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Endometrial Cancer and Hyperplasia

Endometrial Cancer and Hyperplasia. V. Capstick 2010. What are the 3 most common gynecologic presenting complaints?. Bleeding Pain Bleeding and Pain. Objectives. Describe the approach to the woman with abnormal vaginal bleeding-Drs Sagle and Motan are also talking about this-

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Endometrial Cancer and Hyperplasia

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  1. Endometrial Cancer and Hyperplasia V. Capstick 2010

  2. What are the 3 most common gynecologic presenting complaints? • Bleeding • Pain • Bleeding and Pain

  3. Objectives • Describe the approach to the woman with abnormal vaginal bleeding-Drs Sagle and Motan are also talking about this- • Describe the risk factors and symptoms/findings characteristic of endometrial cancer, the staging of same, the methods of diagnosis and the typical disease course.

  4. This lecture 1. differential diagnosis of vaginal bleeding in a postmenopausal woman 2. investigation of PMB (post menopausal bleeding) 3. Endometrial cancer/hyperplasia

  5. Endometrial Cancer/Hyperplasia • Most common gynecologic cancer in Canada. • Best cure rate of gynecologic cancers in Canada. • Why? Diagnosed early in many women-bleeding is usually an early symptom-most are stage one.

  6. Trends in Incidence, Cancer, Canada, Females, 1971-2000Age Standardized per 100,000 women Name the cancer site • Breast • Lung • Colorectal • Uterine • Ovary • Cervix 100 50 10 1971 2000

  7. Lung Breast Colorectal Ovary Uterus (endo) Cervix Trends in Mortality, Females, CanadaAge-Standardized Mortality Rates / 100,000, 1971 - 2009 50 40 30 20 10 1971 1980 1990 2000

  8. Uterine malignancies • Endometrium • endometrial Ca (most common) • Endometrial Stromal Sarcoma • Myometrium- leiomyosarcoma – this is a malignancy that arises in the muscle of the uterus (myometrium)

  9. Endometrial Adenocarcinoma • Age: Median 58 • Risk Factors: Main one is prolonged stimulation by unopposed estrogen. (‘unopposed’ means no progesterone) • Situations of unopposed estrogen: • Anovulation (reproductive age women), • Obesity have extra estrogen • Tamoxifen (breast cancer ‘antiestrogen’ –increases ca endometrium by 2-3X), usually opposes it but not in endometrium, and • Hormone replacement with out progesterone are the classic scenarios.

  10. Menstrual Cycle

  11. Why is Obesity a risk factor? • Extraovarian aromatization of androstenedione to estrone in fat cells. Androstenedione is secreted by the adrenal glands. • Estrone is estrogen • Consequently:Being overweight in menopause gives higher levels of estrogen, but no progesterone

  12. Other ‘risk factors’ • Nulliparity-probably related to anovulation • ‘Late’ menopause • Diabetes mellitus-?obesity connection • Hypertension- obesity connection • Gallbladder disease- obesity connection • Breast, colon or ovarian cancer • Lynch syndrome (HNPCC) hereditary non polypsis colon cancer • NOT ALL ENDOMETRIAL CANCER IS ESTROGEN LINKED. JUST THE NICE ONES.

  13. Presentation of Endometrial Cancer Abnormal VaginalBleeding (90%) • Postmenopausal Vaginal Bleeding: PMB • Perimenopausal bleeding with intermenstrual bleeding or increasingly heavy periods • Premenopausal patients with abnormal bleeding (>35yo). Especially if history of anovulation. (Rule out pregnancy!)

  14. Remember: • Endometrial cancer can happen in reproductive age women-especially those not ovulating.

  15. Other presentations of Endometrial Cancer (the 10 % who do not have bleeding) • Abnormal pap smear- endometrial cells on the pap smear, needs to be investigated as some women have endometrial cancer (but this is not why we do paps) • Metastatic disease (uncommon) • Hematometrium (cervical stenosis) – blood accumulating in the uterus

  16. Postmenopausal Bleeding: All Causes • Exogenous estrogens (HRT) 20-30% • Atrophic endometritis total lack estrogen, vaginitis 30% • Endometrial Cancer 10-15% • Endometrial or cervical polyps 10% • (benign) • Endometrial hyperplasia 5% • Other (ca cervix, sarcomas, trauma) 10% • Exogenous estrogens are less common now.

  17. Physical findings of endometrial cancer • Uterus-normal or enlarged - majority • Advanced disease- • Cervical extension (obvious or occult) • Vaginal metastasis (pelvic exam) • Lung metastasis (Chest X-ray) • Nodal metastasis (at Surgery)

  18. Investigation of Abnormal Uterine Bleeding: OFFICE • 1. Pap smear, if cervix looks normal, (if not normal, do punch biopsy) • 2. Endometrial biopsy • 3. Transvaginal ultrasound • Measures the endometrial ‘stripe’ (thickness) – depends on the age of the patient • Hypoestrogenic state<5mm • Abnormal is > 10 mm and suggests an problem but does not make a diagnosis, you need histology.

  19. Office: Endometrial Biopsy

  20. Investigation of Abnormal Uterine Bleeding: Operating Room-D&C • Fractional Curettage +/- hysteroscopy • General or Spinal Anaesthetic • Endocervical canal curetted • Cervix dilated • Endometrial cavity scoped (hysteroscopy) (optional) • Endometrium curetted/biopsied • Same principle as terminating a pregnancy

  21. Pathology • Adenocarcinoma (75% of endometrial cancers) • Grade 1,2,or 3 • Glandular carcinoma • Serous Papillary Carcinoma – looks like ovarian cancer and acts like it (can spread throughout abdominal cancer – it is high risk) • Clear cell Carcinoma – Grade 3 • Small Cell Neuroendocrine – Small cell carcinoma • Sarcomas of the endometrium – usually due to fibroids and when you go to check it is a carcinoma • Leiomyosarcomas are found at hysterectomy, rarely at D&C-thought to be fibroids until pathologist sees it.

  22. Patterns ofSpread • Ovaries-lymphatic or down the tubes – stage 1 • Cervix-direct extension – stage 2 • Pelvic/Para aortic nodes • lymphatic • Vagina • lymphatic • Lungs/bones/liver/brain • Hematogenous – very rare

  23. Patterns of spread: special types • Serous Papillaryacts like ovarian cancer with intraabdominal spread typical-so is surgically staged like ovary and is almost always treated with chemotherapy (carboplatin and taxol) even if confined to uterus. • Small Cell Neuroendocrine (oat cell) also acts badly and is treated with chemotherapy after surgery (cisplatin and Etoposide).

  24. Carcinoma of the Endometrium • IA         Tumor confined to the uterus, no or < ½ myometrial invasion • IB         Tumor confined to the uterus, > ½ myometrial invasion • II          Cervical stromal invasion, but not beyond uterus • IIIA      Tumor invades serosa or adnexa • IIIB      Vaginal and/or parametrial involvement • IIIC1    Pelvic node involvement • IIIC2    Para-aortic involvement • IVA       Tumor invasion bladder and/or bowel mucosa • IVB       Distant metastases including abdominal metastases and/or inguinal lymph nodes Don’t need to memorize. Stage 1 is split into 2 groups. Good at curing Stages 1 and 2.

  25. Treatment • Surgery, • Postoperative Radiotherapy • Very center specific • Postoperative Chemotherapy • If poor prognostic features-pos nodes, other metastatic disease, high risk features with out metastasis • Inoperable (medical) patients are given radiotherapy without surgery and occ chemotherapy • Uterus packed with radioactive capsules • THERE IS NO STANDARD WAY OF TREATING IN THE WORLD.

  26. Surgery • Most patients appear to be stage one at presentation and are offered an operation: • Total abdominal hysterectomy, bilateral salpingo-oophorectomy • +/-pelvic lymph node dissection

  27. Post surgical treatment: • We will never ask you this on a test! • North American Cancer Centers Vary Widely in practice but in general: • Chemotherapy and/or radiotherapy if positive lymph nodes (stage 3) • Chemotherapy and/or radiotherapy if cervical involvement (stage 2) • Chemotherapy if serous papillary • Numerous other practices from center to center.

  28. Recurrent Endometrial Cancer • Recurrence can happen in vagina, lung or nodes, most commonly. Brain and liver also possible. • Treatment for recurrence can be curative in two situations. • 1. isolated vaginal recurrence-radiate if not already radiated • 2. Hormonally sensitive cancer – high dose progesterone. Medroxyprogesterone acetate 100mg TID. X years. • Provera – dose of estrogen to stop nasty bleeding. It is given 100 mg for years here.

  29. 5 year Survival in Endometrial Cancer • Stage%# Patients • Stage 1 86% 8603 • Stage 2 66% 1650 • Stage 3 44% 1181 • Stage 4 16% 399

  30. Endometrial hyperplasia • Precursor to some cancers of the endometrium (estrogen dependent ones- no serous papillary or small cell endocrine) • Hyperplasia is overgrowth of the endometrium in response to an estrogen dominant hormonal ‘milieu’. • Hyperplasia is the ‘abnormal proliferation of both glandular and stromal elements showing altered histologic architecture.’ • Speculate that at least ‘6 months’ of unopposed estrogen stimulation required.

  31. Classification of endometrial hyperplasia • Simple (cystic) • Complex (Adenomatous without atypia) • Atypical (Adenomatous with atypia) • 20-30 % chance of malignant transformation • Recommend a hysterectomy, bso Don’t need to know this

  32. Estrogen independent Endometrial Cancer • Women who do not have the usual risk factors and tend to: • Be Thinner • No hyperplasia associated • Poorly differentiated cancers • Papillary serous/clear cell histology • Poorer prognosis

  33. Screening for Endometrial Cancer • Not for general population: • However consider yearly endometrial biopsy for: • women on tamoxifen • anovulatory women not on progesterone • Women on estrogen only HRT

  34. Case 1 • 18 year old G0P0 with Gonadal Dysgenesis (turner’s syndrome, had ovaries that would never mature). Started on Premarin (estrogen alone) 1.25 mg daily. At 25 years of age presents with heavy bleeding. D&C shows grade 1 adenocarcinoma.

  35. Case 1 • TAH BSO (total abdominal hysterectomy, bilateral salpingo-oophorectomy) • Grade 1 Adenocarcinoma endometrium with 2 mm invasion of myometrium. No cervical involvement. Myometrial thickness is 10mm. • She wishes to go back on HRT. • So she does.

  36. Estrogen use after endometrial cancer diagnosis • Historically HRT is contraindicated. • There are women who have taken it quite safely, so appropriately councelled, it can be done. • This case demonstrates the risks, however.

  37. Case 1 • 1.5 years later a chest x-ray shows 3 lesions in the lungs consistent with metastasis. Biopsy confirms metastatic adenocarcinoma consistent with endometrial primary. • Estrogen stopped. • Original slides stained for estrogen and progesterone receptors-strongly positive for both. • Medroxyprogesterone acetate 100mg tid po. • One year later chest x-ray is clear. • 17 years later we decide to stop the drugs.

  38. Case 2 • 65 year old G3 P3 (3 kids) BMI 45 • Postmenopausal spotting for 1 month • Endometrial biopsy in office-grade 2 endometrial cancer • Pelvic exam unremarkable, chest xray Normal • TAHBSO Pelvic Node Dissection • Grade 2 endometrial cancer invading half the thickness of the myometrium • Nodes negative • Postoperative vaginal radiotherapy (edmonton) • Cured. • Typical case

  39. Case 3 • 59 year old G0P0 • Postmenopausal bleeding 5 years. Endometrial biopsy: papillary serous carcinoma endometrium Sudden onset abdominal distension- massive ascites-paracentesis shows adenocarcinoma. CT scan abdomen and pelvis-small omental nodules. Started on chemotherapy-Carboplatin and Taxol. No expectation of cure.

  40. Case 4 • 55 year old woman has enlarging abdomen for five years. Onset bleeding and vaginal discharge. • Huge uterus, ascites, intraabdominal disease and vaginal metastasis (8 cm) • Diagnosis: leiomyosarcoma.

  41. Uterine sarcoma

  42. Most important message • Vaginal bleeding in the menopause is not okay. • It is not to be ‘watched’. • It must be investigated. • A ‘reassuring’ ultrasound is not sufficient. If bleeding recurrs, need to persue.

  43. Wednesday • Lecture on Premalignant disease of Cervix and Cervical cancer. • It would help you to have reached part four on the PBL before you come to this lecture. • It would also help if you do your learning issues from the PBL, the lecture content is intended to help clarify what you have already tried to learn, not teach it from scratch. • Bring questions • Look at HOMER for Alberta relevant info.

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