Neoplasia of the cervix

Done by khozama jehad

An overview of cervical neoplasia

Most tumors of the cervix are of epithelial origin and are caused by oncogenic strains of human papillomavirus (HPV)

HPV, the causative agent of cervical neoplasia, has a tropism for the immature squamous cells of the transformation zone

Most HPV infections are transient and are eliminated within months by an acute and chronic inflammatory response

A subset of infections persists, however, and some of these progress to cervical intraepithelial neoplasia (CIN)

veryimport.

khozamaHighlightHPV infection take place in the junction btw endoderm + ectoderm transformation zone

khozamaHighlightzone in endo with time transform to squamous(( from immature squamous to mature one ))

khozamaHighlight

khozamaHighlightimmunologically by inflammation

khozamaSticky Notemost HPV infection transient ((immunologically by inflammation )) The remaining ones :type 6 ,11 : cause infection (condyloma acuminatum )type 16 ,18 : transform to CIN1, CIN2, CIN3

khozamaHighlight

khozamaHighlight

khozamaHighlightwhich persists

Cervical neoplasia, pathogenesis

HPV is detectable by molecular methods in nearly all cases of CIN and cervical carcinoma

Risk factors for CIN & invasive squamous cell carcinoma:

1- Related to HPV exposure:

2- Cigarette smoking

3- Human immunodeficiency virus

especially in progression from CIN to cancer

khozamaHighlightare HPV positive if we apply DNA HPV assay we detect HPV CIN + cervical carcinoma associated with HPV vaginal +valvur

khozamaHighlight

khozamaHighlightthe most import. one

khozamaSticky Notehigh risk to HPV( increase the likelihood of infection with HPV)

khozamaHighlight

khozamaHighlight HPV cervical neoplasia hpv infection

khozamaSticky Note cervical neoplasia multiple risk factors hpv infection malignancy ( CIN ......)

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaSticky NoteHPV alone not enough to progression from CIN to cancer

Cervical neoplasia, pathogenesiscontd

HPV infection occurs in the most immature squamous cells of the basal layer

Replication of HPV DNA takes place in more differentiated overlying squamous cells

squamous cells at this stage of maturation do not normally

replicate DNA, but HPV-infected squamous cells do, as a

consequence of expression of two potent HPV oncoproteins: E6 & E7

khozamaHighlight HPV BASAL LAYER

khozamaHighlight

khozamaSticky Noteinfection take place in basal layer where as the replication of HPV DNA happened by the replication of overlying squamous cells (that normally not replicate but the HPV DNA make oncoproteines -E6+E7-make the overlying squamous cells replicate )

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

E6 & E7

khozamaHighlight p53 (tumor suppressor gene )so the cells will proliferation

khozamaHighlightrelease E2F from RB (which is tumor suppressor gene inhibit the E2F from enter the cell and cause cells proliferation ) when E2F release it will enter to nucleus and cause cells proliferation

khozamaHighlight

khozamaHighlight

khozamaHighlightare cyclin dependent kinase inhibitor when the E7 inhibit it cyclin dependent kinase cause cell to enter to cell cycle (proliferation +mitosis )

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

Cervical neoplasia, pathogenesiscontd

More recently, somatically acquired mutations in the tumor suppressor gene LKB1 were identified in more than 20% of cervical cancers

khozamaHighlight

khozamaHighlight

khozamaSticky Note LKB1 mutation +pigmented lesions on lips + polyps in gi ( hamartomatous polyps ) = Peutz-Jegher Syndromethese syndrom has many tumors _epithelial neoplasm _ one of them : cervical cancer in female

khozamaHighlight

Cervical neoplasia, pathogenesiscontd

khozamaHighlight

Most HPV infections are transient and are eliminated

khozamaSticky Note HPV

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight 1

khozamaHighlight

khozamaSticky Noteviral integration : virus DNA integrate to host cells DNA like the latent infection occur with high risk HPV (16,18) cause prolong presiste of virus in the body then cause malignant cancer

low risk( 6,11) : episomal infeation the virus DNA presiste outside the cells cause condyloma and not continue to cancer

CIN (Cervical intraepithelial neoplasia)

Usually precedes the development of an overt cancer by many years, sometimes decades

CIN peaks in incidence at about 30 years of age, whereas invasive carcinoma peaks at about 45 years of age

In many cases, even high-grade lesions fail to progress to cancer and may even regressthe regression rate is much higher in low-grade lesions

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaSticky NoteCIN happened early so the screening happened early in female specially with sexual behavior

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaSticky Note HPV enviromental+genetic factors

khozamaHighlightCIN3 CIN1

CIN, contd

very importamt

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaSticky Notenot all CIN transform to cancer

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlighthigh grade more persistant

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

Pap smear

The most successful cancer screening test ever developed

Cervical cancer no longer ranks among the top 10 causes of cancer deaths in U.S. women

paradoxically, the incidence of CIN has increased to its present level of more than 50,000 cases annually. Increased detection has certainly contributed to this The recently introduced quadrivalent HPV vaccine for types 6, 11, 16, and

18 is very effective in preventing HPV infectionsbut Pap smear is still needed, Why?

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlightrelatively

khozamaHighlight

khozamaHighlightbut its less effective than pap smear

khozamaHighlight

khozamaSticky Note1)Some people were infected with the virus and the vaccine was taken after the infection2)there are oncogenic strains other than 6,11,16,18 like :33

CIN, some management notes

CIN is asymptomatic and comes to clinical attention through an abnormal Pap smear result

Followed up by colposcopy, during which acetic acid is used to highlight the location of lesions and the areas to be biopsied

LSIL: follow up (conservative management)

HSIL: surgery (e.g., cone biopsy)

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight PAP SMEAR LSIL pap smear

khozamaHighlight cone biopsy biopsy :

khozamaSticky Note smear LSILHSIL

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight vagina follow up biopsy lesion cervix

khozamaHighlighthighlight the lesions

Invasive carcinoma of the cervix

Squamous cell carcinomas (75%)

followed by:

Adenocarcinomas and mixed adenosquamous carcinomas (20%)

and

small cell neuroendocrine carcinomas (less than 5%)

All types are caused by HPV

The relative proportion of adenocarcinomas has been increasing in recent decades

1)

2)

3)

khozamaHighlight

khozamaHighlight

khozamaHighlight3 types

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlightlike small cell carcinoma in lung

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlightm.c : squamous cell carcinoma

khozamaHighlight

khozamaHighlight

khozamaHighlightin contrast with squamous cell carcinoma why ??cuz we prevent squamous cell carcinoma by pap smear which is more effective in it than in adenocarcinoma

khozamaHighlight

Cervical squamous cell carcinoma

Peak incidence at the age of about 45 years

Progression of CIN to invasive carcinoma is variable and unpredictable and requires HPV infection as well as mutations in genes such as LKB

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

Cervical squamous cell carcinoma, morphology

Range from microscopic foci of stromal invasion to grossly conspicuous exophytic tumors

Barrel cervixwhen the tumor encircles the cervix and penetrates into the underlying stroma

easily palpated The grading is based on squamous differentiation The likelihood of spread to pelvic lymph nodes correlates with the depth of

tumor invasion (less or more than 3mm) and the presence of tumor cells in vascular spaces

1)

2

3

base on : **

**

khozamaHighlight

khozamaSticky Note1)tumor dyplasia CIN3... + foci of stromal invasion by squamous epithelial malignant 2)exophytic growth on cervix (large tumor3) Barrel cervix ... when the tumor encircles the cervix and penetrates into the undering stroma

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlightin pubes region

khozamaHighlight

khozamaHighlight

khozamaHighlightwell differentiation : low grade

khozamaHighlightvery important and we must write it in pathology report

khozamaHighlight

khozamaHighlight

khozamaSticky Notemore than 3mm : more mets

khozamaHighlightincrease the risk of metastases

Cervical squamous cell carcinoma, clinically:

Symptoms especially appear in those who were not previously screened

Vaginal bleedinge.g., postcoital bleeding

Leukorrhea

Painful coitus (dyspareunia)

Dysuria

Mortality is most strongly related to tumor stage

Neuroendocrine carcinoma is bad

Death in advanced disease is mainly due to direct invasion rather than metastasis, especially the invasion into bladder & ureter with resultant obstruction & renal failure

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlight

khozamaHighlightpus (WBCs in vaginal secretion)

khozamaHighlightpainful intercourse

khozamaHighlight

khozamaHighlight

khozamaHighlightbleeding after intercourse

khozamaHighlight

khozamaHighlight

khozamaHighlightgrade has role but less than stage

khozamaHighlight

khozamaHighlightthan squamous +adeno

khozamaHighlightin cervical cancer by invasion more by in mets invasive to bladder then urinary obstruction then renal failure