Endometrioid carcinoma of the uterine corpus is a malignant epithelial neoplasm characterized by varying architectural patterns and is predominantly found in postmenopausal women, with a high incidence in high human development index countries. The carcinoma is classified into four molecular subtypes, with clinical features often presenting as postmenopausal bleeding, and an alignment of pathogenesis with prolonged estrogen exposure and genetic syndromes like Lynch syndrome. Histopathological assessment, including grading per FIGO criteria, and immunohistochemistry are crucial for differentiating subtypes and informing prognosis and treatment strategies.

1. Endometrioid carcinoma
of the uterine corpus
Based on WHO Classification of female genital tumors, 5th edition
Dr Abu Suraih Sakhri

2. Definition
• Malignant epithelial neoplasm
• varying proportions of glandular, papillary, and
solid architecture
• Neoplastic cells showing endometrioid
differentiation

3. Subtypes
Four molecular subtypes
1. POLE-ultramutated endometrioid carcinoma
2. Mismatch repair-deficient endometrioid
carcinoma
3. p53-mutant endometrioid carcinoma
4. No specific molecular profile (NSMP) endometrioid
carcinoma.

4. Clinical features
• Postmenopausal women (90% > 50 years)
• Median patient age - 63 years
• Typically present with abnormal/postmenopausal
bleeding.
• Advanced disease presents with pelvic/
abdominal symptoms resemble ovarian
carcinoma !

5. Epidemiology
• Sixth most commonly diagnosed cancer in women
• Second most commonly diagnosed female genital
organ cancer.
• The highest rates were found in very high Human
Development Index (HDI) countries (more than half
of the cases)

6. • Post-menopausal bleeding- Most common
symptom leading to diagnosis
• High-income countries-5-year survival rate is high
(-80% in the USA)
• Worldwide- 14th leading cause of cancer death.
• Close to 90,000 deaths/ year

7. Etiology
• Prolonged exposure to unopposed estrogen-
Mainly

8. Pathogenesis
• Shared molecular alterations with endometrial atypical hyperplasia /
endometrioid intraepithelial neoplasia.
• Association with Lynch syndrome and Cowden syndrome
• Exposure to higher total concentrations of estrogens
o early menarche
o Late menopause
o Nulliparity
o Obesity
o Tamoxifen
o Polycystic ovary syndrome
o Estrogen-producing ovarian tumours

9. Gross appearance
• Exophytic or diffusely
infiltrative
• Varying degrees of
necrosis and
haemorrhage
• Some cases arise within
the lower uterine
segment
Source- WHO classification of female genital tumors

10. Histopathology
• Typically displays (villo)glandular architecture
o cells that are usually columnar with pseudostratified
nuclei.
o Cytoplasm - eosinophilic and granular
o Smooth luminal outline
o Nuclear atypia - mild to moderate, inconspicuous nucleoli
(except in high-grade EEC)
o Mitotic count - highly variable

11. o Squamous differentiation is frequent (10-25%)
⁻ As morules or solid sheets of eosinophilic cells
⁻ Keratinization +

12. Histological patterns, which are not associated
with different prognosis
1. Secretory patterns
Resemble early secretory endometrium, either focal or diffuse,
mimicking clear cell carcinoma
Which are
o Small non-villous papillae
o Microglandular pattern
o Spindle cell pattern
o Sertoliform pattern
o sex cord-like formations and hyalinization

13. Stromal Invasion
• Differentiate from Hyperplasia and invasive cancer
• Defined as
oLoss of intervening stroma (a confluent glandular, cribriform, maze-like
pattern)
oor An altered endometrial stroma (desmoplastic stromal
reaction)
oor Complex (mostly villoglandular) architecture.

14. Endometrioid endometrial cancer with mucinous
differentiation –difficult to distinguish from atypical
mucinous glandular proliferations
How to differentiate?
cribriform or confluent architecture and cytological
atypia in the latter.

15. Grading
• FIGO grading criteria
Grade 1 < 5%
Grade 2 6-50% Solid non-glandular, Non-squamous growth
Grade 3 > 50%
• Binary Grading
------ Low Grade
------ High Grade

16. • Severe cytological atypia in the majority of
cells (> 50%) increases the grade by one level
• Exclude Serous carcinoma - nuclear atypia out
of proportion to the architecture!
• In low-grade EEC- Usually endometrioid
differentiation
• In high-grade - squamous differentiation
strongly favours EEC

17. Immunohistochemistry
Low Grade EEC
Endocervical
adenocarcinoma
ER/ PR
Diffuse strong
immunoreactivity
Negative
p16 Patchy positivity Diffuse immunoreactivity

18. may be difficult to distinguish
from serous endometrial carcinoma, but it is usually solid and
shows less-pronounced nuclear pleomorphism. raises
serous carcinoma as a possibility. Loss of immunoreactivity for
ARID1A, PTEN, or one of the mismatch repair proteins favours
high-grade EEC. Abnormal p53 expression is reported in 2-5%
of low-grade and 20% of high-grade EECs {274,1465B,1465D}.

19. High Grade EEC
Serous Endometrial
carcinoma
 solid and shows less-pronounced
nuclear pleomorphism
 Loss of immunoreactivity for
ARID1A, PTEN, or one of the
mismatch repair proteins favours
high-grade EEC
 Diffuse high grade atypia out of
proportion to architectural features
EEC- Endometrioid endometrial carcinoma

20. Lymphovascular invasion
 Present in 5-15% of cases
 Associated with the microcystic, elongated, and
fragmented (MELF) pattern of invasion and with
mismatch repair
deficiency.
 Particular artefacts, such as displacement of
tumour cells in spaces and retraction of tissue due to
delayed fixation, may mimic lymphovascular invasion
and should be excluded

21. POLE-
ultramutated EC
MMR-deficient
EC
p53-mutant EC
NSMP EC
Associated
molecular
features
> 100
mutations/Mb,
SCNA very
low, MSS
10-100
mutations/Mb,
SCNA low,
MSI
< 10 mutations/Mb,
SCNA high,
MSS
< 10 mutations/Mb,
SCNA low,
MSS, 30-40% with
CTNNB1
mutations
Associated
histological
features
Often high-grade,
ambiguous
morphology with
scattered tumour
giant cells,
prominent TILs
Often high-grade,
prominent TILs,
mucinous
differentiation,
MELF-type invasion,
LVSI
Mostly high-grade
with diffuse
cytonuclear atypia;
glandular and
solid forms exist
Mostly low-grade
with frequent
squamous
differentiation or
morule,
absence of TILs
Molecular classification of endometrioid carcinoma (EC)

22. Diagnostic
tests
NGS / Sanger
sequencing /
hotspot
analysis
MMR-IHC:
MLH1, MSH2,
MSH6,
and PMS2; MSI
assay; NGS
p53-IHC:
mutant-like
staining3
pathogenic
MMR-
proficient, p53-
wildtype, and
PO LE variant
absent
Associated
clinical
features
Younger age at
presentation
May be
associated with
Lynch
syndrome
Advanced stage
at presentation
Higher body
mass index
Prognosis Excellent Intermediate Poor
Intermediate to
excellent
POLE-
ultramutated EC
MMR-deficient
EC
p53-mutant EC NSMP EC

23. Cytology
Not clinically relevant

24. Essential and desirable diagnostic criteria
Essential: invasive endometrial carcinoma with
endometrioid differentiation.
Desirable: some degree of squamous, secretory,
or mucinous differentiation.

25. Staging
TNM classification
FIGO staging system.

26. Molecular prevalence in EEC

27. Prognosis and prediction
• FIGO and UICC staging is based on depth of myometrial
invasion (< 50% or > 50%) and on endocervical stromal,
adnexal, and lymph node involvement.
• Unequivocal lymphovascular invasion is used in treatment
algorithms
• Distinction between focal and extensive lymphovascular
invasion (> 5 vessels) have prognostic significance.

28. Synchronous endometrioid carcinomas of
endometrium and ovaries
• Most are clonally related
• Conservative management when the following four
criteria are met:
(1) both tumours are low-grade
(2) < 50% myometrial invasion
(3) no involvement of any other site
(4) absence of extensive lymphovascular invasion.

29. • For treatment purposes, these neoplasm
should be managed as independent tumours.

30.  The efficacy of conservative treatment of grade 1
endometrioid carcinoma or endometrial atypical
hyperplasia / endometrioid intraepithelial neoplasia
with hormonal agents may be monitored by
histology, but this is not yet standard clinical practice

31. Endometrioid carcinoma. High-grade endometrioid endometrial carcinoma
(FIGO grade 3), p53-mutant

32. Endometrioid carcinoma. A High-grade endometrioid endometrial carcinoma (EEC) (FIGO grade 3), mismatch
repair-deficient. Note the abundance of tumour-infiltrating lymphocytes and the substantial lymphovascular
space invasion frequently observed in mismatch repair-deficient EEC. B Low-grade EEC (FIGO grade 1), no specific
molecular profile (NSMP). This tumour was mismatch repair-proficient and p53-wildtype and did not carry a
pathogenic PO LE variant; it was therefore designated NSMP. Note the squamous differentiation frequently
observed in low-grade EEC.

33. The p53 immunohistochemistry of this tumor shows abnormal diffuse nuclear overexpression
associated with the presence of TP53 mutation.

34. High-grade endometrioid endometrial carcinoma (FIGO grade 3),
POLE-mutant. Note the solid non-squamous growth

35. Thank you
Send feedbacks at abusuraihsakhri@gmail.com