Pathology of cervix &uterus

1. Pathology of the
Cervix & Uterus
Dr. Aye Aye Tun
Senior Lecturer, Pathology Unit
RCMP,UniKL

2. Learning Objective
 Etiopathogenesis
 Morphological features
 Clinical features
 Complications
 Investigations and

3. Learning Objective
The aetiopathogenesis, morphological features, clinical
features, investigations and complications of
 CARCINOMA CERVIX
 Congenital anomalies of the uterus
 Endometrial hyperplasia
 Endometriosis & adenomyosis
 Uterine tumors: benign & malignant

4. PATHOLOGY OF CERVIX
 INFLAMMATION
 METAPLASIA
 POLYPS
 DYSPLASIA
 CIN
 INFILTRATING CARCINOMA

7. Endocervical Polyps
 Benign exophytic growths
 Occur in 2% to 5% of adult women
 Irregular vaginal “spotting” or bleeding
Treatment - Simple curettage or surgical
excision effects a cure

8. Site:
within the
endocervical canal
Size:
small and sessile to
large
(5-cm masses that
protrude through the
cervical os)
Consistency:
soft& mucoid

9. Microscopic -
fibromyxomatous stroma
mucus secreting endocervical glands
often accompanied by inflammation
Endocervical Polyps

10. Premalignant and Malignant Neoplasms
CERVICAL INTRAEPITHELIAL NEOPLASIA
Nearly all invasive cervical squamous cell
carcinomas arise from
precursor epithelial changes referred to as
CIN

11. CERVICAL INTRAEPITHELIAL NEOPLASIA
Not all cases of CIN progress to invasive
cancer
persist without change or even regress

12. Classification Systems for
Premalignant Squamous Cervical Lesions
Dysplasia CIN Squamous Intraepithelial Lesion
(SIL)
Mild dysplasia CIN I Low-grade SIL (LSIL)
Moderate dysplasia CIN II High-grade SIL (HSIL)
Severe dysplasia CIN III High-grade SIL (HSIL)
Carcinoma in situ CIN III High-grade SIL (HSIL)

13. Papanicolaou (Pap) smear
Cytologic examination (Papanicolaou (Pap) smear)
can detect CIN long before any abnormality can be
seen grossly
The Pap smear - the most successful cancer
screening test
In populations that are screened regularly, cervical
cancer mortality is reduced by as much as 99%

14. The cytology of CIN as seen on the Papanicolaou smear
Normal
exfoliated superficial squamous epithelial
cells CIN I
CIN II CIN III

15. DYSPLASIA / CIN (CERVICAL INTRAEPITHELIAL NEOPLASIA )
Spectrum of cervical intraepithelial neoplasia:
A. normal squamous epithelium for comparison
B. CIN I with koilocytotic atypia
C. CIN II with progressive atypia in all layers of the epithelium
D. CIN III (carcinoma in situ) with diffuse atypia and loss of
maturation

16. Carcinoma Cervix
second most common cancer in women
 Squamous cell carcinomas (75%)
 Adenocarcinomas & adenosquamous
carcinomas (20%)
 Small-cell neuroendocrine carcinomas
(<5%)

17. Nobel Prize in 2008
HARALD ZUR HAUSEN was awarded
For discovery of HPV as a cause of cervical
cancer

18. Pathogenesis of Carcinoma Cervix
High oncogenic risk HPVs are currently
considered to be the single most important
factor in cervical oncogenesis
HPV 16 and HPV 18

19. Pathogenesis of Carcinoma Cervix
The risk factors for cervical cancer are related to
both host and viral characteristics
HPV exposure
viral oncogenicity
inefficiency of immune response
presence of co-carcinogens

20. Risk Factors
1. Multiple sexual partners
2. A male partner with multiple previous or current sexual
partners
3. Young age at first intercourse
4. High parity
5. Persistent infection with a high oncogenic risk HPV, e.g.,
HPV 16 or HPV18
6. Immunosuppression
7. Certain HLA subtypes
8. Use of oral contraceptives
9. Use of nicotine

21. Smoking, Hormone, Oral contr. parity,
Altered immune response etc.
Cervical Transformation Zone
Sexual Exposure
HPV Infection
Squamous Ep Columnar Ep
Squamous Ca Adeno Ca
High Risk Types (16,18)
Low Risk-6,11
PATHOGENESIS

22. Role of HPV in carcinoma cervix
How does HPVtransform cells?
Viral oncoproteins E6 and E7
 E6 binds - the product of tumor
suppressor gene TP53 and inactivates it
 E7 binds - the retinoblastoma gene (RB)
protein

23. MORPHOLOGY
pink-tan, friable
Fungating (exophytic) lesion
on the anterior cervical lip

24. Squamous cell carcinoma of the cervix
Microinvasive squamous cell carcinoma
with invasive nest breaking through the basement membrane of HSIL
MORPHOLOGY
Invasive nest of tumor cells

25. squamous cell carcinomas are composed of
nests and tongues of malignant squamous epithelium
either keratinizing or non keratinizing
invading the underlying cervical stroma
MORPHOLOGY

26. MORPHOLOGY
Adencarcinoma in situ
Adenocarcinomas are characterized by proliferation of glandular epithelium
composed of malignant endocervical cells with large, hyperchromatic nuclei
and relatively mucin-depleted cytoplasm, resulting in dark appearance of the glands
as compared with the normal endocervical epithelium
Invasive adencarcinoma

27. CLINICAL FEATURES
 Asymptomatic
 unexpected vaginal bleeding
 Leukorrhea
 painful coitus (dyspareunia)
 Dysuria

28. BODY OF UTERUS AND
ENDOMETRIUM
The uterus has two major components:
Myometrium - composed of tightly
interwoven bundles of smooth muscle that
form the wall of the uterus
Endometrium - composed of glands
embedded in a cellular stroma

29. BODY OF UTERUS AND
ENDOMETRIUM
Diseases of uterus result from
 endocrine imbalances
 complications of pregnancy
 neoplastic proliferation

30. BODY OF UTERUS AND
ENDOMETRIUM
 D.U.B. (Dysfunctional Uterine Bleeding)
 Inflammation
 Adenomyosis/Endometriosis
 Polyps/Hyperplasia
 Malignant Tumors of the Endometrium
 Tumors of the Endometrium with Stromal
Differentiation
 Tumors of the Myometrium

32. Adenomyosis/Endometriosis
Endometriosis
presence of endometrial tissue both endometrial glands and
stroma outside of the uterus
It occurs in the following sites
(1) Ovaries
(2) uterine ligaments
(3) rectovaginal septum
(4) cul de sac
(5) pelvic peritoneum
(6) large and small bowel and appendix
(7) mucosa of the cervix, vagina, and fallopian tubes
(8) laparotomy scars

33. Adenomyosis
characterizedby functional endometrial nests
within the myometrium
producing foci of hemorrhagic cysts within the uterine wall

34. Endometrosis in ovary
cystic and contains dark blood and debris resembling chocolate
described as “chocolate cysts

35. Polyps/Hyperplasia
Endometrial Polyps
Exophytic masses of variable size that project
into the endometrial cavity
Asymptomatic or cause
abnormal bleeding
(intramenstrual, menometrorrhagia, or
postmenopausal) if they ulcerate or undergo
necrosis

36. single or multiple
usually sessile, measuring from 0.5 to 3 cm in diameter
occasionally large and pedunculated
MORPHOLOGY

38. Endometrial Hyperplasia
defined as an increased proliferation of the
endometrial glands relative to the stroma
resulting in an increased gland-to-stroma
ratio
when compared with normal proliferative
endometrium
an important cause of abnormal bleeding

39. Endometrial Hyperplasia
associated with
prolonged estrogen stimulation of the
endometrium
Have the malignant potential of endometrial
hyperplasia
endometrial hyperplasia and carcinoma share
specific molecular genetic alterations
inactivation of the PTEN tumor suppressor
gene

40. MORPHOLOGY
Simple hyperplasia without atypia
with architectural abnormalities including mild glandular crowding
cystic glandular dilatation

41. MORPHOLOGY
Complex hyperplasia without atypia
increased glandular crowding with areas of back-to-back glands
cytologic features similar to proliferative endometrium

42. MORPHOLOGY
Complex hyperplasia with atypia
similar to complex hyperplasia without atypia
the cytologic features have changed

43. MORPHOLOGY
High magnification of complex hyperplasia
with atypia showing rounded, vesicular nuclei with prominent nucleoli

44. Malignant Tumors of the Endometrium
Carcinoma of the endometrium
peak incidence is in 55 - 65 year
classification of endometrial carcinoma
two broad categories
type I and type II

46. Characteristics of Type I and Type II Endometrial
Carcinoma
Characteristics Type I Type II
Age 55–65 yr 65–75 yr
Clinical setting Unopposed estrogen Atrophy
Thin physique
Obesity
Hypertension
Diabetes
Morphology Endometrioid Serous
Clear cell
Mixed m?llerian

47. Characteristics of Type I and Type II
Endometrial Carcinoma
Characteristics Type I Type II
Precursor Hyperplasia Endometrial intraepithelial carcinoma
Molecular genetics PTEN p53
PIK3CA Aneuploidy
KRAS PIK3CA
MSI β-catenin
p53

48. Characteristics of Type I and Type II
Endometrial Carcinoma
Characteristics Type I Type II
Behavior Indolent
Aggressive
Spreads via lymphatics Intraperitoneal and
lymphatic spread

49. Schematic diagram depicting
the development of type I endometrial carcinoma
arising in the setting of hyperplasia
molecular genetic alterations are shown at the time
during the progression of the disease
Type I Adenocarcinoma endmetrium

50. MORPHOLOGY
Sagittal section of the uterus shows
a friable, tan-yellow tumor
that is filling the uterine cavity
and extending into the myometrium

51. MORPHOLOGY
Endometrial adenocarcinoma
a fungating mass
in the fundus of the uterus
Well-differentiated (grade 1)
endometrioid adenocarcinoma
preserved glandular architecture
lack of intervening stroma
Moderately differentiated (grade 2)
endometrioid adenocarcinoma
glandular architecture admixed
with solid areas
Poorly differentiated (grade 3)
endometrioid adenocarcinoma
with predominantly solid growth

52. Schematic diagram of the development of type II endometrial carcinoma.
Type II Adenocarcinoma endmetrium

53. MORPHOLOGY
Endometrial intraepithelial carcinoma
Strong, diffuse expression of p53
as detected by immunohistochemistry
in endometrial intraepithelial carcinoma
Serous carcinoma of the endometrium
with papillary growth pattern
Strong, diffuse expression of p53
as detected by immunohistochemistry
in serous carcinoma endometrium

54. Clinical course of adenocarcinoma of the
endometrium
irregular or postmenopausal vaginal bleeding
excessive leukorrhea
Uterine enlargement may be absent in the early
stages
The diagnosis of endometrial cancer must
ultimately be established by biopsy or
curettage and histologic examination of the
tissue

55. Staging of types I and II of endometrial
adenocarcinoma
Stage I
Carcinoma is confined to the corpus uteri itself
Stage II
Carcinoma involves the corpus and the cervix
Stage III
Carcinoma extends outside the uterus but not
outside the true pelvis
Stage IV
Carcinoma extends outside the true pelvis or
involves the mucosa of the bladder or the
rectum

56. Tumors of the Myometrium
Leiomyoma(commonly called fibroids)
 most common tumor in women
 benign smooth muscle neoplasms
approximately 40% have a simple chromosomal abnormality
Several cytogenetic subgroups have been recognized
t(12;14)(q14–q15;q23–q24)), del(7)(q22–q32)), trisomy
12
rearrangements of 6p, 3q, and 10q
The rearrangements of 12q14 and 6p involving the
HMGIC and HMGIY genes

57. Morphology
 Site – Leiomyoma can occur
within the myometrium - intramural
just beneath endometrium - submucosal
beneath the serosa - subserosal
 Size - varying in size from small to massive
tumors that fill the pelvis
 Number – single or most often multiple

58. Morphology
 Shape - sharply circumscribed, discrete,
round
 Color & Consistency - firm, gray-white
tumors
 on cut section - characteristic whorled
pattern of smooth muscle bundles
 red degeneration- areas of yellow-brown to
red softening in large tumors

59. Morphology
On histologic examination
leiomyoma is composed of
whorled bundles of smooth muscle cells that
resemble the uninvolved myometrium
the individual muscle cells
- uniform in size and shape
- have the characteristic oval nucleus
- long, slender bipolar cytoplasmic processes

61. Leiomyomas of the myometrium
The uterus is opened to reveal multiple tumors
in submucosal (bulging into the endometrial cavity)
intramural, and subserosal locations
a firm white appearance on sectioning
MORPHOLOGY
well-differentiated, regular
spindle-shaped smooth muscle cells
associated with hyalinization

63. Leiomyosarcoma
A large hemorrhagic tumor mass
distends the lower corpus
is flanked by two leiomyomas
MORPHOLOGY
Leiomyosarcoma