LESIONS OF THE CERVIX

CERVIX :
 Cervix is divded into 2 parts : ECTOCERVIX
ENDOCERVIX

9/14/2019
ECTOCERVIX : Non keratinizing stratified squamous
epitelium.

ENDOCERVIX : Mucous secreting tall columnar

epithelium .

Transformation Zone : Area bet. the original and

new squamocolumnar Junction.
Site from which 90% Cervical carcinomas arise 2
9/14/2019
3
9/14/2019
4
9/14/2019
5
9/14/2019
6
ETIOPATHOGENESIS:
 HPV – Most imp. Agent in cervical oncogenesis

9/14/2019
RISK FACTORS FOR CERVICAL CANCER :
 Early age at first intercourse

 Multiple sexual partners

 Male partner with multiple previous sexual partners

 Persistent detection of high risk HPV

 Oral contraceptive use

 Smoking

 Family history

 Associated genital infections

 Immunosuppression 7
HPV AND CERVICAL ONCOGENESIS
 HPV DNA can be detected in 95% of cervical CA

9/14/2019
 Low risk (Non-oncogenic) – 6,11, 42& 44
–condyloma acuminata
– low grade CIN nonprogessing
- Do not integrate into host cell genome , present
as free / episomal form

 High Risk( Oncogenic) – 16, 18 & 31, 33, 35

(39, 45, 51, 56 & 58)
– high grade CIN
– invasive cancer
- Viral genes E6 & E7 are integrated into 8
cervical epithelial cells
 MECHANISM OF ONCOGENESIS

↓
INTEGRATION OF VIRAL GENES (E6 & E7) INTO HOST

9/14/2019
GENOME

↓
ACTIVATE CELL CYCLE GENE( CYCLIN E ) &
INACTIVATE TUMOR SUPPRESSOR GENES (P 53 & RB-1)

↓
UNCONTROLLED CELLULAR PROLIFERATION

↓
CA CERVIX
9
9/14/2019
10
Natural History of HPV Infection

Persistent infection critical for

development of neoplastic change
CERVICAL INTRAEPITHELIAL
NEOPLASIA ( CIN)
 Cervical intraepithelial neoplasia is a
precancerous lesion and characterized by
abnormal cell proliferation confined within the
epithelium that begins in the basal layers &
progressively involves other layers
 Induced by HPV

 CIN is not cancer, and is usually curable.

 Most cases of CIN remain stable, or are

eliminated by the host's immune system
without intervention. Lt
 However a small percentage of cases progressRitu
Col

to become cervical cancer if left untreated.[ Lakh

takia
CERVICAL INTRAEPITHELIAL
NEOPLASIA ( CIN)

Dysplasia CIN System Bethesda

9/14/2019
system System
( SIL)
Mild dysplasia CIN I LSIL

Moderate CIN II HSIL

dysplasia
Severe CIN III HSIL
dysplasia or
13
Carcinoma- in
Situ
CIN classification is based on : Cellular atypia
& Involv. of diff thickness of epithelium

9/14/2019
 It is characterised by :
 Koilocytosis

 Inc. nucleo- cytoplasmic ratio ( N:C ratio )

 Hyperchromasia

 Variation in nuclear size

 Loss of polarity

 Inc. mitotic figures

14
9/14/2019
15
 Lt Col Ritu Lakhtakia
NORMAL ECTOCERVIX
CIN I / MILD
DYSPLASIA:

Defined by
dysplastic
squamous cells
in the lower
third of the
epithelium
along with HPV
changes

Nuclear
abnormalities
slight and more
marked in
basal third.
.
17
CIN II
Defined by
presence of
dysplastic
squamous cells
in the basal
two-thirds of
the epithelium

Nuclear
abnormalities
are more
marked than in
CIN 1
18
CIN III
Defined by the
prsence of
dysplastic
squamous cells
in > 2/3 or
throughout the
whole thickness
of the epithelium

Marked nuclear
abnormality all
layers

19
 CERVICAL CANCER SCREENING
I. PAP SMEAR :

9/14/2019
 It is a screening procedure for
cervical cancer.
 Detects the presence of
precancerous or cancerous cells
on the cervix.
 Simple , safe & non invasive
method
 Strong sensitivity & specificity
20
 It is a procedure to test for cervical
cancer in women.

9/14/2019
 The reason for the effectiveness of
this test in preventing cervical
cancers is the fact that majority of
these cancers are preceeded by a
long standing precancerous
condition.

21
9/14/2019
22
9/14/2019
23
BETHESDA SYSTEM ( of cytologic
evaluation )

9/14/2019
 First , pap smears are evaluated as
regards adequacy of the specimen

 General categorization : Normal /

abnormal

 Descriptive diagnosis

24
9/14/2019
25
INVASIVE CERVICAL CARCINOMA
9/14/2019
27
 EPIDEMIOLOGY :

Peak incidence : 40 -45 yrs

9/14/2019

 Indian women : 50 -54 yrs

 Slightly younger age d/t

combination of 2 factors:
Earlier onset of sexual activity
 Pap smear screening programmes
28
RISK FACTORS FOR CERVICAL CANCER:
 Persistent infection with a high
oncogenic risk HPV 16 or HPV 18
 Multiple sexual partners
 A male partner with multiple
previous or current sexual partners
 Young age at first intercourse
 High parity
 Immunosuppression
 Use of oral contraceptives
 Use of nicotine/smoking
9/14/2019
30
 Carcinoma cervix – Morphology
3 gross types

9/14/2019
 Exophytic / fungating: Cauliflower like
growth protuding into the vaginal cavity –
Most common type

 Ulcerative

 Infiltrative : Cervix appears diffusely

enlarged , thickened , hardened & barrel
shaped
31
9/14/2019
32
GROSS CERVICAL SCC: (STAGE 1)

http://library.med.utah.edu/WebPath/FEMHTML/FEMIDX.html#2
CERVICAL SCC (GROSS) EXTENSIVE:

http://library.med.utah.edu/WebPath/FEMHTML/FEMIDX.html
KERATINISING SQUAMOUS CARCINOMA

Lt
Col
Ritu
Lakh
takia
ADENOCARCINOMA OF THE CERVIX
Spread :
 DIRECT :
 Down – Vagina , labia

9/14/2019
 Lateral – Adnexa , ureter ,ovary , pelvic wall
 Anterior – bladder
 Posterior – rectum

 LYMPHATIC :
 Paracervical , obturator , Ext & Int iliac , Sacral
, Common iliac

 BLOOD : Liver , Lungs, bone marrow , kidneys

etc. 37
STAGING ( FIGO )
 Stage 0 : Carcinoma in situ ( CIN III)

9/14/2019
 Stage I : Carcinoma confined to the cervix

 Stage II: Carcinoma extends beyond the cervix

but not onto the pelvic wall . Carcinoma involves
the vagina but not the lower third.
 Stage III : Carcinoma has extended onto the
pelvic wall . Carcinoma involves the lower third
of the vagina.
 Stage IV : Carcinoma has extended beyond the
true pelvis or has involved the mucosa of bladder 38
or rectum + metastatic dissemination .
PROGNOSIS:
 5-year survival rates:
 Stage Ia = ~95%
 Stage Ib = ~80-90%
 Stage II = ~75%
 Stage III+ = <50%
 Stage IV most common cause of death is local
extension
 The prognosis of adenosquamous and
neuroendocrine carcinomas are worse than
adenocarcinomas and SCCs
CERVICAL SCREENING:
 Pap smears are the most efficient way to
diagnose pre-invasive and invasive cervical
carcinomas
 Studies show that there is an ~80% decrease in
cervical cancer (incidence & mortality rate) for
women that get regular Pap smears

 HPV DNA Testing:

 Determines positive/negative infection for
HPV strands most likely to cause cervical
carcinoma
9/14/2019
41
NORMAL CERVIX (GROSS):

http://library.med.utah.edu/WebPath/jpeg4/FEM002.jpg
9/14/2019
43
PREVENTION:
 Vaccines: Gardasil and Cervarix
 Cervarix protects against HPV 16 &
18 (High oncogenic risk HPVs ~70%)
 Gardasil protects against HPV 16 &
18 (High oncogenic risk HPVs ~70%)
and HPV 6 & 11 (Low oncogenic risk
HPVs ~90%)
9/14/2019
45
9/14/2019
46
9/14/2019
47
LESIONS OF THE
ENDOMETRIUM
NORMAL ENDOMETRIUM :
 Endometrium changes cyclically in response to the
hormones produced by ovary .

9/14/2019
The normal endometrial cycle has the follo. Phases:

49


 Proliferative/ Pre ovulatory Phase:

Lasts for 14 days under the influence of estrogen
There is regeneration of the endometrium (glands &
stroma )
Glands are straight & tubular . Stroma is dense .
9/14/2019
50
 Secretory / Post ovulatory phase :
Follows ovulation on or around 14 day , under
the influence of progesterone.

9/14/2019
Endometrial glands become enlarged & tortuous
& filled with secretions

51
Stroma is loose & edematous .

 Menstrual phase :
 Superficial 2/3 of endometrium is shed . Basal
1/3 does not respond to ovarian steroids & is
retained
9/14/2019
52
DYSFUNCTIONAL UTERINE BLEEDING ( DUB)
 Defined as excessive bleeding occurring during or b/n
menstrual periods
 Not associated with any organic cause

9/14/2019
 May be divided into 2 categories : OVULATORY
ANOVULATORY

53
 Anovulatory Cycle : Most common cause of DUB
Causes : Extremes of menstrual life
Endocrine disorder
Ovarian lesion
Obesity
Malnutrition
 Failure of ovulation results in excessive prolonged
estrogenic stimulation
 OVULATORY CYCLE :

9/14/2019
Inadequate luteal phase :
• Decreased corpus luteum function & low

54
progesterone output
• Manifests clinically as infertility
ADENOMYOSIS & ENDOMETRIOSIS:

Adenomyosis : Presence of benign endometrial

9/14/2019
tissue deep in the myometrium along with myometrial
hypertrophy

55
Pathogenesis : Metaplasia
Excessive estrogenic stimulation
Grossly : Uterus slightly or markedly enlarged
C/S: Diffuse thickness of the uterine wall

9/14/2019
Microscopically :

56
Presence of endometrial glands & stroma deep
within the muscular wall .
 Minimum distance : 1 LPF (2-3 mm)