3. Uterine cervix pathology

Question 1

Portions of the uterine cervix

Answer 1

• Ectocervix: lower 1/3 of the organ, continuous with the vagina
• Endocervix: inner part connected to the body of the uterus

Question 2

Ectocervix

Answer 2

• Non-keratinizing squamous epithelium tich in glycogen –> specific staining ( Lugol/Shiller test)
• Basal layer is responsible for tissue regeneration and is responsive to estrogen stimulation

Question 3

Endocervix

Answer 3

• Mucus producing columnar epithelial cells

- Under control of sex hormone

Question 4

Transition zone

Answer 4

• Squamous to columnal junction

- Subcolumnar reserve cells (regenerative foci) –> most of the squamous metaplasia take place in this zone

Question 5

Ectropion vs erosion

Answer 5

• Presence of endocervical tissue in the ectocervi, whereas erosion refers ot a lack of epithelial covering
• Reddish patch in the transition zone, extension depends on age and n. of pregnancies.

Question 6

Schiller test

Answer 6

The Schiller (lugol) iodine test is based on the interaction between iodine and glycogen: the squamous epithelium is uniformly coloured dark-brown, the altered epithelium does not take up iodine, the columnar epithelium does not contain glycogen and therefore there is no uptake of iodine.
A colposcopic lesion may take all the nuances between brown-red (normal squamous epithelium) to a more light staining which is due to the glycogen charge. Yellow colour is characteristic for atypical or immature epithelium. This test helps to define the limits between the epithelium and the lesion.

Question 7

Squamous cell metaplasia

Answer 7

• Focal or extensive replacement of endocervical glands by a nonkeratinizing quamous epithelium
• Result of adaptation of the subcolumnar reserve cells to damage
• Can be immature (mucus cells are conserved) or mature (replacement is complete)

Question 8

Keratosis

Answer 8

• Stratum corneum and granulosum develop

Question 9

First line exam

Answer 9

Colposcopy

• Assess ectocervix status
• Guide biopsy

Question 10

Agents specific for HPV lesions

Answer 10

• Lugol’s/Schiller’s reagent: thick, mustard or saffron yellow area
• Acetic acid reagent: discolors the affected area

Question 11

Transitional metaplasia

Answer 11

• Focal or extensive replacement of the ectocervical epithelium by urothelium
• Typical of elderly patients, related to atrophy of the ectocervic epithelium

Question 12

Tubar and endometrioid metaplasia

Answer 12

• Focal or extensive replacement of endocervical epithelium by tubal or endometrial epithelium.
• These reactions respond to true erosion and tehy often appear along with squamous metaplasia

Question 13

Endometriosis

Answer 13

• Appearance of endometrioid epithelium in combination with stromal cells
• Foci are red nodules that may cause bleeding
• Stromal cells can undergo SM metaplasia

Question 14

Condition frequent during pregnancy

Answer 14

• Decidual rection –> multiple yelloish nodules that may bleed and stimulate cancer development

Question 15

Endocervical polyp

Answer 15

• Focal hyperplasia induced by chronic inflammatory status

- Not a direct preneoplastic lesion but they can be colonized by neoplasia

Question 16

Main cervical lesions

Answer 16

• Squamous cell metaplasia
• Transitional metaplasia
• Tubar and endometrioid metaplasia
• Endometriosis
• Decidual reaction -> may induce cancer
• Endocervical polyps

Question 17

HPV virus

Answer 17

• Human DNA virus
• Infect epithelial covering
• More than 200 types identified
• Classification based of nucleotide sequence of ORF coding for capsid protein L1, identified through molecular tests (PCR)
• Epidemiology: 80% of the general population is likely to become infected during their lifetime
• Transmission: upon direct mucosal contact (sexual, skin to skin)
• Different HPV –> tropism for different mucosal districts

Question 18

Cellular alteration induced by HPV infection

Answer 18

• Koilocytosis or koilocytic atypia
• HPV infects basal layer of squamous epithelia through microabrasion, but cellular ateration are typically seen in surface and intermediate cells

Question 19

Koilocytosis

Answer 19

• Nuclear enlargement
• Irregular nuclear contour
• Nuclear hyperchromasia
• Peri nuclear white halo

Question 20

Viral HPV replication

Answer 20

• ENters the cell, translocated in the nucleus, start replication
• Early proteins (E6, E7) produced by viral mRNA, inhibit p53 (E6) and RB (E7), promoting cellular proliferation
• Late proteins: produced progressively in time, required for virion assembly

Question 21

Difference between transient and persistent HPV infection

Answer 21

• Transient: genuine infection, virions replicate, forming episomes and released when cells are sloughed –> benign disease, no oncogenic potential –> warts/condyloma
• Persistent: viral DNA is integrated in the host’s DNA, it may give rise to dysplastic lesions (oncogenic infection)
• -> LGHPVs lead to low grade squamous intraepithelial lesions that cannot progress to invasive cancer
• -> HGHPVs cause high grade SIL, variabl associate with invasive cancer

Influencing factors can promote the progression to cancer.

Question 22

Low and high risk HPV strains

Answer 22

Low risk:

• 6 and 11
• Low impact on p53 and RB inhibition
• -> low grade dysplasia with low risk for oncogenic transformation

High risk:

• 16 and 18
• Accumulate high levels of early genes –> have an higher impact on p53 and RB inactivation –> development of non-invasive and invasive lesions

Question 23

HPV at the HN region

Answer 23

• HPV LG –> benign squamous papilloma, laryngeal papillomatosis
• HPV HG –> 1/4 of cancers in the mouth and upper throat, exposure is related to oral sex

Question 24

HPV strain identification

Answer 24

Hybrid capture reaction that implies the use of probes directed at different genes