GYNECOLOGIC PATHOLOGY- ENDOMETRIUM

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I. ENDOMETRIUNL NORMAL HISTOLOGY
II. ENDOMETRIUM: INFLAMMATIONS
III. ENDOMETRIUM: ECTOPIC
IV. ENDOMETRIUM: FUNCTIONAL DISORDERS
V. ENDOMETRIUM: HYPERPLASIA
VI. ENDOMETRIUM: POLYPS
VII. ENDOMETRIUM: CARCINOMA
VIII. ENDOMETRIUM: RISK FACTORS FOR ADENOCARCINOMA
IX. ENDOMETRIUM: ENDOMETRIOID ADENOCARCINOMA
X. ENDOMETRIUM: POORLY DIFFERENTIATED SEROUS PAPILLARY AND CLEAR CELL ADENOCARCINOMA
XI. ENDOMETRIUM: TREATMENT AND PROGNOSIS OF CARCINOMA
XII. ENDOMETRIUM: STROMAL TUMORS
XIII. ENDOMETRIUM: CARCINOSARCOMA

I. ENDOMETRIUM: NORMAL HISTOLOGY

Menstrual Cycle (usually 28 days)- Controlled by hormonal interactions among the hypothalamus, pituitary and ovary

• Proliferative Phase
  
  
  • First half of cycle
  • Growth phase of cycle driven by estrogen
  • Straight tubular glands lined by pseudostratified columnar cells with mitotic figures and a cellular stroma
    
    
• Secretory Phase
  
  
  • Post-ovulatory phase controlled by progesterone from the corpus luteum of the ovary
  • If 50% of glands have subnuclear vacuoles then considered day 17 and ovulation has occurredcan be dated by histologic appearance to help assess hormonal status and causes of bleeding or infertility
  • Glands--no mitotic figures, no pseudostratification and presence of vacuoles, intraluminal secretions, serrated outlines depending on date
  • Stroma--develops edema, prominent spiral arterioles, and predecidual change depending on date
    
    
• Menstrual Phase
  
  
  • Upper two thirds of endometrium shed
  • The lower third (basalis) does not shed-source for regenerating endometrium in next cycle
  • Exhausted late secretory endometrium with glandular and stromal breakdown, hemorrhage, fibrin, and neutrophils

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II. ENDOMETRIUM: INFLAMMATIONS

• Acute Endometritis- Uncommon bacterial infection (strep, staph) usually after delivery or miscarriage secondary to retained products of conception
  
  
  • Histopathology--neutrophils filling and destroying glands
    
    
• Chronic Endometritis
  
  
  • Bleeding, pain, discharge, infertility pelvic inflammatory disease
  • Retained products of conception
  • IUD
  • Tuberculosis
  • Non-specific--possibly due to Chlamydia
  • Histopathology--plasma cells/spindle stroma/ dysynchronous glands and stroma

III. ENDOMETRIUM: ECTOPIC

• Adenomyosis- Nests of endometrium deep within the myometrium (at least 2-3mm beneath basalis)
  
  
  • 15-20% of uteri
  • Menorrhagia, dysmenorrhea, dyspareunia, pelvic pain
    
    
• Endometriosis- endometrial glands or stroma outside the uterus
  
  
  • Ovaries>uterine ligaments>rectovaginal septum>pelvic peritoneum>laparotomy scars>umbilicus=vagina=vulva=appendix
  • Infertility, dysmenorrhea, pelvic pain
  • Pathogenesis- regurgitation/metaplasia/lymphovascular
  • Histopathology- two of three elements: glands, stroma, hemosiderin

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IV. ENDOMETRIUM: FUNCTIONAL DISORDERS

• Anovulatory Cycles- prolonged estrogenic effect resulting in persistent proliferative(disordered) endometrium with mild architectural changes and stromal breakdown
  
  
• Inadequate luteal phase- low progesterone from inadequate corpus luteum resulting in secretory endometrium which lags behind expected date
  
  
• Oral Contraceptives- exogenous hormones resulting in inactive endometrial glands within a decidualized stroma
  
  
• Postmenopausal Changes- anovulatory cycles and ovarian failure resulting in mild architectural changes and eventually developing into cystic atrophy

V. ENDOMETRIUM: HYPERPLASIA

• Can be caused by exposure to increased levels of unopposed estrogen
  
  
  • Anovulation
  • Polycystic ovarian disease (Stein-Leventhal syndrome)
  • Functioning granulosal cell tumors of ovary
  • Cortical stromal hyperplasia of ovary
  • Estrogen replacement therapy
    
    
• Hyperplasia Without Cytologic Atypia (low grade)
  
  
  • Simple hyperplasia
    • Increase in glands (irregular and cystic) and stroma
    • Rarely progress to carcinoma
  • Complex hyperplasia
    • Glandular crowding and branching with a complex growth pattern
    • Less than 5% progress to carcinoma
  • Treatment- usually hormone therapy-progestins/surgery
    
    
• Atypical Hyperplasia (high grade)
  
  
  • Histopathology- architectural complexity combined with atypical nuclear features
    • Irregular epithelial lining--tufting, stratification, scalloping
    • Cytomegaly, loss of polarity, hyperchromatism, prominence of nucleoli, increased nuclear to cytoplasmic ratio
  • Approximately 25% progress to carcinoma
  • Treatment
    • Progestins
    • Surgery

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VI. ENDOMETRIUM: POLYPS

• Sessile masses of variable size (0.5-3.0 cm) projecting into endometrial cavity which may be asymptomatic, bleed or become necrotic
  
  
• Types of Polyps
  
  
  • Functional- cycle with adjacent endometrium
  • Hyperplastic- non-cyclic and usually cystic
    
    
• Rarely carcinomas arise in polyps
  
  
• Some are associated with Tamoxifen therapy used in the treatment of breast cancer

VII. ENDOMETRIUM: CARCINOMA

• Most common cancer of female genital tract(34,000 new cases/year)
  
  
• 7% of all invasive cancer in women excluding skin cancer
  
  
• Usually arise in postmenopausal women-uncommon under 40
  
  
• Often present with postmenopausal bleeding
  
  
• Infrequently endometrial and breast carcinoma occurs in same patient

VIII. ENDOMETRIUM: RISK FACTORS FOR ADENOCARCINOMA

• Obesity
  
  
• Diabetes
  
  
• Hypertension
  
  
• Infertility
  
  
• Single, nulliparous, anovulatory cycles

IX. ENDOMETRIUM: ENDOMETRIOID ADENOCARCINOMA

• Arises in a background of prolonged estrogen stimulation and endometrial hyperplasia
  
  
• Associated with above mentioned risk factors
  
  
• Usually well differentiated with a favorable prognosis
  
  
• Histopathology--adenocarcinoma with malignant stratified columnar cells often with foci of squamous differentiation
  
  
• Contiguous spread through myometrium with late distant metastases

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X. ENDOMETRIUM: POORLY DIFFERENTIATED SEROUS PAPILLARY AND CLEAR CELL ADENOCARCINOMA

• Older Women
  
  
• Poorer Prognosis
  
  
• Predisposing Factors are Unclear
  
  
• Histopathology- superficial endometrial involvement with a papillary to solid growth pattern with high grade nuclear atypia
  
  
• May be extensive peritoneal disease via tubal or lymphatic spread rather than direct invasion
  
  
• Distant Metastases More Common

XI. ENDOMETRIUM: TREATMENT AND PROGNOSIS OF CARCINOMA

• 80% of women have stage I disease and have 90% 5 year survival after surgery and/or radiation
  
  
• Stage II disease has a 30-50% 5 year survival
  
  
• Higher stages have less than 20% 5 year survival

XII. ENDOMETRIUM: STROMAL TUMORS

• Benign Stromal Nodules- well circumscribed aggregates of stroma
  
  
• Low Grade Stromal Sarcoma (endolymphatic stromal myosis)
  
  
  • Well differentiated stromal cells infiltrating the myometrium and lymphatic channels
  • 50% of cases recur after 10-15 years
  • 15%of cases result in distant metastases and death
    
    
• High Grade Stromal Sarcoma
  
  
  • Sarcoma comprised of markedly atypical stromal cells having numerous mitoses and with infiltrate indistinct margins
  • Hematogenous spread typical of sarcomas resulting in distant metastases
  • 50% 5 year survival

XIII. ENDOMETRIUM: CARCINOSARCOMA (MALIGNANT MIXED MULLERIAN TUMOR)

• Carcinomatous and sarcomatous elements probably derived from same cell (both may stain positive for epithelial markers)
  
  
• Bulky, polypoid tumors occurring in postmenopausal women with bleeding and sometimes history of radiation
  
  
• Heterologous Type- extrauterine mesenchymal tissue cartilage, bone, striated muscle
  
  
• Homologous Type- intrauterine mesenchymal tissue stroma, smooth muscle
  
  
• Usually metastasize as carcinomas
  
  
• 25-30% five year survival

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