robbins cervix and basics on pap smear

1. Cervix
Dr. Madhumitha
Assistant professor

2. Topics……
• Basic anatomy and histology
• Benign lesions – cervicitis and metaplasias
• Precancerous conditions
• Invasive carcinoma
• Cervical screening
• Liquid based cytology

3. Anatomy
• Narrow cylindrical part
connects the vagina and
uterus
• The upper end
communicates with the
uterine body via the
internal os
• Lower end opens into the
vagina at the external os

5. Histology
• EC is lined by a single layer
of tall columnar mucus-
secreting epithelial cells
• Ectocervix covered by
nonkeratinizing, stratified
squamous epithelium, either
native or metaplastic; has
basal, midzone and
superficial layers

6. Histology
• The junction between the ecto- and endocervical
epithelium is quite abrupt and is normally located at the
external os, the point at which the endocervical canal
opens into the vagina
• At the squamocolumnar junction, the cervical stroma is
often infiltrated with leucocytes, forming part of the
defence against ingress of microorganisms.

7. Cytology
Superficial squamous
cells
Intermediate squamous
cell
Parabasal cell

8. Cervicitis
Acute and chronic

9. • Cervicitis – inflammation of cervix
• Non-specific symptoms: abnormal vaginal discharge,
intermenstrual bleeding, dysuria, lower abdominal pain, or
dyspareunia
• Clinical findings: mucopurulent or purulent cervical discharge,
easily induced cervical bleeding
• 50% of women with clinical cervicitis have no symptoms

10. • Cervicitis is most often caused by sexually transmitted
pathogens, but may also be caused by
• systemic diseases (such as autoimmune diseases, Stevens-
Johnson Syndrome, or viral infections),
• neoplasia,
• mechanical/chemical trauma.
• The two main sexually transmitted agents responsible
for clinically apparent mucopurulent endocervicitis are
• C. trachomatis (CT)
• N. gonorrhoeae (GC).
• Herpes simplex virus (HSV) causes an ectocervicitis, as
may Trichomonas vaginalis.

11. Acute and chronic cervicitis
Speculum examination

12. Pathogenesis
• Menarche- the production of estrogens by the ovary
stimulates maturation (glycogen uptake) of cervical and
vaginal squamous mucosa.
• These cells are shed, the glycogen provides a substrate for
endogenous vaginal aerobes and anaerobes, streptococci,
enterococci, Escherichia coli, and staphylococci.
• Dominant microbial species lactobacilli maintains the vaginal
ph below 4.5 , suppressing the growth of other pathogenic
organisms
• At low ph , lactobacilli also produce bacteriotoxic H2O2

13. Acute and chronic cervicitis include:
• Epithelial spongiosis (intercellular edema),
• Submucosal edema, and a combination of epithelial and stromal changes.
Acute cervicitis:
• Acute inflammatory cells, erosion, and reactive or reparative epithelial
change.
Chronic cervicitis:
• Mononuclear, with lymphocytes, macrophages, and plasma cells. Necrosis
and granulation tissue may also be present.
Morphology

14. HSV :
• Epithelial ulcers (often with intranuclear inclusions in
epithelial cells) and a lymphocytic infiltrate
cowdry type A inclusion – amorphous eosinophilic inclusion
three “Ms” margination, multinucleation and nuclear
moulding
C. Trachomatis:
• Lymphoid germinal centers and a prominent plasmacytic
infiltrate.

15. Diagnosis
• Physical examination and medical history of the patient is
done.
• Pelvic exam is done where the cervix can be visually inspected.
There can be redness and ulceration seen in the cervix. Some
patients can also have vaginal discharge.
• Urine tests are done.
• Pap smear exam is done where a swab of cells are taken from
the cervix and are examined under the microscope.
• A culture of the vaginal discharge or cervical tissue is done.
• Biopsy can also be done where a tissue sample from the cervix
is taken and sent to lab for analysis.

16. Treatment
• Symptomatic treatment to reduce inflammation
• Antibiotics and antivirals
• Procedures such as cryotherapy
• Avoiding sexual intercourse

17. Complications
• The infection can spread from the cervix to the uterus,
endometrium (endometritis), urinary bladder (cystitis),
fallopian tube and ovaries, all of which can ultimately result in
pelvic inflammatory disease (PID).
• Pelvic inflammatory disease (PID) can cause ectopic pregnancy
and infertility.
• Pregnant women suffering from untreated chronic cervicitis
are more susceptible for complications, which include
premature labor and miscarriage.
• Patient develops increased susceptibility to HIV infection.

18. Precancerous condition and cervical cancer
• Cervical cancer is the third most common cancer in women
• Approx 75% cases occur in low resources nations
Risk factors of cervical cancer
• HPV infection
• Early age at first intercourse
• Multiple sexual partners
• Increased parity
• A male partner with multiple previous sexual partners
• The persistent detection of a high-risk HPV, particularly in high
concentration (viral load)
• Genital infections (chlamydia)

19. Pathogenesis
• HPV, the causative agent of cervical neoplasia, has a tropism
for the immature squamous cells of the transformation zone.
• Human papiloma is a double stranded DNA virus with atleast
70 genetically distinct types which are classified
1) High risk groups (16,18)
2) Low risk groups (6,11)
based on their oncogenetic potential.
• Activity of two viral protein encoding E6 and E7 protein

22. Course of disease

23. Squamous intraepithelial lesion (SIL)
• Precancerous epithelial change – termed as SIL
Current terminology
– two tiered system
based on biology and
disease management
SIL
LSIL (CIN I)
HSIL (CIN II & CIN III)

24. Morphology

25. Morphology
• LSIL – Dysplastic changes in lower third of squamous epithelium
plus koilocytic changes in the superficial layers.
• HSIL (CIN II) – Dysplasia extending to middle third with
occasional koilocytes.
• HSIL (CIN III) – full thickness dysplasia with no koilocytic
changes

26. Cytology – PAP smear

27. Management
• LSIL – conservative management with careful observation
• HSIL or persitant LSIL – Cone biopsy & follow up.

28. Invasive carcinoma of cervix
MORE THAN 80% LESS THAN 20%

29. Squamous carcinoma of cervix
• occur at any age from the second decade of life to senility.
• peak incidence: 40 to 45 years for invasive cancer and about
30 years for high-grade precancers.
• Progression from SIL is variable and unpredictable.
• Only reliable way – vigilant physical examination coupled with
PAP smear and biopsy of suspicious lesions.
.

30. Clinical
course

31. Clinical features
• Asymptomatic – Abnormal cells in smears
• Vaginal Bleeding
• 80% Squamous Ca, 20% other.
• Early diagnosis by cytological PAP test.
• Adenocarcinoma, Adenosquamous, Clear-cell carcinoma etc.
• 40-50 peak age.
• Treatments – Cone biopsy, hysterectomy
• 5 year survival
• Stage1->80%, Stage2–75%, Stage3-35% & 10-15% with Stage 4
disease.

32. Morphology
• Invasive cervical carcinoma manifests in three
somewhat distinctive patterns:
• 1-Fungating (or exophytic),
• 2-Ulcerating
• 3-Infiltrative cancers.
• When obvious to the naked eye, the most common variant is
the fungating tumor, which produces an obviously neoplastic
mass that projects above the surrounding mucosa.

33. Histology
• Microscopically,the invasive tumors often consist of tongues
and nests of squamous cells that produce a desmoplastic
stromal response.
• Currently histologic grading divides squamous cell carcinomas
into three groups,
1) well differentiated (grade 1),
2) moderately differentiated (grade 2), and
3) poorly differentiated (grade 3).

34. Gross
This is the gross appearance of a cervical squamous cell carcinoma that is still limited
to the cervix (stage I). The tumor seen here is a fungating red to tan to yellow mass
that obscures the cervical os.

35. Histology

37. Spreading
• Direct:
• Down – Vagina, Labia
• Lateral – adnexa, ureter, ovary, Pelvic wall
• Anterior – bladder
• Posterior – Rectum
• Lymphatic:
• Paracervical, Obturator, Int & Ext iliac, Sacral,Common iliac, Aortic.
• Blood: Liver, lungs etc.

38. TNM classification
T – primary tumour
T1 Confined to the cervix
T1a diagnosed only by microscopy
T1b clinically visible lesion
T2 beyond uterus but not to pelvic wall or lower third of
vagina
T3 extends to pelvic wall, lower third of vagina
T4 mucosa of bladder or rectum, beyond true pelvis
N1 – Regional lymphnode
M1 – distant metastasis

39. Staging
T N M
Stage 1 T1 N0 M0
Stage 2 T2 N0 M0
Stage 3 T3 N1 M0
Stage 4 T4/Any T Any N M1

40. Management
• Very early invasive cancers (microinvasive carcinomas) may
be treated by cone biopsy alone
• Most invasive cancers are managed by hysterectomy with
lymph node dissection and, for advanced lesions, radiation.
• The prognosis and survival for invasive carcinomas depend
largely on the stage
• Radiation and chemotherapy for inoperable lesions.
• Early detection has reduced the number of patients with
stage IV cancer by over two-thirds in the past 50 years

41. Prevention
• The quadrivalent HPV vaccine for types 6, 11, 16, and 18,
• more recently introduced 9-valent vaccine are very effective
in preventing HPV infections.
• Despite its efficacy, vaccination does not supplant the need
for routine cervical cancer screening.

42. Cervical screening – PAP smear
Georgios Papanikolaou
“PAP smear is the most effective cancer
screening test so far”

43. Definition
• It is a type of exfoliative cytology test.
• Simple, safe, non-invasive method.
• Exfoliated cells from cervix are collected usually enhanced by
using a variety of spatulas or brushes.
• The specimen is processed and studied for morphology.

44. Basic principle
** Ideal focus area is the transformation zone

45. How to perform
• Not done during menstruation.
• Insert a speculum into the Patient's
vagina, to allow access to the cervix.
• Samples are collected from the outer
opening or os of the cervix using an
Ayre’s spatula, an endocervical brush, or
a plastic-fronded broom.

47. Types
PAP
TESTING
CONVENT
-IONAL
LBC

48. Conventional

49. LBC

50. Liquid based cytology

51. Liquid Based Cytology
• Liquid based cytology (LBC) is a thin layer or monolayer slide
preparation technology
• Introduced to overcome shortcomings of conventional Pap
smears
• Aim - To improve the transfer of cells from the collection
device to a microscope slide

52. Types FDA approved
THIN PREP SURE PATH

53. 1. Sure Path : centrifugation and sedimentation
through a pressure gradient
2. Thin Prep: filtration and collection of Vaccum –
packed cells on membrane and transferring to slide
Sensitivity and specificity has high range of 90%

55. Reporting pap smears (Bathesda system) 2014
Specimen type Conventional LBC
Adequacy Epithelial 8000-12,000
cells
Glandular
components(10 well
preserved cells in
groups/single)
epithelial 5000
squamous
cells
Glandular
components(10
well preserved cells
in
groups/single)

56. Other uses of LBC
• Non-gynaecologic cytopreparation
1. thyroid cyst fluid examination
2. Oral pathology lesions
3. body fluids –pleural effusions, urine
4. brushing samples

57. Conventional LBC

58. MCQs
• Which of the following statement is correct about invasive
squamous cell carcinoma of cervix?
a) Most often associated with HPV 6 and 11
b) Most often associated with HPV 16 and 18
c) Reactive atypia is a precancerous lesion
d) Most commonly seen in women of higher socioeconomic
status.

59. MCQs
• Cervical biopsy reveals changes shown in the picture
a) HSIL
b) LSIL
c) Invasive carcinoma
d) Chronic cervicitis

60. MCQs
• Which of the following about RB protein is correct?
a) RB is activated when phosphoyrlated by CDK
b) RB binds with E2F and prevents cells to enter S phase
c) RB is a transcription factor
d) When mitogenic signal is received, RB binds with E2F and
stimulate S phase.