Gynaecopathology - Ovarian and Fallopian Cancers Flashcards
What is the ovary
The ovary is a highly specialised organ physiologically dedicated to ovum production
It is mainly composed of stromal cells that support maturing germ cells, covered by a monolayer modified mesothelium (so called ovarian surface epithelium)
What is the epidemiology of Ovarian Cancer
8th most common cancer in women
Incidence is declining, even in areas with germline BRCA1/2 mutation
What are the protective factors of Ovarian Cancer
- contraceptive pills
- high parity
- breast feeding
- tubal ligation
- hysterectomy
What are the risk factors of ovarian cancer
Family history
Endometriosis
PCOS
BRCA 1/2 (autosomal dominant)
Hereditary nonpolyposis colorectal cancer (Lynch syndrome) mutations in DNA MMR genes (MLH1, MSH2, MSH6, PMS2)
What are the syndromes that are risk factors for ovarian cancer
- Peutz-Jeghers syndrome (g.m in STK11)
- Cowden syndrome (g.m in PTEN)
- Coffin-Siris Syndrome (g.m in ARID1A)
- Li-Fraumeni Syndrome (g.m in TP53/p53)
What is the classification of ovarian cancer
Epithelial ovarian cancer is the most common (90% of ovarian cancer)
Within this, serous carcinoma is the most common type of carcinoma (68-71%)
Well-differentiated (low grade) serous tumours were thought to progress to moderately and, ultimately, poorly differentiated (high grade) serous carcinomas
What are the cells of origin in ovarian cancer
Ovarian surface epithelium (OSE)
What is the mechanism
OSE is modified mesothelium which undergoes metaplasia, acquiring a Mullerian or non-Mullerian epithelial phenotype and successively undergoes neoplastic transformation
What are the characteristics of low grade serous carcinomas
- Often bilateral
- Fine papillary, nodular growth
- Little to no necrosis
- Calcification in the ovary and extraovarian lesions can be extensive
What is the architecture of a low grade serous carcinoma
Non-invasive pattern: micropapillary or cribriform with significant expansile growth
Invasive pattern (>5mm):
- micropapillary or complex papillae
- compact cell nests
- inverted macropapillae (with broad fibrovascular cores)
- cribriform
- glandular or cystic
- solid sheets with slit-like spaces and single cells
What is the cytology of low grade serous carcinoma
- Uniform nuclei
- Infrequent mitotic figures
- Low nuclear atypia of well-differentiated tumours
What is high grade serous carcinoma
Accounts for majority of ovarian carcinoma
Often bilateral, solid and cystic ovarian masses
Variable in size: often large
Exophytic with solid or papillary growth
Fallopian tube can be grossly involved at fimbriated end
What is the histology of high grade serous carcinoma of the ovary
Solid masses of columnar to cuboidal cells with eosinophilic cytoplasm and slit-like spaces (fusion to papillae)
There is hierarchical papillary branching, glandular and cribriform patterns common
High mitotic index
Necrosis is frequent
Psammoma bodies are variable
Nuclear pleomorphism and frequent mitotic figures
What are the controversies surrounding ovarian cancer
- No ovarian surface epithelial carcinomas resemble OSE
- Metaplasia of OSE is difficult to demonstrate and almost never observed.
- There are no intermediate/hybrid phenotypes of OSE metaplasia tumours
- Real mesotheliomas are rare
- Most ovarian tumours do not express OSE molecular markers
How are BRCA1/BRCA2 mutations linked to hereditary ovarian cancer, and what was discovered after prophylactic surgery?
BRCA1/2 mutations (tumor suppressor genes) are associated with hereditary ovarian cancer.
Patients often undergo prophylactic salpingo-oophorectomy.
Dysplastic precursor lesions (later called Serous Tubal Intraepithelial Carcinoma, STIC) were found in the fallopian tubes, not the ovaries.
What did examination of the fallopian tubes reveal
Early fallopian tube cancer in sporadic high grade serous carcinomas and multifocal
What are the overlapping molecular alterations with STIC and high grade serous carcinoma?
p53
p16
FAS
RSF1
CCNE1
centrosome amplification
This suggests a clonal relationship
What evidence backs up the role played by fallopian tubes in ovarian cancer
Tubal ligation reduces the incidence of ovarian endometrioid, clear cell carcinoma and high grade serous carcinoma.
What is the emerging pathogenic views: cells of origin
- extra-ovarian Mullerian Epithelia (Endometrium or fallopian tube epithelium)
- ovary (endometriosis or fallopian tube epithelium seeded on the ovary as inclusion cysts)
What is the emerging pathogenic views: mechanism
Genetically normal or initially transformed epithelial cells from fallopian tube or endometrium seed the ovary, its microenvironment promotes their neoplastic transformation
Mucinous carcinomas are composed of tumours with different genesis, including mature cystic teratoma and extra-ovarian Mullerian epithelium (Brenner tumours or endometriosis)
