Endometrial and Myometrial Neoplasia Flashcards
Endometrial Hyperplasia Definition
Excessive growth of endometrial tissue (increased density of gland units) with tissue architectural alterations.
Endometrial Hyperplasia Incidence
No firm numbers, but not rare. Occurs primarily in the later reproductive years and early post-menopause.
Endometrial Hyperplasia Cause
•Prolonged estrogen stimulation of the endometrium (important!)
a) Increased endogenous estrogen (obesity, polycystic ovarian disease, estrogen producing tumors of ovary)
b) Exogenous: estrogen replacement therapy
Endometrial Hyperplasia Effect
Abnormal bleeding
Endometrial Hyperplasia Classification
a. Architectural: SIMPLE: Increased gland number and irregularity of glands in size, shape and spacing. COMPLEX: More densely packed glands with marked irregularity in size and shape.
b. Cytological:
- WITHOUT ATYPIA: Nuclear enlargement and size variation; chromatin evenly distributed; nucleoli not prominent; multilayering of cells may occur.
- WITH ATYPIA: Greater increase in nuclear size, pleomorphism, prominent nucleoli and coarse, irregularly distributed chromatin; loss of cellular polarity.
c. New alternative terminology: Endometrial intraepithelial neoplasia (EIN). It is roughly synonymous with “complex atypia with atypia”
Endometrial Hyperplasia Treatment
Remove source of excessive estrogen, curettage, progesterone suppression, hysterectomy are possible means.
Endometrial Hyperplasia Clinical Course
- Immediate problem of abnormal bleeding usually can be managed satisfactorily (transfusions, hormones, etc.).
- However, hyperplasia is an important risk factor for adenocarcinoma. Carcinoma risk ranges from 1% (simple hyperplasia w/o atypia) to 29% (complex with atypia). The presence of atypia (or EIN) is especially important, as it indicates a high risk for carcinoma.
Endometrial intraepithelial neoplasia (EIN)
- EIN is a more recently introduced term
- It may be a more reproducible diagnostic entity
- It is considered a precursor for type I endometrial carcinoma (i.e. endometrioid adenocarcinoma)
- The diagnostic features overlap those of atypical endometrial hyperplasia (AEH)
Endometrial Carcinoma
•Endometrial cancer is currently classified as 2 types.
- Type I endometrial cancer is estrogen-driven with the prototype being endometrioid adenocarcinoma.
- Type II endometrial carcinoma is non-estrogen driven with the prototype being serous carcinoma.
Endometrial Carcinoma Incidence
- Most common invasive cancer of female genital tract.
- 90% of patients are older than 40 years, mainly 50-60’s.
- Incidence is on the rise, supplanting cervical cancer as the #1 GYN cancer.
-There is both an absolute increase in endometrial cancer cases and a relative increase due to the decreasing incidence cervical cancer.
Endometrial Carcinoma Cause
•Excess estrogen (see hyperplasia) is common in Type I cancer. A higher risk of endometrial carcinoma is seen in the following:
a. Obesity
b. Diabetes
c. Hypertension
d. Infertility
•There is no known cause for type II cancers.
Endometrial Carcinoma Effect
- PMB (post-menopausal bleeding) or abnormal bleeding.
- The uterus may remain small (especially in type II tumors) or become enlarged.
Endometrial Carcinoma Morphology
•Diffuse or polypoid growth pattern. Spread via direct myometrial invasion to surrounding tissues. Two major categories of carcinoma are recognized:
a. Endometrioid adenocarcinoma (Type I, 85% of endometrial carcinoma) showing gland patterns that resembles normal endometrium. These are usually lower grade tumors with a relatively good prognosis.
b. Aggressive sub-types (Type II cancers): 15 to 20% of cases are serous, clear cell, and carcinosarcoma. They occur in older women (average age of 60-70’s) and are usually high grade tumors.
Endometrial Carcinoma Histological Grading
a. FIGO Grade 1: well-defined glands with solid areas less than or equal to 5%
b. FIGO Grade 2: tumor with solid areas between 6% to 50%
c. FIGO Grade 3: tumor with solid areas more than 50%
Endometrial Carcinoma Nuclear Grading
a. Nuclear Grade 1: Nuclei of the tumor cells with minimal atypia and pleomorphism
b. Nuclear Grade 2: Nuclei of the tumor cells shows intermediate level of atypia and pleomorphism
c. Nuclear Grade 3: Nuclei of the tumor cells with dramatic atypia and pleomorphism
Endometrial Carcinoma Treatment
- Treatment is usually hysterectomy and bilateral salpingo-oophorectomy.
- Depending on the type of tumor and tumor stage, there may also be a lymph node resection, radiation therapy and/or chemotherapy
Endometrial Carcinoma Clinical Course
•Prognosis depends heavily on clinical stage, histologic grade and subtype.
-For example, surgery (+/- irradiation), gives about a 95% 5-year survival in patients with stage I and grade 1 or 2 diseases. This rate drops to 50% for stage II and III endometrial carcinomas.
Carcinosarcoma a (mixed müllerian malignancy) Definition
- Endometrial adenocarcinomas in which there is also a malignant stromal differentiation.
- The stroma can differentiate into malignant muscle, cartilage and bone.
- The epithelial and mesenchymal components are derived from the same tumor cells and represent two faces of the same tumor.
- They occur in postmenopausal women
Carcinosarcoma a (mixed müllerian malignancy) Cause
Not related to estrogen
Carcinosarcoma a (mixed müllerian malignancy) Effect
Postmenopausal bleeding
Carcinosarcoma a (mixed müllerian malignancy) Morphology
- Grossly, a large mass often beyond uterus at diagnosis.
- Histologically consist of adenocarcinoma mixed with the stromal (sarcoma) elements
Carcinosarcoma a (mixed müllerian malignancy) Clinical Course
- Outcome is determined by depth of invasion and stage.
- Highly malignant: 25-30% 5-Year Survival.
Mesenchymal Malignancies
•Two types, both uncommon:
- Leiomyosarcoma
- Endometrial Stromal Tumors
•Common features: Late reproductive years or after menopause, mass or abnormal bleeding, no estrogen connection, hematogenous spread
Mesenchymal Malignancies: Leiomyosarcoma
- Peak incidence 40-60 yrs.
- Bulky, often hemorrhage mass, often with necrosis.
- Microscopic: high mitotic rate > 5 mitoses/10HPF, pleomorphic nuclei, coagulation necrosis.
- 40% 5-Year Survival.
Mesenchymal Malignancies: Endometrial Stromal Tumors
•Comprise a spectrum of tumors from benign stromal nodules (mature monotonous cells, non-invasive) to undifferentiated sarcomas with invasion into myometrium and vasculature, pleomorphic nuclei, numerous mitoses, and 50% 5 Year Survival.
Benign Mesenchymal Neoplasm: Leiomyoma
Benign smooth muscle tumor. Not restricted to uterus but stimulated by estrogen in this site.
Benign Mesenchymal Neoplasm: Leiomyoma Incidence
The most common tumor in women; occur in 25% women during reproductive years; multiple lesions common.
Benign Mesenchymal Neoplasm: Leiomyoma Cause
Localized, heightened sensitivity to normal levels of estrogen.
Benign Mesenchymal Neoplasm: Leiomyoma Effect
Asymptomatic, mass, abnormal bleeding (if submucosal), impaired fertility, dystocia (difficult labor), and rarely sarcoma.
Benign Mesenchymal Neoplasm: Leiomyoma Morphology
- Characteristic gross appearance (whorled, gray-white, sharp circumscription).
- Location intramural > subserous > submucous.
- Microscopic: mature smooth muscle with rare mitoses
Benign Mesenchymal Neoplasm: Leiomyoma Treatment
None unless symptomatic; myomectomy, hysterectomy
Benign Mesenchymal Neoplasm: Leiomyoma Clinical Course
Develop and grow in reproductive years; degenerate and shrink after menopause.
Benign Mesenchymal Neoplasm: Leiomyoma Clinical Manifestations
•Clinical manifestations vary depending on the tumor locations (heavy menstruation with submucosal, asymptomatic with intramural, and torsion with subserosal tumors), size (small asymptomatic and increasing pelvic pressure in large tumors), and specific events (sharp pain in tumors with hemorrhage).
Endometrial Adenocarcinoma
Endometrial Adenocarcinoma
Endometrial Serous Carcinoma
Endometrial Serous Carcinoma
- CLEAR CELL CARCINOMA (CCC)
- Architecture: Papillary, tubulo-acinar, and solid
- Cytoplasm: Clear or eosinophilic cytoplasm
- Cytology: Usually high-grade, irregular nuclei, sometimes with hobnailing features
Clear Cell Carcinoma
- CARCINOSARCOMA MALIGNANT MIXED MULLERIAN TUMOR (MMMT)
- Malignant epithelium (adenocarcinoma) with malignant stromal/mesenchymal component (sarcoma)
- Both components arise from endometrial epithelial cells (de-differentiation)
- Age: Postmenopausal
- Sign: Abnormal bleeding
- Carcinoma component metastasizes more frequently than sarcomatous component
- 25-30% 5 year survival
Leiomyosarcoma
