Flashcards in Cervix and Uterus Path Deck (76)
What is the "cervical os?"
The center hole in the cervix that basically connects the cervix to the uterus (it will be wider in a woman who gave birth vaginally).
What kind of epithelium is found in the exocervix/ectocervix? What about the endocervix? What happens in between the exo and endo?
Exo is squamous, Endo is columnar. In between there is "Squamous metaplasia."
What is the "transformation zone" and what kind of cells are found here and what's important about this?
The zone where the endocervix becomes the exocervix, and it is composed of squamous metaplasia, this is the area where we look for dysplasias.
What is a "Nabothian Cyst?"
Completely benign, these are caused when the squamous epithelium overgrows and sheds, they cover the columnar pappilae and obstruct the crypts, thus the mucus gets obstructed and collects in the deeper crypts of the columnar cells --> formation of a Nabothian Cyst.
What is the major bacterial endogenous flora in a woman's vagina and what does it do?
Lactobacilli, it secretes hydrogen peroxide and lowers the vaginal pH, killing off the overgrowth of other bacteria.
Squamous metaplasia occurs naturally and via trauma and infections, how?
Naturally, when a woman reaches menarchy, cervical sq mucosa uptakes glycogen (due to estrogen spikes) which allows for the growth of bacteria, and their waste product acidifies the environment. The vagina responds with a sq metaplasia. Trauma and infections will also cause this metaplasia as a protective mech.
What do we expect to see in an acute cervicitis?
Neutrophils (acute inflammatory cells), erosions, reactive/repairative epithelial changes.
What do we expect to see in chronic cervicitis?
Mononuclear inflammatory cells such as macrophages, lymphocytes, plasma cells. Necrosis and granulation tissues may be involved.
What do we see in a cervix in response to Herpes infection causing cervicitis?
Intranuclear inclusions, epithelial ulcerations, lymphocytic infiltration.
How do "Trichomonas Vaginalis" look? (They cause cervicitis)
Anarobic, flagellated protozoa that is "pear shaped."
What does "Chlamydia Trachomatis" look like? (They cause cervicitis).
Small gram neg obligate intracellular organisms, associated with lymphoid germinal centers and prominent plasmacytic infiltrate.
What do we see in Candida Albicans? (They cause cervicitis).
They are fungus/yeast, we see pseudohyphae.
What are "Endocervical Polyps?"
Benign, inflammatory polyp found in the endocervical canal that can cause irregular "spotty" bleeding.
How are endocervical polyp tx-ed?
Surgical excision or curettage.
How do endocervical polyps look?
Soft, mucoid, dilated, showing inflammation and sq metaplasia.
What is "Microglandular Hyperplasia?"
Found in the endocervix, associated with Oral contraceptives (OC's), Looks like a polyp or erosion, can be mistaken for an adenocarcinoma.
What is Koilocytic Atypia?
A nuclear atypia with a perinuclear halo in the sq epithelium of the cervix, as seen in a HPV infection.
Which strains of HPV is associated with condylomata (Genital warts)?
6,11,42, 44, 53, 54, 62. 6 and 11 especially.
Which HPV strains are associated with cancer?
16 and 18 specially, 31 33 35 39 45 58 and 68 as well.
What class of a virus is HPV and what is its target?
It is a DNA virus and its target is Lower Genital tract, especially the cervix in the transformation zone.
What needs to occur with respect to HPV infection to result in CIN?
Persistant infection, HPV is cleared relatively well by our immune system so there needs to be a persistant infection for progression to CIN.
What is it about the HPV that makes the virus such a high risk for cervical cancer, yet other subtypes arent as high risk?
They produce 2 proteins, E6 and E7. E6 destroys p53, whereas E7 destroys retinoblastoma, and both of these are tumor suppressor proteins.
What is the job of p53?
It's job is to regulate the progression of the cell from G1 to S phase, to check to see if the DNA produced is damaged. If there's no damage the cell proceeds to S phase, however if there is damage the p53 will stop the cell and signal to repair enzymes in an attempt to fix the damage, and if damage is too intense apoptosis is induced instead.
Assuming the cell is damaged, what steps does p53 take to fix this? What does it do if damage is too severe?
It calls in repair enzymes to try to fix the damage, however if the damage is too severe p53 will call BAX. BAX will destroy bcl 2, whose job is to maintain the stability of the mitochondria. Once bcl 2 is out, cytochrome c leaks out of the cell and induces apoptosis.
What is the job of Rb (Retinoblastoma)?
It holds the molecule "E2F," and this is needed for the progression of the cell to go from G1 to S. However for this molecule to be released Rb's need to be phosphorylated, and if Rb's are destroyed the E2F are floating around freely and not regulated, all cells can take it up.
What is CIN?
Cervical Intraepithelial Neoplasia, characterized by koilocytic change, nuclear atypia, and increased mitotic activity. This is divided into different grades based on how immature and dysplastic the cells are.
What are the 4 different staging of CIN?
CIN grade I is dysplasia in the first 1/3 of cervical epithelium, II is 2/3, III is most of the thickness of the epithelium, and if the entire thickness of the epithelium is involved its called Carcinoma in situ.
What's the difference between dysplasia from carcinoma? How does that relate to CIN grading?
Dysplasia can reverse, carcinoma cannot. CIN I, II, and rarely even III can reverse because they are dysplasias at that point. CIS (Carcinoma in situ) is irreversible.
What is the general progression of CIN?
1 to 2 to 3 to CIS to invasive carcinoma. However, 1 has a 66% chance to go back to normal, 2 has a 33% chance to turn back into 1, and 3 rarely ever goes back to 2 but it is possible. Once you go to CIS, it wont reverse.
What distinguishes CIS from invasive carcinoma?
CIS is the entire thickness of the epithelium of the cervix, invasive carcinoma will invade the basement membrane in addition.
How does invasive cervical carcinoma present?
Presents in middle aged women 40-50 years of age and the frist sign is vaginal bleeding, or post coital bleeding.
What is the key risk factor for cervical carcinoma, and secondary risk factors?
Key is HPV (high risk variety of 16,18,33,34), secondary is smoking and immunodifficiency.
Smoking causes a variety of cancers, which are they? (There are 7).
Oropharyngeal carcinoma, Esophageal sq cell carcinoma and Lung cancer (smoke directly hits these areas), also kidney cancer and urothelial cancer because the toxins from the cig smoke is filtered by the kidneys and concentrated into the urine. Also, 2 weird ones that smoking increases the risk of cancer is pancreatic cancer and cervical cancer.
What are the two types of cervical cancer?
Cervical Sq cell carcinoma, which is a carcinoma of the exocervix, and cervical adenocarcinoma, which is a cancer of the exocervix. Both are caused by HPV but Sq cell varient much more common.
What is a classical sign of advanced carvical cancer? What is one of the most common reason patients with cervical cancers die?
Hydronephrosis, because the cancer will grow in size and impinge the bladder causing obstruction, leading to hydronephrosis and post renal failure. Patients often die due to post renal failure and hydronephrosis, NOT METASTASIS. Cervical cancers will metastasize very late, before that it will cause local, often life threatening problems.
What is the gold standard of screening for cervical cancers?
PAP smear, where a brush will be inserted to scrape cells off of the transformational zone and viewed in a microscope to see dysplasias (i.e. high nuclear:cytoplasm ratios, dark, hyperchromatic nucleus, weird looking cells, etc).
If the PAP smear is positive, what is the confirmatory test?
A colposcopy (insert a magnifying glass into the vagina, stain with acid to see abnormal parts and then get a biopsy of that part.
What is a limitation of PAP smears?
Cannot detect adinocarcinomas very well, because the adenocarcinomas are not sq cells, it doesnt follow the same grading as sq cell carcinoma and its a lot harder to detect.
What is the vaccine against HPV?
A quadravalent vaccine that hits 6 and 11, (for genital warts) and 16,18 (for cancer). Will only last 5 years however.
What is the "endometrium" and the "myometrium?"
The endometrium is the mucosal lining of the uterine cavity and the myometrium is the smooth muscles under the endometrium
What is the sequence of changes that the endometrium will undergo and what precipitates these changes?
Growth --> preparation --> shedding. Growth of endometrium is due to estrogen, the preperation stage is the secretion stage of the endometrium where it prepares for implantation of the ovum, this is due to progesterone. Once progesterone support is removed, the endometrium will shed resulting in menstruation.
What is the "basalis" of the endometrium?
It is the regenarative layer of the endometrium where the stem cells are located. It is the layer responsible for growing the "functionalis" layer, which is the layer that is shed. Once shed, the basalis will grow a new functionalis layer, which will be shed, and cycle goes on.
What is "Asherman Syndrome?"
This is secondary amenorrhea due to a loss of the basalis layer, which may be due to overaggressive dilation and curettage (cervical procedure to remove polyps).
What is an "anovulatory cycle" and when is this classically seen?
It is a lack of ovulation classically seen during menarchy and menopause, where basically there is estrogen induced growth of endometrium but no ovulation, so the progesterone preperation stage doesn't kick in. The next cycle then begins and once again the estrogen will now induce growth of endometrium on TOP of existing endometrium, and the cells will grow beyond the blood supply and degenerate --> results in irregular bleeding.
What is "acute endometritis?" How does it present?
Bacterial infection of the endometrium usually due to retained products of conception (i.e. something is left behind after delivery of the baby or an abortion left overs, etc). Presents as fever, abdominal uterine bleeding and pelvic pain.
If lymphocytes are seen in the endometrium can one diagnose chronic endometritis? What is chronic endometritis?
Lymphocytes are commonly present in the endometrium anyway, so we would need to see PLASMA CELLS to call it chronic endometritis. Chronic endometritis is chronic inflammation of the endometrium.
What causes chronic endometritis?
Retained contents after delivery/conception, PID (particularly induced by chlamydia, aand also gonorrhea), IUD, and TB.
What are the clinical symptoms of chronic endometritis?
Abnormal uterine bleeding, pelvic pain and infertility.
What causes an endometrial polyp? What drug can cause this?
Hyperplasia of the endometrium, which will then result in abnormal bleeding. Can arise as an adverse effect of the drug tamoxifen (which is anti-estrogen in the breast, but weak pro estrogen in the uterus, resulting in endometrial hyperplasia).
What is the classic definition of "Endometriosis?" How does it present?
Misplacement of the endometrial glands and stroma, which ends up being outside the uterine endometrial lining. Presents in dysmenorrhea and pelvic pain, can also cause infertility.
What is the leading theory of endometriosis?
Retrograde menstruation where some of the menstrual products go up rather than down and goes up the uterus into the fallopean tubes, into the ovaries and then the pelvis.Other theories exist, such as metaplasia and dissemination through the lymph.
What is the most common site of endometriosis? What are other less common sites and how would they present?
The ovary, particularly the "chocolate cyst." Uterine ligament endometriosis will cause pelvic pain. Pouch of douglas will cause pain with defication. Bladder wall will cause pain with urination. Bowel serosa will cause abdominal pain with adhesions. And fallopian tube will cause infertility and scarring. also ectopic pregnancy.
What is "chocolate cyst?"
When the endometriosis implants into the ovary, it will grow and shed continuously and leave its bloody debris in the ovary, resulting in a cyst that looks like chocolate. This is the most common site of endometriosis.
What are "gun powder lesions?"
Soft hemorrhagic lesions of endometriosis when soft tissues become involved.
What is "Adenomyosis?"
Endometriosis of the myometrium, where the endometriosis seeds in the myometrium.
What is a feared complication of endometriosis?
Increased risk of cancer, especially if it involves the ovary.
What defines "Endometrial Hyperplasia?"
Endometrial gland proliferation increases relative to the stroma, generally we should have lots of stroma not many glands, but in endometrial hyperplasia there is increased number of glands, less stroma.
What causes endometrial hyperplasia and how does it present?
Unopposed estrogen secretion causes it, and it presents as postmenopausal uterine bleeding.
What is "Endometrial carcinoma?" How will it present?
Malignant proliferation of the endometrial cells, caused by either hyperplasia or sporadic. Presents as post menopausal bleeding.
What is "Endometrioid cancer?"
The cancer looks like the cells of the endometrium. Seen in hyperplasia induced endometrium cancer.
What causes the sporadic endometrium cancer? What kind of histology is seen here?
NO HYPERPLASIA, it is caused via an atrophic endometrium. Serous histology is seen.
Describe the serous histology found in the sporadic form of endometrial cancer.
It is papillary serious in looks.
What is the different associations between the hyperplasia and sporadic induced endometrial cancers?
Hyperplasia induced is usually found in women in the range of 50-60, whereas sporadic is 70 and above. Further, the sporadic variant is associated with a p53 mutation.
Summarize the hyperplastic pathway of endometrial cancer.
Caused due to unopposed estrogen exposure leading to hyperplasia, seen in women 50-60 yrs old, and the histology looks endometrioid.
Summarize the sporadic pathway of endometrial cancer.
Atrophic endometrium with no evident precursor lesions. Women are 70+ years old, histology is serous, and associated with a p53 mutation.
Which kind of endometrial cancer is associated with psamomma bodies? What are psamomma bodies?
Psamomma bodies are concentric calcififed layers, found in several different cancers but in terms of endometrial cancers it is found in the sporadic variant. This is because the histology of sporadic endometrial cancer is serous papillae, and the papillae can undergo necrosis and calcify --> psamomma bodies.
What are the tumors where we will see psamomma bodies?
Papillary cancer of the thyroid, Meningioma, Papillary serous carcinoma, and mesothelioma.
What is Leiomyoma?
Leiomyo means smooth muscle, oma means mass, this is a benign tumor of the myometrium, which is the smooth muscle layer of the uterus.
What causes Leiomyomas?
Related to estrogen exposure, there will be multiple, well defined white whorled masses. Tends to occur in pre-menopausal woman, grow in pregnancy and reduce in size after menopause, all related to estrogen exposure.
How do leiomyomas classically look like?
MULTIPLE well defined WHITE WHORLED masses. Had it not been multiple we would suspect leiomyosarcoma, which is malignant (whereas leiomyoma is benign).
What are 3 key distinguishing factors between leiomyomas and leiomyosarcomas?
Leiomyomas are multiple, leiomyosarcoma is single. Leiomyomas are white whirly regular masses whereas leiomyosarcoma has necrosis, hemorrhages, in the center of the masses. Leiomyosarcomas are seen in old women 70+ years old, leiomyomas are seen in young women pre menopause.
What is the most common clinical presentation of leiomyomas?
Nothing, they are usually asymptomatic. Possible to have abnormal uterine bleeding, infertility and abdominal mass
What does "sarcoma" mean?
Malignant mesenchymal proliferation.
What are some characteristics of leiomyosarcomas and what is it?
This is a malignant proliferation of smooth muscles, arising from the myometrium. Arises denovo, seen in post menopausal women.
How do leiomyosarcomas look?
Necrosis and hemorrhages within the mass, which tends to be a single lesion. Also, there will be increased mitotic activity and cell atypia as well as necrosis in histology.