Benign and Malignant conditions of the Uterus - Gemer Flashcards
What is the incidence of uterine fibroids?
What increases and decreases the risk of fibroids?
Ultrasound examination: cumulative incidence by age 50 is >80% for black women and nearly 70% for white women
Pathological examination: prevalence of fibroids is as high as 77%
The leading cause of gynecological morbidity in women
Cause symptoms in approximately 20-25% of reproductive-aged women
The leading reason for hysterectomies in USA: 40% (>200,000 procedures) annually.
Increased risk in: African americans, age 25-54, family history and younger age at menarche
Reduced risk in: multiparity, smoking, older age at last birth and menopause, post-menopause
What are the classifications of uterine fibroids?
Submucosal: A fibroid which distorts the uterine cavity.
type 0 = pedunculated fibroid without intramural extension
type I = sessile with intramural extension of fibroid < 50%
type II = sessile with an intramural extension of >50%
Intramural: A fibroid which does not distort the uterine cavity and with < 50% of it protruding into the serosal surface of the uterus.
Subserosal: A fibroid is considered subserosal If > 50% of fibroid protrudes out of the serosal surface of the uterus.
What are the characteristics of leiomyomas?
How do hormones interact?
Estrogen receptors more highly expressed so estrogen increases proliferation
TGF-beta is overexpressed, hormonally-regulated and both mitogenic and fibrogenic
EGF is mediatory
What is the possible pathophysiology of bleeding in leiomyomas?
Of infertility?
Ulceration over submucous tumors
Increase in size of the endometrial surface area
Compression of the venous plexus of the adjacent myometrium and endometrium.
Increased vascularity and vascular flow to the uterus as it enlarges
Interference with normal uterine contractility
Dysregulation growth factors or their receptors
Mechanical disruption of gamete and embryo transport
Alterations in endometrial histology- impairing implantation site
Alterations in vascular flow
Reduced compliance for uterine growth
Intracavitary and subserosal are most associated with infertility, intramural are controversial
What are the dangers of fibroids during pregnancy?
Fibroids affect approximately 1-4% of pregnancies.
The majority of fibroids do not enlarge during pregnancy.
In 80% of women fibroids will either decrease in size during pregnancy or not change significantly
Approximately 10% will undergo red degeneration.
Increased risk for:
First-trimester bleeding
Premature rupture of membranes
Abruptio placentae
Breech presentation
Prolonged labor
Cesarean section
Low Apgar scores
Low-birth weight
How are uterine fibroids diagnosed?
Pelvic exam (referring to the tumor in gestational size in weeks)
Ultrasonography
CT / MRI
Hysteroscopy (leading instrument for intracavitary fibroids)
What are the treatments for leiomyomas?
Not until symptomatic( otherwise Expectant management)
Medical- GnRH agonists (downregulates receptors, decreases estrogen- cause medical menopause, only done before surgery)
-progesterone antagonists, Mirena, estrogen receptor modulators, aromatase inhibitors, growth factor antagonists
Uterine artery embolization (through the femoral artery using PVC particles, creates infertility)
High Frequency/MRI guided Focused Ultrasound (creates pulses of thermal energy to targeted tissue to induce necrosis)
Cryomyolysis (thin needles guided with laproscopy or ultrasound to freeze tumors)
Surgical
- Myomectomy: Abdominal / Laparoscopic / Hysteroscopic (with electric knife) - depends on location
- Total / Subtotal (retaining the cervix) abdominal hysterectomy (remove ovaries with family history of breast and ovarian cancer)
- Vaginal hysterectomy (if prolapsed, best cosmetic but poor ability to deal with other pelvic pathologies, can’t remove ovaries)
- Laparoscopic assisted vaginal hysterectomy
- Total / Subtotal Laparoscopic hysterectomy (shortest hospital stay and recovery period, minimal recuperative pain)
What are the indications for surgery of leiomyomas?
Not before symptoms!
Abnormal uterine bleeding with resultant anemia unresponsive to hormonal management (try other treatments first).
Chronic pain with severe dysmenorrhea or lower abdominal pressure and or pain
Acute pain as in torsion of pedenculated or prolapsing submucosal fibroid or necrosis.
Urinary symptoms or signs such as hydronephrosis.
Rapid uterine enlargement (related to malignancy)
Infertility, with leiomyoma as the only abnormal finding (especially if submucosal, need to do full workup to make sure)
Enlarged uterine size with compression symptoms and discomfort.
What is adenomyosis and how is it diagnosed?
What are symptoms?
How is it managed?
Histological diagnosis: the presence of endometrial glands within the myometrium At least one high power field away from the basis of the endometrium
Often coexistent with uterine leiomyoma
Average age of symptomatic women -40 or older
Islands of endometrial tissue with spongy appearance
Symptoms: Excessively heavy or prolonged menstrual bleeding, Dysmenorrhea- beginning prior to onset of menstrual follow
Signs: Enlarged soft and tender uterus
Diagnosis: Clinical- tentative with MRI support, Confirmed pathologically only at hysterectomy
Tx: NSAIDs, OCP (to stop menstruation), GnRH agonists, hysterectomy
What are the difference between noninvasive endometrial proliferations and how are they treated?
Simple hyperplasia
Complex hyperplasia
-If not atypical, can treat with progesterone and anti-estrogen medications (then follow up in 3-6 months)
-Can do D&C
Simple atypical hyperplasia
Complex atypical hyperplasia
-Have cytologic atypia
-CAH: More commonly progress to carcinoma
-Hysterectomy unless high risk
-Complex means glands in the back and irregular architecture
How common is endometrial carcinoma?
What increases and decreases risk?
Who should undergo screening
Most common gynecological malignancy
Median age 61 years
20-25% diagnosed before menopause
Documented relationship to unopposed estrogen exposure (PCOD, ERT – ext.)
Increased risk with tamoxifen exposure
Decreased risk with oral contraception
HNPCC gene (AD mismatch repair, 80% chance of colon cancer and 40-60% chance of endometrial cancer)
Obesity
Nulliparity
Late menopause (over 52 years)
Screening for postmenopausal women on estrogen, obese postmenopausal women esp wil HNPCC, and premenopausal women with anovulatory cycles (PCOS)
Any postmenopausal bleeding should be evaluated, 15% will be cancer
What are the subtypes of endometrial cancer?
How common is each?
Most to least common:
Endometroid (59.6%)
Adenocanthoma (21.7%)
Adenosquamous carcinoma
Clear Cell Carcinoma
Serous Papillary
Secretory Carcinoma
How are endometrial cancers spread?
Direct extension to adjacent structures (most common, can go through wall and into bladder and other structures).
Transtubal passage of exfoliated cells (through fallopian tubes).
Lymphatic dissemination.
Hematogenous dissemination.
How is endometrial cancer diagnosed?
Ultrasound –endometrial thickness
- <4-5mm after menopause
- If bleeding and thick biopsy
Endometrial biopsy
- Indicated if there is postmenopausal thick endometrium and bleeding
- Done with a thin cannula, anesthesia not required
Diagnostic curettage
Hysteroscopy
How is endometrial cancer staged?
Clincal and surgical staging from preoperative and intraoperative findings. Need to biopsy lymph nodes as well.
Stage I* Tumor confined to the corpus uteri
-80% of presenting patients
-86% survival rate
IA* No or less than half myometrial invasion
IB* Invasion equal to or more than half of the myometrium deep into uterine sidewall
Stage II* Tumor invades cervical stroma, but does not extend beyond the uterus
-If reaches cervix, treat like cervical cancer
Stage III* Local and/or regional spread of the tumor
IIIA* Tumor invades the serosa of the corpus uteri and/or adnexae (fallopian tubes and ovaries)
IIIB* Vaginal and/or parametrial involvement
IIIC* Metastases to pelvic and/or para-aortic lymph nodes
IIIC1* Positive pelvic nodes
IIIC2* Positive para-aortic lymph nodes with or without positive pelvic nodes
Stage IV* Tumor invades bladder and/or bowel mucosa, or distant metastases
IVA* Tumor invasion of bladder and/or bowel mucosa (rectum)
IVB* Distant metastases (lung), intra-abdominal metastases and/or inguinal lymph
What are the FIGO criteria for grading of endometrial cancer?
Primarily architectural (not cytological) according to the amount of non squamous solid growth overtaking glands.
Grade 1: 5% or less (more glands)
Grade 2: 6% - 50%
Grade 3: > 50%. (mostly solid areas)
The presence of marked tumor atypia increases the grade by one.
What are factors in the prognosis of endometrial cancer?
Age
Histologic type (clear cell worse)
Histologic grade
Myometrial invasion (more is worse)
Vascular space invasion (and lymph bad)
Tumor size (big is bad)
Lower uterine segment involvement (bad)
Peritoneal cytology
Hormone receptor status (presence of estrogen receptors is less aggressive because sign of differentiation, will respond to inhibitors)
DNA ploidy
Type of therapy (surgery vs. radiation)
What is the management of endometrial cancer?
Surgery: total abdominal hysterectomy and bilateral salpingo-oophorectomy
Surgical staging: peritoneal washings, pelvic and para-aortic lymph node biopsies, do with higher grades to determine treatment
Radiotherapy
Chemotherapy
Progestative treatment for those with estrogen receptors
Post-op:
Observation
Vault irradiation (if more advanced but lymph-negative, decreases recurrence)
External pelvic irradiation (to decrease risk and treat lymph nodes)
Extended-field irradiation (with para-aortic lymph involvement)
Whole abdominal irradiation
What are uterine sarcomas?
What is the treatment?
Rare tumors of mesodermal origin (not ectoderm, not glands, but stroma)
Highly malignant biological behavior
Symptoms aren’t distinguished from large leiomyomas (pain, pressure, bleeding)
2-6% of uterine malignancies
Increased risk following pelvic radiation
Bad prognosis if outside the uterus
Histological Types:
- Leiomyosarcoma (LMS)
- myometrial origin
- 1/3 of uterine sarcomas
- 0.5% of presumed fibroids after hysterectomy, diagnosis often post-op
- Factors for diagnosis include mitosis (>10/HPF), necrosis, bizarre giant cells - Endometrial stromal sarcoma (ESS)
- arise from endometrial stroma
- 15-25% of uterine sarcomas
- Subtypes: stromal nodule, low (with hormonal receptors) and high grade stromal sarcoma
- Mitotic rates and nuclear pleomorphism under microscope
- Diagnosed with curettage - Mixed mesodermal tumor (MMT)
- Previously diagnosed as sarcoma, malignant epithelial and stromal elements
- Usually postmenopausal
- Often protrudes into vagina through cervix
- Diagnose through curettage
Surgery: only treatment of proven curative value
Radiation: generally not effective, may improve local control without influencing outcome
Chemotherapy: moderate response rate
Prognosis: related to stage, survival similar among the 3 main histological variants
