Lymphoproliferative conditions

Question 1

what sort of test is required for lymphoma diagnosis?

what sort of test is required for lymphoproliferative disorder?

Answer 1

1. tissue biopsy, usually with architecture/structure
2. peripheral blood is usually sufficient for lymphoprolif, but some times may also need BMAT FNA is low yield

Question 2

what are the CD markers that help define CLL?

What about the cell surface light chains?

Significance of this?

Answer 2

1. The co-expression of T and B cell markers is important - CD 19/20/23 (B cell) and CD5 (T cell)
2. This helps to define clonality. Normally there should a balance between cell surface light chains - kappa and lambda. Each cell expresses one or the other. When there is clonality, we see a change in the ratio - with a massive overexpression in one sub type.

Question 3

If someone has a immunophenotyping performed for CLL, what are the major differentials that we need to consider?

Answer 3

CLL is about the co-expression of T and B cell markers.

CD5+ CD19+ CD 20/23/79b the major differentials are:

prolymphocytic leukaemia

• they have a proportion that lack CD5
• they have a much nastier/aggressive light chain expression

Mantle Cell

• CD23 negative (v important)

Hairy cell:

• rare

Question 4

how do we stage patients with CLL?

Answer 4

we typically use the Rai staging system.

It’s about the spread of disease (as is expected), but it’s really about describing survival.

See image

Major take home message is, once there is splenomegaly, the disease is different (more aggressive and more meaningful for survival)

Question 5

what are some of the complications of CLL?

Answer 5

1. autoimmune complications, particularly haemolysis, sometimes ITP

this complicates approx 3 - 5%

2. hypogammaglobulinaemia
   - up to 50% will lose immunoglobulins

IMPORTANT FACT

3. transformation to large cell lymphoma
   - also named Richter’s transformation
4. cutaneous malignancy
   - there is mounting evidence that CLL is due to some environmental factors, and this is reflected in the increased rates of coexisting malignancies
5. genitourinary/GI malignancy

Question 6

what is the treatment of CLL?

Answer 6

Fludarabine has changed the prognosis of CLL

apparently it can be dose adjusted and nearly all populations can take it

The standard of care is FCR

fludarabine (a purine analogue that impacts DNA polymerase, DNA primase)

cyclophosphamide

ritux

Question 7

what is the treatment of follicular lymphoma?

Answer 7

CHOP-R or CVP-R

maintenance with ritux is standard of care

However - with low risk features, and otherwise well, watchful waiting is valid

Question 8

what is the higher risk cytogenetic change/translocation associated with MALT lymphoma?

it is also associated with other marginal zone lymphomas, and suggests that removal of the infectious agent/irritant is unlikely to resolve the problem

Answer 8

the API2-MALT fusion protein is usually associated with this

it is a t(11;18)

Question 9

what is lymphoplasmacytic lymphoma?

Answer 9

THIS IS THE NEW NAME FOR WALDENSTROM’S MACROGAMMAGLOBULINAEMIA

this accounts for 1.2% of NHL

most cases are characterised by IgM paraproteinaemia

bone marrow is typically involved in these patients

the spleen can be enlarged

If someone has IgM paraproteinaemia, then a bone marrow is important, because the cells are rarely seen in peripheral blood by flow cytometry

Question 10

Q3 A 57 year old man presents with iron deficiency. Endoscopyrevealsdiffuse gastritis and several small ulcers. Biopsy reveals changes consistent with gastric MALT lymphoma. No Helicobacter organisms are identified.

The next best step is:

a) radiotherapy
b) Helicobacter eradication therapy

c) rituximab
d) Helicobacter serology
e) repeat endoscopy and biopsy

Answer 10

the best option is to repeat endoscopy and biopsy.

the initial scope was done for iron deficiency anaemia, and the result is unexpected.

Diagnosis of MALT requires specific sampling and testing, and we first need to go back and do this.

H. pylori may be found at the second assessment.

Question 11

Q 1

A 64 year old female presents with an isolated lymphocytosis (6500 cells/uL) on an otherwise normal blood film. There are no abnormal findings on clinical examination. Flow cytometry reveals a population of B- cells with an immunophenotype as follows:

CD 5 +
CD19/20/23 +
surface Ig Kappa restriction

This patient is most likely to have:

a) non-mutated Vh genes
b) a high ZAP-70 expression
c) Mantle cell lymphoma

d) a median survival of >10 years
e) a serum Beta-2-microglobulin level of >3.0

Answer 11

a- this is a high risk phenotype finding

b - this is a high risk

c - the CD markers exclude Mantle cell

D - this patient is low risk CLL (based on the clinical findings and the CD markers)

e - this is a high risk

overall, D is the most likely, because clinically the patient appears to be low risk, with no associated nasty things like splenomegaly or LNs

Question 12

the question asks about treatment of a patient with CLL with small cervical LNs, with hypogammaglobulinaemia - who has had 2 pneumonias recently

• what is the appropriate treatment?

Answer 12

IVIg is the most appropriate treatment for their hypogammaglob

Question 14

what are smear cells?

Answer 14

these are a blood film finding associated with CLL

very important to be aware of

when put under the microscope, they are fragile and smear out

Question 15

patient bleeding

IgM level 60 (very high)

other cytopenias

what is the treatment?

Answer 15

the most important thing is to bring down the plasma viscosity

the best method of achieving this would be to initiate plasma exchange

once the viscosity is brought down, you would want to treat the Waldenstroms