1.
Approach to Endometrial Biopsy
Dr.CSBR.Prasad, MD.,
Professor & HOD
Deptt. of Pathology
Sri Devaraj Urs Medical College
Kolar-563101

2.
What do you think of this EM biopsy?

3.
What is the finding here?

4.
What is your impresion on this biopsy?
http://www.webpathology.com/image.asp?n=1&Case=568

5.
Some fundamentals
• Only endometrium from the fundus is suitable for
diagnosis
• The functionalis layer is particularly ideal
• Basalis layer is generally of little diagnostic value except
in two conditions:
1. Carcinoma
2. Irregular shedding
• Irregular development is best detected in larger
fragments of tissue where structural units retain their
relationship
• EM from the isthmic region is unsuitable for functional
diagnosis as they fail to respond to hormonal changes

6.
Some fundamentals
• Proliferative phase may fluctuate between 10-
20days – Dating is not possible
• Secretory phase is fixed and hence dating is
possible
• Cystic dilatation of an occasional gland is not
necessarily a sign of hyperplasia
• Ovulation may recur sporadically, even years
after menopause, the associated corpus
luteum is insufficient

7.
EM Biopsy
• Different methods of obtaining endometrial
sample
– Curetting (D&C)
– Pipelle biopsy or other equivalent technique
– Hysteroscopy and direct biopsy
– Endometrial cytology

8.
Adequacy
• There are no definitive guidelines / agreements *
• If you can make a diagnosis, it is adequate
• Clinical details are very important
– Eg: Strips of endometrium in a post menopausal
woman
• Don’t write “inadequate”
– Sign out
• No stroma
• Proliferative without definite stroma
• No endometrium
• No tissue
*Phillips V, McCluggage WG. Results of a questionnaire regarding criteria for
adequacy of endometrial biopsies. J Clin Pathol 2005;58:417–9.

9.
EM biopsy, Post menopausal

10.
Algorithm for assessment of the adequacy
of an endometrial biopsy specimen
McCluggage WG. My approach to the interpretation of endometrial biopsies and curettings .
J Clin Pathol 2006;59:801–12.

11.
Indications for EM Biopsy*
4 Main INDICATIONS Other Indications
Determine the cause of AUB AGC /EM cells in PAP smear
Assessment of response of the EM to
hormone Tx
Finding thickened EM in US
in post menopausal women
Status of EM in infertile patients /
dating
Evacuation of POC (Spontaneous or
MTP)
*Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach
By Michael Mazur, Robert J. Kurman

12.
DDs for presence of adipose tissue in
EM samples
• Uterine Perforation (Critical value)
• Lipoleiomyoma

13.
Myometrium in the curettings
• Notify the clinician how much myometrium
was there in the curettings
• This helps in two ways:
1. Gives info regarding the consistency of
myometrium
2. Gives information about the technique of
curettage

14.
Artefacts
• Telescoping (glands within glands)
• Artefactual crowding and compression of
glands
• Pseudopapillary architecture of superficial
strips of EM
• Crushed endometrial glands and stroma may
be extremely cellular and can cause concern

15.
Telescoping (gland within gland)

16.
Crushed endometrial glands

17.
Pseudopapillary architecture of
superficial strips of EM

18.
Normal EM

19.
Proliferative endometrium

20.
Proliferative endometrium

21.
Mitosis - indicator of proliferative activity
• Non-reactive endometrium (No mitosis)
• Mitosis in post menopausal EM
– May be associated with hyperplasia
– If there is no hyperplasia:
• Continued estrogen stimulation
• Prolapse
• EM polyp

22.
EM – Status Post menopusal

23.
Secretory endometrium

24.
Endometritis
Common components in EM:
• Lymphocytes, including natural killer cells and lymphoid
aggregates
• PMNs: Premenstrual and menstrual phases
Plasma cells: *
• Plasma cells: Is it always endometritis?
• Other morphological features that favour endometritis:
– Disturbance in maturation—focal areas that are out of cycle
with other areas
– Stromal edema and
– Characteristically, a spindle-cell alteration of the stroma,
especially around glands
– Glandular architectural complexity and cytological atypia
*Bayer-Garner IB, Korourian S. Plasma cells in chronic endometritis are easily identified when
stained with syndecan-1. Mod Pathol 2001;14:877–9

25.
Lymphoid aggregate

26.
Spindle-cell alteration of the stroma,
especially around glands

27.
Endometritis
In the absence of other
morphological features
exhaustive search for plasma
cells is unnecessary

28.
Endometritis
• Focal necrotising endometritis*
• Granulomatous endometritis
– Tuberculosis
– Sarcoidosis
– Others
*Bennett AE, Rathore S, Rhatigan RM. Focal necrotizing endometritis: a clinicopathologic
study of 15 cases. Int J Gynecol Pathol 1999;18:220–5.

29.
EM polyp
• 40-50yrs (rare before menarche, can occur after menopause)
• Site: Fundus and cornua
• Often pedunculated
• Histology:
– Composed of glands and stroma
– Mostly proliferative changes (cyclical changes are rare)
– Foci of squamous metaplasia
– Smooth muscle may form a component
– Blood vessels are thick walled and tortuous
• Rarely carcinoma can arise (3%)
– Through examination of polyp / stalk is important
– Atypicalities in a post menopausal woman warrants hysterectomy

30.
EM polyp
• Proliferative activity is common in endometrial
polyps, even in postmenopausal women
• A diagnosis of simple hyperplasia should not be
made in the case of an endometrial polyp
• Carcinomas may arise in endometrial polyps
• Endometrial polyps are particularly common in
association with tamoxifen
• There is a peculiar tendency for serous carcinoma
and EIC to arise within endometrial polyps whether
sporadic or associated with tamoxifen*
*Silva EG, Jenkins R. Serous carcinoma in endometrial polyps. Mod Pathol
1990;3:120–8.

31.
EM polyp

32.
Metaplasias - Epithelial
• Epithelial metaplasias: Squamous or mucinous
– Associated with hyperplasia / carcinoma
• Ciliated metaplasia: Applicable only when
extensive resembling fallopian tube
• Papillary syncytial metaplasia:
– May be a reparative response
– When florid, this may be suggestive of a serous
carcinoma or an EIC
• Mucinous metaplasia
• Benign papillary proliferations

33.
Squamous metaplasia

34.
Tubal metaplasia

35.
Benign papillary proliferation

36.
Simple mucinous metaplasia in the
basalis of an atrophic endometrium

37.
Include ichthyosis uteri

38.
Metaplasias - Stromal
• Formation of smooth muscle, cartilage and
bone
Importance: May be it difficult to assess myometrial
invasion in carcinoma.
What are the differentials for stromal metaplasia?
Retained fetal parts
Int J Gynecol Pathol 2007;26:115

39.
Metaplasias - Stromal
Endometrial stromal nodule with smooth muscle metaplasia

40.
Effects of Tamoxifen on the Endometrium
• Tamoxifen is widely used as adjuvant therapy in the
management of breast cancer
• Tamoxifen may exert a proliferative effect on the endometrium
• The risk increases with increasing duration and dosage of
tamoxifen
EFFECTS:
• Benign polyps (most common)
• Stromal fibrosis
• Stromal condensation around glands (DD Adenosarcoma)
• Endometrial hyperplasia
• Endometrioid and Non-Endometrioid carcinomas
• Tamoxifen-associated polyps should be extensively sampled

41.
EM Hyperplasia
Def: Endometrial proliferation with an increase in
gland to stroma ratio (from 2:1 to 3:1).
Classification of endometrial hyperplasia:
– WHO 1994 - Four tier system
– WHO 2014 – Two tier system
Atypia:
• Vesicular nuclei
• Prominent nucleoli
• Rounding of nuclei
• Increased cytoplasmic eosinophilia

42.
New WHO classification of
endometrial hyperplasias - 2014
New term Synonym Genetic changes Coexistent
invasive
endometrial
carcinoma
Progression
to invasive
carcinoma
Hyperplasia
withoutatypia
Non-atypical
EM
hyperplasias
Low level of somatic
mutations
< 1 % RR: 1.01–
1.03
Atypical
hyperplasia/en
dometrioid
intraepithelial
neoplasia
Atypical EM
hyperplasias,
EIN
Many of the genetic
changes typical for
endometrioid
endometrial cancer
are present
25–33 % 2
59 % 1
RR: 14–45
1. Antonsen S L, Ulrich L, Hogdall C. Patients with atypical hyperplasia of the endometrium should be treated in
oncological centers. Gynecol Oncol. 2012;125:124–128
2. Zaino R, Carinelli S G, Ellenson L H, Lyon: WHO Press; 2014. Tumours of the uterine Corpus: epithelial
Tumours and Precursors; pp. 125–126.

43.
EM hyperplasia

44.
Simple hyperplasia without atypia
http://www.webpathology.com/image.asp?n=1&Case=568

45.
Complex hyperplasia without atypia
http://www.webpathology.com/image.asp?n=1&Case=568

46.
Complex hyperplasia without atypia

47.
Atypical hyperplasia

48.
Atypical hyperplasia

49.
Atypical hyperplasia

50.
Complex hyperplasia without nuclear
atypia & Carcinoma

51.
Complex hyperplasia with atypia
• Regresses in about 57% of cases
• Progression to adenocarcinoma occurs in
about 30% of cases
• Hysterectomy soon after biopsy: between 23%
and 48% harbor EM adenocarcinoma
http://www.webpathology.com/image.asp?n=8&Case=568

52.
Benign mimics of EM hyperplasia
• Artefacts
• Endometritis
• Endometrial polyp
• Arias-Stella reaction
• Disordered proliferative endometrium
• Benign papillary proliferations
• Lower uterine segment endometrium

53.
Disordered proliferative endometrium

54.
Immunohistochemical staining of FOXA1 and AR in normal
endometrium, atypical hyperplasias, and endometrial cancer
Qiu, Meiting, Bao, Wei, Wang, Jingyun, Yang, Tingting, He, Xiaoying, Liao, Yun, Wan, Xiaoping . FOXA1
promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer BMC Cancer
2014; 14:78 ·

55.
Cyclin D1 staining
1-Surface epithelium
2-Complex hyperpasia
3-Endometrioid
adenocarcinoma (+)
and adenomyosis(-)

56.
Arias – Stella reaction

57.
Extensive regions of necrosis in
curettings - Causes
• Degenerating carcinoma
• Septic abortion
• Infarcted polyp
• Degenerated submucosal leiomyoma

58.
Extensive regions of necrosis
better microscopic evidence must be sought before
making a definitive diagnosis of carcinoma

59.
Adenocarcinoma of endometrium
• Criteria helpful in distinguishing carcinoma from
hyperplasia: The tumor is probably malignant if:
– Glands are closely packed without intervening stroma for at
least half the low power field
– If gland Lumina containing multiple thin branching papillary
projections with a collagenous core with neoplastic epithelium
occupying more than half of low-power field
– If sheets of squamous cells occupy more than half of low-
power field
– Bridging between the adjacent glands – Cribriform pattern
– Luminal necrosis with PMN infiltration
– If stroma between the glands is collagenous

60.
Some tips
• Interact with your clinician / History is important for interpretation
• Separate the endometrial tissue proper from the blood clots for
processing
• Endometrium with surface epithelium is best for interpretation. Absence
of surface epithelium compromises interpretation
• Do not report hyperplasia on secretory endometrium
• In all cases of abnormal uterine bleeding, consider the possibility of polyp
• Finding fat in EM curetting is a critical value. It should be intimated to the
clinician
• Aware of the mimics
• All endometrial cancers should be typed and, if appropriate, graded, even
for small biopsy specimens

61.
Thank you