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Definition of cytopathology

Cytopathology is the study of normal and abnormal

exfoliated cells in tissue fluid.

The individual cells reflect the normal and abnormal

morphology of the tissue from which they are derived.

Types of exfoliated cyto-pathology

Natural spontaneous exfoliation
Natural covering epithelium: skin, urinary tract, vagina, and

Glandular epithelial secretion: Breast (Nipple secretion).
Exudates and transudate:




Peritoneal fluid
Joint fluid


Artificial enhanced exfoliation:

Scrapings from cervix, vagina, oral cavity, and skin
Brushing and lavage: bronchi, GIT, and urinary tract
Fine needle aspiration (FNA) for:

cavity fluid: pleural, pericardial & peritoneal


neck, breast & ovary

tissue: body organs, tumors & other swell

Role of cytopathology
Early detection of unsuspected diseases (malignant

or pre-malignant lesions).
Confirmation of suspected diseases without surgical

Diagnosis of hormonal imbalance.
Useful in flow up the course of disease or

monitoring therapy.

Advantage of Cytopathology
Rapid diagnosis

- Inexpensive

- Simple

It is better in evaluating the infectious diseases.

Supplement or replace frozen section or biopsy
No injury to tissue allowing repeated sampling
It is better for hormonal assay
Cytopathological smear cover a wider surface than

that involved in surgical biopsy.

Disadvantage of Cytopathology
Interpretation of the morphological cellular changes is

based only on individual cell observation.

Not always finally diagnosis, so it is confirmed by

histopathology in some cases.

Not determine the size and type of lesion of some cases.

Factors that determine the appearance of

Type of the technique used.
Level of cell maturation at the time of cell collection.
Nature of the parents tissue: soft tissue, cyst, or solid organ.
Medium of the exfoliated cells.
Interval between the stain of the exfoliated cells and collection

of samples.
Type of fixative, stain, and processing of the technique


PAP smear: named after

Dr. George Papanicolaou (1883-1962)
Vaginal smears from guinea pigs (1917)
Women (1920)

Pathological conditions (1928)

Normal Cervix

Taking the Sample

Liquid Based Cytology lab processing

Cytologic screening for cervical cancer

Cervical cancer screening has decreased morbidity and

Deaths from cervical cancer decreased from 26,000 to

less than 5,000 between 1941 and 1997

Pap smears are not perfect

For a high grade lesion, the sensitivity of a single pap

smear is only 60-80%

Estimated false negative rate is 30-50%
Requires adequate specimen collection
Requires adequate cytological review

Requires adequate patient and physician follow-up

10% of women with cervical cancer had inappropriate

Requires access to care
50% of women with cervical cancer were never

screened and 10% had not been screened within 5 years

of diagnosis.

Who to screen
Any woman with a cervix who has ever had sexual


When to screen
Start within 3 years of onset of sexual activity or by age

of 21, whichever is first.

Risk factors for cervical dysplasia
Early onset of sexual activity
Multiple sexual partners
Oral contraceptives

Screening frequency
Yearly until three consecutive normal pap smears, then

may decrease frequency to every three years

Annual screening for high-risk women is highly


When to stop routine screening

Age 65 and adequate recent screening
Three consecutive normal pap smears
No abnormal pap smears in last 10 years
No history of cervical or uterine cancer

Hysterectomy for benign disease

Hysterectomy for invasive cervical cancer

Original Squamous Epithelium

Vagina and outer ectocervix
4 cell layers
Well-glycogenated (pink) unless atrophic

Columnar Epithelium
Upper and middle endo-cervical canal
Single layer of columnar cells arranged in

Mucin producing (not true glands)

Squamous Metaplasia
Central ectocervix and proximal endocervical canal
Replacement of columnar cells by squamous epithelium
Progressive and stimulated by
Acidic environment with onset of puberty
Estrogen causing eversion of endocervix

Transformation Zone
Zone between original squamo-columnar junction and

the new squamo-columnar junction

Nabothian cysts visually identify the transformation

zone if present

Original Squamo-columnar Junction

Placement determined between 18-20 weeks gestation
Most often found on ectocervix
Can be found in vagina or vaginal fornices
Less apparent over time with maturation of


New Squamo-columnar Junction

Border between squamous epithelium and columnar

Found on ecto-cervix or in endo-cervical canal
Majority of cervical cancers and precursor lesions

arise in immature squamous metaplasia, i.e. the

leading edge of the squamo-columnar junction

Squamous Epithelium

Parabasal Cells

Intermediate Cells




Endocervical Cells

Endometrial Cells

Non-Epithelial Cells




Normal smear

Ectropion / Erosion
At puberty & pregnancy the endocervical cells are

pushed out to lie on the ectocervix



Wide Ectropion

The endocervical cells are transformed into squamous

cells through the process of squamous metaplasia

Metaplastic Cells