L14: importance of tumour classificaiton

Question 1

What is tumour behavioural classification?

Answer 1

o Benign (wart, can still cause harm, for example, in airways can bleed) versus malignant (metastasize, spreads, invades)

Question 2

What is tumour histogenic classification?

Answer 2

• Histogenetic classification
  o Resemblance to tissue of origin
  o Implies site of origin

Question 3

What are the major tumour categories?

Answer 3

• Epithelial origin (commonest, from epithelia that line organs; lung, breast, colon cancer)
• Connective tissue origin (mesenchymal) (bone/fat tumours)
• Lymphoid / haemotopoetic origin (lymphomas, laeukemia; intrinsically metastatic, because can get anywhere)
• Germ cell tumour (can divert to any directions)

Question 4

What are benign epithelial tumours called?

Answer 4

• Benign epithelial tumours are either papillomas (if they make hands-like structures) or adenomas (more solid structure)

Question 5

How do epithelial ovarian tumours differ by malignancy?

Answer 5

• Benign
  o Epithelia just growing in the wrong place, but single layer, no threat
• Borderline
  o Cytological abnormalities
  o No stromal invasion
  o Haven’t invaded through BM yet
• Malignant
  o Stromal invasion

Question 6

What are the terms for benign, borderline and malignant epithelial ovarian tumours?

Answer 6

Epithelial ovarian tumours
- Mucinous cystadenoma
o Very large
o Made up of cysts called daughter cysts
o benign
- Serous borderline tumours
o Produce cauliflower-like structures
o Could be malignant
- High grade serous carcinoma
o Solid, quite soft

Question 7

What are germ cell ovarian tumours?

Answer 7

Ovarian tumours: germ cell tumours
- 15-20% of all ovarian tumours
- Teratoma
- Mature (benign, cystic) – ‘dermoid cyst’
o 95% of germ cell tumours (in women, in men mostly malignant)
o Cystic, containing sebum and hair
o Contain ectoderm, mesoderm, endoderm
o Skin, respiratory epithelium, gut, fat common
o Can rarely become malignant

Question 8

What are the possible sex cord / stromal tumours?

Answer 8

Sex cord / stromal tumours
- Fibroma / thecoma (most common)
o Benign
o May produce oestrogen, causing uterine bleeding
- Granulosa cell tumour
o All are potentially malignant
o May be associated with oestrogenic manifestations
o ‘all’ adult-type tumours have C134W FOXL2 mutation
- Sertoli-leydig cell tumours
o Rare
o May produce androgens
o Associated with DICER1 mutation

Question 9

What are the originis of ovarian carcinomas?

Answer 9

• High grade serous carcinomas: from Fallopian tube or ovaries
• Endometrioid and clear cell carcinomas: from endometriosis
• Mucinous tumours: very often metastatic from stomach, colon and appendix

Question 10

Describe high grade serous carcinoma cancers

Answer 10

High-grade serous carcinoma
- Called serous because serous epithelium is that makes thin or fluid
- Loss of BRCA1/BRCA2 function
o Germline/somatic mutation, loss of heterozygosity
o Promoter hypermethylation
o Amplification of EMSY
- Homologous recombination deficiency (HRD)
o Unable to repair dsDNA breaks
o Complex karyotypes
- TP53 mutation in almost all high-grade serous carcinomas
- WT1 (marker of serous) immunopositive and p53 abberant (diffuse or absent)
- Most of tubal origin
- They’re not all the same genetically, and classic split is between homologous recombination deficient and homologous recombination proficient

Question 11

Describe low grade serous tumours

Answer 11

• BRAF and KRAS mutation common in borderline and invasive tumours
• TP53 mutation absent and usually diploid
• Fewer karyotypic and other molecular abnormalities than high-grade tumours
• Diagnosis
  o Two-tier grading system based on nuclear atypia alone
  o WT1/p53 immunohistochemistry useful but DNA sequencing may be required
• Treatment
  o Differences in chemosensitivity (low grade responds really poor to chemo)
  o Emerging role for MEK inhibitors

Question 12

describe endometrioid carcinomas

Answer 12

• Make glandular structures
• Have smooth luminal borders
• WT1 histochemistry tells if serous or not serous – major split
• Subdivided by CTNNB1 and TP53 mutation