Path Pt 3: Uterus and Endometrium

Question 1

precocious puberty (hypothalamic, pituitary, or ovarian origin)

Answer 1

prepuberty

Question 2

dysfunctional uterine bleeding

• anovulatory cycle
• anatomic lesions (carcinoma, hyperplasia, polyps)

Answer 2

perimenopausal

Question 3

endometrial atrophy causing abnormal bleeding

- anatomic lesions (carcinoma, hyperplasia, polyps)

Answer 3

postmenopausal

Question 4

endometrial glands and stroma outside of the uterus

- the “ectopic” endometrial tissue may undergo cyclic bleeding

Answer 4

endometriosis

Question 5

what are the most common sites of endometriosis?

Answer 5

within the abdominal cavity, but occasionally it is found at distant sites

Question 6

what are the proposed theories to explain the distribution of endometriosis?

Answer 6

• regurgitation: endometrial tissue implants at ectopic sites via retrograde flow of menstrual endometrium
• metaplasia: endometrium arises directly from coelomic epithelium, mesonephric ducts may undergo endometrial differentiation and give rise to ectopic endometrial tissue
• metastasis: endometrial tissue from the uterus can “spread” to distant sites

Question 7

bleeding produces nodules with a red-blue to yellow-brown appearance on or just beneath the mucosal and/or serosal surfaces at sites of involvement

Answer 7

endometriotic lesions

Question 8

when endometriotic lesions are extensive, organizing hemorrhage causes what?

Answer 8

extensive fibrous adhesions between tubes, ovaries, and other structures and obliterates the pouch of Douglas

Question 9

what are chocolate cysts/endometriomas?

Answer 9

the ovaries may become markedly distorted by large cystic masses (3-5cm in diameter), filled with brown fluid resulting from previous hemorrhage

Question 10

aggressive forms of endometriosis can invade tissues and what?

Answer 10

cause fibrosis and subsequent adhesions

Question 11

what is the likely precursor to endometriosis-related ovarian carcinoma?

Answer 11

atypical endometriosis

Question 12

what are the two morphologic appearances of atypical endometriosis?

Answer 12

1. cytologic atypia of the epithelium lining the endometriotic cyst without major architectural changes
2. glandular crowding due to excessive epithelial proliferation, often associated with cytologic atypia, producing an appearance that resembles complex atypical endometrial hyperplasia

Question 13

what is the cardinal feature of non-atypical endometrial hyperplasia?

Answer 13

increase in gland-to-stroma ratio

- the glands show variation in size and shape and may be dilated

Question 14

what causes non-atypical endometrial hyperplasia?

Answer 14

they are an endometrial response to persistent estrogen stimulation

• they rarely progress to adenocarcinoma (1-3%)
• may evolve into cystic atrophy when estrogen is withdrawn

Question 15

composed of complex patterns of proliferating glands displaying nuclear atypia

• glands are commonly back-to-back and often have complex outlines due to branching structures
• individual cells are rounded and lose the normal perpendicular orientation to the basement membrane

Answer 15

atypical hyperplasia

Question 16

the features of atypical hyperplasia have considerable overlap with what?

Answer 16

well-differentiated endometrioid adenocarcinoma

Question 17

an accurate distinction between atypical hyperplasia and cancer may not be possible without what?

Answer 17

hysterectomy

- 23-48% of women with a dx of atypical hyperplasia are found to have carcinoma with a hysterectomy is performed

Question 18

metaplastic epithelium is benign and the diagnosis of hyperplasia is based on what?

Answer 18

the appearance of the nonmetaplastic areas

Question 19

an increase in the number of glands relative to the stroma, appreciated as crowded glands, often with abnormal shapes

Answer 19

endometrial hyperplasia

Question 20

what is most commonly caused by unopposed estrogen stimulation, and is an important cause of abnormal vaginal bleeding?

Answer 20

endometrial hyperplasia

Question 21

what type of hyperplasia is associated with an increased risk of endometrial carcinoma?

Answer 21

atypical hyperplasia

Question 22

what tumor suppressor gene is mutated in approximately 20% of endometrial hyperplasias?

Answer 22

PTEN

Question 23

age: 55-65 years
- unopposed estrogen, obesity, HTN, diabetes
- endometrioid morphology
- hyperplasia
- PTEN, ARID1A, PI3K, KRAS, FGF2, MSI, CTNNB1

Answer 23

Type I endometrial carcinoma

Question 24

age: 65-75 years
- atrophy, thin physique
- serous, clear cell, mixed mullerian morphology
- TP53, aneuploidy, PI3K, FBXW7, CHD4
- aggressive behavior, intraperitoneal and lymphatic spread

Answer 24

Type II endometrial carcinoma

Question 25

can take the form of a localized polypoid tumor that diffusely infiltrates the endometrial lining - spread generally occurs by myometrial invasion followed by direct extension to adjacent structures/organs

Answer 25

endometrioid carcinoma

Question 26

endometrioid carcinoma invasion of the broad ligaments may create what?

Answer 26

a palpable mass

Question 27

dissemination to the regional lymph nodes eventually occurs, and in the late stages, the tumor may metastasize to where?

Answer 27

lungs, liver, bones, and other organs

Question 28

what type of endometrioid cancer demonstrates glandular growth patterns resembling normal endometrial epithelium?

Answer 28

adenocarcinoma

Question 29

what grade of endometrioid adenocarcinoma is composed almost entirely of well-formed glands?

Answer 29

well differentiated

Question 30

what grade of endometrioid adenocarcinoma show well-formed glands mixed with areas composed of solid sheets of cells, which by definition make up 50% or less of the tumor?

Answer 30

moderately differentiated

Question 31

what grade of endometrioid adenocarcinoma is characterized by greater than 50% solid growth pattern?

Answer 31

poorly differentiated

Question 32

how can you distinguish well differentiated endometrioid tumors from hyperplasias?

Answer 32

lack of intervening stroma

Question 33

up to 20% of endometrioid carcinomas contain foci of what?

Answer 33

squamous differentiation - squamous elements may be histologically benign-appearing when they are associated with well-differentiated adenocarcinomas

Question 34

less commonly, moderately or poorly differentiated endometrioid carcinomas contain squamous elements that appear what?

Answer 34

frankly malignant

Question 35

what stage of endometrioid adenocarcinoma is confined to the corpus uteri itself

Answer 35

Stage I

Question 36

what stage of endometrioid adenocarcinoma involves the corpus and the cervix?

Answer 36

Stage II

Question 37

what stage of endometrioid adenocarcinoma extends outside the uterus but not outside the true pelvis?

Answer 37

Stage III

Question 38

what stage of endometrioid adenocarcinoma extends outside the true pelvis or involves the mucosa of the bladder or the rectum?

Answer 38

Stage IV

Question 39

mutations in what, are present in at least 90% of serous endometrial carcinomas?

Answer 39

TP53

Question 40

these cancers arise in small atrophic uteri and are often large bulky tumors or deeply invasive into the myometrium

Answer 40

serous carcinoma

Question 41

what is the precursor lesion to serous endometrial carcinoma?

Answer 41

serous endometrial intraepithelial carcinoma

Question 42

these lesions consist of malignant cells identical to those of serous carcinoma that are confined to the epithelial surfaces - the invasive lesions may have a papillary growth pattern composed of cells with marked cytologic atypia including high nuclear-to-cytoplasmic ratio, atypical mitotic figures, hyperchromasia, and prominent nucleioli

Answer 42

serous endometrial intraepithelial carcinoma

Question 43

how are serous endometrial intraepithelial carcinoma distinguished from endometrioid carcinoma?

Answer 43

they have a predominantly glandular growth pattern NOTE: all tumors in this category are classified as grade 3 irrespective of histologic pattern

Question 44

what is serous carcinoma associated with, despite relatively superficial endometrial involvement?

Answer 44

extensive peritoneal disease | - suggesting spread by routes, other than direct invasion

Question 45

bulky and polypoid, and may protrude through the cervical os - tumors usually consist of adenocarcinoma (endometrioid, serous, or clear cell), mixed with the malignant mesenchymal (sarcomatous) elements

Answer 45

malignant mixed mullerian tumors (MMMT) | - tumor may contain two distinct and separate epithelial and mesenchymal components

Question 46

sarcomatous components of MMMT's may also mimic what?

Answer 46

extrauterine tissues - striated muscle, cartilage, adipose tissue, and bone - metastases usually only contain epithelial components

Question 47

what is the most common malignant of the female genital tract?

Answer 47

endometrial carcinoma

Question 48

these endometrial carcinomas are low-grade, and usually indolent

Answer 48

Type I

Question 49

these endometrial carcinomas are high-grade aggressive tumors that have a poor prognosis

Answer 49

Type II

Question 50

which grade of endometrial carcinoma is often preceded by atypical hyperplasia and commonly has mutations in the PTEN, PIK3CA, KRAS, and ARID1A genes?

Answer 50

Type I

Question 51

which grade of carcinoma is associated with serous endometrial intraepithelial carcinoma and the most common mutations are in TP53

Answer 51

Type II serous carcinoma | - TP53 mutations also found in the precursor lesion

Question 52

what remains the most important factor in outcome?

Answer 52

stage

Question 53

which tumor type is more likely to present at advanced stages and have a decidedly worse prognosis?

Answer 53

serous tumors

Question 54

carcino-sarcomas that resemble endometrial carcinoma genetically and have poor outcomes with current therapies

Answer 54

MMMT's

Question 55

sharply circumscribed, discrete, round, firm, gray-white tumors varying in size from small, barely visible nodules to massive tumors that fill the pelvis

Answer 55

leiomyomas

Question 56

except in rare instances, leiomyomas are found where?

Answer 56

within the myometrium of the corpus | - infrequently, they involve the uterine ligaments, lower uterine segments, or cervix

Question 57

these tumors can occur within the myometrium (intramural), just beneath the endometrium (submucosal) or beneath the serosa (subserosal)

Answer 57

leiomyomas

Question 58

characteristic whorled pattern of smooth muscle bundles (resembling myometrium) on cut section usually makes these lesions readily identifiable

Answer 58

leiomyomas - large tumors may develop areas of yellow-brown to red softening - individual muslce cells are uniform in size and shape and have the characteristic oval nucleus and long, slender bipolar cytoplasmic process - mitotic figures are scarce

Question 59

these variants include atypical or bizarre (symplastic) tumors with nuclear atypia and giant cells, and cellular leiomyomas - both have a low mitotic index, helping to distinguish these from leiomyomas

Answer 59

benign variants of leiomyomas

Question 60

uterine leiomyoma that extends into vessels and spreads hematogenously to other sites, most commonly the lung

Answer 60

benign metastasizing leiomyoma | - extremely rare variant

Question 61

this variant presents as multiple small peritoneal nodules | - considered benign despite its unusual behavior

Answer 61

disseminated peritoneal leiomyomatosis

Question 62

these tumors grow within the uterus in two somewhat distinctive patterns 1. bulky, fleshy masses that invade the uterine wall 2. polypoid masses that project into the uterine lumen

Answer 62

leiomyosarcomas | - exhibit a wide range of cytologic atypia, from extremely well differentiated to highly anaplastic

Question 63

the distinction from what, is based of nuclear atypia, mitotic index, and zonal necrosis

Answer 63

leiomyoma from leiomyosarcoma

Question 64

the presence of 10 or more mitoses per 10 high power fields indicates what?

Answer 64

malignancy, particularly if accompanied by cytologic atypia and/or necrosis

Question 65

if the tumor contains muclear atypia or large (epithelioid) cells, and five mitoses per 10 high power fields?

Answer 65

malignant

Question 66

what are the rare exceptions of leiomyomas?

Answer 66

mitotically active leiomyomas in young or pregnant women | - caution should be exercised in interpreting such neoplasms as malignant

Question 67

a portion of smooth muscle neoplasms may be impossible to classify and are called what?

Answer 67

smooth muscle tumors of "uncertain malignant potential"

Question 68

these tumors include stromal nodules, low-grade stromal sarcomas, and high-grade stromal sarcomas

Answer 68

endometrial stromal tumors

Question 69

stromal nodules are what?

Answer 69

benign, well-circumscribed tumors

Question 70

these resemble stromal nodules, but infiltrate into the surrounding myometrium - associated with fusion of JAZF1 gene and various polycomb factor genes, usually SUZ12

Answer 70

low-grade stromal sarcomas

Question 71

these show marked atypia and are associated with other fusion genes

Answer 71

high-grade stromal sarcomas

Question 72

both low and high-grade stromal sarcomas are prone to what?

Answer 72

late recurrences

Question 73

common, benign smooth muscle tumors that cause significant morbidity and are often associated with MED12 mutations

Answer 73

leiomyomas

Question 74

malignant smooth muscle tumors that are uncommon, highly malignant myometrial tumors that usually arise de novo

Answer 74

leiomyosarcomas