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4. endometrial cancer

This is a lecture note on Endometrial Cancer.

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4. endometrial cancer

  1. 1. Endometrial Cancer Hale Teka, M.D., OB-GYN Resident Mekelle University, College of Health Sciences, Dep't of OB-GYN
  2. 2. • Contents 1. Introduction 2. Endometrial Hyperplasia 3. Endometrial Cancer Hale T., M.D., Resident PhysicianSaturday, January 7, 2017 2
  3. 3. • Epidemiology – Most common gynecologic malignancy in US – 3% in US – Incidence is increasing – Easily diagnosed • Patients seek care early because of vaginal bleeding • Endometrial biopsy leads quickly to diagnosis – 4th leading cause of cancer in women – 8th leading cause of cancer death Saturday, January 7, 2017 Hale T., M.D., Resident Physician 3
  4. 4. • Management – 75% stage I at diagnosis – TAH + BSO + Staging lymphadenectomy – Patients with more advanced disease typically require postoperative combination chemotherapy, radiotherapy, or both. Saturday, January 7, 2017 Hale T., M.D., Resident Physician 4
  5. 5. • Risk Factor (An excessive estrogen environment) – Advanced maternal age • 60 years average age at diagnosis, 70 years the incidence peaks – Obesity – Low parity – Unopposed estrogen therapy – Menstrual and reproductive factors – Environment – Family history – Tamoxifen use Saturday, January 7, 2017 Hale T., M.D., Resident Physician 5
  6. 6. • Obesity – Excessive adipose tissue leads to aromatization of androstenedione to estrone – Excessive estrone leads to negative feedback inhibition of HPO axis resulting oligo-anovulation – Oligo-anovulation resutls in continuos estrogen exposure without subsequent progestational effect without menstrual withdrawal bleeding Saturday, January 7, 2017 Hale T., M.D., Resident Physician 6
  7. 7. • Unopposed estrogen therapy – Its effect recognized 3 decades a go – Now estrogen alone not given to women with uterus – For women with uterus estrogen and progesterone is being given Saturday, January 7, 2017 Hale T., M.D., Resident Physician 7
  8. 8. • Menstrual and reproductive factors – Anoovulation and uninterrupted menstrual cycles – Early age at menarche or late age of menopause – PCOS Saturday, January 7, 2017 Hale T., M.D., Resident Physician 8
  9. 9. • Environment – Western women have higher chance of having endometrial cancer than their black counter parts • Animal fat • Obesity • Low parity Saturday, January 7, 2017 Hale T., M.D., Resident Physician 9
  10. 10. • Age – Less than 40 years: 5% – Age > 55 years: 80% – Average age at diagnosis: 60 years – Age incidence peaks: 70 years Saturday, January 7, 2017 Hale T., M.D., Resident Physician 10
  11. 11. • Family history – Endometrial Ca is the most common extracolonic manifestation of HNPCC – “Sentinel cancer” for HNPCC – Carries 40-60% risk – More than colorectal cancer – But only 5% of endometiral cancers are due to HNPCC – Slight risk of BRCA1 and BRCA2 carriers due to frequent tamoxifen treatment Saturday, January 7, 2017 Hale T., M.D., Resident Physician 11
  12. 12. • Tamoxifen use – Unopposed estrogen use – 2-3 fold higher risk – In postmenopausal women Saturday, January 7, 2017 Hale T., M.D., Resident Physician 12
  13. 13. • Coexisting diseases which are sequelae of obesity and chronic estrogen exposure – DM – HTN – Gallbladder disease Saturday, January 7, 2017 Hale T., M.D., Resident Physician 13
  14. 14. • Protective Factors – COC and Mirena users • 1 year use: decrease risk by 30-50% • Risk reduction extends for 10-20 years • The progestin component has a chemopreventive biologic effect on endometrial cancer – Smoking • Reduced levels of circulating estrogens through weight reduction, • An earlier age at menopause, and • Altered hormonal metabolism Saturday, January 7, 2017 Hale T., M.D., Resident Physician 14
  15. 15. Endometrial Hyperplasia • The only known direct precursor of invasive disease • Endometrial hyperplasia is defined as endometrial thickening with a proliferation of irregularly sized and shaped glands and an increased gland-to-stroma ratio • In the absence of such thickening, lesions are best designated as disorderly proliferative endometrium or focal glandular crowding Saturday, January 7, 2017 Hale T., M.D., Resident Physician 15
  16. 16. • World Health Organization Classification of Endometrial Hyperplasia Saturday, January 7, 2017 Hale T., M.D., Resident Physician 16
  17. 17. • Classification based on – Glandular crowding – Ratio of gland to stroma > 1 – Nuclear atypia Saturday, January 7, 2017 Hale T., M.D., Resident Physician 17
  18. 18. • Endometrial intraepithelial neoplasia (EIN) – Using this system, anovulatory or prolonged estrogen- exposed endometria without atypia are generally designated as endometrial hyperplasias • Polyclonal diffusely responding to hormone Saturday, January 7, 2017 Hale T., M.D., Resident Physician 18
  19. 19. – In contrast, endometrial intraepithelial neoplasia (monoclonal intrinsically proliferating) is used to describe all endometria delineated as premalignant by a combination of three morphometric features that reflect • Glandular volume, • Architectural complexity, and • Cytologic abnormality Saturday, January 7, 2017 Hale T., M.D., Resident Physician 19
  20. 20. • Clinical Features – 2/3rd present with postmenopausal bleeding – Thickened endometrium (>10 mm) • Warrants biopsy – Endometrium <5 mm • Bleeding secondary to endometrial atrophy – Features of the endometrium – Adnexal mass Saturday, January 7, 2017 Hale T., M.D., Resident Physician 20
  21. 21. • The following are not indicated – Further work up for premenopausal women who have endometrial thickness < 10 mm with AUB – Hysteroscopy • Hyperplastic endometrium is not distinctive so hysteroscopy is inaccurate Saturday, January 7, 2017 Hale T., M.D., Resident Physician 21
  22. 22. • Endometrial abnormal echostructural changes on sonography – Cystic endometrial changes suggest polyps, – Homogeneously thickened endometrium may indicate hyperplasia, and – A heterogeneous structural pattern is suspicious for malignancy Saturday, January 7, 2017 Hale T., M.D., Resident Physician 22
  23. 23. Saturday, January 7, 2017 Hale T., M.D., Resident Physician 23
  24. 24. • Occasionally, an adnexal mass may be palpable on examination – Most likely is a benign ovarian cyst, – Any solid features noted during transvaginal sonography should raise the possibility of a coexisting ovarian granulosa cell tumor – These tumors produce an excessive estrogenic environment that results in up to a 30-percent risk of endometrial hyperplasia or less commonly, carcinoma Saturday, January 7, 2017 Hale T., M.D., Resident Physician 24
  25. 25. • Management – Depends on • Patient’s age • Presence or absence of cytologic atypia • Risks for surgery – Option relies on clinical judgment – Options • Surgical • Nonsurgical – Inherently risky Saturday, January 7, 2017 Hale T., M.D., Resident Physician 25
  26. 26. • Nonatypical endometrial hyperplasia – Premenopausal • Provera  given orally for 12 to 14 days each month at a dose of 10 to 20 mg daily • Mirena • COC – Menopausal • Be sure first! • Annual endometrial biopsy follow up • Low dose provera: 2.5 mg daily regimen • Simple hyperplasia: Follow without treatment Saturday, January 7, 2017 Hale T., M.D., Resident Physician 26
  27. 27. • Indications for biopsy – New bleeding after treatment – Postmenopausal women • Pipelle sampling  usually sufficient sample is not obtained through this method • D & C • Biopsy can be taken with IUD in-situ Saturday, January 7, 2017 Hale T., M.D., Resident Physician 27
  28. 28. • Response of nonatypical hyperplasia to progestins – Exceed 90% – Persistent disease: shift to high dose regimen • MPA: 40 – 100 mg daily • Megestrol acetate (Megace) : 160 mg daily – Hysterectomy for refractory cases Saturday, January 7, 2017 Hale T., M.D., Resident Physician 28
  29. 29. • Atypical Endometrial Hyperplasia – High dose progestin therapy • Highly motivated patients who does not compelete their family size • Unfit for surgical removal – Hyterectomy • Main stay Saturday, January 7, 2017 Hale T., M.D., Resident Physician 29
  30. 30. Endometrial Cancer Saturday, January 7, 2017 Hale T., M.D., Resident Physician 30
  31. 31. • Prevention – No screening needed for low risk women – For high risk women • Screening starting at 35 years • Prophylactic hysterectomy – +BSO  10-12% of life time risk of ovarian Ca – Criteria for screening • Colorectal or other Lynch syndrome-associated cancers in three first-degree relatives, occurring in at least two successive generations, and in one individual under the age of 50 years Saturday, January 7, 2017 Hale T., M.D., Resident Physician 31
  32. 32. • Lynch syndrome cancers include – Colon, – Endometrium, – Small bowel, – Renal pelvis and ureter, and – Ovary, among others Saturday, January 7, 2017 Hale T., M.D., Resident Physician 32
  33. 33. • Diagnosis – Historically • Irregular vaginal bleeding • Abnormal vaginal discharge • Pelvic pressure and pain in advanced cases • Signs and symptoms of advanced disease – Pap smear  Not sensitive – Endometrial sampling – Lab workup – Imaging studies Saturday, January 7, 2017 Hale T., M.D., Resident Physician 33
  34. 34. • Pap smear – Sensitivity 50% – Three possible findings • Normal • Benign endometrial cells • Atypical glandular cells  concerning Saturday, January 7, 2017 Hale T., M.D., Resident Physician 34
  35. 35. • Endometrial sampling – Office Pipelle biopsy – D & C – Outpatient hysteroscopy not sensitive for hyperplasia and may increase risk of peritoneal contamination Saturday, January 7, 2017 Hale T., M.D., Resident Physician 35
  36. 36. • Lab – CA-125 • The only lab work up which is helpful • Preoperatively, an elevated level indicates the possibility of more advanced disease • It is most useful in patients with advanced disease or serous subtypes to assist in monitoring response to therapy or during posttreatment surveillance • However, even in this setting, its utility in the absence of other clinical findings is limited Saturday, January 7, 2017 Hale T., M.D., Resident Physician 36
  37. 37. • Imaging – Chest x-ray – CT (to see advanced disease) and MRI (to see origin) Saturday, January 7, 2017 Hale T., M.D., Resident Physician 37
  38. 38. • Role of the generalist – Grade 1 type I  Hysterectomy – Consultations • Preoperative consultations for advanced disease • Intraoperative consultations for cancers extending to the cervix • Postoperative consultations for hysteroectomy done for other indications and biopsy proving endometrial cancer Saturday, January 7, 2017 Hale T., M.D., Resident Physician 38
  39. 39. • Histopathologic Criteria for Assessing Grade Saturday, January 7, 2017 Hale T., M.D., Resident Physician 39
  40. 40. • In addition to percent of solid growth nuclear atypia raises the grade by 1 • The simplicity of dividing tumors into low-grade lesions and high grade lesions based on the proportion of solid growth ( ≤50 percent or >50 percent, respectively) is attractive and appears to have value Saturday, January 7, 2017 Hale T., M.D., Resident Physician 40
  41. 41. • World Health Organization Histologic Classification of Endometrial Carcinoma Saturday, January 7, 2017 Hale T., M.D., Resident Physician 41
  42. 42. • Endometroid adenocarcinoma – The most common (75% of cases) • Hyperplastic endometrium  low grade • If glandular component decreases and endometrium is atrophic  high grade Saturday, January 7, 2017 Hale T., M.D., Resident Physician 42
  43. 43. • Serous carcinoma – 5-10% – Highly aggressive, even the mixed ones – Commonly referred to as uterine papillary serous carcinoma (UPSC), its histologic appearance resembles epithelial ovarian cancer, and psammoma bodies are seen in 30 percent of cases – Exophytic – Omental caking – Secrete CA-125 Saturday, January 7, 2017 Hale T., M.D., Resident Physician 43
  44. 44. • Clear cell carcinoma – < 5% – High aggressive – Poor prognosis – Microscopically it can be • Solid • Cystic • Papillary or • Tubular Saturday, January 7, 2017 Hale T., M.D., Resident Physician 44
  45. 45. • Mucinous carcinoma – 1-2% – Almost all are stage I grade 1 lesions with a good prognosis – The main diagnostic dilemma is differentiating this tumor from a primary cervical adenocarcinoma – Immunostaining may be helpful, but MR imaging may be required to further clarify the most likely site of origin – For defining anatomy, MR imaging tool offers superior contrast resolution at soft-tissue interfaces Saturday, January 7, 2017 Hale T., M.D., Resident Physician 45
  46. 46. • Mixed Carcinoma – An endometrial cancer may demonstrate combinations of two or more pure types – To be classified as a mixed carcinoma, a component must comprise at least 10 percent of the tumor – Except for serous and clear cell histology, the combination of other types usually has no clinical significance – As a result, mixed carcinoma usually refers to an admixture of a type I (endometrioid adenocarcinoma and its variants) and a type II carcinoma Saturday, January 7, 2017 Hale T., M.D., Resident Physician 46
  47. 47. • Undifferentiated Carcinoma – In 1 to 2 percent of endometrial cancers, there is no evidence of glandular, sarcomatous, or squamous differentiation – These undifferentiated tumors are characterized by proliferation of medium-sized, monotonous epithelial cells growing in solid sheets with no specific pattern – Overall, the prognosis is worse than in patients with poorly differentiated endometrioid adenocarcinomas Saturday, January 7, 2017 Hale T., M.D., Resident Physician 47
  48. 48. • Rare Histologic Types – Fewer than 100 cases of squamous cell carcinoma of the endometrium have been reported – Diagnosis requires exclusion of an adenocarcinoma component and no connection with the squamous epithelium of the cervix – Typically, the prognosis is poor – Transitional cell carcinoma of the endometrium is also rare, and metastatic disease from the bladder or ovary must be excluded during diagnosis Saturday, January 7, 2017 Hale T., M.D., Resident Physician 48
  49. 49. • Pathology – Degree of differentiation is important – Tumors that arise following pelvic radiation • High stage • High grade • High risk histologic subtype Saturday, January 7, 2017 Hale T., M.D., Resident Physician 49
  50. 50. • Type II serous and clear cell carcinomas have a particular propensity for extrauterine disease, in a pattern that closely resembles epithelial ovarian cancer • Patterns of Spread (for type I endometrioid tumors) – Direct extension – Lymphatic metastasis – Hematogenous dissemination, and – Intraperitoneal exfoliation • In general, the various patterns of spread are interrelated and often develop simultaneously Saturday, January 7, 2017 Hale T., M.D., Resident Physician 50
  51. 51. • Lymphatic spread – Haphazard – No pattern identified • Hematogenous – Lung and less commonly liver , brain and bone • Retrograde transtubal and serosal perforation – Mechanisims by which malignant cells reach the peritoneal cavity • Port-site metastatis – After laparascopy Saturday, January 7, 2017 Hale T., M.D., Resident Physician 51
  52. 52. • Treatment – TAH + BSO – Extrafacial or type I hysterectomy is sufficient for early diseases – Type III hysterectomy may be required if there is cervical extension – TVH with or without BSO is an option in selected cases Saturday, January 7, 2017 Hale T., M.D., Resident Physician 52
  53. 53. • Steps of surgical staging – Vertical abdominal incision is preferred – Collect ascites upon entry or peritoneal washing with 50-100 mL of saline – Systematic exploration – Hysteroectomy with BSO – Frozen dissection – Pelvic and para-aortic lymphadenectomy Saturday, January 7, 2017 Hale T., M.D., Resident Physician 53
  54. 54. • Contraindications for surgery – A desire to preserve fertility, – Massive obesity, – High operative risk, and – Clinically unresectable disease Saturday, January 7, 2017 Hale T., M.D., Resident Physician 54
  55. 55. FIGO Staging of Carcinoma of the Endometrium Saturday, January 7, 2017 Hale T., M.D., Resident Physician 55
  56. 56. Saturday, January 7, 2017 Hale T., M.D., Resident Physician 56
  57. 57. Saturday, January 7, 2017 Hale T., M.D., Resident Physician 57
  58. 58. Distribution of Endometrial Cancer by FIGO Stage (n 5281 patients) Saturday, January 7, 2017 Hale T., M.D., Resident Physician 58
  59. 59. – Surveillance • Pelvic examination every 3 to 4 months for the first 2 years and twice yearly for an additional 3 years before returning to annual visits • Pap tests are not a mandatory part of surveillance since they identify an asymptomatic vaginal recurrence in less than 1 percent of patients and are not cost effective • Women who have more advanced disease that requires postoperative radiation or chemotherapy or both warrant more aggressive monitoring. Saturday, January 7, 2017 Hale T., M.D., Resident Physician 59
  60. 60. • Serum CA-125 measurements may be valuable, particularly for UPSC • Intermittent imaging using CT scanning or MR imaging may also be indicated • In general, the pattern of recurrent disease depends on the original sites of metastasis and the treatment received – Chemotherapy (Primary, Adjuvant) – Radiotherapy (Primary, Adjuvant) – Hormonal (Primary, Adjuvant) Saturday, January 7, 2017 Hale T., M.D., Resident Physician 60
  61. 61. • Chemotherapy – Paclitaxel (Taxol), doxorubicin (Adriamycin), and cisplatin (TAP) chemotherapy is the adjuvant treatment of choice for advanced endometrial cancer following surgery – In practice, cytotoxic chemotherapy is frequently combined, sequenced, or sandwiched with radiotherapy in patients with advanced endometrial cancer following surgery Saturday, January 7, 2017 Hale T., M.D., Resident Physician 61
  62. 62. • Radiation therapy – Primary radiation • Poor surgical candidates • Intracavitary brachytherapy such as Heyman capsules • 10-15% less success than surgical management – Adjuvant • Controversial for early stage disease • Indicated for advanced disease Saturday, January 7, 2017 Hale T., M.D., Resident Physician 62
  63. 63. • Hormonal therapy – Primary treatment • For excessively high operative risk • Should be used with caution – Adjuvant • Tamoxifen modulates the expression of the progesterone receptor and is postulated to thereby improve progestin therapy efficacy • Clinically, high response rates have been noted with tamoxifen used adjunctively with progestin therapy Saturday, January 7, 2017 Hale T., M.D., Resident Physician 63
  64. 64. • Fertility sparing management – Hormonal therapy without hysterectomy is an option in carefully selected young women with endometrial cancer who desperately wish to preserve their fertility – ART may be required – High dose progestin – 3-4 months D &C biopsy follow up – Delivery of healthy infant is the expectation Saturday, January 7, 2017 Hale T., M.D., Resident Physician 64
  65. 65. Poor Prognostic Variables in Endometrial Cancer Saturday, January 7, 2017 Hale T., M.D., Resident Physician 65
  66. 66. • Relapse – Site of relapse is the most important factor – If not previously irradiated  good prognosis – Vaginal relapse is curable – Combinations of options available – Palliation may be the goal for some of the patients Saturday, January 7, 2017 Hale T., M.D., Resident Physician 66
  67. 67. References 1. Barbara L. Hoffman, et al., Williams Gynecology 2ed 2012: The McGraw-Hill Companies, Inc. 2. James R. Scott, 2008. Danforth’s Obstetrics and Gynecology, 9th edition Hale T., M.D., Resident PhysicianSaturday, January 7, 2017 67
  68. 68. Saturday, January 7, 2017 Hale T., M.D., Resident Physician 68
  69. 69. Thank you for listening! Hale T., M.D., Resident PhysicianSaturday, January 7, 2017 69

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