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endometrial path
R-GU II
49
Medical
10/24/2010

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Term
what is dysfunctional uterine bleeding (DUB)?
Definition
abnormal bleeding in the absence of a well defined organic lesion. the cause depends somewhat on the pt's age.
Term
what is the etiology for DUB?
Definition
anovulatory cycle: an excess of estrogen relative to progesterone may cause the endometrium to go through a proliferative phase w/o a secretory phase (builds up and collapses). the corpus luteum may fail to mature or may regress prematurely - leading to a relative lack of progesterone (endometrium has a delay in development). DUB may be due to any dysfunction of the hypothalamus, pituitary gland, or thyroid or an ovarian lesion, malnutrition, obesity, and stress. it is common at both ends of reproductive life. (OCP used to contain enough estrogens and progestin to produce a lush endometrial stroma with inactive nonsecretory glands)
Term
what characterizes endometritis?
Definition
endometritis is part of pelvic inflammatory disease and may be associated with retained products of conception (POC), foreign bodies such as an IUD, or infection (chlamydia/trichomonas). there are chronic and acute forms (chronic may lead to ectopic pregnancy). endometritis can cause fever, pain, ectopic pregnancy, and menstrual irregularities.
Term
how does chronic endometritis appear histologically?
Definition
infiltration of chronic inflammatory cells - lymphocytes (dark dots), plasma cells (eccentrically located nucleus, perinuclear huff)
Term
what characterizes endometrial polyps?
Definition
these sessile lesions are covered w/columnar cells and adenomatous stroma. the stromal cells have a cytogenetic rearrangement of 6p21. they are more common around menopause and may produce abnormal uterine bleeding. endometrial polyps can rarely progress to CA.
Term
what is adenomyosis?
Definition
a growth of endometrial glandular basal layer into the myometrium. the uterine wall is thickened and menorrhagia, dysmenorrhea, and pelvic pain may be produced. cyclic bleeding can occur - but is unusual.
Term
what is endometriosis?
Definition
endometrial tissue outside the uterus: ovaries, fallopian tubes, pouch of douglas, uterine ligaments, rectovaginal septum and less commonly: lungs, heart.
Term
do endometrial foci undergo cyclic bleeding?
Definition
yes
Term
what can endometriosis cause?
Definition
infertility, dysmenorrhea, and pelvic pain.
Term
what characterizes incidence of endometriosis?
Definition
endometriosis is seen during active reproductive life, often in the 3rd and 4th decades of life in approx 10% of women.
Term
what are the two major theories for endometriosis?
Definition
the metastatic and metaplastic theory
Term
what is the metastatic endometriosis theory?
Definition
metastatic - refers to the implantation of endometrial tissue in abnormal (extrauterine) locations. this could be due to *retrograde menstruation through the fallopian tubes mediating the spread of endometrial tissue to the peritoneal cavity. (this does not indicate malignancy)
Term
what is the metaplastic endometriosis theory?
Definition
endometrium may arise directly from the coelomic epithelium (which is mesothelium in origin). mullerian ducts and endometrium originate from this tori (total) embryonic development. essentially: there are primitive embryonic cells that have their own ability of undergoing metaplastic change.
Term
is there an inflammatory component to endometriosis?
Definition
yes there is activation of the inflammatory cascade - high levels of prostaglandin E2, IL-1 beta, IL6, and TNF
Term
what is the hormonal component to endometriosis?
Definition
there is upregulation of estrogen production by stromal cells due to high levels of *steroidogenic enzyme aromatase - which is absent in normal endometrial stroma.
Term
what is the genetic component to endometriosis?
Definition
there have been found epigenetic changes in genes that encode 2 nuclear receptors: *steroidogenic factor 1 and *estrogen receptor beta. this results in overexpression leading to overproduction of estrogen and prostaglandin - as well as resistance to progesterone action.
Term
what characterizes the foci of endometriosis?
Definition
the foci can respond to both extrinsic cyclic and intrinsic hormonal stimulation w/periodic bleeding. they produce nodules w/a red blue to yellow-brown appearance (can become confluent).
Term
what are some complications associated with endometriosis?
Definition
hemorrhage may cause *extensive fibrous adhesions* between tubes, ovaries, and other structures (bowel). *chocolate cysts may also form, which are cystic masses in the ovaries filled w/brown fluid from previous hemorrhages.
Term
what does histologic dx of endometriosis require?
Definition
presence of both *endometrial glands and *stroma (also r/o malignancy - can have endometrioid CA that can metastasize)
Term
what are the clinical features of endometriosis?
Definition
severe dysmenorrhea, dyspareunia, pelvic pain, occasional pain on defecation, menstrual irregularities, and infertility (if in tube/ovary, will interfere with movement of the eggs)
Term
what is an important cause of endometrial bleeding?
Definition
*endometrial hyperplasia, which is an increase in proliferation of the endometrial *glands relative to the stroma - which results in an increased gland:stroma ratio when compared w/normal proliferative endometrium.
Term
can endometrial hyperplasia be premalignant or contribute to endometrial CA?
Definition
yes - therefore it needs to be monitored
Term
what is endometrial hyperplasia associated with etiologically?
Definition
prolonged estrogen stimulation of the endometrium and therefore: obesity, menopause, PCOS, functioning granulosa cell tumors of the ovary, excessive cortical function and prolonged administration of estrogenic substances such as estrogen replacement therapy.
Term
what genetics are associated with endometrial hyperplasia?
Definition
*inactivation of the PTEN tumor suppressor gene*, which encodes a dual specificity phosphatase capable of dephosphorylating both lipid and protein molecules. it dephosphorylates the lipid molecule phosphatidylinositol triphosphate which blocks the phosphorylation of *AKT - a central factor in the phosphatidylinositol 3 kinase growth regulatory pathway (breakdown of the regulatory mechanism can cause large amounts of glands to be produced). when PTEN is inactive, AKT phosphorylation is enhanced, stimulating protein synthesis and cell proliferation, while inhibiting apoptosis (net effect: increase in glands). *loss of PTEN may activate pathways normally activated by estrogen (if both occur = additive effect).*
Term
what are the different categories of endometrial hyperplasia? how are they differentiated?
Definition
simple/complex and w/ or w/o atypia - differentiated via D & C.
Term
what characterizes simple hyperplasia w/o atypia?
Definition
in simple hyperplasia w/o atypia, there is a *mild increase in the gland:stroma ratio* and glands of various sizes and irregular shapes w/cystic dilatation. the epithelial growth pattern/cytology are similar to proliferative endometrium w/less prominent mitoses. this will uncommonly progress to adenocarcinoma. (simple refers to the architecture of the glands - the cells "look normal").
Term
what characterizes simple hyperplasia w/atypia?
Definition
the architecture of the glands will still appear mostly normal, but along with simple hyperplasia, there is *cytological atypia w/in the glandular epithelial cells.* the glands may *lose polarity (cells become rounded and lose normal perpendicular orientation to the basement membrane) and contain *vesicular (bubbly) nuclei and prominent nucleoli. approx. 8% will progress to CA.
Term
what characterizes complex hyperplasia w/o atypia?
Definition
this is marked by an *increased number and *size of endometrial glands, leading to marked *gland crowding, *branching of glands, and abundant mitotic figures. the glands still remain distinct and the epithelial cells remain *cytologically normal. 3% progress to CA.
Term
what characterizes complex hyperplasia w/atypia?
Definition
the architectural features are similar to complex hyperplasia w/o atypia (increase in abnormally formed glands) - but the cytologic features have changed, the cells show *atypia w/rounded vesicular nuclei and prominent nucleoli. histologically: abnormal glands/abnormal cells lining them (lost polarity, bubbly cytoplasm, stratified nuclei) and the stroma may be difficult to see. this can overlap w/well-differentiated endometrioid adenocarcinoma (may occur side by side).
Term
what characterizes incidence of CA of the endometrium?
Definition
this is the most common invasive CA of the female genital tract, which accounts for 70% of all invasive CA in women (excluding skin CA). it is seen in mainly postmenopausal women and presents as *abnormal bleeding (should be a red flag in postmenopausal women). these women have been exposed to estrogen all their life and it is worse if they are obese. endometrial CA is uncommon in women younger than 40 - more common in 55-65 range.
Term
what is the progression towards endometrial CA?
Definition
proliferative endometrium -> simple hyperplasia develops from some abnormalities (increased in number of glands) -> complex hyperplasia becomes more abnormal -> complex atypical hyperplasia (increased glands lined by abnormal cells) -> endometrial carcinoma
Term
what is the most common type of endometrial CA? what is it associated with?
Definition
CA of the endometrium type I or *endometrioid CA or adenocarcinoma*, which accounts for 80% of cases. most are well differentiated and mimic proliferative endometrial glands. endometrioid CA typically arises in the setting of *endometrial hyperplasia and is therefore subject to obesity, DM, HTN, infertility, and unopposed estrogen stimulation.
Term
what genetic associations does CA of the endometrium type I have?
Definition
mutations of the *PTEN tumor suppressor gene (30-80%). *mutations in PIK3CA*, (which is the catalytic subunit of Pl3K, a lipid kinase that phosphorylates PIP2 to PIP3, directly antagonizing the action of PTEN), microsatellite instability/mutations in K-ras/beta catenin, and mutations in p53. (mutations in PTEN has similar effects of estrogen stimulation and the problems associated with it).
Term
how does endometrial CA type I present?
Definition
either a *discrete polypoid mass or a *diffuse tumor involving the endometrial surface which directly invades the myometrium, eventually extending into the periuterine structures (usually there is time to catch it before this point). dissemination can then occur to the regional lymph nodes, lungs, liver and other organs.
Term
what is the grading system for type I endometrial CA? (*know this*)
Definition
G1: well differentiated and <5% solid growth pattern. G2: moderately differentiated and <50% solid growth pattern. G3: poorly differentiated and >50% solid growth pattern. (solid growth = more aggressive)
Term
what do 20% of endometrial CA type I contain foci of?
Definition
squamous differentiation, which are generally benign appearing. occasionally, moderately to poorly differentiated endometrioid CA have malignant squamous elements.
Term
what characterizes CA of the endometrium type II?
Definition
this usually occurs in women a *decade later than type I and arises in the setting of *endometrial atrophy. CA of the endometrium type II is *by definition grade III* and the most common type is serous CA (b/c it resembles *ovarian serous CA). the most common genetic mutation associated w/it is to the p53 tumor suppressor gene.
Term
what is the precursor to CA of the endometrium type II?
Definition
*endometrial intraepithelial CA* (consistent malignant cells in the gland surface w/o stromal invasion). serous CA seems to begin as a surface epithelial neoplasm that extends into the gland structures and invades the stroma.
Term
how does CA of the endometrium type II often present grossly at the time of dx?
Definition
tumors are often large, bulky, or deeply invasive into the myometrium (b/c of high grade).
Term
how does CA of the endometrium type II appear histologically?
Definition
these tend to be aggressive, poorly differentiated lesions consisting of papillary growth patterns with marked cytologic atypia, high nuclear to cytoplasmic ratio, atypical mitotic figures, heterochromasia (darkening chromatin) and prominent nucleoli. the growth pattern is *predominately glandular.
Term
what is the progression to CA of the endometrium type II?
Definition
*atrophic endometrium (as opposed to hyperplastic) -> develops cytoplasmic abnormality (high N:C ratio, lose polarity, crowding, prominent nuclei) and progresses to endometrial intraepithelial carcinoma which then progresses to serous CA (papillary projections can make up a large percentage of these tumors)
Term
what is the major problem with endometrial CA?
Definition
it may be asymptomatic for a period of time, but it does usually present w/irregular postmenopausal vaginal bleeding or leukorrhea - so important to work up pts presenting w/this.
Term
what is a malignant mixed mullerian tumor?
Definition
MMMT or carcinosarcoma is usually seen in postmenopausal pts and can present w/nonspecific uterine bleeding or enlargement. these have features of carcinoma and sarcoma (epithelial and mesenchymal cells = abnormal), appear as large, soft polypoid growths and are highly aggressive.
Term
how does MMMT/carcinosarcoma appear histologically?
Definition
abnormal glands w/abnormal cells lining them (as seen in endometrial CA), but the cells of the stroma in MMMT/carcinosarcoma are also abnormal.
Term
what are the 2 tumors of the myometrium?
Definition
leiomyoma and leiomyosarcoma
Term
what is a leiomyoma?
Definition
a benign tumor of smooth muscle cells (aka fibroid, though that is a bit of a misnomer). it is the *most common benign tumor in females and estrogens stimulate their growth.
Term
how do leiomyomas appear? how do pts present?
Definition
leiomyomas are well circumscribed whorls of smooth muscle, gray-white masses which can be very small to very large and may be multiple. they can also have *areas of necrosis/calcification/hemorrhage, but they are still benign. pts may present with menorrhagia or be asymptomatic (though as they grow, they may be palpable).
Term
do leiomyomas have malignant potential?
Definition
no, even though they may have a few mitotic figures
Term
what characterizes leiomyosarcomas?
Definition
these *do not rise from preexisting leiomyomas, are usually *solitary, and may be polypoid, infiltrating or (deceptively) discrete tumors. they have frequent mitoses, cellular atypia, often recur and may metastasize widely. they can be difficult to distinguish from leiomyoma, but are much *less common.