W2L3 - Endometrial Lesions Flashcards
Menstrual Cycle - Proliferative Phase
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
Menstrual Cycle - Secretory Phase
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
Menstrual Cycle - Menstrual Phase
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
Endometrial Elements Encountered in Cervical Smears
Epithelial cells Stromal cells Histiocytes Leukocytes Erythrocytes
Epithelial Endometrial Cells
Usually 3D groups/aggregates
Uniform round to oval nuclei
Salt/pepper chromatin pattern
Occasionally vacuolated cytoplasm
Normal Cytology
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
Superficial and Deep Stromal Cells
Superficial - loose aggregates or single cells - ovoid nucleus - moderate pale, vacuolated cytoplasm Deep - loose aggregates of spindle cells - elongated wisps of cytoplasm
Abnormal Shedding of Endometrial Cells in Pre-menopausal Women
Any shedding after day 14 Possible causes: - hormone therapy - IUCD - endometritis - leiomyoma - instrumentation - dysfunctional bleeding - hyperplasia - malignancy
Out of Phase Endometrial Shedding - Cytology
Hyperchromatic larger crowded groups (3D)
Irregular clusters with scalloped edges
Nuclei small-intermediate and uniform
Ill defined vacuolated cytoplasm
Lower Uterine Segment (LUS)/Directly Scraped Endometrials
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
Abnormal Shedding of Endometrial Cells in Post-menopausal Women
Any shedding of endometrial cells is abnormal Most common causes: - endometrial polyp - hormonal therapy - hyperplasia - malignancy
Endometrial Neoplasms
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
Endometrial Neoplasms - Pathogenesis
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
Endometrial Hyperplasia
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
Concept of Biological Continuum of Disease Progression
Hyperplasia (without atypia)
=> atypical hyperplasia
=> carcinoma
Hyperplasia = increased gland ratio:stromal ratio
Cytological Features of Endometrial Hyperplasia
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
Endometrial Carcinomas
Endometrioid adenocarcinoma has five variants
- mucinous carcinoma
- serous carcinoma
- clear cell carcinoma
- small cell carcinoma
- undifferentiated carcinoma
Endometrial Carcinomas - Clinical Features
Abnormal bleeding
If advanced, patient may have pelvic pain
May be asymptomatic
Endometrial Carcinomas - Histology
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
Endometrial Adenocarcinoma - Cytology
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
Endometrial Adenocarcinoma Cytology - Differences between High and Low Grade Tumours
Nuclear irregularity in higher grade tumours
Nuclei mildy hyperchromatic with small nucleoli in lower grade
High grade tumours show chromatin clearing and prominent nucleoli
Endometrial Cancer (very important apparently)
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
High Risk Patterns
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
Cytology of Endometrial Ca
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 +/-
IUCD Effect
Endometrial shedding at any stage of the cycle
+/- blood
Single and clustered enlarged vacuolated cells +/- polymorphs
Prominent nucleoli
Loop cells
General Rule when Diagnosing
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
