ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.
-
Upload
eustacia-cooper -
Category
Documents
-
view
216 -
download
0
Transcript of ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.
![Page 1: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/1.jpg)
ENDOMETRIAL CANCER
Dr P Mukonoweshuro
Consultant Pathologist RUH Bath
![Page 2: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/2.jpg)
Endometrial tumours
Epithelial Mesenchymal Mixed epithelial and mesenchymal Trophoblastic Lymphoid Miscellaneous tumours e.g. sex cord like
tumours Secondary tumours
![Page 3: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/3.jpg)
Endometrial Carcinoma
Endometrial carcinoma (EC) is the 4th most common cancer in European and North American women
80-85% endometrioid type Aetiology – hormones, obesity, diabetes,
nulliparity, diet and molecular genetics
![Page 4: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/4.jpg)
Endometrial carcinoma
Type 1 - oestrogen related carcinomas – young female, perimenopausal, background hyperplasia, favourable prognosis.
Type II - non oestrogen related – elderly, atrophic endometrium, higher grade, poor prognosis.
Mixed carcinomas Hybrid tumours HNPCC – lower uterine segment
![Page 5: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/5.jpg)
Tamoxifen
Weak oestrogen agonist. In young female- blocks effect of oestrogen. In elderly female – stimulates proliferation of
endometrium. Histology – Hyperplasia, large polyps with
cystic glands, carcinoma ( high grade), carcinosarcoma, metaplasias
![Page 6: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/6.jpg)
Endometrial Hyperplasia
Hallmark – increased glandular tissue relative to stroma.
Simple hyperplasia with or without atypia Complex hyperplasia with or without atypia. Associations – polycystic ovaries, sex cord
stromal tumours etc i.e. excess oestrogen
![Page 7: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/7.jpg)
Atypical hyperplasia
Back to back glands
![Page 8: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/8.jpg)
Hyperplasia
![Page 9: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/9.jpg)
Hyperplasia
![Page 10: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/10.jpg)
Atypical hyperplasia in polyp
![Page 11: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/11.jpg)
Complex atypical hyperplasia in polyp
![Page 12: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/12.jpg)
Polyp with CAH
![Page 13: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/13.jpg)
Atypical hyperplasia
Nuclear atypia
![Page 14: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/14.jpg)
Endometrial intraepithelial carcinoma (EIC)
Markedly atypical cells identical to invasive serous carcinoma lining the surface of glands of polyps or atrophic endometrium
P53 expression Minority p53 negative – truncated or unstable
protein Distinguish from early serous
carcinoma/metaplasia Can disseminate
![Page 15: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/15.jpg)
EIC
![Page 16: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/16.jpg)
Polyp with EIC/Invasive serous carcinoma
![Page 17: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/17.jpg)
Endometrial carcinoma
Type I – endometrioid adenocarcinoma and variants, mucinous adenocarcinoma (80-90%)
Type II – serous adenoca and clear cell ca. Mixed carcinomas Mixed epithelial and mesenchymal tumours Other – squamous cell ca, small cell etc
![Page 18: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/18.jpg)
WHO classification of endometrial Ca
Endometrioid adenoca – villoglandular variant, secretory variant, ciliated cell, variant with squamous differentiation.
Mucinous adenoca Serous adenoca (not papillary) Clear cell adenoca Mixed cell adenoca Small cell carcinoma Undifferentiated carcinoma/de-defferentiated ca others
![Page 19: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/19.jpg)
Molecular pathology
Endometrioid adenoca - microsatellite instability, PTEN, KRAS, PIK3CA, CTNNB1 (beta-catenin).
Familial – HNPCC, MLH1+ MSH2 mutations. Serous carcinoma – P53, HER/NEU
amplification and others. Targeted therapies
![Page 20: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/20.jpg)
LYNCH SYNDROME (HNPCC)
Autosomal dominant, increases risk for multiple cancers, usually patients >50yrs.
Germline mutations in DNA mismatch repair genes – MLH1, MSH2, MSH6, and rarely PMS2
Endometrial cancer – sentinel cancer Predilection for lower uterine segment Immunohistochemistry to screen patients followed
by mutational analysis Consent issues.
![Page 21: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/21.jpg)
EIC VS EIN
EIC – serous intraepithelial carcinoma. EIN – Clonal proliferation of architecturally
and cytologically altered premalignant endometrial glands – Type 1 (endometrioid) adenoca.
![Page 22: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/22.jpg)
Features of endometrial cancer
Uterus – small, normal or enlarged in size On sectioning – single lesion, multiple lesions
or diffuse. Polypoid Commoner on posterior wall Histological types –
Endometrioid,serous,clear cell, squamous cell, mixed types, undifferentiated..
Metastatic tumours.
![Page 23: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/23.jpg)
Prognostic factors.
Histological type Grade Depth of invasion Vascular invasion Stage Age at diagnosis.
![Page 24: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/24.jpg)
Grading (endometrioid/mucinous adenoca) – FIGO.
G1 – 5% or less solid pattern. G2 – 6-50% G3 - >50% Cytology – raise by one grade
![Page 25: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/25.jpg)
Binary grading
Two part grading system better Binarised FIGO (G1/2 – low grade; G3 – high
grade) Binary Gilks’ grading system – can be used
with any cancer. Based on:
2 out of 3 features considered “high grade” – papillary or solid architecture; high nuclear grade; >6 mitotic figures/10 high power field
![Page 26: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/26.jpg)
Immunohistochemistry
Vimentin Cytokeratins ER, PR CEA P16, P53, MIB-1 Immuno available for MSI - DNA mismatch
repair proteins: MLH1, MSH2, MSH6, PMS2 (consent issues and counseling)
![Page 27: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/27.jpg)
Reporting of endometrial Ca
MDS – tumour type,location, size, depth of invasion, distance from serosal surface, involvement of cervix, parametria, ovaries, fallopian tubes, background hyperplasia etc.
Biopsies – tumour type, grade, background endometrium.
FIGO 2009
![Page 28: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/28.jpg)
Endometrioid adenocarcinoma grade 1
![Page 29: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/29.jpg)
MUCINOUS ADENOCA
![Page 30: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/30.jpg)
MUCINOUS ADENOCA
![Page 31: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/31.jpg)
Endometrial adenocarcinoma grade 2
![Page 32: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/32.jpg)
Endometrial Adenocarcinoma grade 3
![Page 33: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/33.jpg)
G3 ENDOMETRIOID ADENOCA
![Page 34: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/34.jpg)
Grade 3 endometrioid adenoca
![Page 35: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/35.jpg)
Clear cell carcinoma
Type II carcinoma 1-5% of endometrial carcinomas Predominantly older patient Frequently diagnosed in advanced clinical
stage Strong expression of p53 associated with
aggressive behaviour
![Page 36: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/36.jpg)
CLEAR CELL CARCINOMA
![Page 37: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/37.jpg)
CLEAR CELL CARCINOMA
![Page 38: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/38.jpg)
Serous adenoca
5-10% of endometrial carcinomas Type II carcinoma Aggressive tumour May show LVSI and peritoneal deposits with
minimal myometrial invasion Staging recommended in patients with pre-
operative diagnosis of SC Non-invasive precursor lesion -
EIC/intraepithelial serous carcinoma.
![Page 39: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/39.jpg)
SEROUS ADENOCA
![Page 40: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/40.jpg)
SEROUS ADENOCA
![Page 41: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/41.jpg)
Serous carcinoma
![Page 42: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/42.jpg)
Mixed adenoca/De-differentiated adenoca?
![Page 43: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/43.jpg)
Hybrid tumours
Some tumours may be difficult to assign a histologic subtype:
gland forming or papillary tumour exhibits nuclear pleomorphism and a high mitotic rate but lacks confirmatory endometrioid or serous features
- FIGO grading inappropriate - useful to use Gilk’s grading system
- P53 can be useful in such cases
![Page 44: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/44.jpg)
Endometrial tumours with a stromal component
Divided into 2 groups
1) Pure stromal tumours
2) Tumours with an epithelial component
![Page 45: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/45.jpg)
Other subtypes
De-differentiated endometrial adenocarcinoma
Undifferentiated adenocarcinoma Endometrioid adenocarcinoma with spindle
cell elements – spindle cell elements never histologically high grade
![Page 46: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/46.jpg)
Carcinosarcoma
Definition – mixed tumour of malignant glands and mesenchyme
Histology Admixed malignant epithelial and mesenchymal
elements Epithelial-
endometrioid,squamous,mucinous,serous,clear cell. Mesenchymal- striated muscle,chondroid,osteoid
etc
![Page 47: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/47.jpg)
Carcinosarcoma/MMMT
<5% of malignant uterine tumours Carcinomas with sarcomatoid differentiation
i.e. biphasic Gynaecologists/oncologists persist in
classifying as sarcomas Mean age - 7th decade, age range 4th to 9th
decades Polypoid tumours Heterologous and homologous elements.
![Page 48: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/48.jpg)
Continuation
Histogenesis – Single progenitor cell?
Metastases usually epithelial
Prognosis dependant on epithelial component
![Page 49: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/49.jpg)
Malignant Mixed Mullerian Tumour
Malignant epithelial component
Malignant spindle component.
Chondroid differentiation
![Page 50: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/50.jpg)
MMMT
![Page 51: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/51.jpg)
LVSI
![Page 52: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/52.jpg)
Pure stromal tumours
Endometrial stromal nodule
Endometrial stromal sarcoma
Undifferentiated uterine sarcoma
![Page 53: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/53.jpg)
Tumours with an epithelial component
Adenofibroma Adenomyoma Atypical polypoid adenomyoma
Adenosarcoma
Carcinosarcoma- with homologous or heterologous elements
![Page 54: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/54.jpg)
Atypical Polypoid Adenomyoma
![Page 55: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/55.jpg)
Atypical polypoid adenomyoma
![Page 56: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/56.jpg)
Endometrial stromal nodule
Well circumscribed Fleshy and focally yellow in appearance
Histology Densely cellular Maybe
hypocellular,fibrous,hyalinized,myxoid/oedematous
Arterioles ( spiral arteriole calibre)
![Page 57: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/57.jpg)
PATHOLOGY REPORT
Histological type of tumour High grade/ low grade LVSI Stage – FIGO Margins – if any
Biopsy specimen – type of tumour and grade.
![Page 58: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/58.jpg)
Is immunohistochemistry of value?
Tumours don’t read books! Serous ca – p53, p16, ER, PR, MIB-1, WT-1 EIC – p53 useful Low grade endometrioid – p53, vimentin, ER,
PR, PTEN Grade 3 endometrioid – limited value Clear cell – ER and PR negative.
P53,p16and Ki-67 intermediate between serous and endometrioid ca
![Page 59: ENDOMETRIAL CANCER Dr P Mukonoweshuro Consultant Pathologist RUH Bath.](https://reader037.fdocuments.us/reader037/viewer/2022103005/56649d895503460f94a6f224/html5/thumbnails/59.jpg)
Thank you
Questions?
Quiz
Highly recommend: Histopathology Volume 62 Number 1 January 2013.