Lymphoid Malignancy

Question 1

Lymphoma

Answer 1

A cancer of lymphoid origin. This can present with enlarged lymph nodes, extranodal involvement or bone marrow involvement.

Question 2

Systemic B Symptoms

Answer 2

Weight loss (> 10% in 6 months), fever, night sweats, pruritus, fatigue

Question 3

How is the classification of lymphoma decided

Answer 3

Biopsy of site of tumour

Clinical examination and imaging (CT) tell us where it is.

Question 4

Science of lymphoma

Answer 4

Malignancy occurs in the lymphoid region (germinal centre). To the lymph glands and the secondary lymphoid tissue.

Question 5

Lymphoproliferative Disorders

Answer 5

Acute lymphoblastic leukaemia (ALL)
Chronic lymphocytic leukaemia (CLL)
Hodgkin lymphoma
Non-Hodgkin lymphoma (NHL)

Question 6

Most common lymphoproliferative disorder

Answer 6

Non-hodgkin Lymphoma (High grade diffuse large B-cell lymphoma)

Question 7

Acute Lymphoblastic Leukaemia

Answer 7

Neoplastic disorder of lymphoblasts diagnosed by >20% lymphoblasts present in the bone marrow.

Question 8

Epidemiology of ALL

Answer 8

Incidence 1-2/100,000 population/year
75% cases occur in children < 6 years
75-90% cases are of B-cell lineage

Question 9

Presentation of ALL

Answer 9

2-3 week history of bone marrow failure (with possible raised white cell count) or bone and joint pain, infection, night sweats

Question 10

Emergency treatment in every lymphoma

Answer 10

Steroids

Question 11

Standard treatment of ALL

Answer 11

Induction chemotherapy to obtain remission

Consolidation therapy

CNS directed treatment

Maintenance treatment for 18 months

Stem cell transplantation if they are high risk (20-30% mortality)

Question 12

Indicators of poor prognosis in ALL

Answer 12

Increasing age

Increased white cell count

Immunophenotype (more primitive forms)

Cytogenetics/molecular genetics t(9,22), t(3;11)

Question 13

Adult outcome ALL

Answer 13

complete remission rate 78–91%

leukaemia-free survival at 5y 30–35%

Question 14

Child outcome ALL

Answer 14

5y overall survival ~90%

Question 15

Chronic Lymphocytic Leukaemia

Answer 15

Diagnosed by blood >5x10^9/L lymphocytes.
Bone marrow >30% lymphocytes
Characteristic Immunophenotyping (CD 19, 20, 23) & CD5 positive (not supposed to be there)

Question 16

Epidemiology of CLL

Answer 16

> 1700 new cases CLL per year in the UK
Commonest leukaemia worldwide
2 males: 1 female

Question 17

Presentation of CLL

Answer 17

Often assymptomatic at presentation

Frequent findings:
Bone marrow failure (anaemia, thrombocytopenia)
Lymphadenopathy 
Splenomegaly (30%) 
Fever and sweats (B-symptoms) (< 25%)

Less common findings:
Hepatomegaly
Infections
Weight loss

Question 18

CLL associated findings

Answer 18

Immune paresis (loss of normal immunoglobulin production)

Haemolytic Anaemia

Question 19

CLL stage A

Answer 19

<3 lymph node areas

median survival is same as age matched control

Question 20

CLL stage B

Answer 20

3 or more lymph node areas

Median survival is around 8 years

Question 21

CLL stage C

Answer 21

Stage B + anaemia or thrombocytopenia

Median survival is around 6 years

Question 22

Indications for treatment of CLL

Answer 22

Progressive bone marrow failure
Massive lymphadenopathy 
Progressive splenomegaly
Lymphocyte doubling time <6 months or >50% increase over 2 months
Systemic symptoms
Autoimmune cytopenias

Question 23

Treatment of CLL

Answer 23

Often nothing – “watch and wait”

Cytotoxic chemotherapy e.g. fludarabine, bendamustine

Monoclonal antibodies e.g. Rituximab, obinutuzamab

Question 24

Poor Prognostic Markers of CLL q

Answer 24

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

Question 25

Presentation of lymphoma

Answer 25

lymphadenopathy/hepatosplenomegaly Extranodal disease “B symptoms” bone marrow involvement

Question 26

Assessment (staging)

Answer 26

Lymph node biopsy CT scan Bone marrow aspirate Trephine

Question 27

Stage 1 lymphoma

Answer 27

One area of lymph node disease (usually the neck)

Question 28

Stage 2 lymphoma

Answer 28

2 areas of lymph node disease both above the abdomen

Question 29

Stage 3 Lymphoma

Answer 29

Above and below the abdomen

Question 30

Stage 4 lymphoma

Answer 30

Extranodal disease

Question 31

How is Non-Hodgkin Lymphoma classified

Answer 31

lineage (B-cell or T-cell) -Majority are B-cell in origin grade of disease (high grade or low grade) histological features of disease

Question 32

Low grade lymphoma

Answer 32

Indolent, often asymptomatic responds to chemotherapy but incurable median survival varies by subtype

Question 33

High grade lymphoma

Answer 33

Aggressive, fast-growing Require combination chemotherapy, steroids, antibodies (anti-CD20 monoclonal antibody + chemo) Can be cured, but again varies widely

Question 34

Diffuse large-B cell lymphoma

Answer 34

Sheet of lymphoma Commonest subtype of lymphoma (of any kind) High-grade lymphoma

Question 35

Follicular Lymphoma

Answer 35

2nd commonest type of lymphoma (low grade lymphoma) Looks like balls under the microscope

Question 36

Epidemiology of Hodgkin Lymphoma

Answer 36

``` 30% of all lymphomas bimodal age curve: -1st peak at 15-35y -2nd peak later in life 1.9 males: 1 female ```

Question 37

Treatment of Hodgkin Lymphoma

Answer 37

Combination chemotherapy (ABVD) +/- radiotherapy Use of PET scan to assess response to treatment and to limit use of radiotherapy