LM 9.1: Endometrial/Uterine Cancers Flashcards
what is the most common gynecologic malignancy in the US?
endometrial cancer
typically in postmenopausal women
majority are diagnosed in early stages due to abnormal bleeding
what are the types of endometrial carcinomas?
type 1 and type 2
type 1 risk factors are related to excess estrogen states –> excess unopposed estrogen leads to overgrowth of endometrium
type 2 isn’t associated with estrogen excess
what are the risk factors for endometrial cancer?
- older age
- living in north america
- higher level of education or income
- white race
- nulliparity
- infertility
- mensrual irregularities
what is Lynch syndrome?
syndrome characterized by germline mutation of one of the mismatch repair genes
increased colon cancer, ovarian cancer, and type 1 endometrial cancer
AD
prophylactic hysterectomy with bilateral salpingo-oophorectomy is recommended when affected women reach 35 to 40 after childbearing is complete
who should get genetic screening for Lynch syndrome?
patients with endometrial or colorectal cancer and tumor evidence of:
1. microsatellite instability or
- DNA mismatch repair protein loss
first-degree relative with endometrial or colorectal cancer who was diagnosed:
1. before age 60 years or
- is at risk for Lynch syndrome based on personal and medical history
what is simple vs complex hyperplasia without atypic?
simple: glandular and stromal cell elements proliferate excessively –> glands are modestly crowded and typically display normal tubular shape or mild gland-shape abnormalities
complex: abnormal proliferation of primarily glandular elements – some specimens show architectural abnormalities such as papillary infolding
what does simple and complex hyperplasia with atypia look like histologically?
simple: glands are only mildly crowded – occasional glands show nuclear atypia characterized by nuclear rounding and visible nucleoli
complex: glands are markedly crowded and some have papillary infoldings – nuclei show variable atypia
what is the cancer risk associated with hyperplasia without atypia?
low chance of progression to cancer
may spontaneously regress without therapy
treatment is typically using synthetic progestins
how do you treat hyperplasia without atypia?
treatment is typically using synthetic progestins which:
- alter enzymatic pathways to convert estradiol into weaker estrogens
- decrease number of estrogen receptors in endometrial glandular cells
- stimulation of progesterone receptors leads to thinning of the endometrium and stromal decidualization
what is hyperplasia with atypia?
aka endometrioid intraepithelial neoplasia
significant numbers of glandular elements
exhibit cytologic atypia and disordered maturation
precursor to endometrial adenocarcinoma
how do you treat hyperplasia with atypia?
hysterectomy
can attempt high-dose progestin therapy for those wishing to preserve fertility and poor surgical candidates
what are endometrial polyps?
focal, accentuated, benign hyperplastic process composed of endometrial glands, fibrous stroma, and surface epithelium
most common presenting symptom is abnormal bleeding
most frequently in perimenopausal or immediately postmenopausal women
malignant transformation occurs in approximately 5%
what are the types of endometrial cancer?
- endometriod adenocarcinoma
2. non-endometrioid adenocarcinoma
what is endometriod adenocarcinoma?
type 1 endometrial cancer
endometrioid adenocarcinomas are composed of neoplastic glands resembling those of the normal endometrium
cells are typically tall columnar with mild to moderate nuclear atypia – they form glands that are abnormally crowded or “back-to-back”
gland cribriforming, confluence and villous structures with disappearance of intervening stroma distinguish well-differentiated endometrioid adenocarcinoma from complex hyperplasia
subtypes: endometrioid, endometrioid with squamous differentiation, villoglandular, secretory endometrioid
this is the most common type (80%)
“estrogen-dependent” risk factors
what is non-endometriod adenocarcinoma?
type 2 endometrial cancer
subtypes: serous, clear cell, mucinous, squamous, transitional cell, menonephric, undifferentiated
high grade with poorer prognosis than type 1 cancer
“estrogen independent” risk factors
occurs spontaneously characteristically in thin, postmenopausal women with an atrophic endometrium rather than hyperplastic
what do clear cell adenocarcinomas look like histologically?
type 2 endometrial cancer
composed of cells with clear to eosinophilic granular cytoplasm
cells are arranged in papillae, sheets, tubulocystic structures, or most often, some combination of these
eosinophilic hyaline globules are common
what is a common presenting history that’s associated with endometrial cancer?
most (98%) patients come in with abnormal uterine bleeding
in more advanced disease, patient may have pelvic discomfort or pressure
between 5-20% of women found to have endometrial cancer are asymptomatic
what pap smear result should make you worried about endometrial/cervical neoplasia?
atypical glandular cells found on Pap test carry higher risks for underlying cervical or endometrial neoplasia and requires further evaluation with colposcopy and endocervical curettage for endometrial sampling
if someone is presenting with pelvic pain, when must you do an endometrial biopsy to rule out carcinoma?
- patient is over 45
- patient is under 45 but with risk factors
D&C with hysteroscopy and directed endometrial biopsy can be performed if outpatient endometrial biopsy is unable to be completed
transvaginal ultrasound may also be used as an adjunct for evaluating endometrial thickness and looking for polyps, leiomyomas, and structural abnormalities of the uterus
endometrial thickness of >4mm in postmenopausal patient is an indication for further evaluation with endometrial biopsy
how does CA-125 levels play a role in endometrial cancer diagnosis and treatment?
pre-operative measurement of CA-125 level may be appropriate for assisting in predicting treatment response or in post-treatment surveillance but is not used for screening purposes
what are the grades of endometrial cancer?
G1: well-differentiated adenomatous carcinoma
G2: moderately differentiated adenomatous carcinoma
G3: poorly differentiated or undifferentiated
what are the stages of endometrial cancer?
I: tumor confined t the corpus uteri
IA: no or less than 1/2 myometrial invasion
IB: invasion equal to or more than half of the myometrium
II: tumor invades cervical stroma but does not extend beyond the uterus
II: local and/or regional spread of the tumor
IIIA: tumor invades the serosa of the corpus uteri and/or adnexae
IIIB: vaginal and/or parametrical involvement
IIIC: metastases to pelvic and/or paraaortic lymph nodes
IIIC1: positive pelvic nodes
IIIC2: positive paraaortic lymph nodes with or without positive pelvic lymph nodes
IV: tumor invasion of bladder and/or bowel mucosa and/or distant metastases
IVA: tumor invasion of bladder and/or bowel mucosa
IVB: distant metastases including intraabdominal metastases and/or inguinal lymph nodes
what are the poor prognostic variables in endometrial cancer?
- advanced surgical stage
- older age
- histologic type: UPSC or clear cell adenocarcinoma
- advanced tumor grade
- presence of myometrial invasion
- presence of lymphovascular space invasion
- peritoneal cytology positive for cancer cells
- increased tumor size
- high tumor expression levels of ER and PR
how do you treat endometrial cancer?
hysterectomy with complete surgical staging including bilateral salpino-oophorectomy, lymph node dissection, and peritoneal washings
women wishing to preserve fertility with G1 endometroid adenocarcinoma may be treated with high dose progestin and monitoring with serial endometrial sampling
women who are poor surgical candidates may be treated with therapeutic radiation and continuous chronic progestin treatment or levonorgesterel-releasing IUD, though results are suboptimal.
which patients are good candidates for conservative treatment of endometrial cancer?
- a well-differentiated, grade 1, endometrioid endometrial carcinoma
- no myometrial invasion
- no extrauterine involvement (no synchronous ovarian tumor or metastases, no suspicious retroperitoneal nodes)
- strong desire for fertility sparing
- no contraindications for medical management
- patient understands and accepts that data on cancer-related and pregnancy-related outcomes are limited (informed consent)
when would you use postoperative radiation for endometrial cancer?
postoperative radiation is used for known metastatic disease, positive lymph nodes, and cases of recurrence
women with intraperitoneal disease are treated with surgery followed by chemotherapy, radiation, or both
how do you do surveillance after treating endometrial cancer?
speculum and rectovaginal examinations every 3-4 months for 2-3 years then twice a year to detect recurrent disease, particularly in the vagina, for women who do not receive radiation therapy
serum CA-125 levels and CT or MRIs may be indicated for more advanced cancers that require radiation or chemotherapy
recurrent vaginal disease has better prognosis than pelvic recurrence
may respond to high-dose progestin therapy if estrogen-dependent cancer
what is a uterine sarcoma?
sarcomas originate from the myometrium or stromal components of endometrium
these tumors are very aggressive and are more likely to spread hematogenously
symptoms include progressive uterine enlargement, abnormal uterine bleeding, pelvic pain, increase in unusual vaginal disease
rare gynecologic malignancy accounting for approximately 3% of all cancers involving body of uterus and 0.1% of all myomas
how do you diagnose and treat uterine sarcomas?
diagnosis through surgical removal
treatment is hysterectomy with surgical staging
radiation and chemotherapy provide little survival advantage but can decrease recurrence rate
