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Transcript of به نام خداوند جان وخرد. BENIGN &MALIGNANT DISEASE OF CERVIX Benign and malignant...
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BENIGN &MALIGNANT DISEASE OF CERVIX
Benign and malignant BE diseases of cervix
PREINVASIVE DISEASE AND SCREENING
Cervical Anatomy
Smooth and pink, with clear mucoid secretion and is composed of columnar epithelium,which lines the endocervical canal,and squamous epithelium,which covers the cervix.
The point at which they meet is called squamocolumnar junction(SCJ)
Cervical intraepithelial lesion
The concept of cervical intraepethelial lesion(CIN) was introduced in 1968
Term CIN is equivalent to the term dysplasia,which means abnormal maturation,cellular disorganization,nuclear abnormalities and increased mitotic activity.
The extent mitotic activity,immature cellular proliferation and nuclear atypicality identify the degree of neoplasia.
If the mitosis are present only in 1/3 of epithelium,the lesion is designed as CINI and involvement of the middle and upper third is diagnosed as CINII and CINIII.
Most CIN I and some CINII regress spantaneously if untreated,however may progress to invasive carcinoma.
Metaplasia without mitotic activity should not be called dysplasia,and it does not progress to invasive cancer.
Morphologic changes of cervical cancer
SIL and CIN
Squamocolumnar Junction
The SCJ is a dynamic point and changes in response to puberty,pregnancy,menopause
At menarche,the production of estrogen causes the vaginal epithelium to fill with glycogen,Lactobacilli act on the glycogen to lower the PH stimulating the subclumnar reserve cells to undergo metaplasia.
Metaplasia advances from the original SCJ inward,toward external OS
The T.Z extends from the original SCJ to the physiologically active SCJ.
In most cases,CIN is originate as a single focus in the transfomation zone at the advancing SCJ. Once the metaplastic epithelium matures and forms glycogen, is called healed T.Z and relatively resistant to oncogenic stimuli. The only way to determine original SCJ are nabothian cysts or
cervical cleft opening CIN is most likely to begin during menarch or after
pregnancy and after menopause there is a lower risk of C.I.N The ant. Lip of cervix is twice post. lip. CIN I-II may regress to normal as high as %75 at five years for adults and up to %91 at 3 years in adolescents.
Types of Prevention
•Primary prevention: Keeps disease from occurring at all by removing its cause. administering folic acid to prevent neural tube defects, giving immunizations and counseling patients to adopt healthy lifestyles (such as helping patients to stop smoking, to eat foods low in saturated fats and cholesterol, to exercise appropriately, and safe sexual practices)• Secondary prevention: detects early disease when it is asymptomatic and when treatment can stop it from progressing such as Pap smears, mammograms, and fecal occult blood tests
•Tertiary prevention: refers to activities that reduce complications such as use of beta-blocking drugs to decrease the risk of death in myocardial infarction,or good control of blood glucose, regular ophthalmologic examinations and monitoring for proteinuria in diabetics.
Cervical cancer is a preventable disease
17
Primary prevention:
- Avoidance of tobacco- Safe sexual practice,avoid exposure to HPV- Use barrier contraception- High folate, beta carotene, Vit C & E diet
-ImmunizationSecondary prevention: -Screening of asymptomatic population for
premalignant conditions or early stage disease before they progress to cancer
Criteria for a good screen test
•High sensitivity:The proportion of all those with disease that the test correctly identifies as positive.•High specificity:The proportion of all those without disease (normal) that the test correctly identifies as negative.•High positive predictive value• Simplicity •Low cost• Safety• Available
THE PAPANICOLAOU SMEAR
• George N. Papanicolaou, developed a microscopic technique that involved examination of vaginal debris to study the estrous cycle of guinea pigs.• The papanicolaue smear screening test for cervical cancer was introduced in the united states in 1941
...Pap Smear
- False negative : 49% - Sensitivity for CIN detection : 51 % - Sensitivity after 3 test : 87 %This is NOT a diagnostic testDetect premalignant, malignant processes of
cervix. Sample cervical cells from T.Z Sent to cytology for review of cells. Classified according to Bethesda System.
pap test
False negative error (%49) 1- sampling error : small lesion with no
exfoliated cell, device did not pick up cell, cell did not transfer from device to slide
2- preparation error : poor fixation, bloody,thick,mucus
3- interpretation error : screener fault
sample collection
Avoiding vaginal cream ,coitus,tampon for 48 h0urs No Lubricant gelClear cervical mocus and dischargeEndocervical with swab or brushExocervical with spatulaImmidiately smearedFixation promptlyLabel smear -Conventional smear -Liquid base smear
23
Equipment
Conventional Kit Thin PrepThin Prep
CONVENTIONAL PAP SMEAR
%30- %80 sensivity and %86-%100 specifityThe conventional pap smear consist of
cells,sampled from cervix using a brush or spatula,are placed on a slide and fixed with a chemical fixative in office.
• In 1990 a new technology(LBC) replaced for sreening cervical cancer•demonstrated 65% increase in detection of cancerous lesions with LBC.
• Pre-cancerous lesions can be detected 8 to10 years earlier than old PAP Smear
• Improved sensivity without loss of specefity 1- All Cells collected (%80-%90) are preserved for
analysis. 2-Remove the blood and mucus,so clearer field of vision.
3-A single specimen for HPV 4-Reflex HPV testing of the specimen may be used to test for HPV for evaluation ASC-US in cytology 5-The slides can be read by the cytopathologist more quickly 6-Better detection glandular lesion,ASC-US,LSIL than conventional PAP 7-fewer unsatisfactory specimens 8-specimen adequacy is to be improved .
LIQUID BASE CYTOLOGY
LIQUID BASAE PAP SMEAR
Liquid base cytology consists of cells that are sampled similarly but suspended in a liquid transport medium and then cells filtered in the laboratory and plated as thin layers on slides.
Conventional Pap Smear Liquid base pap smear
Conventional Pap ThinPrep Pap Test
f
Cervical screening cytology
Guideline American society cancer
ACOG
Initial screening Age 21 or 3 years after vaginal sex
Age 21 or 3 years after vaginal sex
Interval 1/year for con.papevery 2 y. for L.B.PEvery 2-3y. after 30y with 3 normal p
Every 1 y. for L.B.P or conventional papEvery 2-3 y.after 3o y. with 3 normal
Discontinue 70 y. if 3 normal pap in 10 years
No upper limit of age
Classification of Pap smear results
Papaniculau classification:Class I-VDysplasia classification(1963)CINI,II,III(1968)Bethesda classification Squamous cell ASC : atypical squamus cell ; ASC -US , ASC -H LSIL : low grade squamus intraepithelial lesion(HPV ,CIN I) HSIL: high grade squamus intraepithelial lesion(CIN II/III/Insitu) Invasive scc Glandular Cell
Atypical Glandular cells (AG) Undetermined Significance (AG-US) or NOS Favors Neoplasm
Adenocarinoma In Situ (AIS) Adenocarcinoma
Comparison of cervical cytology classification systems
Bethesda CIN Dysplasia Papanicol. NL
NL NL I
Infection , reactive,repair
Inflammatory atypia
Inflammatory atypia
II
ASC-US Squamus+HPV atypia
Squamus+HPV atypia
IIR
LSIL CIN I Mild dysplasia
III
HSIL
CIN II CIN III CIN III
Moderate dyspl. Severe dyspl.Carcinoma insitu
III IV IV
SCC SCC SCC V
•The most common cervical cytology abnormality is ASC(ASC-H or ASC-US) and is seen in %3-%4 of smears•ASC :In Bethesda 2001 cellular atypia cannot fill criteria for dysplasia•ASC-H need to more rapid evaluation of potential CIN II or CINIII•LSIL %2 and HSIL %0.5-%1•Present of AGC or AIS on cervical cytology is a significant marker for neoplasia of endometrium as well as cervix•A smear with AGC is assosiated with a premalignant or malignant lesion of endocervix or endomertrium in %10-%40 cases.•All women with AGC or AIS should be referred for colposcopy with directed cervical biopsy and sampling endocervical canal,and >35 years should have an endometrial biopsy.
Bethesda system 2001
Specimen type (conventional pap or liquid base) Specimen adequacy:-Satisfactory(notation presence or absence of endocervical/T.Z)-Unsatisfactory for evaluation-- Lable--Squamous cellularity--Obscuring factors(inflammation,blood)--Clinical information--poor preservation General categorization-Negative for intraepithelial lesion or malignancy-Epithelial cell abnormality Atypical squamous cell (ASC,LSIL,HSIL)
…BETHESDA
Glandular cells:Atypical-Endocervical cells(NOS)-Endometrial cells(NOS)Atypical-Endocervical cells favor of neoplasm-Glandular cells favor of neoplasmEndocervical adenocarcinoma insituAdenocarcinoma-Endocervical-Endometrial
.…BETHESDA
Organisms-Trichomonas vaginalis-Fungal organisms-Shift flora suggestive Bacterial vaginosis-Bacteria morphologically consistent with Actinomyces-Cellular change consistent with herpes simplex virus Other non neoplastic finding Reactive cellular changes associated with -Inflamation(include typical repair) -Radiation -I.U.D -Glandular cells status post hysterectomy -Atrophy Other-Endometrial cells in women 40 years of age(endometrial
pathology like polyp,hyperplasia or cancer)
CHOOSING CONVENTIONAL SMEARS VERSUS LIQUID-BASED CYTOLOGY
depends upon a variety of factors, including ability to perform concurrent testing, and cost.
These factors vary by health care setting, thus, no general recommendation can be made.
Liquid-based systems provide greater specimen adequacy, particularly for women with cervical bleeding or inflammation, which may obscure interpretation of a conventional Pap smear.
Liquid-based and conventional smears appear to perform equally well for detection of HSIL
Liquid-based methods perform better for detection of glandular abnormalities, ASCUS, and LSIL.
The ability to obtain reflex HPV testing, when needed, from a single liquid-based specimen is another advantage
Satisfactory smear
Minimum of 5000 well-visualized squamous cells on a liquid-based preparation
8000 squamous cells on a conventional smear
Notation regarding the presence or absence of endocervical or T.Z
Properly labeledPatient history
Unsatisfactory smears
Unsatisfactory cervical cytology tests should always be repeated in two to four months
If the cells are obscured by inflammation, an attempt should be made to clear the inflammatory process (eg, treat cervicitis or vaginitis) prior to repeating the cytology tests.
If the test is repeatedly unsatisfactory, then additional clinical evaluation with colposcopy and/or biopsies is appropriate because women with unsatisfactory cervical cytology tests are more likely to have intraepithelial lesions or cancer on follow-up than women with satisfactory tests
Endocervical cells not present
The presence of metaplastic and endocervical cells indicates adequate sampling of the transformation zone of the cervix, the area at greatest risk for neoplasia.
The follow-up of patients whose cervical cytology tests lack these cells is controversial.
Repeat 6-12 month later
Management of abnormal Pap smear
Negative Routine smearASC-US -Colposcopy -Repeat cytology at 6-12 months -Reflex HR HPVASC-H -Colposcopy LSIL -Colposcopy -in adolescents ASC-US,LSIL repeat cytology in 12-24
months if persistant or HSIL colposcopyHSIL -ColposcopyAGC-NOS-Colposcopy +_EMB and HPV HRAGC favor neoplasm-Colposcopy +_EMBCarcinomaBiopsy +Colposcopy if no gross lesion
Management of CIN
CIN I proven with biopsy %15 risk of CIN II/III in 2 years,so expectant management(cytology month 6 and 12 or HPV rest at 12 months) if negative annual screen and HR HPV positive or ASC or greater colposcopy
CIN II/III with few exception need treatment with ablatin or excisional techniques
Exception in adolscents (%60 regression CIN II at 1 year) so cytology at 6 month interval up to 2 years with satisfactory colposcopy
o AIS cold knife conization and ECC(%20 residua with negative margin),in adolsecents conservative follow up with Pap,colposc0py,ECC,every 6 months
Other screening modalities
Visual inspection with colposcopyHPV testing HPV testing, in combination with
Pap smear testing, in women over age 30 may have better sensitivity than in younger women.
Negative HPV DNA and cytology >30 years N.P.V >%99,so until 3 years need no evaluation
HUMAN PAPILLOMAVIRUS TEST
99.7% of cervical cancer are positive for HPVNecessary but insufficient precursor,Host factorsGenital warts: HPV 6 and HPV 11Presence of high risks
HPV(16,18,31,33,35,39,45,51,52,56,58,59,68,69,82) is assosiated with an increased risk of cervical cancer
Presence of HPV appears to be necessary for development of both squamous and adenocarcinoma
HPV 16 account for %60 and HPV 18 for an additional %10-%20 of cases.(%67 16 &18 invasive cancer)
HPV 16 is seen in %16 LSIL and %14 of normal smears.
HPV 18 is seen in %23 invasive cancer,%5 CINII,III,%5 CINI and%2 normal smears.
Dysplasia and HPV
HPV related genital disease ranges from genital wart(LR) to cytologic abnormalities and cevical,vulvar,anal and vaginal cancer(HR HPV)
Gardasil Vaccine
Decrease preinvasive and cervical cancerAgainst HPV 6, 11, 16, 183 Doses: 0, 2, 6 monthsAges: 9-26 y/oEfficacy >%85 in persistant infection and
%93 cytologic abnormality Reduced vulvar and vaginal intraepithelial
neoplasia and anogenital disease Bivalent HPV 16/18 virus like particle
vaccine (Cervarix)
COLPOSCOPY
Colposcopy is initial step in evaluation abnormal pap smear, diagnostic procedure in which a colposcope(disecting microscope with various magnification lenses)is used to provide a magnified view of cervix,vagina and vulva
Target biopsy of areas with Abnormal morphology
Adequate & conclusive evaluation require: complete visualization of T - zone
INDICATION OF COLPOSCOPY
Specefic abnormal cytology--persistant ASC-US or ASC-US with high risk
HPVASC-HAGCLSILHSILAssesment of women exposed to DESEvaluation of palpably or visually abnormal
cervix,vagina or vulvaPost coital bleeding
COLPOSCOPIC FINDING
Leukoplakia(CIN,Carcinoma,HPV,Radiation)Acetowhite epitheliumIodine negative or positive schiller testAtypical vascular patternPunctationMussaism
Summary Understand the current recommendations for PAP smear
screening and follow-up Start within 3 years of onset of sexual activity or
age 21 Screening at least every 3 years after 30 years with
3 normal smear Stop at age 70 due to recommendation of American
cancer society Stop after hysterectomy for benign disease Continue screening after hysterctomy for malignant
lesion
Recognize the role of HPV in cervical cancer(%99) and determine patients who are candidates for Vaccination Approved for age 9-26
Benign conditions
Benign conditions
InfectionsEndocervical polypsNobothian cystColumnar epithelium eversion or
ectropionCervical leiomyoma( fibroma )Cervical endometriosis
Cervical polyp
Endocervical pedunculated
lesion , friable,several mm to several cm
Etiology : chronic papillary endocervicitis
D.Dx : - cervical cancer - retained tissue - prolapsing leiomyoma - endomtrial polypSymptoms : AUB ,
leukorrhea ,contact bleeding Treatment : is grasped &
twisted , send for pathology
POLYP
اکتروپیون مختلف مراحل در سرویکس حجم
و بلوغ زمان در خصوص به زندگیترشح افزایش که بارداری اولین
یابد می دارد،افزایش وجود استروژنتلیوم اپی اورزیون به منجر که
موقعیت به اندوسرویکال ای استوانه . شود می اکتوسرویکس
و اندوسرویکس مخاط اورزیونبه ای استوانه تلیوم اپی شدن نمایان
. نامند می اکتروپیون را واژن می بالینی عالئم بندرت اکتروپیون
کشف. بالینی معاینه در ومعموال دهدیا لکوره به منجر شود،گاهی می. شود می تماس از بعد خونریزی
اکتروپیون...
گرانولیشن قرمزمشابه نمای یافته اورزیون تلیوم اپی. شود پوشیده زرد ترشح با است ممکن و دارد
سنین در این adolesenseاکتروپیون از است،بعد شایعکه های خانم در می ocpسنین دیده کنند، می مصرف
شود. به منجر که مواردی در مگر ندارد درمان به نیاز اکتروپیون
از بعد خونریزی ویا بینی لکه موکوئیدی، شدید ترشحات. شود تماس
: که کرایو،کوتریزاسیون این invasiveدرمان در هستندشود رد بدخیمی شده بررسی باید بیمار موارد
: مثل اسیدی ترکیبات با ای هفته دو درمان درمان آلترناتیواسید بوریک های شبانه 600شیاف میلیگرم
سرویسیت حاد سرویسیت
است،در - واژن چرکی ترشح عالمت تنها اغلب و ترین شایعملتهب،ادماتو،شکننده مختلف درجات با سرویکس مشاهده
. است موکوپروالنت ترشحات ودارایگنوره،کالمیدیا - پارتنر - و بیمار درمان
مزمن سرویسیتهای - نمونه بیوپسی در هیستولوژیک غلط اصطالح یک
است نابالغ متاپالزی علت به سرویکس بیوپسی ) وجود) واقع در تلیال اپی ساب التهابی انفیلتراسیون
نمی عفونت علت به بیوپسی نمونه در ها لکوسیت. است متاپالزی طبیعی پروسه از قسمتی باشد،بلکه
Nobothian cyst
occlution of endocervical glands opening & mucinous retention , physiologic finding due to squamus metaplasia .
a finding in P/E , rarely causes symptom
CERVICAL CANCER
EPIDEMIOLOGY
Cervical cancer ranks as the third most common gynecologic neoplasm in the United States, behind cancer of the corpus and ovary.
Cervical cancer is a disease of sexually active women and infection with high risk HPV is central to the pathogenesis of cervical cancer
Cervical cancer has typically a long preinvasive state and the treatment is effective
500,000 new cases identified each year 80% of the new cases occur in developing countries At least 200,000 women die of cervical cancer each year %50 0f women diagnosed with cervical cancer had never
been screened,%10 no smear in last 5 years %70 reduction in deaths from cervical cancer because
of cytology
68
Epidemiology
The lifetime probability of cervical cancer is 1: 128(%0.4 in israel-%5.3 in colombia)
The mean age for cervical cancer in the United States is 52y
Distribution of cases is bimodal,with peaks at 35 to 39 years and 60 to 64 years of age.
%25 of cervical cancers and %41 of deaths occur in women over 65 years old
Risk factors
Young age at first intercourse «16 years(twice than >20 y) Multiple sexual partners of lifetime High parity Cigarette smoking in SCC (two Fold ) Race(twice in black,Hispanic and higher in native American) Lower socioeconomic status Long term O.C.P>5y ?( glandular abnormalities) two fold Barrier methods especially chemical decrease risk HPV : causal factor detected in 99% by inactivation of tumor suppressor genes ( P53 & Rb ) by
viral proteins E6 & E7 Herpes virus and Chlamydia likely acting as cofactors. The role of HIV in cervical cancer is thought to be mediated
through immune suppression.(cell mediated)
Clinical presentation
Symptoms- Most common : vaginal bleeding or
discharge most often PCB ,postmenopausal,irregular
bleeding- Advanced :Malodor vaginal
discharge ,weight loss, obstructive uropathy,Hematochezia,Hematuria,fistula,Lumbosacral Pain due to L.S nerve involvement
- Asymptomatic.
Cervical cancer
P/E :- Early stage :normal P/E , diagnosis by
colposcopy directed biopsy or conization- Cervical inspection : large cervix ulcerative
(errosive ) , tumoral exophytic , endophytic- Digital vaginal or rectovaginal exam : firm and
enlarged cervix in endophytic tumors- parametrial involvment:nodularity in T.R- Lymph node(axillary,inguinal,supraclavicular)
in advanced
Cervical cancer
Pathology
SCC : most common variety - large cell with or without keratinization,better
prognosis - Small cell , poorly differentiated - small cell anaplastic carcinoma , most aggressive -Verrucous and transitional(papillarey)rare metastasis Adenocarcinoma : increasing incidence(%10-%15) Prognose:poorer than squamous? - endocervical(mucin): 80 % - endometriod -clear cell ,intestinal type,mixture of above
types,minimal change adenocarcinoma(malignant adenoma)
- villoglandular papillary type(young ,pregnant,good prognose)
Cervical cancer pathology...
Adenosquamus
Poor prognose -Mature adenosquamous
-Glassy cell carcinoma - adenoid cystic and basal carcinoma Sarcoma - embryonal rhabdomyosarcomaMalignant melanoma : rare,prognose
related to deep invasion
Cervical cancer pathology
Metastatic cancer : - genital malignancies : endometrium , ovary , vagina ?? ( vag + cervix : cervical primary )
- adjacent organs : colon , bladder - systemic malignancies spread : lymphoma,leukemia,breast,kidney,
stomach
Rareovarian involvement occurs through the
lymphatic connections between the uterus and adnexal structures
In patients undergoing surgical treatment for early-stage disease, ovarian metastasis in <1% of SCC and slightly >1% of adenocarcinoma
Ovarian Metastasis
Patterns of spread Direct invasion into the cervical stroma,
corpus,vagina, and parametriumLymphatic metastasisBlood-born metastasis(uncommon) Intraperitoneal implantation. Pelvic lymph node the first site %20 of patients with tumor extending to pelvic wall biopsy
proven bladder invasion The upper vagina is frequently involved (50% of cases)
when the primary tumor has extended beyond the confines cervix.
Endometrium involvement in %2-%10 surgeries Ovarian involvement in %0.5-%1.7
Cervical cancer staging
FIGO staging allowed procedures :- P/E(T.R,Vaginal exam under anesthesia and
lymph node)- Radiologic studies : IVP, Barium enema ,Chest x ray, skeletal x-ray- Procedures : colposcopy, biopsy,conization,ECC,cystoscopy,
proctoscopy - Optional ( not change staging ) : CT ,MRI ,sonography, lymphangiography,
laparoscopy/laparotomy,radionucleotide
Staging
FIGO System : five stages Stage 0: Carcinoma in situStage 1 :Limited to cervixStage 2: spread out of cervixStage 3:Pelvic wall, spread to the lower part of the vagina.
Stage 4: spread to nearby organs; metastasis.
Cervical cancer staging
Stage 0 : Carcinoma in situStage I : tumor confined to cervixStage Ia : diagnosis only by microscopy ,
tumor depth< 5 mm , width< 7 microinvasive ca
- Ia1 : = 3mm depth of invasion - Ia2 : >3 - 5 mm depth, < 7mm widthStage Ib : depth > 5mm & or width >
7mm - Ib1 : lesion less or equal 4 cm - Ib2 : lesion more than 4 cm
Cervical cancer staging
Stage II : extend beyond cervix but no to pelvic wall,no involvment 1/3 lower vagina
- IIa : No obvious parametrial involve - IIb : Obvious parametrial involvementStage III : extension to pelvic wall or
hydronephros,1/3 lower vagina - IIIa :No extension to pelvic wall - IIIb : hydronephrosis or nonfunction
kidney
Cervical cancer staging
Stage IV : carcinoma extend beyond true pelvis or
to bladder or rectal mucosa - IV a : spread to adjacent organs - IV b : spread to distant organs
Clinical staging of cervical cancer
Cervical cancer staging
Staging- At diagnosis : stage I : 38 % stage II : 32 % stage III : 26 % stage IV : 4 %
Five-year survival
stage IA :97%stage IB : 70% - 85%stage II :60% to 70% stage III :30% to 45% stage IV :12% -18%
Independent prognostic variables
Tumor Histology
No difference in overall survival between SCC and adenocarcinoma.•adenosquamous histology was associated with decreased survival
Independent prognostic variables
Histologic grade :• 5-year survival in well-diff tumors :74.5%•moderately differentiated tumors :63.7%•poorly differentiated carcinomas:%51.4Lymph node status : For all stages of disease, when both pelvic and paraaortic lymph nodes are negative, the 5-year survival is 75.2% and 45.6% with positive pelvic nodes
Treatment
Primary treatment 1 - surgery : limited to stage I & IIa 2- radiation : applicable to all stages The 5-year survival rate for stage I cancer of the
cervix is approximately 85% with either radiation therapy or radical hysterectomy.
Adjuvant treatment after primary modality to decrease recurrence
risk IIB-IVA Radiation curative,preferably in
combination chemotherapy
..…TreatmentSurgery
Preinvasive cervical cancer Cryosurgery Laser surgery Conization
Invasive cervical cancer Simple hysterectomy Radical hysterectomy and pelvic lymph node dissection
Removal of entire uterus, surrounding tissue, upper part of the vagina, and lymph nodes
RadiationChemotherapy:extrapelvic metastasis,recurrence
Source: American Cancer Society
Surgery Stage 0 : conization versus HysterectomyStage IA1 : negligable possibility of lymph
node involvement , extrafascial hysterectomy,conization
Stage IA2 : Type II radical hysterectomy & pelvic lymph node dissection
Stage IB,IIA : Type III radical hysterectomy & pelvic lymph node dissection
Stage IIB-IVA:Radiotherapy+chemotherapyStage IVB:Systemic
chemotherapy+paliative radiation
Cone biopsy
Cervix Cone biopsy of the cervix serves both a diagnostic and therapeutic role in cervical cancer( stageIA1)
Because stage IA1 cancers have less than a 1% risk of lymph node metastasis, lymphadenectomy is not necessary
For effective treatment, there must be no evidence of lymph-vascular space invasion, and both endocervical margins and curettage findings must be negative for cancer or dysplasia.
IA2 class II Hysterectomy with PLNDRadical trachelectomy is a procedure for
women with stage la2 and Ibl disease who desire uterine preservation and fertility.
This procedure may be performed vaginally or abdominally and it usually is accompanied by pelvic lymphadenectomy and cervical cerclage placement.
The risk of positive pelvic lymph nodes with stage IA2 cancer may be as high as 8%, indicating the need for lymphadenectomy.
There are limited data on subsequent pregnancy outcomes after radical trachelectomy; however, successful outcomes have been reported.
Radiotherapy Can be used in all stages Cure rate :
stage I :70% stage II : 60%o stage III : 45% stage IV : 18% Standard plan:Combination of external
(teletherapy ) +internal(brachytherapy)as a boost for central tumor
Ovarian failure in all, %70 vaginal fibrosis,%8 proctosigmoiditis,%3 hemorrhagic cystitis,small bowel obstruction in %2, fistula in %1
Radical Hysterectomy
Radical hysterectomy is reserved for women in good physical condition.
With improvements in anesthesia, elderly patients withstand radical surgery almost as well as their younger counterparts
not to operate larger than 4 cm in diameter because these patients will require postoperative radiation therapy.
When selected in this manner, the urinary fistula rate is less than 2% and the operative mortality rate is less than 1%
Metastasis to the ovaries occurs in 0.5% of S.C.C and 1.7% of cases of adenocarcinomas, so ovarian preservation and transposing the ovaries out of the planned radiation field may be considered.
some studies suggest that normal ovarian function is preserved in fewer than 50% of patients.
Surgery and radiation
There are advantages to the use of surgery instead of radiotherapy, particularly in younger women for whom conservation of the ovaries is important.
Chronic bladder and bowel problems occur in up to 8% of patients undergoing radiation therapy .
Such problems are difficult to treat because they result from fibrosis and decreased vascularity.This is in contrast to surgical injuries,which in general are easily repaired and without long-term complications.
Sexual dysfunction is less likely to occur after surgical therapy than radiation because of vaginal shortening,fibrosis, and atrophy of the epithelium associated with radiation.
The epithelium does not become atrophic because it responds either to endogenous estrogen or to exogenous estrogens if the patient is postmenopausal.
Follow up
Patients who receive radiotherapy should be closely monitored
Tumors may be expected to regress for up to 3 months after radiation.
During the pelvic examination, progressive shrinkage of the cervix and possible stenosis of the cervical os and surrounding upper vagina is expected and should be noted.
During rectovaginal examination, careful palpation of the uterosacral and cardinal ligaments for nodularity
Cytologic assessment by FNA and CT of palpable pelvic mass Pelvic examination and lymph node evaluation, including
supraclavicular and inguinal nodes and smear,should be performed every 3 months for 2 years and then every 6 months for an additional 3 years
Endocervical curettage may be performed in patients with large central tumors.
Chest x Ray yearly in advanced(metastasis to the lung in 1.5% of cases)
I.V.P if pelvic mass or urinary symptom Patients who have had radical hysterectomy and who
are at high risk for recurrence routine CT urogram 6 to 12 months after surgery may be beneficial.
%50 in 1 year and %80 recurrence in 2 years after radical hysterectomy
Large mass lower time for recurrence
Host factors in outcome
Anemia(Hb 12 or less) is associated with a higher incidence of pelvic recurrences and decreased survival, primarily due to more frequent radiation therapy failures.(Tumor hypoxia)
Thrombocytosis (>400,000/mm3), which has been associated with decreased survival after controlling for cell type, stage, and age.
Whether or not patient age at diagnosis of cervical cancer is a significant and independent predictor of clinical outcome remains controversial
Medical problems(Diabete ,Hypertension) due to decreased blood supply and hypoxia
Persistant& Recurrent
•Persistant:detection within the first 6 months after therapy• recurrent disease:later diagnose• Appropriate treatment of recurrent cervical cancer is dictated by both the site of recurrence and the modality of primary therapy.• In general, patients in whom locally recurrent disease develops following primary surgery should be considered for salvage radiation therapy. Conversely, surgical treatment should be considered for those patients with recurrent central disease who initially received irradiation.• Distantly metastatic recurrent tumor is an indication for palliative chemotherapy and possibly radiation therapy for local control.
Adjuvant Therapy following Surgery
For patients with risk factors(large tumor,deep stromal invasion,tumor in capillary lymphatic space) and negative pelvic lymph nodes, adjuvant pelvic radiation associated with a statistically significant 47% reduction in the risk of disease recurrence.
Even after extensive follow-up, the addition of radiation therapy was not associated with a statistically significant improvement in overall survival.
Cervical cancer inpregnancy
Cervical cancer is one of the most common malignancies in pregnancy
Incidence ranging from 1/1,200 to 1/2,200 pregnancies.
1 /34 women diagnosed with cervical cancer is pregnant at the time of diagnosis.
The most common complaint:abnormal bleeding Delay in diagnosis.
Diagnose : In the presence of a grossly visible lesion with by biopsy.
Cervical cancer in pregnancy.....
Conization is indicated only for those patients with apparent microinvasive disease on directed biopsy or for patients with persistent cytologic evidence of invasive cancer in the absence of a colposcopically visible lesion.
The optimal time to perform conization is between 14 -20 weeks or after the time of fetal viability has been reached.
Cervical cancer in pregnancy....
Staging like nonpregnant Treatment recommendations are
individualized and are dependent on the stage of disease, gestational age at the time of diagnosis, and the desires of the patient regarding continuation of the pregnancy.
Patients with well-documented stage IA1 disease (conization with negative surgical margins) may be managed with vaginal delivery and reevaluation postpartum. If the patient has completed childbearing, a simple extrafascial hysterectomy would be appropriate
.…cervical cancer in pregnancy
For patients with stage IA2 modified radical cesarean hysterectomy with pelvic lymph node dissection is the preferred treatment.
Patients with stage IB or IIA disease may be treated with surgery in the form of radical hysterectomy and pelvic lymph node dissection, either in conjunction with cesarean section or with the fetus in situ, depending on the gestational age.
Radiation therapy is the treatment of choice for patients with stage IIB to IVA
Spantaneous abortion 4-5 after start radiationDelay treatment 6-12 weeks for stage I
HYPERPLASIA
Endometrial Hyperplasia
Classic teaching has been that endometrial hyperplasias represent a continuum of morphologic severity; the most severe form, termed atypical adenomatous hyperplasia or carcinoma in situ, was considered the immediate precursor of endometrial carcinoma .
Endometrial hyperplasia and endometrial neoplasia are two biologically different diseases.
The only important distinguishing feature is the presence or absence of cytologic atypia.
Ferenczy et al. (92) suggested that the term endometrial hyperplasia be used for any degree of glandular proliferation devoid of cytologic atypia and the term endometrial intraepithelial neoplasia for lesions with cytologic atypia. Using similar criteria in a long-term follow-up study of 170 patients with endometrial hyperplasia, Kurman et al. (91) reported a 1.6% risk of progression to carcinoma in patients devoid of cytologic atypia, compared with a 23% risk in patients with cytologic atypia.
HyperplasiaSimpleComplex (adenomatous)Atypical hyperplasiaSimpleComplex (atypical adenomatous)
Endometrial Hyperplasia
Endometrial hyperplasia represents a spectrum of morphologic and biologic alterations of the endometrial glands and stroma, ranging from an exaggerated physiologic state to carcinoma in situ.
Clinically significant hyperplasias usually evolve within a background of proliferative endometrium as a result of protracted estrogen stimulation in the absence of progestin influence.
Endometrial hyperplasias are important clinically because they may cause abnormal bleeding, be associated with estrogen-producing ovarian tumors, result from hormonal therapy, and precede or occur simultaneously with endometrial cancer.
Simple or Complex Differential point is complexity and crowding of the glandular
elements. Simple hyperplasia is characterized by dilated or cystic
glands with round to slightly irregular shapes, an increased glandular to-stromal ratio without glandular crowding, and no cytologic atypia.
Complex hyperplasia has architecturally complex (budding and infolding), crowded glands with less intervening stroma without atypia.
Atypical hyperplasia refers to cytologic atypia and can be categorized as simple or complex, depending on the corresponding glandular architecture.
Criteria for cytologic atypia include large nuclei of variable size and shape that have lost polarity, increased nuclear-to-cytoplasmic ratios, prominent nucleoli, and irregularly clumped chromatin with parachromatin clearing
The risk of endometrial hyperplasia progressing to carcinoma is related to the presence and severity of cytologic atypia.
Kurman and colleaguesretrospectively studied endometrial curettings from 170 patients with untreated endometrial hyperplasia followed a mean of 13.4 years. They found that progression to carcinoma occurred in 1% of patients with simple hyperplasia, 3% of patients with complex hyperplasia, 8% of patients with atypical simple hyperplasia, and 29% of patients with atypical complex hyperplasia. Most of the hyperplasia seemedto remain stable(18%) or regress(74%).
The premalignant potential of hyperplasia is influenced by age, underlying ovarian disease, endocrinopathy, obesity, and exogenous hormone exposure
As many as 25% to 43% of patients with atypical hyperplasia detected in an endometrial biopsy or curettage specimen will have an associated, usually well-differentiated endometrial carcinoma detected during hysterectomy.
Marked cytologic atypia, a high mitotic rate, and marked cellular stratification are features of atypical endometrial hyperplasia most often associated with the finding of an undiagnosed carcinoma at hysterectomy.
In a report of 85 menopausal women with endometrial hyperplasia treated with medroxyprogesterone acetate (10-20 mglday), 84% of 65 who did not have cytologic atypia had complete reversal of the lesions, 6% developed recurrent hyperplasia, but none developed cancer at a mean follow-up interval of 7 years (17).
By contrast, of 20 patients with cytologic atypia, only 50% responded to progestin, 25% developed recurrent hyperplasia, and 25% developed adenocarcinoma.
In another study, hyperplasia resolved in 94% of 32 patients with atypical endometrial hyperplasia who were treated with megestrol acetate (20-40 mglday); however, relapse occurred in all 7 patients who discontinued progestin therapy.
Conversely,high-dose progestin therapy (medroxyprogesterolleacetate,200 mglday, or megestrol acetate, 160 mglday) has been reported to have successfully reversed atypical hyperplasia and well-differentiated endometrial adenocarcinoma in 16 (94%) of 17 and 9 (75%) of 12 premenopausal women younger than age 40, respectively.
The average treatment course required to achieve disease regression was 9 months (range 3-18 months)
Subsequent pregnancies after progestin treatment of endometrial hyperplasia and even well-differentiated cancer have occurred and can apparently be enhanced by the use of assisted reproductive technologies.
Progestin therapy is very effective in reversing endometrial hyperplasia without atypia but is less effective for endometrial hyperplasia with atypia.
For women with endometrial hyperplasia without atypia, ovulation induction, cyclical progestin therapy(e.g., medroxyprogesterone acetate, 10-20 mg/day for 14 days per month), or continuous progestin therapy (e.g., megestrol acetate, 20-40 mg/day) appear to be effective.
Continuous progestin therapy with megestrol acetate (40-160 mg/day) is probably the most reliable treatment for reversing complex or atypical hyperplasia.
Therapy should be continued for 2 to 3 months, and endometrial biopsy should be performed 3 to 4 weeks after completion of therapy to assessresponse.
Periodic endometrial biopsy or transvaginal ultrasonography is advisable in patients being monitored after progestin therapy for atypical hyperplasia because of the presence of undiagnosed cancer in 25% of cases, the 29% progression rate to cancer, and the high recurrence rate after treatment with progestins.
For women with atypical complex hyperplasia who no longer desire fertility, hysterectomy is recommended.
Treatment
Most women with endometrial hyperplasia respond to progestin therapy. Patients who do not respond are at a significantly increased risk of progressing to invasive cancer and should be advised to have a hysterectomy. Patients who are unlikely to respond can be identified on the basis of cytologic atypia.
Ferenczy and Gelgand reported on 85 women with endometrial hyperplasia treated with medroxyprogesterone (93). The 65 patients who had no cytologic atypia received 10 mg daily for 14 days per month, whereas the 20 patients with cytologic atypia received 20 mg daily. Both groups had endometrial sampling every 3 months. In the group without cytologic atypia, 14% had persistence of their hyperplasia, but none progressed to carcinoma. Of the 20 patients with cytologic atypia, 50% had persistence of their hyperplasia, and 25% developed frank carcinoma at a mean of 5.5 years after initiation of hormonal therapy.
The type of progestin used does not appear to be important, the optimal dosage has not been investigated, and the regimens advocated are essentially arbitrary (96). High doses of progestins are often better tolerated than low doses. The main side effects are weight gain, edema, thrombophlebitis, and occasionally hypertension. The incidence of venous thrombosis and embolism may also be slightly increased.
Other approaches to hormonal therapy include levonorgestrel-releasing intrauterine devices (97), the use of danazol in a dose of 400 mg daily for 3 months (98), and the combined use of gonadotropin-releasing hormone (GnRH) analogues and progestins (99).
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