A 37-Year-Old Woman With Post-Coital Bleeding

A Powerpoint companion to: LABORATORY MEDICINE CASEBOOK. An introduction to clinical reasoning

Jana Raskova, MD Professor of Pathology & Laboratory MedicineStephen Shea, MD Professor of Pathology & Laboratory MedicineFrederick Skvara, MD Associate Professor of Pathology & Laboratory MedicineNagy Mikhail, MD Assistant Professor of Pathology & Laboratory Medicine

UMDNJ-Robert Wood Johnson Medical SchoolPiscataway, NJ

Eugene G. Martin, Ph.D. Associate Professor of Pathology & Laboratory Medicine

History and Presentation 37 year old woman seen in physician’s office complaining of a

two week history of post-coital vaginal bleeding. Previous history – Two normal pregnancies. Family history

unremarkable Physical Exam:

Slightly overweight female in no acute distress BP: 120/85 HR 85 bpm - regular Temperature – 98 oF Chest and abdominal examination uremarkable.

Colposcopy Cervix – White patches following the application of acetic acid, a

well as distinct vascular punctuation pattern. PAP smear obtained. Previous PAP reviewed.

PAP SMEAR

Kilocytic atypia: Mature squamous cells,demonstrating a

large perinuclear, lightly stained area. Surrounding peripheral cytoplasm normal Slightly enlarged nuclei

Stains much more intensely. Chromatin appears relatively No secretory or malignant cells present

PAP smear One Year Earlier Normal PAP smear

Normal mature squamous cellsSmall, pyknotic nucleiNo perinuclear haloYellow color is due to cytoplasmic glycogen

PAP SMEAR

Mature squamous cells,demonstrating a large perinuclear, lightly stained area.

Surrounding peripheral cytoplasm stains much more intensely.

Chromatin appears relatively normal

PAP smear: One Year Earlier PAP smear: Current

High Nuclear/cytoplasmic ratio Variation in nuclear size anisokaryosis Irregular nuclear membranes Hyprchromatic nuclei Course chromatin patternDX: Severe dysplasia or CIN IIIHigh-Grade squamous intraepithelial lesion - HGSIL

Cervical Biopsy: HPV In-Situ Hybirdization for types 16 and 18

Note Purple precipitate indicating the site of hybirdization between target and probe DNA

Human Papilloma Virus

HPV types 6,11,42 and 44 – associated with development of low risk benign condylomas

Majority of low-grade cervical intraepithelial cells (CIN 1) exhibit features of HPV infection.

Only a small percentage develop cervical carcinoma

HPV 16,18,31 and 33 - associated with development of high risk cervical carcinoma.

Oncoprotein E6 of HPV types 16, 18 transforms cells in culture by inactivation of human suppressor gene p53.

15% of cervical carcinoma IS NOT associated with HPV

Cervical Biopsy

Normal maturation visible Hyperchromatic basal cells Flattened squamous surface

cells Clear areas represents

normal glycogen deposition

Norma H&E x78l Patient H&E x78

Squamous epithelium – no evidence of maturation Loss of cell polarity Nuclei – hyperchromatic Nuclear size variablePATTERN: Severe dysplasia or Carcinoma in situ

Predisposing factors for cervical carcinoma

Sexual behaviors Early age at first

intercourse Multiple sexual

partners Male partner with

previous multiple sexual partners

Non-sexual risk factors Cigarette smoking Use of oral

contraceptives Lack of

circumcision in male partners

Family history of cervical carcinoma

Treatment Considerations –

CIN: Cervical Cone Biopsy Genital warts:

Liquid N2 Laser Electrocautery Imiquinoid cream Podophyllin Podofilox

Treatment eliminates the wart, but not the virus!

Complications: Although most HPV

infections, fail to progress to cancer, it is important in the presence of cervical dysplasia to have regular PAP smears

1:500 of CIN III will develop invasive carcinoma later

Pregnancy – physical obstruction, modification of the elasticity of the vaginal wall is reduced