Pre-management Ca cervix & Uterus

1. Cervix & Uterus
• Anatomy With Lymphatic Drainage
• Etiology & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors
Dr. Varshu Goel
First Year Post-Graduate Resident
Department of Radiotherapy
Maulana Azad Medical College, Delhi

2. Cervix & Uterus
• Anatomy With Lymphatic Drainage
• Etiology & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors

3. 3
DevelopmentOf The
GenitalDucts
A. Week 5. The paired
paramesonephric (Müllerian)
ducts begin to form along the
lateral surface of the urogenital
ridge and grow in close
association to the mesonephric
duct
B. Week 6. The paramesonephric
ducts grow caudally and project
into the dorsal wall of the
cloaca and induce the formation
of the sinovaginal bulbs.
BRS Embryology, 6th ed.

4. 4
DevelopmentOf The
GenitalDucts
A. Week 5.
B. Week 6.
C. Week 9. The caudal portions of the
paramesonephric ducts fuse in the
midline to form the uterovaginal
primordium, and the sinovaginal bulbs
fuse to form the vaginal plate at the
urogenital sinus
D. Genital ducts in the indifferent
embryo.
E. Lateral view showing the dual origin of
the vagina.
BRS Embryology, 6th ed.

5. Uterus
• Hollow, thick-walled, pear-shaped,
muscular organ located in the pelvis
• On average - approximately 7 to 8 cm
long, 5 to 7 cm wide, and 2 to 3 cm thick
• Wall of the uterus has three layers:
• outer serosal layer
• middle myometrium - approximately
12 to 15 mm of muscle
• inner coat called the endometrium
• Cervix : approximately 3 by 3 cm fibrous
organ
• upper or supravaginal portion :
endocervical canal
• vaginal portion, projecting in the
vaginal vault
DC Dutta’s Textbook of Gynecology, 6th ed.Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.
5

6. 6
Uterus
• Angle of ante-flexion : 1700
• Angle of ante-version : 900
• Relations of uterus :
• Anteriorly:
• The body of the uterus is
related anteriorly to the
uterovesical pouch and the
superior surface of the
bladder
• The supravaginal cervix is
related to the superior
surface of the bladder.
• The vaginal cervix is related
to the anterior fornix of the
vagina
Snell’s Clinical Anatomy by Regions, 9th ed.

7. 7
Relationsof Uterus
• Posteriorly: The body of the
uterus is related posteriorly to
the rectouterine pouch (pouch of
Douglas) with coils of ileum or
sigmoid colon within it
• Laterally:
• The body of the uterus related
to the broad ligament and the
uterine artery and vein
• The supravaginal cervix is
related to the ureter as it
passes forward to enter the
bladder
• The vaginal cervix is related to
the lateral fornix of the vagina
Snell’s Clinical Anatomy by Regions, 9th ed.

8. 8
Supports of Uterus
• Mainly by the tone of the
levatores ani muscles and the
condensations of pelvic
fascia, which form three
important ligaments
• Transverse Cervical
(Cardinal) ligaments
• Pubocervical ligaments
• Sacrocervical ligaments
• Attached to the surrounding
structures in the pelvis by
broad and the round
ligaments
Ligamentous supports of uterus as seen from below
Coronal section of the pelvis
Snell’s Clinical Anatomy by Regions, 9th ed.

9. Lymphatics
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.
Shaw’s Textbook of Gynecology, 16th ed.
• Drains principally into the paracervical (parametrial, sacral and pre sacral)
lymph nodes  external iliac (obturator) and the internal iliac (hypogastric)
lymph nodes
• The pelvic lymphatics drain into the common iliac and the para-aortic lymph
nodes
• Fundus: para-aortic lymph nodes, some part into inguinal nodes (along the
round ligament) and common iliac lymph nodes
9

10. Cervical Cancer

11. • Fourth most common cancer in women, and the seventh overall, with
an estimated 528,000 new cases seen in 2012
• Future burden of cervical cancer (in term of incidence or mortality) in
Indian population in 2020 will be 148,624 new cases against 122,844 in
2012
(International Agency for Research on Cancer GLOBOCAN, 2012)
• Occur in approximately 1 in 53 Indian women during their lifetime
(Institute of Health Metrics and Evaluation. 2011)
• In medical research, the most famous cell line known as HeLa was
developed from cervical cancer cells of Henrietta Lacks in 1951
11
CervicalCancer

12. • One of the leading cause of cancer mortality, accounting for
17% of all cancer deaths among women aged between 30 and
69 years
(International Agency for Research on Cancer GLOBOCAN, 2012)
12
CervicalCancer

13. 13
Cervix
• Lower third of uterus
• Endocervical canal - lined by glandular or columnar epithelium
• Vaginal portion of cervix - exocervix - squamous epithelium
• New squamocolumnar junction located at the external cervical os
where the endocervical canal begins
• Original squamocolumnar junction located on the ectocervix, vaginal
fornix or upper vagina
• The area between the two junctions is the transformation zone - site
of majority of carcinoma cervix
AJCC Cancer Staging Manual, 8th ed.

14. Cervix
• Anatomy With Lymphatic Drainage
• Etiology & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors

15. 15
Etiology: HumanPapillomaVirus
• >90% of cervical cancers are related to the presence of HPV
• HPV 16 and 18, as well as less frequent subtypes, including but not
limited to HPV 31, 33, 35, 39, 45, 51, 52, 56, and 58
• The ability of high-risk HPVs to transform human epithelia relates to
the transcription of specific viral gene products
• Transcription from the HPV genome occurs in two waves :
• Early phase with seven to eight gene products - critical role in viral
DNA replication (E1, E8) and in the regulation of transcription (E2,
E8)
• Late phase with two gene products - L1 and L2 genes code for the
capsid’s primary and secondary proteins, respectively
DeVita's Cancer : Principles and Practice of Oncology, 10th ed.

16. 16
Riskfactors
• Developing countries including parts of Asia, Africa, Central and
South America (confounders : socio- economic status, access to
health care, cigarette smoking, poor genital hygiene, immune status,
and other factors affecting host immunity such as nutritional status)
• Age : incidence increases from 35 years and peaks at 55-64 years
• Early age of first intercourse
• multiple sexual partners or male partner with such history
• Large number of pregnancies
• History of STDs, including gonorrhea, chlamydia,HSV II, HIV
• Male partner have a history of penile carcinoma
• DES exposure in-utero (clear cell adenocarcinoma)
• Protective factor : IUD, potentially through an increase in cellular
immunity triggered by the device
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

17. 17
E6 protein inactivates the major tumor suppressor p53; this causes
chromosomal instability, inhibits apoptosis, and activates
telomerase
E7 protein affects the retinoblastoma protein (Rb), resulting in a
loss of regulation of the cell’s proliferation and immortalization
HPV genome integrates into the host cell chromosomes in cervical
epithelial cells and codes for six early and two late open reading
frame proteins, of which three (E5, E6, and E7) alter cellular
proliferation
Pathology
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.
Dysplasia (CIN)
Invasive Carcinoma
20-40% of CIN3 (CIS)

18. • Direct Invasion
• Lymphatic spread
• Blood-borne metastasis
Corpus 10-30% Urinary Bladder
Cervical Epithelium Cervical Stroma Parametrium
Vagina Rectum
Spreadof tumor
LN Involvement (%) Pelvic Stage Para-Aortic
0.5 Ia1 0
4.8 Ia2 2.0
15.9 Ib 2.2
30.0 II 15
50 .0 III 25

19. • Squamous cell carcinoma -
• Large cell keratinizing squamous cell carcinoma
• Large cell non - keratinizing squamous cell carcinoma
• Small cell carcinoma
• Basaloid squamous cell carcinoma
• Papillary squamous cell carcinoma
• Verrucous squamous cell carcinoma
• Warty carcinoma
• Lymphoepithelioma-like squamous cell carcinoma
• Adenocarcinoma
• Mucinous : Endocervical, intestinal, signet-ring cell, minimal deviation and
villoglandular type
• Endometrioid adenocarcinoma
• Clear cell adenocarcinoma
• Serous adenocarcinoma
• Mesonephric adenocarcinoma
• Adenoid cystic adenocarcinoma
19
WHOhistologicalclassificationof Cervix
WHO Classification Of Cervix, IARC Press, 2005

20. • Adenosquamous carcinoma : Glassy cell carcinoma variant
• Adenoma malignum
• Neuroendocrine tumours
• Mesenchymal tumors
• Mixed epithelial and mesenchymal tumors
• Melanocytic tumors
• Lymphoid and haematopoietic tumors
• Secondary tumors (metastases to cervix from breast, ovary, kidney)
• Miscellaneous (germ cell type) 20
WHOhistologicalclassificationof Cervix
WHO Classification Of Cervix, IARC Press, 2005

21. Cervix
• Anatomy With Lymphatic Drainage
• Etiology & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors

22. 22
Clinical Presentation
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.
• Most common symptom : Irregular vaginal bleeding such as
metrorrhagia (inter-menstrual bleeding) or menorrhagia (heavier
menstrual flow)
• Most specific symptom : post-coital bleeding
• If chronic bleeding occurs : fatigue or other symptoms related to
anemia
• Advanced cases :
• Bowel obstruction : Rectal bleeding, obstipation
• Flank pain : para-aortic lymph node involvement with extension
into the lumbosacral roots or hydronephrosis
• Renal failure : Dysuria, hematuria
• Foul-smelling serosanguinous or yellowish vaginal discharge
• Pelvic pain (tumor necrosis or associated pelvic inflammatory
disease)
• Persistent edema of lower extremities due to lymphatic/venous
blockade by pelvic sidewall disease

23. DiagnosticWorkup
23
• General –
• History
• Menstrual History
• Smoking (SCC)
• OCP (adenoca.)
• Physical examination
• Bimanual Examination (mobility, tenderness)
• Lymph nodes
• Bony tenderness
• Lower limb edema
• Per Vaginal Examination - nature of growth, size,
bleeds to touch, fornices involvement, vaginal walls,
adnexa
• Rectovaginal Examination - parametrium and rectal
mucosa involvement
• Per Speculum Examination
• Blood investigations including CBC, KFT, LFT, HIV
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

24. DiagnosticWorkup
• Urinalysis : routine microscopy, culture sensitivity
• Histopathology : PAP smear if not bleeding, Colposcopy,
Conization (subclinical tumor), Punch Biopsy (edge of gross
tumor, four quadrants), endocervical dilatation and curettage,
Cystoscopy and rectosigmoidoscopy
• Radiographic –
• FIGO recommended for staging : Chest X-ray (lung
metastases/mediatinal lymphadenopathy), Skeletal X-rays,
IVP, barium enema
• Not to used for staging : CEMRI (abdomen and pelvis) -
method of choice, CECT (para-aortic LNs), PET/CT (bone
metastases), USG (role in detecting uterine perforation during
ICRT)
24
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

25. FIGO 2018 Staging
25
FIGO 2018
FIGO
stage
Definition
I Cervical carcinoma confined to uterus (extension to corpus should
be disregarded)
IA Invasive carcinoma diagnosed only by microscopy, with maximum
depth of invasion < 5 mm
IA1 Stromal invasion < 3.0 mm in depth (measured from the base of
the epithelium)
IA2 Stromal invasion  3.0 mm and < 5.0 mm in depth
IB Clinically visible lesion confined to cervix or microscopic lesion
with deepest invasion  5.0 mm (greater than Stage IA)
IB1 Invasive carcinoma  5.0 mm in depth of stromal invasion and <
2.0 cm in greatest dimension
IB2 Invasive carcinoma  2.0 cm and < 4.0 cm in greatest dimension
IB3 Invasive carcinoma  4.0 cm in greatest dimension

26. 26
FIGO
stage
Definition
II Cervical carcinoma invades beyond uterus, but has not extended
onto the lower third of vagina or to the pelvic wall
IIA Involvement limited to the upper two-thirds of vagina without
parametrial involvement
IIA1 Invasive carcinoma < 4.0 cm in greatest dimension
IIA2 Invasive carcinoma  4.0 cm in greatest dimension
IIB Tumor with parametrial involvement but not to the pelvic wall
III The carcinoma involves the lower third of the vagina and/or
extends to the pelvic wall and/or causes hydronephrosis or
nonfunctioning kidney and/or involves pelvic and/or para-aortic
lymph nodes
IIIA Tumor involves lower third of vagina, no extension to pelvic wall
FIGO 2018 Staging
FIGO 2018

27. 27
FIGO
stage
Definition
IIIB Tumor extends to pelvic sidewall and/or causes hydronephrosis or
nonfunctioning kidney
IIIC Involvement of pelvic and/or para-aortic lymph nodes, irrespective
of tumor size and extent
IIIC1 Pelvic lymph node metastasis only
IIIC2 Para-aortic lymph node metastasis
IV The carcinoma has extended beyond the true pelvis or has
involved (biopsy proven) the mucosa of the bladder or rectum
IVA Spread to adjacent organs
IVB Spread to distant organs
FIGO 2018 Staging
FIGO 2018

28. Cervix
• Anatomy With Lymphatic Drainage
• Etiology & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors

29. 29
1. Patient Related Factors:
a) Age : decreased survival in women younger than 35 or 40 years
b) Racial differences existed in patterns of admission, type of therapy,
and severity of illness
2. General Medical Condition :
a) Anemia and Tumor Hypoxia : impact on tumor radiosensitivity
(Hypoxic tumors are more likely to recur locoregionally than well-
oxygenated tumors)
b) Other medical factors :
• Arterial hypertension (diastolic pressure of >110 mm Hg) : pelvic
recurrences and complications
• Temperature of >101°F : distant metastases
• HIV positive or acquired immunodeficiency syndrome : tumor
recurrence
3. Treatment Duration: overall treatment time should be as short as
possible, all intracavitary insertions within 4.5 weeks from initiation of
irradiation yield lower pelvic failure rates (1% loss of tumor control per
day of prolongation of treatment time beyond 30 days - Fyles et al.)
PrognosticFactors
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

30. 30
4. Tumor Factors:
a) Stage
b) HPV subtype : higher risk of lymph node and other distant
metastases with HPV 18
c) Tumor Dimension - tumor size, clinical tumor diameter
d) Depth of stromal invasion (≥10 mm or >70% invasion)
e) Parametrial, pelvic and para-aortic node involvement
f) Histology
g) Uterine Body Involvement
h) LVSI or margin status after radical hysterectomy
PrognosticFactors
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

31. 31
1. Angiogenesis/Hypoxia (HIF-2α/CD68, VEGF, thymidine phosphorylase,
NOS, CA9, CA12, micro vessel density)
2. Flow cytometry studies on DNA S-phase fraction
3. Apoptosis (Bax, Bcl-2, p53)
4. Cell Cycle G2/M checkpoint : targeting compounds interfering with
G2/M transition enhance the effect of irradiation
5. Cellular oncogenes (p27, p53, p21, c-myc, Gadd45)
6. Cytokeratin Markers and EGFR pathway
PrognosticBiomarkers
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

32. 32
7. Elevated levels of CEA, CA 19.9 and CA 125
8. SCC-Antigen : persistently elevated SCC-Ag level 3 months after RT
was a stronger predictor for treatment failure
9. EBV, TGF, β3-integrin
10. Cyclooxygenase-2 expression more in adenocarcinoma; high
locoregional recurrence in coexpression of COX-2 and thymidine
phosphorylase
11. Hormonal receptors : significantly higher disease-free survival rate of
progesterone receptor PgR-positive patients
PrognosticBiomarkers
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

33. 33
• Pap smear screening should begin at age 21 years and continue
every 2 years until age 30 years
• If there are three normal consecutive Pap smears and no history of
CIN2, CIN3, DES exposure, or HIV infection and the woman is not
otherwise immunocompromised, screening should be every 3
years
• Co-testing of the Pap smear with an HPV DNA test is appropriate
for low-risk women older than age 30 years
• Women who have been treated for CIN2 or CIN3 need annual
screening for at least 20 years
• If the cytologic smear shows atypia or mild dysplasia (class II), it
should be repeated no sooner than 2 weeks after the initial test to
allow representative cellular exfoliation to occur
Screening
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

34. 34
• Gardasil :
• quadrivalent human papillomavirus recombinant vaccine for HPV
types 6, 11, 16, and 18,
• FDA approved in 2006 for girls and women ages 9 to 26 years
• 3 doses over 6 months
• Also available for boys ages 9 to 26 years
• Goal of eradicating HPV- related gynecologic, penile, anal, and
oropharyngeal cancers
• Cervarix : vaccine with strong immunogenicity to HPV types 16 and
18, approved for girls 9 to 25 years old, is more frequently
administered in Europe
HPVVaccination
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

35. Endometrial Cancer

36. • Affects predominantly postmenopausal women but with 5% to 30%
of women <50 years of age at the time of diagnosis
• Causes unknown but several risk factors have been associated with
endometrial cancer - chiefly unopposed estrogen
(endogenous/exogenous)
• Endometrial Hyperplasia : (progression to carcinoma)
• Simple - without atypia (<1%), with atypia (8%)
• Complex - without atypia (3%), with atypia (29%)
36
EndometrialCancer

37. Endometrium
• Anatomy With Lymphatic Drainage
• Risk Factors & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors

38. 38
Riskfactors
• Menstruation Span : early age at menarche (estimated RR 1.5 to 2) and
late age at menopause (RR 2 to 3)
• Nulliparity (RR 3)
• Obesity (RR 5)
• After menopause : major source of estrogen is via peripheral
conversion, mostly within adipose tissue, of androgens that continue
being produced by the adrenal glands and ovaries. Thus with obesity
there is an increase in the amount of bioavailable estrogens in the
circulation and the endometrial tissue
• In premenopausal women : via chronic hyperinsulinemia, which
appears to be a key factor for the development of ovarian
hyperandrogenism, associated with anovulation and progesterone
deficiency
• Non–insulin-dependent diabetes mellitus and hypertension (RR 1–3)
secondary to obesity
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

39. 39
Riskfactors
• Use of estrogen-only hormone-replacement therapy and sequential
oral contraceptives(RR 10 to 20), whereas combined preparations,
that is, those that contain a progestogen as well as estrogen
throughout the treatment period, have a protective effect
• Use of tamoxifen in patients with breast cancer (RR 3 to 7)
• Inherited genetic predisposition, especially in the setting of
hereditary nonpolyposis colorectal cancer (HNPCC) with mutations in
one of the four mismatch repair genes (hMLH1, hMSH2, hMSH6, or
hPMS2) with lifetime cumulative risk of endometrial cancer being
40% to 60% - recommended screening starting at age 35 years,
including annual transvaginal ultrasound and endometrial biopsy
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

40. • Endometrioid adenocarcinoma
• Not otherwise specified - most common
• Villoglandular
• Secretory adenocarcinoma
• Ciliated carcinoma
• adenocarcinoma with squamous differentiation
• Uterine papillary serous : Psammoma bodies(33%)
• Clear cell carcinoma (not related to DES)
• Squamous cell carcinoma
40
WHOhistologicalclassificationof Endometrium
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

41. • Mucinous carcinoma : CEA positive
• Transitional cell carcinoma
• Mixed-cell type
• Undifferentiated carcinoma
• Metastatic carcinoma to the endometrium
• Simultaneous tumors : field effect of the Müllerian System; site of
the largest tumor is assigned the primary origin
41
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.
WHOhistologicalclassificationof Endometrium

42. 42
Type I Type II
strong correlation with prior estrogen
stimulation
no prior history of estrogen stimulation
premenopausal and perimenopausal
women
postmenopausal women
Indolent in nature, with minimal
myometrial invasion and low-grade
histology
often high grade, such as serous or clear-
cell cancers with deep invasion, and at a
more advanced stage at the time of
presentation
Altered PI3K/PTEN/AKT pathway
K-ras mutation
Microsatellite instability
B-Catenin mutation
Loss of E-cadherin expression
Amplification and overexpression of
HER2
Inactivation of the p53 tumor suppressor
gene
MolecularBiology of Endometrial
carcinoma
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

43. Endometrium
• Anatomy With Lymphatic Drainage
• Etiology & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors

44. 44
Clinical Presentation
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.
• Most common symptom : post menopausal bleeding (recurrent
episodes)
• with history of diabetes, older age, high BMI
• Vaginal discharge
• Abnormal Papanicolaou smear
• Thickened endometrium on routine transvaginal ultrasound
• Advanced disease :
• urinary or rectal bleeding
• constipation
• pain in abdomen
• lower-extremity lymphedema,
• abdominal distension due to ascites
• cough and/or hemoptysis

45. DiagnosticWorkup
45
• General –
• History
• Menopausal History
• Physical examination
• Bimanual Examination (mobility, tenderness)
• Lymph nodes
• Bony tenderness
• Lower limb edema
• Per Vaginal Examination
• Rectovaginal Examination
• Per Speculum Examination
• Blood investigations including CBC, KFT, LFT, Serum CA 125 levels
• Urinalysis : routine microscopy, culture sensitivity
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

46. DiagnosticWorkup
• Histopathology : Endometrial Tissue Sampling (Gold Standard) via
biopsy or dilatation and curettage
• Transvaginal ultrasonography (TVU) : endometrial thickness of 5 mm
or greater is abnormal
• If the TVU is abnormal but the biopsy is negative/ nondiagnostic or the
uterine cavity is inaccessible, then saline-infusion sonography or
hysteroscopy should be considered to help exclude intracavitary
lesions
• CEMRI - most accurate imaging study to assess tumor extension,
especially myometrial invasion
• CECT/PET-CT : limited role
46
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

47. FIGO StagingFor UterineCarcinoma
47
AJCC Cancer Staging Manual, 8th ed.
FIGO
stage
Definition
I Tumor confined to corpus uteri, including endocervical glandular
involvement
IA Tumor limited to endometrium or invades less than one-half of the
myometrium
IB Tumor invades one-half or more of the myometrium
II Tumor invades stromal connective tissue of the cervix but does
not extend beyond uterus (does not include endocervical
glandular involvement)
IIIA Tumor involves serosa and/or adnexa (direct extension or
metastasis)
IIIB Vaginal involvement (direct extension or metastasis) or
parametrial involvement

48. FIGO StagingFor UterineCarcinoma
48
AJCC Cancer Staging Manual, 8th ed.
FIGO
stage
Definition
IIIC1 Regional lymph node metastasis to pelvic lymph nodes
IIIC2 Regional lymph node metastasis to para-aortic lymph nodes, with
or without positive pelvic lymph nodes
IVA Tumor invades bladder mucosa and/or bowel mucosa (bullous
edema is not sufficient to classify a tumor as IVA)
IVB Distant metastasis (includes metastasis to inguinal lymph nodes
intraperitoneal disease, or lung, liver, or bone. It excludes
metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or
adnexa)

49. Histopathology: Degreeof Differentiation
49
AJCC Cancer Staging Manual, 8th ed.
Grade Definition
G1 5% or less of a nonsquamous or nonmorular solid growth pattern
G2 6-50% of a nonsquamous or nonmorular solid growth pattern
G3 More than 50% of a nonsquamous or nonmorular solid growth
pattern. Papillary serous, clear cell, and carcinomasarcomas are
considered high grade.
• Notable nuclear atypia exceeding that which is routinely expected for the
architectural grade increases the tumor grade by 1 (i.e., 1 to 2 and 2 to 3).
• Serous, clear cell, and mixed mesodermal tumors are high risk and considered
grade 3.
• Adenocarcinomas with benign squamous elements (squamous metaplasia) are
graded according to the nuclear grade of the glandular component.

50. FIGO StagingFor UterineSarcoma
50
AJCC Cancer Staging Manual, 8th ed.
FIGO
stage
Leiomyosarcoma and
Endometrial Stromal Sarcoma
Adenosarcoma
I Tumor limited to the uterus Tumor limited to the uterus
IA Tumor 5 cm or less in greatest
dimension
Tumor limited to the
endometrium/ endocervix
IB Tumor more than 5 cm Tumor invades to less than half of
the myometrium
IC Tumor invades more than half of
the myometrium
II Tumor extends beyond the
uterus, within the pelvis
Tumor extends beyond the
uterus, within the pelvis
IIA Tumor involves adnexa Tumor involves adnexa
IIB Tumor involves other pelvic
tissues
Tumor involves other pelvic
tissues

51. FIGO StagingFor UterineSarcoma
51
AJCC Cancer Staging Manual, 8th ed.
FIGO
stage
Leiomyosarcoma and
Endometrial Stromal Sarcoma
Adenosarcoma
III Tumor infiltrates abdominal
tissues
Tumor infiltrates abdominal
tissues
IIIA One site One site
IIIB More than one site More than one site
IIIC Regional lymph node metastasis Regional lymph node metastasis
IVA Tumor invades bladder or
rectum
Tumor invades bladder or rectum
IVB Distant metastasis (excluding
adnexa, pelvic and abdominal
tissues)
Distant metastasis (excluding
adnexa, pelvic and abdominal
tissues)

52. Endometrium
• Anatomy With Lymphatic Drainage
• Etiology & Pathology
• Clinical Presentation & Investigative
Workup
• Prognostic Factors

53. 53
1. Age : local-regional recurrence in women >60 years
2. Race : African Americans have high risk tumors
3. Histologic Subtype : 5-year survival rate better for endometrioid
adenocarcinoma
4. Grade
5. Myometrial Invasion
6. LVSI
PrognosticFactors
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

54. 54
7. Lower Uterine Segment Involvement
8. Cervical Involvement
9. Peritoneal Cytology : In recent FIGO staging (2009), having
positive peritoneal cytology is no longer considered stage IIIA
10. Adnexal/Serosal Involvement
11. Pelvic and Para-aortic Lymph Node Involvement
12. Molecular Factors :
• Over expression of p53 and HER-2 : poor outcome
• PTEN mutation : favourable
PrognosticFactors
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

55. 55
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.
Nomogram for predicting overall survival in patients with endometrial cancer

56. 56
Thank You