Lymphoid Malignancies

Question 1

What is the presentation of lymphoma?

Answer 1

Can present with enlarged lymph nodes (lymphadenopathy)
or 
with extranodal involvement
or
with bone marrow involvement
Hepatosplenomegaly
Systemic (B) symptoms
Weight loss (> 10% in 6 months), fever (swinging), night sweats, pruritus, fatigue

Question 2

Where does the mutation happen in lymphomas?

Answer 2

In the lymph node when the B cells are differentiating and trying to form antibodies against antigens

Question 3

What are the two classes of lymphoma?

Answer 3

Hodgkin Lymphoma

Non-Hodgkin Lymphoma - can be high or low grade

Question 4

Name a high and low grade Non-hodgkin lymphoma

Answer 4

High-grade (diffuse large B-cell lymphoma)

Low-grade (follicular, marginal zone)

Question 5

How does Hodgkin’s lymphoma differ to Non-Hodgkin’s?

Answer 5

It is characterised by the presence of Hodgkin’s cells and Reed-Sternberg cells.

Question 6

What investigations should be done in lymphoma?

Answer 6

FBC with differential-Low Hb and platelets
Metabolic panel
ESR
CXR
PET-CT scan
Contrast CT neck, chest, and abdomen/pelvis
Excisional lymph node biopsy
Immunohistochemical studies

Question 7

What is the staging of lymphoma?

Answer 7

Ann Arbor staging
Stage one to four, with four being extranodal involvement
A-no B symptoms
B-B symptoms present

Question 8

What virus can Hodgkin’s lymphoma be linked to?

Answer 8

Epstein Barr Virus

Question 9

What is the management of Hodgkin’s Lymphoma?

Answer 9

Combination chemotherapy (ABVD)
\+/- radiotherapy
Monoclonal antibodies (anti-CD30) (as cells express CD30)
Immunotherapy (checkpoint inhibitors)

Question 10

What is the management of Non-Hodgkin’s lymphoma?

Answer 10

Diffuse large B cell lymphoma and follicular lymphoma both treated with a combination chemotherapy – typically anti-CD20 monoclonal antibody + chemo

Question 11

What is acute lymphoblastic leukaemia?

Answer 11

Acute lymphocytic leukaemia (ALL) is a malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered through somatic changes and undergoes uncontrolled proliferation. This progressive clonal expansion eventually leads to ALL, characterised by early lymphoid precursors replacing the normal haematopoietic cells of the bone marrow and further infiltrating various body organs
Most are B cell lineage but can also be T cell

Question 12

What is the presentation of ALL?

Answer 12

Lymphadenopathy
Hepatosplenomegaly
Pallor, ecchymoses, or petechiae
Fever
Fatigue, dizziness, palpitations, and dyspnoea
Epistaxis, menorrhagia
Papilloedema, nuchal rigidity, and meningismus
Focal neurological signs
Painless unilateral testicular enlargement
Renal enlargement
Bony pain (limping child)
Abdominal pain
Mediastinal or abdominal mass
Pleural effusion
Skin Infiltration

Question 13

What investigations should be done in ALL?

Answer 13

FBC-anaemia, leukocytosis, neutropenia, and/or thrombocytopenia
Peripheral blood smear
Lactic dehydrogenase
Bone marrow aspiration and trephine biopsy
Immunophenotyping (on bone marrow, or peripheral blood if cell count is raised)
Thiopurine methyltransferase (TPMT) phenotype
Cytogenetics
Molecular studies

Question 14

What is the management for ALL?

Answer 14

Induction chemotherapy to obtain remission
Consolidation therapy
CNS directed treatment as cancer can hide in CNS
Maintenance treatment for 18 months
Stem cell transplantation (if high risk)

Question 15

What are poor risk factors in ALL?

Answer 15

Increasing age
Increased white cell count
Cytogenetics/molecular genetics
t(9;22); t(4;11) (philadelphia chromosome can be present in leukaemia)
Slow/poor response to treatment

Question 16

What is chronic lymphocytic leukaemia?

Answer 16

Chronic lymphocytic leukaemia (CLL) is an indolent lymphoproliferative disorder in which monoclonal B lymphocytes (>5 x 10⁹/L [>5 x 10³/microlitre]) are predominantly found in peripheral blood.
Classic example of a low-grade condition
Requires a lymphocyte count of > 5 (normal is < 4)

Question 17

What is the presentation of CLL?

Answer 17

Often asymptomatic at presentation
Bone marrow failure (anaemia, thrombocytopenia)
Lymphadenopathy 
Splenomegaly
Fever and sweats
Hepatomegaly 
Infections 
weight loss
Immune paresis (loss of normal immunoglobulin production)
Haemolytic anaemia

Question 18

What is the staging used in CLL?

Answer 18

Binet
Stage A, B and C
Stage A and B are contained to lymph nodes and stage C means it is in the blood

Question 19

What are the indications to treat in CLL?

Answer 19

Progressive bone marrow failure
Massive lymphadenopathy
Progressive splenomegaly
Lymphocyte doubling time <6 months or >50% increase over 2 months
Systemic symptoms
Autoimmune cytopenias
Otherwise don’t need to treat, just monitor

Question 20

What investigations should be done in CLL?

Answer 20

WBC count with differential-elevated with absolute lymphocytosis
Blood film
Haemoglobin
Platelet count-possible thrombocytopenia
Flow cytometry
Fluorescent in situ hybridisation (FISH)
Molecular genetic analysis
Direct antiglobulin test (DAT)
Immunoglobulin levels
Bone marrow aspirate and trephine biopsy
CT scan

Question 21

What is the management of CLL?

Answer 21

Often nothing

Cytotoxic chemotherapy e.g. fludarabine, bendamustine
Monoclonal antibodies e.g. Rituximab, obinatuzumab
Novel agents
-Bruton tyrosine kinase inhibitor eg ibrutinib
-PI3K inhibitor eg idelalisib
-BCL-2 inhibitor eg venetoclax

Question 22

What are poor prognostic markers in CLL?

Answer 22

Advanced disease (Binet stage B or C)
Atypical lymphocyte morphology
Rapid lymphocyte doubling time (<12 mth)
CD 38+ expression
Loss/mutation p53; del 11q23 (ATM gene)
Unmutated IgVH gene status