neoplasia of the cervix - medicinebau.com · lkb1 mutation +pigmented lesions on lips + polyps in...
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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 ))
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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
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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
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khozamaHighlightthe most import. one
khozamaSticky Notehigh risk to HPV( increase the likelihood of infection with HPV)
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khozamaHighlight HPV cervical neoplasia hpv infection
khozamaSticky Note cervical neoplasia multiple risk factors hpv infection malignancy ( CIN ......)
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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
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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 )
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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
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khozamaHighlightare cyclin dependent kinase inhibitor when the E7 inhibit it cyclin dependent kinase cause cell to enter to cell cycle (proliferation +mitosis )
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Cervical neoplasia, pathogenesiscontd
More recently, somatically acquired mutations in the tumor suppressor gene LKB1 were identified in more than 20% of cervical cancers
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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
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Cervical neoplasia, pathogenesiscontd
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Most HPV infections are transient and are eliminated
khozamaSticky Note HPV
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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
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khozamaSticky NoteCIN happened early so the screening happened early in female specially with sexual behavior
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khozamaSticky Note HPV enviromental+genetic factors
khozamaHighlightCIN3 CIN1
CIN, contd
very importamt
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khozamaSticky Notenot all CIN transform to cancer
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khozamaHighlighthigh grade more persistant
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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?
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khozamaHighlightrelatively
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khozamaHighlightbut its less effective than pap smear
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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)
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khozamaHighlight PAP SMEAR LSIL pap smear
khozamaHighlight cone biopsy biopsy :
khozamaSticky Note smear LSILHSIL
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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)
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khozamaHighlight3 types
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khozamaHighlightlike small cell carcinoma in lung
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khozamaHighlightm.c : squamous cell carcinoma
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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
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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
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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 : **
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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
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khozamaHighlightin pubes region
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khozamaHighlightwell differentiation : low grade
khozamaHighlightvery important and we must write it in pathology report
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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
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khozamaHighlightpus (WBCs in vaginal secretion)
khozamaHighlightpainful intercourse
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khozamaHighlightbleeding after intercourse
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khozamaHighlightgrade has role but less than stage
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khozamaHighlightthan squamous +adeno
khozamaHighlightin cervical cancer by invasion more by in mets invasive to bladder then urinary obstruction then renal failure