Case Presentation

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

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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

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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

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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

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Diagnosis

• Serous Endometrial Intraepithelial Carcinoma
  (EIC)
• with extrauterine omental metastases

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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.

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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

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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

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Uterine Serous Carcinoma
22
EIC
P16
P53
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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

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Endometrial Glandular Dysplasia
25
EmGD
P53 P16
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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.

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Clinical outcome of Serous EIC/ Minimal USC

• Wheeler et al Am J Surg Pathol, 2000. 24797-806
• 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.

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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