Path Pt 3: Uterus and Endometrium Flashcards
precocious puberty (hypothalamic, pituitary, or ovarian origin)
prepuberty
dysfunctional uterine bleeding
- anovulatory cycle
- anatomic lesions (carcinoma, hyperplasia, polyps)
perimenopausal
endometrial atrophy causing abnormal bleeding
- anatomic lesions (carcinoma, hyperplasia, polyps)
postmenopausal
endometrial glands and stroma outside of the uterus
- the “ectopic” endometrial tissue may undergo cyclic bleeding
endometriosis
what are the most common sites of endometriosis?
within the abdominal cavity, but occasionally it is found at distant sites
what are the proposed theories to explain the distribution of endometriosis?
- 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
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
endometriotic lesions
when endometriotic lesions are extensive, organizing hemorrhage causes what?
extensive fibrous adhesions between tubes, ovaries, and other structures and obliterates the pouch of Douglas
what are chocolate cysts/endometriomas?
the ovaries may become markedly distorted by large cystic masses (3-5cm in diameter), filled with brown fluid resulting from previous hemorrhage
aggressive forms of endometriosis can invade tissues and what?
cause fibrosis and subsequent adhesions
what is the likely precursor to endometriosis-related ovarian carcinoma?
atypical endometriosis
what are the two morphologic appearances of atypical endometriosis?
- cytologic atypia of the epithelium lining the endometriotic cyst without major architectural changes
- glandular crowding due to excessive epithelial proliferation, often associated with cytologic atypia, producing an appearance that resembles complex atypical endometrial hyperplasia
what is the cardinal feature of non-atypical endometrial hyperplasia?
increase in gland-to-stroma ratio
- the glands show variation in size and shape and may be dilated
what causes non-atypical endometrial hyperplasia?
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
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
atypical hyperplasia
the features of atypical hyperplasia have considerable overlap with what?
well-differentiated endometrioid adenocarcinoma
an accurate distinction between atypical hyperplasia and cancer may not be possible without what?
hysterectomy
- 23-48% of women with a dx of atypical hyperplasia are found to have carcinoma with a hysterectomy is performed
metaplastic epithelium is benign and the diagnosis of hyperplasia is based on what?
the appearance of the nonmetaplastic areas
an increase in the number of glands relative to the stroma, appreciated as crowded glands, often with abnormal shapes
endometrial hyperplasia
what is most commonly caused by unopposed estrogen stimulation, and is an important cause of abnormal vaginal bleeding?
endometrial hyperplasia
what type of hyperplasia is associated with an increased risk of endometrial carcinoma?
atypical hyperplasia
what tumor suppressor gene is mutated in approximately 20% of endometrial hyperplasias?
PTEN
age: 55-65 years
- unopposed estrogen, obesity, HTN, diabetes
- endometrioid morphology
- hyperplasia
- PTEN, ARID1A, PI3K, KRAS, FGF2, MSI, CTNNB1
Type I endometrial carcinoma
age: 65-75 years
- atrophy, thin physique
- serous, clear cell, mixed mullerian morphology
- TP53, aneuploidy, PI3K, FBXW7, CHD4
- aggressive behavior, intraperitoneal and lymphatic spread
Type II endometrial carcinoma
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
endometrioid carcinoma
endometrioid carcinoma invasion of the broad ligaments may create what?
a palpable mass
dissemination to the regional lymph nodes eventually occurs, and in the late stages, the tumor may metastasize to where?
lungs, liver, bones, and other organs
what type of endometrioid cancer demonstrates glandular growth patterns resembling normal endometrial epithelium?
adenocarcinoma
what grade of endometrioid adenocarcinoma is composed almost entirely of well-formed glands?
well differentiated
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?
moderately differentiated
what grade of endometrioid adenocarcinoma is characterized by greater than 50% solid growth pattern?
poorly differentiated
how can you distinguish well differentiated endometrioid tumors from hyperplasias?
lack of intervening stroma
up to 20% of endometrioid carcinomas contain foci of what?
squamous differentiation
- squamous elements may be histologically benign-appearing when they are associated with well-differentiated adenocarcinomas
less commonly, moderately or poorly differentiated endometrioid carcinomas contain squamous elements that appear what?
frankly malignant
what stage of endometrioid adenocarcinoma is confined to the corpus uteri itself
Stage I
what stage of endometrioid adenocarcinoma involves the corpus and the cervix?
Stage II
what stage of endometrioid adenocarcinoma extends outside the uterus but not outside the true pelvis?
Stage III
what stage of endometrioid adenocarcinoma extends outside the true pelvis or involves the mucosa of the bladder or the rectum?
Stage IV
mutations in what, are present in at least 90% of serous endometrial carcinomas?
TP53
these cancers arise in small atrophic uteri and are often large bulky tumors or deeply invasive into the myometrium
serous carcinoma
what is the precursor lesion to serous endometrial carcinoma?
serous endometrial intraepithelial carcinoma
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
serous endometrial intraepithelial carcinoma
how are serous endometrial intraepithelial carcinoma distinguished from endometrioid carcinoma?
they have a predominantly glandular growth pattern
NOTE: all tumors in this category are classified as grade 3 irrespective of histologic pattern
what is serous carcinoma associated with, despite relatively superficial endometrial involvement?
extensive peritoneal disease
- suggesting spread by routes, other than direct invasion
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
malignant mixed mullerian tumors (MMMT)
- tumor may contain two distinct and separate epithelial and mesenchymal components
sarcomatous components of MMMT’s may also mimic what?
extrauterine tissues
- striated muscle, cartilage, adipose tissue, and bone
- metastases usually only contain epithelial components
what is the most common malignant of the female genital tract?
endometrial carcinoma
these endometrial carcinomas are low-grade, and usually indolent
Type I
these endometrial carcinomas are high-grade aggressive tumors that have a poor prognosis
Type II
which grade of endometrial carcinoma is often preceded by atypical hyperplasia and commonly has mutations in the PTEN, PIK3CA, KRAS, and ARID1A genes?
Type I
which grade of carcinoma is associated with serous endometrial intraepithelial carcinoma and the most common mutations are in TP53
Type II serous carcinoma
- TP53 mutations also found in the precursor lesion
what remains the most important factor in outcome?
stage
which tumor type is more likely to present at advanced stages and have a decidedly worse prognosis?
serous tumors
carcino-sarcomas that resemble endometrial carcinoma genetically and have poor outcomes with current therapies
MMMT’s
sharply circumscribed, discrete, round, firm, gray-white tumors varying in size from small, barely visible nodules to massive tumors that fill the pelvis
leiomyomas
except in rare instances, leiomyomas are found where?
within the myometrium of the corpus
- infrequently, they involve the uterine ligaments, lower uterine segments, or cervix
these tumors can occur within the myometrium (intramural), just beneath the endometrium (submucosal) or beneath the serosa (subserosal)
leiomyomas
characteristic whorled pattern of smooth muscle bundles (resembling myometrium) on cut section usually makes these lesions readily identifiable
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
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
benign variants of leiomyomas
uterine leiomyoma that extends into vessels and spreads hematogenously to other sites, most commonly the lung
benign metastasizing leiomyoma
- extremely rare variant
this variant presents as multiple small peritoneal nodules
- considered benign despite its unusual behavior
disseminated peritoneal leiomyomatosis
these tumors grow within the uterus in two somewhat distinctive patterns
- bulky, fleshy masses that invade the uterine wall
- polypoid masses that project into the uterine lumen
leiomyosarcomas
- exhibit a wide range of cytologic atypia, from extremely well differentiated to highly anaplastic
the distinction from what, is based of nuclear atypia, mitotic index, and zonal necrosis
leiomyoma from leiomyosarcoma
the presence of 10 or more mitoses per 10 high power fields indicates what?
malignancy, particularly if accompanied by cytologic atypia and/or necrosis
if the tumor contains muclear atypia or large (epithelioid) cells, and five mitoses per 10 high power fields?
malignant
what are the rare exceptions of leiomyomas?
mitotically active leiomyomas in young or pregnant women
- caution should be exercised in interpreting such neoplasms as malignant
a portion of smooth muscle neoplasms may be impossible to classify and are called what?
smooth muscle tumors of “uncertain malignant potential”
these tumors include stromal nodules, low-grade stromal sarcomas, and high-grade stromal sarcomas
endometrial stromal tumors
stromal nodules are what?
benign, well-circumscribed tumors
these resemble stromal nodules, but infiltrate into the surrounding myometrium
- associated with fusion of JAZF1 gene and various polycomb factor genes, usually SUZ12
low-grade stromal sarcomas
these show marked atypia and are associated with other fusion genes
high-grade stromal sarcomas
both low and high-grade stromal sarcomas are prone to what?
late recurrences
common, benign smooth muscle tumors that cause significant morbidity and are often associated with MED12 mutations
leiomyomas
malignant smooth muscle tumors that are uncommon, highly malignant myometrial tumors that usually arise de novo
leiomyosarcomas
