Lymphoid Malignancies Flashcards
What is the presentation of lymphoma?
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
Where does the mutation happen in lymphomas?
In the lymph node when the B cells are differentiating and trying to form antibodies against antigens
What are the two classes of lymphoma?
Hodgkin Lymphoma
Non-Hodgkin Lymphoma - can be high or low grade
Name a high and low grade Non-hodgkin lymphoma
High-grade (diffuse large B-cell lymphoma)
Low-grade (follicular, marginal zone)
How does Hodgkin’s lymphoma differ to Non-Hodgkin’s?
It is characterised by the presence of Hodgkin’s cells and Reed-Sternberg cells.
What investigations should be done in lymphoma?
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
What is the staging of lymphoma?
Ann Arbor staging
Stage one to four, with four being extranodal involvement
A-no B symptoms
B-B symptoms present
What virus can Hodgkin’s lymphoma be linked to?
Epstein Barr Virus
What is the management of Hodgkin’s Lymphoma?
Combination chemotherapy (ABVD) \+/- radiotherapy Monoclonal antibodies (anti-CD30) (as cells express CD30) Immunotherapy (checkpoint inhibitors)
What is the management of Non-Hodgkin’s lymphoma?
Diffuse large B cell lymphoma and follicular lymphoma both treated with a combination chemotherapy – typically anti-CD20 monoclonal antibody + chemo
What is acute lymphoblastic leukaemia?
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
What is the presentation of ALL?
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
What investigations should be done in ALL?
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
What is the management for ALL?
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)
What are poor risk factors in ALL?
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
What is chronic lymphocytic leukaemia?
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)
What is the presentation of CLL?
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
What is the staging used in CLL?
Binet
Stage A, B and C
Stage A and B are contained to lymph nodes and stage C means it is in the blood
What are the indications to treat in CLL?
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
What investigations should be done in CLL?
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
What is the management of CLL?
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
What are poor prognostic markers in CLL?
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
