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Case Presentation

Case Presentation. Dr Elizabeth Benjamin UCL/UCL Hospitals NHS Foundation Trust. Case History. February 2006. Female aged 58 years Post menopausal bleeding Cervical smear: Glandular dysplasia Hysteroscopy: Cervical and endometrial polyps

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Case Presentation

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  1. Case Presentation Dr Elizabeth Benjamin UCL/UCL Hospitals NHS Foundation Trust

  2. Case History February 2006 • Female aged 58 years • Post menopausal bleeding • Cervical smear: Glandular dysplasia • Hysteroscopy: Cervical and endometrial polyps • Polypectomy Endometrium: “Severe atypical hyperplasia in a benign polyp” Cervix: Benign endocervical polyp

  3. Endometrial Polyp

  4. Endometrial Polyp

  5. Case History April 2006 Hysterectomy and bilateral salpingo-oophorectomy Findings: • Endometrial Polyp 18mm • Endometrial thickness 5mm • Subserosal fibroids • Ovaries and Fallopian tubes: Normal Peritoneal washings: Malignant cells

  6. Uterus

  7. Endometrium

  8. Endometrium

  9. p53 WT1

  10. MIB1

  11. Pathology Report Serous Endometrial Intraepithelial Carcinoma (EIC) involving endometrium / endometrial polyp Comment: Serous EIC is capable of metastatic spread in the absence of invasive disease

  12. Case History March 2007 • CA 125: 1244 u/mL • Ascites • Omentum: supra and infracolic infiltrates • Normal liver, spleen and pancreas • No pelvic masses. No lymphadenopathy • Thick walled small bowel loops, likely peritoneal deposits Omental biopsy performed

  13. Omentum

  14. CA 125 Omentum WT1

  15. Case History June 2007 • Chemotherapy: 3 cycles carbotaxol • CT scan: no residual disease • Omentectomy: metastatic serous carcinoma • Died of disease

  16. Diagnosis Serous Endometrial Intraepithelial Carcinoma (EIC) with extrauterine omental metastases

  17. Endometrial Cancer Type I Endometrioid Carcinoma Precursor: Atypical Hyperplasia/EIN Type II Serous Carcinoma (USC) Clear cell cancer Precursor: EIC ? EmGD

  18. Serous EIC • Endometrial Intraepithelial Carcinoma (EIC); • Endometrial surface epithelium and/or glands replaced by flat or micropapillary proliferation of cells similar to serous carcinoma. • No stromal or myometrial invasion.

  19. Is Serous EIC a pre-cancer? • Shares features of uterine serous carcinoma: clinical/ pathological/ molecular biology • Does not behave as classic intraepithelial cancer • Associated with extra-uterine serous carcinoma (40 %) • An early form of UPSC

  20. Features of Serous EIC • Post menopausal patients ( 65 years) • Atrophic endometrium/ endometrial polyps • Co-existent serous carcinoma, sometimes clear cell carcinoma • Isolated EIC rare; extra-uterine disease • Endocervix and fallopian tubes involved. • Immunohistochemistry : P53 +ve. P16 +ve. Increased proliferation MIB1 . Loss of ER/ PR

  21. Uterine Serous Carcinoma

  22. EIC P16 P53

  23. Endometrial Glandular Dysplasia (EmGD) • Putative precursor of serous EIC. • Found in association with serous EIC (53%) • Less common with endometrioid carcinoma (2%) • Nine fold increased risk of developing UPSC • Immunohistochemistry: P53 +ve. MIB1 • IMP3 expression: EmGD 14%, serous EIC 89%, serous Ca 94% • Identification of EmGD to the development of serous EIC or UPSC :16-98 months , av 33 months Zheng et al . Int J Gynecol Pathol 2007,26, 38-52

  24. Endometrial Glandular Dysplasia

  25. EmGD P53 P16

  26. Mimics/ Differential Diagnosis of EIC in uterus Malignant. • Endometrioid adenocarcinoma • Clear cell carcinoma • Endocervical adenocarcinom in-situ Benign • Papillary syncitial metaplasia • Tubal metaplasia of endometrium • Arias Stella reaction • Degenerating endometrium.

  27. Clinical outcome of Serous EIC/ Minimal USC Wheeler et al: Am J Surg Pathol, 2000. 24:797-806 • 21 cases-Hysterectomy and staging; follow-up 27 months average. • Stage I / II: No recurrence/ tumour related deaths • Stage III / IV : All alive with recurrence or died of disease within 38 months. Hui et al. Mod Pathol, 2005.18: 75-82 • 40 cases- Hysterectomy and staging; follow-up 26 months average. • 44 % of patients with extrauterine tumour at presentation died within 36 months.

  28. Management • Clinical behavior is stage dependent • Favourable outcome in Stage 1/11 • Extrauterine tumour at presentation behaves as advanced stage USC • Full surgical staging recommended: Hysterectomy, BSO, pelvic washings, omentectomy and nodes. • Adjuvant therapy for extra-uterine spread

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