Uterus Pathology (Gianani) - MT Flashcards
What are the 4 phases of endometrial cycle (in order) that are regulated by ovarian produced hormones?
- Proliferative phase (6-14 days)
- Ovulation ( day 14)
- Secretory phase (14-28 days)
- Menses (1-5 days)
What other cycles are occuring concomitantly with the proliferative phase after menses?
With the Secretory phase after ovulation?
- Follicular phase and proliferative phase
- Luteal phase and secretory phase
Estrogen is one of the main factors that promotes endometrial growth in the proliferative phase.
What is the main source of this hormone?
Tertiary follicle (dominant follicle)
Progesterone is one of the main driving forces of endometrial secretory phase after ovulation.
What is the main source of progesterone during this time?
Corpus Luteum
What endometrial phase does the histology slide indicate?
Proliferative phase
(mitotic features)
What endometrial phase does the histology slide indicate?
Early secretory phase
(subnuclear vacuoles) arrow
Endometrial phase indicated by histo slide?
Late secretory exhaustion and predecidual changes (eosinophilic) arrow sign
Endometrial phase indicated by histo slide?
Menses
(stromal breakdown, hemorrhage, blue balls)
The most common cause of abnormal uterine bleeding is?
hormonal disturbances that produce
Dysfunctional uterine bleeding
Uterine bleeding that lacks an underlying organic structural abnormality is called?
Dysfunctinal uterine bleeding (d/t hormonal distrubances)
Uterine bleeding causes (age dependent)
- Prepuberty? x1
- Adolescence? x2
- Reproductive age? x3
- Perimenopausal? x2
- postmenopausal? x2
- precocious puberty (hypothalamic, pituitary, ovarian origins)
- Anovulatory cycle, coagulation disorder
- Complications of pregnancy, Anatomic lesions, Dysfunctional uterine bleeding
- Dysfunctional uterine bleeding, Anatomic lesions
- Endometrial atrophy, Anatomic lesions
A woman of child bearing age presents with a uterine bleed. What is usually the first Dx to r/o and test to do it with?
Pregnancy
Beta HCG test
*what secretes beta HCG?
what secretes beta HCG?
syncitiotrophoblast epithelial covering of the placenta
Anatomic lesions that can cause uterine bleeding? x5
- Leiomyomas (uterine fibroids)
- adenomyosis
- polyps
- endometrial hyperplasia
- carcinomas
Two possible causes of dysfunctional uterine bleeding are?
- anovulatory cycle
- ovulatory dysfuntional bleeding (inadequate luteal phase)
What pathology causing dysfunctinal uterine bleeding is shown in the top histologic slide?
What pathology is shown on the bottom slide?
- top shows anovulatory endometriumm w/ stromal breakdown which is associated with proliferative glands
- chronic endometritis w numerous plasma cells
Inflammatory disorder of acute endometritis:
- limited to what?
- predisposing influence?
- causative agents? x2
- inflammatory response limited to mostly where?
- Tx involves?
- limited to bacterial infectinos that arise after delivery or miscarriage
- retained products of conception
- Group A hemolytic streptococci
- chiefly in the stroma, nonspecific
- removal of retained gestational fragments by curettage, accompanied by antibiotic therapy to clear infection
Inflammatory disorder of Chronic endomeritis usually occurs in association with what other pathology?
Chronic pelvic inflammatory disease (PID)
Dx of chronic endometriosis requires the detection of what type of cells in the endometrial stroma?
plasma cells
The presence of endometrial tissue (endometrial glands and stroma) outside the uterus is called?
endometriosis
When endometrial tissue is present in the uterine wall but outside the endometrium, the term used to decribe the condition is?
Adenomyosis
Endometriosis occurs primarily in what population of women?
women of child bearing age
Common Sx of endometriosis include? x3
- Dysmenorrhea (painful menses)
- Dyspareunia (painful intercourse)
- Lower back pain that is worse during menses
Can infertility be associated with endometriosis?
yes
The pathologic diagnosis of endometriosis is made if….(what two endometrial structures are observed outside the uterus)?
Endometrial glands
and
Stroma
are observed outside of the uterus
The most common sites of endometriosis are where? x1
Dr. Gianani emphasized what other specific locations? x6
- Abdominal cavity
(Scars from C-section, Skin, Ovaries, GI tract, Vagina, Cervix)
The histo slide shows endometriosis occuring in what region of the body?
GI tract
Endometrial polyps:
- usual growth pattern
- Sx?
- chromosomal rearrangements similar to?
- exophytic mass (outward growth on surface), sessile, but can be large and pedunculated sometimes
- asymptomatic or cause of abnormal bleeding if ulcerating/necrotic
- similar to other benign mesenchymal tumors
Endometrial hyperplasia is an important cause of abnormal bleeding and frequent precursor to the most common type of what?
Endometrial carcinoma
type I being the most common type of endometrial carcinoma
A pathologist asks what defines endometrial
hyperplasia. You answer?
defined as the increased proliferation of endometrial glands relative to stroma.
This results in increased gland to stroma ratio when compared with normal proliferative endometrium
Endometrial hyperplasia is associated with anovulation, endogenous, exogenous sources, Obesity, Polycystic ovarian syndrome, excessive ovarian cortical function, and HRT.
All of these things prolong the stimulation of the endometrium through what hormone?
Estrogen
How does obesity cause endometrial hyperplasia, thus putting a woman at increased risk for type I endometrial carcinoma?*
x3
*(this is a bonus / FYI card)*
- adrenal secretion is increased, thus there is more androgen precursor to convert
- Adipse tissue is a major conversion site of androstendione to estrone, and is increased in obese patients
- SHBG is decreased, thus there is more plasma estradiol that reaches targe tissue (endometrium)
Two types of endometrial hyperplasia are?
which one is associated with type I endometrial carcinomas?
- Non atypical and Atypical hyperplasia
- Atypical hyperplasia is associated with type I endometrial carcinomas
Non- atypical hyperplasia is defined by what cardinal feature?
increased gland to stroma ratio
In addition to glandular crowding, what other features are indicative of atypical hyperplasia? x2
- Rounded vesicular nuclei with prominent nucleoli
- loss of normal perpendicular orientation of basement membrane
The features of atypical hyperplasia have considerable overlap with those of what other pathologic condition?
Well differentiated endometrioid adenocarcinoma
What is the behavior of spread of type I vs. type II endometrial carcinoma
- Type I = indolent spread via lymphatics
- Type II = Aggressive intraperitoneal and lymphatic spread
Precursor of Type I vs. Type II Endometrial carcinomas?
- Type I endometrial carcinomas = atypical hyperplasia
- Type II endometrial carcinomas = Serous endometrial intraepithelial carcinoma
Clinical signs of type I Endometrial carcinoma (x4) vs. Type II endometrial carcinoma (x2)
- type 1 = unopposed estrogen, Obesity, HTN, Diabetes
- type 2 = Atrophy, thin physique
Gianani was adamate about memorizing the mutated genetic abnormalities for type I endometrial carcinomas.
The main one being _________.
What are the 7 other genes?
- Increased signaling through PI3K/AKT ptwy.
hallmark of type I endometrial carcinoma.
2.
PTEN,
ARID1A (chromatin),
KRAS,
FGF2,
MSI,
CTNNB1 (Wnt signaling),
TP53
PI3K/AKT signaling augments expression of what?
Estrogen receptor dependent target genes in endometrial cells.
What is the grade of this type I endometrial carcinoma, what 2 features indicate it?
- grade 1 well differentiated
- preserved glandular architecture
- lack of intervening stroma
What is the grade of this type I endometrial carcinoma?
What feature indicates it?
- Grade 2 moderately differentiated
- glandular architecture admixed with solid areas
(<50% of tumor is solid)
What is the grade of this type I endometrial carcinoma?
What feature indicates it?
- grade 3 poorly differentiated
- predominantly solid growth pattern >50%
What is the age of the women affected by type I vs type II endometrial carcinomas?
- type I 55-65
- type II 65-75
What is the most common invasive cancer of the female genital tract, which accounts for 7% of all invasive cancer in women, excluding skin cancer?
Endometrial carcinomas
Type II endometrial carcinomas can display what type of morphology? x3
(differs from the endometrioid morphology of type I)
- Serous
- Clear cell
- Mixed mullerian tumor
Mutations in what gene are present in at least 90% of serous endometrial carcinomas (type II)?
- what are the consequences to the resulting protein that this gene encodes for? x2
- TP53 tumor suppresor gene mutation
- missense mutation results in accumulation and decreased function of tumor suppresing proteins
(hence P53, when mutated can be stained for)
The precursor to a serous type II endometrial carcinoma is usually a _______?
Endometrial intraepithelial carcinoma
What kind of stain is this which identifies endometrial intraepithelial carcinoma?
What is the brown coloration indicative of?
- P53 IHC stain
- P53
malignant cells and strong diffuse expression of p53
serous type II carcinomas of endometrium display what histologic features? (just know these exist according to Gianani) x5
- Papillary growth pattern
- malignant cells w/ marked cytologic atypia of high nuclear to cytoplasmic ratio
- atypical mitotic figures
- hyperchromasia
- accumulation of p53 protein in nucleus
How are endometrioid adenocarcinomas staged? (type I and type II)
Number of stage and what defines it?
- Stage I = carcinoma confined to corpus uteri
- Stage II = Carcinoma involves corpus and cervix
- Stage III = Carcinoa extends outside uterus but not outside true pelvis
- Stage IV = Carcinoma extends outside true pelvis r involves mucosa of the bladder or rectum
Tumors of the endometrial stroma include what 2 types?
- adenosarcomas
- stromal tumors
Malignant tumors of the endometrial epithelium include what two types of tumors?
- Endometrial carcinomas
- Malignant mixed mullerian tumors
A patient presents with a mass protruding through her cervical os. Micrograph of the biopsy from the mass shows both malignant epithelial and stromal components.
- What type of tumor is this?
1. What is the population of women that this type of tumor affects?
2. Metastases of this tumor usually only includes what type of tissue component?
3. What other clinical presentation could this tumor present with? x1
- Malignant mixed mullerian tumor
1. Postmenopausal women
2. epithelial component on metastasis only
3. Vaginal bleeding
A woman presents with a large broad based endometrial polypoid growth that has prolapsed throught the cervical os. Light microscopy of the biopsy sample indicates malignant stroma, and abnormally shapped endometrial glands. On her history, she is a 55 year old.
- What type of tumor is this?
- Why is it important to distinguish this type of tumor from large benign polyps?
- Adenosarcoma
- adenosarcomas are estrogen sensitive and respond to oophorectomies
The common mutation found in 70% of leiomyomas (uterine fibroids), is?
- MED12 gene
*affects mediator, a multiprotein complex that stimulates gene expression by serving as a bridge b/t long range DNA regulatory elements (enhancers) and gene promoters
What is the most common tumor in women?
Uterine leiomyomas
(Leiomyomas)
(Uterine Fibroids)
What type of tissue composes a leiomyoma?
Uterine smooth muscle cells (myometrial tumor)
Is a leiomyoma malignant?
no it is benign
What features does this histologic slide of myometrium show? x2
- What kind of tumor is it?
- The gross picture indicates what subtypes of this tumor?
- Spindle shaped/ cigar shaped nuclei of well defined smooth muscle cells of the myometrium.
- associated with hyalinization
1. Characterizes a leiomyoma
2. Multiple Submucosal, intramural, and subserosal leiomyoma
Are leiomyosarcomas malignant?
Yes
Leiomyosarcomas arise out of what type of cells?
Myometrium or endometrial stromal precursor cells.
*do not usually arise out of leiomyomas
- What kind of tumor is indicated by this gross specimen?
- What growth pattern does this display?
- Cells of these tumors can contain what mutation?
- leiomyosaroma
- bulky fleshy mass that invades uterine wall, necrotic, hemorrhagic tissue
- MED12mutation
What histologic features help you identify the tumor characterized in this LM? x3
- irregular cell size
- hyperchromatic nuclei
- numerous mitotic figures indicated by arrows
How do leiomyosarcomas spread?
hematogenously to distant organs like lungs, bone, brain
Leiomyosarcomas occur in what patient subset?
Prognosis?
- women who are 40-60 y/o pre and post menopausal
- usually bad 40% 5 year, with anaplastic lesions 13% 5 year.
d/t high recurrence rate after surgical resection, and hematogenous metastasis to distant organs
