Endometrial Hyperplasia and Carcinoma

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APGO educational topic number 50 for
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endometrial hyperplasia and carcinoma
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uterine carcinoma is the most common
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gynecologic malignancy and approximately
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2 to 3 percent of women will develop
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uterine cancer during their lifetime if
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the cancer arises from the glands of the
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endometrium it is an endometrial
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carcinoma if the cancer arises from the
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mesenchymal uterine components than it
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is a sarcoma 97 percent of uterine
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cancers are endometrial cancers and 3%
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are sarcomas fortunately most patients
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with endometrial cancer will have early
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presentation and 90 percent of women
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with endometrial cancer will develop
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symptomatic bleeding or discharge this
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can facilitate early diagnosis and most
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endometrial cancers are diagnosed in
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stage 1 the 5-year survival for women
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older than 65 is 81 percent for white
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women and 53% for black women the
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etiology for this disparity of outcomes
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is unclear and needs to be further
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investigated the objectives of this
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video are to identify risk factors for
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endometrial hyperplasia and cancer to
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describe the symptoms and physical exam
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findings with endometrial hyperplasia
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and cancer and to outline the causes
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diagnosis and management of
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postmenopausal bleeding endometrial
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hyperplasia is the most common precursor
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to endometrial carcinoma endometrial
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hyperplasia is organized into 4
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different World Health Organization
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classifications in simple hyperplasia
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both the glands and stromal cell
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elements proliferate excessively here
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are the glands G and the stroma s
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histologically the glands vary markedly
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in size from small to systole enlarged
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complex hyperplasia represents an
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abnormal proliferation of primarily the
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glandular elements without proliferation
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of the stromal elements thus will be an
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increased gland to stromal ratio the
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glands appear to be almost back-to-back
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the hyperplasia are then further
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classified depending on the presence or
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absence of nuclear a tibia we can thus
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have simple hyperplasia without a tibia
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and complex hyperplasia without a tibia
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simple hyperplasia with a tibia and Here
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I am drawing the simple glands again and
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complex hyperplasia with a tibia the
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difference is that atypical cells have
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disordered mature
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with nuclear enlargement thus have
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increased nuclear – cytoplasmic ratios
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which I am drawing here each of these
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four classifications has a defined risk
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of progression to cancer simple
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hyperplasia without atypia has a 1% risk
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complex hyperplasia without atypia has a
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3% risk simple hyperplasia with atypia
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has an 8% risk and complex hyperplasia
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with atypia has a 29% risk of
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progression of cancer as a fun aside
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notice how easy these numbers can be
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remembered if you think of multiples of
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3 1 3 9 27 or you could think of penny
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nickel dime quarter it’s close enough
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here is a histological slide of simple
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hyperplasia without atypia courtesy of
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dr. rich lieberman here is a gland G and
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stroma S this next histological slide is
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complex hyperplasia with atypia note the
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increased gland to stroma ratio and the
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increased nuclear to cytoplasmic ratio
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of these cells here the most significant
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risk factor for endometrial hyperplasia
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is exposure to unopposed estrogen which
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causes overgrowth of the endometrium
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this unopposed estrogen can come from
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exogenous or endogenous sources we will
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now move on to risk factors using our
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patient miss Edna metrium miss Edna is
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getting on in years and older age is our
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first risk factor the next risk factor
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is obesity for adipose tissue contains
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aroma taste which converts androstenone
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to ester own now miss Edna is receiving
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pills if these are high dose
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postmenopausal estrogen pills and this
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will significantly increase your risk of
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endometrial hyperplasia and cancer
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remember that estrogen must be given
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with progesterone for any patient with a
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uterus if she has a history of breast
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cancer and is taking tamoxifen then this
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would also be a risk factor tamoxifen is
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a selective estrogen receptor modulator
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and acts as an estrogen agonist on the
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endometrium poor miss Edna also has an
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ovarian mass and one specific type of
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ovarian cancer the granulosa cells to
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myrrh produces estrogen thus will be a
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risk factor other risk factors would
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include characteristics that increase
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the duration that the endometrium was
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exposed to estrogen stimulation so
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Nullah parity early menarchy and late
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menopause are all risk factors last
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Leith living in North America or
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northern Europe are risk factors as well
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here is a table that summarizes the risk
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factor and the estimated relative risk
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of developing endometrial hyperplasia or
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cancer older age two to threefold
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obesity two to fivefold high-dose
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estrogen ten to twenty fold tamoxifen
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three to seven fold infertility and
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nella parity threefold estrogen
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producing tumor greater than fivefold
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and residency in North America or
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Northern Europe three to eighteen fold
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notice that these three risk factors the
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high dose estrogens tamoxifen and
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residency in North America and Europe
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have the highest relative risks let’s
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move on to symptoms and physical exam
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findings we discussed earlier in this
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video that patients usually present
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early for the symptoms are often obvious
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to the patient I am having abnormal
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uterine bleeding having a high index of
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suspicion is important and an
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endometrial biopsy should be performed
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on any patient with abnormal uterine
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bleeding over 35 and a younger woman
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with additional risk factors that we
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have previously discussed transvaginal
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ultrasound may be used as an adjunct
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evaluation for postmenopausal women for
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an endometrial stripe of less than four
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millimeters indicates a low probability
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for endometrial cancer this point let’s
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start thinking about management to
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review we had early presentation with
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abnormal uterine bleeding we performed
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an endometrial biopsy which demonstrated
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endometrial hyperplasia what do we do
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now it will depend on what type of
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hyperplasia she has for simple and
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complex hyperplasia without atypia
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medical therapy with progesterone is the
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first-line therapy the risk of
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progression of cancer is very low and
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the progesterone therapy will decrease
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the glandular proliferation the most
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common progesterone therapy is oral
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Madrasi progesterone acetate when atypia
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is present there is more concern for
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progression at endometrial cancer of
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note simple hyperplasia with atypia is a
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relatively rare finding and we will
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focus on complex hyperplasia with atypia
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definitive therapy with hysterectomy is
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recommended once childbearing is
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complete for women with complex atypical
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hyperplasia for women who desire future
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fertility long term high-dose
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progesterone therapy may be attempted to
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avoid hysterectomy however this does
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require frequent endometrial sampling to
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ensure that disease progression has not
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occurred as we have discussed the
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etiology for most endometrial cancers is
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secondary to excess estrogen exposure
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and Dmitry all cancers
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estrogen dependent are classified as
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type one 90% of endometrial cancers are
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type one the more aggressive variety of
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endometrial cancer type two accounts for
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10% of cases there is no clear
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epidemiological profile for type 2
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cancers type 2 cancers tend to have
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aggressive high-grade nuclei or clear
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cell histology let’s discuss
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postmenopausal bleeding for a moment
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this is bleeding that occurs after 12
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months of amenorrhea the risk of
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endometrial cancer is 10 to 15 percent
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for these patients so endometrial
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sampling must occur other causes include
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endometrial atrophy which accounts for
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60 to 80 percent of postmenopausal
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bleeding hormone therapy 15 to 25
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percent endometrial polyps 2 to 12% and
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endometrial hyperplasia 5 to 10%
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therefore when a patient presents with
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postmenopausal bleeding the evaluation
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should include an endometrial biopsy
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careful physical and pelvic examination
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pelvic ultrasound and don’t forget to
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screen for cervical cancer with a pap
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smear this concludes the aapko
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educational video on endometrial
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hyperplasia and cancer we have reviewed
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risk factors symptoms physical exam
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findings and management for women with
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endometrial hyperplasia cancer and
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postmenopausal bleeding
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