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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
cervix.
 Glandular epithelial secretion: Breast (Nipple secretion).
 Sputum
 Urine
 Exudates and transudate:

Pleural fluid
Peritoneal fluid

Pericardial fluid
Joint fluid
CSF
Artificial enhanced exfoliation:
 Scrapings from cervix, vagina, oral cavity, and skin
 Brushing and lavage: bronchi, GIT, and urinary tract
 Fine needle aspiration (FNA) for:

Body cavity fluid: pleural, pericardial & peritoneal
fluids

Cysts: neck, breast & ovary

Solid 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
trauma.
 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
cells
 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
used.
PAP smear: named after
Dr. George Papanicolaou (1883-1962)
 Vaginal smears from guinea pigs (1917)
 Women (1920)


Hormonal cycles
Pathological conditions (1928)
Normal Cervix
Taking the Sample
Liquid Based Cytology – lab processing
The Pap Smear
Cytologic screening for cervical cancer
 Cervical cancer screening has decreased morbidity and
mortality
 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
follow-up.
 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
activity.
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
 Tobacco
 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
recommend.
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
Cervical histology
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 folds
 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 epithelium
“New” Squamo-columnar Junction
 Border between squamous epithelium and columnar
epithelium
 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
Superficial
Cells
Endocervix
Endocervical Cells
Endometrial Cells
Non-Epithelial Cells
Lymphocytes
Polymorphs
sperms
Normal smear
Ectropion / Erosion
 At puberty & pregnancy the endocervical cells are
pushed out to lie on the ectocervix
Normal
Ectropion
Wide Ectropion
Metaplasia
 The endocervical cells are transformed into squamous
cells through the process of squamous metaplasia
Metaplastic Cells