tumors of the endometrium

Question 1

Defined as increased proliferation of endometrial glands relative to stroma that results in increased gland-to-stroma ratio: what does it cause, and what is its significance

Answer 1

endometrial hyperplasia:

Endometrial hyperplasia important cause of abnormal bleeding Frequent precursor to most common type of endometrial carcinoma

Question 2

what are the associated conditions of endometrial hyperplasia?

Answer 2

Associated conditions

1. Obesity
2. Menopause
3. Polycystic ovarian syndrome
4. Functional granulosa cell tumors of ovaries
5. Excessive ovarian function
6. Prolonged administration of estrogenic substances

Question 3

genetics in endometrial hyperplasia and cancer

Answer 3

PTEN tumor suppressor mutation- controls AKT/PIK13 pathway which regulates target genes

shares PTEN mutation with endometrial carcinoma, making Ehyperplasia a potential precursor lesion

Question 4

non-aytpical endometrial hyperplasia genetic sequence vs aytpical endometrial hyperplasia genetic seq

Answer 4

Non-atypical hyperplasia:

MLH1 mutation—> KRAS mutation —> non-atypical hyperplasia –> cancer

atypical hyperplasia:

ARIDA1A/PIK3ACA/OTHERS—> atyp hyperplasia –> cancer

Question 5

Sequencing of genomes of type 1 endometrioid carcinomas show most common mutations act to increase

Answer 5

P13k/AKT pathways

Question 6

morphology of endometrial adenocarcinoma

Answer 6

1) Well differentiated Entirely well formed glands that are distinguished from hyperplasias by lack of intervening stroma
2) Moderately differentiated: well formed glands with “mixed areas” composed of solid sheets of cells making up less than 50% of tumor
3) Poorly differentiated: Characterized by greater than 50% of solid in tumor

Question 7

Morphology of endometrioid carcinoma

1. Localized polypoid tumor or tumor that diffusely infiltrates endometrial lining
2. Spreads through myometrial invasion
3. Metastasis to lymphatics late state, lungs/liver/bone Metastasis to broad ligament bump

Answer 7

Morphology of endometrioid carcinoma

1. Localized polypoid tumor or tumor that diffusely infiltrates endometrial lining
   
   1. Spreads through myometrial invasion
      
      1. Metastasis to lymphatics–> late state, lungs/liver/bone
      2. Metastasis to broad ligament bump

Question 8

type 2 endometrial tumor

Answer 8

1. Poorly differentiated (grade 3) tumors
   
   1. ​Serous carcinoma
   2. clear cell carcinoma
   3. mixed mullerian carcinoma
2. TP53 mutations = 90% of T2E Carcinomas
3. Usually arise in the setting of endometrial atrophy
4. 15% of endometrioid carcinoma
5. Most common subtype is *serous carcinoma*
6. TP53: majority are missense mutations
7. Precursor lesion: Serous endometrioid intraepithelial carcinoma

Question 9

type II endometrial carcinomas of the uterus: morphology

Answer 9

Morphology

1. Arise in small atrophic uteri
2. Often large and bulky or deeply invasive into myometrium
3. Serious endometrial intraepithelial carcinoma (precursor lesion)
   
   1. ​consists of malignant cells identical to those in fullblown carcinoma but confined to surfaces
4. High nuclear-to-cytoplasm ratio
5. Atypical mitotic figures
6. Hyperchromasia
7. Prominent nucleoli
8. Also present in glandular pattern
9. Whatever pattern, all are grade 3

Question 10

type 2 endometrial carcinoma:

age groups, ethnic preferences, peak incidence, mortality rate, symptoms

Answer 10

1. Uncommon in women younger than 40
2. Peak incidence in postmenopausal w 55-65 yo
3. irregular/postmenopausal bleeding
4. More frequent in women of African American descent
   
   1. Difference accounts for a 2 fold higher mortality rate
5. 5 yr survival is 18-27% for serous carcinoma

Question 11

Malignant Mixed Mullerian Tumors

1. Referred to as…
2. Are what?
3. what forms do the present?
4. most of them are:
5. Mutations found in MMT

Answer 11

1. Referred to as carcinosarcomas
2. Are endometrial adenocarcinomas with malignant mesenchymal component
3. Mesenchymal can take # of forms
   
   1. Stromal sarcoma
   2. Leiomyosarcoma
   3. Rhabdomyosarcoma
   4. Chondrosarcoma
4. Vast majority are carcinomas with sarcomatous differentiation
5. Mutations found in MMT tend to involve the same genes found in endometrial carcinomas: PTEN, TP53, PIK3CA

Question 12

MMMT

MMMT:

Morphology (5 points)

Clinical Occur

1. Present with
2. Outcome determined by

Answer 12

MMMT Morphology

1. Bulky
2. Polypoid
3. Mary protrude through cervical os
4. Consists of adenocarcinoma
5. Sarcomatous (mesenchymal) component may mimic extrauterine tissues: striated muscles, cartilage, adipose tissue, bone.

Clinical

1. Occur in postmenopausal women
2. Present with bleeding
3. Outcome determined by depth of invasion and stage
4. Poor outcomes with current therapies

Question 13

Stromal tumors

1. categories
2. kinds of genetic findings
3. likelihood of recurrance after treatment
4. rate of metastasis
5. survival rate

Answer 13

1. Stromal Tumors: Occasionally gives rise to neoplasms that resemble normal stromal cells
2. Two categories: benign stromal nodules and endometrial stromal sarcomas
3. two subtypes: Low grade and high grade types
4. Several recurrent aberrations
   
   1. Low grade: Translocations of JAZF1 gene to SUZ12
   2. High grade: Translocations unspecified
5. Half of all stromal tumors relapse
6. 15% = fatal metastasis
7. 5 yr survival = 50%

Question 14

Leiomyomas:

1. relative contribution to total cancers in women
2. what they are
3. karyotypes
4. genetics

Answer 14

Uterine leiomyoma = “fibrinoids”

1. Perhaps most common tumor in women
2. Benign smooth muscle neoplasms: occur singly or in multiple
3. 60% have normal karyotypes
4. 40% have simple chromosomal abnormalities
   
   1. Rearrangements: Chromosome 12 (HMGIC) and Chromosome 6 (HMGIY)
   2. Mutations: MED12 ~70% of fibrinoids

Question 15

morphology of leiomyomas

1. General
2. where they occur (3)

Answer 15

Morphology

1. Sharply circumscribed
2. Discrete
3. Round
4. Firm
5. Small to huge
6. Can fill whole pelvis
7. Composed of bundles of smooth muscle
8. Infrequently involve uterine ligaments, cervix
9. Occur
   
   1. Intramural (within myometrium) mostly
   2. Less common: under endometrium (submucosal) or within serosa (subserosa)

Question 16

Leiomyomas: morphology, benign variants, disseminated forms, how to distinguish them from leiomyomasarcomas, and symptoms of spread

Answer 16

1. Characteristic “whorled pattern of smooth muscle cells”
2. Mitotic figures scarce
3. Uniform muscle cells in size/shape
4. Benign variants: Nuclear atypia, Giant cells
5. Low mitotic index: Helps distinguish from leiomyosarcomas
6. Rare: benign metastasizing leiomyoma
   
   1. Uterine
   2. Extends into vessels and moves hematogenously, largely to lungs
   3. Disseminated peritoneal leiomyomatosis
      
      1. Commons signs and symptoms include
         
         1. Abnormal bleeding
         2. Urinary frequency due to bladder compression
         3. Sudden pain from infarction of large or pedunculated tumor
         4. Impaired fertility
         5. Fetal malpresentation
         6. Postpartum hemorrhage

Question 17

Leiomyosarcoma:

how common ar ethey?

arise from what?

genetics

Answer 17

1Leiomyosarcomas

1. Uncommon malignant neoplasms
2. Arise from myometrium or endometrial stromal precursor lesions rather than leiomyomas
3. Karyotypes vary
4. Deletions common

Question 18

Leiomyosarcomas

1. Morphology
   
   1. growth patterns
   2. Range of cytologic atypia
   3. Distinction from leiomyoma
2. Clinical
   
   1. Occur, Peake incidence, recurrence, how they spread

Answer 18

Two distinctive growth patterns in uterus

1. Bulky/fleshy masses
   
   1. Invade uterine wall
2. Polypoid masses
   
   1. Project into uterine lumen
3. Wide range of cytologic atypia

Distinction from leiomyoma based on

1. Nuclear atypia
2. Mitotic index
3. Zonal necrosis

Clinical

1. Occur both before and after menopause
2. Peake incidence: 40-60 yo
3. Often recur after tx
4. ~1/2 eventually metastasize hematogenously
5. Lungs
6. Bone