Uterine Malignancy Flashcards
When do endometrial polyps occur?
- around/after menopause
What are the types of endometrial hyperplasia?
simple
complex
atypical (precursor of CA)
What is endometrial hyperplasia?
- overgrowth of endometrial glands and stroma
Where is the endometrial polyp in the uterus on slide 4
- at the fundus
Describe appearance of the polyp.
smooth shiny surface
Describe the microscopy of Simple endometrial hyperplasia.
- incr. in volume of stroma and glands
- normal nuclear fts/cytology
- glands NOT crowded
Describe complex endometrial hyperplasia.
- glands are very crowded
- –normal cytology
What is it if the cells are atypical and crowded glands are seen?
- atypical endometrial hyperplasia
When is a complex atypical hyperplasia considered to be malignant?
- once glands fuse= Malignancy
Most common endometrial CA?
endometroid ca
IS post-menopausal bleeding bad?
- yes
- at risk of CANCER
Which enodmetrial CA is at risk of spreading elsewhere?
-serous CA
What are the diff. types of endometrial ca?
- clear cell (high grade)
- Serous CA (high grade)
- Endometroid Ca
Where is the endometrial tumor likely to spread to?
- directly into the MYOMETRIUM and CERVIX —-once its in the OUTER path of myometrium- this is concerning; d.t presence of LARGE blood vessels
- Lymphatic
- Hematogenous
Most endometrial ca is _______
well differentiated and ADENOCARCINOMAS
What drives the growth of endometrium?
- estrogen
Why is obesity a risk factor of endometrialk cancer?
- adipocytes express aromatase that CONVERTS ovarian androgens into estrogens
- when they are obese SEX- hormone binding globulin levels are lower; SO HIGH unbound, active hormone
- altered insulin axn; insulin-binding globulin levels also reduced= HIGH free insulin levels –>Insulin/insulin-like growth factors (IGF) exert proliferative effect on endometrium.
Is LYNCH syndrome a RISK factor of endometrial cancer?
- YES
- HIGH RISK OF COLORECTAL CANCER, ENDOMETRIAL cancer and probability of developing ovarian cancer
How to test for Lynch Syndrome?
- immunohistochemistry staining of the TUMOR for mismatch repair proteins (identifies tumors d.t Lynch $)
- Lynch syndrome tumours also show microsatellite instability (MSI), a characteristic of defective mismatchrepair.
Testing cancer tissue for MSI can be useful.
What occurs after receiving positive lynch $ with genetic testing?
- genetic counselling follows if positive
Which is more common out of Type I or TYPE II tumors?
- serous Type II tumors
How may type ii tumors spread t the peritoneum?
- SPREADS along the fallopian tubes to the peritoneal surfaces = extra-uterine disease
- therefore spreads EARLY to the peritoneal cavity
Does endometrial ca have good prognosis?
Which type is most aggressive - Serous or Endometroid?
- yes because it is usually CONFINED to the uterus at presentation
- SEROUS!
Why is Grade 3 endomtrial cancer aggressive?
- has more mutations
- forgotten how to behvae (poorly differentiated)
At what stage does the tumor reach the serosa
—what occurs to it then?
- At stage IIIA
- —reaches serosa and/or the fallopian tubes, ovaries and ligaments of the uterus
Metastases to para-aortic and pelvic LN occurs at what stage?
- IIIC
If the tumor arises from the endometrial stromal; what is it called?
- endometrial stromal sarcoma
What is a carcinosarcoma?
- carcinoma that has gone rogue
- produces MESENCHYMAL tissue (forms cartilage/bone/all malinant tissues )—-mixed tumor with MALIGNANT epithelial and stromal elements
Which endometrial tumor has poor prognosis?
- malignant, mixed MULLERIAN tumor
How to recognize if Endometrial stromal Sarcoma is high grade?
- incr. atypia
- proliferative activity
How does endometrial stromal sarcoma present as?
- abnormal uterine bleeding
- initial presentation may be as metastasis (mostly OVARY/LUNG)
Which component of the carcinosarcoma gives the worst prognosis?
- rhabdomyosarcomatous
heterologous elements seen in 50% of cases
How common are leiomyomas?
- VERY
- –a.w menorrhagia, (d.t STRETCH of the ENDOMETRIUM- prone to bleeding)
- infertility (inability for blastocyst to implant)
How to know if the tumor is malignant?
- under microscope; evidence of necrosis and hemorrhage
Appearance fo leiomyoma under the microscope?
- smooth muscle proliferation
- foci of calcification, fibrosis may be seen
- absence of necrosis and bleeding
Is leiomyosarcoma common?
Who is at risk?
NO; only 1-2% of uterine malignancies
- those >50y.o
Symptoms of leiomyosarcoma?
abnormal vaginal bleeding, palpable pelvic mass and pelvic pain
What is the prognosis of leiomyosarcoma?
POOOR
- even if confined to uterus
- —5 year survival rates 15-25%
How does endometrial hyperplasia present as?
abnormal bleeding (dysfunctional UTERINE bleeding/postmenopausal bleeding)
Describe the histological difference btwn simple and complex endometrial hyperplasia
- stroma still visible in simple hyperplasia (as glands are not crowded)
- not much stroma in COMPLEX hyperplasia and nuclei lined up along BM (Cigar shaped)
Look at slide 10. What change is seen in the nuclei of complex atypical hyperplasia?
Nuclei is no longer lined up at the BM of the gland
When is the peak incidence of endometrial CA?
- 50-60 years old
- RARE under 40
If endometrial ca presents in a young woman. What medical conditions should be considered?
- Lynch $
- PCOS
What is the precursor lesion of Endometroid carcinoma?
- precursor ATYPICAL hyperplasia
What is the precursor lesion of serous CA?
precursor serous intra-epithelial carcinoma
Name the 2 main types of endometrial carcinoma.
- Endometroid (and Mucinous) -TYPE 1
2. Serous (and clear cell) - TYPE 2
Which type of endometrial carcinoma is a.w unopposed estrogen?
TYPE 1
(the endometroid ca- mucinous)
—–
Which type is most likely to affect post-menopausal women?
Serous (clear cell)- TYPE 2
Which endometrial ca may have a mutated TP53?
Serous (clear cell)
—-has the mutation and OVEREXPRESSES it
What mutations are a.w Type 1 Endometrial CA?
- PTEN
- KRAS
- PIK3CA
What is microsatelite instability?
- condition of genetic hypermutability results from IMPAIRED DNA mismatch repair
- —seen in Type I endometrial CA
Why is Lynch $ a predisposition to cancer?
- d.t INHERITANCE of a defective DNA mismatch repair gene
- autosomal dominant inheritance
How to manage type II tumors?
- with surgery (more extensive)
- adjuvant chemo-/radiotherapy
What is seen histologically for Serous Carcinoma?
- complex papillary and/or GLANDULAR architecture
- w/ diffuse, marked nuclear pleomorphism
What s meant by pleomorphism?
- cells of all shapes and sizes
Describe serous carcinoma.
- tufts and papillae (not glands)
- tubules with LOBSTER claw appearance containing highly pleomorphic tumor cells
What does the prognosis of endometrial CA depend on?
- Stage
- Histological Grade
- Depth of myometrial invasion
Do you grade endometrial ca; if so what are the grades?
YES ; mainly for endometroid carcinoma
- Gr.1: 5% of less solid
- Gr. 3: >50% solid growth
At what stage does the tumor INVADE the bladder/ bowel mucosa
- Stage IV
Why is endometrial stromal sarcoma high grade?
- infiltrate myometrium
- lymphovascular spaces
How does a carcinosarcoma look like grossly?
- large, bulky tumor (fills the cavity)
- protrudes through the cervical canal
Name myometrial lesions.
- Leiomyoma (V.COMMON)
2. Leiomyosarcoma (RARE)
Describe the gross appearance of leiomyomas.
- sharply circumscribed
- FIRM
- WHORLED cut surface
- may occur singularly or MULTIPLE!
Does leiomyosarcoma arise from leiomyoma?
NO
—-they arise de novo from the mesenchymal cells of the myometrium