Rick Allen PATHOPHYSIOLOGY OF LYMPHOMAS LYMPHOMA 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. CLASSIFICATION BASED ON CELL ORIGIN 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) ROBBINS P 599 NHL – PREM B AND T ALL That is all NHL – PERIPHERAL B CELL NEOPLASM 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-κB. Immune function buggered by unknown mechanism NHL – PERIPHERAL B CELL NEOPLASM 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) NHL – PERIPHERAL B CELL NEOPLASM 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 NHL – PERIPHERAL B CELL NEOPLASM 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. NHL – PERIPHERAL B CELL NEOPLASM 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 G1S phase progression Pathophysiolology: Painless lymphadenopathy. Spleen and gut involvement symptoms. NHL – PERIPHERAL B CELL NEOPLASM 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. PERIPHERAL T CELL LYMPHOMA 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-κB. Bad prognosis. Large Granular Lymphoblastic Lymphoma (rare) Extranodal NK/T cell Lymphoma Surrounds and invades small vessels ischaemic necrosis. EBV involved HODGKIN’S LYMPHOMA Classical HL Nodular sclerosis Mixed cellularity Lymphocyte rich (rare) Lymphocyte depletion (rare) Lymphocyte pre-dominance (rare) Difference? Immunophenotypes of ReedSternberg (RS) Cells. HODGKIN’S LYMPHOMA Aetiology: B-cells are from germinal/post-germinal centre A mechanism (commonly EBV infection via LMP1) NF-κB inhibitor mutation act. Transcription factor NF-κB 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. ROBBINS P621 HODGKIN’S LYMPHOMA Pathophysiology: Node spleen liver marrow/other tissues Suppressed Th1 immune response. Mediastinal involvement breathing issues. Generally slower progression HL VS. NHL HL NHL more often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) Orderly spread by contiguity More frequent involvement of multiple peripheral nodes. Mesenteric nodes and Waldeyer ring rarely involved Waldeyer ring and mesenteric nodes commonly involved Extra-nodal presentation rare. Extra-nodal presentation common Noncontiguous spread