W2L3 - Endometrial Lesions

Question 1

Menstrual Cycle - Proliferative Phase

Answer 1

Days 5-14
Due to effect of estrogen on developing follicle
Epithelial cells lining the glands have pseudostratified appearance
Loose stroma of spindled cells
Mitoses present within glands and stroma
Cytology
- uniform nuclei with finely granular chromatin pattern

Question 2

Menstrual Cycle - Secretory Phase

Answer 2

Days 14-28
Due to changing levels of estrogen and progesterone
First sign is presence of subnuclear vacuoles
Outlines of the glands becomes markedly irregular in contrast to rounded contours of proliferative glands
Stromal cells become decidualised
Cytology
- diffuse cytoplasmic vacuolisation with a hazy appearance

Question 3

Menstrual Cycle - Menstrual Phase

Answer 3

If pregnancy has not occured, corpus luteum fails leading to marked fall in progesterone
Leads to menstrual phase characterised by crumbling of the stroma and glandular collapse

Question 4

Endometrial Elements Encountered in Cervical Smears

Answer 4

Epithelial cells
Stromal cells
Histiocytes
Leukocytes
Erythrocytes

Question 5

Epithelial Endometrial Cells

Answer 5

Usually 3D groups/aggregates
Uniform round to oval nuclei
Salt/pepper chromatin pattern
Occasionally vacuolated cytoplasm

Question 6

Normal Cytology

Answer 6

Pre-menopausal women
- from days 1-14, endometrial elements may normally be encountered during the menstrual and proliferative phases
Menstruation
- blood in background
- large aggregates of hyperchromatic small cells with minimal cytoplasm
Days 5-14 (Proliferative phase)
- may see blood
- small aggregates of small hyperchromatic cells with small round nuclei and minimal cytoplasm

Question 7

Superficial and Deep Stromal Cells

Answer 7

Superficial
- loose aggregates or single cells 
- ovoid nucleus
- moderate pale, vacuolated cytoplasm
Deep
- loose aggregates of spindle cells
- elongated wisps of cytoplasm

Question 8

Abnormal Shedding of Endometrial Cells in Pre-menopausal Women

Answer 8

Any shedding after day 14
Possible causes:
- hormone therapy
- IUCD
- endometritis 
- leiomyoma
- instrumentation
- dysfunctional bleeding
- hyperplasia
- malignancy

Question 9

Out of Phase Endometrial Shedding - Cytology

Answer 9

Hyperchromatic larger crowded groups (3D)
Irregular clusters with scalloped edges
Nuclei small-intermediate and uniform
Ill defined vacuolated cytoplasm

Question 10

Lower Uterine Segment (LUS)/Directly Scraped Endometrials

Answer 10

Endocervical collection can inadvertently sample LUS or endometrium
- in patients that have undergone cone biopsy
- when endocervical canal is abnormally shortened due to treatment/therapy
Characteristic features:
- large fragments/complex structures
- crushed stroma
- resemble endocx cells but have higher NC ratio
- more hyperchromatic but uniform
- evidence of mitoses

Question 11

Abnormal Shedding of Endometrial Cells in Post-menopausal Women

Answer 11

Any shedding of endometrial cells is abnormal
Most common causes:
- endometrial polyp
- hormonal therapy
- hyperplasia
- malignancy

Question 12

Endometrial Neoplasms

Answer 12

Most common malignant tumour of the FGT
Mostly seen in post-menopausal women
Mean age presentation = 55yrs
Less than 3% occur < 40yrs
80-85% are estrogen dependent neoplasms
- tend to be low grade
- well to moderately differentiated
Remaining 10-15% are non-estrogen dependent tumours
- tend to occur in older postmenopausal women
- high grade

Question 13

Endometrial Neoplasms - Pathogenesis

Answer 13

Unopposed estrogen stimulation is the driving force behind oestrogen dependent tumours
Estrogen source may be exogenous or endogenous
Exogenous sources:
- HRT
- Tamoxifen
Endogenous sources:
- early menarche
- ovarian lesions
- obesity
- reproductive factors
- pelvic irradiation

Question 14

Endometrial Hyperplasia

Answer 14

The endometrial hyperplasias are a heterogenous group of proliferative disorders
Thought to result from excessive stimulation by estrogens
WHO classification
- endometrial hyperplasia (simple & complex)
- atypical endometrial hyperplasia (simple & complex)
Simple vs complex refers to gland outline
- e.g. architecture, contour
Atypical refers to the cytology of the cells lining the glands

Question 15

Concept of Biological Continuum of Disease Progression

Answer 15

Hyperplasia (without atypia)
=> atypical hyperplasia
=> carcinoma
Hyperplasia = increased gland ratio:stromal ratio

Question 16

Cytological Features of Endometrial Hyperplasia

Answer 16

Smear well estrogenised
Normal endometrial cells present (not in keeping with menstrual cycle ie. after day 14)
Normal endometrial cells present in post-menopausal smears
Atypical endometrial cells in atypical hyperplasia

Question 17

Endometrial Carcinomas

Answer 17

Endometrioid adenocarcinoma has five variants

• mucinous carcinoma
• serous carcinoma
• clear cell carcinoma
• small cell carcinoma
• undifferentiated carcinoma

Question 18

Endometrial Carcinomas - Clinical Features

Answer 18

Abnormal bleeding
If advanced, patient may have pelvic pain
May be asymptomatic

Question 19

Endometrial Carcinomas - Histology

Answer 19

Characterised by the presence of neoplastic glands
Grading
- 1. = <5% solid areas
- 2. = 6-50% solid areas
- 3. = >50% solid areas
Degree of cytological atypia increases with grade
Stage refers to the depth of invasion

Question 20

Endometrial Adenocarcinoma - Cytology

Answer 20

Well organised
Background
- +/- blood
- +/- watery background/cell debris or tumour diathesis
Atypical or malignant endometrial cells
Single cells or aggregates with crowding and overlapping
Cytoplasm may contain vacuoles and have engulfed material
Nuclear changes vary with grade with higher grades showing more obvious malignant features
Nuclei oval to round

Question 21

Endometrial Adenocarcinoma Cytology - Differences between High and Low Grade Tumours

Answer 21

Nuclear irregularity in higher grade tumours
Nuclei mildy hyperchromatic with small nucleoli in lower grade
High grade tumours show chromatin clearing and prominent nucleoli

Question 22

Endometrial Cancer (very important apparently)

Answer 22

New CST is NOT considered a screening test for endometrial pathology
Cervical smears can pick up endometrial adenocarcinoma
Many cases of endometrial adeno lack conclusive features of malignancy but contain cells that are suspicious of malignancy
Patient’s age and history play important role in dx benign, atypical and malignant endometrial cells

Question 23

High Risk Patterns

Answer 23

Heavily bloodstained/necrotic smears
Abnormal shedding in women >50yrs
Increased no. of histiocytes
High maturation index in post-menopausal smear
Necrotic debris
Single cells, small groups, 3D clusters of endometrial cells
Single columnar cells with cytoplasmic tags

Question 24

Cytology of Endometrial Ca

Answer 24

Nuclei may be eccentric
Nuclear pleomorphism
Nucleoli range in size and number but often prominent
Chromatin finely to coarsely granular with even to uneven distribution
Scant to abundant cytoplasm, often vacuolated
Ingested polymorphs +/-

Question 25

IUCD Effect

Answer 25

Endometrial shedding at any stage of the cycle
+/- blood
Single and clustered enlarged vacuolated cells +/- polymorphs
Prominent nucleoli
Loop cells

Question 26

General Rule when Diagnosing

Answer 26

In a pre-menopausal woman, any endometrial shedding after day 14 is abnormal
Any endometrial shedding in a post-menopausal woman is abnormal
Any atypical endometrial cells deserve further investigation
Beware of pitfalls when diagnosing malignancy