B6M1 Case 5 TG

• Risk factors for endometrial carcinoma


  • Prolonged, unopposed estrogen stimulation of the endometrium
  • Infertility and a history of irregular menses as a result of anovulatory cycles
  • Late menopause
  • Excess estrone as a result of peripheral conversion of adrenally derived androsetenedione by aromatization in fat
  • Polycystic ovary syndrome
  • Functioning ovarian tumors
• Pathogenesis of endometrial carcinoma

  1. Estrogen-dependent tumors: Hyperplastic endometrium progresses to carcinoma

  2. Estrogen-independent tumors: Arise in atrophic endometrium, less differentiated, poorer prognosis
• Clinical manifestations of endometrial carcinoma

  • Vaginal bleeding or discharge as the most common presenting symptom
  • Pelvic pressure or discomfort
  • Asymptomatic in less than 5% of cases
• Tests for diagnosis of endometrial carcinoma


  • Office endometrial biopsy
  • Pap smear
  • Hysteroscopy and D&C
  • Transvaginal ultrasound
• Differential diagnosis of endometrial carcinoma

  • Endometrial atrophy
  • Endometrial polyps
  • Endometrial hyperplasia
  • Traumatic bleeding from atrophic vagina
• Classification of endometrial hyperplasia

  • Simple hyperplasia
  • Complex hyperplasia
  • Atypical hyperplasia
• Cytologic atypia in endometrial hyperplasia


  • Large nuclei of variable size and shape that have lost polarity
  • Increased nuclear-to-cytoplasmic ratios
  • Prominent nucleoli
  • Irregularly clumped chromatin with parachromatin clearing
• Risk of endometrial hyperplasia progressing to carcinoma is related to the presence and severity of cytologic atypia
• About 25% of patients with atypical hyperplasia have an associated endometrial carcinoma seen at hysterectomy
• Types of endometrial carcinoma

  • Endometrioid adenocarcinoma
  • Mucinous carcinoma
  • Papillary serous carcinoma
  • Clear cell carcinoma
  • Squamous carcinoma
• Endometrioid adenocarcinoma


  • Composed of glands resembling normal endometrial glands
  • Become less differentiated with more solid areas, less glandular formation and more cytologic atypia
• Variants of endometrioid adenocarcinoma

  • With squamous differentiation
  • Villoglandular
  • Secretory
• Mucinous carcinoma


  • More than half of tumor is composed of cells with intracytoplasmic mucin
  • Most have well-differentiated glandular architecture and good prognosis
• Papillary serous carcinoma


  • Resemble serous carcinoma of ovary and fallopian tube
  • Psammoma bodies frequently observed
  • Often associated with lymph-vascular space and deep myometrial invasion
  • Aggressive with poor prognosis
• Clear cell carcinoma


  • Usually has mixed histologic pattern
  • Cells often have a hobnail configuration
  • Characteristically occurs in older women and is a very aggressive type
• Squamous carcinoma


  • Rare, must have no connection with or spread from cervical squamous epithelium
  • Often associated with cervical stenosis, chronic inflammation and pyometria
  • Poor prognosis
• Types of uterine sarcoma

  • Endometrial stromal sarcoma
  • Leiomyosarcoma
  • Malignant mixed Mullerian tumor
• Endometrial stromal sarcoma


  • Composed of cells resembling normal endometrial stroma
  • Three types based on mitotic activity, vascular invasion and prognosis
• Leiomyosarcoma


  • Number of mitoses is most reliable microscopic indicator of malignant behavior
  • Tumors with <5 mitotic figures/10 hpf behave in benign fashion
  • Tumors with >10 are frankly malignant with poor prognosis
• Malignant mixed Mullerian tumor


  • Almost all occur after menopause
• Nuclear grading


  Takes precedence over histologic type in carcinoma
• Adenocarcinomas with squamous differentiation


  Graded according to the nuclear grade of the glandular component
• FIGO is the International Federation of Gynecology and Obstetrics
• Low-grade endometrial stromal sarcoma (ESS) or endolymphatic stromal myosis


  • Less than 10 mitotic figures per 10 high power fields; more protracted course; late recurrences
• High-grade or undifferentiated ESS


  • More than 10 mitotic figures per 10 high power fields; more aggressive
• There is no relationship between leiomyosarcoma (LMS) and parity and incidence of associated diseases
• History of prior pelvic radiation therapy is elicited in 4% of patients with leiomyosarcoma
• Number of mitoses


  Most reliable microscopic indicator of malignant behavior in leiomyosarcoma
• Leiomyosarcoma tumors


  • Tumors with less than 5 mitotic figures per 10 high power fields behave in benign fashion
  • Tumors with more than 10 mitotic figures per 10 high power fields are frankly malignant with poor prognosis
• Almost all malignant mixed Mullerian tumors (MMMT) occur after menopause
• Malignant mixed Mullerian tumor (MMMT)


  • Manifested as polypoid mass protruding from the endocervical canal in up to 50% of patients
  • Histologically a mixture of sarcoma and carcinoma
  • Carcinomatous element is usually glandular and sarcomatous element may resemble normal endometrial stroma (homologous or the so-called carcinosarcoma) or it may be composed of tissues foreign to the uterus, such as cartilage, bone or striated muscle (heterologous)
• Most patients should undergo surgical staging based on 1988 FIGO system (updated 2009)
• FIGO Surgical Staging for Endometrial Carcinoma (1988)


  • Stage Ia G123: No myometrial invasion
  • Stage Ib G123: Less than half myometrial invasion
  • Stage Ic G123: More than half myometrial invasion
  • Stage IIa G123: Extension to endocervical glands
  • Stage IIb G123: Cervical stromal invasion
  • Stage IIIa G123: Positive uterine serosa, adnexa, and/or peritoneal cytology
  • Stage IIIb G123: Vaginal metastasis
  • Stage IIIc G123: Metastasis to pelvic and/or para-aortic lymph nodes
  • Stage IVa G123: Tumor invasion of bladder and/or bowel mucosa
  • Stage IVb: Distant metastasis including intra-abdominal and/or inguinal lymph nodes
• Primary surgery followed by individualized radiation therapy has become the most widely accepted treatment for early stage endometrial cancers
• Five to fifteen percent of endometrial cancer patients have severe medical conditions that render them unsuitable for surgery
• Radiation alone can produce excellent survival and local control, but should be considered for definitive treatment only if operative risk is estimated to exceed the 10-15% risk for uterine recurrence expected with radiation treatment alone
• Ovarian cancer may be due to increased number of ovulation cycles. More common with nulliparity, early menarche, late menopause. There is some evidence to suggest ovulation induction may increase the chance for ovarian cancer. 1% of cases: BRCA-1 gene mutation
• Classification of ovarian cancers

  • Serous
  • Mucinous
  • Endometrioid
  • Clear cell
• Serous ovarian cancers


  • Epithelium similar to that of fallopian tube
  • Cyst contents: serous fluid
  • Solid papillary tumors
  • Most common type of epithelial cancers (75%)
• Mucinous ovarian cancers


  • Epithelium is similar to endocervical glands
  • Cyst content is mucin
  • Typically multilocular, thin-walled cysts with smooth external surface
  • 20% of epithelial cancers