W1L1 - Invasive Gynaecological Malignancy Flashcards
Aetiology of CxCa
HrHPV DNA Immune status Smoking Hormones - contraception Vit A deficiency Early first sexual intercourse Multiple sex partners
Cervical Intraepithelial Neoplasm (CIN)
The abnormal growth of precancerous cells in the cervix
Squamous Cell Carcinoma
May occur at any age from 20 - P.menopausal
Most common tumour of the cervix
STI with HrHPV is the main aetiological factor for cervical cancer
Other Risk Factors for SCC - Females
Early age of first coitus
Multiple partners
STI
Low socioeconomic status
Other Risk Factors for SCC - Males
Early age of first coitus Multiple partners Prostatitis Penile HPV infection Carcinoma of penis
Risk Factor for SCC - Drugs
Cigarette smoking - oxidative stress and DNA damage
OCP - for >5 yrs may increase risk
Alcohol
Diethylstilboestrol (DES) - prevalent in glandular lesions
Immunosuppressive drugs - HIV/autoimmune conditions
Pathogenesis - HPV Oncogenes
HPV E2 protein serves as transcriptional repressor for E6 and E7 genes
Integration of HPV DNA into host genome disrupts E2 gene allowing production of E6 and E7 proteins
These proteins inhibit p53 and pRb tumour suppressor proteins
Types of Invasive SCC
Non-keratinising SCC (50%) - large cell or intermediate cell types - may be few single keratinised cells Keratinising SCC (35%) - often a well differentiated SCC with epithelial pearls and single keratinised cells Small cell carcinoma/Basaloid SCC (15%) - uncommon - poorly differentiated SCC - reserve cell carcinoma, neuroendocrine carcinoma
WHO Classification of SCC
Micro invasive SCC
- invasion through basement membrane of not more than 5mm depth and 4mm width into submucosa
Invasive SCC
- invasion through submucosa > 5mm into underlying mucosa, or extension into vagina, lymph nodes or other surrounding tissue
Verrucous carcinoma
- exophytic papillae growth resembling condylomas
Warty (condylomatous) carcinoma
- rare
- aggressive SCC of the cervix
Papillary squamous cell (transitional) carcinoma
- epithelium resembles transitional cell carcinoma of urinary tract
Definition of Microinvasive SCC
HSIL with evidence of stromal invasion by squamous cells in one or more foci
Can occur in any grade of CIN but is more commonly seen in CIN 2/HSIL lesions
Morphology of Invasive Carcinoma - Things to Look For
Number of cells identified Monomorphism or polymorphism Architecture - single cells - aggregate - glandular differentiation Tumour diathesis - granular material derived from tumor cell necrosis and fragmented RBC associated with ulceration Range of abnormal malignant cells (HSIL/LSIL)
Cytological Criteria for Invasive Carcinoma
Size and shape of atypical cells Nuclear/cytoplasmic ratio Cytological and nuclear pleomorphism Chromatin amount and distribution Nucleoli Nuclear border Mitosis
Cytology of Non-Keratinising SCC
Malignant cells - smaller than normal squamous cells - usually round or oval/elongated - moderate basophilic, occasionally orangeophilic cytoplasm Nuclei - high N/C ratio - nuclear mean area twice normal - hyperchromatic - pleomorphic - irregular coarse granular chromatin - small, large or multiple nucleoli
Morphology of Keratinising SCC
Highly cellular smears
Background of fresh blood or tumor diathesis
Sheets, syncytia or single cells dispersed
Presence of squamous pearls and anucleated squamous cells
Cytology of Keratinising SCC
Tumour cells
- most cells similar in size or larger than normal squamous cells
- often round, very pleomorphic (sometimes bizarre shapes)
- round, oval , polygonal, spindles, caudate shapes
- keratinised (refractile orange or pink) cytoplasm or non-keratinised blue cytoplasm
- increased N/C ratio
- coarse granular chromatin
- usually no nucleoli
