13.1 - 13. 4: Vulva, vagina, cervix, and Endometrium Flashcards
What are the boundaries of the vulva?
Vagina external to the hymen
What is a Bartholin cyst? Who do they usually occur in?
- Inflammation/infection of the vestibular glands in the vagina (located in the posterolateral corners) 2/2 obstruction
- Women of reproductive age
What is a Condyloma accumata, and what causes it? What are the histological characteristics? Does it progress to carcinoma?
- Wart
- HPV 6 or 11
- Koilocytic change on histo
- Rarely progresses to CA
What are the HPV strains that cause warts? Cervical cancer?
- 6, 11 cause warts
- 16, 18, 31, 33, 35 cause CA
Where in the female genitalia are the three locations where HPV classically infects?
- Vaginal canal
- Cervix
- Vulva
How does koilocytic change appear? What pathology does this occur in?
- Crumpled raisins nuclei
- HPV infections
What is the viral family and genetic content of HPV? Enveloped?
- Papillomaviridae
- dsDNA
- Non-enveloped
What are CIN, VaIN, and VIN, respectively?
Cervical CA in situ
- Vaginal carcinoma in situ
- Vulvar carcinoma in situ
True or false: the koilocytic change that is characteristic of HPV infection occurs regardless of in the cell in cancerous or just a wart
True
What is Lichen Sclerosis? What are the clinical characteristics of this? In whom is this seen in?
- Thinning of the epidermis and fibrosis of the underlying dermis
- White, Parchment-thin paper
- Postmenopausal women
Is Lichen Sclerosis malignant or benign? If benign, does it have a risk of developing to SCC?
Benign, but has a slightly increased risk for developing into SCC
What is Lichen Simplex Chronicus? What are its clinical features?
- Hyperplasia of the vulvar squamous epithelium, that is associated with chronic scratching
- Leukoplakia with thick, leathery vulvar skin
Is Lichen simplex chronicus malignant or benign? If benign, does it have a risk of developing to SCC?
Benign with NO increased risk for the development of SCC
What are the major differences between lichen sclerosus and Lichen simplex? What is the treatment, generally, for both of them?
Sclerosis = thinning of the epidermis with white plaques
Simplex = hyperplasia with red, velvety lesions
Steroids to treat
What type of cancer arises in the vulva? How common is this?
SCC
Relatively rare
SCC of the vulva presents are what? What, generally, does this appear similar to? How can you differentiate?
Leukoplakia, which looks similar to the lichen lesions
Bx to confirm
What is Lichen planus?
Inflammatory, desquamative lesions of the skin
What are the two general etiologies of SCC of the vulva? In whom are each of these seen?
- HPV related (40-50 yo)
- Non-HPV related (postmenopausal woman)
What is Non-HPV related SCC? Who is this usually seen in?
- Arises from the inflammation caused by chronic lichen sclerosis
- Older women
What is the cause of extramammary Paget’s disease? How does this present?
Malignant epithelial cell in the epidermis of the vulva
-Presents as erythematous, pruritic, ulcerated skin
True or false; Extramammary Paget’s disease represents underlying carcinoma
False- represents carcinoma in situ, not underlying carcinoma
What are the histological characteristics of Paget’s disease?
Cells with clear halos about the nucleus
What are the two things that HAVE to be in your differential when Paget’s disease of the vulva presents?
Carcinoma vs melanoma
Paget’s cells and melanoma are distinguished using stains. For each, what are the results of the following stains:
- PAS
- Keratin
- S100
Paget’s:
- PAS(+)
- keratin (+)
- S100 (-)
Melanoma:
- PAS (-)
- Keratin (-)
- S100 (+)
What is Keratin? Why is this seen with Paget’s cells?
Intermediate filament that is present in epithelial cells. Why is this seen with Paget’s cells?
-Keratin means it comes from the epidermis, of which means it’s carcinoma (Paget’s)
Why are Paget’s cells PAS +?
PAS stains mucus, and only epithelial cells produce mucus (as Paget’s is a carcinoma)
—What is the major difference between Paget’s disease of the nipple, vs Paget’s disease of the vulva?—-
Nipple = there is an underlying CA
What is the epithelial type that lines the vagina?
Non-keratinized stratified squamous epithelium
The lower 1/3 of the vagina is derived from what? Upper 2/3?
- Urogenital sinus = lower 1/3
- Mullerian duct = upper 2/3
What are the derivatives of the mullerian ducts?
Upper 2/3 of the vagina and all the way up to the tubes
What is the epithelium of the upper 2/3 of the vagina during development? What changes occurs?
Initially simple columnar, but becomes stratified squamous by ascending growth of the stratified squamous epithelium of the lower 1/3
What is adenosis of the vagina?
Failure of the upper 2/3 of the vagina to transform to stratified squamous epithelium
Increased exposure to DES in utero leads to what two developmental pathologies? Why?
-Adenosis of the vagina
disrupts the development of the vaginal epithelium
-lack of development of the uterine muscle wall
Increased exposure to DES in utero leads to what two neoplastic pathologies?
- Clear cell adenocarcinoma
- Smooth muscle formation issues in smooth muscles
Are there any significant complications of DES use in male pregnancies? How about for mom?
- None for sons
- Breast cancer in women
What is embryonal rhabdomyosarcoma (sarcoma botryoides)? How common is this? What age does this occur in?
- Malignant mesenchymal proliferation of immature skeletal muscle
- Rare
- Less than 5 yo
What are the clinical features of embryonal rhabdomyosarcoma?
Bleeding and grape-like mass protruding from the vagina or the penis
What is the classic cell on histology for rhabdomyosarcoma? Features? What are the two stains that this is positive for?
- Rhabdomyoblast
- Cytoplasmic cross-striation
- Positive IHC staining for desmin and myogenin
Cytoplasmic cross-striation = ?
Rhabdomyoblast of rhabdomyosarcoma
What is desmin?
Intermediate filament that is present in muscle cells
What is myogenin?
Nuclear transcription factor that is present in immature skeletal muscle
What causes vaginal carcinoma?
Usually related to high risk HPV
What is the precursor lesion to vaginal carcinoma?
Vaginal intraepithelial neoplasia
Cancer from the lower 1/3 of the vagina goes to what lymph nodes?
Inguinal nodes
Cancer from the upper 2/3 of the vagina goes to what lymph nodes?
—–
Regional iliac nodes
——-
What is the epithelium of the endocervix? Exocervix?
Endo = columnar Exo = stratified squamous epithelium
Where in the cervix in particular is at risk for the development of cervical CA from HPV?
Transformation zone
True or false: most of the time HPV infections clear on their own, and thus does not usually present as a risk factor for cervical cancer
True–it is the PERSISTENT infection that is a risk
What are the two proteins in HPV that cause cervical cancer? What is the function of each? (2)
E6 = destroys p53 E7 = destroys Rb
What is the major function of p53
Regulates the transition between G1 to S phase of the cell cycle
What is the molecule that is recruited if p53 senses too much DNA damage? What does this do? What is the cascade of events that follows this to kill the cell?
Bax, knockout Bcl-2, destabilizing the mitochondria, and causing apoptosis
What is the molecule that Rb holds, in order to prevent progression of the cell into the G1/S phase? What must be done in order for Rb to release this?
E2F
Rb must be phosphorylated
What are the histological characteristics of CIN? (3)
- Koilocytic change
- Nuclear atypia
- Increased mitotic activity
What is the key difference between carcinoma and dysplasia?
Dysplasia is reversible
What are the four grades of CIS? At what point is it no longer reversible?
- I
- II
- III –last stage at which it is reversible
- CIS
True or false: Stages I, II and III of dysplasia and CIS are not inevitable–they may regress
False–I, II, and III are reversible, but once at CIS, not reversible
What is the distinguishing factor between cervical carcinoma, and cervical CIS?
Invasion of the BM = carcinoma
How does cervical carcinoma usually preset?
- Vaginal bleeding
e. g. Postcoital bleeding
What general age range of women usually develop cervical carcinoma?
Middle aged women
What are the two major risk factors for the development of cervical CA?
- Smoking
- Immunodeficiency
What are the two organ systems that smoking can cause cancer in, that is not immediately obvious (doesn’t touch)?
Pancreas
Cervix
True or false: cervical carcinoma is an AIDS-defining illness
True
What are the two subtypes of cervical cancer that can develop from HPV infection?
- Squamous cell carcinoma
- Adenocarcinoma
What is the classic finding associated with advanced cervical cancer? Why?
Hydronephrosis–invasion through the anterior uterine wall into the bladder
True or false: cervical carcinoma metastasizes early, and often
False– rarely and late
What is the gold standard for screening for cervical carcinoma?
Pap smear
What are the histological findings on a pap smear that are suggestive of cervical carcinoma? (2)
- Cells with low nuclear:cytoplasm ratio
- hyperchromatic nuclei
What is the next step with an abnormal pap smear?
Colposcopy and bx
What is the major reason for a false negative with a pap smear?
Sample does not reach the transformation zone
Pap smears has limited efficacy for screening cervical carcinoma or adenocarcinoma
Adenocarcinoma
What are the four subtypes of HPV that are protected against with he gardasil vaccine? Which cause condyloma, and which cause carcinoma?
6, 11 = condyloma
16, 18 = carcinoma
True or false: pap smears are no longer necessary, with the gardasil vaccine
False–still need to assess for other subtypes
What is the hormone that causes the endometrium to grow? To mature?
——
Grow = estrogen Mature = progesterone
What type of muscle comprises the myometrium?
Smooth muscle
What is asherman syndrome? Usual cause?
Secondary amenorrhea due to a loss of basalis and scarring
-usually caused by overaggressive D and C
What is the layer of the endometrium that is lost with asherman syndrome, and is the layer of stem cells in the uterus?
Stratum basalis
What is the layer of the uterine endometrium that regenerates the stratum functionalis?
Stratum basalis
What is the pathophysiology behind the abnormal uterine bleeding in an anovulatory cycle?
No ovulation means there’s no corpus luteum to secrete progesterone. No loss of progesterone = no shedding, so sheds is small amounts
What are the two time periods where anovulatory cycles are usually seen?
Menarche
Menopause
What usually causes acute endometritis?
-Bacterial infection of the endometrium, 2/2 retained products of conception
What are the s/sx of acute endometritis? (3)
- Fever
- Abnormal uterine bleeding
- Pelvic pain
True or false: lymphocytes are usually found in a normal uterine lining
True
What is the classic cell that is found with chronic endometritis, and is needed to diagnose it?
Plasma cells
What are the common causes of chronic endometritis?
- Retained POC
- PID
- IUD
- TB
What are the s/sx of chronic endometritis?
- Abnormal uterine bleeding
- Pelvic pain
- Infertility
What, generally, is an endometrial polyp?
Hyperplastic protrusion of endometrium
What is the classic presentation of an endometrial polyp? Why?
Abnormal uterine bleeding–polyp stretches away from its BM
What drug can produce an endometrial polyp? Why?
Tamoxifen–has pro-estrogen effects on the uterus
What, generally, is endometriosis?
Abnormal placement of endometrial glands and stroma outside the uterine endometrial lining
What is the classic presentation of endometriosis? (3)
- Dysmenorrhea
- Pelvic pain
- Deep Dyspareunia
What are the three theories of endometriosis?
- Retrograde menstruation
- Metaplastic (mullerian duct)
- Lymphatic dissemination theory
What is the most common site of endometriosis? What does this form, once there?
Ovary
Chocolate cysts
If the uterine ligaments are involved in endometriosis, what is the usual presentation?
Pelvic pain
If the pouch of douglas is involved with endometriosis, what is the usual presentation?
dyschezia
If the bladder wall is involved with endometriosis, what is the usual presentation?
Dysuria
If the bowel serosa is involved with endometriosis, what is the usual presentation?
Abdominal pain and adhesions
If the fallopian tube is involved with endometriosis, what is the usual presentation?
Scarring and thus infertility or ectopic tubal pregnancy
How can endometriosis cause an ectopic pregnancy?
Scarring of the tubes leads to incorrect implantation
What are the “gunpowder lesions” associated with endometriosis?
Speckles of endometrial tissue in tissue
What is adenomyosis?
Endometriosis with involvement of the myometrium
What area in particular is at increased risk of forming carcinoma 2/2 endometriosis?
Ovary
What is the general histological change that defines endometrial hyperplasia?
Increase in the number of glands of the endometrium relative to the stroma
What is endometrial hyperplasia? What usually causes it? How does it present?
- Hyperplasia of endometrial glands relative to stroma
- Consequence of unopposed estrogen
- Presents as postmenopausal uterine bleeding
What is the estrogen that is converted from androstenedione in adipose tissue?
Estrone
What are the two ways of defining endometrial hyperplasia?
Architectural growth and cellular atypia
What is the most important predictor for progression of endometrial hyperplasia to carcinoma?
Cellular atypia
What is the consequence of untreated endometrial hyperplasia?
Endometrial carcinoma
What is endometrial carcinoma? How does is usually present?
- Malignant proliferation of endometrial glands
- Postmenopausal bleeding
What is the sporadic pathway of endometrial carcinoma? What is the type of histology found with this? What age group does this usually occur in? What is the gene associated with this?
Sporadic CA from atrophic endometrium
- Serous or papillary
- Older women (70s)
- Mutations in p53
What is the hyperplasia pathway of endometrial carcinoma? What is the type of histology found with this? What age group does this usually occur in?
- Hyperplasia leads to CA
- Endometrioid (looks like endometrium)
- Younger women (60s)
Is sporadic endometrial CA aggressive or benign?
Aggressive
What lung cancer can also develop psammoma bodies?
Mesothelioma
What, generally, is a leiomyoma?
Benign proliferation of smooth muscle, arising from the myometrium
True or false: leiomyomas are related to estrogen exposure, enlarge with pregnancy, and shrink with menopause
True
What are the gross characteristics of leiomyomas? (single vs multiple. well or ill defined. color. shape, etc)
Multiple, well defined, white whorled masses
Are multiple lesions suggestive of benign leiomyomas, or malignant leiomyosarcomas?
Benign
How can you differentiate leiomyosarcomas from leiomyomas grossly, not relating to number
White = leiomyoma Necrotic = leiomyosarcoma
What is the age range for leiomyomas? Leiomyosarcomas?
Premenopausal - leiomyomas
Postmenopausal = leiomyosarcomas
What is the usual presentation of leiomyomas?
Asymptomatic
What are the s/sx of leiomyomas, if symptomatic?
- Abnormal uterine bleeding
- infertility
- pelvic mass
True or false: leiomyosarcomas generally arise from leiomyomas
False false false–leiomyosarcomas arise de novo
Which is usually a single lesion, and which has multiple: leiomyomas vs leiomyosarcoma?
Single = leiomyosarcoma Multiple = leiomyoma
