Pathology of Pathology of Cervical Cervical

CarcinomaCarcinoma

Cancer of Cervix

Shashi. 04/20/23

Introduction:Introduction:

Best example of cancer prevention.Best example of cancer prevention. US Statistics:US Statistics:

Leading cause - PAP – 8Leading cause - PAP – 8thth Cause. >60% Cause. >60% Over 1M PAP positive & 13,000 invasive/yOver 1M PAP positive & 13,000 invasive/y

Potentially curable if detected earlyPotentially curable if detected early Long pre-cancer state.Long pre-cancer state. Shed abnormal cells – cytological test - Shed abnormal cells – cytological test -

PAPPAP Easy access to biopsy and treatment.Easy access to biopsy and treatment.

Cancer of Cervix

Shashi. 04/20/23

Pathogenesis:Pathogenesis: Early age at sex, Multiple partners.Early age at sex, Multiple partners. Oral contraceptives, smoking, F hist etc.Oral contraceptives, smoking, F hist etc. HPV infection – central to cancer (>85%)HPV infection – central to cancer (>85%)

High risk types – 16, 18, 31, 33 (Bound-DNA)High risk types – 16, 18, 31, 33 (Bound-DNA) Low risk types – 6, 11, 42-44 (Free DNA)Low risk types – 6, 11, 42-44 (Free DNA) Oncogene E6 (p53) & E7 (Rb)Oncogene E6 (p53) & E7 (Rb)

Other viral/mutations can cause rarely.Other viral/mutations can cause rarely.

Cancer of Cervix

Shashi. 04/20/23

Cervical Transformation ZoneCervical Transformation Zone

Pathogenesis:Pathogenesis:Sexual ExposureSexual Exposure

HPV InfectionHPV Infection

Squamous EpSquamous Ep Columnar EpColumnar Ep

Squamous CaSquamous Ca Adeno CaAdeno Ca

High Risk Types (16,18)High Risk Types (16,18)

Low Risk-6,11Low Risk-6,11Smoking, Hormone, Oral contr. parity,

Altered immune response etc.

Cancer of Cervix

Shashi. 04/20/23

Cervical Intraepithelial Neoplasia Cervical Intraepithelial Neoplasia (CIN)(CIN)

Dysplasia within Ep. – (no infiltration)Dysplasia within Ep. – (no infiltration) Squamo-Columnar junction – common siteSquamo-Columnar junction – common site Dysplasia + Koilocytes - Plenty of HPV DNADysplasia + Koilocytes - Plenty of HPV DNA May Progress or Regress - Risk of cancer.May Progress or Regress - Risk of cancer. Classification:Classification: Mild – Moderate – Severe dyspalasia0 (CIS)Mild – Moderate – Severe dyspalasia0 (CIS) CIN-I, CIN-II & CIN-III (CIS)CIN-I, CIN-II & CIN-III (CIS)

Cancer of Cervix

Shashi. 04/20/23

Normal Cervix:Normal Cervix:

Cancer of Cervix

Shashi. 04/20/23

Condyloma Cx.Condyloma Cx.

Cancer of Cervix

Shashi. 04/20/23

Normal Cervix :Normal Cervix :

SUPER F INTERM BASAL

Cancer of Cervix

Shashi. 04/20/23

Cervical Dysplasia:Cervical Dysplasia:

Cancer of Cervix

Shashi. 04/20/23

Cervical HPV infection:Cervical HPV infection:

Cancer of Cervix

Shashi. 04/20/23

Pap Smear Results:Pap Smear Results:

Cancer of Cervix

Shashi. 04/20/23

Morphology:Morphology: Raised (acuminatum) or flat Raised (acuminatum) or flat

(macular).(macular). Koilocytotic atypiaKoilocytotic atypia Abundant HPV nucleic acids.Abundant HPV nucleic acids. Atypical cells in the basal region Atypical cells in the basal region

(CIN-1) or completely replace normal (CIN-1) or completely replace normal cells (CIN-3)cells (CIN-3)

Cancer of Cervix

Shashi. 04/20/23

Ca Cx - MorphologyCa Cx - Morphology 3 gross types3 gross types

Exophytic/Fungating, Ulcerating & Exophytic/Fungating, Ulcerating & Infiltrative. Infiltrative.

80% Squamous-Ca, 20% other.80% Squamous-Ca, 20% other. Adeno-carcinoma, Adenosquamous, Adeno-carcinoma, Adenosquamous,

Clear-cell carcinoma etc.Clear-cell carcinoma etc. 40-50 peak age.40-50 peak age.

Cancer of Cervix

Shashi. 04/20/23

Staging:Staging: Stage 0 – CIN-IIIStage 0 – CIN-III Stage 1 – Ca limited to CxStage 1 – Ca limited to Cx

1a – Preclinical – diagnosed by microscopy1a – Preclinical – diagnosed by microscopy 1a1- Minimal invasive1a1- Minimal invasive 1a2 – Microscopic invasion <5mm1a2 – Microscopic invasion <5mm

1b – more than 5 mm invasion1b – more than 5 mm invasion Stage 2 – Beyond but pelvic wall freeStage 2 – Beyond but pelvic wall free Stage 3 – Pelvic wall/lower vagina Stage 3 – Pelvic wall/lower vagina

involveinvolve Stage 4 – Extension beyond pelvis.Stage 4 – Extension beyond pelvis.

Cancer of Cervix

Shashi. 04/20/23

Clinical Features:Clinical Features: Asymptomatic – Abnormal cells in Asymptomatic – Abnormal cells in

smearssmears Vaginal BleedingVaginal Bleeding Treatments – Cone biopsy, Treatments – Cone biopsy,

hysterectomyhysterectomy 5 year survival5 year survival

Stage1->80%, Stage2–75%, Stage3-35% Stage1->80%, Stage2–75%, Stage3-35% & 10-15% with Stage 4 disease.& 10-15% with Stage 4 disease.

Cancer of Cervix

Shashi. 04/20/23

Ulcerating Ca Cx:Ulcerating Ca Cx:

Cancer of Cervix

Shashi. 04/20/23

Fungating Ca CxFungating Ca Cx

Cancer of Cervix

Shashi. 04/20/23

Stage IV – Ca Cx Stage IV – Ca Cx (Block (Block Dissection)Dissection)

Cancer of Cervix

Shashi. 04/20/23

Spread:Spread: Direct:Direct:

Down – Vagina, LabiaDown – Vagina, Labia Lateral – adnexa, ureter, ovary, Pelvic Lateral – adnexa, ureter, ovary, Pelvic

wallwall Anterior – bladderAnterior – bladder Posterior – RectumPosterior – Rectum

Lymphatic: Lymphatic: Paracervical, Obturator, Int & Ext iliac, Paracervical, Obturator, Int & Ext iliac,

Sacral,Common iliac, Aortic.Sacral,Common iliac, Aortic. Blood:Blood: Liver, lungs etc. Liver, lungs etc.

Cancer of Cervix

Shashi. 04/20/23

Stage IV – Ca Cx Stage IV – Ca Cx (Block (Block Dissection)Dissection)

Cancer of Cervix

Shashi. 04/20/23

Carcinoma Cervix:Carcinoma Cervix:

Cancer of Cervix

Shashi. 04/20/23

Infiltrating Carcinoma Cx:Infiltrating Carcinoma Cx:

Cancer of Cervix

Shashi. 04/20/23

Squamous Carcinoma:Squamous Carcinoma:

Cancer of Cervix

Shashi. 04/20/23

Summary:Summary: Carcinoma cervix is related to HPV Carcinoma cervix is related to HPV

infection with other risk factors. infection with other risk factors. (smoking)(smoking)

Early diagnosis by cytological PAP Early diagnosis by cytological PAP test.test.

Predominantly Squamous type(80%).Predominantly Squamous type(80%). Clinically divided into 1- 4 stages. Clinically divided into 1- 4 stages. Spread by direct, lymphatic & blood.Spread by direct, lymphatic & blood.