Pathology Of Cervix Flashcards
1
Q
Estrogen effect on cervical tissue
A
- Stimulates the maturation of cervical and vaginal squamous mucosa and formation of intracellular glycogen vacuoles in the squamous cells - As the cells shed the glycogen provides a substrate for endogenous vaginal aerobes and anaerobe - Normal cervical flora contains abundant lactobacilli which produces lactic acid
2
Q
Causes of Cervicitis
A
- Changes in vaginal pH - Decrease in lactobacilli - Infections - Gonococci, chlamydiae, mycoplasms and HSV - Cervical inflammation may alter the findings of a PAP smear
3
Q
Chronic endocervicitis Histology
A
4
Q
HSV of cervix Histology
A
- Intense non-specific inflammation
- Ulceration potentially
- Characteristic finding: Multinucleated Giant cells and intranuclear inclusions
5
Q
Multinucleated giant cells
A
- Histological finding for HSV infection
- Cells w/ large nuclei
6
Q
Endocervical polyps
A
- Non-neoplastic glandular lesion of the cervix
- Not true neoplasms; benign growths in women
- Result from Chronic inflammatory changes
- Range in size
- Dilated glands w/ an edematous, inflamed fibrotic stroma
- Surface epithelium but responds to the inflammation through squamous metaplasia
- May have a branching papillary structure
- May cause bleeding
- Composed of dense stroma covered by endocervical columnar epithelium
- Most are in the endocervical canal and may protrude from the cervical os
7
Q
Nabothian Cysts
A
- Non-neoplastic glandular lesion of the cervix
- Due to blockage of endocervical glands from inflammation
- Grossly appear as cystic spaces filled w/ mucoid
- Microscopicallly have cystically dilated glands lined by flattened epithelium
- May extend into the cervical wall which may mimic malignancy
8
Q
Tunnel Clusters
A
- Non-neoplastic glandular lesion of the cervix
- Localized proliferation of endocervical glands w/ side channels growing out
- Secretions may dilate the lumens
- Some have a florid glandular proliferation and a certain degree of atypia
9
Q
Microglandular hyperplasia
A
- Non-neoplastic glandular lesion of the cervix
- Involves the endocervical epithelium
- Complex proliferation of glands linded by flat epithelial cells w/ little or no atypia
- Squamous metaplasia may also be present
- Chronic inflammation is usually present in the stroma
10
Q
Diffuse laminar endocervical glandular hyperplasia
A
- Proliferation of medium sized, evenly spaced, well differentiated glands in the inner third of the cervical wall
- They are separated from the stroma
- Often has chronic inflammation
11
Q
Mesonephric duct rests
A
- Non-neoplastic glandular lesion of the cervix
- Undergo cystic dilation or have atypical hyperplastic changes
- May have a lobular, diffuse or ductal pattern
- Rarely malignant tumors can arise from these structures
- May be involved by CIN and other malignancies assoc. w/ it
12
Q
Cervical Carcinoma Risk Factors
A
- PAP smears have decreased deaths
- Multiple sex partners
- Male partner w/ multiple sex partners
- Young age at first intercourse
- Persistent infection of HPV 16 or 18
- Immunosuppression
- Certain HLA subtypes
- Use of OCP
- Use of nicotine
13
Q
Cervical Carcinoma Clinical Features
A
- Dysplasia early on is often asymptomatic
- Invasive cervcial carcinoma may present w/ irregular bleeding, postcoital spotting, pelvic pain, vaginal discharge and dysuria w/ renal failure in advanced cases (from closing the ureters)
14
Q
HPV Infection
A
- HPV infection is fairly common
- Most infections are transient and are eliminated by the immune response over several months
- Persistent infections increase the risk of precancerous and cancerous lesions
- HPVs infect the immature basal cells of the squamous epithelium in areas of epithelial breaks or immature metaplastic squamous cells at the squamocolumnar junction
- They do not infect mature superficial squamous cells covering the ectocervix, vagina or vulva
- Infection at these sites requires damage to surface epithelium, giving the virus access to the immature cells in the basal layer of the epithelium
- The cervix is susceptible due to a large amt of immature squamous metaplastic epithelium
- Replication occurs in the maturing squamous cells resulting in a cytopathic change-koilocytic atypia
- Prevents replicative senescence by up regulating telomerase
- Net result is an extension of the life span of epithelial cells which lead to tumor development
15
Q
Koilocytic atypia
A
- Seen on PAP smear of HPV infected individual
- When HPV virus gains access to immature squamous basal cells allowing for replication resulting in a morphologic change that is seen microscopically called koilocytosis
- Koilocytosis: shrinking of the nucleus w/ a perinuclear halo around it
- Telling of HPV infection
16
Q
HPV Replication
A
- Replication occurs in the maturing squamous cells resulting in a cytopathic change-koilocytic atypia
- Replication requires DNA synthesis in the host cells
- Replicates by activating mitotic activity in the maturing cells by interfering w/ the function of Rb and P53
- Viral E6 protein increases destruction of P53 while viral protein E7 increases destruction of Rb
- Induces centrosome duplication and genomic instability
17
Q
Cervical Intraepithelial Neoplasia (CIN) Morphology
A
- High N/C ratio
- Hyperchromatic nuclei
- Course chromatin granules
- Nuclear pleomorphism
- May be assoc. w/ perinuclear halos caused by disruption of the cytoskeleton (koilocytosis)
18
Q
CIN Grading
A
- Based on the expansion of the immature cell layer from the basal location to more superficial locations
19
Q
Cervical Intraepithelial Neoplasia (CIN) 2 Tiered Classification
A
Original Classification:
- CIN I: mild dysplasia (1/3 dysplastic)
- CIN II: moderate dysplasia (2/3 dysplastic)
- CIN III: severe dysplasia and carcinoma in situ (full thickness of the epithelium is now dysplastic)
Now use 2 tiered classification:
- LSIL: low grade intraepithelial lesion includes CIN I
- HSIL: high grade intraepithelial lesion includes CIN II, CIN III
20
Q
LSIL
A
- Low grade intraepithelial cervical lesion
- Atypical immature squamous cells limited to the lower 1/3rd of the epithelium
- Show no significant disruption of the host cell cycle and most regress spontaneously while a small percentage progresses to HSIL
- Does NOT progress directly to invasive carcinoma
- Is not considered premalignant
21
Q
HSIL
A
- High grade cervical intraepithelial lesion
- Atypical immature squamous cells expand to the lower 2/3rd of the epithelial thickness
- Assoc. w/ a progressive deregulation of the cell cycle by HPV causing increased cell proliferation and/or decreased cell maturation and a lower rate of viral replication
- HSILs are 1/10th as common as LSILs
22
Q
Cervical Intraepithelial Neoplasia (CIN)
A
- Also known as cervical dysplasia, is the potentially premalignant transformation and abnormal growth (dysplasia) of squamous cells on the surface of the cervix
- Major cause is HPV
23
Q
Cervical Carcinoma
A
- Squamous cell cancer is the most common type of cervical cancer
- All are assoc. w/ oncogenic risk HPVs
- May have adenosquamous cancer and neuroendocrine tumors; PAP screening less effective in detecting
- Peak incidence of invasive cervical cancer is 45yrs
24
Q
Microinvasive squamous cell cancer of cervix
A
- Depth of invasis is 5mm or less
- Natural history is diff. than the ordinary invasive carcinoma
- Tx is more conservative
- Area of microinvasion almost always originates from a focus of CIN
- Breach in the basement membrane
- Often have a desmoplastic stroma
- Risk of LN mets is only 1%
25
Invasive squamous cell carcinoma
- Most common malignant tumor of the female genital tract in most countries
- Incidence in the US has decreased during the last several decades
- High risk types of HPV are implicated
- 3 Major categories: **large cell nonkeratinizing, keratinizing and small cell carcinoma**
- The better differentiated form of keratinizing squamous cell cancer lacks a strong relationship to HPV and CIN
- Spreads by direct extension to vagina, corpus, lower urinary tract and uterosacral ligaments
26
Invasive squamous cell carcinoma progression
- Becomes more infiltrative over time
- Can invade bladder, rectum, ureters other surrounding organs
- Cases of metastatic dissemination
27
Adenocarcinoma of the cervix
- No distinguishing gross characteristics
- **HPV 16 and 18** found in most endocervical adenocarcinomas
- Overall prognosis is less favorable than for squamous cell carcinoma
28
Adenoma malignum
- AKA minimal deviation adenocarcinoma
- Very well differentiated
- Distorted glands w/ irregular outlines deeply postitioned in the cervix and a portion of the tumor is assoc. w/ a stromal response
- Usually **NOT assoc. w/ HPV**
- May be seen w/ **Peutz-Jeghers syndrome**
29
Adenosquamous carcinoma of the cervix
- Combines the **patterns of adenocarcinoma w/ a well defined squamous component**
- Common during **pregnancy**
- Has a **worse overall prognosis t**han pure squamous cell carcinoma or adenocarcinoma
- Generally poorly differentiated tumors
30
Neuroendocrine carcinoma of the cervix
- Similar to **small cell carcinoma** of the cervix
- May have trabecular, glandular, and spindle cell growth patterns
- May stain for **chromogranin**
**-** Mitoses and necrosis is common
