Endometrial and myometrial pathology (Pathoma + mahmoud)

what are the *early* characteristics of glands in post ovulatory endometrium?

Secretory *subnuclear* vacuoles Dilated glands Tortuous Serrated

what are the characteristics of glands in proliferative endometrium?

Straight Tubular Pseudostratified Increased mitosis No vacuolation /no secretory activity

what does anovulation represent?

a common cause of abnormal uterine bleeding, especially during menarche (child bearing age) and menopause

what is the presentation of chronic endometritis?

abnormal uterine bleeding pain infertility

what is the definition of abnormal uterine bleeding (AUB)?

any change in menstrual period: flow, duration, frequency, bleeding between cycles

what is the origin of leiomyosarcoma?

arises de nova, *do not arise from leiomyomas*

hyperplasia pathway of endometrial carcinoma

arises from endometrial hyperplasia risk factors are related to estrogen exposure and include *early menarche/late menopause, nullparity, infertility with anovulatory cycles, and obesity* inactive *PTEN tumor suppressor gene* average age = *50-60*

sporadic pathway of endometrial carcinoma

arises in atrophic endometrium with no evident precursor lesion mimics serous adenocarcinoma of ovary *Tp53 missense mutation* average age = *70*

what is the purpose of dating the uterus?

assess *hormonal status* document *ovulation* determine the cause of *endometrial bleeding*

what is the presentation of endometrial polyp?

asymptomatic, *abnormal uterine bleeding*, infertility malignancy uncommon

acute endometritis

bacterial infection of the endometrium

what are the layers of proliferative endometrium?

basalis layer glands and stroma estrogen => acts on stromal cells, stromal cells release growth factor which stimulate glands

leiomyoma (fibroids)

benign neoplastic proliferation of smooth muscle arising from meometrium

what are the characteristics of menstrual phase endometrium?

blood in stroma in functionalis layer

histology of normal proliferative endometrium

both glands and stroma proliferate glands are *straight, tall* regular pseudostratified columnar cells, numerous mitotic figures, *no secretory* activity in glands, no mucin, no vacuoles

stage I endometrial cancer

carcinoma confined to *corpus uteri*

stage IV endometrial cancer

carcinoma extends *outside the true pelvis* or involves the mucosa of the *bladder or the rectum*

stage III endometrial cancer

carcinoma extends *outside the uterus* but not outside the true pelvis

stage II endometrial cancer

carcinoma involves the *corpus and the cervix*

complex hyperplasia with atypia

cells are round and loose, normal perpendicular orientation to basement membrane

what are organic/structural causes of AUB?

chronic endometritis endometrial polyp submucosal leiomyoma endometrial neoplasm

what does "dating" the uterus refer to?

correlating the histological appearance of the uterus to the time of the uterine cycle

gross morphology of endometrial hyperplasia

diffusely enlarged

what causes acute endometritis?

due to retained products of conception (i.e. after delivery or miscarriage)

what are causes of anovulatory cycle?

during menarche and in the perimenopausal period of anovulations endocrine disorder (i.e. thyroid, adrenal, or pituitary tumor) granulosa-theca cell tumor, polycystic ovaries obesity, severe malnutrition

what does endometriosis of the fallopian tube increase risk for?

ectopic tubal pregnancy

what is the most common invasive carcinoma of the female genital tract?

endometrial carcinoma

endometriosis

endometrial glands and stroma *outside* of the uterine endometrial lining almost always contain *functioning endometrium*, which undergoes *cyclic bleeding*

what is adenomyosis?

endometriosis (endometrial glands) extended into *myometrium*

what are leiomyomas related to?

estrogen exposure: - common in *pre*menopausal women - often multiple - enlarge during pregnancy; shrink after menopause

what is the presentation of acute endometritis?

fever abnormal uterine bleeding pelvic pain

simple endometrial hyperplasia without atypia microscopy

glands of various sizes and irregular shapes with *cystic dilatation* mild increase in the *gland-to-stroma* ratio similar to *proliferative* endometrium

how is endometrial hyperplasia classified?

histologically based on architectural growth pattern (simple or complex) and presence or absence of cellular atypia

what has the highest sensitivity and specificity for identifying endometrial polyps?

hyesteroscopy

atypical hyperplasia microscopy

hyperchromatic nuclei, mitotic figures commonly progresses to adenocarcinoma

what are the 2 distinct pathways of endometrial carcinoma?

hyperplasia pathway (75%) sporadic pathway (25%)

endometrial polyp

hyperplastic protrusion of endometrium = *glands, stroma, blood vessels* *localized* single or multiple sessile or pedunculated

what causes anovulatory cycle?

in an estrogen-driven proliferative phase without a subsequent progesterone-driven secretory phase = *no corpus luteum*

endometrial hyperplasia

increased proliferation of *endometrial glands* relative to stroma has a *malignant potential*

what is the pathogenesis of endometriosis?

inflammation cascade is activated, high level of prostaglandins (explains why COX-2 inhibitors are used in treatment) estrogen production is upregulated (explains why *inhibitors of aromatase* are used in treatment)

what is the most common tumor in females?

leiomyoma, most common indication for hysterectomy affects 30% of american women

when does shedding of the endometrium occur?

loss of progesterone support = menstrual phase

leiomyosarcoma

malignant proliferation of smooth muscle arising from myometrium seen in *post*menopausal women

what are inorganic/hormonal/dysfunctional causes of AUB?

menarche: anovulatory cycle endocrine disorder granulosa cell tumor metabolic: obesity, DM

grade 2 of endometrial carcinoma

moderately differentiated showing *well-formed glands* mixed with *solid sheets* of malignant cells

endometrium

mucosal lining of uterine activity

what is the most common site of involvement in endometriosis?

ovary => *chocolate cyst*

what is chronic endometritis characterized by?

plasma cells

grade 3 of endometrial carcinoma

poorly differentiated with *solid sheets* of cells with barely recognizable glands

how does endometrial carcinoma present?

postmenopausal bleeding

what is the classic presentation of endometrial hyperplasia?

postmenopausal uterine bleeding

what is the role of progesterone and the endometrium?

preparation for implantation = secretory phase

what is the most important predictor for progression to carcinoma from endometrial hyperplasia?

presence of cellular *atypia*

what causes chronic endometritis?

products of conception chronic pelvic inflammatory disease (i.e. *Chlamydia*) IUD TB

what is the role of estrogen and the endometrium?

proliferative phase = growth

what degeneration changes happen to fibroids?

red degeneration = hemorrhagic hyaline degeneration = hyalinization of smooth muscle calcification

what is the most likely cause of endometriosis?

retrograde menstruation with implantation at an ectopic site

asherman syndrome

secondary amenorrhea due to loss of *basalis* common cause = result of overaggressive dilation and curettage

myometrium

smooth muscle wall underlying the endometrium

what are the characteristics of stroma in proliferative endometrium?

spindle cells minimal cytoplasm

what is the morphology of adenomyosis?

uniformly *enlarged, soft*, globular uterus

what is the presentation of leiomyoma?

usually *asymptomatic* when present, symptoms include *abnormal uterine bleeding*, infertility, and a pelvic mass

where does endometriosis occur in descending order of frequency (after ovaries)?

uterine ligaments rectoveginal septum cul de sac pelvic peritoneum large and small bowel and appendix mucosa of the cervix, vagina, and fallopian tubes laporotomy scars

Grade 1 of endometrial carcinoma

well differentiated, with easily recognizable *glandular* pattern

histology of leiomyoma

well-differentiated, regular, *spindle-shaped* smooth muscle cells associated with *hyalinization*

how do endometriosis implants classically appear?

yellow-brown "gun-powder" nodules

what are the phases of the endometrium?

1) proliferative 2) ovulatory 3) postovulatory 4) endometrium during menses

what is the percent risk of complex atypical hyperplasia moving into malignant transformation?

20-30% risk

what is the sensitivity of endometrial biopsy?

98-99% in diagnosing cancer, but misses 50% of benign diagnosis (i.e. polyps, fibroids, endometritis)

what does endometriosis present as?

*PAIN!* severe *dysmenorrhea* *pelvic pain* pain on defecation, pain on urination may cause infertility

what are the *late* characteristics of glands in post ovulatory endometrium?

*apical* vacuoles

how does spread of endometrial carcinoma occur?

*direct* myometrial invasion with eventual extension into periuterine structures spread into the *broad ligaments* may create a palpable mass dissemination to the regional *lymph nodes* (para-aortic) *metastasize* to the lungs, liver, bones, and other organs

what is seen on histology of the hyperplastic pathway of endometrial carcinoma?

*endometrioid* = well differentiated

what are the characteristics of stroma in post ovulatory endometrium?

*functionalis* layer *progesterone* down regulates estrogen receptors and decreases proliferation spiral arterioles increased ground substance eosinophilia in cytoplasm (*predecidual*) lymphocytes and PMNs

what are the microscopic features of endometrial polyps?

*glands* undergo hyperplasia or atrophy, they are reactive to stromal prolifeartion

what is a common genetic alteration found in endometrial hyperplaisa?

*inactivation* of the *PTEN* tumor suppressor gene associated with prolonged estrogen stimulation of the endometrium

what does gross exam show of leiomyoma?

*multiple*, well-defined, *white whorled masses* => may distort the uterus and impinge on pelvic structures

what is the gross morphology of endometriosis?

*nodules*, red-blue to yellow-brown *hemorrhage* causes extensive *fibrous adhesions* *large cystic masses* in ovary filled with brown fluid resulting from previous hemorrhage = *chocolate cysts*

what is the morphology of anovulatory cycle?

*proliferative changes with cystic dilatation*

what are the characteristics of glands in post ovulatory endometrium?

*secretory* under effect of progesterone

what is seen on histology of the sporadic pathway of endometrial carcinoma?

*serous* and characterized by *papillary structures* with *psammoma body* formation *p53* mutation is common tumor exhibits aggressive behavior

what is seen on gross exam of leiomyosarcoma?

*single* lesion with areas of *necrosis and hemorrhage*

what is a common drug induced cause of endometrial polyp?

*tamoxifen* = has weak pro-estrogenic effects on the endometrium

what causes endometrial hyperplasia?

*unopposed estrogen* => i.e. obesity, polycystic ovary syndrome, and estrogen replacement