This ppt is intended for teaching cervical pathology to medical graduates. It covers anatomy, basic inflammatory conditions, dysplasia and malignancy and its pathogenesis and diagnosis

1. CERVIX
Dr. SnehilAgrawal

2. Anatomy
 The cervix (from the Latin collare, neck) is the inferior portion
of the uterus that connects the corpus to the vagina.
 Outer portion (exocervix, ectocervix or portio vaginalis)
protrudes into the upper vagina and is covered by glycogen-
rich squamous epithelium.
 The endocervix is the canal that leads to the endometrial
cavity. It is lined by longitudinal mucosal ridges made of
fibrovascular cores lined by a single layer of mucinous
columnar cells.
 The external os is the macroscopically visible junction
between the exocervix and endocervix.
 The squamocolumnar junction is the microscopic anatomical
junction of the squamous and mucinous columnar epithelia.

3. Squamo-columnar junction

7. CERVIX
 Inflammations
- Acute cervicitis & Chronic Cervicitis
 Endocervical polyps
 Tumors
-Intraepithelial Neoplasia
-Invasive Neoplasms

8.  Microorganisms- endogenous vaginal aerobes
and anaerobes, Streptococcus, Staphylococcus,
and Enterococcus, Chlamydia trachomatis,
Neisseria gonorrhoeae, and occasionally herpes
simplex, type 2
Acute cervicitis:
 Grossly red, swollen, and edematous, with
copious pus dripping from the external os.
 Microscopically, the tissues exhibit an extensive
infiltrate of polymorphonuclear leukocytes and
stromal edema.

9. CHRONIC CERVICITIS
 Common organism – streptococci, E coli, gonococii,TV,
Candida
 Backache (frequent), vaginal discharge and dyspareunia are
the symptoms
Gross
 Eversion of ectocervix with edema, hyperaemia and granular
surface
Microscopy
 Infiltration of lymphocytes, plasma cells and few neutrophils
 Squamous metaplasia
 Surface keratinisation (epidermidisation)
 Obstruct the mouth of the endocervical glands to produce
nabothian cysts

10. Chronic cervicitis

11. Chronic
Cervicitis
Nabothian
Cysts

12. CERVICAL POLYPS
 Cervical polyps are localised benign proliferations of
endocervical mucosa though they may protrude through the
external os.
 2-5% of adult women
 Irregular vaginal spotting.
Grossly
 small (up to 5 cm in size), bright red, fragile growth which is
frequently pedunculated but may be sessile.
Microscopically
 Covered with endocervical epithelium which may show
squamous metaplasia.
 The stroma of the polyp is composed of loose and oedematous
fibrous tissue with variable degree of infammatory infiltrate and
contains dilated mucus secreting endocervical glands.

14. Endocervical polyp

15. MICROGLANDULAR HYPERPLASIA
 Benign
 Closely packed proliferation of endocervical
glands without intervening stroma.
 Cause: Progestrin stimulation such as during
pregnancy, postpartum period and in women
taking oral contraceptives.
 May be mistaken for well differentiated
adeno carcinoma.

16. CIN & CARCINOMA CERVIX

17. Squamous Intraepithelial Lesion
(Cervical Intraepithelial Neoplasia, CIN)
• Cervical dysplasia is a precursor lesion for cancer (CIN-Cervical
Intraepithelial Neoplasia)
• Dysplasia: characterized by disordered epithelial growth and
loss of polarity and nuclear hyperchromasia which begins at
the basal layer and extends toward the surface
• Occurs at the “T” zone
 Depending upon the thickness of squamous epithelium
involved by atypical cells, dysplasia is conventionally graded
as mild, moderate and severe.
 Carcinoma in situ is the full-thickness involvement by atypical
cells,

18. CIN classification
 CIN-1 represents less than one-third
involvement of the thickness of epithelium
(mild dysplasia).
 CIN-2 is one-third to two-third involvement
(moderate dysplasia).
 CIN-3 is full-thickness involvement or
equivalent to carcinoma in situ (severe
dysplasia and carcinoma in situ).

20. SIL
According to the Bethesda system
Squamous intraepithelial lesions (SIL)—
 Low-grade SIL (L-SIL)
 High grade SIL (H-SIL)

21. L-SIL
 Corresponds to CIN-1 and is a flat condyloma,
having koilocytic atypia.
 Related to HPV 6 and 11 infection
 Mild dysplasia

22. H-SIL
 Corresponds to CIN-2 and 3
 HPV 16 and 18 are implicated in the etiology
of H-SIL
 Moderate dysplasia, severe dysplasia, and
carcinoma in situ.

23. • CIN or SIL can develop at any age though it is
rare before puberty.
• Low-grade reversible changes arise in young
women between 25 and 30 years
• Progressive higher grades of epithelial
changes develop a decade later.

26. ETIOPATHOGENESIS.
4 most important risk factors:
i)Women having early age of sexual activity.
ii)Women having multiple sexual partners.
iii) Women with persistent HPV infection with
high-risk types of oncogenic virus.
iv) Potential role of high risk male sexual partner
having previous multiple sexual partners, having
history of penile condyloma, or male who had
previous spouse with cervical cancer.

27. Other epidemiological
features
High incidence of cervical cancer in
• Lower socioeconomic strata,
• In multiparous women,
• Users of oral contraceptives
• HIV infection
• Immunosuppression,
Low incidence in
• virgins and nuns.

28. Virologic studies
• Human papilloma virus (HPV) infection is strongly
implicated in the etiology of cervical cancer.
• High-risk type HPV, most commonly of types 16 and
18 (in 70% cases), and less often types 31, 33, 52 and
58, are present in 70-100% cases of cervical cancer.
• Low-risk type HPV types 6 and 11 in condylomas.
• Mixed high and low risk types of HPV in dysplasias.
• HIV, HTLV-1 and EBV infection may adversely affect
the prognosis but do not have etiologic relationship

29. Molecular studies
• Immunohistochemical, cytogenetic and
molecular studies have shown that low-risk HPV
types do not integrate in the host cell genome,
while high-risk HPV types are integrated into the
nucleus of cervical epithelial cells.
• Upon integration, protein product of HPV-16 and
18, E7 and E6 proteins respectively, inactivate
tumour suppressor genes, p53 and RB-1 gene,
thus permitting uncontrolled cellular
proliferation.

30. Molecular studies
 All women who harbour HPV infection with
high-risk type do not develop invasive cancer
of the cervix.
 Women who have persistence of this
infection or those who have another cofactor
such as cigarette smoking or
immunodeficiency, are at greater risk to
develop progression of lesions.

32. Immunologic studies
 Circulating tumour specific antigens and
antibodies are detected in patients of cervical
cancer.
 Antibodies to virus specific antigens are
identified on tumour cells and in sera of
patients

33. MORPHOLOGIC FEATURES
Gross
• No specific picture
• Changes begin at the squamocolumnar
junction or transitional zone.

34. Microscopy
• In mild dysplasia (CIN-1), the abnormal cells
extend up to one-third thickness from the basal
to the surface layer;
• In moderate dysplasia (CIN-2) up to two-thirds;
• In severe dysplasia (CIN-3), these cells extend
from 75-90% thickness of epithelium
• In carcinoma in situ (included in CIN-3), the entire
thickness from the basement membrane to the
surface shows dysplastic cells.

35. Microscopy
• The individual dysplastic or abnormal cells in
these grades of atypia show various cytologic
changes such as:
• Crowding of cells
• Pleomorphism
• High nucleocytoplasmic ratio
• Coarse and irregular nuclear chromatin
• Numerous mitoses
• Scattered dyskaryotic cells.

36. Normal Cervix :
SUPER F INTERM BASAL

37. Koilocytic change

39. CERVICAL CARCINOMA
 Peak - 45 years.
 Detected at a subclinical stage, during evaluation of an
abnormal Pap smear
 Squamous cell carcinoma most common histologic
subtype (80% of cases).
 Adenocarcinoma(15% of cervical cancers)
 Adenosquamous and neuroendocrine carcinomas (5% of
cases).
 HSIL is an immediate precursor of cervical squamous cell
carcinoma.
 All of the above tumor types are caused by high oncogenic
risk HPVs.

40. Cervical cancer - Squamous
cell carcinoma
 Clinical
 Hemorrhage – post coital bleeding
 Blood stained discharge with offensive odour
 Cachexia
 Pain- late symptom with infiltration of
surrounding structures,
 On examination – cervix bleeds on touch,
friable and in advanced cases has fixity and
induration

41. Ca Cx - Morphology
 3 gross types
 Exophytic/Fungating, Ulcerating & Infiltrative.

42. Carcinoma cervix

43. Fungating Ca Cx

44. Microscopy squamous cell
carcinomas
 Composed of nests and tongues of malignant
squamous epithelium, either keratinizing or
nonkeratinizing, invading the underlying
cervical stroma

46. Infiltrating Carcinoma Cx:

47. Squamous Carcinoma:

48. Squamous Cell Carcinoma of the Cervix

49. Adenocarcinoma
 Proliferation of glandular epithelium composed
of malignant endocervical cells with large,
hyperchromatic nuclei and relatively mucin-
depleted cytoplasm.

50. Adenocarcinoma

52. Adenosquamous carcinoma
 Adenosquamous carcinomas are tumors
composed of intermixed malignant glandular
and malignant squamous epithelium.

53. Adenosquamous carcinoma

54. Other malignant tumours:
Rare
Sarcoma, malignant melanoma and lymphoma.
Small cell (neuroendocrine) carcinoma of the
cervix

55. Spread:
• 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.

56. Staging:
 Stage 0 – CIN-III
 Stage 1 – Ca limited to Cx
 1a – Preclinical – diagnosed by microscopy
 1a1- Minimal invasive
 1a2 – Microscopic invasion <5mm
 1b – more than 5 mm invasion
 Stage 2 – Beyond cervix but pelvic wall free
 Stage 3 – Pelvic wall/lower vagina involved
 Stage 4 – Extension beyond pelvis.

57. Cervical Cytology- (Pap
smear)
 Screening procedure
 Ayre’s spatula
 Cervical brush
 Papanicolou stain

58. Cervical cytology (Pap smear)
 3 types of cells:
 Para basal cells
 Intermediate cells
 Superficial cells

59. CIN I
CIN II
CIN
III
LSIL
LSIL

60. Koilocytic atypia - Cytology

61. Colposcopic examination
 CIN lesions appear white patches on application
of acetic acid (3 – 5 %)
 Vascular mosaic pattern
 Punctuation
 Dilated capillaries terminating on the surface which
appear from the ends as a collection of dots.
 Prominent blood vessels:
 Indicates severe dysplasia and CIS

62. Mosaic pattern

63. Schiller Iodine Solution

64. Treatment in cervical cancer
 Precursor lesions (CIN)
 Follow-up Pap smears (LSIL), cryotherapy, laser,
cone biopsy (conization), LEEP for HSIL
 Invasive cancers
 Hysterectomy with radiation for advanced cancers
 Prevention - ? vaccine