C. Malignant Tumors Of Endometrium And Myometrial Tumors

Front 1

What is really the only benign tumor of the endometrium that you will see?

Back 1

Polyps

Front 2

What are endometrial polyps?

Back 2

OVERgrowths of endometrial stroma and glands that project into the endometrial cavity.

Front 3

At what age are benign endometrial polyps typically seen?

Back 3

Perimenopause

Front 4

How do small vs large polyps typically manifest?

Back 4

Small = Asymptomatic
Large = May ulcerate/bleed or protrude thru cervix

Front 5

What do benign endometrial polyps consist of histologically?

Back 5

Polypoid endometrium with cystically dilated glands

Front 6

How often do benign endometrial polyps transform into malignancy?

Back 6

Very rarely!

Front 7

What is the most common invasive malignant carcinoma in the female genital tract?

Back 7

Carcinoma of the endometrium

Front 8

What can carcinoma of the endometrium develop from?

Back 8

Atypical endometrial hyperplasia

Front 9

What % of endometrial carcinoma is derived from
-Complex hyperplasia w/o atypia
-Atypical endometrial hyperplasia

Back 9

Complex: <5%
Atypical: 23%

Front 10

So what is atypical endometrial hyperplasia really considered to be?

Back 10

A premalignant disorder

Front 11

What 2 factors in atypical endometrial hyperplasia correlate with increased cancer risk?

Back 11

-PTEN gene loss
-Degree of atypia

Front 12

How is atypical endometrial hyperplasia treated in young females that still want to have a family?

Back 12

-Remove the estrogen source and give high dose progestin

Front 13

How treatment is considered for atypical endometrial hyperplasia in older females?

Back 13

Hysterectomy

Front 14

And what is the malignancy that atypical EM hyperplasia has a 23% risk of transforming into?

Back 14

Carcinoma of the endometrium

Front 15

What USED to be the most common invasive carcinoma of the female genital tract? Why isn't it anymore?

Back 15

Invasive cervical carcinoma - its incidence has been greatly reduced by pap smears

Front 16

Every year, how many new cases develop of:
-Carcinoma of the endometrium
-Invasive cervical carcinoma

Back 16

Carc of EM: 34,000
Cervical: 13,000

Front 17

Where does carcinoma of the endometrium rank among most common cancers in women?

Back 17

4th

Front 18

In what age groups is carcinoma of the endometrium
-Uncommon
-Peak

Back 18

Uncommon <40
Peak in 55-65 yr olds

Front 19

Will my mom get carcinoma of the EM?

Back 19

nope not possible

Front 20

What 4 factors can increase the risk of a woman to get carcinoma of the EM?

Back 20

-Obesity
-Diabetes
-Hypertension
-Infertility

Front 21

What are 3 reasons a woman might be infertile?

Back 21

-Single
-Nulliparous
-DUB/Anovulatory cycles

Front 22

Why are patients with EM carcinoma more likely to have anovulatory cycles?

Back 22

Becuase of the repeated stimulation of estrogen and continuous high levels of it.

Front 23

So what is the predominant pathogenesis in development of endometrial carcinoma?

Back 23

Prolonged and excessive estrogen stimulation

Front 24

And what may precede endometrial carcinoma?

Back 24

Endometrial hyperplasia

Front 25

In what conditions is incidence of EM carcinoma
-increased
-decreased

Back 25

-Increased in ovarian tumors that secrete estrogen
-Decreased in castration or ovarian agenesis

Front 26

What increases the risk of endometrial carcinoma in perimenopausal women?

Back 26

Use of estrogen for menopause symptoms

Front 27

Why does obesity increase the risk of endometrial carcinoma?

Back 27

Bc fat has aromatase and it makes more estrogen

Front 28

What gene inactivation is associated with increased risk of endometrial carcinoma?

Back 28

PTEN

Front 29

Do ALL patients with EM carcinoma have hyperestrinism?

Back 29

No there is a subset that doesn't

Front 30

How does EM carcinoma NOT associated w/ hyperestrinism compare to that which is?

Back 30

-Not preceded by EM hyperplasia
-More aggressive

Front 31

In what age of women is Endometrial carcinoma not due to estrogen more likely?

Back 31

Older

Front 32

How does endometrial carcinoma usually present clinically?

Back 32

As abnormal bleeding

Front 33

What kind of gross tumor can endometrial carcinoma appear as?

Back 33

-Localized polypoid
-Diffuse involving most of the endometrial surface

Front 34

Which type of tumor is EM carcinoma usually and how does that affect diagnosis?

Back 34

-Most often diffuse (anterior and posterior surfaces)
-Harder to see

Front 35

Once you cut into the specimen of an EM carcinoma what do you need to look for?

Back 35

The degree of extension into the Myometrium.

Front 36

What will you see in myometrial extension of endometrial carcinoma?

Back 36

Subserosal nodules

Front 37

Why is it important to determine the depth of myometrial extension?

Back 37

For staging (1a,b, or c)

Front 38

What is the most common pattern of spread of endometrial carcinoma?

Back 38

To the periuterine structures like the broad ligaments

Front 39

What is a more aggressive but fortunately more rare pattern of EM carcinoma spreading?

Back 39

Via the lymph nodes

Front 40

What TYPE of carcinoma are >85% of endometrial carcinomas?

Back 40

Adenocarcinoma - glands

Front 41

How are endometrial adenocarcinomas graded?

Back 41

Based on degree of differentiation

Front 42

What are the 3 grades of EM adenocarcinomas and what % of each is solid area?

Back 42

G1 = well diff <5% solid
G2 = mod diff <50% solid
G3 = poorly diff >50% solid

Front 43

How else are endometrial tumors graded?

Back 43

Based on nuclear atypia

Front 44

Do the grades of EM carcinoma tumors for nuclei and differentiation always match up?

Back 44

No; tumors can be well differentiated (G1) but with nuclear atypia (G3)

Front 45

What grade overall would a two-tiered tumor be?

Back 45

G2

Front 46

What % of endometrial cancer is endometrial adenocarcinoma?

Back 46

85%

Front 47

What are the 4 uncommon types of endometrial cancer that make up the other 10-15%?

Back 47

-Clear cell carcinoma
-Papillary serous
-Mucinous
-Secretory

Front 48

Which of the uncommon EM carcinomas are the most common?

Back 48

-Clear cell
-Papillary serous

Front 49

What grade are Papillary serous and Clear cell carcinomas automatically?

Back 49

Grade 3 - highly aggressive

Front 50

What do endometrial Papillary serous carcinomas and Clear cell carcinomas resemble?

Back 50

Their ovarian counterparts

Front 51

Why do endometrial Papillary serous carcinomas and Clear cell carcinomas have the tendency to disseminate fast?

Back 51

Because of papillae which can break off and go into the lymphatic channels

Front 52

What is highly important for determining prognosis in endometrial carcinoma?

Back 52

STAGE

Front 53

How is grading done?

Back 53

Based on histology (differentiation)

Front 54

How is STAGING done? How many stages are there for endometrial carcinoma?

Back 54

-Based on how much of the genital tract is involved
-4 stages (1-4)

Front 55

What is Stage I EM carcinoma?

Back 55

-Limited to the corpus of the uterine body

Front 56

What are 3 subsets of stage I endometrial carcinoma?

Back 56

Ia - limited to endometrium
Ib - invades <1/2 myometrium
Ic - invades >1/2 myometrium

Front 57

How does degree of invasion into the myometrium affect prognosis?

Back 57

It changes the ability of the cancer to invade the lymphatics

Front 58

What is stage II EM carcinoma?

Back 58

Extension into the CERVIX

Front 59

What is stage III EM carcinoma?

Back 59

Spread outside of the uterus, but confined to the true pelvis

Front 60

What is stage IV EM carcinoma?

Back 60

Distant metasasis outside the true pelvis

Front 61

What are the 2 most common symptoms of endometrial carcinoma?

Back 61

-Menorrhagia/abnormal bleeding
-Excessive leukorrhea

Front 62

Why is endometrial carcinoma such a silent killer?

Back 62

Because it may remain asymptomatic for a long time and there is no screening test like the pap smear.

Front 63

What is the most common method of diagnosis for endometrial carcinoma?

Back 63

EM biopsy in dr office or if quantity insufficient for eval do a D/C; histologic exam

Front 64

So what are the 2 most important factors in determining prognosis in EM carcinoma?

Back 64

-Histologic grade
-Clinical stage

Front 65

What are 80% of EM cancers at diagnosis?

Back 65

-Stage I (confined to EM)
-Grade 1 or 2 (well/med diff)

Front 66

What is the 5-yr survival rate for
-Stage I EM carcinomas
-Stage II
-Stages III/IV

Back 66

Stage I = 80-90%
Stage II = 30-50%
Stage 3/4 = 15-25%

Front 67

Why does prognosis decline so quickly with increasing stage?

Back 67

Because there are more blood vessels the deeper the tumor invades so it can spread more easily

Front 68

What is the therapy for endometrial carcinoma?

Back 68

Surgery w/ or w/o adjuvant radiation

Front 69

What is chemoradiation done up front for in EM carcinoma?

Back 69

To make tumors that have spread beyond the true pelvis more resectable.

Front 70

So what structure of the endometrium is involved in most cancers?

Back 70

Glands

Front 71

What % of endometrial cancers involve the STROMA?

Back 71

<5%

Front 72

What are the 3 EM tumors with STROMAL differentiation?

Back 72

-Carcinosarcomas
-Adinosarcomas
-Pure stromal neoplasms

Front 73

What is an endometrial Carcinosarcoma?

Back 73

When there is malignancy of both the endometrial GLANDS and the STROMA components

Front 74

What is an endometrial Adenosarcoma?

Back 74

-Benign gland proliferation
-Malignant stromal proliferation

Front 75

What are the 2 ways that pure stromal neoplasms can be?

Back 75

-Stromal nodules - benign
-Stromal sarcomas - malignant

Front 76

What are Carcinosarcomas often called?

Back 76

Triple MT's
Malignant Mixed Mullerian Tumors

Front 77

How do Carcinosarcomas develop?

Back 77

-Endometrial Adenocarcinoma is present
-Stromal differentiation into malignancy takes place

Front 78

How are the 2 components of Carcinosarcomas (gland + stroma) related?

Back 78

They are derived from the same cell type stemline

Front 79

In what age group does Carcinosarcoma of the endometrium occur?

Back 79

Postmenopausal women (70's)

Front 80

And what are the malignant components of Carcinosarcoma?

Back 80

-Malignant glands (carcino)
-Malignant stroma (sarcoma)

Front 81

What are the malignant components of Adenosarcoma?

Back 81

Just the stroma - that's why the glands are still adeno, not carcino.

Front 82

How do the doubly malignant Carcinosarcomas look grossly?

Back 82

Large bulky polypoid tumors that fill the EM cavity

Front 83

What do Carcinosarcomas consist of histologically?

Back 83

Mixed - malignant glands and stroma

Front 84

What can the stromal component of carcinosarcomas do?

Back 84

Differentiate into muscle, cartilage or osteoid

Front 85

So what is the most common clinical presentation of Carcinosarcoma?

Back 85

Vaginal bleeding in a POSTmenopausal woman

Front 86

How aggressive are adenocarcinomas and what is the 5-yr prognosis at diagnosis?

Back 86

-Highly malignant
-25-30% 5 yr survival

Front 87

What are the 2 types of PURE stromal carcinoma?

Back 87

-Benign Stromal Nodules
-Malignant low grade Stromal Sarcoma

Front 88

How do the low grade stromal sarcomas often present?

Back 88

-As a BULKY UTERUS due to mass
-Rarely with bleeding

Front 89

Why does stromal sarcoma usually present after much growth has occurred to make a bulky uterus?

Back 89

Bc it is very infiltrative and invades the myometrium

Front 90

Because the stromal tumors tend to invade the myometrium, what do they often do?

Back 90

Penetrate lymphatic channels

Front 91

What % of endometrial stromal sarcomas recur after surgery?

Back 91

50%

Front 92

What % of stromal sarcomas metastasize to distant sites and cause death?

Back 92

15%

Front 93

How does high grade EM stromal sarcoma compare to low grade, histologically?

Back 93

-Wide range of cell atypia
-Frequent mitoses

Front 94

What are the 2 tumors of the myometrium? Which is benign vs malignant?

Back 94

-Leiomyomas (benign)
-Leiomyosarcomas (malignant)

Front 95

What is the colloquial term for Leiomyomas of the uterus?

Back 95

Fibroids

Front 96

Why are fibroids clinically significant? (2 reasons)

Back 96

-Most common genital tumor in women!!
-Causes vaginal bleeding

Front 97

What is the prevalence of fibroids/leiomyomas in women in active reproductive life?

Back 97

1/4

Front 98

In what ethnicity are leiomyomas more common?

Back 98

African americans

Front 99

What happens to leiomyomas after menopause usually?

Back 99

They regress

Front 100

What can leiomyomas do?

Back 100

Hemorrhage and/or Calcify

Front 101

Where do these leiomyomas originate?

Back 101

From the myometrium

Front 102

What are 3 subtypes of Leiomyomas based on location?

Back 102

-Subserosal
-Intramural
-Submucosal

Front 103

What subtype of Leiomyoma will cause most severe vaginal bleeding and why?

Back 103

Submucosal - bc it pushes into the endometrial cavity

Front 104

What is a good thing about the severe bleeding in submucosal leiomyomas?

Back 104

They will be picked up at relatively earlier stages

Front 105

What % of women >30 have leiomyomas? What is the peak age?

Back 105

30% of women >30
Peak: 40-50

Front 106

Why do leiomyomas regress after menopause?

Back 106

Bc there is an estrogen component of stimulation

Front 107

When can leiomyomas increase?

Back 107

In pregnancy

Front 108

What does clinical diagnosis and treatment of leiomyomas depend on?

Back 108

Location, location, location

Front 109

What DON'T leiomyomas commonly do?

Back 109

Transform into malignancy

Front 110

What is the gross appearance of a leiomyoma?

Back 110

Whorled

Front 111

What will you see on histology of a leiomyoma?

Back 111

Whorled bundles of smooth muscle cells

Front 112

What are the malignant tumors of myometrium?

Back 112

Leiomyosarcomas

Front 113

Define leiomyosarcoma:

Back 113

Malignant tumor with smooth muscle differentiation

Front 114

How common are leiomyosarcomas?

Back 114

Very rare

Front 115

How do leiomyosarcomas most often develop, if at all?

Back 115

De novo - NOT a malignant transformation from something benign.

Front 116

What are 2 gross patterns of development of leiomyosarcoma?

Back 116

-Polypoid mass in lumen
-Invasion of uterine wall

Front 117

What 3 factors are important for diagnosing/determining prognosis of leiomyosarcomas?

Back 117

-Mitoses present
-Atypia (well diff to anapl)
-Necrosis

Front 118

What is usually the best way to confirm that a leiomyoma is malignant leiomyosarcoma?

Back 118

>10 mitoses per hpf

Front 119

At what age can leiomyosarcomas develop?

Back 119

Either BEFORE or AFTER menopause - they are equally common

Front 120

What is the peak age group of leiomyosarcoma?

Back 120

40-60 yrs

Front 121

What do leiomyosarcomas tend to do after surgical removal?

Back 121

Recur

Front 122

What is seen in >50% (!!!) of cases of leiomyosarcomas?

Back 122

Distant metastases

Front 123

What are the 3 commonest sites of metastasis from leiomyosarcomas?

Back 123

-Lung
-Bone
-Brain

Front 124

What is the 5-yr survival rate of leiomyosarcoma?

Back 124

40%

Front 125

What are the 4 methods of diagnosis of endometrial or myometrial cancer?

Back 125

-EM currettage (D/C)
-EM biopsy
-EM aspirate
-PAP smear

Front 126

What will usually give an adequete sample for accurate diagnosis?

Back 126

D/C

Front 127

Which method of diagnosis is less accurate?

Back 127

EM biopsy

Front 128

Why is EM biopsy easier than EM curettage?

Back 128

EM Biopsy requires no anesthesia; D/C does

Front 129

What is NOT a good method of diagnosing endometrial malignancy? Why?

Back 129

EM Aspirate - this only shows cytology, and you need to see ARCHITECTURE (glands/stroma) to differentiate hyperplasia and malignancy

Front 130

Why isn't a PAP smear a good method of diagnosing EM neoplasms?

Back 130

-Very low yield
-High rate of false negatives

Front 131

In what patients should EM biopsy always be done for any case of abnormal vaginal bleeding?

Back 131

Postmenopausal!!