Uterus and Endometrium Flashcards
(128 cards)
1
Q
What is the myometrium and endometrium?
A
- Myometrium = tightly woven bundles of smooth muscle cells that form the wall of the uterus
- Endometrium = glands embedded in stroma that line the internal cavity of the uterus.
2
Q
What are the myometrium and endometrium hormonally responsive to?
A
- Myometrium = Oxytocin during parturition (childbirth)
- Endometrium = Sex-steroid hormones
3
Q
A drop in _____ causes the functionalis layer to degenerate or shed due to a breakdown/bleeding into stroma.
A
Progesterone, when the CL involutes at day 15 if ovulation does not occur.
4
Q
Proliferative phase is driven by ________ =>
A
Estrogen => proliferation of glands and stroma from the basalis to form a new functionalis
5
Q
Features of the Proliferative phase
-Glands, stroma, mitotic figures, mucus secetion/vaculoizeation-
A
- Glands = straight, tubular structures with regular, tall pseudostratified columnar cells
- Stroma = actively prolifearting spindle cells with SCANT cytoplasm
- Numerous mitotic figures
- No mucus secretion/vacuoliztion
6
Q
Proliferative phase ends at ______
A
ovulation
7
Q
What hormone begins the secretory phase?
A
Progesterone downregulates of estrogen receptors in the glands and stroma => supresses proliferation
8
Q
How does the location and histology of the secretory vacuoles change over the course of the secretory phase (post-ovulation) during the menstrual cycle?
A
- Marked by the appearance of secretory vacuoles
- Day 16-17: Early secretory phase with secretory Subnuclear vacuoles –> supranuclear vacuoles (3rd week of cycle)
- Day 18-24: Glands dilate when secretion is maximal –> tortuous and serrated or “saw-toothed” by week 4
9
Q
What stromal changes are seen in the late secretory phase of the menstrual cycle, which is IMP FOR DATING THE ENDOMETRIUM.
A
- Day 21-22: Prominent spiral arterioles appear + ↑ ground substance and edema btw stromal cells
- Day 23-4: Stromal hypertrophy –> ↑ cytoplasmic eosinophilia (predecidual change) + increase stromal mitoses
- Day 24-28- Predecidual changes spread throughout functionalis + sparse infiltrate of neutrophils and lymphocytes
10
Q
- Which hormone is responsible for driving the proliferation of glands and stroma during the proliferative phase of the menstrual cycle?
- Between which days of the menstrual cycle will you see dilation of gland which appear tortuous and serrated or “saw-toothed?”
A
- Estrogen
- Day 18-24
11
Q
“Dating” the endometrium by its histologic appearance may be used to assess hormonal status, document ovulation, and determine causes of endometrial bleeding and infertility
A
12
Q
what may contribute to the development of ectopic endometrial tissue and endometrial cancer?
A
endometrial stem cells
13
Q
What is the most common cause of AUB (abnormal uterine bleeding)?
A
DUB due to anovulation (failure to ovulate) due to subtle hormone imbalances => no progesterone => unopposed estrogen stimulates the endometrium.
14
Q
Anovulation leading to dysfunctional uterine bleeding is most common during what 2 periods of a woman’s life?
A
Menarche and peri-menopausal period
15
Q
Endocrine causes of hormonal imbanlance that can lead to anovulation?
A
- Thryoid,
- Adrenal
- Pituitary
16
Q
Ovarian causes of hormonal imbanlance that can lead to anovulation?
A
- PCOS (Stein-Leventhal syndrome)
- Granuloma cell tumors
17
Q
Metabolic causes of hormonal imbanlance that can lead to anovulation?
A
- Obesity
- Malnutrition
- Chronic systemic disease
18
Q
What is the most common cause of abnormal uterine bleeding in the pre-puberty age group?
A
Precocious puberrt (hypothalamic, pituitary, or ovarin origin)
19
Q
When their is failure of ovulation what hormonal imbalance occurs?
A
Excessive endometrial stimulation by estrogen that is unopposed by progesterone
20
Q
What is the most common appearance of the endometrium during anovulation?
A
- Lacks progesterone-dependent features (glandular secretory changes and stroma pre-deciduation)
- Contains pseudostratified glands and scattered mitotic figures
21
Q
What is inadequate luteal phase?
When do we see when we biopsy?
A
- Infertility + increased bleeding or amenorrhea due to inadequare progesterone during post-ovulatory period.
- Biopsy: slow, developing “secretory endometrium”, lagging behind for expected dates.
22
Q
Why are the endometrium and myometrium relatively resistant to infection?
A
Endocervix forms a barrier to ascending infection
23
Q
Acute endometritis is uncommon and caused by what?
A
- Bacterial infections that arise after delivery or miscarriage due to retained products of conception.
- Bacteria: Group A hemolytic strep (GAHS), staphylococci, and others
24
Q
In acute endometritis, there is _________ of the stroma.
A
Nonspecific inflammation
25
**Treatment** of acute endometritis.
**Curettage** of fragments + **AB** (B-lactams for staph and strep)
26
What finding does the diagnosis of **chronic endometritis** depend on?
**Plasma cells** in the stroma of the endometrium
27
What is the MCC of **chronic endometritis?**
**Ascending infection** (especially ***chlamydia***)
28
**Chronic Endometritis** is associated with:
1. PID (mostly chylamidia)
2. Retained gestational tissue
3. IUD
4. TB = rare in western countries
5. Chylamydia
29
**Chronic endometritis** presentaion
1. **ABNL bleeding**
2. **Pain**
3. **Discharge**
4. **Infertility**
30
**Pelvic TB** MC infects what?
1. BOTH fallopian tubes + endometrium (50%) of the time
2. RARELY infects: [cervix, vagina, uterus]
3. If ovaries, only surface.
31
Morphology of **Pelvic TB** (2)
- Detected on what stain?
1. Multinucleated giant cells
2. Histiocytes
Seen on [**Kinyoun** or **Ziel-Neelsen fast-acid stain**]
32
What is **endometriosis**?
When is it most common?
* **Ectopic** endometrial tissues seen outside of the uterus (**stroma** and maybe glands).
* **30-40YO** (active reproducing childbearing years)
33
Symptoms of **endometriosis**
1. Infertility (30-40%)
2. Severe dysmenorrhea (cramps)
3. Colicky pelvic pain
34
List the 8 most common sites of **endometriosis** in descending order of frequency.
1. **Ovaries**
**2. Uterine lig.**
**3. Rectovaginal septum**
**4. Cul de sac**
**5. Pelvic peritoneum**
6. Large and small bowel and appendix
7. Mucosa of cervix, vagain, and fallopian tubes
8. Laparotomy scars
35
How does ectopic tissue form in endometriosis?
1. **Regurgitation theory**: retrograde flow of menstrual endometrium through the fallopian tubes =\> implants at ectopic sites (occurs in 90% of W)
36
What is the **benign metastases theory** in relation to the pathogenesis of endometriosis?
Endometrial tissue spreads via **blood** and **lymph** to distant sites
37
What is the **metaplastic theory** in relation to the pathogenesis of endometriosis?
Endometrium arises from **coelomic mesothelium** or **mesonephric remnant** that undergo **endometrial differentiation** giving rise to **ectopic tissue**
38
What is the **extrauterine stem/progenitor cell theory** in relation to the pathogenesis of endometriosis?
**Bone marrow derived stem/progenitor cells** differentiate into endometrial tissue
39
How is ectopic endometrial tissue (which still undergoes menstruation) **different** from regular endometrial tissue?
1. Ectopic endometrial stroma has **high levels of the aromatase** (not present in normal endometrium) =\> **make its own estrogen** =\> **survival** and **persist**.
2. Secretes **pro-inflammatory factors.**
40
**Epigenetic alterations** seen in **endometriosis** lead to what kind of response to estrogen and progesterone?
* ↑ responsivness to **estrogen**
* ↓ responsivness to **progesterone**
41
Women with **endometriosis** have a 3x greater risk for development of what 2 cancers?
**Ovarian** and **clear cell types**
42
**Endometriotic lesions** bleed periodically in response to *extrinsic* (ovarian) and *intrinsic* *hormones,* producing what?
**Red-blue** =\> **yellow-brown** **nodules** on or just beneath the mucosal and/or serosal surfaces at site involved
43
When the lesions of endometriosis are **extensive**, organizing hemorrhage causes what?
**Fibrous adhesions** btw structures (tubes, ovaries and other structures) and **obliterates the pouch of Douglas**
44
What can form when ectopic endometrial tissue forms on **ovaries**?
C**hocolate cysts/ endometrioma=** **large cysts filled with brown fluid** as a result of previous hemorrhage
45
What is the significance of **atypical endometriosis?**
**Precursor to cancer** (endometrosis-related ovarian and cell cell carcinoma)
46
Based on histology what must be present for the diagnosis of ***endometriosis*** to be readily made?
When both **endometrial GLANDS** and **STROMA** are present, with or without **hemosiderin**.
47
Why might a patient with **endometriosis** present with **pain during defecation** or **dysuria**?
Involvement of the
* **Rectal wall** = pain on defecation
* **Bladder serosa** = dysuria
48
Treatment of **endometriosis**?
**Aromatase inhibitors** or surgery
49
What is **adenomyosis**?
Endometrial tissue **WITHIN** the uterine wall (myometrium) that can co-exist with endometriosis.
50
What is seen on microscopic examination of **adenomyosis**?
**Irregular nests of endometrial stroma**, w/ or w/o glands, arranged **within myometrium,** separated from basalis by at least **2-3mm**
51
What is the appearance of **endometrial polyps?**
MC when?
- **Exophytic masses (**single or multiple) and usually sessile in the endometrial cavity.
- Occasionally large and pedunculated
- Reproductive age, peri and postmenopausal F.
52
Endometrial polyps **may become hyperplastic** in association with what; what is their response to hormones?
- In assoc. w/ **generalized endometrial hyperplasia**
- Responsive to **estrogen** but show **little or no response to progesterone**
53
**Endometrial polyps** have been observed in association with what drug?
**Tamoxifen**, used in breast cancer therapy due to its **anti-estrogenic activity** on the **breast**; has **weak pro-estrogenic effects on endometrium**
54
**Endometrial hyperplasia** is defined as an increase in the proliferation of what?
↑ proliferation of glands relative to the stroma = **↑ gland:stroma ratio** due to **prolonged estrogenic** stimulation of the endometrium,
55
**Endometrial hyperplasia** is an important cause of ____________ and is also important due to what?
* Abnormal bleeding
* Frequent **precursor** to the **most common type of endometrial carcinoma**
56
What associated clinicopathologic and epidemiologic conditions cause **increased estrogen**, which can lead to **endometrial hyperplasia?**
1. **Anovulation**
2. **Obesity** = peripheral conversion of androgens --\> estrogens
3. **Menopause**
4. **Prolonged administration of estrogenic substances** (estrogen replacement therapy)
- Polycystic ovarian syndrome
- Granulosa cell tumor of the ovary
- Excessive ovarian corticalfunction (cortical stromal hyperplasia)
57
What mutation is a common in both **endometrial hyperplasia** and **endometrial carcinomas;** which pathway does this regulate?
* **PTEN**, a tumor supressor that **regulates PI3K/AKT pathway**
* **Loss of PTEN** =\> overactivation of **PI3K/AKT pathway**
58
Which **AD disorder** is due to **germline mutations of PTEN** and is associated with **high incidence of endometrial carcinoma** and **breast cancers**?
**Cowden syndrome (multiple harmatoma syndrome)**
59
What is the relation of the **PI3K/AKT pathway** to **estrogen**?
PI3K/AKT signaling enhances the ability of the estrogen receptor to **stimulate gene expression in target**
60
Is the loss of PTEN seen in endometrial hyperplasia predictive of progression to carcinoma?
***NO***
61
What are the 2 major categories of **endometrial hyperplasia (precursor lesions)** recommended by the WHO?
1. **Non-atypical hyperplasia**
2. **Atypical hyperplasi**a (aka **endometrial intraepithelial neoplasia**)
62
Cardinal morphological feature of **non-atypical hyperplasia** of the endometrium
**- ↑ in gland-to-stroma ratio** due to persistant estrogen stimulation
- Glands **MAY** be back-to-back, but **usually** there is intervening stroma
63
What is the likelihood of **non-atypical hyperplasia** of the endometrium progressing to **adenocarcinoma**; what may be seen morphologically when estrogen is withdrawn?
- **Rarely** progress to cancer (1-3%)
- When estrogen with withdrawn after menopause =\> undergoes **cystic atrophy**
64
What are the morphological and cellular features (chromatin and nucleoli) which encompass **atypical hyperplasia (EIN**) of the endometrium? (4)
1. Complex pattern of proliferating gland with nuclear atypia
1. Back-to-back glands that branch
2. Loss of orientation of nuclei to BM
3. Chromatin is open (vesicular) chromatin
4. Conspicuous nucleoli
65
Morphology of **atypical hyperplasia of the endometrium** _IS VERY SIMILAR_ to **well-differentiated endometrioid adenocarcinoma;** how can the distinction be made?
May not be possible without **hysterectomy,** where 1/2 patients are found to have cancer.
66
In patients who want to be fertile, how do we treat **endometrial intraepithelial neoplasia (EIN)?**
* **Progesterone therapy** and close follow up.
* If it does NOT regress =\> **hysterectomy**
67
What is the most common _invasive_ cancer **of the female genital tract?**
* Peak age
* Earliest sign
**Endometrial adenocarinoma**
* 55-65 YO
* Vaginal bleeding in older women
68
Of the 2 classifications of endometrial carcinoma, which is the most common type accounting for **80% o**f cases?
**Type I (endometriod) Adenocarcinoma**
69
**5 disorders** associated with development of **Type 1 (endometriod)** **Endometrial Carcinoma**?
1. **Obesity**
2. **DB** (abnormal GTT in 60%)
3. **HTN**
4. **Infertility**
5. Unopposed **estrogen** stimuulation
70
**Type 1 Endometroid Carcinoma**
* Age
* Morphology
* Precursor
* Mutated genges
* Behavior
* **Age** = 55-65YO
* **Morphology** = endometriod (most are well-differentiated and mimic endometrial glands)
* **Precursor**= atypical hyperplasia
* **Mutated genes** = MSI
* **Behavior**= low grade, indolent, spreads via lymphatics
71
**Type 2 Serous Carcinoma**
1. Age
2. Morphology
3. Precursor
4. Mutated genes
5. Behavior
1. Age: **65-75** YO; more common in **AA**
2. Morphology: Poorly-differentiated; [Serous, clear cell or mixed mullerian tumor]
3. Precursor: serous endometrial intraepithelial carcinoma
4. Mutated genes
5. Behavior: aggressive and spreads intraperitoneal and lymphatcs
72
What is the **hallmark mutation** associated with **type I endometrial carcinoma**?
Multiple mutations =\> **↑ signaling via PI3K/AKT pathway** =\> increase sensitivity to estrogen.
73
What mutation is commonly found in: [**type I endometrial carcinoma, ovarian endometroid** AND **clear cell carcinomas** that arise in endometriosis]?
LOF of **ARID1A**
74
Why are **endometrial carcinomas** common in women from families w/ **HNPCC (aka Lynch Syndrome)**?
Epigenetic silencing (**hypermethylation**) of **DNA mismatch repair genes**
75
What mutation has a important role in the **INVASION** of type 1 endometrial carcinomas?
activation of **PIK3CA oncogene**
76
In **sporadic** endometrioid carcinomas, loss of expression of DNA mismatch repair genes is commonly caused by what? (like in Lynch Syndrome)
**Epigenetic silencing (via promoter hypermethylation)**
77
What does **Endometroid carcinoma (Type 1)** typically look like?
* **Localized polypoid tumor** or one that **diffusely infiltrates the endometrial lining**
78
How does **Endometriod carcinoma** spread?
1. **Myometrial invasion** =\> direct extension into adjacent structures =\>
1. If broad ligament=\> palpable
2. Regional LN =\> **lymphatics** to lungs, liver bone.
79
How is **Endometroid** **Adenocarcinoma** graded histologically ?
1. Grade 1 = well-differentiated, well-formed lgands
2. Grade 2 = Moderately differentiated, well formed glands + solid sheets of cells causing \< 50% solid growth
3. Grade 3 = Poorly differentiated with 50% solid growth
80
**Well- differentiated endometrial carcinomas** may be differentiated from hyperplasia by what?
Cancer has **lack of intervening stroma** btw glands (top right)
81
**Stage I-IV** for [Type I and II Endometrial Adenocarcinoma] & [malignant mixed mullerian tumor]
- **Stage I:** confined to **corpus uteri**
- **Stage II:** involves **corpus** AND **cervix**
- **Stage III:** extends **outside the uterus**, but **NOT outside true pelvis**
- **Stage IV:** extends **outside the true pelvis** or involves **mucosa** of **bladder** or **rectum**
82
A **52 year** old **Caucasian** female presents with **abnormal vaginal bleeding.** Menarche age 12, last normal menstrual period age 49. Pap smear history normal. PE: **BMI 32,** BP 140/92, Pulse 85, normal external genitalia, uterus slightly enlarged on bimanual exam. Hgb 10 g/dl. Transvaginal ultrasound reveals **endometrial thickness of 14mm** (normal 8-11), and endometrial biopsy performed. Most likely diagnosis in this setting?
Type 1 Endometriod Adeno
## Footnote
**- white, between 55-65, obese-**
83
Type II (serous) endometrial carcinoma is most in who?
**African-Americans**
84
**Type II endometrial carcinoma** typically arises in the setting of \_\_\_\_\_\_\_\_\_
**Endometrial atrophy** =\> Serous endometrial intraepithelial carcinoma (precursor lesion)
85
What are the 3 morphological subtypes of **type II endometrial carcinoma** and which is most common?
1. **Serous** = most common
2. **Clear cell**
3. **Mixed müllerian tumor**
86
**Type II endometrial carcinomas** are by definition what grade of tumor?
At presentation, already spread where?
* **Poorly differentiated (Grade 3)** with poor prognosis bc travel through fallopian tube =\> implants on peritoneal
* Uterus
87
Mutations in what gene are seen in at least **90% of type II (serous) endometrial carcinomas;** what does this mutation cause?
**- TP53 missense mutations**
- Mutations results in **accumulation of the altered protein in the nucleus**
88
What is the precursor of **type II (serous) endometrial carcinoma** and what can be this lesion be stained for immunohistochemically?
- **Serous endometrial INTRAepithelial carcinoma** (pic top left)
- Can stain for **TP53** (pics on right)
89
What is the behavior of **type II (serous) endometrial carcinomas** and how does it spread?
- **Aggressive**, when found already attacks _uterus_
- **Intraperitoneal** --\> travel through fallopian tubes and implants on peritoneal surfaces and lymphatic spread
90
What is necessary for establishing the diagnosis of endometrial carcinoma?
**Histological examination** of tissue obtained by biopsy or curettage
91
What is the 5-year prognosis for **stage I (grade 1 or 2) endometrial carcinomas** following surgery +/- irradiation?
**90% = excellent**
92
What makes **serous endometrial intraepithelial carcinoma** a pre-malignant lesion if the cells are the same as serous carcinoma?
**Confined to epithelial surface** and HAS NOT invaded stroma.
93
What is the morphology of Type II serous endometrial carcinoma?
1. **Papillary** like growth-pattern
2. **Malignant cells with cytologic atypia:** high nuclear:cytoplasmic ratios, atypical mitotic figures, hyperchromasia, prominent nucleoli.
94
**Some** type II (serous) endometrial carcinomas will have a **predominantly glandular growth pattern;** how can they be distinguished from type I (endometrioid) carcinoma?
**Marked cytologic atypia**
95
If a women has endometrial cancer and presents with **post-menopausal bleeding**, we can often assure her that what?
Can be cured bc often **leads to early detection**
96
What are **malignant mixed müllerian tumors** (aka carcinosarcomas)?
**Endometrial adenocarcinomas** w/ a **malignant mesenchyma componen**t (has malignant glandular + mesechynak cells)
97
The **epithelial** and **stromal** components of **malignant mixed müllerian tumor**s are derived from what?
**The _same_ founding cell**
98
Which genes are involved in **malignant mixed müllerian tumors?**
Same genes mutated in endometrial carcinomas, such as **PTEN, TP53, and PIK3CA**
99
What is the gross morphology and size of **malignant mixed müllerian tumor**s?
Histo?
Often **bulky** and **polypoid**, and may **protrude through the cervical os**
* Glandular (adenocarcinoma) + sarcomatous (malignant mesenchymal) elements
100
The **sarcomatous** component of **malignant mixed müllerian tumors** may mimic what tissues?
Outcome?
**Heterogenous elements** = Striated muscle, cartilage, adipose tissue, and bone = **worse outcome**
101
**Metastases** from m_alignant mixed müllerian tumors_ usually contain which component of the tumor?
**Epithelial components**
102
What is the common presentation and in whom for **malignant mixed müllerian tumors?**
**Postmenopausal female w/ bleeding**
103
The **outcome/prognosis** of malignant mixed müllerian tumors is dependent on what?
Which has the WORST prognosis?
- **Depth of invasion** AND **stage \*\*\*\***
- Also the differentiation of the mesenchymal component
- Heterologous mesenchymal components = worse prognosis
104
Genetically, what do malignant mixed mullerian tumors (MMMTs) resemble genetically?
survival?
**Endometrial carcinoma; POOR outcome (25-30% 5year survival if high stage)**
105
Diagnosis of **adenosarcomas** of the endometrium is dependent on the finding of a tumor composed of what?
**Malignant-appearing stroma**, which **coexists** w/ **benign** but **abnormally shaped endometrial glands**
106
What type of malignancy are adenosarcomas?
Low grade
107
How do **adenosarcomas of the endometrium** most typically present and what is the principle diagnostic dilemma w/ these tumors?
**- Large, broad, polypoid growths t**hat can prolapse thru the cervical os
- Dilemma = **distinguishing** these tumors from **large benign polyps**
108
Why is it important to make the distinction between **adenosarcomas** and large **benign polyps** of the endometrium?
Adenosarcoma is **estrogen-sensitive** and responds to **oophorectomy**
109
**Endometrial stromal neoplasms** are divided into what 2 categories?
1) **Benign stromal nodules** = well-circumscribed
2) **Endometrial stormal sarcomas** (high- or low-grade)
110
_Endometrial stromal sarcomas are associated with translocations that create fusion genes._
Which chromosomal translocation has been linked to **low-grade endometrial stromal sarcomas**?
**JAZF1-SUZ12 fusion gene**
111
Which benign neoplasm of the myometrium is perhaps the **most common tumor in women?**
**Uterine leiomyomas (fibroids)** = Smooth m. neoplasm
112
How do **leiomyomas** most often present and there is an increased incidence in which ethnic group?
Most often presents as **multiple, well-circumscribed grey-white benign tumors**
- ↑ incidence in African Americans
113
Rearrangements of what chromosomes and involving what genes implicated in other benign neoplasms are seen in about **40% of leiomyomas?**
**Cr. 12q14** and **6p** --\> **HMGIC** and **HMGIY**
114
Mutation of _______ =\> allows uncontrollable cell division has been implicated in **70% of leiomyomas (fibroid)?**
**MED12,** a mediator that controls cell division
115
Leiomyomas that occur **beneath endometrium** =\> \_\_\_\_\_
**Submucosal**
116
What are the characteristic microscopic features which distinguish **leiomyomas**? (3)
1. - Bundles of **whorled smooth m. cells,** which are uniform in size and shape
2. - **Oval** nucleus + **long bipolar cytoplasmic processes**
3. - **RARE** mitotic figures
117
How can we distinguish **leiomyomas** from **leimyosarcomas**?
Leiomyomas have **SCARCE mitotic figures.**
118
What is the typical clinical presentation of **leiomyomas**?
- Often **asymptomatic**
- Common sx's: [_abnormal bleeding]_ + [_urinary frequency (bc compressed bladder)]_ + [_sudden pain]_from infarction of a large or pedunculated tumor and [impaired fertility]
119
What are the **complications** which may arise due to **leiomyomas** in a **pregnant woman?**
1. ↑ frequency of
1. **Spontaneous abortion**
2. **Fetal malpresentation**
3. **Uterine inertia (failure to contract w/ sufficient force)**
4. **Post-partum hemorrhage**
120
What is the likelihood of a **leiomyoma** undergoing malignant transformation to a **leiomyosarcoma**?
**Extremely rare**
121
How does the **karyotype** of **leiomyosarcomas** differ from that of **leiomyomas**?
- **Leiomyosarcoma** = complex, highly variable karyotypes that frequently include deletions; subset contains MED12 mutations
- **Leiomyomas** = normal karyotypes
122
What are **leiomysosarcomas**?
MC occur when?
* Uncommon, **malignant** neoplasms that arise from **myometrium** or **endometrial stromal precursor cells** (RARELY from leiomyomoas).
* STUMP = smooth muscle tumor of uncertain malignant potential
* **40-60YO** (before and after menopause)
123
What mutations are virtually unique to **uterine smooth muscle tumors?**
**MED12**
124
What are the 2 distinct patterns by which **leiomyosarcomas** grow within the uterus?
1) **Bulky, fleshy masses** that invade uterine wall
2) **Polypoid masses** that project into uterine lumen
125
Distinction of **leiomyosarcoma** from **leiomyoma** is based on what cellular features?
**Nuclear atypia** + **mitotic index** + **zonal necrosis**
126
What is the **behavior** and **prognosis** of **leiomyosarcomas** like?
- OFTEN **recur** after surgey
- **\> 50% metastasize hematogenously** ---\> lungs, bone, and brain; may also disseminate throughout abdominal cavity
- Overall 5-year survival = 40%, but anaplastic lesions = 10-15%
127
Based on the anatomy why do **leiomyosarcomas** often metastasize to the **lung**?
Tumor invades **uterine vein** and goes **straight to lungs**
128
**Leiomyosarcomas** are malignant if:
1. **10 mitosis/hpf**
2. **5 mitosis/hpf** + nuclear atypia or large cells.
