Precancerous lesion
of FGT
• Premalignant or precancerous lesions are
epithelial changes of the FGT, which if left
without treatment could progress (over an
interval; may extend into several years) into
carcinoma.
The general features of precancerous cells
 Loss of stratification: loss of the normal
arrangement of epithelial cells into layers.
 Distorted
cells
with
enlarged
irregular
hyperchromatic nuclei.
 Increased Nuclear / Cytoplasm (N/C) ratio
 Nuclear mitosis are present at high level at the
top layer more than the basal layers.
Types of precancerous lesions
 Epithelial endometrial and cervical hyperplasia
 Leukoplakia: patches of keratosis. It is visible as adherent white patches on the mucous
membranes.
 Atypical squamous metaplasia of the cervix
 Parakeratosis: mode of keratinization characterized by the retention of nuclei
in the stratum corneum.
 Cervical dysplasia: abnormality of development show expansion of immature cells,
with decrease in the number and location of mature cells.
 Endocervical polyp (Adenoma of the cervix)
 Cervical intraepithelial neoplasm (CIN)
Epithelial hyperplasia
Cervical hyperplasia
 Squamous cell hyperplasia:
 Thickness of the whole epithelium due to chronic irritation.
 Basal cell hyperplasia:
 Hyperactive proliferation of the basal cell layer to form several
layers instead one or two layers.
 Reserve cell hyperplasia:
 Presence of patchy layer of small cells immediately beneath
basal cell layer.
Endometrial hyperplasia
Endometrial
hyperplasia
is
overgrowth
of
both
glandular and stromal endometrial layers due to over-
stimulation by estrogen .
Types:
 Mild (cystic) hyperplasia (G I)
 Moderate (adenomatous) hyperplasia (GII)
 Sever (atypical) hyperplasia (GIII)
 Cervical
smear:
Thick
clusters
of
reactive
endometrial cells with or without atypia.
 N.B. Sever atypical endometrial hyperplasia is
considered as GI (well differentiated) endometrial
adenocarcinoma.
Cervical atypical squamous metaplasia
 Definition: It is a transformation of the fragile cervical
cells at the squamo-columnar junction of endocervical
canal into more resistant stratified squamous epithelial
cells with cellular atypia.
 Cervical smear: Squamous cells with a nuclear
enlargement
irregular
(increased
nuclear
hyperchromasia.
N/C
ratio),
membrane
binucleated,
and
slightly
Endocervical polyp (cervical adinoma)
 Definition:
It
is
a
pedunculated
vascular
connective tissue core containing inflammatory
cells (acute & chronic), with dilated endocervical
glands,
and
covered
by
ulcerated
epithilium or squamous metaplasia
cervical
Cervical dysplasia
Cervical intraepithelial neoplasia (CIN)
 Definition: It is an abnormal growth or disordered
development of primitive immature basal cell layer and
abnormal cell maturation; i.e. begin in the lower portion
of cervical epithelium.
 Site: Usually at squamo-columnar junction ; it may be
multifocal and involve the endocervical cleft.
Features of cytological smears of dysplastic
cells
• Enlarged hyperchromatic nucleus ( N/C ratio).
• Increased number of abnormal mitotic figures
according to the severity of dysplasia
• Nuclear chromatin clumping.
Classification (types) of Dysplasia (CIN)
 Dysplasias are subclassified according to the degree by
which the epithelium is replaced by immature dysplastic
cells; Mild (GI) CIN dysplasia: involve the lower 1/3 of the cervical
epithelium.
 Moderate (GII) CIN dysplasia: involve the lower 2/3of the
cervical epithelium.
 Severe (GIII) CIN dysplasia or carcinoma in situ: involve
the whole thickness of the covrring epithelium
Cervical Disease Progression in Cells of the
Basement Membrane
LSIL
HSIL
Koilocytosis CIN1
Basement
membrane
Normal
squamous
epithelium
Mild
Koilocytosis - Cell changes showing perinuclear vacuolization
LSIL - Low-grade Squamous Intraepithelial Lesion
HGSIL or HSIL - High-grade Squamous Intraepithelial Lesion
CIN2
CIN3
Moderate Severe Carcinoma
in situ
Dysplasia
CIN - Cervical Intraepithelial Neoplasia
CIN1 - Mild dysplasia
CIN2 - Moderate dysplasia
CIN3 - Severe dysplasia to carcinoma in situ (CIS)
Precursor Lesions of Cervical Carcinoma
LSIL
CIN 1
Normal Mild
Dysplasia
HSIL
CIN 2
CIN 3
Moderate
Severe Carcinoma
Dysplasia
Dysplasia
in situ
Precancerous Lesions of the Cervix.
LSIL = Low Grade Squamous Intraepithelial Lesion
CIN = Cervical Intraepithelial Neoplasia
HSIL = High Grade Squamous Intraepithelial Lesion
• Above, left. Squamous carcinoma in situ (CIS), cervix. To the right is normal
squamous epithelium with its basal cell layer & orderly maturation upwards.
• The left side shows CIS characterized by lack of maturation, altered cell polarity,
nuclear pleomorphism & increased nuclear / cytoplasmic ratio.
• As is characteristic of CIS, neoplastic cells are confined to the epithelial layer & have
not invaded through the epithelial basement membrane, under which, the submucosal
stroma contains chronic inflammatory cells.
A
C
B
D
Carcinoma of the cervix
1- Carcinoma in situ:
• It is a lesion in which all thickness of cervical
epithelium is replaced by malignant cells without
invasion of the underlying stroma; i.e. with intact
basement membrane.
2- Micro-invasive carcinoma
• These are buds of malignant epithelial cells invading
the cervical stroma beneath the carcinoma in situ to a
depth of 2-3 mm from the site of the origin, without
lymphatic or vascular invasion.
3- Invasive carcinoma
• Malignant epithelial cells that invade the underlying
stroma of the cervical epithelium by infiltration or
destruction of the basement membrane, with or
without lymphatic or vascular invasion.
Types of invasive carcinoma
Primary type
•
•
•
•
Squamous cell carcinoma
Adenocarcinoma
Adeno-squamous carcinoma
Adeno-acanthoma
(squamous cell mataplasia +
adenocarcinoma).
• Choriocarcinoma
(Malignant tumor of the
placenta).
Secondary type
 Metastatic
Cytology of malignant cells
Cytological features of normal and benign tumors
 The cells are uniform in size and shape.
 The cells are uniform in nuclear and cytoplasmic ratio.
 The normal C/N = ½
 Normal polarity (normal arrangement of cells to
neighbouring cells).
 In benign tumors, the appearance of cells are usually
give normal appearance of origin cells;
 E.g. fibroma: show the increased number of normal
appearance of fibroblasts.
Cytological features of malignant tumors
• A and B: mature squamous metaplasia.
• C: immature squamous metaplasia.
• D: immature squamous metaplasia with pattern of transitional metaplasia.
Cervical dyskaryosis
• Changes in nuclear-cytoplasmic ratio
• Changes in nucleoli
• Changes in mitotic index
Severe dyskaryosis
Atypical immature metaplastic
squamous cells with increased
nuclear/cytoplasmic ratio and
hyperchromasia.
Mild-moderate dyskaryosis
Squamous carcinoma
1- Nuclear criteria
 Nuclear enlargement
 Nuclear shape and size variation
 Disturbed chromatin (abnormal chromatin distribution in the
nucleus)
 Changes of nuclear membrane
 Irregular enlarged prominent nucleoli.
 Multinucleated malignant giant cells
 Abnormal mitosis
 Hyperchromasia: deep blue hyperchromatic nuclei due to
increase DNA content of the nucleus.
Enlarged nuclei with increased N/C
ratio
Enlarged nuclei with irregular nuclear
membrane
2- Cytoplasmic criteria
• Scanty cytoplasm
• Increased N/C ratio
• Tight holding of membrane around nucleus
• Secretory or inclusion of cytoplasm
3- Malignant cells intrcellular relationship
• Variation of the size and shape of malignant cells
• Decreased cohesiveness between cells
• Abnormal stratification and polarity
General consideration about malignant criteria
1- No single morphologic malignant criteria alone is
pathogenic for malignancy; a combination of criteria is
necessary.
2- Nucleus is the most important part of the ell to show
malignant changes; but the cytoplasmic changes could
help in cell differentiation and cell typing.
3- The presence of acini or papillae in an abnormal location
(such as in pleural cavity) -------- increase suspicion of
malignancy even in absence of the prominent features of
malignancy because of their high degree of
differentiation.
So, the question should always to be answered in this form:
- It is a cancer?
- What type of cancer is it?
Factors affecting the distribution of malignant
cells
 Collection and processing technique:
 Direct smearing or scraping ------ exfoliate
malignant cells in clusters or sheets rather
than isolated cells in spontaneous exfoliation
(aspiration).
 Nature of the lesion:
 Adenocarcinoma -------- exfoliate malignant cells in
clusters as acini or papillary structures.
 Dysplastic cells and carcinoma in situ of squamous cell
carcinoma ----- single scattered exfoliated squamous
cancer cells throughout the smear.
 Sarcomatous cells are usually arranged as single
malignant cells and are separated by thin fibrous tissue.