Lecture 7.1: Body of th Uterus and Endometrium Flashcards
Which autosomal dominant disorder is due to germline mutations of PTEN and is associated with high incidence of endometrial carcinoma and breast cancers?
Cowden syndrome
Why is it important to make the distinction between adenosarcomas and large benign polyps of the endometrium?
Adenosarcoma is estrogen-sensitive and responds to oophorectomy
Type II endometrial carcinomas are by definition what grade of tumor?
Poorly differentiated (grade 3) tumors
An inactivating mutation of which tumor suppressor gene is a common genetic alteration in both endometrial hyperplasia and endometrial carcinomas; which pathway does this regulate?
- PTEN important regulator of PI3K/AKT pathway
- Loss of PTEN leads to overactivation of this pathway
Between which days of the menstrual cycle will you see dilation of gland which appear tortuous and serrated or “saw-toothed?”
Glands dilate days 18-24
When the lesions of endometriosis are extensive, organizing hemorrhage causes what?
Fibrous adhesions btw tubes, ovaries and other structures and obliterates the pouch of Douglas
What is the appearance of endometrial polyps?
- Exophytic masses which may be single or multiple and usually sessile
- Occasionally large and pedunculated
What is the gross morphology and size of malignant mixed müllerian tumors?
Often bulky and polypoid, and may protrude through the cervical os
Ascending infection by which organism is a common cause of both acute and chronic endometritis?
Chalmydia trachomatis
Women with endometriosis have a 3x greater risk for development of what 2 cancers?
Ovarian and clear cell types
Briefly describe what stage I-IV indicate for both type I and II endometrial adenocarcinoma and malignant mixed mullerian tumors?
- Stage I: confined to corpus uteri
- Stage II: involves corpus AND cervix
- Stage III: extends outside the uterus, but NOT outside true pelvis
- Stage IV: extends outside the true pelvis or involves mucosa of bladder or rectum
Distinction of leiomyosarcoma from leiomyoma is based on what cellular features?
Nuclear atypia + mitotic index + zonal necrosis
Based on histology what must be present for the diagnosis of endometriosis to be readily made?
When both endometrial GLANDS and STROMA are present, with or without the presence of hemosiderin
The sarcomatous component of malignant mixed müllerian tumors may mimic what tissues?
Striated muscle, cartilage, adipose tissue, and bone
Based on the anatomy why do leiomyosarcomas often metastasize to the lung?
Tumor invades uterine vein and goes straight to lungs
Endometriotic lesions bleed periodically in response to extrinsic (ovarian) and intrinsic hormonal stimulation producing what?
Nodules w/ red-blue to yellow-brown appearance on or just beneath the mucosal and/or serosal surfaces at site involved
What are 5 disorders associated with development of endometrial carcinoma?
- Obesity
- Diabetes (abnormal GTT in 60%)
- HTN
- Infertility
- Unopposed estrogen stimuulation
What is the histology of the glands seen in the endometrium during the proliferative phase of the menstrual cycle?
Straight, tubular structures lined w/ regular, tall, pseudostratified columnar cells
What is the most frequent cause of dysfunctional uterine bleeding; resulting from what?
Anovulation (failure to ovulate); due to subtle hormone imbalances
What is the behavior and prognosis of leiomyosarcomas like?
- OFTEN recur after surgey
- More than 1/2 metastasize hematogenously —> lungs, bone, and brain; may also disseminate throughout abdominal cavity
- Overall 5-year survival = 40%, but anaplastic lesions = 10-15%
What is the likelihood of non-atypical hyperplasia of the endometrium progressing to adenocarcinoma; what may be seen morphologically when estrogen is withdrawn?
- Rarely progress to cancer (1-3%)
- May evolve into cystic atrophy when estrogen is withdrawn (after menopause)
In sporadic endometrioid carcinomas, loss of expression of DNA mismatch repair genes is commonly caused by what?
Epigenetic silencing (via promoter hypermethylation)
Endometrial hyperplasia is an important cause of abnormal bleeding and is also important due to what?
Frequent precursor to the most common type of endometrial carcinoma
What makes serous endometrial intraepithelial carcinoma a pre-malignant lesion if the cells are the same as serous carcinoma?
Lack of identifiable stromal invasion (are confined to epithelial surface)
When their is failure of ovulation what hormonal imbalance occurs?
Excessive endometrial stimulation by estrogen that is unopposed by progesterone
What is the peak age range for type I endometrial carcinoma and what is an early sign?
- Age = 55-65 y/o = post-menopausal
- Vaginal bleeding in older women = early sign
What is necessary for establishing the diagnosis of endometrial carcinoma?
Histological examination of tissue obtained by biopsy or curettage
What are the morphological and cellular features (chromatin and nucleoli) which encompass atypical hyperplasia (EIN) of the endometrium?
- Complex patterns of proliferating glands displaying nuclear atypia
- Glands are commonly back-to-back and branching
- Nuclei w/ open (vesicular) chromatin and conspicuous nucleoli
Which chromosomal translocation has been linked to low-grade endometrial stromal sarcomas?
JAZF1-SUZ12
Endometrial stromal neoplasms are divided into what 2 categories?
1) Benign stromal nodules
2) Endometrial stormal sarcomas: either high- or low-grade
What is the metaplastic theory in relation to the pathogenesis of endometriosis?
Endometrium arises from coelomic mesothelium or mesonephric remnant that undergo endometrial differentiation giving rise to ectopic tissue
Of the 2 classifications of endometrial carcinoma, which is the most common type accounting for 80% of cases?
Type I
What stromal changes are seen in the late secretory phase of the menstrual cycle?
- Prominent spiral arterioles appear by day 21-22 accompanied by ↑ ground substance and edema btw stromal cells
- Stromal hypertrophy –> ↑ cytoplasmic eosinophilia (predecidual change) + resergence of stromal mitoses
- Sparse infiltrate of neutrophils and lymphocytes appear
Defects in what are associated with a higher prevalence of endometrial carcinomasa arising in women from families w/ HNPCC (aka Lynch Syndrome)?
DNA mismatch repair genes
What is the morphology of type I endometrial carcinoma?
- Endometrioid –> most are well-differentiated
- Can take form of localized polypoid tumor or one that diffusely infiltrates the endometrial lining
Mutation in which gene encodign a component of Mediator allowing uncontrollable cell division has been implicated in 70% of leiomyomas?
MED12
Activating mutations in which gene associated with endometrial carcinomas seems to play a role in invasion?
PIK3CA
What is the behavior of type II (serous) endometrial carcinomas and how does it spread?
- Aggressive
- Intraperitoneal –> travel through fallopian tubes and implants on peritoneal surfaces and lymphatic spread
What are the 2 distinct patterns by which leiomyosarcomas grow within the uterus?
1) Bulky, fleshy masses that invade uterine wall
2) Polypoid masses that project into uterine lumen
List the 8 most common sites of endometriosis in descending order of frequency.
- Ovaries
- Uterine lig.
- Rectovaginal septum
- Cul de sac
- Pelvic peritoneum
- Large and small bowel and appendix
- Mucosa of cervix, vagain, and fallopian tubes
- Laparotomy scars