Download Challenges in Endometrial biopsy

Common Challenges
in Endometrial Biopsy
Interpretation

Aaron Haig
Conflict of Interest Disclosures
Aaron Haig

I have not had in the past 3 years, a financial interest,
arrangement or affiliation with one or more organizations
that could be perceived as a direct or indirect conflict of
interest in the content of this presentation.
Endometrial biopsies
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Abnormal uterine bleeding (>95%),
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Pre or post menopausal
Other
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endometrial cells in pap
infertility
missed products
Adequate?
A. Adequate
 Photo
B.
Inadequate
C. Depends
Biopsy Adequacy
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No universal standards
Individual judgment
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Adequate for one situation, may not necessarily be
adequate for another
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At a minimum, need …
some glandular and stromal tissue from the fundus (to ensure
entry into the endometrial cavity)
Biopsy Adequacy
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If suspected atrophic …. minimal tissue is expected

However,
minimal tissue with hyperplasia or
 high clinical suspicion
Then a comment suggesting repeat biopsy is warranted.
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Biopsy Adequacy
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No formal criteria
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Unassessable (or insufficient) has been suggested as a
more appropriate term
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If fits with clinical than repeat biopsy is not needed
Outline
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Endometrial malignancy, subtyping
Benign mimics
Endometrial vs endocervical carcinoma
Vanishing carcinoma
Endometrial Malignancies
Type I
• Endometrioid
• variants
• Mucinous
Type II
• Serous
• Clear Cell
Other
• Mixed cell
adenocarcinoma
• Small cell
carcinoma
• Squamous cell
• Undifferentiated
• Others
Subtyping endometrial malignancy……
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Can be difficult
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Variant or unusual
morphologies
Scant tissue
High grade
Mixed
Non endometrial primary
What is it?
A: Endometrioid
B: Serous
C:Villoglandular
D: Clear cell
What is it?
A: Endometrioid
B: Serous
C:Villoglandular
D: Clear cell
Serous with a pseudoglandular pattern
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Serous with a prominent glandular pattern
Can be mistaken for low grade endometrioid Ca
Look for extreme discordance between architectural and
cytologic features
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Irregular luminal borders
Cells lack polarity
Marked pseudostratification, and
nuclear pleomorphism,
Brisk mitiotic activity
Single cell apoptosis
Serous vs Endometrioid
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Different treatments and prognosis
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type I vs type II
Morphology the most important tool
Serous vs Endometrioid
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Clinical history
Background
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EIC/atrophy
hyperplasia
Immunohistochemistry
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if interpreted properly
Webpathology.com
p53
How many are Serous?
A
B
C
D
How many are Serous?
A. 1
B. 2
C. 3
D. 4
How many are Serous?
Endometrioid,
nonvillous papillae
Serous
Endometrioid,
villoglandular
Endometrioid Adenocarcinoma with
Papillary Architecture
Villoglandular
1.
slender, finger-like papillae
- lacks branching and budding
2.
columnar cells, minimal
nuclear pseudostratification
3.
smooth apical luminal border,
preserved nuclear polarity
4.
mild cytologic atypia
- (grade 1, or only focal grade 2)
Wikimedia commons
Endometrioid Adenocarcinoma with
Papillary Architecture
Nonvilloglandular
1.
small pseudopapillae budding
into endometrioid type glands
2.
relatively uniform distribution of
pseudopapillae
3.
cohesive, polygonal cells with
abundant eosinophilic cytoplasm
4.
mild cytologic atypia
- usually grade 1 to focal 2
1.
can have overt squamous
differentiation
Endometrioid vs Serous
Immunohistochemical Panel

Proposed panel: p16, p53, ER, PR
p16 and p53
ER/PR
Serous
+
-
Endometrioid
-
+
Endometrioid vs Serous
Immunohistochemical Panel
Serous
Endometrioid
p16
p53
ER/PR
70-90% +
80%
5-50% +
40%+
10-20% (grade 3)
80%+
(falls to 15-50%
in grade3)
Note:
1. WT1 not reliable for endometrial serous (compared to ovarian serous)
2. p53 can be completely negative in ESC due to a truncated mutation (all or
none pattern)
Arch Pathol Lab Med, Vol 137, Nov 2013
Take home
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Not all that is papillary is serous
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High grade nuclear atypia and luminal irregularity helpful
for serous
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Also, increased mitotic figures and background endometrium
ER, PR, p16, p53 good panel
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but use with caution (especially grade 3 endometrioid).
Endometrioid with focal clear cells
Secretory endometrioid
Endometrioid with clear cell squamous
component
Serous carcinoma with clear cells
Clear cell features NOT favouring clear cell
carcinoma
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Columnar cells
Distinctive shape of vacuoles
Bland nuclear features
No high grade cytologic atypia,
tubulocytsic, papillary or solid
patterns
Immunohistochemistry
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Negative ER and diffuse p53 favour CCC
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Significant proportion do not show this
Clear cell
Endometrioid
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ER/RP
p53
Weak or absent
present
Diffuse and strong
less
Ki67 50% CCC; 20% endometrioid
p16 too much overlap
Endometrial Epithelial Metaplasia
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Morphology seen elsewhere in Mullerian tract.
Mullerian derived structures retain some degree of
plasticity
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Major mechanisms
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Degenerative/reparative
Hormonal
Neoplastic
Endometrial Epithelial Metaplasia
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Ciliary (tubal)
Eosinophilic
Squamous
Mucinous
Hobnail
Clear cell
Papillary syncytial
Adv Anat Pathol,Vol 16, Jan 2009
Endometrial Epithelial Metaplasia
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May be present in the full spectrum of endometrial
patterns
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Normal proliferative to adenocarcinoma
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No clinical significance
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However, potential for misinterpretation
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eg. Atypia in tubal metaplasia, carcinoma in clear cell, hobnail
and pap metaplasia
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Picture of diff patterns AP104 pg23
Squamous metaplasia
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Keratinizing or not keratinizing (morular)
Can be seen in reactive, hyperplasia or carcinoma
Squamous Metaplasia
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Degenerative changes or repair
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No risk of progression
Chronic endometritis, infarcted endometrial polyp, IUD
Also seen with ….
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Complex hyperplasia, atypical polypoid adenomyoma (APA),
adenocarcinoma
Seen in approx 25% of adenoCa
Things to remember of Squamous
Metaplasia
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Assessment is based only on glandular component
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Necrosis or solid growth do not alter interpretation
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Look for minimal mitotic activity and low proliferation rate
Hormonally inert
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No ER/RP receptors, do not regress with hormones
Things to remember of Squamous
Metaplasia
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Diagnosis based on glandular component
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E.g. simple hyperplasia with squamous morules
If extensive squamous differentiation, with no definitive
underlying glandular structure
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Recommend re-biopsy
Papillary Syncytial Metaplasia
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Commonly seen with
endometrial breakdown
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Regenerative process
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Can raise concern for
ESC or EIC.
Papillary Syncytial Metaplasia
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Minimal/reactive cytologic atypia
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Look for other signs of breakdown
- stromal balls
- fibrinous material
- neutrophilic infiltation
- apoptotic bodies
Also consistent with
features of tumour
diathaisis
Papillary Syncytial Metaplasia
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Immunohistochemistry has been shown:
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ER is down regulated
P16 strongly expressed
Increased p53 expression
Overlapping with serous
immunophenotype
- Look for low MF and decreased Ki-67
McCluggage Int J Gynecol Pathol Vol.31, May 2012
Papillary Syncytial Metaplasia
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Look for hyperplasia or EIC
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Look for high MF with increased Ki-67
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Immunohistochemistry can be helpful
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But do not over interpret
Significant overlap with serous carcinoma
Carcinoma:
Endocervical vs Endocervical
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Histologic overlap
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Both can have:
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endometrioid differentiation
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mucinous differentiation
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5% of endocervical
10% of endometrial
Treatment and prognostic
implications
Webpathology.com
Endometrial
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Mass centered in uterine
corpus or LUS
Co-existing hyperplasia
Squamous morules
Scant intervening stroma
Foamy histocytes
Endocervical
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Mass in cervix
Co-existing AIS (or SIL)
Marked associated stromal
desmoplasia
Endometrioisis
Webpathology.com
Immunohistochemical Panel
Endocervical
ER -
Vimentin -
CEA +
p16 diffuse
strong
Endometrioid
ER +
Vimentin +
CEA -
p16 neg, wk, or
focal strong
Note: significant overlap – IHC not definitive; use a panel
Endocervical vs Endometrial
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Need to correlate:
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clinical, radiological and IHC findings
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Still a significant number of cases it is not possible to tell, even
after resection
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Recommendation
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Biopsy:
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give differential diagnosis
Resection:
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provide appropriate staging information for both locations with a
comment of the diagnostic challenge
‘Vanishing Carcinoma’
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Cases with:
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Biopsy proven endometrial carcinoma
No residual carcinoma or biopsy site in subsequent
hysterectomy
0 – 19% (~3%)
T. Colgan Int J Gynecol Pathol 2007
‘Vanishing Carcinoma’
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Term has been described in prostate
Concept may be useful in both clinical and medicolegal
practice
‘Vanishing Carcinoma’
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Criteria for diagnosis of VCa
Malignant dx must be reviewed and confirm
1.
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r/o floaters etc…
2. Embed and examine entire endometrium
3. Document neoadjuvant tx
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high dose progestins and preop radiation therapy can eradicate EmCa
‘Vanishing Carcinoma’
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Well documented problem
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not to be assumed lab or Pathologist error.
DNA profiling can be use in cases with any suspicious of
mix-up or medico-legal cases
Questions….