Rick Allen

 Leukaemia involves widespread bone marrow involvement and a presence in peripheral blood.  Lymphoma’s arise in discrete tissue masses (commonly lymph nodes), with potentially only minor peripheral blood presence.

 Precursor B cell neoplasms (premature B)  Peripheral B cell neoplasms (mature B)  Precursor T cell neoplasm (premature T)  Peripheral T cell and NK cell neoplasm (mature T and NK)  Hodgkin (Reed-Sternberg cells and variants) Non Hodgkins Lymphoma (NHL)

 ALL  That is all

 CLL/Small Lymphocytic Lymphoma  Tissue manifestation of CLL. Psuedofollicular.  Immunophenotype: CD 19/20/23/5  Aetiology: deletion of 13q (TSG), 14q, 17p and trisomy 12q  Pathophysiolology: Growth confined to proliferation centres. Microenvironment stimulates NF- κ B. Immune function buggered by unknown mechanism

 Follicular Lymphoma  Most common form of indolent NHL  Immunophenotype: CD19/20/10, Ig, BCL 2 and 6  Aetiology: Germinal centre B cells, t(14:18) [BCL2]  Pathophysiolology: BCL2 antagonises apoptosis and promotes survival. Calls in reactive cells. Marrow, spleen and liver involvement common. Goes where B cells go (white pulp)

 Diffuse Large B-cell Lymphoma  Most common NHL. Diffuse growth, massive cells  Immunophenotype: CD19/20, Ig, BCL 6  Aetiology: BCL6 overexpression mutation: represses germinal B cell differentiation and growth arrest, silences p53  Pathophysiolology: rapidly enlarging mass. Waldeyer ring is common. Destructive mass in liver or spleen (1 or 2). Aggressive, commonly fatal

 Burkitt Lymphoma  Mature B cells. “Starry sky” pattern. Diffuse.  Immunophenotype: CD19/20/10, IgM, BCL6  Aetiology: t(8,2/14/22), c-MYC gene with a promoter  ↑ expression. p53 point mutation. EBV involvement  Pathophysiolology: extranodal sights in kids and young adults. Jaw and abdo viscera.

 Mantle cell Lymphoma  Resemble mantle B cells (surround germinal centre). Nodular or diffuse  Immunophenotype: ↑ cyclin D1, CD19/20/5, Ig.  Aetiology: t(11;14)  cyclin D1 upregulation  G1- S phase progression  Pathophysiolology: Painless lymphadenopathy. Spleen and gut involvement  symptoms.

 Marginal zone Lymphoma  Extranodal sites and MALT’s  Arise:  Chronic inflammation due to autoimmunity or infection (thyroid – Hashimoto, stomach – Heliobacter)  Localised for a fair period  May regress if ‘stimulant’ is removed.

 Immunophenotype: CD2/3/5  Types  Anaplastic Large-cell Lymphoma (rare)  Mycosis Fungoides/Sezary syndrome  CD4 Th cells go to the skin, invading the upper dermis and epidermis. 3 distinct phases. Uses adhesion molecule.  Adult T cell  Infected with Human T cell leukaemia retrovirus type 1 (HTLV-1),  NF- κ B. Bad prognosis.  Large Granular Lymphoblastic Lymphoma (rare)  Extranodal NK/T cell Lymphoma  Surrounds and invades small vessels  ischaemic necrosis. EBV involved

 Classical HL  Nodular sclerosis  Mixed cellularity  Lymphocyte rich (rare)  Lymphocyte depletion (rare)  Lymphocyte pre-dominance (rare)  Difference? Immunophenotypes of Reed- Sternberg (RS) Cells.

 Aetiology:  B-cells are from germinal/post-germinal centre  A mechanism (commonly EBV infection via LMP- 1)  NF- κ B inhibitor mutation  act. Transcription factor NF- κ B  act. Lymphocyte proliferation and survival genes  Theory: saves defective B cell from apoptosis, mutates to RS cell  RS secretes cytokines (IL-5,10,13, TNF-β) and chemokines calling reactive cells (majority)  release factors to promote tumour growth and survival.

 Pathophysiology:  Node  spleen  liver  marrow/other tissues  Suppressed Th1 immune response.  Mediastinal involvement  breathing issues.  Generally slower progression

HLNHL more often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) More frequent involvement of multiple peripheral nodes. Orderly spread by contiguityNoncontiguous spread Mesenteric nodes and Waldeyer ring rarely involved Waldeyer ring and mesenteric nodes commonly involved Extra-nodal presentation rare.Extra-nodal presentation common