Table 18.1 Nomenclature of bone tumors
Cervical dysplasia
BASIC INFORMATION
DEFINITION
Cervical dysplasia refers to atypical development of immature squamous epithelium that does not penetrate the basement epithelial membrane. Characteristics include increased cellularity, nuclear abnormalities, and increased nuclear to cytoplasm ratio. A progressive polarized loss of squamous differentiation exists beginning adjacent to the basement membrane and progressing to the most advanced stage (severe dysplasia), which encompasses the complete squamous epithelial layer thickness.
Classification systems:
Modified Papanicolaou: Class I, II, III, IV, and V
Dysplasia: Normal, atypia (mild, moderate, and severe), carcinoma in situ, and cancer
CIN: Normal, atypia (CIN I, II, or III), and cancer
BETHESDA 2001 UPDATED CLASSIFICATION:
Interpretation/result (including specimen adequacy)
• Negative for intraepithelial lesion or malignancy
• Organisms (i.e., Trichomonas vaginalis, Candida sp., bacterial vaginosis), reactive cellular changes (inflammation), atrophy
• Epithelial cell abnormalities: atypical squamous cells (ASC), of undetermined significance (ASC-US), cannot exclude HSIL (ASC-H), LSIL (CIN 1 and HPV), HSIL (CIN 2 & 3, CIS), squamous cell carcinoma
• Glandular cell abnormalities: atypical glandular cells (AGC): (specify endocervical, endometrial, or NOS), atypical glandular cells, favor neoplastic (specify endocervical, endometrial, or NOS) endocervical adenocarcinoma in situ (AIS), adenocarcinoma
• Other: endometrial cells in a woman 40 years of age
SYNONYMS
Class III or class IV Pap smear
Cervical intraepithelial neoplasia (CIN)
Low-grade or high-grade squamous intraepithelial lesion (LGSIL or HGSIL)
EPIDEMIOLOGY & DEMOGRAPHICS
PEAK INCIDENCE:
• Age 35 years
• Abnormal Pap smear rate revealing dysplasia approximates 4% to 5%, depending on population risk factors and false-negative rate variance
• False-negative rate approaching 45%
• Average age-adjusted incidence of severe dysplasia 35 cases/100,000 persons
BASIC INFORMATION
DEFINITION
Cervical dysplasia refers to atypical development of immature squamous epithelium that does not penetrate the basement epithelial membrane. Characteristics include increased cellularity, nuclear abnormalities, and increased nuclear to cytoplasm ratio. A progressive polarized loss of squamous differentiation exists beginning adjacent to the basement membrane and progressing to the most advanced stage (severe dysplasia), which encompasses the complete squamous epithelial layer thickness.
Classification systems:
Modified Papanicolaou: Class I, II, III, IV, and V
Dysplasia: Normal, atypia (mild, moderate, and severe), carcinoma in situ, and cancer
CIN: Normal, atypia (CIN I, II, or III), and cancer
BETHESDA 2001 UPDATED CLASSIFICATION:
Interpretation/result (including specimen adequacy)
• Negative for intraepithelial lesion or malignancy
• Organisms (i.e., Trichomonas vaginalis, Candida sp., bacterial vaginosis), reactive cellular changes (inflammation), atrophy
• Epithelial cell abnormalities: atypical squamous cells (ASC), of undetermined significance (ASC-US), cannot exclude HSIL (ASC-H), LSIL (CIN 1 and HPV), HSIL (CIN 2 & 3, CIS), squamous cell carcinoma
• Glandular cell abnormalities: atypical glandular cells (AGC): (specify endocervical, endometrial, or NOS), atypical glandular cells, favor neoplastic (specify endocervical, endometrial, or NOS) endocervical adenocarcinoma in situ (AIS), adenocarcinoma
• Other: endometrial cells in a woman 40 years of age
SYNONYMS
Class III or class IV Pap smear
Cervical intraepithelial neoplasia (CIN)
Low-grade or high-grade squamous intraepithelial lesion (LGSIL or HGSIL)
EPIDEMIOLOGY & DEMOGRAPHICS
PEAK INCIDENCE:
• Age 35 years
• Abnormal Pap smear rate revealing dysplasia approximates 4% to 5%, depending on population risk factors and false-negative rate variance
• False-negative rate approaching 45%
• Average age-adjusted incidence of severe dysplasia 35 cases/100,000 persons
PREVALENCE:
• Dysplasia: peak age, 27 years (3600 cases/100,000 persons)
• CIS: peak age, 30 years (1100 cases/100,000 persons)
• Invasive cancer: peak age, 75 years (800 cases/100,000 persons)
PHYSICAL FINDINGS & CLINICAL PRESENTATION
• Cervical lesions associated with dysplasia usually are not visible to the naked eye; therefore physical findings are best viewed by colposcopy of a 3% acetic acid-prepared cervix.
• Patients evaluated by colposcopy are identified by abnormal cervical cytology screening from Pap smear screening
• Colposcopic findings:
1. Leukoplakia (white lesion seen by the unaided eye that may represent condyloma, dysplasia, or cancer)
2. Acetowhite epithelium with or without associated punctation, mosaicism, abnormal vessels
3. Abnormal transformation zone (abnormal iodine uptake, “cuffed” gland openings)
ETIOLOGY
• Not clearly elucidated
• May be caused by abnormal reserve cell hyperplasia resulting in atypical metaplasia and dysplastic epithelium
• Strongly associated and initiated by oncogenic HPV infection (high-risk HPV types 16, 18, 31, 33, 35, 45, 51, 52, 56, and 58; low-risk HPV types 6, 11, 42, 43, and 44)
• Dysplasia: peak age, 27 years (3600 cases/100,000 persons)
• CIS: peak age, 30 years (1100 cases/100,000 persons)
• Invasive cancer: peak age, 75 years (800 cases/100,000 persons)
PHYSICAL FINDINGS & CLINICAL PRESENTATION
• Cervical lesions associated with dysplasia usually are not visible to the naked eye; therefore physical findings are best viewed by colposcopy of a 3% acetic acid-prepared cervix.
• Patients evaluated by colposcopy are identified by abnormal cervical cytology screening from Pap smear screening
• Colposcopic findings:
1. Leukoplakia (white lesion seen by the unaided eye that may represent condyloma, dysplasia, or cancer)
2. Acetowhite epithelium with or without associated punctation, mosaicism, abnormal vessels
3. Abnormal transformation zone (abnormal iodine uptake, “cuffed” gland openings)
ETIOLOGY
• Not clearly elucidated
• May be caused by abnormal reserve cell hyperplasia resulting in atypical metaplasia and dysplastic epithelium
• Strongly associated and initiated by oncogenic HPV infection (high-risk HPV types 16, 18, 31, 33, 35, 45, 51, 52, 56, and 58; low-risk HPV types 6, 11, 42, 43, and 44)
• Risk factors:
1. Any heterosexual coitus
2. Coitus during puberty (T-zone metaplasia peak)
3. DES exposure
4. Multiple sexual partners
5. Lack of prior Pap smear screening
6. History of STD
7. Other genital tract neoplasia
8. HIV
9. TB
10. Substance abuse
11. “High-risk” male partner (HPV)
12. Low socioeconomic status
13. Early first pregnancy
14. Tobacco use
15. HPV
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Metaplasia
• Hyperkeratosis
• Condyloma
• Microinvasive carcinoma
• Glandular epithelial abnormalities
• Adenocarcinoma in situ
• VIN
• VAIN
• Metastatic tumor involvement of the cervix
WORKUP
Periodic history and physical examination (including cytologic screening), depending on age, risk factors, and history of preinvasive cervical lesions
• Consider screening for sexually transmitted disease (Gc, Chlamydia, VDRL, HIV, HPV)
• Abnormal cytology (HSIL/LSIL, initial ASC/ASC-US/ASC-H in high-risk patients, recurrent in low-risk/postmenopausal patients) and grossly evident suspicious lesions; refer for colposcopy and possible directed biopsy/ECC (examination should include cervix, vagina, vulva, and anus)
• For glandular cell abnormalities (AGC): refer for colposcopy and possible directed biopsy/ECC, and consider endometrial sampling
• In pregnancy: abnormal cytology followed by colposcopy in the first trimester and at 28 to 32 weeks; only high-grade lesions suspect for cancer biopsied; ECC contraindicated
LABORATORY TESTS
• Gc, Chlamydia to rule out STD
• Pap cytology screening (requires appropriate sampling, preparation, cytologist interpretation and reporting)
• Colposcopy and directed biopsy, ECC for indications (see “Workup”)
• HPV-DNA typing if identified abnormal cytology
IMAGING STUDIES
• Cervicography
• Computer-enhanced Pap cytology screening (e.g., PAPNET)
TREATMENT
NONPHARMACOLOGIC THERAPY
• Superficial ablative techniques (cryosurgery, CO2 laser, and electrocoagulation diathermy) considered for colposcopy-identified dysplasia (moderate to severe dysplasia or CIS) and negative ECC; mild dysplasia followed conservatively in a compliant patient
• Cone biopsy (LEEP, CO2 laser, “cold knife” cone biopsy) considered for colposcopy-identified dysplasia (moderate to severe dysplasia or CIS) and positive ECC or if there is a two-grade or more discrepancy between the Pap smear, colposcopy, and biopsy or ECC findings
• Hysterectomy if patient has completed child bearing and has persistent or recurrent severe dysplasia or CIS
• In pregnancy: treatment for cervical dysplasia deferred until after delivery
ACUTE GENERAL Rx
Topical 5-fluorouracil (5-FU) is rarely used for recurrent cervicovaginal lesions.
CHRONIC Rx
• Because of the risk for persistent and recurrent dysplasia, long-term follow-up is individualized based on patient risk factors, Pap smear and colposcopy results, treatment history, and presence of high-risk HPV (e.g., Pap smear q3-4mo/yr, then q6mo/1 yr, then annually [if all normal], or repeat colposcopy examination and treat as indicated).
• Mild dysplasia with negative ECC should be followed conservatively in a compliant patient as a majority of these lesions persist or regress.
DISPOSITION
• Because of the large numbers of women in high-risk groups, the prevalence of HPV, and the high false-negative Pap smear rate, routine Pap smear screening should be reinforced for all women, especially those with a history of cervical dysplasia.
• Success rates for treatment approach 83% to 93%.
• Detection of persistence of recurrence requires careful follow-up.
• Cervical treatment possibly results in infertility (cervical stenosis or incompetence), which requires careful consideration and discretion for use of LEEP and cone biopsy.
• Appropriate counseling and informed consent needed when considering any form of management of cervical dysplasia.
• There has been no case of cervical dysplasia progressing to invasive cancer with appropriate screening, diagnosis, treatment, and follow-up.
1. Any heterosexual coitus
2. Coitus during puberty (T-zone metaplasia peak)
3. DES exposure
4. Multiple sexual partners
5. Lack of prior Pap smear screening
6. History of STD
7. Other genital tract neoplasia
8. HIV
9. TB
10. Substance abuse
11. “High-risk” male partner (HPV)
12. Low socioeconomic status
13. Early first pregnancy
14. Tobacco use
15. HPV
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Metaplasia
• Hyperkeratosis
• Condyloma
• Microinvasive carcinoma
• Glandular epithelial abnormalities
• Adenocarcinoma in situ
• VIN
• VAIN
• Metastatic tumor involvement of the cervix
WORKUP
Periodic history and physical examination (including cytologic screening), depending on age, risk factors, and history of preinvasive cervical lesions
• Consider screening for sexually transmitted disease (Gc, Chlamydia, VDRL, HIV, HPV)
• Abnormal cytology (HSIL/LSIL, initial ASC/ASC-US/ASC-H in high-risk patients, recurrent in low-risk/postmenopausal patients) and grossly evident suspicious lesions; refer for colposcopy and possible directed biopsy/ECC (examination should include cervix, vagina, vulva, and anus)
• For glandular cell abnormalities (AGC): refer for colposcopy and possible directed biopsy/ECC, and consider endometrial sampling
• In pregnancy: abnormal cytology followed by colposcopy in the first trimester and at 28 to 32 weeks; only high-grade lesions suspect for cancer biopsied; ECC contraindicated
LABORATORY TESTS
• Gc, Chlamydia to rule out STD
• Pap cytology screening (requires appropriate sampling, preparation, cytologist interpretation and reporting)
• Colposcopy and directed biopsy, ECC for indications (see “Workup”)
• HPV-DNA typing if identified abnormal cytology
IMAGING STUDIES
• Cervicography
• Computer-enhanced Pap cytology screening (e.g., PAPNET)
TREATMENT
NONPHARMACOLOGIC THERAPY
• Superficial ablative techniques (cryosurgery, CO2 laser, and electrocoagulation diathermy) considered for colposcopy-identified dysplasia (moderate to severe dysplasia or CIS) and negative ECC; mild dysplasia followed conservatively in a compliant patient
• Cone biopsy (LEEP, CO2 laser, “cold knife” cone biopsy) considered for colposcopy-identified dysplasia (moderate to severe dysplasia or CIS) and positive ECC or if there is a two-grade or more discrepancy between the Pap smear, colposcopy, and biopsy or ECC findings
• Hysterectomy if patient has completed child bearing and has persistent or recurrent severe dysplasia or CIS
• In pregnancy: treatment for cervical dysplasia deferred until after delivery
ACUTE GENERAL Rx
Topical 5-fluorouracil (5-FU) is rarely used for recurrent cervicovaginal lesions.
CHRONIC Rx
• Because of the risk for persistent and recurrent dysplasia, long-term follow-up is individualized based on patient risk factors, Pap smear and colposcopy results, treatment history, and presence of high-risk HPV (e.g., Pap smear q3-4mo/yr, then q6mo/1 yr, then annually [if all normal], or repeat colposcopy examination and treat as indicated).
• Mild dysplasia with negative ECC should be followed conservatively in a compliant patient as a majority of these lesions persist or regress.
DISPOSITION
• Because of the large numbers of women in high-risk groups, the prevalence of HPV, and the high false-negative Pap smear rate, routine Pap smear screening should be reinforced for all women, especially those with a history of cervical dysplasia.
• Success rates for treatment approach 83% to 93%.
• Detection of persistence of recurrence requires careful follow-up.
• Cervical treatment possibly results in infertility (cervical stenosis or incompetence), which requires careful consideration and discretion for use of LEEP and cone biopsy.
• Appropriate counseling and informed consent needed when considering any form of management of cervical dysplasia.
• There has been no case of cervical dysplasia progressing to invasive cancer with appropriate screening, diagnosis, treatment, and follow-up.
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