Molecular Pathology of Haem Cancers

Question 1

In 2003 NICE guidelines recommended what for lymphoma management?

Answer 1

Specialist reporting and MDTs

Question 2

What percentage of lymph node biopsy reporting involves misdiagnosis?

Answer 2

5-20%

Question 3

The 2008 BCSH guidelines for lymphoma recommended what?

Answer 3

Integrated reporting

Question 4

Clonality PCR can help differentiate between what cells?

Answer 4

Reactive Vs Neoplastic cells.
T vs B Cells.

Question 5

What value does molecular haemopathology offer?

Answer 5

Diagnosis (malign vs benign, disease monitoring, sub-classification), prognosis, and treatment stratification.

Question 6

What do you need to begin classifying tumours?

Answer 6

You need analysis of all aspects of many different cases of the disease. Then find distinct disease entities with a consensus process. Then you need to create terminology and diagnositc criteria.

Question 7

Once you can classify tumour really well you can then start to do what?

Answer 7

Do class prediction early on

Question 8

What does a haemopathologist require in a sample to maximise their effectiveness?

Answer 8

Tumour content in remaining tissue block >10%
Microdissection to enrich the suspected cells OR an indication of the areas of lymphoma/lesion on the blocks.
Interphase for FISH?

Question 9

What 3 proteins have been important in diagnosis of Follicular Lymphoma in situ?

Answer 9

BCL2, MIB1, CD10

Question 10

What knowledge helps to discriminate between benign and malignany tumours for a haemopathologist?

Answer 10

Cytogenetic changes, B and T cell clonality, Somatic gene changes

Question 11

The reciprocal translocation (11;14)(q13;q32) is the classical translocation pattern in which disease, and how is it detected?

Answer 11

Mantle cell lymphoma, using dual fusion probes

Question 12

In mantle cell lymphoma what important gene is involved in the translocation? What does it lead to?

Answer 12

CCND-1 at 11q13. Leads to overexpression of Cyclin D1 which is essential in MCL progression

Question 13

FISH with break apart probes has a high sensitivity for rearrangements. What does it look for in Burkitt’s lymphoma?

Answer 13

Chr8;14 translocation involving MYC

Question 14

What genes are affected in Follicular lymphoma translocation?

Answer 14

BCL2 and MYC

Question 15

Translocations can exist in multiple types of haematological malignancies. MYC rearrangements can be in Burkitts lymphoma and Diffuse Large B-Cell Lymphoma (DLBCL), how do you distinguish them?

Answer 15

BL - MYC translocation associated with IG gene. Simple or no cytogenetic changes and other translocations.
DLBCL - MYC translocations with non-IG genes. Complex cytogenetic changes, CNVs and other translocations.

Question 16

What pathways is MYC involved in?

Answer 16

Apoptosis and proliferation

Question 17

MYC+ B cell lymphoma becomes more aggressive with what other changes?

Answer 17

P53 and BCL2 changes

Question 18

DLBCL can be split up into what 2 subtypes?

Answer 18

Germinal centre and non-germinal centre.

Question 19

What technique is used to distinguish between DLBCL cases that are germinal centre or non-germinal centre?

Answer 19

IHC by looking at patterns of CD10, BCL6 and MUM-1

Question 20

Non-germinal centre DLBCL can also be called what?

Answer 20

Activated B Cell like group … ABC-DLBCL.

Question 21

What algorithm is used form a study to diagnose the cell of origin of DLBCL and inform prognosis?

Answer 21

COO Classification

Question 22

Which has a poorer prognosis? GC-DLBCL or ABC-DLBCL?

Answer 22

ABC-DLBCL has lower survival rate

Question 23

Accurately determine a BCL type in terms of MYC translocation, double or triple hit, ACB or GC subtypes have implications for which 3 therapies?

Answer 23

BTK inhibitors, MALT1 inhibitors, and proteasome inhibitors