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Cancer of endometrium
(endometrioid adenocarcinoma)
Dr. Alwin
David Chia-Chi Wu
Basic data
• IC number : Pb80129
• Gender : female
• Age : 52
• Allergy : no know drug allergy
Past history
• Past medical history : 1. dyslipidemia 2.knee
osteoarthtritis (left)
• Menstrual history : menopause for the past 2
years
• Past OB/GYN history : Previous 2 Lower
Segment Caesarean Section
2013.10
Abnormal pap smear (+)
Postmenopausal bleeding (-)
Abdominal pain (-)
Postmenopausal bleeding (-)
Histology : endometrial carcinoma
D&C with biopsy
Physical examination
• Alert and comfortable
• Vital sign stable
• Heart : S1,S2 no murmurs
• Lung : clear
• Abdomen : soft no tender
• Total hysterectomy and bilateral salpingo-
oophrectomy
• Endometrial curettage : complex atypical
endometrial hyperplasia with areas consistent
with endometrioid adenocarcinoma
• Indication for op : complex with areas
consistent with endometrioid
adenocarcinoma
• Post op : patient well and stable on discharge
on 2014.2.14
Gross description
• Total hysterectomy and bilateral salpingo-
oophrectomy speciman
• Uterus : reveals a polypoidal lesion occupying the
entire endometrial cavity measuring 4.5*4.2*2cm
• Cervix : 3cm*3cm, no tumor
• Right ovary : 2.3*2.2*0.5cm No tumor
• Left ovary : 2.2*1.5*0.7 No tumor
• Tubes : unremarkable, No tumor
Microscopic description
• Tumor type : adenocarcinoma of
endometrium, endometrioid type
• Histologic grade : FIGO grade I
• Nuclear grade : nuclear grade 1-2
Depth of tumor invasion
• Tumor is limited to the endometrium
• Invasive tumor is confined to the
endometrium with an irregular endometrial
junction
• Lymphocytic infiltrate is seen around the
tumor
• Suspicious for superficial myometrial
invasion(A14)
• Endocervical invasion : no invasion is
identified
• Vascular invasion : no invasion is identified
• Uterine serosal involvement : no
• Adnexal involvement : no
• Vaginal involvement : not assessable
• Parametrial involvement : no
• Myometrium : foci of adenomyosis is seen
• Cervix : A8&A23 show squamous metaplasia
as well as a hemorrhagic and denuded
endocervical region, without malignancy
• Adnexae : corpus luteum cyst is noted in left
ovary ; corpora albicantes and follicular cyst at
both ovaries
Diagnosis
• Endometrial endometrioid adenocarcinoma,
FIGO I , tumor predominately confined to the
endometrium , lymphovascular invasion
identified
80% accounts for endometrial carcinoma
Endometrioid carcinoma
Arise from endometrioid hyperplasia
Well differentiated (tomaxifen affect)
Prior pelvic radiation increase the risk
HNPCC increase 40~60% in endometrial cancer
Microscopic features
Tumor wthin endometrium typically has tubular gland
Squamous differentiation is common
Patterns of endometrial invasion
Myoinvasion
Glands, Nets, Cords, Single tumor cells
Irregular border with the myometrium
Pushing border with myometrium
Well-circumscribed, expansile
Change in therapy
• Radiation-induced changes : complete
disappearance of the tumor, necrotic tumor,
increased volume, vacuolation of cytoplasm,
bizarre, pyknotic, karyorrhectic nuclei,
enlarged nucleoli
Effects
• Cytologic changes : Decreased N:C ratio
• An increased amount of eosinophilic
cytoplasm and a decrease in nuclear size
Immunohistochemical findings
• Helpful in distingushing endometrium
carcinoma from endocerviacl adenocarcinoma
CEA Vimentin ER PR
Endometrial endometrioid carcinoma - + + +
Endocervical adenocarcinoma + - - -
P16
Endometrial endometrioid adenocarcinoma Weak
Endocervical adenocarcinoma Strong
CD34 CD10
Endocervical stroma Positive Negative
Endometrial stroma Negative Positive
Introduction
• Mutations in AT-rich interactive domain 1A
(ARID1A) have been detected in a wide variety
of human cancers, most frequently in
endometrium-related carcinomas
• ARIDA1 encodes BAF250A is a member of
SWI/SNF complex
Neoplasia (2012) 14, 986–993
SWI/SNF complex
Cellular differentiation
Tissue development
Control gene expression
Inactivation on SWI/SNF system
• Inactivation of several components of this
complex had can be associated with certain
type of cancer
Inactivation INI1
Rhabdoid tumor ,atypical
teratoid/rhabdoid tumor
Inactivation BRG1
and BRM
15%-20% primary non-small cell
lung cancers
Mutation in ARID1A
43%-57% ovarian clear cell
carcinomas
30% ovarian endometrioid
carcinomas
J Gynecol Oncol Vol. 24, No. 4:376-381
Inactivating mutations of ARID1A in
gynecologic tumors
• ARID1A has a tumor suppressor role
• Mutation in ARID1A cause Breast carcinoma
Esophageal adenocarcinoma
Gastric carcinoma
Pancreatic carcinoma
Hepatocellular carcinoma
Prostate carcinoma
Neuroblastoma/Medulloblastoma
Uterine/ovarian tumor
Burkitt lymphoma
Transitional cell carcinoma
AR1DA1 as tumor suppressor
Siliencing/deleted of ARIDA1
Expression of ARIDA1
Enhance proliferation
Suppress proliferation
Neoplasia (2012) 14, 986–993
Different appearance of ARID1A
• ARID1A is a nucleocytoplasmic protein whose
stability depends on its subcellular localization
Stable
Unstable ubiquitin-proteasome system
Alteration of ARID1A in ovarian tumors
Ovarian endometrioid carcinoma (30%)
Ovarian clear cell carcinoma (43%-57%)
Loss of ARIDA1
Cystic type (43%)
Adenofibromatous type (61%)
Inactivation of ARID1A occurs in the
early stages of tumor development
Borderline ovarian tumors (43%-57%)
Loss of ARIDA1
Endocervical-type mucinous
borderline tumors (33%)
borderline endometrioid tumor
(13%)
Alteration of ARID1A in uterine carcinomas
• ARID1A mutations frequently co-occurs with
other mutations
• Loss of ARID1A is associated with mismatch
repair deficiency
Endometrioid carcinoma
Mutation (40%)
Loss of expression in low-grade (26%-29%)
Loss of expression in high-grade (39%)
Clonal loss in ARIDA1
16% complex atypical hyperplasia
24% low-grade endometrioid carcinoma
10% high-grade endometrioid carcinoma
Complete loss in ARIDA1
0% complex atypical hyperplasia
25% low-grade endometrioid carcinoma
43% high-grade endometrioid carcinoma
ARID1A plays important role not only in tumor
initiation, but also in tumor progression.
Negative Low-grade PositiveLow-gradePositiveHigh -grade
Conclusion
• High prevalence of somatic mutations in
ovarian and endometrial cancers indicates a
pivotal role of ARID1A in their development
• Understanding the roles of ARID1A in the
pathogenesis of endometrium-derived tumors
is fundamental for future translational studies
Thanks for your listening !
Pap smear ?? Not useful !
Single dominant mass
Friable neoplasm
Undetectable
Different types of Adenocarcinoma (80%)
1. Squamous cells + glandular cells =>
adenosquamous carcinomas
2. Squamous cells + glandular cells => adenocarcinoma
with squamous differentiation
3. Squamous cells + glandular cells => adenoacanthoma
Classification
• Grade 1 tumors have 95% or more of the
cancerous tissue forming glands.
• Grade 2 tumors have between 50% and 94%
of the cancerous tissue forming glands.
• Grade 3 tumors have less than half of the
cancerous tissue forming glands. Grade 3
cancers are called "high-grade."
Risk factor
Endogenous
Increasing age
Early menarche
Late menopause
Polycystic ovary
syndrome
DM
Nulliparity
Exogenous
Unopposed
estrogen therapy
Tamoxifen therapy
• Lynch syndrome

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Endometrioid adenocarcinoma

  • 1. Cancer of endometrium (endometrioid adenocarcinoma) Dr. Alwin David Chia-Chi Wu
  • 2. Basic data • IC number : Pb80129 • Gender : female • Age : 52 • Allergy : no know drug allergy
  • 3. Past history • Past medical history : 1. dyslipidemia 2.knee osteoarthtritis (left) • Menstrual history : menopause for the past 2 years • Past OB/GYN history : Previous 2 Lower Segment Caesarean Section
  • 4. 2013.10 Abnormal pap smear (+) Postmenopausal bleeding (-) Abdominal pain (-) Postmenopausal bleeding (-) Histology : endometrial carcinoma D&C with biopsy
  • 5. Physical examination • Alert and comfortable • Vital sign stable • Heart : S1,S2 no murmurs • Lung : clear • Abdomen : soft no tender
  • 6. • Total hysterectomy and bilateral salpingo- oophrectomy • Endometrial curettage : complex atypical endometrial hyperplasia with areas consistent with endometrioid adenocarcinoma
  • 7. • Indication for op : complex with areas consistent with endometrioid adenocarcinoma • Post op : patient well and stable on discharge on 2014.2.14
  • 8. Gross description • Total hysterectomy and bilateral salpingo- oophrectomy speciman • Uterus : reveals a polypoidal lesion occupying the entire endometrial cavity measuring 4.5*4.2*2cm • Cervix : 3cm*3cm, no tumor • Right ovary : 2.3*2.2*0.5cm No tumor • Left ovary : 2.2*1.5*0.7 No tumor • Tubes : unremarkable, No tumor
  • 9. Microscopic description • Tumor type : adenocarcinoma of endometrium, endometrioid type • Histologic grade : FIGO grade I • Nuclear grade : nuclear grade 1-2
  • 10. Depth of tumor invasion • Tumor is limited to the endometrium • Invasive tumor is confined to the endometrium with an irregular endometrial junction • Lymphocytic infiltrate is seen around the tumor • Suspicious for superficial myometrial invasion(A14)
  • 11. • Endocervical invasion : no invasion is identified • Vascular invasion : no invasion is identified • Uterine serosal involvement : no • Adnexal involvement : no • Vaginal involvement : not assessable • Parametrial involvement : no
  • 12. • Myometrium : foci of adenomyosis is seen • Cervix : A8&A23 show squamous metaplasia as well as a hemorrhagic and denuded endocervical region, without malignancy • Adnexae : corpus luteum cyst is noted in left ovary ; corpora albicantes and follicular cyst at both ovaries
  • 13. Diagnosis • Endometrial endometrioid adenocarcinoma, FIGO I , tumor predominately confined to the endometrium , lymphovascular invasion identified
  • 14. 80% accounts for endometrial carcinoma Endometrioid carcinoma Arise from endometrioid hyperplasia Well differentiated (tomaxifen affect) Prior pelvic radiation increase the risk HNPCC increase 40~60% in endometrial cancer
  • 15. Microscopic features Tumor wthin endometrium typically has tubular gland Squamous differentiation is common
  • 16. Patterns of endometrial invasion Myoinvasion Glands, Nets, Cords, Single tumor cells Irregular border with the myometrium Pushing border with myometrium Well-circumscribed, expansile
  • 17. Change in therapy • Radiation-induced changes : complete disappearance of the tumor, necrotic tumor, increased volume, vacuolation of cytoplasm, bizarre, pyknotic, karyorrhectic nuclei, enlarged nucleoli
  • 18. Effects • Cytologic changes : Decreased N:C ratio • An increased amount of eosinophilic cytoplasm and a decrease in nuclear size
  • 19. Immunohistochemical findings • Helpful in distingushing endometrium carcinoma from endocerviacl adenocarcinoma CEA Vimentin ER PR Endometrial endometrioid carcinoma - + + + Endocervical adenocarcinoma + - - - P16 Endometrial endometrioid adenocarcinoma Weak Endocervical adenocarcinoma Strong CD34 CD10 Endocervical stroma Positive Negative Endometrial stroma Negative Positive
  • 20.
  • 21. Introduction • Mutations in AT-rich interactive domain 1A (ARID1A) have been detected in a wide variety of human cancers, most frequently in endometrium-related carcinomas • ARIDA1 encodes BAF250A is a member of SWI/SNF complex Neoplasia (2012) 14, 986–993
  • 22. SWI/SNF complex Cellular differentiation Tissue development Control gene expression
  • 23. Inactivation on SWI/SNF system • Inactivation of several components of this complex had can be associated with certain type of cancer Inactivation INI1 Rhabdoid tumor ,atypical teratoid/rhabdoid tumor Inactivation BRG1 and BRM 15%-20% primary non-small cell lung cancers Mutation in ARID1A 43%-57% ovarian clear cell carcinomas 30% ovarian endometrioid carcinomas J Gynecol Oncol Vol. 24, No. 4:376-381
  • 24. Inactivating mutations of ARID1A in gynecologic tumors • ARID1A has a tumor suppressor role • Mutation in ARID1A cause Breast carcinoma Esophageal adenocarcinoma Gastric carcinoma Pancreatic carcinoma Hepatocellular carcinoma Prostate carcinoma Neuroblastoma/Medulloblastoma Uterine/ovarian tumor Burkitt lymphoma Transitional cell carcinoma
  • 25. AR1DA1 as tumor suppressor Siliencing/deleted of ARIDA1 Expression of ARIDA1 Enhance proliferation Suppress proliferation Neoplasia (2012) 14, 986–993
  • 26. Different appearance of ARID1A • ARID1A is a nucleocytoplasmic protein whose stability depends on its subcellular localization Stable Unstable ubiquitin-proteasome system
  • 27. Alteration of ARID1A in ovarian tumors Ovarian endometrioid carcinoma (30%) Ovarian clear cell carcinoma (43%-57%) Loss of ARIDA1 Cystic type (43%) Adenofibromatous type (61%)
  • 28. Inactivation of ARID1A occurs in the early stages of tumor development Borderline ovarian tumors (43%-57%) Loss of ARIDA1 Endocervical-type mucinous borderline tumors (33%) borderline endometrioid tumor (13%)
  • 29. Alteration of ARID1A in uterine carcinomas • ARID1A mutations frequently co-occurs with other mutations • Loss of ARID1A is associated with mismatch repair deficiency Endometrioid carcinoma Mutation (40%) Loss of expression in low-grade (26%-29%) Loss of expression in high-grade (39%)
  • 30. Clonal loss in ARIDA1 16% complex atypical hyperplasia 24% low-grade endometrioid carcinoma 10% high-grade endometrioid carcinoma Complete loss in ARIDA1 0% complex atypical hyperplasia 25% low-grade endometrioid carcinoma 43% high-grade endometrioid carcinoma
  • 31. ARID1A plays important role not only in tumor initiation, but also in tumor progression. Negative Low-grade PositiveLow-gradePositiveHigh -grade
  • 32. Conclusion • High prevalence of somatic mutations in ovarian and endometrial cancers indicates a pivotal role of ARID1A in their development • Understanding the roles of ARID1A in the pathogenesis of endometrium-derived tumors is fundamental for future translational studies
  • 33. Thanks for your listening !
  • 34.
  • 35.
  • 36. Pap smear ?? Not useful !
  • 37.
  • 38. Single dominant mass Friable neoplasm Undetectable
  • 39. Different types of Adenocarcinoma (80%) 1. Squamous cells + glandular cells => adenosquamous carcinomas 2. Squamous cells + glandular cells => adenocarcinoma with squamous differentiation 3. Squamous cells + glandular cells => adenoacanthoma
  • 40. Classification • Grade 1 tumors have 95% or more of the cancerous tissue forming glands. • Grade 2 tumors have between 50% and 94% of the cancerous tissue forming glands. • Grade 3 tumors have less than half of the cancerous tissue forming glands. Grade 3 cancers are called "high-grade."
  • 41.
  • 42. Risk factor Endogenous Increasing age Early menarche Late menopause Polycystic ovary syndrome DM Nulliparity Exogenous Unopposed estrogen therapy Tamoxifen therapy