Cervical Intraepithelial Neoplasia[CIN]

Cervical Intraepithelial Neoplasia[CIN] written by 양경훈

Concept:
① invasive cancer but confined to the epithelium
② if not treated, may progress into cervical cancer
③ all dysplasia(metaplasia without mitotic activity) have the potential for progression

Criteria for CIN
① celluar immaturity
② celluar disorganization
③ nuclear abnormalities
④ increased mitotic activity

CIN 1: lower ⅓ of epithelium
CIN 2: middle ⅓ of epithelium
CIN 3: upper ⅓ of epithelium

Cervical Anatomy
exocervix: squamous epithelium → squamous cell carcinoma
endocervix: columnar epithelium & glands → adenocarcinoma
squamocolumnar junction- 두 상피가 만나는 부분
① Nabothian cyst를 관찰 할 수 있다.
② gland opening이 관찰된다.
③ squmous metaplasia에 의해 CIN이 생성된다.

Human Papilloma Virus as a pathogen
High risk: type 16(most common), 18
Low risk: type 6,11,42,43

Cytologic Classification System
squamous cell abnormalities
Bethesda Dysplasia/CIN system
ASCUS ----------- squamous atypia
HPV atypia
LSIL ----------- mild dysplasia/ CIN 1
----------- mnderate dysplasia/ CIN 2
HSIL ----------- severe dysplasia/ CIN 3
CIS CIN 3
* ASCUS : atypical squamous cell of undetermined significance
LSIL : low-grade squamous intraepithelial lesion
HSIL : high-grade squamous intraepithelial lesion
CIS[intraepithelial Ca. = stage 0]의 criteria
① all epithelial layer가 undifferentiated cell
② loss of polarity(+)
③ basement membrane intact & no stromal invasion
④ glandular extension(+/-)

Diagnosis.
① Pap smear : 월경일 제 8~12일 사이가 좋다
② colposcopy
Ix:- all women with abnormal cytology
- all women with previous history of abnormal cytology
- gross suspicous cervical lesion
- history of contact bleeding
- any suspicious lesion of vulva or vagina
Abnormal findings :
-(aceto-)white epithelium : epithelium turns white after application of acetic acid
- punctuation : dilated capillaries terminating on the surface
- mosaic : terminal capillary surrounding circular blocks of acetowhite epitehlium
- leukoplakia : because of keratin abnormality(초산용액 도포하지 않아도 하얗게 보임).
hyperkeratosis, parakeratosis
- iodine negative epithlium
- atypical vessel
Normal findings
- original squamous epithelium(혈관모양 관찰X, 분홍색)
- columnar epithelium(acetic acid 도포시 포도송이 모양)
- intact transformation zone
③ Human papillomavirus[HPV] typing
Ix.
- 암세포는 발견되지 않지만 비정상적인 세포진단이 나타날 때
- HPV감염 또는 초기 상피이형증 상태
- 세포진 검사에서 양성 반응을 나타냈지만 질확대경으로 진단이 불가능할 때
- 자궁경부암 발생의 위험이 높은 여성
- 자궁경부 원추절제 수술후 추적검사
④ cervicography
⑤ Schiller test
- mechanism : cervix나 vagina의 정상 상피는 glycogen이 풍부하다.
→ iodine solution(Lugol’s solution)에 dark brown color 보임(mahogany color)
- analysis : dysplasia나 cancer cell
→ iodine(-)이면 schiller test(+) : 착색이 안 됨
- Schiller test (+)인 경우
trauma, eversion, erosion, keukoplakia, benign inflammation, columnar epithelium,
squamous metaplasia, focus of carcinoma
⑥ biopsy(Dx. & Tx.)
punch Bx. : 확진 방법
Ix. : abnormal Pap smear(class II 이상)
cervix의 visible lesion(+)
method : directed punch Bx.
multiple punch Bx. → 12시, 6시 방향
conization of cervix : 가장 정확. 확진 방법
Ix.
Dx.(cold knife cone)
- colposcopy에서 S-C junction이 보이지 않을 때
- lesion이 canal 안으로 extend되고 upper limit가 보이지 않을 때
- Pap smear, colposcopic finding, directed biopsy가 일치하지 않을 때
- endocervical curettage (+)
- microinvasiveness가 의심될 때
- colposcopy 시행할 수 없고 Schiller test(+) area가 없는 경우
Tx.(hot conization)
- chronic cervicitis
- CIN(dysplasia, CIS)

epidemiology of cervical Ca.
- mild dysplasia → CIS : 7yr
- severe dysplasia → CIS : 1yr
- CIS → invasive Ca. : 10yr

very mild carcinoma microinvasive clinical
dysplasia in situ carcinoma cancer
7 14 3 2.5
15% 50~60% 100% 40%
transit time(yr)
percent of pt.
25 32 44 47
progressing
mean age(yrs)


CIS
invasive cervical Ca.의 전단계 : 20~30대 사이에 발생
치료하지 않으면 1/3~2/3에서 invasive Ca.로 진행
80% < SCJ에서 발생
90% < HPV 검출
follow-up : Pap smear를 2회/yr

치료 :
mild~moderate dysplasia
- cone Bx., multiple Bx., endocervical curettage
: young women
- /U with Pap smear, conization, cervix amputation
severe dysplasia, CIS
- R/O invasive Ca. → cone Bx., multiple Bx., endocervical curettage
- 임신하길 원하면 conization → F/U with Pap smear & colposcopy
- hysterectomy


Treatment 종류 및 적응증
① Cryotherpy
destroys the surface epithelium of cervix by crystallizing the intracellular water

Criteria
- CIN grade 1-2
- small lesion
- ectocervical location only
- negative endocervical curretage
- no endocervical gland involvement on biopsy
② Conization
Conization is indicated for dx. in women with HSIL onthe Pap test under the following condition:
- limits of the lesion cannot be visualized with colposcopy
- SCJ is not seen at colposcopy
- endocervical curettage histologic findings are positive for CIN 2 or CIN 3
- lack of correlation between cytology, biopsy and colposcopy results
- microinvasion is suspected based on biopsy, colposcopy, cytology results
- colposcopist is unable to rule out invasive cancer.
③ Laser
Ix.
- large lesions that the cryoprobe cannot adequately cover
- irregular cervix with a "fish mouth" apperance and deep clefts
- extension of diease to the vagina or satellite lesions on the vagina
④ LEEP( loop electrosurgical excision procedure)
contra-Ix.
- patient anxiety
- extremely large lesion
- vaginal extension
- clinical carcinoma