? 40-50 (it takes time to develop dysplasia after virus infection)

You would tend to see non-HPV related vulvar carcinoma in postmenopausal woman. Why? Greater than 70 for example, due to long standing lichen sclerosis.

What is extramammary Paget disease?Malignant epithelial cells in the epidermis of the vulva. ("Paget was a very busy man, he discovered many things; Pagets disease of the nipple, Paget's disease of the vulva, Paget's disease of the bone

etc")


How does Paget's disease of the nipple or vulva present? Presents as erythematous, pruritic, ulcerated skin.

What is this? Extramammary paget's disease. Note the "extra" cells in there that doesn't belong.

What is your DDx when you have extramammary Paget's disease? How do you distinguish?

Carcinoma vs melanoma Stains: Paget cells: PAS+ (only epithelial cells make mucus which this stains), Keratin + (it's a carcinoma), S10

0- Melanoma cells: PAS-, Keratin-, S100+

What does extramammary Paget's disease represent? Carcinoma in situ.

When a patient has Paget's disease of the nipple, it means that _____________.

they have cancer somewhere in the breast, while in extramammaryPaget's disease there usually is no underlying carcinoma.

What is adenosis?Focal persistence of columnar epithelium (normally it is nonkeratinizing squamous cells) in upper third of vagina. (Lower two thirds sho

uld replace upper one third)

The cells lining the lower two thirds of the vagina in females are derived from __________. Urogenital sinus

The upper one third of cells in the vaginal canal are derived from ______________. the mllerian duct


There is an increased incidence of adenosis in females exposed to ________________ which would increase the risk for what? DES in utero (diethylstilbestrol) Clear cell adenocarcinoma

What is clear cell adenocarcinoma of the vagina? Malignant proliferation of glands with clear cytoplasm. Rare complication of DES-associated vaginal adenosis.

What is an embryonal rhabdomyosarcoma? Malignant mesenchymal proliferation of immature skeletal muscle. It is very rare.

How does embryonal rhabdomyosarcoma present?Bleeding and grape-like mass protruding from vagina or penis in a child. Usually < 5 years of age. Also

called sarcoma botryoides.

Malignant cells in rhabdomyosarcoma is called a _________. What are some important characteristics of this cell?

Rhabdomyoblast Important: (1) Cytoplasmic cross-striations (2) Immunohistochemical stain positive for desmin (intermediate lament pr

esent in muscle cells) and myoglobin

Describe the region of lymph node spread if the patient gets a vaginal carcinoma.

(1) Cancer from lower 2/3 of vagina goes to inguinal nodes (2) Cancer from uppwer 1/3 of vagina goes to regional iliac nodes

The cervix is the _______ of the uterus. 'neck'

How is the cervix divided? Exocervix and endocervix. Diering types of epithelium cover them.


What types of epithelium line the cervix?(1) Exocervix: Squamous epithelium (2) Endocervix: Columnar epithelium Exocervix is to the left of the

transformation zone.

HPV is a ___________ transmitted _______ (DNA/RNA) virus. sexually; DNA

HPV especially likes to infect what? Cervix at the transformation zone.

What is most likely to happen when you get an immune infection.Most of the time the immune system rids itself of the virus. It's only when persistent infection occurs we see a risk for progression to

CIN.

What makes high risk HPV high risk? It produces two proteins: E6: Destruction of p53 E7: Destruction of Rb (normally "holds" E2F)

CIN is characterized by what? (1) Koilocytic change (2) Nuclear atypia (3) Increased mitotic activity

CIN grade is based on what? Extent of dysplasia. E.g. lower third = CIN I

What is the key feature that distinguishes dysplasia from carcinoma? Reversibility


CIN I reverses about ________% of the time. 66%

CIN II reverses about _____ % of the time. 33%

How often does CIN III reverse? It is unlikely that it will reverse.

What is this? It is taken from the cervix. Carcinoma in situ, maybe CIN III to the left.

True or false: Carcinoma from CIN is inevitable. False.

We have CIN I, CIN II, CIN III, CIS, so what is cervical carcinoma? When CIS invades we call that cervical carcinoma.

Cervical carcinoma is MC seen in? Middle-aged women (40-50)

How does cervical carcinoma present? As vaginal bleeding. Could be postcoital bleeding.


Secondary risk factors for cervical carcinoma? (1) Smoking (2) Immunodeciency

A patient with HIV infection develops cervical carcinoma. What is the signicance of this? Cervical carcinoma is an AIDS dening illness.

What types of cervical carcinoma are there? (1) Squamous cell carcinoma (more common) (2) Adenocarcinoma BOTH types are related to HPV.

True or false: Cervical carcinoma metastasize early. False. They tend to metastasize very late. Advanced tumors often invade through the anterior uterine wall into the bladder.

One of the classic ndings when you have an advanced cervical carcinoma is ___________. hydronephrosis

One of the MCC of death in patients with advanced cervical cancer? Postrenal failure These cancers tend to locally create symptoms rather than metastasize.

Gold standard for screening for dysplasia in cervix?Papanicolaou smear It is the most successful screening test develope

d to date.

You have an abnormal pap smear. What now? You have to follow it with a conrmatory colposcopy and biopsy.


There are some limitations with pap smear, what is it?(1) Inadequate sampling of the transformation zone results in false negative screenings. (2) It does not detect adenocarcinoma very w

ell (doesn't go through same CIN sequence as squamous)

True or false: The incidence of adenocarcinoma of the cervix has decreased signicantly after introduction of the pap smear. False. Pap smear has limited ecacy in detecting adenocarcinoma.

Immunization is ________ (moderately eective/eective) in preventing HPV infections. eective

The current HPV vaccine we use is composed of what? How long does it last?

Quadrivalent vaccine that covers HPV 6,11, 16 and 18. Protection lasts for 5 years.

A doctor tells a young female adult with previous history of HPV immunization that she doesn't have to worry about pap smears any

more. Is he right?

He is not right, pap smear is still necessary. You're not protecting against other somewhat less common subtypes but still high risk str

ains of HPV.

Normal uterus histology.

How does the uterus respond to hormones? (1) It grows with estrogen (2) It prepares for implantation with progesterone Shedding occurs with loss of progesterone support

What is Asherman syndrome? What is the cause?

Secondary amenorrhea because of loss of basalis layer (regenerative layer) and scarring. Result of overaggressive dilation and curettag

e ("scraping away") [D&C].


What is anovulatory cycle? Describe.It means lack of ovulation. No ovulation results in estrogen-driven proliferative phase without progesterone-driven secretory phase (out

grow blood supply).

Anovulatory cycle is a common cause of what? Dysfunctional uterine bleeding, especially during menarche and menopause.

What is acute endometritis usually due to? Retained products of conception (nidus for bacterial infection)

A woman presents with fever, abdominal pain with bleeding from her vagina and pelvic pain 2 days after conception. What could this

be?Acute endometritis

What inammatory cells are normally present within the endometrium? Lymphocytes

What is chronic endometritis? What characterizes it? Chronic inammation of endometrium. Characterized by plasma cells.

Common causes of chronic endometritis? (1) Retained products of conception (2) Chronic PID (e.g., chlamydia) (3) IUD (4) TB (granulomas)

It's common for __________ biopsies to be performed in patients with infertility. endometrial


How does chronic endometritis present? (1) Abnormal uterine bleeding (2) Pelvic pain (3) Infertility

What is an endometrial polyp? How does it present?Hyperplastic protrusion of endometrium. Presents as abnormal uterine bleeding (stretches endometrium

).

A woman undergoing therapy for breast cancer. She now presents with abnormal uterine bleeding. What might be going on?

Tamoxifen has anti-estrogenic eects on the breast but weak pro-agonistic eects on the endometrium. Could cause a polyp which cou

ld bleed.

What is endometriosis? Endometrial glands and stroma outside the uterine endometrial lining.

How does endometriosis present? (1) Dysmenorrhea - Displaced tissue can cycle as well. (2) Pelvic pain It may cause infertility (covers ovaries).

What theories do we have for how endometriosis develops?(1) Retrograde menstruation theory - Prevailing theory (however doesn't explain everything) (2) Metaplastic theory (3) Lymphatic disse

mination theory - Endometriosis has been seen in the lung.

Common sites of involvement in endometriosis?(1) Ovary (chocolate cyst) (2) Uterine ligaments (pelvic pain) (3) Pouch of Douglas (pain with defecation) (4) Bladder wall (pain with urination) (5) Bowel serosa (abdominal pain and adhesions) (6) Fallopian

tube mucosa (scarring; risk of ectopic pregnancy; infertility)

MC site of involvement in endometriosis? Ovary


What is this? Chocolate cyst (it's gonna grow and shed, grow and shed, grow andshed etc., accumulating bloody debree)

What is this? Gunpowder lesions. Endometriosis involving soft tissues.

You can get endometriosis that involves the myometrium. What is this called? Adenomyosis

One of the important complications of endometriosis is ________. Increased risk of carcinoma at the site of endometriosis; especially the ovary

What is endometrial hyperplasia?Hyperplasia of endometrial glands relative to stroma. Consequenceof unopposed estrogen. Instead of having glands and stroma equally spaced out, you start getting a lot of glands relative to the strom

a.

How does endometrial hyperplasia present? Postmenopausal uterine bleeding. Androgen gets converted to estrone in adipose.

What is this? Endometrial hyperplasia

How do we classify endometrial hyperplasia? It is classied histologically. Based on architectural growth (simple or complex) and cellular atypia. E.g. "Simple hyperplasia with atypia"


What is the most important predictor for progression to carcinoma in endometrial hyperplasia? Cellular atypia

How does endometrial carcinoma present? Postmenopausal bleeding (just like hyperplasia)

Endometrial CA can arise via what two pathways? (1) Hyperplasia (2) Sporadic

What histology do we see in endometrial carcinoma that has arisenvia the hyperplasia pathway?

Endometrioid (cancer looks very much like the normal endometrium)

What histology do we see in endometrial carcinoma that has arisenvia the sporadic pathway?

We don't have hyperplasia in this pathway. You get cancer from an ATROPHIC endometrium. Histology is "serous" which often have for

mation of papillae or papillary structures.

The sporadic pathway leading to endometrial CA usually occurs in the _________ (young/elderly). elderly (woman greater than 70)

The hyperplastic pathway leading to endometrial CA usually occurs in the __________ (middle-aged/elderly). middle-aged (~50-60)

What drives the sporadic type of endometrial carcinoma? p53


What is the precursor lesion to sporadic endometrial carcinoma? There is no precursors lesion.

What could happen in the sporadic type of endometrial carcinoma on histology?

Papillae could necrose and undergo calcication (psammoma bodies).

What is this? Endometrial carcinoma.

How did this endometrial carcinoma arise?

This is the endometrioid pattern. The cancer has arisen from hyperplasia. Note how piled up the glands

are with minimal stroma.

How did this endometrial carcinoma arise?

Note the papillary projection with brovascular core. This is the sporadic type. We could see psammomabodies here (remember we can also see that in papillary carcinoma o

f the thyroid).

What is a leiomyoma? Leiomyoma is related to what? Benign proliferation of smooth muscle arising from myometrium. Related to estrogen exposure.

Leiomyomas tend to occur in __________ (pre-/postmenopausal women). premenopausal women (related to estrogen exposure)

Leiomyomas are _____________ (single/often multiple). often multiple (multiple masses within the uterine wall that grow with pregnancy)


Leiomyomas tend to _________ (grow/shrink) after menopause. shrink (estrogen exposure)

How do leiomyomas appear in the uterus? Multiple, well-dened white whorled masses.

What is this?Leiomyoma. When they are multiple it indicates that its benign. Lei

omyosarcomas are single. White-whorley masses also indicates benign.

Leiomyomas are usually ___________ (asymptomatic/symptomatic). asymptomatic

When leiomyomas present with symptoms how do they present? Abnormal uterine bleeding, infertility, pelvic mass.

True or false: Leiomyosarcomas arise from leiomyomas. False. They arise de novo.

Leiomyosarcomas are usually seen in? Postmenopausal women

Leiomyosarcoma is usually _____________ (multiple/a single) lesion with _________ and _________. a single; necrosis; hemorrhage


What is seen on histology of a leiomyosarcoma? (1) Necrosis (2) Mitotic activity (3) Cellular atypia


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Pathoma - Chapter 13 - FemaleGenitalSys