Uterus - Hyperplasia, Malignant tumors of Endometrium, Stroma, and Myometrium & Fallopian Tubes Flashcards
What is endometrial hyperplasia defined as?
- An increase in the number of glands relative to the stroma, appreciated as crowded glands, often with abnormal shapes
What causes endometrial hyperplasia?
- The balance between estrogen and progesterone is disturbed, resulting in absolute or relative increases in the amount of estrogen, with consequent hyperplasia of the endometrial glands
What does endometrial hyperplasia cause?
- Abnormal uterine bleeding
What conditions cause increased estrogen?
- Anovulation
- Obesity
- Menopause
- Prolonged administration of estrogenic substances
- Polycystic ovarian syndrome
- Excessive ovarian cortical funciton
- Functioning ovarian tumors
What is a common genetic alteration seen in endometrial hyperplasia and endometrial cancer?
- Inactivation of PTEN tumor suppressor gene
What is Cowden syndrome?
- Multiple hamartoma syndrome
- Germline PTEN mutation and high incidence of endometrial and breast cancer
What does a loss of PTEN lead to?
- Overactivation of the PI3K/AKT pathway
What does the PI3K/AKT pathway do?
- Up-regulates the activity of glucose transporters and multiple glycolytic enzymes, thus increasing glycolysis
- Promotes shunting of mitochondrial intermediates to pathways leading to lipid biosynthesis
- Stimulates factors that are required for protein synthesis
What are the two major types of endometrial hyperplasia?
- Typical hyperplasia
2. Atypical hyperplasia
What is the cardinal feature of typical hyperplasia?
- Increase in gland to stromal ratio
What are some features of typical hyperplasia?
- Variation in size and shape of glands (dilated)
- Can be back to back glands but usually intervening stroma remains
- Rarely progresses to cancer
What is seen in atypical hyperplasia?
- Complex pattern of proliferating glands displaying nuclear atypia
- Glands are back to back and branching
- Loss of orientation of nuclei to basement membrane
- Nuclear chromatin open
- Conspicuous nuclei
- Overlap with well differentiated cancer
What is the most common invasive cancer of the female genital tract?
- Endometrial cancer
What is the peak age for type 1 endometrial cancer?
- 55-60
What are some clinical features of endometrial cancer?
- No screening test available
- May be asymptomatic for a period, usually produces irregular or postmenopausal bleeding which helps lead to early detection and cures
How is a diagnosis made in endometrial cancer?
- Histologic examination of tissue obtained by biopsy or curettage
- Analyzed for evidence of DNS mismatch repair defects because 3%-5% of women with endometrial cancer have Lynch syndrome and are at high risk for colon cancer
What is the peak age for type 2 endometrial cancer?
- 65-75
What is the clinical setting for type 1 endometrial cancer?
- Unopposed estrogen
- Obesity
- Hypertension
- Diabetes (abnormal GTT in 60%)
- Infertility
What is the clinical setting for type 2 endometrial cancer?
- Atrophy
- Thin physique
What is the morphology of type 1 endometrial cancer?
- Endometrioid
What is the morphology of type 2 endometrial cancer?
- Serous
- Clear cell
- Mixed Müllerian tumor
What is the precursor lesion in type 1 endometrial cancer?
- Hyperplasia
What is the precursor lesion in type 2 endometrial cancer?
- Serous endometrial intraepithelial carcinoma
What mutated genes are seen in type 1 endometrial cancer?
- PTEN
- MSI
What mutated genes are seen in type 2 endometrial cancer?
- TP53
What is the behavior of type 1 endometrial cancer?
- Indolent
- Spreads via lympatics
What is the behavior of type 2 endometrial cancer?
- Aggressive
- Intraperitoneal and lymphatic spread
What are the different stages of endometrial cancer?
- Stage 1: confined to corpus uteri itself
- Stage 2: Involves the corpus and the cervix
- Stage 3: Extends outside the uterus but not outside the true pelvis
- Stage 4: Extends outside the true pelvis or involves the mucosa of the bladder or rectum
What are malignant mixed müllerian tumors?
- Endometrial adenocarcinomas with a malignant mesenchymal component
- Mutations similar to endometrial carcinomas in the epithelial component (TP53, PTEN, PIK3CA)
- Sarcomatous mesenchymal component
What is the presentation of malignant mixed müllerian tumors?
- Postmenopausal bleeding
- Outcomes depend on depth of invasion and stage
- Heterologous elements (cartilage, muscle, adipose tissue, bone) = worse outcome
What genes are involved in leiomyoma?
- HMGIC and HMGIY
- MED12 in 70% (encodes a component of Mediator which allows cells to divide in an uncontrolled way)
What are the gross features of a leiomyoma?
- Sharply circumscribed
- Single of multiple
- Small or large
- Firm grey-white mass
- Subswersal, myometrial, submucosal
- Rarely uterine ligaments, LUS, or cervix
What are some microscopic features of leiomyoma?
- Bundles of smooth muscle cells
- Uniform in size and shape, oval nucleus, long bipolar processes
- Rare mitoses
- Can degenerate
What are some clinical signs of a leiomyoma?
- Even when large, could be asymptomatic
- Abnormal bleeding
- Urinary frequency
- Sudden pain from infarction of a large or pedunculated tumor
- Impaired fertility
What do leiomyomas cause in pregnant women?
- Increase the frequency of spontaneous abortion/premature delivery, fetal malpresentation, uterine inertia, and postpartum hemorrhage
Do leiomyomas transform to leiomyosarcomas?
- Rarely
What are some features of leiomyosarcomas?
- Uncommon
- Peak age 40-60
- Arise from myometrium or a stromal precursor cell
- Complex karyotypes that include deletions (also the MED12)
- Recurrence common
- More than half metastasize
What are some microscopic features of a leiomyosarcoma?
- Nuclear atypia
- Increased mitotic index (10 or greater is diagnostic) = malignant
- Zonal necrosis
What is the outcome for leiomyosarcoma?
- 5 year survival is 40%
- High grade tumors only 10%-15%
Why is lung the most common site of mets for leiomyosarcoma?
- Uterine vein goes up to the IVC which goes to the lung
What are the major disorders that affect the fallopian tubes?
- Infections associated inflammatory conditions
- Ectopic pregnancy
- Endometriosis
What are the most common bacteria that cause infection in the fallopian tubes?
- N. gonorrhea in 60%
- Chlamydia in the rest
What is tuberculous salpingitis?
- Rare in this country
- Cause of infertility where endemic
- Have necrotizing granulomas
What is the most common primary lesion of the fallopian tube?
- Translucent cysts that are filled with a clear serous fluid calle paratubal cysts
- If found near the fimbriated end of the tube, they are call hydatids of Morgagni
What is a benign tumor of the fallopian tubes?
- Adenomatoid tumors (mesothelioma)
What is a malignant tumor of the fallopian tubes?
- Primary adenocarcinoma of the fallopian tubes (rarest gynecological malignancy)
