Cervix

Question 1

ECTOCERVIX vs. ENDOCERVIX

Answer 1

Ectocervix –> outermost aspect and adjacent to the vaginal wall –> SQUAMOUS EPITHELIUM (like the vaginal wall)

Endocervix – surrounds the external os, the opening of the cervix –> GLANDULAR COLUMNAR EPITHELIUM

The transition between squamous and glandular epithelium is the SQUAMOCOLUMNAR JUNCTION and this is where METAPLASIA OCCURS –> most uterine cancers here!!!!!!

As we age, the other region of the endocervix recedes, transitioning from glandular to squamous - so there is an old and new squamocolumnar junction

Question 2

Cervicitis

Answer 2

Most women have some degree of chronic cervicitis (lymphocytes, plasma cells)

ACUTE cervicitis –> caused by CHLAMYDIA, NEISSERIA, HERPES, TRICHOMONAS and YEAST (PMNs on biopsy); follicular cervicitis - chlamydia; granulomatous inflammation - TB

Question 3

Nabothian Cysts

Answer 3

As cell morphology changes in transition zone, SQUAMOUS CELLS may block gland drainage, resulting in Nabothian cysts

Extremely common, normal variants

Question 4

Cervical Polyps

Answer 4

Between the 4th and 6th decades of life, women may present with cervical polyps

Highly vascular, appear red grossly; PRONE TO BLEEDING

Benign; clip and cauterize

2-5% of adult women

Question 5

Benign Cellular Changes

Answer 5

Infections (cervicitis), non-specific inflammation, interventional radiation all cause “benign cellular changes” in the cervix, as classified by the BETHESDA SYSTEM - seen on pap smears

Herpes –> multinucleated, ground-glass appearance, inclusion bodies

Trichomonas –> sexually transmitted parasitic infection that presents with discharge

Gram + –> following changes in vaginal vault, gram + can outgrow the commensal LACTOBACILLI, causing bacterial vaginosis

Candida –> tend to aggregate epithelial cells via the yeast’s pseudo-hyphae; fish on a string appearance

Question 6

Cervical epithelial cells

Answer 6

Originate at the BASEMENT MEMBRANE

As they mature, they migrate superficially

Basal cells = largest nuclei, smallest cytoplasm

As the cells migrate, their nuclei shrink and their cytoplasm gets larger and larger

Basal –> parabasal –> intermediate –> superficial

Estrogen influences these cells to DIFFERENTIATE into superficial cells with pin-point nuclei and large cytoplasms

Most cells from paps are superficial/intermediate

Question 7

SQUAMOUS CELL ABNORMALITIES

Answer 7

All abnormalities are compared against normal intermediate cells

Atypical Squamous Cells (ASC)
Of Undetermined Significance (ASC-US) – enlarged cytoplasm
Cannot rule out high grade lesion (ASC-H) – smaller cytoplasm

Low grade squamous intraepithelial lesion (LSIL) – irregular, ground glass, more cytoplasm
High grade squamous intraepithelial lesion)–irregular, ground glass, smaller cytoplasm

SQUAMOUS CANCER –> irregular shape, prominent macronucleolus, granular chromatin, solid looking cytoplasm; very irregular chromatin pattern

Question 8

GLANDULAR CELL ABNORMALITIES

Answer 8

Glandular cell dysplasia is also possible

Lesions may be described as aeither ENDOCERVICAL ADENOCARCINOMA or ENDOMETRIAL ADENOCARCINOMA

If unsure – atypical glandular cells of undetermined significance

Present as ABNORMAL GLANDULAR CELLS THAT PILE UP with LARGE NUCLEI and CHROMATIN CHANGES

Question 9

90% of HPV infections are…

Answer 9

TRANSIENT!

Question 10

CIN

Answer 10

Cervical Intrapeithelial Neoplasms

CIN 1 = Koilocytic changes –> epithelial changes secondary to HPV infection –> in the bottom 1/3 of epithelium (LSIL)

CIN 2 = Characterized by changes in 2/3 of the epithelium (HSIL)

CIN 3 = koilocytosis THROUGHOUT THE EPITHELIUM (HSIL)

CIN lesions are “pre-cancerous”/in situ lesions –> not invasive on their own

Question 11

HPV Testing and Abnormal Paps

Answer 11

Test for HPV 16 and 18 (highest risk types)

If cytology and HPV are both NEGATIVE, proceed normally (every 3 years for 21-29, every 5 years 30+)

If both are POSITIVE –> treat as necessary

If HPV positive by CYTOLOGY negative –> repeat co-testing in 12 months or test HPV serotype –> if 16/18 are there, do a COLPOSCOPY

Question 12

Colposcopy

Answer 12

Colposcope is a low-powered microscope used to BETTER VISUALIZE THE CERVIX and potential METAPLASTIC LESIONS

Strawberry spots are inflammation (usually Trichmonas)

If a HIGH GRADE LESION is detected –> CONE biopsy to rule out invasive disease

Question 13

Pap Smear overview

Answer 13

Do pap –> checks for cells cytology –> this is where we would see LSIL/HSIL/ASC-US etc.

IF abnormal, then do HPV reflex testing (also chlamydia and gonorrhea for preggos)

HPV+ AND abnormal –> TREAT!!!

If Both negative –> fine, usual screening rules
If cytology is abnormal but HPV is negative –> fine, usual screening rules

If CYTOLOGY is fine but HPV is found on reflex testing, repeat co-testing in 12 months…OR immediate HPV genotype –> if HPV 16/18 are found –> COLPOSCOPY

THEN we can do a biopsy to check for invasive disease if we see a high grade lesion

So, if LSIL, HSIL, HPV+ 16/18 or any combo are found, do a colposcopy/biopsy

CIN1 found (watch and wait likely, or just remove via laser ablation etc)

CIN2/3 - DEFINITELY remove lesion as these can progress to cancer

Question 14

Prevention and Treatment

Answer 14

VACCINES – 2 available (Gardasil and Cervarix)

Cervarix protects against HPV 16/18
Gardisil protects against HPV 6, 11, 16, 18

Nearly 100% effective at reducing CIN 3+ lesions

Once 70% of population is vaccinated, then the number of CIN3+ lesions found will be reduced by up to 95%

Treating lesions –> watch and wait, laser ablation, loop electrosurgical excision procedure (LEEP), cold knife cone (not if pregnant!!)

Question 15

Cervical Cancer Overview

Answer 15

Most common among women who do not get regular screening; prognosis depends on AGE

Types –> SQUAMOUS CELL CARCINOMA, ADENOCARCINOMA, SMALL CELL CARCINOMA

Those with glandular abnormalities will also usually have squamous abnormalities (often co-exist)

HPV 16 accounts for 55-60% of all cervical cancer

HPV 18 accounts for 10-15% of all cervical cancer

Most stain positive for P16

Question 16

Staging of Cervical Cancers

Answer 16

0 = Carcinoma in Situ
I = Confined to CERVIX (80% 5 year survival)
II = Beyond cervix, but not to pelvic wall, in upper 2/3 of cervix --> 75% 5 year
III = Tumor in pelvic wall or lower 1/3 of vagina --> < 50%

IV = Beyond the pelvis or to mucosa of bladder or rectum or metastatic

Question 17

P16

Answer 17

Positive stain are highly indicative of a high risk HPV infection

Not specific