Diseases of Cervix Flashcards

1
Q

Inflammatory Diseases of the Cervix

A
  • Acute and Chronic Cervicitis
  • Endocervical Polyps
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2
Q

Inflammatory Diseases of the Cervix: Acute and Chronic Cervicitis

A
  • Nonspecific inflammation of the cervix is a constant finding in adult women and is usually of little or no clinical significance.
  • Specific infections by sexually transmitted pathogens (gonococci, chlamydia, mycoplasma, and herpesvirus), however, can produce severe cervicitis and lead to secondary inflammatory involvement of the upper genital tract (pelvic inflammatory disease).
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3
Q

Inflammatory Diseases of the Cervix: Endocervical Polyps

A
  • Endocervical polyps are benign inflammatory tumors that arise within the endocervical canal.
  • They are relatively common and can be seen in 2% to 5% of adult women.
  • They consist of a loose fibromyxomatous stroma lined by endocervical epithelium and range in size from small sessile lesions to large 5 cm pedunculated masses.
  • Dilated, mucus secreting endocervical glands, inflammation, and squamous metaplasia are common findings.
  • They may present with “spotting” and bleeding raising suspicion of some more serious lesions.
  • The treatment consists of surgical removal or endocervical curettage and in most cases is curative.
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4
Q

The Pap Test

A

• The majority of cervical cytologic samples are now submitted as liquid-based cytology

– Cells on collecting device are washed off into a preservative solution

– Slides are then prepared from the cell suspension

• This new method of sampling is an improvement on the direct smear because

– They are easier to interpret (cleaner background, even dispersion of cells)

• Detection rates are better

– Multiple tests can be done on the same sample

* Microscopic examination

*Molecular analysis for Chlamydia, gonnorrhea, HPV

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5
Q

Utility of the Pap Test

A

• Identification of infectious agents

– Infections in the cervix can spread to the upper reproductive tract, resulting in pelvic inflammatory disease (PID)

• MOST IMPORTANT: Identification of preneoplastic (dysplastic) lesions and carcinomas

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6
Q

HPV and the Cervix

A

• The cervix is not the only site to be infected by HPV, and it is not the only site for HPV related cancers, but it is the most commonly infected site

– HPV can’t infect intact, mature squamous epithelium

– The virus needs access to immature basal or metaplastic cells to establish infection

*This is why HPV likes the cervix so much

*This is why the transformation zone is so important and why it is where pap smears and biopsies should be sure to sample

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7
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix

A
  • LSIL
  • HSIL
  • Cervical Carcinoma
  • Squamous Carcinoma of the Cervix
  • Adenocarcinoma of the Cervix
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8
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: LSIL

A
  • Low grade squamous intraepithelial lesions of the cervix are similar in appearance to condyloma acuminatum of the vulva, but exophytic papillary growth is rare in cervical lesions.
  • Usually, these are flat lesions, with prominent koilocytic change in the superficial layers which is easily detected on pap testing.
  • Proliferation and an increase in immature cells are present, but by definition, the proliferation and immaturity is confined to the bottom third of the epithelium in LSIL.
  • The majority of LSIL will regress on their own with time. However, unlike condyloma acuminatum, which are all associated with low risk HPV subtypes, most LSIL of the cervix is associated with high risk HPV subtypes, and a percentage of cases will evolve into high grade lesions if left untreated.
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9
Q

LSIL

A
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10
Q
A
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11
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: HSIL

A
  • High grade squamous intraepithelial lesions of the cervix are defined by the extension of immature cells and proliferation into the upper two thirds of the epithelium.
  • When there is maturation in the more superficial layers, koilocytic changes may be seen, but these changes are absent when there is a lack of maturation in the entire epithelium.
  • Because immature cells, which have relatively less cytoplasm and less keratinization in the cytoplasm are closer to the surface in HSIL, they may be detected in the pap test as cells with a higher nuclear to cytoplasmic ratio and blue rather than pink cytoplasm.
  • Like LSIL may progress to HSIL, HSIL, in turn, may progress to carcinoma.
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12
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: Pap Detecting SILs

A
  • Following detection of an abnormality on the pap test, the cervix is examined by colposcopy, using magnification.
  • On colposcopic examination, SILs appear as aceto-white lesions (white patches after the application of acetic acetic), and abnormal vascular patterns (mosaic or punctuation patterns). Any areas which appear abnormal are biopsied and submitted for histologic confirmation before definitive treatment can be instituted.
  • The treatment of SIL depends on the stage of the lesion and includes watchful waiting with follow-up with Papanicolau smear or ablative treatments (cryotherapy or laser) for LSIL and electric loop excision procedure (LEEP), and cone excision for HSIL.
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13
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: Carcinoma of the Cervix

A
  • Risk factors for the development of cervical carcinoma include early age at first intercourse, multiple sexual partners, male partner with multiple sexual partners, increased parity, human papillomavirus (HPV) infection, oral contraceptives, nicotine, and genital infections.
  • HPV is considered to be the most important factor in the pathogenesis of cervical cancer.
  • The cervix is composed of squamous and glandular epithelium, and both types may be infected by HPV, and both may develop intraepithelial lesions and invasive carcinoma.
  • Squamous carcinomas of the cervix are all related to infection with high risk HPV subtypes, most commonly types 16 and 18. Most cervical adenocarcinomas are also HPV related. Squamous carcinoma is much more common, comprising over 75% of cervical cancers, and is also easier to detect early in its development.
  • The pap test is not as good at detecting glandular intraepithelial lesions (called adenocarcinoma in situ or AIS) as it is at detecting squamous lesions, so glandular lesions may not be detected as early, and adenocarcinomas tend to present with more advanced disease.
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14
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: Molecular Evidence linking HPV to cervical cancer

A
  • Detection of HPV DNA in 95% of cervical cancers
  • Disregulation of important cell cycle proteins (RB, Cyclin E, p16INK4, p63) by highrisk HPV types (genes E6 and E7)
  • Integration of the virus into the host DNA in invasive lesions
  • Demonstration of certain chromosomal abnormalities in association with specific high-risk HPV types (3q deletion/amplification in HPV 16)
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15
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: Carcinoma of the Cervix - Squamous Carcinoma

A
  • The peak incidence occurs at age 40-45.
  • Morphologically, squamous cell carcinoma can occur in three different patterns: fungating (exophytic), ulcerating, and infiltrative.
  • Advanced squamous cells carcinoma extends by involving adjacent structures including vagina, urinary bladder, ureters, rectum, and peritoneum.
  • Local lymph node metastases, and distant metastases to lymph nodes, liver, lung, bone marrow, and other organs can also occur.
  • Microscopically, approximately 95% of squamous cell carcinomas are composed of large neoplastic cells and are well-differentiated (keratinizing) or moderately differentiated (nonkeratinizing). The remaining tumors are poorly-differentiated squamous cell carcinomas and small undifferentiated carcinomas.
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16
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: Carcinoma of the Cervix - Adenocarcinoma

A
  • Adenocarcinomas are not grossly distinguishable from squamous carcinomas, but microscopically the tumors show glandular differentiation resembling carcinomas of the endometrium.
  • Precursor is adenocarcinoma in situ (AIS)

– Often diagnosed with accompanying HSIL

*24-75% of cases have both

  • AIS and adenocarcinoma can be detected on pap smear, but not as reliably as squamous lesions, so may present at more advantaged stage
  • Patients with AIS and adenocarcinoma are often younger than those with squamous carcinoma

– The incidence of adenocarcinoma seems to be increasing in women under age 40

17
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: Carcinoma of the Cervix - Staging

A
  • The prognosis for all types of cervical carcinoma depends on how extensive the disease is at diagnosis, which is why the prognosis for adenocarcinoma is worse than for squamous carcinoma.
  • Patients with very limited disease may not even require extensive surgery or adjuvant treatments.
  • Patients with advanced disease require extensive surgery, and often must be treated first with radiation to shrink the tumor before surgery can even be attempted to remove it.
  • The 5-year survival rate for patients with stage IA tumors is >95%, while for those with stage III or higher is less than 50%. This dramatic difference in survival underscores the importance of early diagnosis.

Staging of Cervical Cancer

Stage 0 Carcinoma in situ (CIN I)

Stage I Carcinoma confined to the cervix

Stage II Carcinoma extends beyond the cervix

Stage III Extension into pelvic wall/lower third vagina

Stage IV Extension into true pelvis, mucosa of rectum or bladder, distant metastases

18
Q

Intraepithelial and Invasive Squamous Neoplasia of the Cervix: Carcinoma of the Cervix - Management

A

• Minimally invasive disease or adenocarcinomain-situ can be treated by simple hysterectomy or cervical conization

– Slightly different procedure, with more tissue removed, than used for HSIL

  • More deeply invasive disease is treated with surgery to remove at least the entire uterus, cervix, paracervical tissue and adnexae (radical hysterectomy)
  • Adjuvant radiation therapy may be used prior to or following surgery, depending on extent of disease
19
Q

HPV and Cervical Cancer

A
  • DNA of high risk HPV subtypes is detected in 95% of cervical cancers
  • Pathogenesis:

– Viral proteins E6 and E7 interfere with the function of important cell cycle proteins (Rb,cyclin E, p16)

– Viral DNA is integrated into host DNA in high grade and invasive tumors (not in low grade lesions)

20
Q

Clinical Presentation of Cervical Cancer

A
  • More than half of patients have not had regular screening (paps)
  • Early disease (stage I) is rarely symptomatic
  • Symptoms of more advanced disease include

– Abnormal bleeding

– Bloody discharge

– Pain

– Hematuria

– Weakness, pallor, weight loss

• Tumor may be palpable on pelvic and/or rectal exam

21
Q
A

Cervical Cancer

22
Q
A

Cervical Cancer

23
Q
A

Cervical Cancer

24
Q

HPV Vaccine

A
  • Vaccination against HPV, which can protect against high risk subtypes 16 and 18 and low risk types 6 and 11, could significantly decrease the future incidence of cervical, vaginal and vulvar carcinomas, SILs and condylomata acuminata
  • . It is estimated that up to 75% of cervical carcinomas could be prevented by the vaccines currently available.
  • The vaccine is currently recommended for children ages 11-12, but it is not mandatory and many parents refuse it.
  • How much disease will be prevented depends on how many children get vaccinated.
  • At this time, it seems that the decrease in HPV disease in the United States will be far less than in other developed nations with more successful vaccination programs.