2023 Female Reproductive Tract Pathology 2 - Cervical intra epithelial neoplasia (CIN) and carcinoma .pptx

Pathology of the Female Reproductive Tract Tony Williams Consultant Histopathologist Brighton and Sussex University Hospitals 2023 Module 203 • Microscopic anatomy of the female reproductive tract and terminology of neoplasia + endometriosis • Cervical intra epithelial neoplasia (CIN) and carcinom...

Pathology of the Female Reproductive Tract Tony Williams Consultant Histopathologist Brighton and Sussex University Hospitals 2023 Module 203 • Microscopic anatomy of the female reproductive tract and terminology of neoplasia + endometriosis • Cervical intra epithelial neoplasia (CIN) and carcinoma • Endometrial carcinoma – Virtual microscopy: Cervix & cervical carcinoma – Virtual microscopy: Endo/myometrium & endometrial carcinoma • The testis and spermatogenesis – Semen analysis Cervical intra epithelial neoplasia (CIN) and carcinoma • Dysplasia and the histologic features of CIN • Recognition of CIN by cytologic screening • The pathogenesis of cervical cancer • Trends in the incidence of cervical cancer Learning outcomes Describe the concept of pre-invasive lesions and the histologic and cytologic features of CIN in the cervix; outline the pathogenesis of cervical cancer; compare trends of incidence of cervical cancer with endometrial cancer with reference to risk factors and preventative measures Dysplasia Dysplasia • For some malignant neoplasms a ‘premalignant’ state is identified • This state is termed dysplasia • It is especially well recognized in preinvasive epithelial neoplasms Recognition of dysplasia • There is an accumulation of cells which look somewhat like malignant cells but do not invade the basement membrane • Dysplastic lesions may (but don’t always) progress to invasive malignancy • Recognising dysplastic lesions allows early treatment before invasion occurs Dysplasia Disordered growth and differentiation characterised by • Increased proliferation (more, and sometimes abnormal, mitoses) • Atypia of nuclei • Decreased differentiation Dysplasia has lots of different terminology for the same process Eg for the squamous cervix: • Generic: Dysplasia • UK: Cervical intra-epithelial neoplasia (CIN) • US: Squamous intra-epithelial lesion (SIL) Different degrees of dysplasia may be recognised microscopically The degree of dysplasia may predict the likelihood of developing invasive malignancy Grade % progress to CIN3 CIN1 CIN2 CIN3 11 22 - 1 5 40 After Ostor and Syrjanen 1993 % progress to SCC Dysplasia often occurs in sites where there is metaplasia • squamous metaplasia of the cervical transformation zone • squamous metaplasia of the bronchial epithelium • glandular metaplasia of the distal oesophagus Cells at the surface of dysplastic epithelium are different from those at the surface of normal epithelium. Normal constituents of a cervical cytology specimen (‘smear’) Endocervical cells Squamous cells Metaplastic cells Normal surface cells have a small nucleus and lots of cytoplasm Dysplasia in cytologic specimens is known as dyskaryosis. Cells in have a higher ratio of nuclear size to cytoplasmic volume, and nuclei show the same features that we associate with malignancy • Increased nuclear:cytoplasmic ratio • Changes in nuclear chromatin staining (hyperchromasia, distribution and granularity) • Irregular nuclear membrane and nuclear contours The critical event in the development of carcinoma from dysplasia is invasion through the basement membrane Dysplasia may less commonly be seen in the endocervical glandular epithelium Known as cervical glandular intra-epithelial neoplasia (CGIN), it is the pre-invasive precursor of HPV associated cervical adenocarcinoma • Up to 90% of cervical cancers are squamous cell carcinomas • Over 95% of these are caused by HPV infection • HPV associated cervical carcinoma is a largely preventable disease • In 2018, WHO issued a global call to eliminate cervical cancer as a public health problem. Human Papillomavirus • Human Papillomaviruses (HPVs) infect epithelium • Confined to local site of infection without viraemia • Over 130 HPV types, some of which infect the anogenital mucosa • Double stranded DNA virus 7.9Kbp HPVs may be grouped according to risk association with malignancy • High Risk HPV 16,18,31,33,35,39,45,51,52,56,58,59,68 • Low Risk HPV 6,11,40,42,43,44,54,61,72,81 Strategies to prevent cervical cancer • HPV Vaccination • Population based screening – Cervical sample HR HPV test – Cervical sample cytology • Colposcopy • Treatment of cervical intraepithelial neoplasia – eg, Large Loop Excision of the Transformation Zone (LLETZ) HPV positive oropharnygeal cancer increases: Cervical cancer prevented by screening stimated age-standardized incidence apillomavirus (HPV)–positive and ancer squamous cell carcinoma cases ears, Stockholm, Sweden, 1970–2006. . Data from Näsman et al. of human HPV-negative tonsillar per 100,000 personError bars indicate 95% Cervical cancer is predominantly a disease of low & middle income countries Cervical Cancer, World Age-Standardised Incidence and Mortality Rates, World Regions, 20 Endometrial cancer is presently most common in North America and Europe Cancer of the Corpus Uteri World Age-Standardised Incidence and Mortality Rates per 100,000 Population, World Regions, 2008 The incidence of cervical cancer has been declining (in europe) Cervical Cancer, European Age-Standardised Incidence Rates, GB, 1975-2008 The reduction in incidence of cervical cancer has been paralleled by reduced mortality A more complex picture emerges looking at age-specific mortality With an explanation emerging in age specific incidence rates ervical Cancer, Average Number of New Cases per Year and Age-Specific Incidence Rates, UK, 2006-20 • The separate peaks in cervical cancer incidence reflect a birth cohort effect • This happens when a group of people experience different circumstances to those born immediately before or after • An increase in cervical cancer incidence and mortality was seen in women reaching the age of sexual debut during WW1 and again in WW2 • The incidence and mortality of cervical cancer in the UK have decreased, particularly since the early 1980s • In the UK this follows the introduction of the NHS cervical screening programme • A birth cohort effect exists, believed to reflect the different exposure to HPV at the time women reached the age of sexual debut • HPV vaccination is creating new birth cohorts Age standardised incidence rates of endometrial cancer (UK 1993-2016) Learning outcomes • Describe the concept of pre-invasive lesions and the histologic and cytologic features of CIN in the cervix; • Outline the pathogenesis of cervical cancer; • Compare trends of incidence of cervical cancer with endometrial cancer with reference to risk factors and preventative measures