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Chapter 17

Female Genital
Tumor
Dr. Yang
Section one

Premalignant
and Malignant
Disorders of the
Uterine Cervix
Dysplasia and Carcinoma in
Situ of the Cervix

 CIN – Cervical intraepithelial


neoplasia. Formerly called dysplasia
– disordered growth and
development of the epithelial lining
of the cervix.
正常子宫颈鳞状上皮


• This is normal
cervical non-
keratinizing squamous
epithelium. The
squamous cells show
maturation from basal
layer to surface.
CIN
 CIN I (mild dysplasia)– disordered
growth of the lower third of the
epithelial lining.
 CIN II (moderate dysplasia) –
abnormal maturation of two-thirds of
the lining.
 CIN III (severe dysplasia) –
encompasses more than two-thirds
of the epithelial thickness with
carcinoma in situ (CIS) representing
 CIN I
 CIN II
 CIN III
 Ca in situ
Bethesda System
 Specimen type – conventional smear (Pap
smear); liquid-based; other
 Result :

*Negative for intraepithelial lesion or no


malignancy
*ASC-US atypical squamous cell of
undetermined significance
*ASC-H cannot exclude HSIL
*LSIL low-grade squamous intraepithelial
lesion(CIN I)
*HSIL high-grade (CIN II CIN III)
*Squamous cell carcinoma
Recommendation
 It is recommended that all patients
with CIN II and CIN III be treated
when diagnosed.
 Because a certain percentage of all
dysplasias, especially high-grade
lesions, will progress to an invasive
cancer if left untreated.
Epidemiology and
Etiology
 CIN -- commonly in their 20s.
 The peak incidence of carcinoma in
situ is in women aged 25-35.
 The incidence of cervical cancer rises
after the age of 40.
Risk factors
 Multiple sexual partners
 Early onset of sexual activity
 High risk sexual partner (history of
multiple sexual partners, HPV
infection, lower genital tract
neoplasia, prior sexual exposure to
someone with cervical neoplasia)
 A history of STDs
 Cigarette smoking;
immunodeficiency; multiparity; long
term oral contraceptive pill use
HPV—high risk factor
 Condoms cannot be against HPV, it can be
transmitted by labial-scrotal contact.
 >80% CIN --HPV(+)
>90% Cx Ca --HPV(+)
 Over 70 subtypes
low-risk – 6, 11, 42, 43, 44( Condylomata ;
CIN I)
intermediate-risk – 33, 35, 51, 52 (CINII
CINIII)
high-risk – 16,18,31,39,45,56,58,59,68
(invasive cancer)
Other HPV18
HPV 14%
types
23%

HPV45
8%
HPV31 HPV16
5% 50%
Pathology
 Adenocarcinoma in situ(ACIS) – the
presence of endocervical glands
lined by atypical columnar epithelium
that cytologically resembles the cells
of endocervical adenocarcinoma, but
that occur in the absence of stromal
invasion.
 Method– cone biopsy.
This is the gross Here is another cervical
appearance of a squamous cell carcinoma.
cervical Note the IUD string
squamous cell protruding from the cervix.
carcinoma that is This implies that someone
still limited to the could have done a Pap
cervix (stage I). smear when it was
The tumor is a inserted. There is a natural
fungating red to history of progression of
dysplasia to carcinoma, so
Clinical Findings
 Symptoms and Signs – most people
no. People with sexually active
should be given cytologic exmination
once a year.
 Special examination -- abnormal pap
smear should be done. eg. Repeat
cytology; HPV testing; the Schiller
test; colposcopy; directed biopsy;
endocervical curettage; cone biopsy.
Special examination
 1 Repeat cytology. AUS-US – repeat
every 4-6 months; AUS-H –
colposcopy
 2 HPV testing.
 3 Schiller test. Glycogen + iodine ---
deep mahogany-brown color.
Nonstaining:
columnar\scar\cyst\cancer.
 4 Colposcopic examination.
 5 Cone biopsy.
Colposcopic examination
 Normal findings:
original squamous epithelium;
transformation zone;
columnar epithelium.
 Abnormal findings:
leukoplakia or hyperkeratosis;
acetowhite epithelium;
mosaicism or punctation reflecting
abnormal vascular patterns of the surface
capillaries
Treatment
 Cryotherapy
 Laser ablation
 Cold knife conization
 Laser cone excision
 Leep– loop electro-surgical excision
procedure.

* It depends on: size of leision; endocervical


gland involvement; margin status of any
excisional specimen; ECC result.
Follow up
 Pap smears every 3-4 months
 Endocervical curettage every 6
months
 Completed childbearing –
hysterectomy

 Figure 17-2
Cancer of the
Cervix
Cancer of the Cervix
 The second common cause of
cancer-related morbidity and
mortality
 The average age is 51
 Over 95% of patients with early
cancer of the cervix can be cured
Etiology and
Epidemiology
 Risk factors – the same with CIN
 HPV – the central
 HPV16 – the most prevalent in
squamous cell carcinoma
 HPV18 – most prevalent in
adenocarcinoma
 Others – immunosuppression \HIV
\STD \tobacco \high parity \oral
contraceptive use.
Pathogenesis and
natural history
 HPV infection: asymptomatic latent
infection; active infection; neoplastic
transformation
 Spread :
direct extension;
lymphatic spread –
main (parametrial, hypogastric, obturator,
external iliac, sacral); stage IIB –pelvic
lymph nodes 30-40% (+) para-aortic
nodes 15-30%(+). Stage IVA– para-aortic
45% (+) blood-borne
metastasis. (liver, lungs, others)
Pathology
 Squamous cell carcinoma – 70-75%
 Adenocarcinoma –20-25%
 Adenosquamous – 3-5%
 Undifferentiated carcinoma
Pathology
 Squamous cell carcinomas and
verrucous carcinomas.
*3types:
large cell nonkeratinizing;
large cell keratinizing;
small cell carcinoma.– worse
prognosis.
Pathology
 Adenocarcinoma :
types:
mucinous;
endometrioid;
clear cell;
Serous.
Clinical findings
 Symptoms:
1.Abnormal vaginal bleeding:
blood-stained leukorrhea; scant
spotting or frank bleeding .
2. leukorrhea: sanguineous or
purulent, odorous, and nonpruritic.
Postcoital bleeding.
3.Others: pelvic pain; fistula
formation; weakness; weight loss;
anemia.
Clinical findings
 Physical signs:
barrel-shaped enlarge; friable;
cauliflower-like; ulceration; necrotic;
adjacent vaginal fornices be
involved; extensive parametrial;
uterosacral and cardinal ligaments
loss mobility and fixation.
Clinical findings
 Biopsy:
adequate– schiller-positive areas;
ulcerative; granular; nodular;
papillary leision.colposcopy;
endocervical curettage; conization.
 Conization: mark the area
Clinical staging
 Is staged by clinical examination, and
evaluation of the bladder, ureters,
and rectum.
 Chest x-ray; IVP; CT; cystoscopy;
proctoscopy; PET; MRI;
lymphangiography
 CT and surgicopathologic can not
change the stage by examination
before.
FIGO staging of cervical
cancer
 Stage o: carcinoma in situ
 Stage I A: invasive Cx Ca by
microscopy only
 Stage I A1: deeper ≤3mm,
wider≤7mm
 Stage I A2: 3mm<deeper<5mm
 Stage I B: visible lesion or
microscopic than IA.
 Stage I B1:<4cm
FIGO staging of cervical
cancer
 Stage II: extend not to pelvic sidewall or lower
third of vagina
 Stage IIA: vaginal involvement without
parametrial.
 Stage IIB: parametrial involvement
 Stage III: extend to pelvic sidewall or/and lower
third of vagina and/or hydronephrosis
 Stage IIIA: lower third of vagina
 Stage IIIB: pelvic sidewall
 Stage IV: extension beyond the true pilvis or
mucosa of rectum or bladder
 Stage IVA: adjacent organ
 Stage IVB: distant metastases
Differential diagnosis
 Cervical ectropion
 Cervicitis
 Condyloma acuminata
 Tuberculosis
 Ulceration (syphilis,
lymphogranuloma, chancroid)
Prevention
 Risk factors
 Screening treatment intervention
 education
Treatment one
 -- Early stage( stage IA2 to IIA):
Radical hysterectomy and pelvic
lymphadenecomy
Primary radiation with concomitant
chemotherapy
Ovaries may be left intact and be
transposed
Early stage A
 Stage IA1 – extrafascial
hysterectomy ; conization for
wishing preserve fertility
 Stage IA2 – modified radical
hysterectomy (ligated uterine artery
where it crosses over the ureter;
divided uterosacral and cardinal
ligaments midway towards their
attachment to sacrum and pelvic
sidewall and resected upper third of
Early stage A
 Stage IB-IIA– type III hysterectomy
(ligated uterine artery at its origin
from the superior vesical or internal
iliac artery; resected uterosacral and
cardinal ligaments at their
attachments to the sacrum and
pelvic sidewall and resected upper
half of the vagina.
Lymphadenectomy.)
Early stage B
 Postoperative adjuvant radiation with
concomitant chemotherapy ---
 Positive lymph nodes; positive or
close resection margins or
microscopic parametrial
involvement.
 Large tumor size; deep cervical
stromal invasion; lymphovascular
space invasion. -- benefit
Early stage C
 Primary radiaton with concomitant
chemotherapy
 External beam radiation is generally
used in combination with
intracavitary irradiation.
 The superiority of radiation with
concomitant platinum-based
chemotherapy over radiation alone
Treatment two
 Locally advanced disease( stage
IIB to IVA): Primary radiaton with
concomitant chemotherapy
 Extended field radiation – para-aortic
lymph node metastases.
Treatment three
 Disseminated primary ( stage
IVB ) and persistent or recurrent
disease. -- radiaton with
concomitant chemotherapy
Treatment four
 Total pelvic exenteration for isolated
central pelvic recurrence of disease
Postreatment
 Invasive cervical cancer – 35%
recurrent or persistent
 50% death in the first year; 25%
second year; 15% third year.
Prognosis
 Factors : stage; lymph node status;
tumor volume; depth of cervical
stromal invasion; lymphovascular
space invasion; lesser extent;
histologic type; grade.
 Survival rate 5 years: stage O 99-
100%; IA >95%; IB-IIA 80-90%; IIB
65%; III 40%; IV <20%
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