Pathology Of Uterus Flashcards
1
Q
Dysfunctional uterine bleeding
A
- The most common form of vaginal bleeding in women
- Abnormal bleeding in the absence of a well defined organic lesion
- Endometrium goes thru a proliferative phase w/o a secretory phase eventually collapses and bleeds
- Common at both ends of reproductive life
2
Q
Dysfunctional uterine bleeding causes
A
- Most common cause: Anovulatory cycle: excess of estrogen relative to progesterone
- Any dysfunction of hypothalamus, pituitary gland, thyroid
- Ovarian lesion, malnutrition, obesity stress
- Inadequate luteal phase
*corpus luteum fails to mature or may regress prematurely leading to a relative lack of progesterone
*endometrium has a delay in development
- Contraceptive induced bleeding
3
Q
A
- Anovulatory bleeding
4
Q
Endometritis
A
- Part of pelvic inflammatory disease
- Endometrium is inflammed
- May be assoc. w/ retained POC (products of conception; like placenta) or FB (foreign bodies) such as IUD
- Acute and chronic forms
- Chronic forms have plasma cells
- Infection
5
Q
Endometritis Symptoms
A
- Fever, pain, ectopic pregnancy, menstrual irregularities
6
Q
Chronic Endometritis Histology
A
7
Q
Endometrial Polyps
A
- Sessile lesions, 0.5-3cm in diameter
- Covered w/ columnar cells, adenomatous stroma
- More common around menopause
- May produce abnormal uterine bleeding
- Foci of adenocarcinoma are rarely present
- Stromal cells have a cytogenetic arrangement of 6P21
- Has been assoc. w/ the use of Tamoxifen
8
Q
Adenomyosis
A
- Growth of endometrial basal layer into the myometrium
*benign growth
- Uterine wall is thickened
- Cyclic bleeding can occur but is unusual
- May produce menorrhagia, dysmenorrhea and pelvic pain
9
Q
Adenomyosis Histology
A
10
Q
Endometriosis
A
- Endometrial tissue outside the uterus
- Benign tissue but can cause complications from bleeding
- Common locations: ovaries, pouch of Douglas, uterine ligaments, tubes, rectovaginal septum
- Uncommonly: LN, lungs, heart
- Endometrial foci often undergoes cyclic bleeding
11
Q
Endometriosis Complications
A
- Can lead to Infertility
- Can cause Dysmenorrhea
- Can cause Pelvic pain
- Seen during active reproductive life
- Affects approx. 10% of women often in 20-30’s
12
Q
Endometriosis Four Major Theories
A
- The regurgitation theory
- Metaplastic theory
- The benign metastasis theory
- The extra uterine stem/progenitor cell theory
13
Q
Endometriosis-regurgitation theory
A
- Endometrial tissue implanted at abnormal locations
- Retrograde menstruation thru fallopian tubes could mediate spread of endometrial tissue to the peritoneal cavity
14
Q
Endometriosis-metaplastic theory
A
- Endometrium arising directly from coelomic epithelium which is mesothelium of the pelvis
- Mullerian ducts and endometrium originates from this during embryonic development
15
Q
The benign metastases theory
A
- Endometrial foci pass thru the lymphatic and hematogenous system
- Can reach distant sites such as the lung, bone and brain
16
Q
The extrauterine stem/progenitor cell theory
A
- Proposes that stem/progenitor cells from the bone marrow differentiate into endometrial tissue
17
Q
Endometriotic tissue characteristics
A
- There are specific abnormalities that distinguish normal endometrium from endometriotic tissue
- Activation of the inflammatory cascade: high lvls of prostaglandin E2, interleukin-1 beta, tumor necrosis factor and interleukin-6
- Upregulation of estrogen production by stromal cells due to high lvls of steroidogenic enzyme aromatase which is absent in normal endometrial stroma
- Epigenetic changes in genes that encode 2 nuclear receptors: steroidogenic factor 1 and estrogen receptor beta
- This results in overexpression causing a cascade leading to overproduction of estrogen and prostaglandin and resistance to progesterone action
- Produces nodules w/ a red-blue to yellow-brown appearance (due to early hemoglobin appearing red-blue and then as it breaks down to hemosiderin you get the yellow-brown)
- Hemorrhage may cause xtensive fibrous adhesions b/w tubes, ovaries and other structures
- Chocalate cysts
18
Q
Endometriosis Diagnosis
A
- Histologic diagnosis of endometriosis requires the presence of both endometrial glands and stroma
19
Q
Chocalate Cysts
A
- Cystic masses in the ovaries filled w/ brown fluid resulting from previous hemorrhage
20
Q
Endometriosis Clincal Features
A
- Severe dysmenorrhea
- Dyspareunia
- Pelvic pain
- Occasional pain on defecation
- Menstrual irregularities
- Infertility
21
Q
Atypical endometriosis
A
- Possible precursor to endometriosis related ovarian carcinoma
- Has 2 morphologic appearances
1) cytologic atypia of the epithelium lining the endometriotic cyst w/o major architectural changes
2) marked glandular crowding from epithelial proliferation often w/ cytologic atypia
22
Q
Endometrios Diagnosis Histology Slide
A
23
Q
Endometrial hyperplasia
A
- An important cause of endometrial bleeding
- Defined as an increase proliferation of the endometrial glands relative to the stroma
- Results in an increased gland to stroma ratio when compared w/ normal proliferative endometrium
- Malignant potential
- Assoc. w/ prolonged estrogen stimulation of the endometrium
24
Q
Endometrial hyperplasia associated diseases
A
- Obesity, menopause, PCOS, functioning granulosa cell tumors of the ovary, excessive cortical function, and prolonged administration of estrogenic substances such as estrogen replacement therapy
25
PTEN Gene
- Tumor suppressor gene
- Common genetic alteration found in hyperplasias and related endometrial carcinomas
- Encodes a dual specificity phosphatase capable of disphosphorylating both lipid and protein molecules
- It dephosphorylates lipid molecule phosphatidylinositol triphosphate which blocks the phosphorylation of AKT a central factor in the phosphatidylinositol 3 kinase growth regulatory pathway
- When **PTEN is inactive AKT phosphorylation is enhanced**, stimulating **protein synthesis** and **cell proliferation** while **inhibiting apoptosis**
- Loss of PTEN may activate pathways normally activated by estrogen
26
Simple hyperplasia without atypia
- Glands of various sizes and irregular shapes w/ cystic dilation
- Milde increase in the gland to stroma ratio
- Epithelial growth pattern and cytology are similar to proliferative endometrium w/ less prominent mitoses
- Uncommonly progress to adenocarcinoma
27
Simple hyperplasia with atypia
- Simple hyperplasia w/ cytologic atypia within the glandular epithelial cells
- Loss of polarity
- Vesicular nuclei and prominent nucleoli
- Cells become rounded and lose the normal perpendicular orientation to the basement membrane
- Approx. 8% progress to carcinoma
28
Complex hyperplasia without atypia
- Characterized by increased number and size of endometrial glands
- Marked gland crowding
- Branching of glands
- Crowded glands w/ abundant mitotic figures
- The glands remain distinct and the epithelial cells are cytologically normal
- 3% progress to carcinoma
29
Complex hyperplasia with atypia
- Can overlap w/ well-differentiated endometrioid adenocarcinom
- Architectural features are similar to complex hyperplasia w/o atypia but the cytologic features have changed
- Cells show atypia w/ rounded vesicular nuclei and prominent nucleoli
30
Carcinoma of the endometrium
- Most common invasive cancer of the female genital tract
- Arise mainly in postmenopausal women and presents w/ abnormal postmenopausal bleeding
- Uncommon in women younger than 40
- Incidence is in 55-65
- Clinicopathologic studies and molecular analysis divide endometrial carcinoma into two **broad categories**
31
Carcinoma of the endometrium type I
- Most common type accounting for greater than 80% of cases
- Majority are well differentiated and mimic proliferative endometrial glands
- Referred to as **endometrioid carcinoma**
- Typically arise in the setting of endometrial hyperplasia
- Contributing factors: **obesity, diabetes, hypertension, infertility and unopposed estrogen stimulation**
32
Carcinoma of the endometrium type I genetic mutations
- **PTEN tumor suppressor gene** has been identified in 30-80%
- **PIK3CA** mutations have been reported and endometrial carcinomas
- PIK3CA is the catalytic subunit of PI3K, a lipid kinase that phosphorylates PIP2 to PIP3, directly antagonizing the action of PTEN
- Microsatellite instability and mutations in the **K-ras** and **beta catenin oncogenes** can also be present
- **Mutations in p53**
33
Carcinoma of the endometrium appearance
- Can be either a localized polypoid tumor or a diffuse tumor involving the endometrial surface
- Direct myometrial invasion and eventual extension to the periuterine structures
- Dissemination to the regional lymph nodes, lungs, liver and other organs can occur
34
Carcinoma of the endometrium type I gradings
- Most are **endometrioid adenocarcinomas** w/ gland patterns resembling normal endometrial epithelium
- 3 step grading system; G1, G2, G3 (**as move up in grade, the more solid the tumor becomes**)
35
Carcinoma of the endometrium type I
- Up to 20% of endometrioid carcinomas contain foci of **squamous differentiation**
**-** The squamous elements are generally benign appearing
- Occasionally moderately to poorly differentiated endometrioid carcinomas have malignant squamous elements
36
Carcinoma of the endometrium type II
- Generally occur in women a decade later than type I
- Usually arises in the setting of endometrial atrophy
- They are by definition poorly differentiated grade 3 tumors
- The most common cell type is serous carcinoma b/c it resembles ovarian serous carcinoma
37
Carcinoma of the endometrium type II genetic mutations
- Most common genetic alteration is a mutation in the **p53 tumor suppressor gene**
38
Carcinoma of the endometrium type II appearance
- Tumors are often **large bulky or deeply invasive** into the myometrium
- **Endometrial intraepithelial carcinoma**: malignant cells in the gland surface w/o stromal invasion
- Invasive lesions: may have a **papillary growth pattern**
39
Carcinoma of the endometrium Symptoms
- May be asymptomatic for a period of time
- Usually presents w/ irregular postmenopausal vaginal bleeding or leukorrhea
- Prognosis depends on stage and histologic grade and type
40
Malignant mixed mullerian tumor
- AKA carcinosarcoma
- Usually seen in post menopausal pts
- Uterine bleeding and enlargement
- Large soft, polypoid growths
- Admixture of carcinomatous and sarcoma-like elements
- Highly aggressive
41
Leiomyoma
- Benign tumors from smooth muscle cells
- AKA fibroids (is NOT fibrotic tissue)
- Most common benign tumor in females
- Estrogens stimulate their growth
- Many have MED 12 gene mutations
- MED 12 stimulates gene expression
42
Leiomyoma appearance
- Well circumscribed, gray white masses
- Small to very large, may be multiple
- May become hemorrhagic or calcifie
- Whorling bundles of smooth muscle
- May be asymptomatic or present w/ menorrhagia
43
Leiomyosarcomas
- **Do NOT arise from preexisting leiomyomas**
- Usually **solitary**
- May be infiltrating, polypoid or discrete tumors
- Frequent mitoses, cellular atypia, coagulative necrosis
- Can be difficult to distinguish from leiomyoma
- Recurrence is common, may metastasize widely
