Cervical Neoplasia Flashcards
Squamocolumnar junction in normal cervix
- Squamous and columnar epithelium meet
- Cells susceptible to HPV infection
- Precancerous lesions and Cervical CA development
Transformation zone in normal cervix
- Columnar epithelium is replaced by squamous epithelium
Squamocolumnar junction histologically shows
- Mature, glycogenized squamous epithelium
- Immature squamous metaplastic cells
- Columnar endocervical glandular epithelium
Endocervical polyps (benign)
- Inflammatory tumors
- Vaginal “spotting” or bleeding
- Located endocervical canal
- Ectocervical locations
- Endocervical polyps
- Small and large (up to 5-cm)
Endocervical polyps (benign) morphology
- Loose fibromyxomatous stroma
- Mucus-secreting endocervical glands
- Squamous metaplasia
Nabothian cysts (also called mucinous retention cysts or epithelial cysts)
- Translucent or opaque, whitish to yellow, measure up to 3 to 4 cm in diameter
- Squamous metaplasia and inflammation may block a gland orifice
- Endocervical columnar cells continue to secrete but are covered by squamous epithelium, forming a mucinous retention cyst
Papanicolauo Cytological Test (PAP test or smear)
- Detection of cervical precancerous conditions
Pathogenesis of sexually transmitted agent causing cervical cancer
- Human Papilloma Virus (HPV)
- Oncogenic DNA virus
HPV / Cervical CA mechanism of transformation
- E6 and E7 viral product expression
- E6 Protein (Anti-apoptotic) degrades p53 and BAX
- E7 Protein (Pro-mitotic) inactivates the CDKIs p21
Degrades RB-E2F
HPV with low oncologic potential (and locations)
- HPV 6, 11
- Perineal
- Perianal
- Vulvar
- (Condyloma Acuminatum)
HPV with high oncologic potential
- Vulvar / vaginal lesions (VIN and SCCA)
High risk HPV types
- Cervical Dysplasia and CA
- HPV 16 (most carcinogenic)
- Sufficient Evidence
(18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59)
HPV low risk types
- Condyloma Acuminatum
- HPV 6, 11
- (42, 44…)
What makes high risk type of HPV
- Viral genome incorportaion
What makes low risk type of HPV
- Viral genome episome in cytoplasm
Other factors encouraging low risk types of HPV
- E7 poor binding affinity to RB
- E6 fail to bind to p53
Microbial carcinogenesis viral infectivity (cervical cells)
- Basal cells
- Immature squamous cells
- Immature metaplastic cells
- Cells at squamocolumnar junction
Koilocytic Atypia
- Seen in maturing squamous cells
- Viral replication continues in mature populations
Cervical neoplasia development
Normal –> metaplastic –> dysplasia –> CA
Risk factors associated with cervical neoplasia
- Early age at 1st intercourse
- Multiple sex partners / males with multiple partners
- High parity
- Persistent detection of a high risk HPV
- OCP
- Genital infections
- Immunosupression
- Nicotine use
Progression of cervical neoplasia to cancer
- 90% of HPV infections cleared within 2 years
- 50% of HPV infections are cleared within 8 months
- Duration of infection depends on HPV type
- Persistent infection correlates with development of precancerous lesions
Precancerous/cancerous classification
- Mild dysplasia
- Moderate dysplasia
- Severe dysplasia
- Carcinoma in situ
Mild dysplasia
- Cervical intraepithelial neoplasia (CIN) I
- Low grade squamous intraepithelial lesion (LGSIL)
Moderate dysplasia
- Cervical intraepithelial neoplasia (CIN) II
- High grade squamous intraepithelial lesion (HGSIL)
Severe dysplasia
- Cervical intraepithelial neoplasia (CIN) III
- High grade squamous intraepithelial lesion (HGSIL)
Carcinoma in situ
- Cervical intraepithelial neoplasia (CIN) III
- High grade squamous intraepithelial lesion (HGSIL)
Normal cervical epithelium
- Stratified squamous epithelium
CIN Grade I (LGSIL)
- Nuclear enlargement
- Viral cytopathic effect
- Koilocytotic atypia
CIN Grade II (HGSIL)
- Increased atypia
- Increased N/C ratio
- Variation in nuclear size
- Loss of polarity
- Increased and abnormal mitotic figures
- Hyperchromasia
CIN Grade III (HGSIL)
- “Flip Affect”
- Invasion
Cervical neoplasia immunohistochemical sitaining / Dx
- In situ hybridization
- Immunoperoxidase Stains
Atypical Squamous Cells of Undetermined Significance (ASCUS)
- Slightly abnormal squamous cells
- Changes don’t clearly suggest that precancerous cells are present
Options when Atypical Squamous Cells of Undetermined Significance (ASCUS) are present
- Test for human papillomavirus (HPV) infection
- Repeat the Pap test in one year
Atypical Squamous Cells of Undetermined Significance (ASCUS) histological findings
- Cervical cells with abundant cytoplasm showing a “pulled-out” or streaming effect
- Nuclei exhibit pleomorphism and some cells have multiple nuclei and prominent nucleoli
- Changes indicate a reparative reaction, nuclear pleomorphism supports ASC-US
- In favor of a reactive process is the generally fine granularity of the chromatin pattern
Atypical glandular cells
- Women will have more serious lesions
- High-grade preinvasive squamous disease
- Adenocarcinoma in situ
- Adenocarcinoma or invasive cancers from sites other than the cervix
- Colposcopic examination is recommended
Atypical glandular cells findings
- Abnormal cells that come from glands in the walls of the cervix (the lower, narrow end of the uterus)
Cervical neoplasia clinical course
- Screening at age 21 or 3 yrs after intercourse
- Abnormal PAP
- Colposcopy shows acetic acid (Aceto-white)
Cervical neoplasia staging
- Stage 0
- Stage I
- Stage II
- Stage III
- Stage IV
Stage 0 cervical neoplasia
- Carcinoma in situ (CIN III)
Stage I cervical neoplasia
- Carcinoma confined to the cervix
Stage II cervical neoplasia
- Carcinoma extends beyond the cervix
Stage III cervical neoplasia
- Carcinoma has extended onto pelvic wall
Stage IV cervical neoplasia
- Carcinoma has extended beyond the true pelvis
Metastatic complications with cervical neoplasia
- Contiguous Structures
- Local and distant lymph nodes (liver, lungs, bone marrow)
Cervical neoplasia sampling and biopsy techniques
- Cytology (PAP Smear)
- Colposcopy (punch BX)
Treatment (CIN II and III no invasion)
- Cone Bx
- Cold knife excision
- LEEP (Loop Electrosurgical Excisional Procedure)
Invasive CA treatment
- TAH
- Radiation / chemotherapy (advanced)
SCCA of cervix characteristics
- Fungating (or exophytic)
- Ulcerating
- Infiltrative
SCCA of cervix histological findings
- Well-differentiated
- Moderately differentiated
- Poorly differentiated
Adenocarcinoma of cervix
- Intraepithelial glandular neoplasm
- Adenocarcinoma in situ
Adenosquamous CA of cervix
- Mixed glandular and squamous patterns
- Basal layer origin of endocervix
