Pathology of the Cervix Flashcards
What is the cervix?
- the “neck” of the uterus
- divided into the EXOcervix (visible on vaginal exam) and ENDOcervix.
What lines the endo- and exocervix, respectively?
- EXOcervix= nonkeratinizing squamous epithelium.
- ENDOcervix= single layer of columnar cells.
What is the junction between the exo- and endocervix called?
transformation zone
What will HPV do to the cervix (since we know it can affect the vulva, vagina, or cervix)?
- condyloma acuminatum or dysplasia in the transformation zone.
** What does persistent HPV infection lead to in the cervix? (HIGH YIELD)
- risk for CIN cervical intraepithelial neoplasia
- dependent on high risk 16, 18, 31, and 33) due to E6 increasing destruction of p53 (checkpoint from G1 to S in cell cycle), and E7 increasing destruction of Rb.
** What is cervical intraepithelial neoplasia (CIN)?
- KOILOCYTIC change (KNOW THIS PICTURE), disordered cellular maturation, nuclear atypia, and increased mitotic activity. These cells begin to pile up in the cervix and can be divided into grades based on the extent of epithelial involvement.
** What are the grades of CIN?
- CIN I= involves lower 1/3 thickness of epithelium; most common.
- CIN II= lower 2/3 thickness of epithelium.
- CIN III= slightly less than entire thickness of epithelium.
- Carcinoma in situ (CIS)= entire thickness of epithelium and will lead to invasive SQUAMOUS CELL CARCINOMA!
- new system uses LSIL (low grade; I) or HSIL (high grade; II or III).
** What is the key feature that distinguishes dysplasia from carcinoma?
- reversibility!
Is progression from CIN I to CIS inevitable?
NO! There is a chance to reverse up to CIN III (but chances decrease as you progress from I to III).
What is cervical carcinoma?
- INVASIVE carcinoma that arises from the cervical epithelium.
- most commonly seen in middle-aged women (40-50).
- presents as VAGINAL BLEEDING (especially after sex).
What is the key risk factor for cervical carcinoma?
HPV
*also smoking and immunodeficiency
Is cervical carcinoma an AIDS defining illness in pts who are HIV +?
YES
What are the 2 types of cervical carcinoma?
- squamous cell carcinoma
- adenocarcinoma (less common)
- BOTH associated with HPV
** What is a finding of ADVANCED cervical carcinoma?
- HYDRONEPHROSIS with postrenal failure bc the tumor invades through the anterior wall of the uterus into the bladder forming a fistula, blocking the ureters.
*** What is the gold standard for cervical cancer screening?
PAP SMEAR and is very helpful bc it takes 10-20 years for dysplasia (CIN) to progress to carcinoma. So if we find CIN early, we can treat!
What is the confirmatory test for pap smear?
- colposcopy= visualization of cervix with a magnifying glass
- biopsy
What are some limitations of pap smear?
- inadequate sampling of transformation zone resulting in a false negative.
- limited efficacy in screening for adenocarcinoma.
How long does the quadrivalent (6, 11, 16, 18) HPV vaccine (Gardasil) last?
5 years
Why are pap smears still necessary after vaccination?
- bc there are many other types of HPV other than 16 and 18 which can lead to carcinoma.
What does estrogen do to the cervical and vaginal squamous cells?
- stimulates their maturation and formation of intracellular glycogen vacuoles.
- as the cells are shed, the glycogen provides a substrate for endogenous vaginal aerobes an anaerobes.
Does the normal cervical flora contain abundant lactobacilli?
YES producing lactic acid (decreasing pH), which produces bacteriotoxic H2O2.
What happens if the cervical pH rises too much?
- overgrowth of bacteria can occur leading to cervicitis.
What are ENDOcervical polyps?
- BENIGN growths in adult women that are dilated glands with papillary polyps and dense stroma occurring due to chronic inflammatory changes.
- may protrude through cervical os
What are nabothian cysts?
- blockage of ENDOcervical glands from inflammation.
- grossly appear as BENIGN cystic spaces filled with mucoid material.
- microscopically look dilated with flattened epithelium.
What is microglandular adenosis of the cervix?
- BENIGN complex proliferation of glands in the cervix lined by flat epithelial cells with little or no atypia.
What is diffuse laminar endocervical glandular hyperplasia?
- proliferation of medium sized, evenly spaced, well differentiated glands in the inner 1/3 of the cervical wall.
- separated from stroma
Is the leading type of cervical carcinoma squamous cell carcinoma?
YES and this is what PAP smears screen for.
What stain is used to help diagnose HPV infection?
Ki-67 and p16
What are the indicators of dysplasia you should look for on histology? (review)
- high N/C ratio
- hyperchromatic nuclei
- course chromatin granules
- nuclear pleomorphism
What is the most common malignant tumor of the female genital tract in most countries?
- Invasive squamous cell carcinoma (large cell nonkeratinizing, keratinizing, or small cell).
What are the stages of invasive cervical squamous cell carcinoma? (he said he won’t ask about staging)
- stage 0 (carcinoma in situ) to stage IV (carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum.
What is important to know about cervical adenocarcinoma?
- 5-15% of all cervical carcinomas.
- no distinguishing gross characteristics.
- well differentiated glandular pattern with mucin secretion.
- HPV 16 and 18
- prognosis is less favorable than for squamous cell carcinoma.
What is adenoma malignum (minimal deviation adenocarcinoma)?
- very well differentiated adenocarcinoma.
- usually NOT associated with HPV
- distorted glands with irruglar outlines and prominent stromal response.
- may be seen with PEUTZ-JEGHERS SYNDROME
What is adenosquamous carcinoma?
- combines the patterns of adenocarcinoma with a well defined squamous component.
- common during pregnancy.
- worse overall prognosis than either alone.
What is a neuroendocrine cervical carcinoma?
- similar to small cell carcinoma of the lung.
- may have trabecular, glandular, and spindle cell growth patterns.
- may stain for CHROMOGRANIN (copper-like appearance).
- AGGRESSIVE